Search Results (6,630)

Cancer immunotherapy has emerged as an effective, personalized treatment for certain patients, particularly for those with hematological malignancies. However, its efficacy in breast cancer has been marginal—perhaps due to cold, immune-excluded, or immune-desert tumors. Natural killer T (NKT) cells play a critical role in cancer immune surveillance and are reduced in cancer patients. Thus, we hypothesized that NKT cells could serve as a surrogate marker for immune function. In order to assess which breast cancer patients would likely benefit from immune cell-based therapies, we have developed a quantitative method to rapidly assess NKT function using stimulation with artificial antigen presenting cells followed by quantitative real-time PCR for IFN-γ. We observed a significant reduction in the percentage of circulating NKT cells in breast cancer patients, compared to healthy donors; however, the majority of patients had functional NKT cells. When we compared BC patients with highly functional NKT cells, as indicated by high IFN-γ induction, to those with little to no induction, following stimulation of NKT cells, there was no significant difference in NKT cell number between the groups, suggesting functional loss has more impact than physical loss of this subpopulation of T cells. In addition, we assessed the percentage of tumor-infiltrating lymphocytes and PD-L1 expression within the tumor microenvironment in the low and high responders. Further characterization of immune gene signatures in these groups identified a concomitant decrease in the induction of TNFα, LAG3, and LIGHT in the low responders. We next investigated the mechanisms by which breast cancers suppress NKT-mediated anti-tumor immune responses. We found that breast cancers secrete immunosuppressive lipids, and treatment with commonly prescribed medications that modulate lipid metabolism, can reduce tumor growth and restore NKT cell responses. Full article

Intra-tumor heterogeneity (ITH) is a fundamental characteristic of breast cancer (BC), influencing tumor progression, prognosis, and therapeutic responses. However, the complexity of ITH in BC makes its accurate characterization challenging. This study leverages deep learning (DL) techniques to comprehensively evaluate ITH in early-stage luminal BC and provide a nuanced understanding of its impact on tumor behavior and patient outcomes. A large cohort (n = 2561) of early-stage luminal BC was evaluated using whole slide images (WSIs) of hematoxylin and eosin-stained slides of excision specimens. Morphological features of both the tumor and stromal components were meticulously annotated by a panel of pathologists in a subset of cases. A DL model was applied to develop an algorithm to assess the degree of heterogeneity of various morphological features per individual case utilizing defined patches. The results of extracted features were used to generate an overall heterogeneity score that was correlated with the clinicopathological features and outcome. Overall, 162 features were quantified and a significant positive correlation between these features was identified. Specifically, there was a significant association between a high degree of intra-tumor heterogeneity and larger tumor size, poorly differentiated tumors, highly proliferative tumors, tumors of no special type (NST), and those with low estrogen receptor (ER) expression. When all features are considered in combination, a high overall heterogeneity score was significantly associated with parameters characteristic of aggressive tumor behavior, and it was an independent predictor of poor patient outcome. In conclusion, DL models can be used to accurately decipher the complexity of ITH and provide extra information for outcome prediction. Full article

The current work proposes the development of composite membranes based on bacterial cellulose (BC) loaded with silver (Ag) and zinc oxide (ZnO) nanostructures by in situ impregnation. The research involves the production and purification of BC, followed by its loading with different types of phases with the help of different precipitating solutions, turmeric extract (green synthesis) and ammonia (classic route). Additionally, the combination of both antibacterial agents into a single BC matrix to valorise the benefits of each, proposing a novel BC-Ag-ZnO composite with distinct characteristics, was explored. Overall, the synthesis was marked by colour changes from the light beige of the BC membrane to dark brown, dark orange and dark green for BC-Ag, BC-ZnO and BC-Ag-ZnO samples, which is proof of successful composites formation. The results proved that the antibacterial phases are attached as nanoparticles or nanosheets on BC fibres, with Ag being in a crystalline state, while ZnO showed a rather amorphous structure. Regarding the antibacterial efficiency, the BC-ZnO composite obtained by employing two precipitating solutions turned out to be the best material against both tested Gram-negative and Gram-positive bacterial strains. Full article

