This study investigated the roles of transactions cost in MSMEs access to finance. This was done by investigating the impact of transactions cost on access to credit from both MSMEs and financial institutions (commercial banks and microfinance banks). From the MSMEs’ side, borrowing experience, decision lag, firm size and borrowers’ distance to the loan office were investigated. On the financial institution’s side, the costs of information gathering, loan administration, monitoring and loan enforcement were investigated. We used the questionnaire survey method, in-depth interviews and case studies, as well as the annual financial statements of the banks. We identified interest rate and collateral value as constraints to access to finance for MSMEs. We also found financial institutions’ attitude to MSMEs access to credit was not friendly. Financial institutions need to do more to bring down transaction cost of lending. This hopefully can be achieved by investing more in agent banking which would lower operating costs, as well as spreading risk, and ultimately increase credit intermediation to small businesses.

Expression analysis of small noncoding RNA (sRNA), including microRNA, piwi-interacting RNA, small rRNA-derived RNA, and tRNA-derived small RNA, is a novel and quickly developing field. Despite a range of proposed approaches, selecting and adapting a particular pipeline for transcriptomic analysis of sRNA remains a challenge. This paper focuses on the identification of the optimal pipeline configurations for each step of human sRNA analysis, including reads trimming, filtering, mapping, transcript abundance quantification and differential expression analysis. Based on our study, we suggest the following parameters for analysis of human sRNA in relation to categorical analyses with two groups of biosamples: (1) trimming with the lower length bound = 15 and the upper length bound = \(Read\ length - 40\% Adapter\ length\); (2) mapping on a reference genome with bowtie aligner with one mismatch allowed (-v 1 parameter); (3) filtering by mean threshold > 5; and (4) analyzing differential expression with DESeq2 with adjusted p-value < 0.05 or limma with p-value < 0.05 if there is very little signal and few transcripts.

Small RNAs (sRNA) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small RNAs function as global regulators. Here, we used small RNA deep sequencing to investigate at how jararhagin, a metalloproteinase toxin produced from the venom of Bothrops jararaca, affected mmu-miRs expression in mice 2 h and 24 h after injection. The findings revealed that seven mmu-miRs were substantially differentially expressed (p-value (p (Corr) cut-off 0.05, FC 2) at 2h after jararhagin exposure, and that the majority of them were upregulated when compared to PBS. In contrast to these findings, a comparison of Jar 24h vs PBS 24hrs demonstrated that the majority of identified mmu-miRs were downregulated. Furthermore, the studies demonstrated that mmu-miR can target the expression of several genes involved in the MAPK signaling pathway. The steady antithetical regulation of mmu-miRs may correlates with the expression of genes that trigger apoptosis via MAPK in the early stages, and this effect intensifies with time. The findings expand our understanding of the effects of jararhagin on local tissue lesions at the molecular level.

[NiFe]-hydrogenases are gas-processing metalloenzymes that catalyze the conversion of dihydrogen (H2) to protons and electrons in a broad range of microorganisms. Within the framework of green chemistry, the molecular proceedings of biological hydrogen turnover inspired the design of novel catalytic compounds for H2 generation. The bidirectional “O2-sensitive” [NiFe]-hydrogenase from Escherichia coli HYD-2 has recently been crystallized; however, a systematic infrared characterization in the presence of natural reactants is not available yet. In this study, we analyze HYD-2 from E. coli by in situ ATR FTIR spectroscopy under quantitative gas control. We provide an experimental assignment of all catalytically relevant redox intermediates alongside the O2- and CO-inhibited cofactor species. Furthermore, the reactivity and mutual competition between H2, O2, and CO was probed in real time, which lays the foundation for a comparison with other enzymes, e.g., “O2-tolerant” [NiFe]-hydrogenases. Surprisingly, only Ni-B was observed in the presence of O2 with no indications for the “unready” Ni-A state. The presented work proves the capabilities of in situ ATR FTIR spectroscopy as an efficient and powerful technique for the analysis of biological macromolecules and enzymatic small molecule catalysis.

Background: It remains unclear whether transfer RNA-derived small RNAs (tsRNAs) play a role in pathological cardiac hypertrophy (PCH). We aimed to clarify the expression profile of tsRNAs and disclose their relationship to the clinical phenotype of PCH and the putative role. Methods: Small RNA sequencing was performed in the plasma of PCH patients and healthy volunteers. In a larger sample size and angiotensin Ⅱ (Ang II)-stimulated H9c2 cells, the data were validated by real-time qPCR. The atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were examined in Ang II-stimulated H9c2 cells. The role of tsRNAs in the pathogenesis of PCH was explored by bioinformatics analysis. Results: A total of 4185 differentially expressed tsRNAs were identified, of which 4 and 5 tsRNAs were observed to be significantly differentially upregulated and downregulated expressed. Of the 5 down-regulated tsRNAs, 4 of them were verified to be significantly down-regulated in the larger sample group, among which tRF-30-3JVIJMRPFQ5D, tRF-16-R29P4PE, tRF-21-NB8PLML3E, and tRF-21-SWRYVMMV0 had areas under the curve to diagnose concentric hypertrophy. The 4 down-regulated tsRNAs were negatively correlated with left ventricular posterior wall dimensions in PCH patients (r=-0.4227; r=-0.4517; r=-0.5567; r=-0.4223). The levels of ANP and BNP as well as cell size were decreased in Ang II-stimulated H9c2 cells with 21-NB8PLML3E mimic transfection. Bioinformatics analysis revealed that the target genes of tRF-21-NB8PLML3E were mainly enriched in the metabolic pathway and involved in the regulation of ribosomes. Conclusion: The plasma tsRNAs tRF-21-NB8PLML3E might be considered biomarkers in patients with PCH with early screening potential.

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

In the rapidly evolving landscape of genetic engineering, the advent of CRISPR-Cas technologies has catalyzed a paradigm shift, empowering scientists to manipulate the genetic code with unprece-dented accuracy and efficiency. Despite the remarkable capabilities inherent to CRISPR-Cas sys-tems, recent advancements have witnessed the integration of small molecule to augment their functionality, introducing new dimensions to the precision and versatility of gene editing applica-tions. This review delves into the synergy between CRISPR-Cas technologies and small molecule drugs, elucidating the pivotal role of chemicals in optimizing target specificity and editing efficiency. By examining a diverse array of applications, ranging from therapeutic interventions to agricultural advancements, we explore how the judicious use of chemicals enhances the precision of CRISPR-Cas-mediated genetic modifications. In this review we emphasize the significance of small molecule drugs in fine-tuning the CRISPR-Cas machinery, which allows researchers to exert meticulous con-trol over the editing process. We delve into the mechanisms through which these chemicals bolster target specificity, mitigate off-target effects, and contribute to the overall refinement of gene edit-ing outcomes. Additionally, we discuss the potential of chemical integration in expanding the scope of CRISPR-Cas technologies, enabling tailored solutions for diverse genetic manipulation challenges. As CRISPR-Cas technologies continue to evolve, the integration of small molecule drugs emerges as a crucial avenue for advancing the precision and applicability of gene editing techniques. This re-view not only synthesizes current knowledge but also highlights future prospects, paving the way for a deeper understanding of the synergistic interplay between CRISPR-Cas systems and chemical modulators in the pursuit of more controlled and efficient genetic modifications.

Small peptides (SPs), ranging from 5 to 100 amino acids, play integral roles in plants due to their diverse functions. Despite their low abundance and small molecular weight, SPs intricately regulate critical aspects of plant life, including cell division, growth, differentiation, flowering, fruiting, maturation, and stress responses. As vital mediators of intercellular signaling, SPs have garnered significant attention in plant biology research. This comprehensive review delves into SPs' structure, classification, and identification, providing a detailed understanding of their significance. Additionally, we summarize recent findings on the biological functions and signaling pathways of prominent SPs that regulate plant growth and development. The review also offers a forward-looking perspective on future research directions in peptide signaling pathways.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

In recent years, the interest in the well-being of companion animals has grown more and more. After discovering the central role of the intestinal microbiota, various nutritional strategies (prebiotics, probiotics and postbiotics) have been evaluated to modulate its composition. However, to date, there are still few studies that analyze the effects of a specific probiotic and even fewer are the studies that evaluate how this strain can have different effects depending on the breed and size of the animal. In this study was investigated the effect of a specific probiotic strain, Limosilactobacillus reuteri NBF 1 DSM 32203, on the fecal parameters and intestinal microbiota of healthy small-sized adult dogs, specifically Chihuahuas and Dachshunds. The results obtained have highlighted how this probiotic is able to improve fecal parameters, reducing fecal humidity with the formation of more compact feces, significantly improving the fecal score. Furthermore, L. reuteri NBF 1 DSM 32203 is able to modulate the microbiota of Chihuahuas and Dachshunds by increasing the number of beneficial bacterial species such as lactobacilli and decreasing that of potentially pathogenic ones such as coliforms.

According to EuroStat data recorded landings of fisheries products from European waters were estimated at about 6 million tons in 2001, down to 3.2 million tons in 2022. Gradual decline slowed after the entering into force of the reform of the European Common Fisheries Policy (CFP) end 2013, but was followed by a steeper decline after 2018 (1). This casts some doubt on claims that the resources are nowadays better managed, even if a warming ocean provokes measurable poleward migration of species. Within this general picture, the broad-brush landscape is influenced by policy applications more in favour of industrial exploitations and regulatory and market environments making it very hard for many small-scale fishers (SSF) to remain in business, let alone attract younger successors for generational transition. In crowded marine spaces it is a challenge to allocate access rights fairly between fisheries, exclusion zones for resource and habitat protection and much needed ecosystem recovery (2), platforms for fossil exploitation, wind farms, underwater cables and recreational uses. Two examples of local initiatives with recovery potential in the Mediterranean are briefly presented. They are spearheaded by artisanal fishers, who seek to restore spawning grounds and other coastal habitats as a way to procure enough fish and other complementary activities to secure their livelihoods in the future and supported by local scientists and nature conservation organisations. While promising, this is still rather the exception. Here it is argued that trust-building between artisanal fishers, conservationists and scientists, and greater systemic support to SSF by governments increase chances for the urgently needed structural shifts that can reverse the on-going decline in biodiversity and ocean productivity which all aspire to.

