bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Accuracy Machine Learning Model for Sarcopenia Severity Diagnosis based on Sit-to-stand Motion Measured by Two Micro Motion Sensors
Authors: Wang Keer , Zhang Hongyu , Cheng Clio Yuen Man , Chen Meng , Lai King Wai Chiu , Or Calvin Kalun , Chen Yonghua , Hu Yong , Vellaisamy Arul Lenus Roy , Lam Cindy Lo Kuen , Xi Ning , Lou Vivian W. Q. , Li Wen Jung 
Published: May 2023

AbstractIn this ageing society, sarcopenia as a geriatric condition that can have significant negative impacts on an individual’s quality of life. Sarcopenia is a kind of aged syndrome associated with loss of muscle mass and function, which may lead to falls, fractures, gait disorders or even mortality. There are multiple ways to diagnose sarcopenia, such as using Magnetic resonance imaging (MRI), Dual-energy X-ray absorptiometry (DEXA) and Bioelectrical impedance analysis (BIA) etc. to calculate muscle mass; using handgrip or sit-to-stand to measure muscle strength; using short physical performance battery (SPPB), gait, and 5-time sit-to-stand to evaluate physical performance.In this work, we use two μIMUs worn on subjects to record their sit-to-stand motion, and then used several machine learning models to diagnose the severity of sarcopenia of the subjects. We recruited 53 elderly subjects in total for this work. The youngest subject is 65 years old and the oldest is 84 years old. Their average age is 70 years old. Among these 53 subjects, there are 12 healthy ones and 41 sarcopenia patients with different severity. The subject is instructed to do the single sit-to-stand (STS) three times, and two μIMUs attached to the subject’s waist and thigh transfer the data to a computer by Bluetooth. We separated the STS motion process into 4 phases based on the angle and angular velocity, extracted a total of 510 features for motion analytics. These features were futher analyzed by sequential feature selection with 5 different machine learning models (SVM, KNN, decision tree, LDA, and multilayer perceptron). With our proposed methodology, all 53 subjects could be classified as healthy or having sarcopenia with risk level 1, 2, or 3. The best accuracy to distinguish the healthy or sarcopenia subjects is 98.32%, and the best results to distinguish sarcopenia risk levels from 0 (healthy) to 3 (most severe) is 90.44%.
Beta blockers, digoxin or both following an incident diagnosis of atrial fibrillation – a prospective cohort study
Authors: Brophy James M , Nadeau Lyne 
Published: May 2023

AbstractBackgroundAtrial fibrillation is one of the most common arrhythmias but the optimal drug choice for a rate control strategy remains uncertain. In particular, controversy and uncertainty exists regarding the safety of digoxin in this context.MethodsThis was a retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta blockers, digoxin or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovas-cular (CV) hospitalization. Secondary outcomes were the individual components of the primary outcome. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. In sensitivity analyses, baseline covariate imbalances were adjusted using a maximum likelihood algorithm and an overall average treatment effect estimand. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model.Results12,723 patients were discharged on beta blockers alone, 406 on digoxin alone, and 1,499 discharged on combined beta blocker / digoxin therapy with a median follow-up time of 356 days. In the unadjusted analyses, the primary outcome occured most frequently in the combined exposure group (15.5%) compared to the isolated digoxin (13.3%) and beta blocker (11.5%) groups (p < 0.001 for trend). There were more CV hospitalizations in the combined beta blocker / digoxin group (14.4%) compared to the BB (10.7%) or digoxin (10.6%) groups (p = 0.006 for trend). There were more deaths in the digoxin group (2.7%) and the combined group (1.1%) groups compared to the BB alone group (0.8%) (p < 0.001 for trend). However, after baseline covariate adjustment, the digoxin alone (hazard ratio (HR) 1.24, 95% CI 0.85 - 1.81) and the combined group (HR 1.09, 95% CI 0.90 - 1.31) were not associated with increased risk for the composite endpoint compared with the beta blocker alone group. These results were robust to sensitivity analyses.ConclusionAfter accounting for baseline imbalances, patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared to those discharged on isolated beta blocker therapy. However, additional studies are required to refine the precision of these estimates.
Five-year Transitions of Symptom Subtypes in Untreated Obstructive Sleep Apnea
Authors: Morris Jonna L. , Scott Paul W. , Magalang Ulysses , Keenan Brendan T , Patel Sanjay R. , Pack Allan I. , Mazzotti Diego R. 
Published: May 2023

