Category: Nevin Manimala

Bioinformatics. 2024 Oct 26:btae642. doi: 10.1093/bioinformatics/btae642. Online ahead of print.

ABSTRACT

SUMMARY: Introgression (the flow of genes between species) is a major force structuring the evolution of genomes, potentially providing raw material for adaptation. Here, we present a versatile Bayesian model selection approach for detecting and quantifying introgression, df0BF, that builds upon the recently published distance-based df statistic. Unlike df, df0BF accounts for the number of variant sites within a genomic region. The underlying model parameter of our df0BF method, here denoted as dfθ, accurately quantifies introgression, and the corresponding Bayes Factors (df0BF) enables weighing the strength of evidence for introgression. To ensure fast computation we use conjugate priors with no need for computationally demanding MCMC iterations. We compare our method with other approaches including df, fd, Dp, and Patterson’s D using a wide range of coalescent simulations. Furthermore, we showcase the applicability of df0BF and dfθ using whole-genome mosquito data. Finally, we integrate the new method into the powerful genomics R-package PopGenome.

AVAILABILITY: The presented methods are implemented within the R-package PopGenome (https://github.com/pievos101/PopGenome) and the simulation as the application results can be reproduced from the source code available from a dedicated GitHub repository (https://github.com/pievos101/Introgression-Simulation).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39460951 | DOI:10.1093/bioinformatics/btae642

Bioinformatics. 2024 Oct 26:btae618. doi: 10.1093/bioinformatics/btae618. Online ahead of print.

ABSTRACT

MOTIVATION: The versatile binding properties of antibodies have made them an extremely important class of biotherapeutics. However, therapeutic antibody development is a complex, expensive and time-consuming task, with the final antibody needing to not only have strong and specific binding, but also be minimally impacted by developability issues. The success of transformer-based language models in protein sequence space and the availability of vast amounts of antibody sequences, has led to the development of many antibody-specific language models to help guide antibody design. Antibody diversity primarily arises from V(D)J recombination, mutations within the CDRs, and/or from a few non-germline mutations outside the CDRs. Consequently, a significant portion of the variable domain of all natural antibody sequences remains germline. This affects the pre-training of antibody-specific language models, where this facet of the sequence data introduces a prevailing bias towards germline residues. This poses a challenge, as mutations away from the germline are often vital for generating specific and potent binding to a target, meaning that language models need be able to suggest key mutations away from germline.

RESULTS: In this study, we explore the implications of the germline bias, examining its impact on both general-protein and antibody-specific language models. We develop and train a series of new antibody-specific language models optimised for predicting non-germline residues. We then compare our final model, AbLang-2, with current models and show how it suggests a diverse set of valid mutations with high cumulative probability.

AVAILABILITY AND IMPLEMENTATION: AbLang-2 is trained on both unpaired and paired data, and is freely available at https://github.com/oxpig/AbLang2.git.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Journal Name online.

PMID:39460949 | DOI:10.1093/bioinformatics/btae618

Semin Ophthalmol. 2024 Oct 26:1-6. doi: 10.1080/08820538.2024.2421475. Online ahead of print.

ABSTRACT

PURPOSE: To describe the presence of pupillary peaking and dysphotopsias in a sample of eyes following glaucoma drainage device (GDD) surgery.

METHODS: Cross-sectional analysis of 68 glaucoma patients with GDD, 45 patients with glaucoma and no GDD, and 50 control patients was conducted in a single academic center. Patients with an appropriate diagnosis that met the inclusion criteria were asked to enroll in the study. All patients received an 8-item dysphotopsia questionnaire and were age-matched. Photographs of pupils were taken to assess pupillary peaking. One-way analysis of variance (ANOVA) testing was performed for statistical analysis.

RESULTS: Of the 68 patients with GDD, 25 (36.76%) had pupillary abnormalities with peaking most commonly occurring in the direction of the tube entry superotemporally, and 50 (73.53%) had reported one or more dysphotopsias. In patients reporting one or more dysphotopsias, the rate of lines, crescents, ghost images, and shadows was significantly higher when compared to glaucoma patients without GDD and control patients (p < .01). This corresponded to a lower best-corrected visual acuity in the GDD group compared to the glaucoma and control groups (p < .001).

CONCLUSIONS: Over a third of glaucoma patients receiving GDD had pupillary abnormalities, and nearly 3 out of 4 patients with GDD reported one or more dysphotopsias when compared to glaucoma patients without GDD and an age-matched control group. Glaucoma specialists and patients should be aware of these complications when proceeding with GDD surgery.

PMID:39460927 | DOI:10.1080/08820538.2024.2421475

Am J Cardiovasc Drugs. 2024 Oct 26. doi: 10.1007/s40256-024-00689-7. Online ahead of print.

ABSTRACT

BACKGROUND: Colchicine has been shown to reduce adverse cardiovascular events (ACE) and stroke among patients with coronary artery disease. However, its efficacy with short- and long-term use and risk of stroke has not been well studied, with conflicting results to date.

OBJECTIVE: We sought to evaluate the efficacy of colchicine for the prevention of stroke and other cardiovascular outcomes and to evaluate the effect of short- and long-term use.

