Browse Articles

A kinetic model of copper homeostasis in Saccharomyces cerevisiae

Genotype distribution of human papillomavirus among women with cervical cancer stratified by HIV status in Tanzania

Background Cervical cancer (CC) is the leading cancer among women in Tanzania, especially among those between the ages of 15 and 44. The prevalence of high-risk Human papillomavirus (HR-HPV)-16/18 women in the general population at any given time is 3.3%. HR-HPVs 16 or 18 are the primary cause of CC. The distribution of HPV genotypes among women with CC according to HIV status is unknown in Tanzania. This study aimed to determine the HPV genotype distribution according to HIV status among women with CC in Tanzania. Methods This cross-sectional study was done at Ocean Road Cancer Institute (ORCI) in Tanzania among women with histologically confirmed CC. HIV serology testing was performed. Biopsy was taken from cervical lesions, and DNA was extracted. HPV DNA was amplified by using a previously validated multiplex HPV PCR assay targeting 14 high-risk HPV genotypes (16,18,30,31,33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) and two low‐risk HPV genotypes (6 and 11). Continuous variables were compared using either a student t-test or the Mann-Whitney U test. Fisher’s exact test was employed to compare discrete variables. A P-value less than 0.05 was considered statistically significant. Results We included 100 women with CC. The prevalence of HIV infection in this study was 42%. The prevalence of any HPV infection was 94%, ranging from 1–3 genotypes per woman. HPV. The median age for women living with HIV (WLWH) with CC patients was 45 years (IQR, 31–60), while the median age for HIV-uninfected women with CC patients was 57 years (IQR, 30–78). (p = 0.0001). WLWH and HIV-uninfected women had similar HPV prevalence, except for HPV 35, which was more common in WLWH. There was a trend of high prevalence of HPV 52 and HPV 58 in WLHH compared to HIV-uninfected women, but this difference was not statistically significant. The prevalence of HPV 16 and/or 18 infection in the entire sample was 85%. The combined prevalence of HPV 16 and/or 18 was 76% WLWH and 91% amongst HIV-uninfected women (p = 0.036).The majority of women (77.9%) had single-genotype HPV infection. There was no difference in the distribution of multiple or single HPV genotypes infection by HIV status (p = 0.25). Conclusion In this study, HIV positive women with CC presented at a significantly younger age (45 years) compared to the HIV-negative women (57 years). The prevalence of high-risk HPV is high among women with CC in Tanzania. Distribution of most high-risk HPV genotypes among women with CC was not significantly influenced by HIV status except for HPV 35, which appeared to be more in HIV positive women compared to HIV-negative women. While the majority of the high-risk HPV infections were with single HPV genotypes, the prevalence of multiple high-risk HPV infections was at 22%, with no significant difference between the two HIV statuses. A vaccination program that aptly targets HPV 16 and 18 could prevent up to 85% of CC cases in Tanzania, regardless of HIV. Keywords: Human papillomavirus, cervical cancer, HIV, Tanzania.

PERK and IRE1α promote exosome secretion via blocking lysosomal degradation of multiple vesicular body

Bayesian robust symmetric regression for medical data with heavy-tailed errors and censoring

Bayesian symmetric regression offers a principled framework for modeling data characterized by heavy-tailed errors and censoring, both of which are frequently encountered in medical research. Classical regression methods often yield unreliable results in the presence of outliers or incomplete observations, as commonly seen in clinical and survival data. To address these limitations, we develop a robust Bayesian regression model that incorporates symmetric error distributions such as the Student-t and Cauchy, providing improved resistance to extreme values. The model also explicitly accounts for both right and left censoring through its likelihood structure. Inference is performed using Markov Chain Monte Carlo (MCMC), allowing for accurate estimation of uncertainty. The proposed approach is validated through simulation studies and two real-world medical applications: lung cancer survival analysis and hospital stay duration modeling. Results indicate that the model consistently outperforms traditional methods when dealing with noisy, censored, and non-Gaussian data, highlighting its potential for broad use in medical statistics and health outcome research.

