bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solvated interaction energy: from small-molecule to antibody drug design
Authors: Purisima Enrico O. , Corbeil Christopher R. , Gaudreault Francis , Wei Wanlei , Deprez Christophe , Sulea Traian 
Published: June 2023

Scoring functions are ubiquitous in structure-based drug design as an aid to predicting binding modes and estimating binding affinities. Ideally, a scoring function should be broadly applicable, obviating the need to recalibrate and refit its parameters for every new target and class of ligands. Traditionally, drugs have been small molecules, but in recent years biologics, particularly antibodies, have become an increasingly important if not dominant class of therapeutics. This makes the goal of having a transferable scoring function, i.e., one that spans the range of small-molecule to protein ligands, even more challenging. One such broadly applicable scoring function is the Solvated Interaction Energy (SIE), which has been developed and applied in our lab for the last 15 years, leading to several important applications. This physics-based method arose from efforts to understand the physics governing binding events, with particular care given to the role played by solvation. SIE has been used by us and many independent labs worldwide for virtual screening and discovery of novel small-molecule binders or optimization of known drugs. Moreover, without any retraining, it is found to be transferrable to predictions of antibody-antigen relative binding affinities and as accurate as functions trained on protein-protein binding affinities. SIE has been incorporated in conjunction with other scoring functions into ADAPT (Assisted Design of Antibody and Protein Therapeutics), our platform for affinity modulation of antibodies. Application of ADAPT resulted in the optimization of several antibodies with 10-to-100-fold improvements in binding affinity. Further applications included broadening the specificity of a single-domain antibody to be cross-reactive with virus variants of both SARS-CoV-1 and SARS-CoV-2, and the design of safer antibodies by engineering of a pH switch to make them more selective towards acidic tumors while sparing normal tissues at physiological pH.
A cross-sectional study of explainable machine learning in Alzheimer’s disease: diagnostic classification using MR radiomic features
Authors: Leandrou Stephanos , Lamnisos Demetris , Bougias Haralabos , Stogiannos Nikolaos , Georgiadou Eleni , Achilleos K. G. , Pattichis Constantinos S. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

IntroductionAlzheimer’s disease (AD) even nowadays remains a complex neurodegenerative disease and its diagnosis relies mainly on cognitive tests which have many limitations. On the other hand, qualitative imaging will not provide an early diagnosis because the radiologist will perceive brain atrophy on a late disease stage. Therefore, the main objective of this study is to investigate the necessity of quantitative imaging in the assessment of AD by using machine learning (ML) methods. Nowadays, ML methods are used to address high dimensional data, integrate data from different sources, model the etiological and clinical heterogeneity, and discover new biomarkers in the assessment of AD.MethodsIn this study radiomic features from both entorhinal cortex and hippocampus were extracted from 194 normal controls (NC), 284 mild cognitive impairment (MCI) and 130 AD subjects. Texture analysis evaluates statistical properties of the image intensities which might represent changes in MRI image pixel intensity due to the pathophysiology of a disease. Therefore, this quantitative method could detect smaller-scale changes of neurodegeneration. Then the radiomics signatures extracted by texture analysis and baseline neuropsychological scales, were used to build an XGBoost integrated model which has been trained and integrated.ResultsThe model was explained by using the Shapley values produced by the SHAP (SHapley Additive exPlanations) method. XGBoost produced a f1-score of 0.949, 0.818, and 0.810 between NC vs. AD, MC vs. MCI, and MCI vs. AD, respectively.DiscussionThese directions have the potential to help to the earlier diagnosis and to a better manage of the disease progression and therefore, develop novel treatment strategies. This study clearly showed the importance of explainable ML approach in the assessment of AD.
Freezing of gait in Chinese patients with multiple system atrophy: prevalence and risk factors
Authors: Chen Yalan , Wang Hui , Huang Hongyan , Chen Yangmei , Xu Yanming 
Published: June 2023