This study presents a detailed investigation of the application of superquadrics in small-angle scattering (SAS), a technique essential in materials science, biology, and physics for investigating structural properties at the nanoscale and microscale. Superquadrics, a family of geometric shapes known for their versatility in representing a wide range of forms, are employed to model complex structures in SAS studies. We examine the parametric nature of superquadrics and their ability to efficiently describe shapes from simple balls to intricate star-like forms. We demonstrate the application of superquadrics through a rigorous analysis of SAS simulated data, including scattering intensity patterns and pair-distance distribution functions. This allows us to reveal insights into key structural characteristics of various materials, such as the size and shape. We also demonstrate the efficacy of superquadrics in accurately modeling experimental small-angle X-ray scattering data from a chimeric protein complex, showcasing their potential in biological systems analysis. The findings offer a robust framework for future research and application in diverse fields, including materials science, nanotechnology, and bioengineering.

The current trend in supply chain development requires the application of new knowledge to meet the challenges posed by new technologies. One such technology is blockchain, which facilitates supply chain solutions through the use of innovative data transfer, storage and verification systems. However, the use of blockchain can be challenging for certain stakeholders, such as small carriers, who may lack the necessary technical expertise or access to the technology. In this paper, we explore the potential for engaging small carriers that provide services within the blockchain supply chain but face technological barriers. We identify the barriers and opportunities for these carriers to participate, focusing on a case study of a small carrier that transports temperature-sensitive cargo. In addition, we introduce in-vehicle temperature measurement for use in cold chains and propose an ecosystem that can benefit different stakeholder groups.

Self-selecting the intensity of aerobic training is a perspective that allows practitioners to develop autonomy (choice of pace), improve physical fitness and achieve weight loss. To compare the effect of four aerobic training protocols on cardiometabolic and psycho-affective responses in physically inactive adult men and women. The sample consisted of 11 individuals aged 56 ± 10 years and BMI 29.2 ± 2.4 kg/m2 performed four different treadmill aerobic training protocols, including: 1-individual with self-selected intensity (ISS), 2-individual with prescribed intensity (IPI) (64-76% of HR max), 3-small group with self-select. selected intensity (SGS) and 4-small group prescribed intensity (SGP) (64-76% of HR max). Heart rate (HR), lactate (LACT), perceived exertion (RPE), affective response (FS), activation scale (FAS), enjoyment (PACES) and intention to repeat the session (INT) were analyzed. Statistical analysis used ANOVA with Tukey's post hoc test (p&lt;0.05). HR, LACT and RPE analyzes did not show significant differences between protocols. The FS showed a smaller decline in the SI protocol (p&lt;0.05), and the intention to repeat the training session was greater in the SI protocol (p&lt;0.05). Conclusion: The data allow us to conclude that the SI training protocol produced superior results in affective response, pleasure and intention to repeat the session.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, in culture, in infected mammalian cells and in patients. Among these noncoding RNAs are both small RNAs (sRNAs) between 50-350 nts in length and smaller RNAs (sncRNA) <50 nts. In this review, we provide an up-to-date synopsis of the identification, designation, and function of these Mtb-encoded sRNAs and sncRNAs. The methodological advances including RNA sequencing strategies, small RNA antagonists and locked nucleic acid sequence specific RNA probes advancing the studies on these small RNA are described. Initial insights into the regulation of the small RNA expression and putative processing enzymes required for their synthesis and function are discussed. There are many open questions remaining about the biological and pathogenic roles of these small non-coding RNAs, and potential research directions needed to define the role of these mycobacterial noncoding RNAs summarized.

The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.

The advent of RNA-sequencing (RNA-Seq) technologies has markedly improved our knowledge and expanded the compendium of small non-coding RNAs, most of which derive from the processing of longer RNA precursors. In this review article, we will discuss about the biogenesis and function of small non-coding RNAs derived from eukaryotic ribosomal RNA (rRNA), called rRNA fragments (rRFs), and their potential role(s) as regulator of gene expression. This relatively new class of ncRNAs remained poorly investigated and underappreciated until recently, due mainly to the a priori exclusion of rRNA sequences—because of their overabundance—from RNA-Seq datasets. The situation surrounding rRFs resembles that of microRNAs (miRNAs), which used to be readily discarded from further analyses, for more than five decades, because we could not believe that RNA of such a short length could bear biological significance. As if we had not yet learned our lesson not to restrain our investigative, scientific mind from challenging widely accepted beliefs or dogmas, and from looking for the hidden treasures in the most unexpected places.

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide and is responsible for numerous deaths. 5-fluorouracil (5-FU) is an effective chemotherapy drug commonly used in the treatment of CRC, either as monotherapy or in combination with other drugs. However, half of CRC cases are resistant to 5-FU-based therapies. To contribute to the understanding the mechanisms underlying CRC resistance or recurrence after 5-FU-based therapies, we performed a comprehensive study integrating in silico, in vitro and in vivo approaches. We identified differentially expressed genes and enrichment of pathways associated with recurrence after 5-FU-based therapies. Using these bioinformatic data as a starting point, we selected a group of drugs that restored 5-FU sensitivity to 5-FU resistant cells. Interestingly, treatment with the novel Rac1 inhibitor, 1A-116, reversed morphological changes associated with 5-FU resistance back to a control-like status. Moreover, our in vivo studies have shown that 1A-116 affected tumor growth and the development of metastasis. All our data allowed us to postulate that targeting Rac1 represents a promising avenue for the development of new therapies for patients with CRC resistant to 5-FU-based therapies.

In recent decades, there has been a startling rise in the number of cancer patients worldwide, which has led to an amazing upsurge in the development of novel anticancer treatment candidates. On a positive note, arylpiperazines have garnered attention in cancer research due to their potential as scaffolds for developing anticancer agents. These compounds exhibit a diverse array of biological activities, including cytotoxic effects against cancer cells. Indeed, one of the key advantages of aryl piperazines lies in their ability to interact with various molecular targets implicated in cancer pathogenesis. Here, we focus on the chemical structures of several arylpiperazine derivatives, highlighting their anti-proliferative activity in different tumor cell lines. The modular structure, diverse biological activities, and potential for combination therapies of arylpiperazine com-pounds make them valuable candidates for further preclinical and clinical investigations in the fight against cancer. This review, providing a careful analysis of different arylpiperazine deriva-tives and their biological applications, allows researchers to refine the chemical structures to improve potency, selectivity, and pharmacokinetic properties, thus advancing their therapeutic potential in oncology.

Blockchain technology (BCT) has the potential for sustainable development, enhancing business efficiency, reducing costs, and strengthening data security. Despite its potential, adoption among small and medium-sized enterprises (SMEs) is low due to the need for significant changes in technology infrastructure and the challenge of interoperability. A cross-sectional survey was done with 226 Hong Kong SMEs. The PLS-SEM results highlighted favorable transformation conditions as the most critical factor for SMEs considering the adoption of BCT. These conditions address both internal and external readiness for adopting the disruptive strategy. Other contributing factors to BCT adoption include trust in BCT developers, perceived usefulness and ease of use, government support, and perceived security. The research results contributed to the literature on disruptive technology acceptance, adoption, transformation conditions, technology readiness, and SMEs’ technology adoption. Government-supported policies and initiatives can promote BCT adoption, including educational programs, case studies, and resources for readiness. Financial support and regulatory frameworks can further encourage adoption. BCT developers can demonstrate the value of their systems, effectively communicate potential ROI and cost savings, and provide user-friendly interfaces to increase SMEs’ intention to adopt BCT.

Plant diseases and pests reduce crop yields, accounting for global crop losses of 30% to 50%. In conventional agricultural production systems, these losses are typically controlled by applying chemical pesticides. However, public pressure is mounting to curtail agrochemical use. In this context, employing beneficial endophytic microorganisms is an increasingly attractive alternative to the use of conventional chemical pesticides in agriculture. A multitude of fungal endophytes are naturally present in plants, producing enzymes, small peptides and secondary metabolites due to their bioactivity, can protect hosts from pathogens, pests and abiotic stresses. The use of beneficial endophytic microorganisms in agriculture is an increasingly attractive alternative to conventional pesticides. The aim of this study was to characterize fungal endophytes isolated from apparently healthy, feral wine grapes in eastern Canada that have grown without agrochemical inputs for decades. Host plants ranged from unknown seedlings to long-lost cultivars not widely propagated since the 1800s. HPLC-MS was used to identify unique endophyte-derived chemical compounds in the host plants, while dual-culture competition assays showed a range in endophytes’ ability to suppress the mycelial growth of Botrytis, which is typically controlled in viticulture with pesticides. Twelve of the most promising fungal endophytes isolated were identified using multilocus sequencing and morphology, while DNA barcoding was employed to identify some of their host vines. These fungal endophyte isolates, which consisted of both known and putative novel strains, belonged to seven genera in six families and five orders of Ascomycota. Exploring the fungal endophytes in these specimens may yield clues to the vines’ survival and lead to the discovery of novel biocontrol agents.

Small bowel non-Meckelian diverticulosis is a rare condition with only few published cases despite being described over 200 years ago. In the midst of the COVID-19 pandemic, studies suggested that a lot of patients may experience gastrointestinal manifestations. Intestinal symptoms could worsen the inflammation and infection associated with small bowel diverticulitis. Here, we present two cases: one with inflammation and rupture in a COVID-19 patient and the other as an asymptomatic detection. Furthermore, we provide a mini-review of the literature to emphasize the importance of considering this entity in the differential diagnosis of an acute abdomen.