METHODS: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until July 20th, 2024. Odds ratios (ORs) were pooled using a random-effect model, and a p value of < 0.05 was considered statistically significant.

RESULTS: A total of 16 RCTs with 24,967 patients were included (12,538 in colchicine group and 12,429 in the control group) in the analysis. Pooled analysis of primary outcomes showed that risk of incidence of stroke was comparable between colchicine and placebo groups (OR 0.78, 95% confidence interval [CI] 0.59-1.02, p = 0.07). Pooled analysis of secondary outcomes showed that colchicine significantly reduced the risk of incidence of ACE by 33% (OR 0.67, 95% CI 0.54-0.82, p < 0.001), and myocardial infarction by 21% (OR 0.79, 95% CI 0.65-0.95, p = 0.01) compared with placebo. However, the risk of all-cause mortality (OR 0.98, 95% CI 0.79-1.21, p = 0.83) and cardiovascular mortality (OR 0.78, 95% CI 0.56-1.08, p = 0.14) were comparable between both groups of patients.

CONCLUSION: Colchicine was associated with an overall reduction in the risk of incidence of ACE and MI; however, no such effect was observed with mortality and stroke.

PMID:39460903 | DOI:10.1007/s40256-024-00689-7

Ophthalmol Ther. 2024 Oct 26. doi: 10.1007/s40123-024-01054-2. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to evaluate intraretinal microvascular abnormalities (IRMA) in eyes with advanced nonproliferative diabetic retinopathy (NPDR) using multimodal approach in co-located areas focusing on central retina (up to 50°) and to look at possible correlations between IRMA and other structural changes, like ischemia and presence of microaneurysms.

METHODS: The RICHARD study (NCT05112445) included 60 eyes from 60 patients with type 2 diabetes with moderate-severe NPDR, diabetic retinopathy severity levels 43, 47, and 53 (DRSS). IRMA were defined as capillary tortuosity covering a minimum circular area of 300 µm (calculated to correspond to the Early Treatment Diabetic Retinopathy Study standard photo 8A) and were identified using multimodal imaging with distinct fields of view (FoV): color fundus photography (CFP) using a Topcon TRC-50DX camera (Topcon Medical Systems, Japan), Optos California ultra wide field fundus fluorescein angiography (UWF-FFA) (Optos plc, UK), and swept-source optical coherence tomography angiography (SS-OCTA) (PLEX® Elite 9000, ZEISS, USA). Different areas of the retina were examined: central macula (up to 20°) and posterior pole (between 20° and 50°).

RESULTS: Multimodal imaging was used to identify IRMA in co-located areas (FoV < 50°) including UWF-FFA, CFP, and SS-OCTA. In eyes with DRSS levels 47 and 53, IRMA were identified in both areas of the retina, while in eyes with DRSS level 43, IRMA were detected only outside of the central macula (FoV > 20°). Our results show that when evaluating the presence of IRMA (FoV < 50°), UWF-FFA detected 203 IRMA, SS-OCTA detected 133 IRMA, and CFP detected 104 IRMA. Our results also show that the presence of IRMA was positively associated with presence of microaneurysms.

CONCLUSIONS: Identification of IRMA in eyes with advanced NPDR is better achieved by UWF-FFA than CFP and SS-OCTA. A statistically significant correlation was found between the presence of IRMA and the increase in number of microaneurysms.

TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05112445.

PMID:39460896 | DOI:10.1007/s40123-024-01054-2

Aging Clin Exp Res. 2024 Oct 26;36(1):212. doi: 10.1007/s40520-024-02864-x.

ABSTRACT

BACKGROUND: Dynapenic abdominal obesity (DAO) may be associated with an increased risk of disability. However, to date, this has not been investigated in low- and middle-income countries (LMICs), while the mediators are largely unknown.

AIMS: Therefore, we aimed to investigate the association between DAO and activities of daily living (ADL) disability, and to identify potential mediators among older adults from six LMICs.

METHODS: Cross-sectional, nationally representative data from the WHO Study on global AGEing and adult health were analyzed. Data on 20,198 adults aged ≥ 60 years were analyzed [mean (SD) age 69.3 (13.1) years; 54.1% females]. Dynapenia was defined as handgrip strength of < 26 kg for men and < 16 kg for women. Abdominal obesity was defined as waist circumference of > 88 cm for women and > 102 cm for men. DAO was defined as having both dynapenia and abdominal obesity. Disability was defined as severe or extreme difficulty in conducting at least one of six types of ADL. Multivariable logistic regression and mediation analysis were conducted.

RESULTS: Compared to no dynapenia and no abdominal obesity, DAO was significantly associated with 2.08 (95%CI = 1.37-3.17) times higher odds for ADL disability Mediation analysis showed that diabetes (mediated percentage 4.7%), hypertension (7.2%), and angina (7.7%) were significant mediators in the association between DAO and ADL disability.

CONCLUSIONS: DAO was associated with increased odds for ADL disability among older adults from LMICs. Future longitudinal studies are warranted to assess temporal associations, and whether addressing or preventing DAO can impact on future occurrence of disability.

