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Insights into the structural dynamics of the secretin family (class B1) G protein-coupled receptors

CYP2B6*6 single nucleotide polymorphism among patients with uncomplicated malaria in Adjumani district, Uganda: Implications on efficacy of artemether-lumefantrine

CYP2B6, one of the most polymorphic enzymes, plays a major role in the metabolism of artemisinin and its derivatives. Variation in the frequency of the most common, yet functionally deficient CYP2B6*6 allele may impact artemisinin exposure, potentially contributing to differences in treatment outcomes. This study assessed the prevalence of the CYP2B6*6 genotype among patients with uncomplicated malaria treated with artemether-lumefantrine at Adjumani District Hospital in the West Nile region, Uganda. A total of 100 randomly selected patients with microscopically confirmed uncomplicated P. falciparum malaria receiving artemether-lumefantrine (AL) were included in the study. Blood samples, 2−3 mL each, were collected using EDTA tubes on days 0 and 3 after AL administration. DNA was extracted using Qiagen DNA Mini kit. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to determine the CYP2B6*6 genotype of the participants. P. falciparum positivity was determined by microscopy and qPCR. For qPCR, parasite clearance was determined using comparative CT value. Data analysis was done using STATA ver 17.0 at a 95% significance level. Among the malaria patients genotyped, 65% were female, and 35% were male, with a mean age of 17 ± 10 years. The CYP2B6*6 variant allele frequency was 0.37, and the genotype frequency was 43% GG, 17% TT and 40% GT. P. falciparum day 3 microscopy positivity was 14% (6/43) among the GG, 37.5% (15/40) among the GT, and 17.64% (3/17) among the TT patients. PCR positivity rates were 58.1% (25/43) in the GG, 72.5% (29/40) in the GT, and 52.9% (9/17) in the TT patients. Heterozygous individuals (GT) had slow parasite clearance by a 10-fold difference compared to the homozygous (GG, TT) individuals (U = 323.0; Z = −2.3442; p = 0.019). Malaria patients in Adjumani district had a high frequency of the CYP2B6*6 variant allele. Interindividual variability in P. falciparum clearance exists, with heterozygous patients demonstrating slow artemether-lumefantrine P. falciparum parasite clearance. There is a need to consider incorporating host genomic factors, such as metabolising enzyme genotype into routine Therapeutic Efficacy Studies (TES).

First-in-class inhibitors of Nsp15 endoribonuclease of SARS-CoV-2: Modeling, synthesis, and enzymatic assay of thiazolidinedione and rhodanine analogs

Prevalence and associated factors for HIV, HBV and syphilis coinfections among pregnant women attending antenatal care in Tanzania

Background Coinfection with HIV, hepatitis B virus (HBV) and syphilis increases the risk of vertical transmission. Hence, affecting overall maternal health and child health outcomes. The Tanzanian government is planning to add HBV screening to the existing Prevention of Mother to Child Transmission (PMTCT) of HIV and syphilis program; however, the burden of coinfections in the country is unknown. Therefore, this study aimed to determine the prevalence of HIV, HBV and syphilis coinfections and their associated factors among pregnant women receiving antenatal care in Tanzania. Methods A facility-based cross-sectional study design was conducted, utilizing data from the national feasibility study of triple testing for HIV, syphilis and HBV among pregnant women. The data were analysed via STATA version 16.1, and bivariate and multivariate logistic regressions were used to check for associations. Variables with a P value of < 0.05 were considered statistically significant. Results A total of 7,828 pregnant women were enrolled, 0.4% (95% CI 0.3–0.6) of whom were coinfected. The prevalence rates for HIV/HBV, HIV/syphilis, HBV/syphilis and HIV/HBV/syphilis coinfections were 0.1% (95% CI 0.1–0.2), 0.2% (95% CI 0.1–0.4), 0.1% (95% CI 0.0–0.2) and 0.0% (95% CI 0.0–0.1), respectively. History of multiple sexual partners (AOR 6.1; 95% CI: 1.3–29.7, P = 0.025) was associated with HIV/HBV coinfection. Age 25–49 years (AOR 13.5; 95% CI 1.8–103.8, P = 0.012) and marital status (AOR 0.2; 95% CI 0.1–0.8, P = 0.018) were associated with HIV/syphilis coinfection. For HBV/syphilis coinfection, marital status (AOR 0.1; 95% CI 0.0–0.9, P = 0.036) and history of multiple sexual partners (AOR 16.8; 95% CI 2.5–114.9, P = 0.004) were independently associated. Conclusion Coinfections are present among pregnant women in Tanzania; therefore, it is important to include hepatitis B screening in the existing PMTCT of HIV and syphilis program. Interventions should focus on single, child-bearing women with multiple sexual partners.

