bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interdisciplinary perspectives on multimorbidity in Africa: developing an expanded conceptual model
Authors: Dixon Justin , Morton Ben , Nkhata Misheck J. , Silman Alan , Simiyu Ibrahim G. , Spencer Stephen A. , Van Pinxteren Myrna , Bunn Christopher , Calderwood Claire , Chandler Clare I.R. , Chikumbu Edith , Crampin Amelia C. , Hurst John R. , Jobe Modou , Kengne Andre Pascal , Levitt Naomi S. , Moshabela Mosa , Owolabi Mayowa , Peer Nasheeta , Phiri Nozgechi , Singh Sally J. , Tamuhla Tsaone , Tembo Mandikudza , Tiffin Nicki , Worrall Eve , Yongolo Nateiya M. , Banda Gift T. , Bickton Fanuel , Bilungula Abbi-Monique Mamani , Bosire Edna , Chawani Marlen Stacy , Chinoko Beatrice , Chisala Mphatso , Chiwanda Jonathan , Drew Sarah , Farrant Lindsay , Ferrand Rashida A. , Gondwe Mtisunge , Gregson Celia L. , Harding Richard , Kajungu Dan , Kasenda Stephen , Katagira Winceslaus , Kwaitana Duncan , Mendenhall Emily , Mensah Adwoa Bemah Boamah , Mnenula Modai , Mupaza Lovemore , Mwakasungula Maud , Nakanga Wisdom , Ndhlovu Chiratidzo , Nkhoma Kennedy , Nkoka Owen , Opare-Lokko Edwina Addo , Phulusa Jacob , Price Alison , Rylance Jamie , Salima Charity , Salimu Sangwani , Sturmberg Joachim , Vale Elizabeth , Limbani Felix 
Published: September 2023

AbstractMultimorbidity is an emerging challenge for healthcare systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but the suitability and utility of this concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to critically consider existing concepts and definitions of multimorbidity, to evaluate their utility and limitations, and to co-develop an context-sensitive, interdisciplinary conceptual framing. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during a three-day concept-building workshop, thematic coding of workshop discussions, and further post-workshop iterative development and refinement. The three main thematic domains that emerged from workshop discussions were: the disease-centricity of current concepts and definitions; the need to foreground what matters to people living with multimorbidity (PLWMM), families, and other stakeholders; and the need for conceptual breadth and flexibility to accommodate the contributions of multiple disciplinary perspectives and heterogeneity within and between different African countries. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity often has for PLWMM, their families and support structures, for service providers, and for resource-constrained healthcare systems.
What Loss Functions Do Humans Optimize When They Perform Regression and Classification
Authors: Ryu Hansol X. , Srinivasan Manoj 
Published: September 2023

AbstractStudying how humans perceive patterns in visually presented data is useful for understanding data-based decision-making and potentially understanding visually mediated sensorimotor control. We conducted experiments to examine how human subjects perform the simplest machine learning or statistical estimation tasks: linear regression and binary classification on 2D scatter plots. We used inverse optimization to infer the loss function humans optimize when they perform these tasks. Minimizing the sum of regression error raised to the power of 1.7 best-described human performing regression on sparse data. Loss functions with lower exponents, which are less sensitive to outliers, were better descriptors for regression tasks performed on less sparse data consisting of more data points. For the classification task, minimizing a logistic loss function was on average a better descriptor of human choices than an exponential loss function applied to only misclassified data. People changed their strategies as data density increased. These results represent overall trends across subjects and trials but there was large inter- and intra-subject variability in human choices. Future work may examine other loss function families and other tasks. Such understanding of human loss functions may inform the design of applications that interact with humans better and imitate humans more effectively.
An accurate probabilistic step finder for time-series analysis
Authors: Rojewski Alex , Schweiger Maxwell , Sgouralis Ioannis , Comstock Matthew , Pressé Steve 
Published: September 2023

