Miracle-dz/UniFAR-FTUs huggingface dataset:
Current and lagged associations of meteorological variables and Aedes mosquito indices with dengue incidence in the Philippines

Background Dengue is an increasing health burden that has spread throughout the tropics and sub-tropics. There is currently no effective vaccine and control is only possible through integrated vector management. Early warning systems to alert potential dengue outbreaks are currently being explored but despite showing promise are yet to come to fruition. This study addresses the use of meteorological variables for predicting both entomological indices and dengue incidences and assesses the added value of additionally using entomological indices for predicting dengue incidences. Methodology/Principal Findings Entomological surveys were carried out monthly for 14 months in six sites spread across three environmentally different cities of the Philippines. Meteorological and dengue data were acquired. Non-linear generalized additive models were fitted to test associations with the meteorological variables and both entomological indices and dengue cases. Rain and the diurnal temperature range (DTR) contributed most to explaining the variation in both entomological indices and number of dengue cases. DTR and minimum temperature also explained variation in dengue cases occurring one and two months later. The number of adult mosquitoes did associate with the number of dengue cases, but contributed no additional value for predicting dengue cases. Conclusions/Significance The use of meteorological variables to predict future risk of dengue holds promise. The lack of added value of using entomological indices confirms several previous studies and given the onerous nature of obtaining such information, more effort should be placed on improving meteorological information at a finer scale to evaluate efficacy in early warning of dengue outbreaks.
Predicting the onset of internalizing disorders in early adolescence using deep learning optimized with AI

Internalizing disorders (depression, anxiety, somatic symptom disorder) are among the most common mental health conditions that can substantially reduce daily life function. Early adolescence is an important developmental stage for the increase in prevalence of internalizing disorders and understanding specific factors that predict their onset may be germane to intervention and prevention strategies. We analyzed ~6,000 candidate predictors from multiple knowledge domains (cognitive, psychosocial, neural, biological) contributed by children of late elementary school age (9-10 yrs) and their parents in the ABCD cohort to construct individual-level models predicting the later (11-12 yrs) onset of depression, anxiety and somatic symptom disorder using deep learning with artificial neural networks. Deep learning was guided by an evolutionary algorithm that jointly performed optimization across hyperparameters and automated feature selection, allowing more candidate predictors and a wider variety of predictor types to be analyzed than the largest previous comparable machine learning studies. We found that the future onset of internalizing disorders could be robustly predicted in early adolescence with AUROCs [≥]~0.90 and [≥]~80% accuracy. Each disorder had a specific set of predictors, though parent problem behavioral traits and sleep disturbances represented cross-cutting themes. Additional computational experiments revealed that psychosocial predictors were more important to predicting early adolescent internalizing disorders than cognitive, neural or biological factors and generated models with better performance. We also observed that the accuracy of individual-level models was highly correlated to the relative importance of their constituent predictors, suggesting that principled searches for predictors with higher importance or effect sizes could support the construction of more accurate individual-level models of internalizing disorders. Future work, including replication in additional datasets, will help test the generalizability of our findings and explore their application to other stages in human development and mental health conditions.
Insights into the Mechanisms and Structure of Breakage-Fusion-Bridge Cycles in Cervical Cancer using Long-Read Sequencing

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and this is one of the first analyses of these events using long-read sequencing. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes and only one BFB breakpoint showed chromothripsis. Five cell lines have a Chr11q BFB event, with YAP1/BIRC2/BIRC3 gene amplification. Indeed, YAP1 amplification is associated with a 10-year earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that cervical cancer patients with YAP1/BIRC2/BIRC3-amplification, especially those of African American ancestry, might benefit from targeted therapy. In summary, we uncovered new insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.
Kombucha fermentation as a modern way of processing vineyard by‐products into cosmetic raw materials

The wine industry generates large quantities of by‐products presenting a remarkably valuable composition in phytochemicals. The process that can significantly increase the content of bioactive compounds is fermentation by yeast and other microorganisms. The current study presents, for the first time, an evaluation of the potential of grape stems extract and its ferments using the Scoby consortium, as a cosmetic raw material for improving the skin care properties of facial cosmetics.
Factors Influencing Genetic Screening Enrollment among a Diverse, Community-Ascertained Cohort