ObjectiveFreezing of gait (FOG) is common in neurodegenerative forms of atypical parkinsonism, but few studies have examined FOG in multiple system atrophy (MSA). In this study, we examined the prevalence of freezing of gait and its relationship to clinical features in a large cohort of Chinese MSA patients.MethodsThis exploratory study included 202 Chinese patients with probable MSA. FOG was defined as a score ≥ 1 on item 14 of the Unified Parkinson’s Disease Rating Scale. Patients with or without FOG were compared in terms of the Unified MSA Rating Scale (UMSARS) as well as cognitive and neuropsychiatric assessments.ResultsThe frequency of FOG was 48.0, 52.1, and 38.7% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. FOG was associated with worse subscores on parts I, II and IV of the UMSARS as well as worse total UMSARS score; greater likelihood of speech difficulties, falls, gait impairment and balance disorder; more severe symptoms of anxiety and depression; and lower activities of daily living. The binary logistic regression model indicated that higher total UMSARS scores were associated with FOG in MSA, MSA-P, and MSA-C patients.ConclusionFreezing of gait may be common among Chinese MSA patients, FOG may correlate with severe motor symptoms, anxiety, depression and activities of daily living. Total UMSARS score may be an independent risk factor for FOG.
A grape seed and bilberry extract reduces blood pressure in individuals at risk of developing type 2 diabetes: the PRECISE study, a double-blind placebo-controlled cross-over intervention study
Authors: Grohmann Teresa , Walker Alan W. , Russell Wendy R. , Hoggard Nigel , Zhang Xuguang , Horgan Graham , de Roos Baukje 
Published: June 2023

BackgroundType 2 Diabetes Mellitus (T2DM) is a major risk factor for the development of cardiometabolic diseases. T2DM prevention is largely based on weight-loss and whole diet changes, but intervention with dietary plant bioactives may also improve metabolic health.ObjectiveTo assess whether supplementation with bilberry and grape seed extract for 12 weeks improves cardiometabolic outcomes in individuals at risk of developing T2DM, and to determine whether individual treatment response is associated with differences in gut microbiota composition and levels of phenolic metabolites in blood and feces.MethodsIn the randomized, double-blind, placebo-controlled, cross-over PRECISE intervention study, 14 participants, aged ≥45 years, with a BMI &gt;28 kg/m2, and having an increased risk of T2DM, received a supplement containing 250 mg of bilberry plus 300 mg of grape seed extract, or 550 mg of a control extract, per day, for 12 weeks each. Blood samples were obtained for the assessment of HbA1c, fasting glucose, oral glucose tolerance tests, insulin, glucagon levels, total, LDL and HDL cholesterol, and phenolic acids. We also assessed advanced glycation end products in the skin, ambulatory 24 hours blood pressure, 7-day dietary intake by weighed food diaries, fecal levels of phenolic metabolites using LC–MS/MS and gut microbiota composition using 16S rRNA gene sequencing analysis.ResultsThe combined bilberry and grape seed extract did not affect glucose and cholesterol outcomes, but it decreased systolic and diastolic ambulatory blood pressure by 4.7 (p &lt; 0.001) and 2.3 (p = 0.0009) mmHg, respectively. Eight out of fourteen participants were identified as blood pressure ‘responders’. These responders had higher levels of phenylpropionic and phenyllactic acids in their fecal samples, and a higher proportional abundance of Fusicatenibacter-related bacteria (p &lt; 0.01) in their baseline stool samples.ConclusionLong-term supplementation with bilberry and grape seed extract can improve systolic and diastolic blood pressure in individuals at risk of T2DM. Individual responsiveness was correlated with the presence of certain fecal bacterial strains, and an ability to metabolize (epi)catechin into smaller phenolic metabolites.Clinical trial registry number: Research Registry (number 4084).
Prognostic analysis of patients with breast cancer based on tumor mutational burden and DNA damage repair genes
Authors: Teng Xu , Yang Tianshu , Yuan Baowen , Yang Yunkai , Liu Jiaxiang , Wang Xin , Wang Yong , Ma Tianyu , Yin Xin , Yu Hefen , Wang Shuang , Huang Wei 
Published: June 2023