We previously showed that feeding mice a diet containing 1% mantle tissue decreased food consumption, leading to death. We also isolated and identified toxic substances in the mantle tissue. In the present study, we investigated the characteristics and stability of mantle tissue toxicity. Treatment of mantle tissue with 1 mM HCl, 1 mM NaOH, 1 mM dithiothreitol, and 1 mM H2O2 and heating did not reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Diets containing 1% and 20% mantle extract showed similar levels of toxicity, demonstrating that feeding of mantle tissue does not lead to acute toxicity. Finally, we examined the toxicity of the mantle tissue against small intestinal tissue. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time PCR analysis showed that mantle tissue feeding caused changes of inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that feeding of mantle tissue causes toxicity after causing initial damage to the small intestinal tissue.

To verify the reliability of the proposed stitching linear scan method for roundness measurement of small cylindrical workpieces, measurement uncertainties of the workpieces with various dimension are conducted. The cross-sectional circle of a cylindrical workpiece is divided into several equal arcs to be measured. Thus, the arc profile can be characterized according to the measured arcs. The roundness profile of the cylindrical part can be obtained by stitching these arc profiles together. Firstly, the measurement uncertainty of the workpiece with a diameter 1.5 mm and length 5.8 mm is evaluated to be 0.095 μm which can meet the uncertainty target of 0.1 μm. Considering the uncertainty of θx and θz which are the alignment around X-axis and Z-axis respectively changing with workpiece dimension changing, relevant uncertainties are carried out. As a result, there is no limitation with respect to workpiece diameter theoretically If the alignment can reach θz = θx = ±0.1° without considering the measurable range of the machine.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

Small-scale fishers are considered as one of the most vulnerable communities in Bangladesh but very few studies focused on the livelihood sustainability and vulnerabilities of this professional group. A fieldwork in lower Padma and upper Meghna hilsa sanctuaries identifies different livelihood characters and associated vulnerabilities of the fishers. A conceptual framework known as Sustainable Livelihood Approaches (SLA) has been introduced to analyses the qualitative and quantitative data. The insights of the livelihood strategies provide on small-scale fishers and fisheries management have been explained and explored. Fishers are found solely dependent on fishing, economically insolvent and neglected. In addition, some socio-economic abstractions such as low income, credit insolvency, lack of substitute earning flexibility make them more vulnerable. A number of effective suggestions are elicited from fishers’ perceptions, the implementation of which is crucial to ensure livelihood sustainability of the small-scale fishers.

Alfalfa, an important legume forage, is an ideal crop for sustainable agriculture and a potential bioenergy plant. Drought, one of the most common environmental stresses, substantially affects plants’ growth, development and productivity. MicroRNAs (miRNAs) are newly discovered gene expression regulators that have been linked to several plant stress responses. To elucidate the role of miRNAs in drought stress regulation of alfalfa, a high-throughput sequencing approach was used to analyze 12 small RNA libraries comprising of 4 samples, each with 3 biological replicates. We identified 348 known miRNAs, belonging to 80 miRNA families, from the 12 libraries and 281 novel miRNAs using Mireap software. 18 known miRNAs in roots and 12 known miRNAs in leaves were screened out as drought-responsive miRNAs. Except for miR319d and miR157a which were upregulated under drought stress, the expression pattern of drought-responsive miRNAs were different between roots and leaves in alfalfa. This is the first study discovering miR157a, miR1507, miR3512, miR3630, miR5213, miR5294, miR5368 and miR6173 are drought-responsive miRNAs. Target transcripts of drought-responsive miRNAs were computationally predicted. All 447 target genes for the known miRNAs were predicted using an online tool. This study provides a significant insight on understanding drought-responsive mechanisms of alfalfa.

In the past decade, RNA fragments derived from full length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions, and are able to fill the role of tumor-suppressor or tumor-promoter in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Lactate plays a critical role in cell metabolism and disease development. Under conditions of hypoxia or high-intensity exercise, cells use the glycolytic pathway to convert glucose into pyruvate, which is then reduced to lactate to quickly obtain energy. The traditional role of lactate is being redefined, as it is not only a provider of energy but also an important signaling molecule that regulates cell physiological functions, including histone lactylation modification, which affects gene expression. However, excessive accumulation of lactate is associated with the development of various diseases, such as liver disease, cancer, and cardiovascular disease. Research has also found that small-molecule drugs can regulate lactate levels, providing new possibilities for treating related diseases.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predo-minantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly pa-tients, particularly those aged 65 and above, remain underexplored due to their underrepresenta-tion in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients recei-ving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3%, 54.1%, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusion: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Detecting small objects in images poses significant challenges due to their limited pixel representation and the difficulty in extracting sufficient features, often leading to missed or false detections. To address these challenges and enhance detection accuracy, this paper presents an improved small object detection algorithm, CRL-YOLOv5. The proposed approach integrates the CBAM attention mechanism into the C3 module of the backbone network, which enhances the localization accuracy of small objects. Additionally, the Receptive Field Block (RFB) module is introduced to expand the model's receptive field, thereby fully leveraging contextual information. Furthermore, the network architecture is restructured to include an additional detection layer specifically for small objects, allowing for deeper feature extraction from shallow layers. When tested on the VisDrone2019 small object dataset, CRL-YOLOv5 achieved an mAP50 of 39.2%, representing a 5.4% improvement over the original YOLOv5, effectively boosting the detection precision for small objects in images.

Chip pad alignment inspection is of great importance in the industrial field. However, due to the fact that chip pads are usually small, problems such as misdetection and missed detection often occur. When applying deep learning methods for chip pad detection, it is necessary to ensure accurate detection of small target chips while meeting the requirements of lightweight detection models for industrial needs. To solve the above problems, this paper proposes a lightweight model based on improved YOLOv5s. Firstly, the feature extraction part is improved to increase the network's focus on the target. Secondly, the feature fusion layer is improved to double the resolution of the prediction head, and the context-aware network is designed to enhance the context-capture ability of key features of small targets. Finally, SIoU is adopted as the loss function to improve the speed and accuracy of the regression frame. The experimental results show that the improved YOLOv5s algorithm improves the detection accuracy by 2.3% and reduces the network parameters by 81.8% compared to the original algorithm. The improved algorithm is combined with image processing techniques to design correction methods for alignment anomalies and realize real-time alignment anomaly correction in industry.

A 58 year old female presented with abdominal pain, vomiting and constipation. Laboratory tests indicated elevated white blood cell count and C-reactive protein levels. Imaging via CT scan revealed a large cystic mass in the right ovary, abscesses and generalized small bowel distension, which initially led to a diagnosis of ovarian cancer with peritoneal carcinomatosis. Despite conservative management, the patient’s condition did not improve, prompting a laparotomy. Intraoperative findings included generalized peritonitis, significant small bowel dilation due to inflammatory adhesions and a perforated dermoid ovarian cyst. The cyst was resected and a prophylactic ileostomy was installed. Histopathological examination confirmed the diagnosis of a benign dermoid ovarian cyst. This case illustrates the rare presentation of a perforated dermoid cyst mimicking peritoneal carcinomatosis and emphasizes the importance of considering such complications in the differential diagnosis of bowel obstruction and peritoneal disease. Early recognition and appropriate surgical intervention are crucial for optimal outcomes.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Peste des Petits Ruminants (PPR) is one of the major transboundary animal diseases that severely impact livestock production and trade worldwide. An investigation was carried into the seroprevalence and risk factors of PPR in small ruminants, camels, and wild ruminants in Bahrain. A total of 1240 serum samples were collected from 119 sheep flocks and 1224 serum samples from 125 goat herds. In addition, 100 sera from camels and 38 sera from wild ruminants, were collected. Serum samples were tested for the presence of PPR specific antibodies using a competitive ELISA. Flock management and health information of the flocks and herds were collected using a semi-structured questionnaire. The individual prevalence of PPR in sheep and goats was 26% and 25.5%, respectively. The flock or herd level prevalence of PPR was 22.7% and 29.6% in sheep and goats, respectively. None of the tested camels or wild ruminants were positive for PPR-specific antibodies. Sheep and goats from the Northern governorate were more likely to be seropositive to PPR than in other governorates. On the individual animal level, the univariate analysis suggested; age (&lt;12 months), sex (male), and health status (weak animals) as risk factors for PPR seropositivity. On the flock/herd level, the multivariable logistic regression analysis identified large flock/herd size and semi-intensive farming as risk factors for PPR seropositivity.

We present the first evidence of lethal interspecific aggressive behavior against Burmeister’s porpoise Phocoena spinipinnis, in a non-predatory context, and the first indications of such behavior in a cetacean from Chilean waters. Two cases, both adult males, are described. Analysis of the fresh tooth rakes, specifically the inter-rake distance, points to common bottlenose dolphin Tursiops truncatus as aggressor. Interdental distances measured on skulls allowed us to exclude Orcinus orca, Globicephala melas, Lagenorhynchus obscurus and Pseudorca crassidens. Evidence of severe blunt trauma, including extensive subdermal hematomas, rupture of pleura and extrusion of lung parenchyma, underscores the level of violent aggression. The reason is unknown but Tursiops truncatus is well-documented to occasionally harass and kill harbour porpoises Phocoena phocoena in the Northern Hemisphere. Considering the scarce information available on the biology and behavioral ecology of Burmeister’s porpoises in Chile and elsewhere, we recommend more systematic field research. Also, as to help formulate effective management measures that can mitigate the main threat for this species in Chile (as in Peru), i.e. fisheries interactions. In Chile, P. spinipinnis is classified as Data Deficient (D.S. N°06-2017), so its real conservation status is unknown.