Microcurrent stimulation induces cell death in p53-mutant and 5-FU-resistant breast cancer

Scalable quality control on processing of large diffusion-weighted and structural magnetic resonance imaging datasets

Thorough quality control (QC) can be time consuming when working with large-scale medical imaging datasets, yet necessary, as poor-quality data can lead to erroneous conclusions or poorly trained machine learning models. Most efforts to reduce data QC time rely on quantitative outlier detection, which cannot capture every instance of algorithm failure. Thus, there is a need to visually inspect every output of data processing pipelines in a scalable manner. We design a QC pipeline that allows for low time cost and effort across a team setting for a large database of diffusion-weighted and structural magnetic resonance images. Our proposed method satisfies the following design criteria: 1.) a consistent way to perform and manage quality control across a team of researchers, 2.) quick visualization of preprocessed data that minimizes the effort and time spent on the QC process without compromising the condition/caliber of the QC, and 3.) a way to aggregate QC results across pipelines and datasets that can be easily shared. In addition to meeting these design criteria, we also provide a comparison experiment of our method to an automated QC method for a T1-weighted dataset of N=1560 images and an inter-rater variability experiment for several processing pipelines. The experiments show mostly high agreement among raters and slight differences with the automated QC method. While researchers must spend time on robust visual QC of data, there are mechanisms by which the process can be streamlined and efficient.

Failed cellular surveillance enables pathogenic matrix deposition in a COL2A1-related osteoarthritis

Study on bearing capacity of Mortise-tenon and joint-flange concrete assembled foundation of transmission line under combined load

Mortise-tenon and joint-flange assembled foundation has excellent application as a new type of slab concrete assembled foundation, but there is a lack of research on its bearing capacity. In order to explore the mechanical characteristics and bearing capacity of this type of foundation under combined load (uplift-horizontal load), which is different from the traditional cast-in-place foundation, the uplift bearing model of mortise-tenon and joint-flange assembled foundation and the uplift model of cast-in-place foundation with the same specification were established based on the actual geological environment by finite element software. The stress distribution, vertical and horizontal displacements, and uplift and horizontal bearing capacities of the foundations were simulated and calculated. This study found that the bearing capacity of the Mortise-tenon and joint-flange assembled foundation has not been fully utilized. Specifically, the deformation of the foundation mainly concentrates on the main column, and the load is unable to be transmitted to the lower structure through the flange. Under combined loading (uplift-horizontal load), the load-displacement relationship curve can be roughly divided into three stages: linear slow rise stage, plastic accelerated rise stage, and linear failure stage. During the pull-out process, the foundation demonstrates stress characteristics of segmented load transmission. After the concrete upper column yields, the mortise-tenon and joint-flange connection node receives the load transmitted by the upper column, and continues to transmit the load to the lower column of the foundation after the displacement of the node reaches its limit. When the uplift cumulative displacement of the foundation reaches approximately 13 mm and the horizontal cumulative displacement reaches around 10 mm, the foundation reaches its ultimate state. At this point, its ultimate bearing capacity surpasses that of the cast-in-place foundation of the same specification, with significant improvement. The ultimate uplift bearing capacity increases by 33.34%, while the ultimate horizontal bearing capacity increases by 48.09%.

GoLoco/GPR motif-dependent regulation of Rap1GAP1 by Gαo is disrupted by Gαo encephalopathy variants

Correction: Effects of a low-carbohydrate diet in adults with type 1 diabetes management: A single arm non-randomised clinical trial

Extensive citrullination of human serum albumin is physiological and not inherently immunogenic in rheumatoid arthritis

Divergent trends in structural landscape connectivity from historic and potential future grassland conversion in Alberta, Canada

Grasslands across the Canadian prairies are crucial for maintaining biodiversity and ensuring landscape connectivity. In Alberta, a large portion of natural grasslands has been converted to agricultural cropland or other land uses, while the remaining natural grasslands are mainly used as rangeland. However, with increasing crop demand and food security concerns, there is a potential risk of further grassland conversion to cropland, particularly in areas where climate change may enhance suitability for farming. Here, we (1) quantified the impact of the present state of grasslands on maintaining landscape permeability; and (2) determined how the conversion of remaining grasslands to croplands could affect structural landscape connectivity at multiple spatial scales. We simulated four progressive scenarios of grassland conversion to cropland, starting with grasslands identified as most suitable for farming. Our results revealed that structural landscape connectivity, quantified as mean normalized current density with resistance values based on naturalness, decreased by up to 43% in southwestern and central areas of the Parkland and Grassland regions with higher rates of conversion. Conversion scenarios introduced new areas with notably constrained ecological flow in the Grassland region in the southeastern part of the province. Conversely, increased current density was observed in the Rocky Mountain and Boreal regions, which appear to act as alternative pathways for redirected ecological flow. Future grassland conversion is expected to further shift current flow from the grasslands westward through the foothills of the Rocky Mountain and northward into the Parkland and Boreal regions. These findings underscore the critical role of grasslands in maintaining structural landscape connectivity across Alberta, which is essential for supporting biodiversity and gene flow among species. Simulated changes in connectivity were most pronounced at the finer spatial scale, revealing key areas of past and future permeability shifts. Incorporating local land management decisions is crucial for improving landscape permeability and effective connectivity planning province-wide.

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.