BackgroundBreast cancer has a high tumor-specific death rate and poor prognosis. In this study, we aimed to provide a basis for the prognostic risk in patients with breast cancer using significant gene sets selected by analyzing tumor mutational burden (TMB) and DNA damage repair (DDR).MethodsBreast cancer genomic and transcriptomic data were obtained from The Cancer Genome Atlas (TCGA). Breast cancer samples were dichotomized into high- and low-TMB groups according to TMB values. Differentially expressed DDR genes between high- and low-TMB groups were incorporated into univariate and multivariate cox regression model to build prognosis model. Performance of the prognosis model was validated in an independently new GEO dataset and evaluated by time-dependent ROC curves.ResultsBetween high- and low-TMB groups, there were 6,424 differentially expressed genes, including 67 DDR genes. Ten genes associated with prognosis were selected by univariate cox regression analysis, among which seven genes constituted a panel to predict breast cancer prognosis. The seven-gene prognostic model, as well as the gene copy numbers are closely associated with tumor-infiltrating immune cells.ConclusionWe established a seven-gene prognostic model comprising MDC1, PARP3, PSMB1, PSMB9, PSMD2, PSMD7, and PSMD14 genes, which provides a basis for further exploration of a population-based prediction of prognosis and immunotherapy response in patients with breast cancer.
Colorectal cancer in patients of advanced age is associated with increased incidence of BRAF p.V600E mutation and mismatch repair deficiency
Authors: Christenson Eric S. , Tsai Hua-Ling , Le Dung T. , Jaffee Elizabeth M. , Dudley Jonathan , Xian Rena R. , Gocke Christopher D. , Eshleman James R. , Lin Ming-Tseh 
Published: June 2023

IntroductionThe highest incidence of colorectal cancer (CRC) is in patients diagnosed at 80 years or older highlighting a need for understanding the clinical and molecular features of these tumors. Methods. In this retrospective cohort study, 544 CRCs underwent next generation sequencing and mismatch repair (MMR) evaluation. Molecular and clinical features were compared between 251 patients with traditional-onset CRC (50-69 years at diagnosis) and 60 with late-onset CRC (&gt;80 years at diagnosis).ResultsLate-onset CRC showed a significantly higher rate of right-sided tumors (82% vs 35%), MMR deficiency (35% vs. 8%) and BRAF p.V600E mutations (35% vs. 8%) and a significantly lower rate of stage IV disease (15% vs 28%) and APC mutations (52% vs. 78%). Association of these features with advanced age was supported by stratifying patients into 6 age groups (&lt;40, 40-49, 50-59, 60-69, 70-79 and &gt;80 years). However, the age-related rise in MMR deficient (dMMR) CRC was only seen in the female patients with an incidence of 48% (vs. 10% in the male patient) in the &gt;80y group. In addition, BRAF p.V600E was significantly enriched in MMR deficient CRC of advanced age (67% in late-onset CRC). Categorizing CRC by mutational profiling, late-onset CRC revealed a significantly higher rate of dMMR/BRAF+APC- (18% vs. 2.0%), dMMR/BRAF-APC- (8.3% vs. 1.2%) and MMR proficient (pMMR)/BRAF+APC- (12% vs. 4.0%) as compared to traditional-onset CRC.DiscussionIn summary, there was a higher rate of dMMR and BRAF p.V600E in late-onset CRC, independently or in combination. The higher incidence of dMMR in late-onset CRC in females is most likely predominantly driven by BRAF p.V600E induced hypermethylation. Prospective studies with treatment plans designed specifically for these older patients are warranted to improve their outcomes.
Risk of venous thromboembolism with janus kinase inhibitors in inflammatory immune diseases: a systematic review and meta-analysis
Authors: Zhang Juqi , Li Wenhui , Gong Mingli , Gu Yanlun , Zhang Hanxu , Dong Bingqi , Guo Qi , Pang Xiaocong , Xiang Qian , He Xu , Cui Yimin 
Published: June 2023