Hypoxia-inducible factor 1α in Schwann cells promotes peripheral nerve myelination

Comparing variable and feature selection strategies for prediction - protocol of a simulation study in low-dimensional transplantation data

The integration of machine learning methodologies has become prevalent in the development of clinical prediction models, often suggesting superior performance compared to traditional statistical techniques. Within the scope of low-dimensional datasets, encompassing both classical and machine learning paradigms, we plan to undertake a comparison of variable selection methodologies through simulation-based analysis. The principal aim is the comparison of the variable selection strategies with respect to relative predictive accuracy and its variability, with a secondary aim the comparison of descriptive accuracy. We use six distinct statistical learning approaches across both data generation and model learning. The present manuscript is a protocol for the corresponding simulation study registration (Study registration Open Science Framework ID: k6c8f). We describe the planned steps through the Aims, Data, Estimands, Methods, and Performance framework for simulation study design and reporting.

CryoEM structure of Rv2531c reveals cofactor-induced tetramer–dimer transition in a tuberculin amino acid decarboxylase

The impact of Evidence-Based Pharmacy on the quality of pharmaceutical care: A survey study

Applying Evidence-Based Pharmacy (EBPharm) principles is essential in pharmacy practice as it allows therapeutic decisions to be grounded in the best available scientific evidence. This approach enables pharmacists to provide patients with more effective and safer therapies, reducing the risk of adverse effects. This study assessed the EBPharm knowledge level among pharmacy professionals. Data were collected using a custom-designed online survey. The study also explored and defined the concept of EBPharm, offering insights into medical databases, types of scientific research, and evaluations of their quality and reliability. The study revealed widespread application of EBPharm principles among Polish pharmacy professionals, with significant associations between their use and factors such as professional experience (Chi² = 7.905518, p = 0.04801) and higher salaries. Respondents with formal EBPharm training demonstrated improved ability to evaluate scientific evidence (Chi² = 12.03125, p = 0.00244), while financial stability was linked to better systematic review skills (Chi² = 43.15693, p = 0.00000) and use of databases (Chi² = 63.14029, p = 0.00000). However, knowledge gaps remain, particularly among less experienced professionals, with only 30.35% of participants receiving formal training and 8.42% deeming it sufficient. Frequent use of informal sources by pharmacy technicians and limited familiarity with frameworks like PICO (Chi² = 37.65817, p = 0.00000) highlight the need for accessible, structured education. Targeted training, financial incentives, and greater reliance on reliable sources could enhance EBPharm integration, improving care quality and patient safety.

Building on the momentum of N-of-1 base editor therapies for rare diseases

Regulation of steady state ribosomal transcription in Mycobacterium tuberculosis: Intersection of sigma subunits, superhelicity, and transcription factors

Prevalence and associated factors of pregnancy induced hypertension among pregnant women in public hospitals of Hadiya Zone, Central Ethiopia: A cross-sectional study

