Search Results (1,115)

Objectives: Ongoing research has begun to develop innovative approaches to deliver local antibiotics while minimizing systemic side effects, antimicrobial resistance, and limited tissue penetration. Autologous platelet concentrates (APCs) offer promise in delivering antibiotics directly to infection sites. Despite the interest, a comprehensive evaluation of their effectiveness is lacking. Therefore, this systematic scoping review aims to collect and appraise studies regarding the efficacy of APCs in delivering antibiotics. Methods: A systematic electronic search of PubMed, Scopus, and Web of Science, using a combination of keywords, was conducted up to February 2024. Articles addressing the use of APCs as a local antibiotic delivery system were included. Results: A total of 13 articles, including 10 in vitro studies, 1 in vitro and clinical study, 1 ex vivo study, and 1 clinical study, were selected. Antibiotic loading capacity and release was confirmed in all studies using doxycycline, gentamicin, linezolid, vancomycin, metronidazole, and penicillin. In addition, the antibacterial effect was obtained mainly against E. coli., P. aeruginosa, S. mitis, H. influenzae, S. pneumoniae, and S. aureus. Conclusions: The incorporation of antibiotics into APCs has been proven to facilitate the effective release of antimicrobial agents at optimal concentrations, potentially reducing the incidence of post-operative infections, substituting, or augmenting systemic antibiotic treatment while retaining APCs’ inherent healing properties. Full article

Background: There is an observed variation in the burden of hepatocellular carcinoma (HCC) across different US populations. Our study aims to comprehensively assess variations in HCC incidence and mortality rates across different regions of the US. Understanding these geographical differences is crucial, given prior evidence indicating variations in the incidence of viral hepatitis and metabolic dysfunction-associated steatotic liver disease and varying access to curative HCC treatment among states. Methods: HCC age-adjusted incidence rates between 2001 and 2021 were obtained from the United States Cancer Statistics (USCS) database (which covers approximately 98% of the US population). HCC age-adjusted mortality rates between 2000 and 2022 were obtained from the National Center of Health Statistics (NCHS) database (covering approximately 100% of the US population). The rates were categorized by US geographical region into West, Midwest, Northeast, and South. Incidence rates were also categorized by race/ethnicity. Time trends [annual percentage change (APC) and average APC (AAPC)] were estimated by using Joinpoint Regression via the weighted Bayesian Information Criteria (p < 0.05). Results: Between 2001 and 2021, there were 491,039 patients diagnosed with HCC in the US (74.2% males). The highest incidence rate per 100,000 population was noted in the West (7.38), followed by the South (6.85). Overall incidence rates increased between 2001 and 2015 and then significantly decreased until 2021 (APC = −2.29). Most cases were in the South (38.8%), which also had the greatest increase in incidence (AAPC = 2.74). All four geographical regions exhibited an overall similar trend with an increase in incidence over the first 10–15 years followed by stable or decreasing rates. While stratification of the trends by race/ethnicity showed slight variations among the regions and groups, the findings are largely similar to all race/ethnic groups combined. Between 2000 and 2022, there were 370,450 patients whose death was attributed to HCC in the US (71.6% males). The highest mortality rate per 100,000 population was noted in the South (5.02), followed by the West (4.99). Overall mortality rates significantly increased between 2000 and 2013 (APC = 1.90), then stabilized between 2013 and 2016, and then significantly decreased till 2022 (APC = −1.59). Most deaths occurred in the South (35.8%), which also had the greatest increase in mortality (AAPC = 1.33). All four geographical regions followed an overall similar trend, with an increase in mortality over the first 10–15 years, followed by stable or decreasing rates. Conclusions: Our analysis, capturing about 98% of the US population, demonstrates an increase in HCC incidence and mortality rates in all geographical regions from 2000 to around 2014–2016, followed by stabilizing and decreasing incidence and mortality rates. We observed regional variations, with the highest incidence and mortality rates noted in the West and South regions and the fastest increase in both incidence and mortality noted in the South. Our findings are likely attributable to the introduction of antiviral therapy. Furthermore, demographic, socioeconomic, and comorbid variability across geographical regions in the US might also play a role in the observed trends. We provide important epidemiologic data for HCC in the US, prompting further studies to investigate the underlying factors responsible for the observed regional variations in HCC incidence and mortality. Full article