ABSTRACTNoisy time-series data is commonly collected from sources including Förster Resonance Energy Transfer experiments, patch clamp and force spectroscopy setups, among many others. Two of the most common paradigms for the detection of discrete transitions in such time-series data include: hidden Markov models (HMMs) and step-finding algorithms. HMMs, including their extensions to infinite state-spaces, inherently assume in analysis that holding times in discrete states visited are geometrically–or, loosely speaking in common language, exponentially–distributed. Thus the determination of step locations, especially in sparse and noisy data, is biased by HMMs toward identifying steps resulting in geometric holding times. In contrast, existing step-finding algorithms, while free of this restraint, often rely onad hocmetrics to penalize steps recovered in time traces (by using various information criteria) and otherwise rely on approximate greedy algorithms to identify putative global optima. Here, instead, we devise a robust and general probabilistic (Bayesian) step-finding tool that neither relies onad hocmetrics to penalize step numbers nor assumes geometric holding times in each state. As the number of steps themselves in a time-series are,a prioriunknown, we treat these within a Bayesian nonparametric (BNP) paradigm. We find that the method developed, Bayesian Nonparametric Step (BNP-Step), accurately determines the number and location of transitions between discrete states without any assumed kinetic model and learns the emission distribution characteristic of each state. In doing so, we verify that BNP-Step can analyze sparser data sets containing higher noise and more closely-spaced states than otherwise resolved by current state-of-the-art methods. What is more, BNP-Step rigorously propagates measurement uncertainty into uncertainty over state transition locations, numbers, and emission levels as characterized by the posterior. We demonstrate the performance of BNP-Step on both synthetic data as well as data drawn from force spectroscopy experiments.SIGNIFICANCEMany time-series data sets exist which are challenging to analyze with current state-of-the-art methods, either because they contain excessive noise or because they violate one or more assumptions inherent to the chosen analysis method. To our knowledge, BNP-Step is the first time-series analysis algorithm which leverages Bayesian nonparametrics to learn the number and location of transitions between states and the emission levels associated to each state, while providing rigorous estimates of uncertainty for the learned quantities. We anticipate our algorithm will allow analysis of data sets at levels of noise or sparsity beyond what current state-of-the-art methods allow, and could potentially reveal previously unknown features in data sets analyzed using existing methods.
TwinsMX: Exploring the Genetic and Environmental Influences on Health Traits in the Mexican Population
Authors: García-Vilchis B. , Román-López T.V. , Ramírez-González D. , López-Camaño X. , Murillo-Lechuga V. , Díaz X. , Sánchez-Moncada I.C. , Espinosa-Méndez I.M. , Zenteno-Morales D. , Espinosa-Valdes Z.X. , Pradel-Jiménez S. , Tapia-Atilano A. , Zanabria-Pérez A.V. , Livas-Gangas F. , Aldana-Assad O. , Caballero-Sánchez U. , Dominguez-Frausto C.A. , Rentería M.E. , Medina-Rivera A. , Alcauter S. , Ruiz-Contreras A.E. 
Published: September 2023

AbstractTwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country’s population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular, and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database which shall allow to study complex traits in the Mexican population, valuable not only for our consortium but for the worldwide scientific community by providing new insights of understudied genetically admixed populations.
Pre-Diagnosis Dietary Patterns and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study
Authors: Castro Francesca , Parikh Richa , Eustaquio Jelyn C. , Derkach Andriy , Joseph Janine M. , Lesokhin Alexander M. , Usmani Saad Z. , Shah Urvi A. 
Published: September 2023