Micro and small wood-processing enterprises represent the heart of the European forest-based industries, being among the key drivers of economic growth in rural, mountainous, and poor regions. Their economic efficiency is of fundamental importance for their existence and the pro-vision of income for the local population in rural areas. Data Envelopment Analysis (DEA) is nonparametric, linear-programming-based approach, commonly used to analyse the efficiency of organizational units. This method allows estimating the economic efficiency of a certain eco-nomic system without assumptions about the functional form between resources and products. Furthermore, DEA determines the efficiency frontier and gives results of whether an enterprise, i.e., a Decision Making Unit (DMU) is efficient or not. The main objective of this study was to investigate and evaluate the economic efficiency of micro and small wood-processing enterpris-es in the EU countries and reveal the hidden inputs that facilitate efficiency generation. The eco-nomic efficiency evaluation was carried out on the basis of the official statistical data for the mi-cro and small wood-processing companies in the EU member states for the period 2015-2020 by performing a two-stage DEA analysis. The data used were standardized by value per employee. In addition to the first stage of DEA, fractional regression probit and logit models with four contextual variables were used to reveal the influence of the hidden inputs in the model. The results showed that the micro and small wood-processing enterprises can be regarded as more scale-efficient than technically-efficient entities. The only contextual variable affecting the eco-nomic efficiency was Investments per Person Employed, improving the efficiency by 2% per 1% increase of the investments.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

Recent advances in embedded antenna and sensor technologies for 5G communications have galvanized a response toward the investigation of their electromagnetic (EM) performance for urban context and civil engineering applications. This article quantitatively investigates the effects of material loading on an evolved antecedent-based design of a hexagonal-stubbed Complementary Split-Ring Resonator (CSRR)-loaded antenna through simulation and experimentation. The optimized antenna design is first conceptualized within a simulation environment to achieve EM resonance at 3.50 GHz before delving into the analysis of operational performance characteristics. As a proof-of-concept, a physical antenna prototype is fabricated on a printed circuit board for the in-situ evaluation of S11 parameter plot. Subsequently, a simulation-based parametric study is conducted on antenna prototypes embedded into Ordinary Portland Cement pastes with varying weight percentages of iron(III) oxide. Simulation-derived and experimental results are mutually verified, achieving a systemic downward shift in resonant frequency and corresponding variations in impedance matching induced by changes in the loading reactance. Finally, an inversion modeling procedure is employed using perturbation theory to extrapolate the relative permittivity of the dielectric embedding materials. Our proposed analysis contributes to optimizing concrete-embedded 5G antenna sensor designs and establishes a foundational framework for estimating unknown EM parameters of cement-based composites.

Background: Lipid disorders are one of risk factors for cardiovascular diseases. The aim of the study was to determine the lipid profile in early childhood in the group of Polish children born small for gestational age (SGA). Materials and Methods: The study included 140 children (93 SGA and 47 controls) aged 5 to 11 years. All children underwent a physical examination and blood tests for the glucose and lipid profile. SGA group was divided in subgroups: symmetrical and asymmetric intrauterine growth restriction (IUGR). Results: Blood sample analysis revealed higher levels of total cholesterol levels (SGA group 190.61 +/- 24.66 mg/dl vs control 143.23 +/- 23.90; p&lt;0.001). The analysis of particular fractions of cholesterol showed significantly higher mean values of triglycerides, LDL-cholesterol as well as lower mean values of HDL-cholesterol in children born as SGA. Children in both groups did not differ significantly according to weight and body mass index. A statistically significantly higher glucose concentration was obtained in the group of children with IUGR with symmetrical type of IUGR. Conclusions: Children born SGA even in their early childhood, without overweight or obesity, have abnormal lipid profile, which may be a risk factor of cardiovascular diseases in adulthood.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

The pathogenesis of Cerebral Small Vessel Disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from 3 groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

Small molecule kinase inhibitors (SMKIs) are one of the heightened concerns in the field of drug research and development. There are seventy-nine (up to July 2023) small molecule kinase inhibitors have been approved by FDA and hundreds kinase inhibitors candidates in clinical trials, which shed light on the treatment of some major diseases. As an important strategy of drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods, such as docking, molecular dynamic, pharmacophore have been applied to the design and optimization of small molecule kinase inhibitors. In the review, we provide an overview of recent advances in CADD and SMKIs; and the application of CADD for discovery of SMKIs.

Appropriate use of perioperative antimicrobials can significantly reduce the risk of postoperative infections. However, inappropriate antimicrobial use can result in the creation of multidrug resistant bacteria, increased costs, host flora disruption, side effects, and increased risk of hospital-acquired infections This survey evaluated the current perioperative use of antimicrobials in small animals by Spanish veterinarians using a web-based questionnaire. Responses were represented using descriptive statistics and a statistical analysis of the association between demographic data and perioperative antimicrobial use was performed. Preoperative antimicrobials were administered in clean surgery by up to 68.3% of participants, 81.0% in clean-contaminated surgery and 71.3% in dirty surgery, while in the postoperative period, antimicrobials were administered by up to 86.3% of participants in clean surgery, 93.2% in clean-contaminated surgery and 87.5% in dirty surgery. Factors considered “very important” for antimicrobial selection were the degree of wound contamination, patient immunosuppression, and use of prosthesis. The most frequently used antimicrobial was beta-lactamase-resistant penicillin. Postoperative antimicrobial use was associated with participants without postgraduate training. This study highlights an overuse of antimicrobials in perioperative procedures in small animal surgery in Spain. Therefore, evidence-based guidelines and further education regarding the correct use of antimicrobial prophylaxis are recommended.

Traditional camera sensors rely on human eyes for observation. However, the human eye 1 is prone to fatigue when observing targets of different sizes for a long time in complex scenes, and 2 human cognition is limited, which often leads to judgment errors and greatly reduces the efficiency. 3 Target recognition technology is an important technology to judge the target category in camera 4 sensor. In order to solve this problem, a small size target detection algorithm for special scenarios was 5 proposed by this paper. Its advantage is that this algorithm not only has higher precision for small 6 size target detection, but also can ensure that the detection accuracy of each size is not lower than the 7 existing algorithm. In this paper, a new down-sampling method was proposed, which could better 8 preserve the context feature information. The feature fusion network was improved to effectively 9 combine shallow information and deep information. A new network structure was proposed to 10 effectively improve the detection accuracy of the model. In terms of accuracy, it is better than: YOLOX, 11 YOLOXR, YOLOv3, scaled YOLOv5, YOLOv7-Tiny and YOLOv8.Three authoritative public data sets 12 were used in this experiment: a) On Visdron data sets (small size targets), DC-YOLOv8 is 2.5% more 13 accurate than YOLOv8. b) On Tinyperson data sets (minimal size targets), DC-YOLOv8 is 1% more 14 accurate than YOLOv8. c) On PASCAL VOC2007 data sets (Normal size target), DC-YOLOv8 is 0.5% 15 more accurate than YOLOv8.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

We develop the theory of Heyting small spaces and prove a new version of Esakia duality for such spaces. To do this, we notice that spectral spaces may be seen as sober small spaces with all smops compact and introduce the method of the standard spectralification. This helps to understand open continuous definable mappings between definable spaces over o-minimal structures.

The accumulation of process waste in the production line causes fluctuations, bottlenecks, and increased inventory in workstations disrupting process flow. In this paper, the aim is the use a simulated value stream mapping (SVSM) as a lean assessment tool for decision-making in the continuous improvement process to influence and provide consideration and consistency on productivity improvement in the production system. The proposed methodology applied discrete event simulation for production process operations improvement to eliminate non-value adding times and provides good quality products at the lowest cost and highest efficiency. The results are the analysis of the current state of the production system in a South African truck manufacturing industry small and medium enterprise (SMEs) as a potential solution for the production system future state. The identified non-value adding times in the 6 most critical workstations was eliminated by SVSM which resulted in a productivity improvement of 4%, most importantly bringing the productivity to 95% and total cycle time improvement to 451 for small units and 466 for large units. The results proposed combined VSM and Simulation techniques which enhance the LEAN application by DES to increase productivity and performance improvement to remain competitive in the global economy.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

Shrinking farm size and fragile farm resources pose a significant challenge to the sustainability of small-scale farms. Efficient resource utilization in small-scale farms is crucial to achieving farm sustainability through endogenous mechanisms. However, the precise mechanisms to integrate physical resources to achieve farm sustainability are not very clear yet. By capturing the interaction among farm resources as a network phenomenon, we identify the discrete resource interactions (RIs) in different types of small-scale farms of Indian Sundarbans, which are associated with higher farm sustainability. Thirty-two linkages, 11 reciprocal linkages, 22 triads, and three ‘core elements’ that occurred and cooccurred on highly sustainable farms are found to be critical in achieving farm sustainability. Using the properties of resource interaction networks as explanators of farm sustainability, we anticipate that sustainability in small-scale farms can be achieved by strategically creating new RIs on the farm. However, there may be limitations to such achievement depending on the nature of RI and type of farm. The analytical approach helps to understand the structural basis of sustainability in small-scale farms, and this approach can be used to achieve farm sustainability through the strategic integration of existing farm resources in the smallholder systems.