Municipal solid waste incineration (MSWI) is essential for tackling urban environmental challenges and facilitating renewable energy recycling. The MSWI process has characteristics of multiple variables, strong coupling, and complex nonlinearity, requiring advanced process control (APC) technology. Although there have been several reviews on the modeling and control of the MSWI process, there is a lack of focus on model predictive control (MPC), a widely used APC technology. This article aims to comprehensively review MPC strategies in the MSWI process. First, it describes MSWI process technology in detail, examining control issues and objectives to highlight the complexity and challenges in controller design while providing an overview of MPC methods and their benefits. Second, it reviews incinerator modeling for control, including traditional modeling techniques and machine learning technologies such as fuzzy neural networks. Third, it reviews the controllers used for MSWI process, emphasizing the advantages of MPC over existing control methods. Fourth, it discusses the current status of MPC design and online updates, covering the need for an accurate dynamic predictive model and objective function and the online updates components such as predictive modeling, rolling optimization, and feedback correction. Finally, the study concludes with a summary of the findings. Full article

Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, p < 2 × 10⁻⁶) and non-COVID sepsis (up to 4.7-fold, p < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, p = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, p = 2 × 10⁻⁴) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364–0.661) and non-COVID sepsis patients (r = 0.535–0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (p = 0.036), 6-fold (p = 3 × 10⁻⁷) and 3-fold (p = 8 × 10⁻⁴) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis. Full article

Atmospheric phase error is the main factor affecting the accuracy of ground-based synthetic aperture radar (GB-SAR). The atmospheric phase screen (APS) may be very complicated, so the atmospheric phase correction (APC) model is very important; in particular, the parameters to be estimated in the model are the key to improving the accuracy of APC. However, the conventional APC method first performs phase unwrapping and then removes the APS based on the least-squares method (LSM), and the general phase unwrapping method is prone to introducing unwrapping error. In particular, the LSM is difficult to apply directly due to the phase wrapping of permanent scatterers (PSs). Therefore, a novel methodology for estimating parameters of the APC model based on the maximum likelihood estimation (MLE) and the Gauss-Newton algorithm is proposed in this paper, which first introduces the MLE method to provide a suitable objective function for the parameter estimation of nonlinear far-end and near-end correction models. Then, based on the Gauss-Newton algorithm, the parameters of the objective function are iteratively estimated with suitable initial values, and the Matthews and Davies algorithm is used to optimize the Gauss-Newton algorithm to improve the accuracy of parameter estimation. Finally, the parameter estimation performance is evaluated based on Monte Carlo simulation experiments. The method proposed in this paper experimentally verifies the feasibility and superiority, which avoids phase unwrapping processing unlike the conventional method. Full article

The spatial characteristics, pollution sources, and risks of soil heavy metals were analyzed on Hainan Island. The results showed that the heavily polluted points accounted for 0.56%, and the number of mildly and above polluted points accounted for 15.27%, respectively, which were mainly distributed in the northern part of the study area. The principal component analysis–absolute principal component score–multiple linear regression (APCS-MLR) and the positive matrix factorization (PMF) revealed four sources of heavy metals: agricultural pollution sources for cadmium, (Cd), industrial and mining pollution sources for arsenic, (As), transportation pollution sources for zinc and lead (Zn and Pb), and natural pollution sources for chromium, nickel, and copper (Cr, Ni, and Cu). The human health risk assessment indicated that the average non-carcinogenic risk (HI) for both adults and children was within the safe threshold (<1), whereas Cr and Ni posed a carcinogenic risk (CR) to human health. In addition, the total non-carcinogenic risk (THI) indicated that heavy metals posed a potential non-carcinogenic risk to children, while the total carcinogenic risk (TCR) remained relatively high, mainly in the northern part of the study area. The results of the Monte Carlo simulation showed that the non-carcinogenic risk (HI) for all heavy metals was <1, but the total non-carcinogenic risk index (THI) for children was >1, indicating a potential health risk above the safe threshold. Meanwhile, nearly 100% and 99.94% of the TCR values exceeded 1 × 10⁻⁴ for children and adults, indicating that Cr and Ni are priority heavy metals for control. The research results provide the necessary scientific basis for the prevention and control of heavy metals in agricultural soils. Full article

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location’s importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma–carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications. Full article

Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) as donors and BALB/c mice as recipients. Slit-lamp examination and optical coherence tomography were performed for clinical evaluations for 16 weeks post-procedure. Criteria for the assessment of corneal opacity were established and the animals were graded weekly. Additionally, we assessed corneal endothelial cell density by harvesting the corneas and staining with zonula occludens-1 (ZO-1). Lastly, lymph nodes were collected, and CD4⁺ T cells were MACS-sorted and co-cultured with syngeneic or allogeneic antigen-presenting cells (APCs) to assess the IFN-γ expression levels by alloreactive Th1 cells (ELISPOT) in response to the direct (donor) or indirect (host) pathways of sensitization. Results: We observed graft failure in four animals, including irreversible corneal opacity, graft detachment, and anterior synechiae in the first four weeks. The remaining animals were graded between 0 and 5 as per the established criteria. The total and graft corneal thickness and endothelial cell density progressively worsened with a higher grade of corneal opacity. The direct allosensitization of Th1 cells was significantly higher in mice with a higher grade of corneal opacity. At 16 weeks follow-up, the grafts remained stable with low opacity scores in syngeneic EK recipients; however, the opacity scores were higher and variable in allogeneic EK recipients. Conclusions: These findings establish a standardized protocol to assess the graft outcomes in a murine model of EK. Furthermore, we delineate the underlying immunological pathway that contributes to the immune-mediated rejection of grafts in this model. Full article

Background and Objectives: Despite a global decrease in HIV incidence, recent trends in Türkiye indicate a concerning rise, particularly among younger populations and women. This study investigates the local and regional dynamics influencing these trends using advanced epidemiological methodologies. Material and Methods: Utilizing Age–period–cohort analysis and joinpoint regression, we analysed HIV incidence and prevalence data from the Global Burden of Disease study for Türkiye. These methods allowed for a detailed examination of changes over time, identifying specific age groups and periods with significant shifts in incidence rates. Results: Key findings include a 13.03% increase in annual percentage change among males aged 15–19 and an 11.37% increase among females in the same age group. Additionally, the incidence rates among females have shown a significant rise after 2008. Conclusions: The rising HIV incidence in Türkiye reflects complex socio-economic, cultural, and biological factors, with significant increases among young people and women. Addressing these challenges requires targeted interventions, comprehensive educational programs, and inclusive healthcare services to align with global efforts and commitments. The study underscores the importance of incorporating young people in decision-making processes to effectively combat HIV in Türkiye. Full article

The incidence of early-onset colorectal cancer (EO-CRC) in individuals under 50 years old is rapidly increasing in the United States. This study aims to evaluate EO-CRC incidence rates using data from the Global Burden of Disease Study (GBD) 2021, providing insights into trends from 1990 to 2021. We employed an age–period–cohort (APC) model analysis to estimate the effects of age, time period, and birth cohort on EO-CRC incidence. Our findings indicate that the number of EO-CRC cases rose from 6256 (95% UI: 6059–6456) in 1990 to 9311 (95% UI: 8859–9744) in 2021, a 49% increase from 1990 to 2021. The age-standardized incidence rate per 100,000 population increased by 34% during this period. The net drift in females (0.22%, 95% CI: 0.20–0.24) was slightly higher than in males (0.21%, 95% CI: 0.19–0.23) (p = 0.45). The APC analysis revealed that being over 25 years old, the period from 2005–2021, and being born after 1983 negatively impacted EO-CRC incidence rates, with a sharp rise after 2000 and a reduction among females from 2017 to 2021. Our study highlights the need for targeted prevention strategies and further research to understand these trends. Full article

The bioavailability of a monoclonal antibody (mAb) or another therapeutic protein after subcutaneous (SC) dosing is challenging to predict from first principles, even if the impact of injection site physiology and drug properties on mAb bioavailability is generally understood. We used a physiologically based pharmacokinetic model to predict pre-systemic clearance after SC administration mechanistically by incorporating the FcRn salvage pathway in antigen-presenting cells (APCs) in peripheral lymph nodes, draining the injection site. Clinically observed data of the removal rate of IgG from the arm as well as its plasma concentration after SC dosing were mostly predicted within the 95% confidence interval. The bioavailability of IgG was predicted to be 70%, which mechanistically relates to macropinocytosis in the draining lymph nodes and transient local dose-dependent partial saturation of the FcRn receptor in the APCs, resulting in higher catabolism and consequently less drug reaching the systemic circulation. The predicted free FcRn concentration was reduced to 40–45%, reaching the minimum 1–2 days after the SC administration of IgG, and returned to baseline after 8–12 days, depending on the site of injection. The model predicted the uptake into APCs, the binding affinity to FcRn, and the dose to be important factors impacting the bioavailability of a mAb. Full article