AbstractBackgroundDespite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters. The Nurses’ Health Study and Health Professionals Follow-up Study (478 MM cases) showed a significantly increased MM risk in men with Empirical Dietary Inflammatory Pattern.MethodsThe NIH-AARP Diet and Health study is a prospective cohort of 567,169 persons who completed a food frequency questionnaire in 1995-1996 and were followed until December 2011. Healthy Eating Index-2015 (HEI-2015), Healthy Diet Score (HDS), alternate Mediterranean Diet (aMED) and healthful Plant-based Diet Index (hPDI) scores were calculated usinga prioridefined methods and grouped into quartiles, with higher scores reflecting healthier eating patterns. We prospectively evaluated the association between pre-diagnosis dietary patterns and MM incidence in this cohort. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using multivariate Cox proportional hazards models adjusted for age at study entry, sex, race, body mass index, education, and total energy intake (by residual method). Sensitivity analysis was conducted to assess reverse causality by excluding MM cases diagnosed within one year of follow-up.ResultsAmong 392,589 participants (after exclusions), a total of 1,366 MM cases (59% males; 92% non-Hispanic whites) were identified during the follow-up period. Analysis revealed a significant association between hPDI scores and reduced MM risk (highest vs lowest quartile, HR 0.85; 95%CI 0.73-1.0; p=0.043) (Table). In sensitivity analysis (1,302 MM cases), the association was no longer significant (HR 0.87; 95%CI 0.74-1.03; p 0.09) but trended in the same direction. This may be due to small sample size, given MM is a rare disease. HEI-2015, HDS and aMED scores were not associated with MM risk.ConclusionsA healthful plant-based diet was associated with reduced MM risk in the NIH-AARP cohort. These results will help oncologists and patients make informed choices about their diet. To our knowledge, this is the largest epidemiologic study to date assessing pre-diagnosis dietary patterns and MM risk.
Estimating changes in antibiotic consumption with the introduction of doxycycline post-exposure prophylaxis in the United States
Authors: Roster Kirstin I. Oliveira , Grad Yonatan H. 
Published: September 2023

AbstractDoxycycline as post-exposure prophylaxis (doxy-PEP) reduces the risk of gonorrhea, chlamydia, and syphilis in studies of men who have sex with men (MSM) and transgender women (TGW) on HIV Pre-exposure Prophylaxis (PrEP) and people living with HIV (PLWH)). Doxy-PEP is an important tool to address the increasing burden of sexually transmitted infections (STIs), but there is concern that increased consumption of doxycycline may drive antimicrobial resistance. We estimated the expected increase in antibiotic use in the US under several doxy-PEP prescribing scenarios. We accounted for doses of antibiotics that may be averted due to the prevention of chlamydia, gonorrhea, and syphilis infections by doxy-PEP. Under a scenario of 75% adoption among the eligible population, with rates of consumption similar to the DoxyPEP trial population, monthly antibiotic consumption would increase by around 2.52 million doses, driven by doxy-PEP consumption of 2.58 million doses and less 62.1 thousand antibiotic doses that would otherwise have been used for chlamydia, gonorrhea, and syphilis treatment.
Lack of genetic evidence for NLRP3-inflammasome involvement in Parkinson’s disease pathogenesis
Authors: Senkevich Konstantin , Liu Lang , Alvarado Chelsea X. , Leonard Hampton L. , Nalls Mike A. ,   Global Parkinson’s Genetics Program (GP2), Gan-Or Ziv 
Published: September 2023

AbstractActivation of the NLRP3-inflammasome has been implicated in Parkinson’s disease based onin vitroandin vivostudies. Clinical trials targeting the NLRP3-inflammasome in Parkinson’s disease are ongoing. However, the evidence supporting NLRP3’s involvement in Parkinson’s disease from human genetics data is limited. In this study, we conducted analyses of common and rare variants in NLRP3-inflammasome related genes in Parkinson’s disease cohorts. We performed pathway-specific analyses using polygenic risk scores and studied potential causal associations using Mendelian randomization with the NLRP3 components and the cytokines IL-1β and IL-18. Our findings showed no associations of common or rare variants, nor of the pathway polygenic risk score with Parkinson’s disease. Mendelian randomization suggests that altering the expression of the NLRP3-inflammasome, IL-1β or IL-18, does not affect Parkinson’s disease risk or progression. Therefore, our results do not support a role for the NLRP3-inflammasome in Parkinson’s disease pathogenesis or as a target for drug development.
Driving Under the Influence of Alcohol in People with Major Depressive Episodes and Alcohol Use Disorder
Authors: Park Ji-Yeun , Peterson Brent M. , Kim Jinsil , Galbadage Thushara 
Published: September 2023