Introduction: Genetic screening for preventable adult-onset hereditary conditions has been proposed as a mechanism to reduce health disparities. Analysis of how race and ethnicity influence decision-making to receive screening can inform recruitment efforts and more equitable population screening design. A study at the University of Washington Medicine that invited unselected patients to participate in genetic screening for pathogenic variation in medically important genes provided an opportunity to evaluate these factors. Methods: We analyzed screening enrollee survey data to understand factors most important and least important in decision-making about screening overall and across different race and ethnicity groups. Electronic health record race and ethnicity and survey-reported race and ethnicity were compared to assist with interpretation. Comments provided about reasons for not enrolling in screening were analyzed using content analysis. Results: Overall, learning about disease risk and identifying risk early for prevention purposes were important factors in decision-making to receive screening, and regrets about screening and screening being against one’s moral code were not viewed as important. Although racial identity was challenging to assign in all cases, compared to other enrollees, African-American and Asian enrollees considered test accuracy and knowing more about the test to be of greater importance. Three themes emerged related to nonparticipation: benefits do not outweigh risks, don’t want to know, and challenges with study logistics. Conclusion: Our results highlight important motivators for receiving screening and areas that can be addressed to increase screening interest and accessibility. This knowledge can inform future population screening program design including recruitment and education approaches.
Social risk and patient‐reported outcomes after total knee replacement: Implications for Medicare policy

Abstract Objective To determine whether county‐level or patient‐level social risk factors are associated with patient‐reported outcomes after total knee replacement when added to the comprehensive joint replacement risk‐adjustment model. Data Sources and Study Setting Patient and outcomes data from the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement cohort were merged with the Social Vulnerability Index from the Centers for Disease Control and Prevention. Study Design This prospective longitudinal cohort measured the change in patient‐reported pain and physical function from baseline to 12 months after surgery. The cohort included a nationally diverse sample of adult patients who received elective unilateral knee replacement between 2012 and 2015. Data Collection/Extraction Methods Using a national network of over 230 surgeons in 28 states, the cohort study enrolled patients from diverse settings and collected one‐year outcomes after the surgery. Patients <65 years of age or who did not report outcomes were excluded. Principal Findings After adjusting for clinical and demographic factors, we found patient‐reported race, education, and income were associated with patient‐reported pain or functional scores. Pain improvement was negatively associated with Black race (CI = −8.71, −3.02) and positively associated with higher annual incomes (≥$45,00) (CI = 0.07, 2.33). Functional improvement was also negatively associated with Black race (CI = −5.81, −0.35). Patients with higher educational attainment (CI = −2.35, −0.06) reported significantly less functional improvement while patients in households with three adults reported greater improvement (CI = 0.11, 4.57). We did not observe any associations between county‐level social vulnerability and change in pain or function. Conclusions We found patient‐level social factors were associated with patient‐reported outcomes after total knee replacement, but county‐level social vulnerability was not. Our findings suggest patient‐level social factors warrant further investigation to promote health equity in patient‐reported outcomes after total knee replacement.
Optimal selection of suitable templates in protein interface prediction

Abstract Motivation Molecular-level classification of protein–protein interfaces can greatly assist in functional characterization and rational drug design. The most accurate protein interface predictions rely on finding homologous proteins with known interfaces since most interfaces are conserved within the same protein family. The accuracy of these template-based prediction approaches depends on the correct choice of suitable templates. Choosing the right templates in the immunoglobulin superfamily (IgSF) is challenging because its members share low sequence identity and display a wide range of alternative binding sites despite structural homology. Results We present a new approach to predict protein interfaces. First, template-specific, informative evolutionary profiles are established using a mutual information-based approach. Next, based on the similarity of residue level conservation scores derived from the evolutionary profiles, a query protein is hierarchically clustered with all available template proteins in its superfamily with known interface definitions. Once clustered, a subset of the most closely related templates is selected, and an interface prediction is made. These initial interface predictions are subsequently refined by extensive docking. This method was benchmarked on 51 IgSF proteins and can predict nontrivial interfaces of IgSF proteins with an average and median F-score of 0.64 and 0.78, respectively. We also provide a way to assess the confidence of the results. The average and median F-scores increase to 0.8 and 0.81, respectively, if 27% of low confidence cases and 17% of medium confidence cases are removed. Lastly, we provide residue level interface predictions, protein complexes, and confidence measurements for singletons in the IgSF. Availability and implementation Source code is freely available at: https://gitlab.com/fiserlab.org/interdct_with_refinement.
Hippocampal, Whole Midbrain, Red Nucleus, and Ventral Tegmental Area Volumes Are Increased by Selective Breeding for High Voluntary Wheel-Running Behavior