Although researchers have investigated widely the impact of IOD phases on human lives, only a few have examined such impacts on fisheries. In this study, we analyzed the influence of negative (positive) of IOD on a chlorophyll a (Chl-a) concentration as an indicator of phytoplankton biomass and small pelagic fish production in the eastern Indian Ocean (EIO) off Java. We also conducted field surveys in the EIO off Palabuhanratu Bay at the peak (October) and the end (December) of the 2019 positive IOD phase. Our findings show that the Chl-a concentration had a strong and robust association with the 2016 (2019) negative (positive) IOD phases. The negative (positive) anomalous Chl-a concentration in the EIO off Java associated with the negative (positive) IOD phase induced strong downwelling (upwelling), leading to the preponderant decrease (increasing) of small pelagic fish production in the EIO off Java.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for translating amino acids for protein synthesis. Their function in pathogen-derived infectious diseases has been well established, which has led to development of small molecule therapeutics. The applicability of ARS inhibitors for other human diseases such as fibrosis has recently been explored in the clinical setting. There are active studies to find small molecule therapeutics for cancers. Studies on central nervous system (CNS) disorders are burgeoning as well. In this regard, we present a concise analysis of the recent development of ARS inhibitors based on small molecules from the discovery research stage to clinical studies as well as a recent patent analysis from the medicinal chemistry point of view.

We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.

In general, remote sensing has proven to be a powerful tool in the overall understanding of natural and anthropogenic phenomena. Satellites have become useful tools for tasks such as characterization, monitoring, and the continuous prospecting of natural resources. This research aims to analyze spatial dynamic and destructive on coral reefs area and correlation between live coral reduction and population on small islands. Landsat MSS, TM, ETM, and OLI-TIRS are used to spatial analyze of coral reef dynamics from 1972 to 2016. The image processing includes gap-filling, atmospheric correction, geometric correction, image composite (true color), water column correction, unsupervised classification, reclassification, accuracy assessment. The statistical analysis identifies the relationship between dynamic population data with a reduction of live coral, namely Principal Component Analysis (PCA) and Multiple Regression Analysis. The effect of the population shows a positive correlation with the reduction in the area of live coral, although it is significant. The fact is the practice of coral destruction on an island; it is usually not only caused or carried out by residents who live on the island but also carried out by other residents of different islands.

We propose a new estimator for creating expansion factors for survey plots in the USDA Forest Inventory and Analysis program. This is a regularized version of the raking estimator widely used in sample surveys. The regularized raking method differs from other predictive modeling methods for integrating survey and ancillary data in that it produces a single set of expansion factors that can have general purpose use to produce small area estimates and wall-to-wall maps of any plot characteristic. This method also differs from other more widely used survey techniques, such of GREG estimation, in that it is guaranteed to produce positive expansion factors. We extend the previous method here to include cross-validation, and provide a comparison to expansion factors between the regularized raking and ridge GREG survey calibration.

Sustainable Development Goal (SDG) 6.2 sets an ambitious target of leaving no one without adequate sanitation by 2030. The key concern is the lack of local human and financial capital to fund the collection of reliable information to monitor progress towards the goal. As a result, national and local records may be telling a different story of the proportion of safely managed sanitation that counts towards achieving the SDGs. This paper unveils such inconsistency in sanitation data generated by urban authorities and proposes a simple approach for collecting reliable and verifiable information on access to safely managed sanitation. The paper is based on a study conducted in Babati Town Council in Tanzania. Using a smartphone-based survey tool, city health officers were trained to map 17,383 housing units in the town. A housing unit may comprise of two or more households. The findings show that 5% practice open defecation, while 82% of the housing units have some forms of sanitation. Despite the extensive coverage, only 31% of the faecal sludge generated is safely contained, while 64% is not. This study demonstrates the possibility of using simple survey tools to collect reliable data for monitoring progress towards safely managed sanitation in the towns of global south.

Simple Summary: This review explores the origin of Leukemic Stem-Like Cells (LSLCs) from (Very) Small Leukemic Stem-Like Cells ((V)SLSLCs) and Cancer Stem Cells (CSCs) from trans-formed Very Small Embryonic-Like Stem Cells (VSELSCs). Understanding this relation is a step toward uncovering the mechanisms behind cancer and leukemia initiation and development. We explore how these very small precursor cell stages might contribute to the initiation and progres-sion of cancer as well as leukemia with a focus on Acute Myeloid Leukemia (AML) as a model. Abstract: Recent experimental findings indicate that CSCs originate from transformed VSELSCs, which are early precursor stages of healthy stem cells. This discovery marks a crucial step in understanding the mechanisms that drive cancer development and initiation. Our team's follow-up studies on leukemia, lung cancer, and healthy embryonic kidney cells have, for the first time, identified stag-es resembling very small precursor stem cells in continuously growing cell lines. These findings suggest the existence of (Very) Small Cancer Stem Cells ((V)SCSCs) or (V)SLSCs within respective subpopulations of CSCs and LSCs in vivo. In this review, we explore theoretical examples of how leukemia progresses through various stages, highlighting the role of these very small precursor cells as fundament primitive stages. We also discuss the potential implications of further research into these unique cellular stages for advancing cancer and leukemia treatment and prevention strategies.

Nursing, a profession known for its compassion and dedication to providing exceptional patient care, relies heavily on the cultivation of caring attributes to uphold the highest standards of practice. Despite the common use of small group work in nursing education, there is a gap in understanding how these caring attributes are developed through this approach. This qualitative study sought to explore the emergence of caring attributes in small group settings as perceived by nursing students and educators. Thirteen nursing students and ten educators participated in semi-structured group interviews at a professional educational institution. The study identified four key sets of caring attributes nurtured through small group work: interpersonal communication with respect, compassion, and empathy; competence and confidence; and accountability to commitment. These findings underscore the essential role of caring in nursing, emphasizing how collaborative group work can facilitate the development of crucial attributes through interpersonal interactions. The cultivation of respectful communication skills among students is highlighted as pivotal for enhancing interactions with healthcare professionals, patients, and families, ultimately improving the quality of care provided. By providing opportunities for interactive learning and ongoing practice, students can effectively embody these caring attributes, fostering their nursing professionalism throughout their careers.

Background: Extensive-stage SCLC (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to 21-question web-based survey about the ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses, the majority were radiation oncologists (89%) with more than 10 years of experience (51%). Preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy before starting immunotherapy (37%), with three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in case of both intrathoracic and extrathoracic response with a RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients.

Gastrointestinal parasites (GIP) are diverse parasitic organisms known to have coevolved with bacterial populations inside the gut of mammalian hosts. These helminths produce small molecules, peptides and proteins to evade or fight their hosts' immune systems. Small molecules include polar compounds, amino acids, lipids and carbohydrates. Metabolomics is an emerging field of research recently applied to study helminth infections and host-parasite interactions. This review comprehensively discusses metabolomics studies of small molecules of GIP in animals, providing insights into the available tools and techniques, databases, and analytical software. Most metabolomics investigations employed LC-MS, MS or MS/MS, NMR, or a combination thereof. Recent advancements in metabolomics platforms, including artificial intelligence (AI)-assisted software tools and databases, have propelled helminth metabolomics forward, offering new avenues to explore host-parasite interactions, immunomodulation, and the intricacies of parasitism. As our understanding of helminth metabolomics continues to expand, it promises to unveil novel perspectives and enrich the knowledge of these complex host-parasite relationships.

The paper considers the possibility of rotating a small moon by 180 degrees from a dynamic point of view using two rocket engines mounted on the surface of the moon. A thrust control law for the engines which allows to turn the moon over and then stabilize it relative to a new equilibrium position by parrying a gravity gradient torque is proposed. The dynamic aspects of such an experiment are discussed using the example of the Mars satellite Deimos.

Small scale carp polyculture plays a key role for food supply in Bangladesh, however, factors including water pollution, limited infrastructure and inadequate disease management hinder its sustainability. This paper reports on a survey of 231 farmers across the 6 major carp producing regions in Bangladesh, analyzing factors including, farmers’ social aspects, farm characteristics, information on disease and approaches adopted to combat them, and biosecurity practices. Almost half (46.8%) of the farms surveyed experienced disease in carp species, with clear regional variations. Eighty four percent of farms reported carp mortalities during disease outbreak, with an average mortality level 10.23±11.81%. Clinical signs during outbreaks lasted between a week and a month, and there was a peak in disease outbreaks in two seasonal periods between June to July and October to December. Disease incidence was related to a range of factors including the farmer experience, ponds/farm type, stocked species, and biosecurity practice. A combination of disinfecting measures during pond preparation and measures during stocking, including discarding fingerling transport water off-farm, fingerling disinfection and check the health of fingerlings before stocking significantly reduced disease occurrence. Treatments involving the antibiotics, ciprofloxacin, erythromycin, and azithromycin were reported as ineffective, raising concerns about non-prudent use, inadequate dosing (perhaps without appropriate veterinary guidance) and the potential for further driving antimicrobial resistance in the environment. The research unveils a concerning pattern of disease high disease incidence across small-scale carp farms in Bangladesh and the significant potential for disease spread highlights the need for responsible disposal practices. The study emphasizes the need for improving training and awareness programs are vital for addressing biosecurity and disease management challenges, ensuring sustainable aquaculture and community well-being.