ABSTRACTObjectivesAlcohol use disorder (AUD) and depression are the most commonly reported psychiatric comorbid conditions. We examined trends in the past-year prevalence of driving under the influence of alcohol (DUIA) among people with major depressive episodes (MDE), AUD, or both in the United States.MethodsWe analyzed 543,573 individuals aged 18 years or older from the 2005-2019 National Surveys on Drug Use and Health (NSDUH). Multivariate logistic regression models were applied to examine the adjusted past-year prevalence of DUIA. To assess trends in DUIA over time, annual average percent change (AAPC) was calculated.ResultsFrom 2005 to 2019, DUIA prevalence among US adults with MDE declined significantly from 18.1% to 9.4% (AAPC = -4.9). Decreasing trends in DUIA were also observed among those with AUD (from 55.4% to 37.8%, AAPC = -3.0) and among those with co-occurring MDE and AUD (from 58.3% to 38.8%, AAPC = -3.1). Compared to those with no AUD or MDE (from 8.42% to 3.99%, AAPC = -5.6), individuals with AUD and those with co-occurring MDE and AUD had significantly lower AAPCs. There was no significant AAPC difference between those with MDE and those with no AUD or MDE. Regarding sociodemographic characteristics, younger adults aged 18-34 exhibited the lowest AAPC among all diagnostic groups.ConclusionsFrom 2005 to 2019, DUIA prevalence declined significantly with varying rates of decrease across different diagnostic groups. Focused public health efforts are needed to engage high-risk groups that have shown a tendency toward less expedient reductions in DUIA.
Altered placental phenotype and increased risk of placental pathology in fetal spina bifida: a matched case-control study
Authors: White Marina , Grynspan David , Arif-Pardy Jayden , Van Mieghem Tim , Connor Kristin L 
Published: September 2023

AbstractOpen spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies and maldevelopment would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies. Placental histopathology (H&E-stained slides) and transcriptome (Clariom D™ microarray) were evaluated for fetuses with isolated open SB undergoing either pregnancy terminations or term deliveries (cases; n=12) and control fetuses without congenital anomalies having term or preterm births (n=22). Associations between study group and placental histopathology were adjusted for fetal sex and gestational age [GA] at delivery. Relationships between placental histopathology and select placental gene expression signatures were also evaluated. Case placentae had lower placental weight than controls (median [IQR]: 263g [175, 370] vs. 455 [378, 560], p=0.001). Placental villi structural phenotype was different in cases, who had a higher proportion of immature intermediate villi than controls (32.5% [6.3, 56.3] vs. 10% [5, 13.8], p=0.01), but similar proportions of mature intermediate (10% [5, 10] vs. 10% [8.75, 11.25]) and terminal villi (22.5% [11.3, 43.8] vs. 30 [20, 36.3]), and similar odds of having many syncytial knots (adjusted odds ratio [aOR]=6 [0.2, 369]) as full-term born controls. Cellular phenotypic differences in case placentae included higher odds of having many Hofbauer cells (aOR=16.2 [1.4, 580], p=0.02) and a thick syncytial membrane (aOR=146 [3, 3.46e5], p=0.007). Expression in gene pathways related to immune/inflammatory processes, spinal cord injury, and Hedgehog and Wnt signaling were associated with placental maturity in cases. This study is the first to characterize placental histopathology in a contemporary cohort of fetuses with SB. Improved knowledge on placental histopathological and genetic phenotypes in spina bifida increases our understanding of mechanisms that may drive comorbidities to ultimately reduce offspring morbidity and mortality.
CD8 T cell hyperfunction and reduced tumour control in models of advanced liver fibrosis
Authors: Madani Jood , Li Jiafeng , Vranjkovic Agatha , Jorritsma Katrina , Hasim Mohamed S , Daneshmand Manijeh , Cheung Angela C , E Ching Angela M , Bruin Jennifer E , Ardolino Michele , Crawley Angela M 
Published: September 2023