Hereditary breast cancer accounts for 5–10% of all cases, with pathogenic variants in BRCA1/2 and other susceptibility genes playing a crucial role. This study elucidates the prevalence and spectrum of germline variants in 13 cancer predisposition genes among high—risk hereditary breast cancer patients from Southern Italy. We employed next-generation sequencing (NGS) to analyze 254 individuals selected through genetic counseling. Pathogenic or likely pathogenic variants were identified in 13% (34/254) of patients, with 54% of these variants occurring in non-BRCA1/2 genes. Notably, we observed a recurrent BRCA1 c.4964_4982del founder mutation, underscoring the importance of population-specific genetic screening. The spectrum of variants extended beyond BRCA1/2 to include PALB2, ATM, TP53, CHEK2, and RAD51C, highlighting the genetic heterogeneity of breast cancer susceptibility. Variants of uncertain significance were detected in 20% of patients, emphasizing the ongoing challenge of variant interpretation in the era of multi-gene panel testing. These findings not only enhance our understanding of the genetic landscape of breast cancer in Southern Italy but also provide a foundation for developing more targeted, population-specific approaches to genetic testing and counseling, ultimately contributing to the advancement of precision medicine in oncology. Full article

Human habitat is much controlled by the landscape and its ongoing processes overtime. Some of these processes occur instantaneously and are often triggered by seismic events with a major destructive impact on the human-built environment. Helike, on the southwest shore of the Gulf of Corinth, is a characteristic case of an ancient habitation site bearing witness to repetitious natural disasters from the Early Bronze Age to the Late Antiquity. The Late Classical-Hellenistic site, revived in the Helike plain after the 373 BC earthquake, has been systematically investigated thanks to the multidisciplinary research and excavations of the Helike Project in the last 35 years. This work has significantly enriched the historical seismicity of the region and shed light on past human-environment relationships. The study of the architectural remains excavated by the Helike Project, coupled with geological and soil micromorphological analysis on archaeological soils and sediments of the settlement, demonstrates a constant effort of the Helike people to reconcile with the elements of nature. Our results underline the destruction of a flourishing textile dyeworks operated at the settlement, due to a strong earthquake which triggered extensive morphological changes in a broader area. These changes include co-seismic liquefaction and lateral spreading, and post-seismic changes in the gradient of river channels. The former changes attest to an uplift in the headwater area and subsidence in the lowland plain of the ravine flowing near the ancient site. Full article

Background/Objectives: The 8th edition of the American Joint Committee on Cancer integrates histology and biomarker status with anatomic extent in breast cancer (BC) pathologic prognostic staging (PPS). However, PPS IB includes anatomic locally advanced hormone-receptor-positive/HER2-negative (LA-HR+/HER2-) and early-stage triple-negative BC (ES-TNBC). Previous research shows that increased nodal involvement is a critical predictor of worse prognosis, raising questions about whether biological subtype or anatomic stage has a greater influence on outcomes in these discordant cases. We hypothesized that overall survival (OS) remains worse for LA-HR+/HER2- BC compared to ES-TNBC, despite both being classified as PPS IB. Methods: Using the National Cancer Database, we identified patients with LA-HR+/HER2- BC (pT3N1 or pT1-3N2, grade 1–2) and ES-TNBC (T1N0, grade 2–3) treated between 2004 and 2017. Patients without complete primary tumor stage, biomarker status, grade, TNM staging, or treated with neoadjuvant therapy were excluded. The primary endpoint was OS. Multivariable Cox regression evaluated OS between LA-HR+/HER2- BC and ES-TNBC. Results: Among 45,818 patients (17,359 LA-HR+/HER2- BC and 28,459 ES-TNBC), LA-HR+/HER2- BC had significantly worse 6-year OS (86.1% vs. 90.4%; HR = 1.63; p < 0.0001). Among patients receiving appropriate therapies, patients with LA-HR+/HER2- BC had 35% relatively higher risk of death (HR = 1.35; 1.24–1.48; p < 0.0001). These results highlight that LA-HR+/HER2- breast cancer has worse survival compared to ES-TNBC, despite both being classified as PPS IB and receiving all appropriate treatments. Conclusions: Anatomic disease extent remains an important factor in patients with discordant AS and PPS. Future iterations of PPS should re-classify LA-HR+/HER2- breast cancer from PPS IB to ensure more accurate prognostic and survival information. Full article