Uncovering relationships between neuroanatomy, behavior, and evolution are important for understanding the factors that control brain function. Voluntary exercise is one key behavior that both affects, and may be affected by, neuroanatomical variation. Moreover, recent studies suggest an important role for physical activity in brain evolution. We used a unique and ongoing artificial selection model in which mice are bred for high voluntary wheel-running behavior, yielding four replicate lines of high runner (HR) mice that run ∼3-fold more revolutions per day than four replicate nonselected control (C) lines. Previous studies reported that, with body mass as a covariate, HR mice had heavier whole brains, non-cerebellar brains, and larger midbrains than C mice. We sampled mice from generation 66 and used high-resolution microscopy to test the hypothesis that HR mice have greater volumes and/or cell densities in nine key regions from either the midbrain or limbic system. In addition, half of the mice were given 10 weeks of wheel access from weaning, and we predicted that chronic exercise would increase the volumes of the examined brain regions via phenotypic plasticity. We replicated findings that both selective breeding and wheel access increased total brain mass, with no significant interaction between the two factors. In HR compared to C mice, adjusting for body mass, both the red nucleus (RN) of the midbrain and the hippocampus (HPC) were significantly larger, and the whole midbrain tended to be larger, with no effect of wheel access nor any interactions. Linetype and wheel access had an interactive effect on the volume of the periaqueductal gray (PAG), such that wheel access increased PAG volume in C mice but decreased volume in HR mice. Neither linetype nor wheel access affected volumes of the substantia nigra, ventral tegmental area, nucleus accumbens, ventral pallidum (VP), or basolateral amygdala. We found no main effect of either linetype or wheel access on neuronal densities (numbers of cells per unit area) for any of the regions examined. Taken together, our results suggest that the increased exercise phenotype of HR mice is related to increased RN and hippocampal volumes, but that chronic exercise alone does not produce such phenotypes.
Comparison of Joint Mobilization and Movement Pattern Training for Patients With Hip-Related Groin Pain: A Pilot Randomized Clinical Trial

Abstract Objective The objective of this study was to assess the feasibility of completing a randomized clinical trial (RCT) and examine the preliminary effects of 2 interventions for hip-related groin pain (HRGP). Methods In this pilot RCT, patients with HRGP, who were 18 to 40 years old, were randomized (1:1 ratio) to a joint mobilization (JtMob) group or a movement pattern training (MoveTrain) group. Both treatments included 10 supervised sessions and a home exercise program. The goal of JtMob was to reduce pain and improve mobility through peripherally and centrally mediated pain mechanisms. The key element was physical therapist-provided JtMob. The goal of MoveTrain was to reduce hip joint stresses by optimizing the biomechanics of patient-specific tasks. The key element was task-specific instruction to correct abnormal movement patterns displayed during tasks. Primary outcomes were related to future trial feasibility. The primary effectiveness outcome was the Hip Disability and Osteoarthritis Outcome Score. Examiners were blinded to group; patients and treatment providers were not. Data collected at baseline and immediately after treatment were analyzed with analysis of covariance using a generalized linear model in which change was the dependent variable and baseline was the covariate. The study was modified due to the coronavirus disease 2019 (COVID-19) pandemic. Results The COVID-19 pandemic affected participation; 127 patients were screened, 33 were randomized (18 to the JtMob group and 15 to the MoveTrain group), and 29 (88%) provided posttreatment data. Treatment session adherence was 85%, and home exercise program component adherence ranged from 71 to 86%. Both groups demonstrated significant mean within-group improvements of ≥5 points on Hip Disability and Osteoarthritis Outcome Score scales. There were no between-group differences in effectiveness outcomes. Conclusions A large RCT to assess the effects of JtMob and MoveTrain for patients with HRGP may be feasible. Preliminary findings suggested that JtMob or MoveTrain may result in improvements in patient-reported pain and activity limitations. Impact The COVID-19 pandemic interfered with participation, but a randomized controlled trial may be feasible. Modification may be needed if the trial is completed during future pandemics.
CircSETD2 inhibits YAP1 by interaction with HuR during breast cancer progression

ABSTRACT CircRNAs have been proven to play a pivotal role in cancer progression. The present study aims to explore the roles and related mechanisms of circSETD2 in breast cancer proliferation, migration and invasion. The expression of circSETD2 in BC was assessed by the GEO database and qRT‒PCR. The biological function and underlying molecular mechanism of circSETD2 in BC were explored using in vitro and in vivo experiments, including CCK8, transwell, RIP, western blot, and xenograft mouse models. The expression of circSETD2 was downregulated in BC tumors, in accordance with the GEO database. Overexpression of circSETD2 significantly suppressed cell growth, cell migration and invasion. Mechanistically, circSETD2 reduced the stabilization of YAP1 by competitively binding with HuR, resulting in inactivation of downstream targets such as CTGF, myc and Slug. Our work suggests that the novel signaling axis circSETD2/HuR/YAP1 plays an important role in BC progression. The molecular mechanism underlying this signaling axis may provide a potential therapeutic target for BC treatment.
In Vitro Genotoxic and Antigenotoxic Effects of Ten Novel Synthesized 4‐Thiazolidinone Derivatives