Entrepreneurial activities in economic and social domains are considered one of the conditional pillars for successful transformation of resource-rich countries to sustainable, knowledge-based and diversified economies. However, there is no, and cannot be, a single recipe for such a transformation as every country or region needs to develop its own strategy, policy toolbox and implementation plan depending on its historical and present socio-economic make up and trajectory. This paper advances the qualitative findings of a previously published work to delve deeper into the complexities of entrepreneurship within resource-based economies, with a particular focus on Qatar. Employing a mixed methodology that blends explanatory and quantitative analysis, this paper aims to validate and refine the entrepreneurship framework proposed previously, ensuring its relevance and adaptability to Qatar's unique economic and cultural context, and its extendibility to similar resource-rich country settings. It systematically focuses on discovering various social, economic, and environmental dimensions critical to fostering entrepreneurship in resource-rich countries. These include examining government policies, cultural and social factors, financial support mechanisms, innovation ecosystem, technology adaptation, and digitization. A primary component of this study is the methodological approach, which includes collecting and analyzing quantitative data through a survey developed based on previous findings on qualitative explorations. This approach allows for an objective assessment of the effectiveness of the proposed recommendations. The paper presents a set of detailed recommendations aimed at various stakeholders, including government bodies, supporting agencies, and entrepreneurs themselves. These recommendations encompass integrating entrepreneurship education into academic curricula, increasing easy access to business and market information, simplifying, unifying and streamlining policies and procedures, and adapting them into the legal system. Other important and unique recommendations include establishing a country-wide entrepreneurship free-zone (Ent-Q) and facilitating its operations though an online digital platform (Ryadah), allocating certain percentage of governmental ministries’, agencies’ as well as large corporations’ budgets into innovative small business development programs and preferred purchasing from small business. These initiatives are validated to become effective tools and avenues to create a conducive entrepreneurial environment, facilitating transformation into a diversified, knowledge-based and sustainable economy. The expected outcomes of implementing these recommendations include an increase in the efficiency of entrepreneurship-related policymaking, a rise in the number, quality and impact of entrepreneurs, and the sustained diversification of the economy into non-oil/gas sectors and actors. In conclusion, this paper provides a comprehensive set of strategies and recommendations expected to significantly contribute to the nurturing and growth of entrepreneurship in resource-based economies.

The application of bacterial metagenomic analysis as biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and Controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed with QIIME2 pipeline. We applied logistic regression for adjusting differences attributable to sex, age and body mass index and compared diagnostic accuracy of our gut signatures with other previously published. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44) and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminoccocaeae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1) were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application to our population of two other published panels. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

Despite UAV multi-target detection exhibits considerable developmental potential worldwide, it suffers distinct challenges compared with traditional tasks in this field. These challenges include insufficient feature extraction capabilities for small targets, limited capabilities for multi-dimensional feature fusion, as well as constraints on hardware computation parameters. Especially in mission scenarios such as disaster detection, these challenges will be further amplified. Consequently, this paper introduces SSE-YOLO, an innovative YOLO framework algorithm specially designed to address these challenges. To enhance the model's feature extraction capability, we employ the SPDConv module to replace the original Conv in the backbone section, utilizing depth-separable convolution instead of traditional convolution pooling. Concurrently, we eliminate the SPPF module at the bottom and address a new Separate Kernel Attention Pyramid Pooling (SKAPP) module, substantially enhancing the feature fusion capability at the model's core. Moreover, to address the challenge of multi-dimensional feature fusion, we replace the Concat module of the neck and head with E-BiFPN, transmitting feature information from the backbone to the lower network through four CBS blocks, which effectively resolves the issue of lost contextual information in the model. Meanwhile, SSE-YOLO undergoes ablation experiments on the VisDrone2019 dataset to evaluate its effectiveness against alternative methods, and experimental results illustrate the model's exceptional precision in detecting UAV targets. In comparison to models with comparable experimental accuracy, SSE-YOLO requires remarkably fewer parameters. On the VisDrone2019-DET-test-dev dataset, SSE-YOLO enhances mAP by 17.3%, with a 42.5% reduction in the parameter amounts. Therefore, the proposed method effectively tackles the challenge of reconciling low parameters and high accuracy, presenting a novel pathway for deep learning-based UAV multi-target detection.

We investigated by Real-time PCR and end point PCR the presence of 10 potential zoonotic viruses in 91 small mammals sold as pets in pet shops of Southern Italy. The animals were analysed for: aichivirus, sapovirus, astrovirus, hepatitis A virus, noroviruses (GI and GII), rotavirus, circovirus, coronaviruses. Among the 9 species of small mammals analysed (golden hamsters, Java squirrels, mongolian gerbils, peruvian guinea pigs, pet mice, pet rats, dwarf rabbits, african hedgehogs and sugar gliders) 12 pet rats, 11 pet mice and 1 golden hamster tested positive to a PCR amplifying a conserved gene (RdRp) of coronavirus. However further characterizaton by sequencing gave not conclusive results. A pet rat resulted instead positive to aichivirus and its sequence showed similarity with a murine kobuvirus-1 strain identified in China. To our knowledge, this is the first study reporting the detection of aichivirus in rodents in Italy, the virus probably introduced through the importation of animals from Asia. Since living in close contact to humans, expecially with children, the continuous monitoring of the small mammals is very important to avoid the spread of new pathologies among animals and humans and further investigation is desirable in order to safeguard public health.

In Bangladesh, family businesses play a significant role in the country's business landscape because so few private companies are set up as large-scale, non-family ownership firms. Thus, it is vital to comprehend family businesses in order to comprehend Bangladeshi company dynamics. In this paper, authors attempted to survey the existing research in the area of family business in Bangladesh. It was found that the area as a research is totally an open field and a lot of new research can be done in the said area. Although a good number of studies can be classified as focused on the SME (small and medium enterprise) domain, a major shortcoming of those SME studies is that the SMEs themselves vary greatly in terms of size, scope, and technology. Whereas most of the family businesses can be predominantly put in the SME category, the particular issue of family business and family dynamics is not very common in those studies. This paper suggests that a good amount of research or studies can be done focusing on family business constitution, family members' participation norm, recruitment and promotion norm, family business succession rules and succession planning, training for family business leadership and management, training for board and directorial supervision, and so on.

Repairing of small and isolated delamination area in carbon fiber reinforced polymer (CFRP) without significantly altering the composite structure is studied in this research. A small drilled hole was introduced at the center of the delamination section of CFRP, providing the channel for epoxy infill of sharp delamination cracks. The pressureless infill repair was achieved through the capillary action of an acetone-diluted resin solution (without hardener) with CNT reinforcement, e.g., 89 m/m% of acetone, 10 m/m% of resin and 1m/m% of CNT. Such an acetone-rich resin pre-coating (RPC) solution is easy to prepare and apply to the drilled hole area. Curing of CNT-toughened resin infill was induced by filling the small-drilled hole with a resin-hardener mixture toughened by CNT/Aramid pulp. The effectiveness of delamination repair with curing periods of two weeks and three months were compared. Flexural strength measurements indicated that 77% (potentially 100%) of the restoration was achievable.

The biodiversity of the State National Natural Park (SNNP) "Buiratau" has not been studied, as it is young in Kazakhstan. The purpose of our study was an independent botanical and geographical study of the vegetation cover of the SNNP "Buiratau". This study have been carried out using the method route-reconnaissance and identifying plants, according to plant guide “Flora of Kazakhstan” (1999), “Key to Plants of Central Asia” (1974). The results showed that depending on the geographical location (Kazakh highland, steppe zone) of the SNNP "Buiratau" territory this natural complex has a very diverse botanical feature. In these types of vegetation of this territory, there are both Red Data Book and rare and endemic plants, such as black alder and birch forests, the peculiarity of which is that some species (Alnus glutinosa (L) Gaertn, Betula Kirghisorum Sav. - Rysz.) are listed in the Red book and very few. Medicinal, plant species and their resource potential are an important component of the flora. The analysis showed that the SNNP "Buiratau" is a unique natural environment, which is characterized by 10 species of plants listed in the Red Book, and 26 species of rare and endangered species.

Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into pro-inflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of SHP promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the pro-inflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK and NF-kB pathways.

Metastasis is the main cause of anti-cancer therapies failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses, relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial to mesenchymal transition (ETM) thus promoting the colonization of distant sites that in turn sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short reviews we will give an overview of the most recent advances related to three main large families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, integrin antagonists and small interfering (siRNAs). Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.

Genetic susceptibility in psoriasis is a topic of interest in the initiative to improve targeted treatment strategies. In this review, we discuss genes linked to psoriasis and the available treatment options in context of targeting respective gene products implicated in the pathogenesis of psoriasis. In order to identify relevant genetic markers and treatments, we developed a literature search utilizing PubMed, Google Scholar, MEDLINE, and Web of Science with keywords, including genetic susceptibility to psoriasis, genetics and psoriasis, psoriasis treatments, biologics treatments in psoriasis. Articles in English from database inception to 1/1/23, were included. Case reports and series were excluded. Gene variant forms commonly implicated in the pathogenesis of psoriasis include those encoding for interleukins, interferons, and other mediators involved in inflammatory pathways, such as JAK/STAT, NFk-B, and others. Most commonly utilized treatments for psoriasis include drugs that target inflammatory markers like IL23, IL12, IL17, and TNF-a. TYK2 inhibition has been discussed as an emerging treatment strategy. Multiple genes are linked to the pathogenesis of psoriasis. This understanding may provide an avenue for further development of pharmacologic strategies targeting underlying genetic pathways. Genetically guided treatment may also allow for greater understanding in the selection of biologics.

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases as well as microvascular eye diseases. Established hypertension leads to chronic vasoconstriction of small arteries as well as to decreased lumen diameter and thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was first demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alteration in small resistance arteries; however microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events, possessing, therefore, a prognostic relevance. New, non-invasive techniques, such as Scanning Laser Doppler Flowmetry or Adaptive Optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in term of cardio- and cerebrovascular events. A rarefaction of capillary network has also been reported in hypertension which may contribute to flow reduction and impairment in oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might concur to microvascular angina, stroke, and renal dysfunction. In addition, they could be a marker useful in monitoring the beneficial effect of antihypertensive treatment. Also conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. The review will address the possible relations between structural microvascular alterations and hypertension-mediated organ damage and their potential improvement with antihypertensive treatment.

Considering the differences between the European and African continents concerning the management of the mining production sector, we decided to carry out this study with the main objective of demonstrating that, in Africa, mining can positively change the quality of life of the populations where it develops and, at the same time, it is possible to respect the environment, which is our main wealth. To achieve these objectives, it is necessary to present the mining activity of the continent, emphasizing both the negative aspects and its strong points. The most important thing is to make a good diagnosis of the situation, which will allow us to cure our "patient", that is, African mining production.