Background: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). Methods: CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999–2019) from the Institute of Health Metrics and Evaluation were analyzed. Trials investigating TKI use in CML were obtained from ClinicalTrials.gov. Site data for eligible trials (N = 30) and DALYs were analyzed. TKI approvals, DALYs, and IRs were summarized by SDI. Results: North America (NA) had significant decreases in annual percent change (APC) in DALYs and incidence rates from 1999 to 2004. IRs were highest in Europe and Central Asia (ECA) and NA, while DALYs were highest in South Asia (SAsia) and Sub-Saharan Africa (SSA). Countries in the high-SDI quintile were likely to have lower DALYs than lower-SDI quintiles. Differences in regional DALYs vs. sites in TKI trials were significant for SAsia, SSA, and ECA. High-SDI countries were included in all 30 trials, and TKI approvals were prominent in high-SDI (142) vs. low-SDI (14) countries. Conclusions: The inclusion of disproportionately affected countries during the design of and recruitment into clinical trials should occur, as should TKI availability. The lack of representation demonstrates healthcare disparities. Full article

The closed-loop material and energy cycles of islands increase the susceptibility of their internal ecosystem components to heavy metal accumulation and transfer. However, limited research on the island scale hinders our understanding of heavy metal environmental geochemistry in this unique environment. This study focused on assessing a tropical island’s ecological risk by investigating heavy metal contamination and potential sources. The results revealed elevated cadmium and nickel concentrations in 0.44–1.31% of soil samples, particularly in coastal plains and developed areas. Using the absolute principal component score-multiple linear regression (APCS-MLR) model assisted by GIS mapping, we identified three contamination sources: geological factors, agricultural activities, and traffic emissions. Network analysis indicated direct exposure risks of vegetation and soil microorganisms to contaminated soil (0.4611 and 0.7687, respectively), with nickel posing the highest risk, followed by Zn, Cd, Pb, Cu, and Cr with risks transferring across trophic levels. These findings provide crucial insights for mitigating ecological risks associated with heavy metals by controlling priority pollutants and their sources in tropical island environments. Full article

Quinoa (Chenopodium quinoa Willd) sprouts are rich in bioactive compounds that offer numerous health benefits. However, limited research exists on their cultivation, nutritional value, and processing potential. This study compared the nutritional composition and antioxidant activity of quinoa sprouts from different varieties at various time points. Results showed a general increase in most nutrients over time. At the 24 h mark, JQ-W3 exhibited a 17.77% increase in leucine, 1.68 times higher than in eggs, along with a 6.11-fold elevation in GABA content. JQ-B1 exhibited the preeminent antioxidant potency composite (APC) score. Saponins, known for their bitter taste, decreased at 12 h but returned to original levels by 24 h. Based on nutritional components and saponin content, 24 h sprouted black quinoa JQ-B1 and white quinoa JQ-W3 were selected, providing a basis for quinoa sprout development in the food industry. These findings contribute to the understanding and utilization of quinoa sprouts. Full article

Phycocyanobilin (PCB) is a small chromophore found in certain phycobiliproteins, such as phycocyanins (PCs) and allophycocyanins (APCs). PCB, along with other phycobilins (PBs) and intermediates such as biliverdin (BV) or phycoerythrobilin (PEB), is attracting increasing biotechnological interest due to its fluorescent and medicinal properties that allow potential applications in biomedicine and the food industry. This study aims to optimize PCB synthesis in Escherichia coli BL21 (DE3) and scale the process to a pre-industrial level. Parameters such as optimal temperature, inducer concentration, initial OD₆₀₀, and stirring speed were analyzed in shake flask cultures to maximize PCB production. The best results were obtained at a temperature of 28 °C, an IPTG concentration of 0.1 mM, an initial OD₆₀₀ of 0.5, and an orbital shaking speed of 260 rpm. Furthermore, the optimized protocol was scaled up into a 2 L bioreactor batch, achieving a maximum PCB concentration of 3.8 mg/L. Analysis of the results revealed that biosynthesis of exogenous PBs in Escherichia coli BL21 (DE3) is highly dependent on the metabolic burden of the host. Several scenarios, such as too rapid growth, high inducer concentration, or mechanical stress, can advance entry into the stationary phase. That progressively halts pigment synthesis, leading, in some cases, to its excretion into the growth media and ultimately triggering rapid degradation by the host. These conclusions provide a promising protocol for scalable PCB production and highlight the main biotechnological challenges to increase the yields of the process. Full article