Objectives: This study aimed to evaluate the risk of venous thrombosis (VTE) associated with Janus kinase (JAK) inhibitors in patients diagnosed with immune-mediated inflammatory diseases.Methods: We conducted a comprehensive search of PUBMED, Cochrane, and Embase databases for randomized controlled trials evaluating venous thromboembolic incidence after administering JAK inhibitors in patients with immune-mediated inflammatory diseases. The studies were screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and a meta-analysis was performed.Results: A total of 16 studies, enrolling 17,242 participants, were included in this review. Four approved doses of JAK inhibitors were administered in the included studies. The meta-analysis revealed no significant difference in the incidence of VTE between patients receiving JAK inhibitors, a placebo, or tumor necrosis factor (TNF) inhibitors (RR 0.72, 95% CI (0.33-1.55); RR 0.94, 95%CI (0.33-2.69)). Subgroup analysis showed a lower risk of VTE with lower doses of JAK inhibitors [RR 0.56, 95%CI (0.36-0.88)]. Compared with the higher dose of tofacitinib, the lower dose was associated with a lower risk of pulmonary embolism [RR 0.37, 95%CI (0.18-0.78)].Conclusion: Our meta-analysis of randomized controlled trials observed a potential increase in the risk of VTE in patients with immune-mediated inflammatory diseases treated with JAK inhibitors compared to placebo or tumor necrosis factor inhibitors, though statistical significance was not attained. Notably, a higher risk of pulmonary embolism was observed with high doses of tofacitinib. Our findings provide valuable insights for physicians when evaluating the use of JAK inhibitors for patients with immune-mediated inflammatory diseases.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023382544, identifier CRD42023382544
Relationship between moderate-to-vigorous, light intensity physical activity and sedentary behavior in a prospective cohort of older French adults: a 18-year follow-up of mortality and cardiovascular events ─ the PROOF cohort study
Authors: Dupré Caroline , Brégère Marlène , Berger Mathieu , Pichot Vincent , Celle Sébastien , Garet Martin , Fundenberger Hervé , Barth Nathalie , Guyot Jessica , Bongue Bienvenu , Barthélémy Jean-Claude , Roche Frédéric , Hupin David 
Published: June 2023

HighlightsAn equivalent daily dose of walking at low intensity (at least 1.5 h at one’s own pace) has already a beneficial effect on health in older adults with a 30% reduction in mortality risk.This reduction in mortality risk is even more strong (80%) from 3 h of walking at low intensity per day.These results are even stronger in those who have chronic conditions (hypertension or type 2 diabetes).
Augmented-reality swim goggles accurately and reliably measure swim performance metrics in recreational swimmers
Authors: Eisenhardt Dan , Kits Aidan , Madeleine Pascal , Samani Afshin , Clarke David C. , Kristiansen Mathias 
Published: June 2023