This study examined the effects of adding CUB alongside HCN sources from fresh cassava diets on HCN reduction, gas production, and in vitro digestibility. A completely randomized design (CRD) with a 2 × 2 × 3 + 1 factorial approach was used, where Factor A was the HCN source [fresh cassava root (FCR) or leaf (FCL)], Factor B was the HCN concentration (300 and 600 mg/kg dry matter (DM)), and Factor C was the bacterial supplement [no-CUB, E. faecium KKU-BF7 (CUB1), and E. gallinarum KKU-BC15 (CUB2)]. Statistical analysis was performed using the PROC GLM procedure in SAS. No interaction was observed among the main factors on gas kinetics and cumulative gas (p > 0.05). The addition of CUB1 or CUB2 enhanced cumulative gas production compared to the no-CUB group (p = 0.04). Cyanide degradation efficiency was high when FCR was included at a high HCN level. At 12 h post-incubation, HCN degradation efficiency was higher in the CUB2 and CUB1 groups, reaching 98.44–99.07% compared to the no-CUB group. The higher HCN level increased in vitro acid detergent fiber digestibility (IVADFD) (p = 0.01) by 7.20% compared to the low HCN level, and CUB2 further improved IVADFD. Compared to the FCL-fed group, FCR supplementation increased total VFA concentration (p = 0.03) and propionic acid (C3) concentration (p = 0.04). The addition of CUB2 further enhanced propionic acid concentration by 8.97% compared to no-CUB supplementation (p = 0.04). These results indicate that supplementing E. gallinarum KKU-BC15 at the highest HCN levels in FCR boosts HCN degradation efficiency, fiber digestibility, total VFA, and C3 concentration. Full article

Induced heavy metals (HMs) phytoextraction from heavily contaminated soils is challenging, as high HM bioavailability causes phytotoxicity and leaching. This study introduces a novel approach for HM immobilization with biochar (BC) and lignin (LN), and later their controlled mobilization with citric acid (CA) in soil. Conocarpus erectus was grown for 120 days in shooting-range soil (SS) polluted with Pb, Cr, Cd, Ni, and Cu. HM concentrations in parts of the plants, their percentage removal, and leaching from SS were measured. Moreover, plant biochemical parameters such as the contents of chlorophyll a (Chl-a), chlorophyll b (Chl-b), protein, ascorbic acid (AsA), amino acids, and total phenolics, along with biophysical parameters such as relative water content (RWC) and water uptake capacity (WUC), were also inspected. Adding BC, LN, and BC+LN to SS improved biomass, as well as the biophysical and biochemical parameters of plants, while efficiently reducing HM concentrations in plant parts, DTPA extract, and leachates compared to the control (CK). However, the greatest amplifications in plant height (82%), dry weight of root (RDW) (109%), and dry weight of shoot (SDW) (87%), plant health, and soil enzymes were noted with the BC+LN+CA treatment, compared with the CK. Moreover, this treatment resulted in Pb, Cr, Cd, Ni, and Cu removal by 68, 30, 69, 59, and 76% from the SS compared to the CK. Surprisingly, each HM concentration in the leachates with BC+LN+CA was below the critical limits for safer water reuse and agricultural purposes. Initial HM immobilization in HM-polluted soils, followed by their secured mobilization during enhanced phytoextraction, can enhance HM removal and reduce their leaching without compromising plant and soil health. Full article

Background/objectives: Blood culture (BC) contamination is a frequent problem which leads to increased laboratory workload, inappropriate use of antibiotics and the associated adverse events, and increased healthcare costs. This study prospectively examined the effect of a care bundle on BC contamination rates in a high workload ICU. Results: During the study, in total, 4236 BC vials were collected. After the intervention, the BC contamination rate decreased significantly from 6.2% to 1.3%. The incidence rate of contaminated BC sets was significantly lower following the intervention: 0.461 vs. 0.154 BC sets per 100 ICU bed-days. Overall compliance with the BC care bundle increased dramatically from 3.4% to 96.9%. Methods: We performed a before–after study in a general ICU from January 2018 to May 2019, with the intervention starting on November 2018. Blood culture sets were classified as positive, contaminated, indeterminate, and negative. We used bivariate and interrupted time series analysis to assess the effect of the intervention on BC contamination rates and other BC quality indicators. Conclusions: The BC care bundle was effective in reducing BC contamination rates and improving several quality indicators in our setting. The indeterminate BC rate is an important but understudied problem, and we suggest that it should be included in BC quality indicators as well. A significant limitation of the study was that the long-term effect of the intervention was not assessed. Full article