The rampant misuse of drones poses a serious threat to national security and human life. Currently, the CNN method has been widely used in drone detection. However, there is a challenge that traditional CNN cannot cope with, which is small drone targets often have reduced amplitude or even lost features in infrared images. This paper proposes a Progressive Feature Fusion Network (PFFNet) that gradually increases the response amplitude of the target in the deep network. The Feature Selection Model (FSM) is designed to improve the utilisation of the output coding graph and enhance the feature representation of the target in the network. A lightweight segmentation head is also designed to achieve progressive feature fusion with multi-layer outputs. Experimental results show that the proposed algorithm can achieve low duration and high accuracy in drone target detection. On the public dataset, the IoU is improved by 2.53% and the detection time is reduced by 81.03%.

Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive spinal cord disorder with no effective treatment. There is much of interest in developing potential biomarkers for predicting the pathogenesis of HAM/TSP disorder. This study used Illumina massive parallel sequencing (MPS) technology to assess the cellular global noncoding RNAome expression profile in HAM/TSP patients (n = 10), asymptomatic HTLV-1 infected carriers (ASP, n = 8), and a second group of healthy controls (n = 5). Using various bioinformatics tools, the sRNA MPS reads were aligned, annotated, and profiled. There were 251 known and 50 potential novel sRNAs among the 402 detected sRNAs in the HAM and ASP groups versus the HC group. Sixty-eight known sRNAs were found to be significantly different between the ASP and HAM groups. In HAM vs ASP subjects, 88 mature miRNAs were downregulated. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The top seven deregulated miRS target genes were linked to a variety of biological processes and molecular functions. Relevant reactome pathways to our findings provide a rich source of data and an opportunity to further understand sRNA regulation and function in HTLV-1 pathophysiology.

The importance of small urban green areas has increased in the context of rapid urbanization and densification of the urban tissue. The analysis of these areas through remote sensing has been limited due to the low spatial resolution of freely available satellite images. We propose a timeseries analysis on 3 m resolution Planet images, using GEOBIA and vegetation indices, with the aim of extracting and assessing the quality of small urban green areas in two different climatic and biogeographical regions – temperate (Bucharest, Romania) and mediterranean (Athens, Greece). Our results have shown high accuracy (over 91%) regarding the extraction of small urban green areas in both cities, across all analysed images. The timeseries analysis showed consistency in location for around 55% of the identified surfaces throughout the entire period. The vegetation indices registered higher values in the temperate region, due to the vegetation characteristics and the planning of the two cities. For the same reasons, the increase in vegetation density and quality, as a result of the distance from the city centre and the decrease in the density of built-up areas is more obvious in Athens. The proposed method provides valuable insights in the distribution and quality of small urban green areas at city level and can represent the ground basis for many analyses, currently limited by poor spatial resolution.

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet Number) leads to formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. Emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.

Plant pathogenic fungi are the largest group of disease-causing agents on crop plants and represent a persistent and significant threat to agriculture worldwide. Conventional approaches based on the use of pesticides raise social concern for the impact on the environment and human health and alternative control methods are urgently needed. The rapid improvement and extensive implementation of RNAi technology for various model and non-model organisms has provided the initial framework to adapt this post-transcriptional gene silencing technology for the management of fungal pathogens. In this review, we describe exogenous RNAi involved in plant pathogenic fungi and discuss small RNA production, formulation, and RNAi delivery methods. We explore some challenges with possible solutions. Furthermore, exogenous RNAi holds great potential for RNAi-mediated plant pathogenic fungal disease control.

Nicotine exposure may affect NSCLC is associated with lung cancer in humans. Whether nicotine exhibits carcinogenesis promoted activities in tumor growth still unknown. Nicotine is known to have dichotomous effects on cancer biology, acting like a pro- or anti-carcinogenesis agent. There are different functions between adenocarcinoma and squamous NSCLC cancer cells. Excess generation of nicotine may inhibit mitochondrial metabolism, protein modification, and DNA cleavage. Materials and Methods: We used the H520 NSCLC line obtained from human lung epithelial cells to detected nicotine growth and toxicity using MTT assay and western blotting. The concentration of nicotine stimulated cell growth to correspond to low concentration, while high concentration was cytotoxic. Results: According to MTT assay results, at 1.0 μM nicotine has significantly enhanced the H520 cell viability (%). Nicotine induced lung cancer carcinogenesis through mechanisms of α7nAchR, EGFR, HDAC2/4/5, Cyclin D/Cyclin E, Bcl-2, p-Akt, and inflammatory proteins of NF-KappaB and COX2 increases at 1.0 μM. Apoptosis proteins were decreases at 1.0 μM nicotine by p21, p27, c-jun, and p38α using western blotting. Nicotine stimulates tumor growth is mediated through α7nicotinic-acetylcholine receptors (α7nAChR), possibly involving inflammation. On the other hand, at high nicotine concentrations (> 1.0 μM) with consistent cytotoxic effects and appeared to be due to direct cell kill. Nicotine can prevent apoptosis induced by NSCLC. Conclusion: Therefore, the effects on chemotherapeutics by NSCLC malignant cell lines, nicotine in concentrations as low as 1.0 μM decreased. These mechanisms are responsible for the genotoxic effects caused by nicotine. This leads to downstream effects on decreased apoptosis, increased cell proliferation and transformation. The malignant NSCLC cells respond to the treatment with nicotine in lung cancer, the nicotine-mediated induction of growth may provide one of its links to α7nAchR or EGFR.

The operation feasibility of small hydropower plants in mountainous sites is subjected to the run-of-river flow which is also depending on a high variability in precipitation and snow cover. Moreover, the management of this kind of systems has to be performed with some particular operation conditions of the plant (e.g. turbine minimum and maximum discharge) but also some environmental flow requirements. In this context, a technological climate service is conceived in tight connection with end users, perfectly answering the needs of the management of small hydropower systems in a pilot area, and providing forecast of river streamflow together with other operation data. This paper presents an overview of the service but also a set of lessons learnt related to features, requirements and considerations to bear in mind from the point of view of climate services developers. In addition, the outcomes give insight into how this kind of services could change the traditional management (normally based on the past experience), providing a probability range of future river flow based on future weather scenarios according to the range of future weather possibilities. This highlights the utility of the co-generation process to implement climate services for water and energy fields but also that seasonal climate forecast could improve the business as usual of this kind of facilities.

Australian regional areas are now receiving significant numbers of migrants from the African continent. Predominantly Anglo-Saxon communities perceive these ‘newcomers’ as physically and culturally different. Asking, however, how African migrants themselves construct relationships with local communities and build a sense of belonging in regional and rural areas is a very different question. This paper explores South Sudanese migrants’experiences conceptualising their sense of belonging in a small county town: Castlemaine, Victoria. Focus group discussions show that even with the welcoming atmosphere and support from the local community, South Sudanese migrants are still attracted to metropolitan environments that have greater diversity, feeling more at home in such settings. Using the theoretical background of a stranger, this paper argues the cities allow strangers be un-noticed letting them feel at ‘home’. Findings from the study show settings with greater diversity encourage negotiating difference openly and easing power imbalances among different groups.Finally, the locality of Castlemaine, within easy commuting distance to metropolitan Melbourne and suburbs, is considered in relation to hypermobility reducing the capacity to construct ‘bridging capital’ within such local communities.

Microbial contamination is now more common than chemical contamination in Tibet, and water-borne microbes can cause a number of diseases that threaten public health. Thus, in order to clarify the spatiotemporal distribution of bacteria in small watersheds for which there is no data in Tibet, we set up four sampling points along an upstream-downstream transect of the Xincang River Basin. We collected 239 water samples in 2014 and 2015, and evaluated their total constituent numbers of bacteria (TB) and coliforms (TC). The results of this study show that the microbial contamination of the Xincang River Basin is mild-to-moderate in terms of TB and TC contents, and that these concentrations vary significantly in different seasons. Results show that in summer TB and TC concentrations in the downstream section of this river were highest and that microbial contamination was most serious. Data also demonstrate that precipitation is the most important factor underlying increases in TB and TC concentrations during the summer months; both these variables are significantly correlated with precipitation, while animal husbandry and domestic sewage are the main sources of microbial contamination overall. The results of this study are likely to reflect the basic characteristics of small watersheds for which there is no data to some extent, and are thus of significant practical importance for protecting their ecological environments and promoting sustainable development.

Metabolic diseases are major diseases affecting animal welfare, health and production of small ruminants´ flocks for dairy and meat purposes. In breeding females, they mainly occur from six to eight weeks before and after parturition, respectively. The pregnancy toxemia and lactational ketosis are manifestations of hyperketonemia, primarily due to energetic deficit. Hypocalcemia and hypomagnesemia are related to the metabolic availably of calcium and magnesium, respectively. This review aimed to identify and discuss the current and most relevant aspects related to individual and herd heath management of these interrelated metabolic diseases with impact in the sheep and goats´ farm sustainability. These diseases are primarily due to nutritional deficit, but homeostatic and homeorhetic disruptions are responsible for clinical signs and forms. Currently, their clinical diagnosis and monitoring are mainly supported by biochemistry from animal fluids, and bromatological evaluation of the feed. Epidemiological studies, measuring risks factors, also contributes for their prevention. Nevertheless, research on specific biomarkers and composite indexes related to these diseases, in a context of herd health management and precision medicine, are new pathways driven to a suitable and efficient animal production.