Heterocyclic compounds are found in a variety of drug molecules, and bioactive natural products. 4‐Thiazolidinones (4‐TZDs), which represent an important class of heterocyclic compounds, are of great interest today with their diverse bioactivities. In this study, ten novel 4‐TZD derivatives (C1–C10) were synthesized, characterized by spectroscopic techniques, and their genotoxic, and antigenotoxic properties were investigated in vitro using the Ames Salmonella/microsome mutagenicity assay in the concentration range of 0.2–1.0 mM/plate. The results revealed that none of the compounds were mutagenic on the three different Salmonella typhimurium strains up to the highest concentration tested. Furthermore, in our study, C1, C4, C6, and C9 showed significant, ranging from moderate to strong, antigenotoxic effects against mutagen‐induced DNA damage at relatively higher doses. Among these, C4 had the best potential to inhibit the number of revertant colonies induced by 9‐aminoacridine (9‐AA), with a maximum inhibition rate of 47.9 % for 1.0 mM/plate. As a result, preliminary knowledge about the safety of the use of ten novel synthesized 4‐TZD compounds likely to exhibit many bioactivities was obtained in this study. In addition, the significant in vitro antimutagenic activity of some derivatives increases the importance of studies for the development of new pharmacological agents for cancer prevention.
TRAF4 is crucial for ST2+ memory Th2 cell expansion in IL-33–driven airway inflammation

Tumor necrosis factor receptor–associated factor 4 (TRAF4) is an important regulator of type 2 responses in the airway; however, the underlying cellular and molecular mechanisms remain elusive. Herein, we generated T cell–specific TRAF4-deficient (CD4-cre Traf4fl/fl) mice and investigated the role of TRAF4 in memory Th2 cells expressing IL-33 receptor (ST2, suppression of tumorigenicity 2) (ST2+ mTh2 cells) in IL-33–mediated type 2 airway inflammation. We found that in vitro–polarized TRAF4-deficient (CD4-cre Traf4fl/fl) ST2+ mTh2 cells exhibited decreased IL-33–induced proliferation as compared with TRAF4-sufficient (Traf4fl/fl) cells. Moreover, CD4-cre Traf4fl/fl mice showed less ST2+ mTh2 cell proliferation and eosinophilic infiltration in the lungs than Traf4fl/fl mice in the preclinical models of IL-33–mediated type 2 airway inflammation. Mechanistically, we discovered that TRAF4 was required for the activation of AKT/mTOR and ERK1/2 signaling pathways as well as the expression of transcription factor Myc and nutrient transporters (Slc2a1, Slc7a1, and Slc7a5), signature genes involved in T cell growth and proliferation, in ST2+ mTh2 cells stimulated by IL-33. Taken together, the current study reveals a role of TRAF4 in ST2+ mTh2 cells in IL-33–mediated type 2 pulmonary inflammation, opening up avenues for the development of new therapeutic strategies.
New horizons in hearing conditions

Abstract Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life. Hearing is affected by multiple factors, including heredity, noise exposure, age, sex, ear disorders and lifestyle factors. Globally, hearing loss affects over 80% of adults aged 80 years and older, is often experienced in combination with other long-term health conditions and is a mid-life risk factor for dementia. To form a themed collection, we searched Age and Ageing for articles on hearing conditions published from 2000 onwards. This resulted in 22 articles included within the collection. They examined a range of important topics related to hearing healthcare and research, including noise-induced hearing loss, health service quality and safety, psychological and psychosocial consequences of hearing loss and co-morbidities of hearing loss. All articles reported on hearing loss; there were no published articles with a primary focus on other hearing conditions such as tinnitus or hyperacusis, on the health of older people from the Deaf community or on users of Cochlear implants, suggesting key gaps in knowledge and targets for future research. This New Horizons article highlights novel directions in research and practice and takes a forward look at how research into hearing conditions may develop in years to come. It highlights opportunities for the growth of patient-centred research and hearing healthcare supported by the better integration of health and care services as well as cross-speciality working to include common co-morbid health conditions.