Garambullo fruit (Myrtillocactus geometrizans) is a rich source of phytochemical compounds that exhibit antioxidant, anti-hyperglycemic, and anti-inflammatory activities, helping to prevent diseases associated with oxidative stress. The objective of this study was to evaluate phenolic compound (PC), betalain (BL), betaxanthin (BX), and betacyanin (BC) contents, and in vitro biological activities (antioxidant, anti-hyperglycemic, and anti-inflammatory) in microencapsulated garambullo extract during in vitro gastrointestinal digestion and storage. Microencapsulation was performed using spray drying. Arabic Gum (GA, 10% in feed solution) and soy protein isolate (SPI, 7% in feed solution) were used as wall materials. After in vitro digestion, the microcapsules (GA, SPI) exhibited higher bioaccessibility (p ≤ 0.05) of PC, BL, BX, and BC, and higher antioxidant activity (AA), compared to the non-encapsulated extract. Both microcapsules showed bioaccessibility in anti-hyperglycemic activity: α-amylase (GA: 90.58%, SPI: 84.73%), α-glucosidase (GA: 76.93%, SPI: 68.17%), and Dipeptidyl peptidase-4 (DPP-4) (GA: 52.81%, SPI: 53.03%); and in anti-inflammatory activity: cyclooxygenase-1 (COX-1) (GA: 78.14%, SPI: 77.90%) and cyclooxygenase-2 (COX-2) (GA: 82.77%, SPI: 84.99%). During storage, both microcapsules showed a similar trend with a significant decrease (p ≤ 0.05) in PC (GA: 39.29%, SPI: 39.34%), BL (GA: 21.17%, SPI: 21.62%), BX (GA: 23.89%, SPI: 23.45%), BC (GA: 19.55%, SPI: 19.84%), and AA (GA: 41.59%, SPI: 42.51%) after 60 days at 30 °C. Both microcapsules retained anti-hyperglycemic activity evaluated by the inhibitory activity of α-amylase (GA: 68.84%, SPI: 70.18%), α-glucosidase (GA: 59.93%, SPI: 58.69%), and DPP-4 (GA: 52.81%, SPI: 53.01%), and anti-inflammatory activity evaluated by the inhibitory activity of COX-1 (GA: 82.18%, SPI: 82.81%) and COX-2 (GA: 81.11%, SPI: 81.08%). Microencapsulation protected the phytochemical compounds and in vitro biological activities by allowing controlled release during in vitro digestion compared to the non-encapsulated extract. However, after 60 days storage at 30 °C, 60% of PC and AA, 80% of BL, BX, and BC, and 20–45% of the anti-hyperglycemic and anti-inflammatory activity were lost. Full article

Supernumerary teats (SNTs) or nipples often emerge around the mammary line. This study performed a genome-wide selective sweep analysis (GWS) at the copy number variant (CNV) level using two selected signal calculation methods (V_ST and F_ST) to identify candidate genes associated with SNTs in goats. A total of 12,310 CNVs were identified from 37 animals and 123 CNVs, with the top 1% V_ST values including 84 candidate genes (CDGs). Of these CDGs, minichromosome maintenance complex component 3, ectodysplasin A receptor associated via death domain, and cullin 5 demonstrated functions closely related to mammary gland development. In addition, 123 CNVs with the top 1% F_ST values were annotated to 97 CDGs. 5-Hydroxytryptamine receptor 2A, CCAAT/enhancer-binding protein alpha, and the polymeric immunoglobulin receptor affect colostrum secretion through multiple signaling pathways. Two genes, namely, RNA-binding motif protein 46 and β-1,3-galactosyltransferase 5, showed a close relation to mammary gland development. Six CNVs were identified and annotated to five genes by intersecting the top 1% of candidate CNVs with both parameters. These genes include LOC102185621, LOC102190481, and UDP-glucose pyrophosphorylase 2, which potentially affect the occurrence of BC through multiple biological processes, such as cell detoxification, glycogen synthesis, and phospholipid metabolism. In conclusion, we discovered numerous genes related to mammary development and breast cancer (BC) through a GWS, which suggests the mechanism of SNTs in goats and a certain association between mammary cancer and SNTs. Full article

Electrocatalytic nitrate reduction enables the recovery of nitrate from water under mild conditions and generates ammonia for nitrogen fertilizer feedstock in an economical and green means. In this paper, Co/biomass carbon (Co/BC) composite catalysts were prepared by co-carbonization of straw and metal–organic framework material ZIF-67 for electrocatalytic nitrate reduction using hydrothermal and annealing methods. The metal–organic framework structure disperses the catalyst components well and provides a wider specific surface area, which is conducive to the adsorption of nitrate and the provision of more reactive active sites. The introduction of biomass carbon additionally enhances the electrical conductivity of the catalyst and facilitates electron transport. After electrochemical testing, Co/BC-100 exhibited the best performance in electrocatalytic nitrate reduction to ammonia, with an ammonia yield of 3588.92 mmol g_cat.⁻¹ h⁻¹ and faradaic efficiency of 97.01% at −0.5 V vs. RHE potential. This study provides a promising approach for the construction of other efficient cobalt-based electrocatalysts. Full article