BackgroundSwimmers commonly access performance metrics such as lap splits, distance, and pacing information between work bouts while they rest. Recently, a new category of tracking devices for swimming was introduced with the FORM Smart Swim Goggles (FORM Goggles). The goggles have a built-in see-through display and are capable of tracking and displaying distance, time splits, stroke, and pace metrics in real time using machine learning and augmented reality through a heads-up display. The purpose of this study was to assess the validity and reliability of the FORM Goggles compared with video analysis for stroke type, pool length count, pool length time, stroke rate, and stroke count in recreational swimmers and triathletes.MethodA total of 36 participants performed mixed swimming intervals in a 25-m pool across two identical 900-m swim sessions performed at comparable intensities with 1 week interval. The participants wore FORM Goggles during their swims, which detected the following five swim metrics: stroke type, pool length time, pool length count, stroke count, and stroke rate. Four video cameras were positioned on the pool edges to capture ground truth video footage, which was then manually labeled by three trained individuals. Mean (SD) differences between FORM Goggles and ground truth were calculated for the selected metrics for both sessions. The absolute mean difference and mean absolute percentage error were used to assess the differences of the FORM Goggles relative to ground truth. The test–retest reliability of the goggles was assessed using both relative and absolute reliability metrics.ResultsCompared with video analysis, the FORM Goggles identified the correct stroke type at a rate of 99.7% (N = 2,354 pool lengths, p &lt; 0.001), pool length count accuracy of 99.8%, and mean differences (FORM Goggles–ground truth) for pool length time: −0.10 s (1.49); stroke count: −0.63 (1.82); and stroke rate: 0.19 strokes/min (3.23). The test–retest intra-class correlation coefficient (ICC) values between the two test days were 0.793 for pool length time, 0.797 for stroke count, and 0.883 for stroke rate. Overall, for pool length time, the residuals were within ±1.0s for 65.3% of the total pool lengths, for stroke count within ±1 stroke for 62.6% of the total pool lengths, and for stroke rate within ±2 strokes/min for 66.40% of the total pool lengths.ConclusionThe FORM Goggles were found valid and reliable for the tracking of pool length time, pool length count, stroke count, stroke rate, and stroke type during freestyle, backstroke, and breaststroke swimming in recreational swimmers and triathletes when compared with video analysis. This opens perspectives for receiving real-time information on performance metrics during swimming.
Effect of Electroejaculation Protocols on Semen Quality and Concentrations of Testosterone, Cortisol, Malondialdehyde, and Creatine Kinase in Captive Bengal Tigers
Authors: Khonmee Jaruwan , Brown Janine L. , Pérez Anabel López , Lertwichaikul Teepakorn , Sathanawongs Anucha , Pornnimitra Patchara , Areewong Chanakan , Supanta Jarawee , Punyapornwithaya Veerasak , Buddhasiri Songphon , Punturee Khanittha 
Published: June 2023

The Bengal tiger (Panthera tigris tigris) is critically endangered, so assisted reproductive technologies, including artificial insemination, are important conservation tools. For wild and domestic felids, electroejaculation (EE) is the most common semen collection method, with protocols optimized to obtain sufficient amounts of viable sperm for artificial insemination. However, less attention has been paid to ensuring animal wellbeing during the process. This study examined the effects of three EE protocols (Low, 2–5 volts; Medium, 3–6 volts; High, 4–7 volts) on semen quality, testicular size, serum testosterone, creatine kinase (CK), and malondialdehyde (MDA) concentrations, and serum cortisol as a proxy for stress. Blood samples were collected before, during, and after each EE series. Seminal plasma pH, and sperm motility, viability, and morphology were evaluated after each procedure. Seminal plasma and sperm pellet MDA concentrations were also determined. Primary sperm abnormalities and seminal plasma MDA were higher in the Low compared to Medium and High voltage groups (p < 0.05). Serum CK in the High voltage group increased during the EE series (p < 0.05), suggesting the potential for muscle damage. However, no significant changes were observed for serum cortisol, testosterone, or MDA concentrations. Results suggest the Medium voltage protocol produced good quality samples at lower voltages than the High protocol with no negative effect on muscle function, which might be better for animal welfare.
Complexity and Chaos Analysis for Two-Dimensional Discrete-Time Predator–Prey Leslie–Gower Model with Fractional Orders
Authors: Hamadneh Tareq , Abbes Abderrahmane , Falahah Ibraheem Abu , AL-Khassawneh Yazan Alaya , Heilat Ahmed Salem , Al-Husban Abdallah , Ouannas Adel 
Published: June 2023

The paper introduces a novel two-dimensional fractional discrete-time predator–prey Leslie–Gower model with an Allee effect on the predator population. The model’s nonlinear dynamics are explored using various numerical techniques, including phase portraits, bifurcations and maximum Lyapunov exponent, with consideration given to both commensurate and incommensurate fractional orders. These techniques reveal that the fractional-order predator–prey Leslie–Gower model exhibits intricate and diverse dynamical characteristics, including stable trajectories, periodic motion, and chaotic attractors, which are affected by the variance of the system parameters, the commensurate fractional order, and the incommensurate fractional order. Finally, we employ the 0–1 method, the approximate entropy test and the C0 algorithm to measure complexity and confirm chaos in the proposed system.