Background Pregnancy-induced hypertension is one of the global public health burdens contributing to several adverse perinatal outcomes. However, data on the prevalence and associated factors of PIH is limited in Hadiya Zone, central Ethiopia. Methods We conducted a cross-sectional study among women attending antenatal care in the four public hospitals in the Hadiya zone from August 1, 2023, to January 30, 2024. The total sample size (433) was proportionally allocated to each hospital. Data were collected by face-to-face interview using a structured questionnaire. Blood pressure was measured by a digital Sphygmomanometer, and Pregnancy-induced hypertension status was considered if systolic blood pressure was ≥ 140 mmHg and/or diastolic blood pressure ≥90 mmHg on two measurements among pregnant women with gestational age > 20 weeks. Factors associated with Pregnancy-induced hypertension were identified by multivariable binary logistic regression analysis, as expressed by adjusted odds ratio (aOR) and its 95% confidence interval. Results The mean age of the participants was 29.4 years (SD = ±4.6), and the majority of women were multiparous (59.6%). The prevalence of Pregnancy-induced hypertension was 13.4% (95% CI: 10.2% – 16.9%), of which 81% were preeclampsia. In the multivariable analysis, PIH was associated with, the poorest wealth index (aOR = 0.26, 95%CI: 0.08–0.90), having a family history of hypertension (aOR = 12.52,95%CI: 4.52–34.62), overweight maternal BMI (aOR = 4.24, 95%CI: 2.06–8.72), and gestational age (aOR = 0.21 at 95% CI: 0.06–0.82). Conclusions More than 13 out of 100 pregnant women were found to have pregnancy-induced hypertension in the Hadiya zone, Southern Ethiopia. The high prevalence of Pregnancy-induced hypertension and its association with wealth index, gestational age, overweight/obesity and family history of hypertension/Pregnancy-induced hypertension underscores the need for targeted, tailored, and contextualized interventions to address Pregnancy-induced hypertension in the Hadiya zone. Creating awareness on Pregnancy-induced hypertension among pregnant women and the general population and enhancing early screening and detection services in the community and healthcare facilities need to be strengthened in the Hadiya zone.

FDA new drug approvals in Q2 2025

Leber's hereditary optic neuropathy–associated ND1 3733G>C mutation ameliorates the mitochondrial quality control and cellular homeostasis

Abdominal organ injury in cardiac arrest: Systematic literature review

Background Both cardiopulmonary resuscitation (CPR) and ischaemia could lead to abdominal organ injury. However, the importance of abdominal injury in cardiac arrest remains uncertain. We aimed to systematically review indexed literature to describe incidence of abdominal injury after non-traumatic cardiac arrest and associations with outcome. Methods We searched MEDLINE/PubMed, Embase, The Cochrane Database of Systematic Reviews and Scopus up to 12th September 2024 for studies reporting differences in outcomes between patients with and without abdominal injury, and all studies reporting abdominal adverse events after cardiac arrest. Two independent reviewers screened articles for eligibility. One reviewer extracted data and assessed risk of bias using the Critical Appraisal Skills Programme checklist. Injuries were defined as traumatic or ischaemic, either in the studies or otherwise by the reviewers. Results were summarized and presented in tables and Forest plots. We followed the PRISMA guidelines, and registered the study in PROSPERO. Results We included 68 studies and 140 case reports. Most studies were single-centre. Quantitative synthesis of evidence was not feasible given high heterogeneity and risk of bias. Traumatic injuries affected mostly liver and spleen, with incidences from 0% to 15%, reaching 29% in one study of mechanical chest compressions. Life-threatening injuries were uncommon. The incidence of ischaemic injury was dependent on assessment method; 7% to 28% had liver injury, 0.7% to 2.5% was diagnosed with non-occlusive mesenteric ischaemia, 82% to 100% had intestinal injury measured by biomarkers. Ischaemic injuries were associated with mortality. Conclusion In this comprehensive review of abdominal injuries following cardiac arrest, CPR-related traumatic injuries were uncommon, but should be considered in patients with unexplained clinical deterioration. Ischaemic injury incidence ranged from 0.7% to 100%, and was consistently associated with mortality. Whether abdominal ischaemia independently contributes to poor outcomes remains unresolved and warrants further investigation. PROSPERO ID: CRD42022311508.

GAPDH heme delivery to Indoleamine 2,3-dioxygenase 1 involves their complex formation and complementary charge pairing at the protein-protein interface

Monetary policy, debt maturity structure and corporate investment efficiency: Evidence from China

This paper examines the impact of monetary policy on corporate investment efficiency from the perspective of debt maturity structure by selecting data on Chinese non-financial listed firms and Chinese macroeconomic data from 2007–2022. The results find that loose monetary policy can have a dual effect on corporate investment efficiency by extending corporate debt maturity structure, which is manifested in alleviating corporate under-investment and promoting corporate over-investment. Heterogeneity analysis shows that in high bank competition areas, the debt maturity structure effect of monetary policy is effective in mitigating under-investment and promoting over-investment by enterprises. In contrast, in low bank competition regions, the debt maturity structure effect of monetary policy promotes corporate over-investment but has no significant effect on corporate under-investment. In addition, the debt maturity structure effect of monetary policy can effectively alleviate under-investment and promote over-investment of enterprises with low financing constraints. And it has no significant effect on the under-investment and over-investment behavior of high financing constraint enterprises. The research in this paper reveals the specific mechanism of monetary policy affecting the investment efficiency of enterprises, which has certain reference value for the objective evaluation of monetary policy effects.