The Axillary Seabream Pagellus acarne is of economic importance for recreational and commercial fisheries in the Atlantic and the Mediterranean, but a decline in total landings has been observed and raised some concern. Although biological information on the species has been provided for the Atlantic and Mediterranean, in the Portuguese continental slope data is restricted to the southern part of the country, which points to the relevance of the present work. A total of 520 individuals, between 7.8 cm and 39.9 cm TL, were monthly collected from September 2020 to August 2022 from commercial landings of fishing vessels operating off mainland Portugal, and used to study age and growth, the reproductive strategy and the annual sexual cycle. Age varied between 0 years (7.8 cm TL) and 15 years (34.2 cm TL) and the von Bertalanffy growth parameters were estimated from whole-otolith readings (L∞ = 35.2 cm, k = 0.133 yr–1 and t 0 = –2.78 yr). Pagellus acarne proved to be a protandric hermaphrodite species with males prevailing until 28.0 cm TL and females between 28.0 cm and 34.0 cm TL with a brief sex change phase. Females presented asynchronous oocyte development with a batch spawning pattern. The spawning season occurred from April to October with a spawning peak between June and August aas shown by histological analysis of the gonads and high levels of GSI during the period.

Opioids have served as a cornerstone in pain management for decades. However, the emergence of increasingly potent synthetic analogs brings forth a range of side effects, including respiratory depression, tolerance, dependence, constipation, and, more importantly, the development of severe and debilitating opioid use disorder (OUD). Search for therapeutics to mitigate OUD has been challenging and this has called for novel approaches that include design of small molecules targeting neuronal circuits involved in addiction (opioid, dopamine, serotonin, norepinephrine, and glutamate receptors, etc.) and development of biologics that target circulating opioids/opiates. In this review, we retrieved and discussed over two dozen of relevant patents filed in the past twelve (12) years that focus on novel approaches to produce therapeutics for OUD. The current review excluded patents on biologics and concentrated on small molecules, which will be discussed separately in a subsequent sequel. The chemical entities disclosed were highlighted and specific examples were provided where necessary. Although the number of patents in the realm of drug discovery for OUD is currently limited, we foresee a continued expansion in the quest for therapeutics for OUD in the years to come.

This study investigated the efficiency of scale-propellers, typically used on small drones. A scale-propeller is accepted as having a diameter of 7 to 21 inches. The Ukraine War has demonstrated the utility of relatively small, low-cost first-person view (FPV) drones, which are attritable. This investigation outlines the development of a MATLAB optimisation code, based on minimum induced loss propeller theory, which calculates the optimal chord and twist distribution for a chosen propeller operating in known flight conditions. The MATLAB code includes a minimum Reynolds number functionality, which provides the option to alter the chord distribution to ensure the entire propeller is operating above a set threshold value of Reynolds (&gt;100,000), as this has been found to be a transition point between low and high section lift-to-drag ratios. Additional functions allow plotting of torque and thrust distributions along the blade. The results have been validated on experimental data taken from an APC ‘Thin Electric’ 10” x 7” propeller, where it was found that both the chord and twist distributions were accurately modelled. The MATLAB code resulted in a 16% increase in the maximum propulsive efficiency. Further work will investigate a direct interface to SolidWorks to aid rapid propeller manufacturing capability.

Acacia dealbata Link, named Mimosa in Portugal, is an invasive hardwood species with potential for construction use, but research is limited. The available stock of small-diameter juvenile wood (sjw) logs can help reduce this gap, but tangential cracking at log ends challenges fastener connections. This study evaluated different treatments to control and reduce end-face cracking in sjw logs during air drying, an economical and environmentally friendly procedure. Extreme two-thirds of sixteen Mimosa logs were subjected to two treatments: one with longitudinal kerfs 15 mm deep along the length (2 and 3 kerfs) and the other with a hollow in the centre up to half the length (16 mm and 30 mm diameters). Over 219 days of air drying and compared with the central part, kerfing treatments significantly reduced outer wood tangential cracking (p &lt; 0.001), with the 3-kerf also reducing crack numbers (p &lt; 0.05) but increasing significantly cracks near the pith (p &lt; 0.01). The 30 mm central hollow significantly reduced central perforation cracking (p &lt; 0.05). Results suggest that a combined treatment approach could help mitigate cracking, enhancing the suitability of wild Mimosa logs for construction use.

Staphylococcus aureus bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. S. aureus, while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in S. aureus that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that S. aureus uses to persist within the intracellular space.

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors it has been shown to have a pleiotropic effect across many cell types and mechanisms resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we have used fluorescence polarisation (FP) assays to determine KD values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1,000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1 whilst faster association was responsible for the effects at mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high throughput manner for small molecule galectin-1 inhibitors.

The purpose of this study is to investigate the failure mechanism and preventive strengthening methods of prefabricated full length small box girder (PSBG) under car explosion. After damage analysis during blast loads using the commercial software Autodyn, three strengthening methods are presented to improve the blast mitigation performance. The results show that the failure modes and bearing capacity are significantly different with various strengthening measures. Adhering U-shaped steel plate can effectively enhance the shear performance of PSBG under blast loads. Strengthening the bottom of the upper flange of box girder with steel plate can effectively mitigate the local bending failure, and enhance the overall flexural capacity during car explosion.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

Climate change is unpredictable and can change rapidly or over time; anthropogenic stressors work synergistically to strengthen their impact on vulnerable ecosystems and the fisheries sector. This study documented the past occurrence of extreme climate change impacts, such as supertyphoon Pablo (ST: Bopha), which severely affected Baganga, Davao Oriental, about ten years ago. A mixed-methods data collection was used, combining semi-structured interviews with small-scale fishers (N=120) in four fishing villages and focus group discussions (N=4, participated by about 4 focus groups) on assessing the impacts and their adaptation after climatic events occurred. Our findings indicate that the four selected fishing villages were exposed to common factors of climate change events that destroyed many lives and their livelihood. Including a decrease in catch per trip and the fishing operations disruption (98%). However, due to the impact of the supertyphoon, small-scale fishers in Baganga developed psychological distress (emotional 44% and physical 24%) due to the extreme event or disaster and economic losses (32%). In order to survive, their adaptation strategies relied on government and non-government-provided provisions and projects, e.g., planting trees, constructing a sea wall with wave breakers, cash for work, and tourism as an alternative livelihood. Despite this, our study revealed that the community had limited knowledge on the impacts of climate change, lack clear management goals especially for fishers, and the widespread use of illegal fishing gears. The local government must strongly implement rules, policies, and adaptation measures that will contribute to better and more resilient communities. This can help them to withstand future shocks and provide sustainable fisheries resources that will benefit all the fishers. The study will be useful to policymakers, disaster management group and organization that will help assist affected communities highly affected by climatic events.

Background: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. Methods: We described a family presenting with a novel variant in the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). Results: This investigation encompassed 53 COL4A1/2 variants in 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs 58.1%, p = 0.0035) was identified in the CA positive group. Conclusions: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small vessel disease or other large vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

Capsizing accidents are regarded as marine accidents with a high rate of casualties per accident. Approximately 89% of all such accidents occur in small ships (vessels with gross tonnage less than 10 tons). Stability calculations are critical for assessing the risk of capsizing incidents and evaluating a ship's seaworthiness. Despite the high frequency of capsizing accidents involving small ships, they are generally exempt from adhering to stability regulations, thus remaining systemically exposed to the risk of capsizing. Moreover, the absence of essential design documents complicates direct ship stability calculations. This study utilizes hull form feature data—obtained from the general arrangement of small ships—as input for a deep learning model. The model is structured as a multilayer neural network and aims to infer hydrostatic curves, which is required data for stability calculations.

The sustainability of agroecological systems, biodiversity protection, animal welfare and consumer demand for higher-quality products from alternative and extensive farming methods, have reinforced interest in local breeds that are well adapted to low-input environments. However, food safety needs to be safeguarded to reinforce consumer confidence. The aim of this study was to conduct a preliminary investigation on the occurrence of Salmonella spp. in eggshells, hen’s cloaca and litter materials from autochthonous Portuguese laying hens raised in a semi-extensive system for small-scale production. A total of 279 samples were obtained, with 63 samples from the “Preta Lusitânica” breed, and 72 samples each from the remaining autochthonous breeds, namely “Branca”, “Amarela” and “Pedrês Portuguesa”. None (0%) of the samples analyzed were positive for Salmonella spp.. To the best of our knowledge, these are the first results of Salmonella evaluation from hen’s cloaca, eggshells, and litter materials in autochthonous Portuguese chickens, suggesting that a semi-extensive production system can contribute to better food security and a lower risk to public health and the environment.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Zoonotic abortive diseases represent a significant health and economic risk for national public health. This cross-sectional survey was conducted from April to October 2021 among 200 selected small ruminant farmers in the three northern regions of Cameroon. Data collection was done through questionnaires administered by exchange with the herder and responses were coded and recorded on an Excel spreadsheet. The data were then analyzed with R software, version 2.13.0. An ANOVA test was used to assess significant differences in mean of Knowledge, Attitudes, Practices and Perception of zoonotic risks (KAPP) scores between regions. Pearson correlations were used to calculate the association between KAPP scores within regions. Small ruminant farmers surveyed had low mean scores for knowledge of abortive Toxoplasmosis and Chla-mydophilosis (0.1 ± 0.2), desirable attitude (0.32 ± 0.07), appropriate practice (0.36 ± 0.13) in managing abortion, and positive perception of zoonotic risks of Toxoplasmosis and Chlamydo-philosis in small ruminants (0.12 ± 0.33), respectively. KAPP was significantly (p<0.01) and posi-tively associated with knowledge (r=0.98) and risk perception (r=0.99). However, attitudes (r=0.06), practices (r=0.05) and risk perception of toxoplasmosis (r=0.07) and Chlamydophilosis (r=0.08) were not associated with farmers' knowledge. This study revealed significant knowledge gaps, low levels of desired attitudes, and high-risk behavioral practices. These results therefore call for capacity building of health professionals and farmers to better integrate the One Health concept in the management of neglected zoonotic diseases.