Background: Assembly factor for spindle microtubules (ASPM) has gained significant attention in cancer research due to its association with tumor growth and progression. Through the analysis of large-scale genomic datasets, ASPM has been identified as the top upregulated gene in breast cancer (BC), characterized by high proliferation. This multicohort study aimed to investigate the clinicopathological and prognostic significance of ASPM mRNA and protein expression in BC. Methods: ASPM mRNA expression was assessed using the Cancer Genome Atlas (TCGA) BC cohort and has been further validated in the Molecular Taxonomy of BC International Consortium (METABRIC) (n = 1980), The Uppsala cohort (n = 249), in addition to the combined multicentric cohort (n = 7252). ASPM protein expression was evaluated in a large BC cohort (n = 1300) using immunohistochemistry. The correlations between ASPM expression, clinicopathological parameters, molecular subtypes and outcome were assessed. The response to taxane treatment was compared to the clinical prognosis of ASPM using the ROC plotter. Results: High ASPM mRNA and protein expression were significantly associated with aggressive BC features and poor survival across all cohorts. The association with poor outcomes was maintained in the adjuvant chemotherapy and radio-therapy-treated patients. Responders to taxane treatment showed significantly elevated ASPM levels compared to non-responders. Conclusions: High ASPM expression predicts poor prognosis in BC. It may play a role in treatment resistance within a specific subgroup of patients. Further clinical trials are warranted to explore the potential of ASPM as a target for therapeutic interventions in cancer. Full article

Strain IBc-114 was isolated from a gray mold lesion and was identified as the fungus Schizophyllum commune. In this strain, two mycoviruses, Schizophyllum commune RNA virus 1 (ScRV1, C_AA053475.1) and Botrytis cinerea mitovirus 9 strain IBc-114 (BcMV9/IBc-114, C_AA053476.1), were isolated and characterized. ScRV1 has flexuous filamentous particles about 20 ± 2.1 nm in diameter and 1000 ± 94.2 nm in length. The genome of ScRV1 is 7370 nt in length and contains two open reading frames (ORFs) which encode a polyprotein and a coat protein, respectively. The polyprotein has 1967 aa, including a helicase domain and an RdRp domain which has the highest identity of 28.21% with that of Entomophthora benyvirus E (EbVE). The coat protein has 241 aa which is mostly phylogenetically close to the coat proteins of Alphatetraviridae. Based on the phylogenetic analysis of ScRV1 and viruses selected, ScRV1 might represent a new family (temporarily named Mycobenyviridae) of the order Hepelivirales. The genome of BcMV9/IBc-114 that infects S. commune is 2729 nt in length and has only one ORF encoding an RdRp protein with 719 aa. BcMV9/IBc-114 has the highest identity of 98.61% with Botrytis cinerea mitovirus 9 (BcMV9) (MT089704). ScRV1, but not BcMV9/IBc-114, has certain effects on the host growth of S. commune. Furthermore, BcMV9/IBc-114 has been demonstrated to replicate in the ascomycetous fungi Botrytis cinerea and Sclerotinia sclerotiorum, and it negatively affects the growth and pathogenicity of B. cinerea, but it does not affect S. sclerotiorum. This is the first report of mycoviruses in S. commune and cross-phyla transmission of mitovirus in nature. Full article

The Brazilian Pantanal region experiences intense biomass burning during the dry season, releasing large quantities of gasses and particles into the atmosphere, which have serious implications on both the climate system and public health. Understanding the dynamics of these emissions is crucial for mitigating the impact on the ecosystem, its functioning, and potential anthropogenic disturbances. This study focused on analyzing emissions in the northern Pantanal during the 2022 drought. Concentrations of fine particulate matter (PM_2.5), black carbon (BC), and 25 chemical elements were measured using gravimetry, reflectance analysis, and X-Ray fluorescence, respectively, from samples collected between August and October 2022. The average concentrations of PM_2.5 and BC increased approximately 4-fold and 2.5-fold, respectively, compared to averages from a decade ago. Significant increases were also observed in elements such as sulfur (S), potassium (K), iron (Fe), and silicon (Si). The maximum concentrations were comparable to values typical of the southern Amazon, a region known for high deforestation rates and land use changes. Elemental analysis revealed substantial shifts in concentrations, primarily associated with biomass burning (BB) and soil suspension. Additionally, enrichment factor (Ef) analysis showed that lead (Pb) levels, correlated with human activities, were 200 times higher than those found under clean atmospheric conditions. Full article