PAXX/Ku interaction is rate limiting for repair of double-strand DNA breaks requiring end processing

Analytical validation and sequencing coverage studies suggest that performance of a liquid biopsy assay is tumor agnostic (DNA-is-DNA)

Per regulatory and standard requirements (e.g., Clinical & Laboratory Standards Institute (CLSI) guidelines, United States Food and Drug Administration (FDA) correspondence), analytical validation (AV) for each companion diagnostic (CDx) biomarker should be repeated using a clinical sample set for each cancer type listed as an indication in labelling for a CDx. Using data from AV studies and Foundation Medicine (FMI)’s clinical database, we evaluated the hypothesis that analytical performance of the FoundationOne®Liquid CDx (F1LCDx) assay is not impacted by cancer type and that large sets of clinical, tumor-specific samples might not be necessary for analytical validation of specific CDx biomarkers. We retrospectively evaluated all liquid biopsy samples from F1LCDx assay AV studies that were executed between April 2019 and November 2021 and clinical samples processed by F1LCDx between September 2020 and October 2021. For the samples from AV studies, we evaluated the precision and concordance performance by F1LCDx between tumor types; and for the clinical samples, we performed analyses comparing the distribution of coverage between tumor types. A total of 31,247 F1LCDx clinical samples and 579 samples from F1LCDx AV studies with a total of 335 disease ontologies (DOs) were included in this study. For precision: the median absolute pairwise difference of mean reproducibility between any pairs of two tumor types is 0.94% [0.01%−2.63%] and the median absolute pairwise difference of mean repeatability between any pairs of two tumor types is 0.91% [0.03%−2.98%]. For concordance: the median absolute ∂PPA between any pairs of two tumor types is 1.39% [0.1%−4.1%] and the median absolute ∂NPA between any pairs of two tumor types is 0.05% [0%−1%]. For coverage, a similar distribution was observed between tumor types using F1LCDx clinical samples. Herein, the results based on the extensive cohort of 31,826 liquid biopsy samples sequenced by the F1LCDx assay demonstrated that both analytical assessment of precision and concordance and coverage are comparable among tumor types (i.e., deoxyribonucleic acid (DNA) is DNA). The tumor type that circulating tumor DNA (ctDNA) was derived from is therefore not a vital consideration for AV studies for F1LCDx assay.

Phosphorylation-mediated regulation of the NADPH-dependent glutamate dehydrogenase, SpGdh1, from Schizosaccharomyces pombe

LTR-Net: A deep learning-based approach for financial data prediction and risk evaluation in enterprises

Financial data prediction and risk assessment represent a complex multi-task problem that requires effective handling of time-series data and multi-dimensional features. Traditional models struggle to simultaneously capture temporal dependencies, global information, and intricate nonlinear relationships, resulting in limited prediction accuracy. To address this challenge, we propose LTR-Net, a multi-module deep learning model that combines LSTM, Transformer, and ResNet. LTR-Net effectively processes the multi-dimensional features and dynamic changes in financial data by incorporating a temporal dependency modeling module, a global information capture module, and a deep feature extraction module. Experimental results demonstrate that LTR-Net significantly outperforms existing mainstream models, including LSTM, GRU, Transformer, and DeepAR, across multiple financial datasets. On the Kaggle Financial Distress Prediction Dataset and the Yahoo Finance Stock Market Data, LTR-Net exhibits higher accuracy, stability, and robustness across various metrics such as MSE, RMSE, MAE, and AUC. Ablation experiments further validate the indispensability of each module within LTR-Net, confirming the pivotal roles of the LSTM, Transformer, and ResNet modules in financial data analysis. LTR-Net not only enhances the accuracy of financial data prediction but also exhibits strong generalization capabilities, making it adaptable to data analysis and risk assessment tasks in other domains.