AbstractImmune dysfunction, both depression and hyperactivation, in liver disease contributes to significant morbidities and mortalities, depending on liver damage severity and etiology. The underlying causes of immune dysfunction in advanced liver disease, whether pathogen or host-mediated, remain unclear. We reported lasting generalized CD8+T cell hyperfunction in individuals with advanced liver fibrosis in chronic HCV infection. The separation of viral and fibrosis-driven effects or the association of this phenomenon with clinical outcomes of advanced liver fibrosis remains to be determined. Here, a hepatotoxic murine model of liver fibrosis was used to decouple liver fibrosis from viral infection. Carbon tetrachloride (CCl4)-treated mice presented progressive liver fibrosis within ≈12 weeks, resulting in severe diffuse fibrosis, focal necrosis and surrounding mixed inflammation; pathology similar to that of chronic HCV infection. Taking advantage of this model, we investigated if liver fibrosis caused systemic CD8+T cell hyperfunction and evaluated its impact on host immune response. At peak liver fibrosis, circulating CD8+T cells presented increased expression of IFN-γ and granzyme B (GrzB) in comparison to control animals. CD8+T cell hyperfunction arose by 8 weeks of CCl4treatment and was sustained with continued liver insult. As a result, fibrotic mice were unable to resist an ectopic tumour challenge and were less responsive to immunotherapy. Furthermore, CD8+T cell dysfunction was observed in other contexts of chronic liver insult such as high fat diet-induced liver steatosis, even in the absence of significant fibrosis. Collectively, this study shows the impact of chronic liver insult on systemic CD8+T cell function and its association with impaired immune response, such as tumour surveillance.
Mapping Structural Distribution and Gating-Property Impacts of Disease-Associated Missense Mutations in Voltage-Gated Sodium Channels
Authors: Ahangar Amin Akbari , Elhanafy Eslam , Blanton Hayden , Li Jing 
Published: September 2023

AbstractThousands of voltage-gated sodium (Nav) channel variants contribute to a variety of disorders, including epilepsy, autism, cardiac arrhythmia, and pain disorders. Yet variant effects of more mutations remain unclear. The conventional gain-of-function (GoF) or loss-of-function (LoF) classifications is frequently employed to interpret of variant effects on function and guide precision therapy for sodium channelopathies. Our study challenges this binary classification by analyzing 525 mutations associated with 34 diseases across 366 electrophysiology studies, revealing that diseases with similar phenotypic effects can stem from unique molecular mechanisms. Our results show a high biophysical agreement (86%) between homologous disease-associated variants in different Navgenes, significantly surpassing the 60% phenotype (GoFo/LoFo) agreement among homologous mutants, suggesting the need for more nuanced disease categorization and treatment based on specific gating-property changes. Using UniProt data, we mapped over 2,400 disease-associated missense variants across nine human Nav channels and identified three clusters of mutation hotspots. Our findings indicate that mutations near the selectivity filter generally diminish the maximal current amplitude, while those in the fast inactivation region lean towards a depolarizing shift in half-inactivation voltage in steady-state activation, and mutations in the activation gate commonly enhance persistent current. In contrast to mutations in the PD, those within the VSD exhibit diverse impacts and subtle preferences on channel activity. This study shows great potential to enhance prediction accuracy for variant effects based on the structural context, laying the groundwork for targeted drug design in precision medicine.
Genome related features of introns and exons reveal new properties and pareto fronts
Authors: Adiguzel Yekbun 
Published: September 2023

AbstractGenome annotations reveal vast amount information, as well as genome related features. We looked at the genome related features of eukaryotes, grouped as primates, rodents, birds, fishes, insects, and plants. Features related to introns and exons reveal distinct assets. Genes’ mean lengths are positively correlated with the collective data of counts of exons in coding transcripts and both the mean lengths and counts of introns in coding transcripts. Mean lengths of introns in non-coding transcripts are also positively correlated and correlations with the counts-data are excluding the data of plants and fishes. These are valid for the median lengths as well. In addition, certain feature comparisons reveal separation of primates, rodents, birds, fishes, insects, and plants. We also observed pareto fronts in the cumulative data with the max length values of genes and introns in coding transcripts, as well as introns in coding and non-coding transcripts.