PMID:39460890 | DOI:10.1007/s40520-024-02864-x

Curr Med Sci. 2024 Oct 26. doi: 10.1007/s11596-024-2932-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the accuracy and parsing ability of GPT 4.0 for Japanese medical practitioner qualification examinations in a multidimensional way to investigate its response accuracy and comprehensiveness to medical knowledge.

METHODS: We evaluated the performance of the GPT 4.0 on Japanese Medical Licensing Examination (JMLE) questions (2021-2023). Questions are categorized by difficulty and type, with distinctions between general and clinical parts, as well as between single-choice (MCQ1) and multiple-choice (MCQ2) questions. Difficulty levels were determined on the basis of correct rates provided by the JMLE Preparatory School. The accuracy and quality of the GPT 4.0 responses were analyzed via an improved Global Qualily Scale (GQS) scores, considering both the chosen options and the accompanying analysis. Descriptive statistics and Pearson Chi-square tests were used to examine performance across exam years, question difficulty, type, and choice. GPT 4.0 ability was evaluated via the GQS, with comparisons made via the Mann-Whitney U or Kruskal-Wallis test.

RESULTS: The correct response rate and parsing ability of the GPT4.0 to the JMLE questions reached the qualification level (80.4%). In terms of the accuracy of the GPT4.0 response to the JMLE, we found significant differences in accuracy across both difficulty levels and option types. According to the GQS scores for the GPT 4.0 responses to all the JMLE questions, the performance of the questionnaire varied according to year and choice type.

CONCLUSION: GTP4.0 performs well in providing basic support in medical education and medical research, but it also needs to input a large amount of medical-related data to train its model and improve the accuracy of its medical knowledge output. Further integration of ChatGPT with the medical field could open new opportunities for medicine.

PMID:39460888 | DOI:10.1007/s11596-024-2932-9

Trop Anim Health Prod. 2024 Oct 26;56(8):359. doi: 10.1007/s11250-024-04197-3.

ABSTRACT

Egg quality is a vital factor in the poultry industry. High-quality eggs not only meet consumer expectations for appearance, taste, and nutritional value but also have high marketability, profitability, and consumer satisfaction. Accordingly, we executed our research with the purpose of determining chromosomal regions and genetic markers associated with egg quality in an F2 cross-bred chicken population under tropical conditions; we determined these through a genome-wide association study and quantitative trait locus (QTL) mapping. This population was created by cross-breeding the L2 line of Taiwan Country chickens, which is adapted to local conditions in Taiwan, with an experimental line (R-line) of Rhode Island Red layer chickens, which was developed by the French National Research Institute for Agriculture, Food and the Environment. A 60 K single nucleotide polymorphism (SNP) genotyping array for chickens was employed to execute the analysis. Our analysis revealed 40 QTLs associated with egg quality under tropical conditions, namely 20 QTLs with genome-wide statistical significance and 20 QTLs with chromosome-wide statistical significance. Furthermore, we identified 93 SNPs exerting discernible effects on egg quality, with 10 of these effects exhibiting genome-wide significance and 83 exhibiting potential significance. The majority of the detected QTL regions and SNPs agreed with those identified as having an association with egg quality or production traits in previous studies, thus supporting the interrelationships determined between the studied characteristics. The findings of this study enhance the understanding regarding the genetic regulation governing chicken egg quality, thereby serving as a valuable reference for future functional investigations.

PMID:39460847 | DOI:10.1007/s11250-024-04197-3

Eur J Health Econ. 2024 Oct 26. doi: 10.1007/s10198-024-01720-z. Online ahead of print.

NO ABSTRACT

PMID:39460843 | DOI:10.1007/s10198-024-01720-z

Environ Monit Assess. 2024 Oct 26;196(11):1108. doi: 10.1007/s10661-024-13254-1.

ABSTRACT

Water quality monitoring is paramount in identifying and mitigating pollution sources, protecting aquatic ecosystems, and ensuring safe water for human and wildlife consumption. This study is aimed at evaluating the quality of drinking water sources in three communities located in a Sustainable Use Conservation Unit in the municipality of Mangaratiba, Rio de Janeiro, Brazil, employing a multivariate statistical analysis. A total of 161 water samples were collected from January to December 2022, encompassing 32 surface water and 129 tap water samples. Physicochemical parameters were determined in situ employing a Horiba U50 multiparameter probe. The samples were stored and transported at 4 °C to the laboratory for microbiological analyses concerning total coliforms and Escherichia coli using a commercial enzymatic test. All samples contained coliforms, while E. coli were detected in 87% of the samples. The multivariate analysis indicated that the microbiological water quality in sampling region R2 was influenced by rainy periods and that, in general, the water quality within R3 was the most affected by the transport of solids to the water sources. The statistical methods applied herein aided in characterizing the study areas and detecting points of attention regarding physicochemical and microbiological parameters that significantly influence the water quality of each sampling point. Representative points for each study region were identified and may be employed for future monitoring and prevention actions.

PMID:39460842 | DOI:10.1007/s10661-024-13254-1