AbstractObjectivesIt is unknown if symptom subtypes of obstructive sleep apnea (OSA) transition over time and what clinical factors may predict transitions.MethodsData from 2,643 participants of the Sleep Heart Health Study with complete baseline and 5-year follow-up visits were analyzed. Latent Class Analysis on 14 symptoms at baseline and follow up determined symptom subtypes. Individuals without OSA (AHI<5) were incorporated as a known class at each time point. Multinomial logistic regression assessed the effect of age, sex, body mass index (BMI) and AHI on specific class transitions.ResultsThe sample consisted of 1,408 women (53.8%) and mean (SD) age 62.4 (10.5) years. We identified four OSA symptom subtypes at both baseline and follow-up visits:minimally symptomatic, disturbed sleep, moderately sleepyandexcessively sleepy. Nearly half (44.2%) of the sample transitioned to a different subtype from baseline to follow-up visits; transitions tomoderately sleepywere the most common (77% of all transitions). A five-year older age was associated with a 6% increase in odds to transit fromexcessively sleepytomoderately sleepy[OR (95% CI) = 1.06 (1.02, 1.12)]. Women had 2.35 times higher odds (95% CI: 1.27, 3.27) to transition frommoderately sleepytominimal symptoms. A 5-unit increase in BMI was associated with 2.29 greater odds (95% CI: 1.19, 4.38) to transition fromminimal symptomstoexcessively sleepy.InterpretationWhile over half of the sample did not transition their subtype over 5 years, among those who did, the likelihood of transitioning between subtypes was significantly associated with a higher baseline age, higher baseline BMI and with women, but was not predicted by AHI.Clinical TrialsSleep Heart Health Study (SHHS) Data Coordinating Center, (SHHS)https://clinicaltrials.gov/ct2/show/NCT00005275,NCT00005275Statement of significanceThere is very little research assessing symptom progression and its contributions to clinical heterogeneity in OSA. In a large sample with untreated OSA, we grouped common OSA symptoms into subtypes and assessed if age, sex, or BMI predicted transitions between the subtypes over 5 years. Approximately half the sample transitioned to a different symptom subtype and improvements in symptom subtype presentation were common. Women and older individuals were more likely to transition to less severe subtypes, while increased BMI predicted transition to more severe subtype. Determining whether common symptoms like disturbed sleep or excessive daytime sleepiness occur early in the course of the disease or as a result of untreated OSA over an extended period can improve clinical decisions concerning diagnosis and treatment.
Ordinary differential equations to construct invertible generative models of cell type and tissue-specific regulatory networks
Authors: Niktab Eliatan , Atkinson Paul H. , Walterfang Mark , Winship Ingrid , Sturley Stephen L. , Munkacsi Andrew B. 
Published: May 2023

1AbstractSingle-cell RNA-Seq (scRNA-seq) transcriptomics can elucidate gene regulatory networks (GRNs) of complex phenotypes, but raw sequencing observations only provide ”snap-shots” of data and are inherently noisy. scRNA-seq trajectory inference has been utilized to solve for the missing observations, but disentangling complex dynamics of gene-gene interactions at different time points from aggregated data is a non-trivial task and computationally expensive. Here we describe our Non-Stiff Dynamic Invertible Model of CO-Regulatory Networks (NS-DIMCORN) to define the genetic nexus underpinning specific cellular functions using invertible warping of flexible multivariate Gaussian distributions by neural Ordinary differential equations. Our results yield a generative model with unbiased density estimation from RNA-seq read-count data only. This resulted in scalable time-flexible sampling of each gene’s expression level thence allowing ab initio assembly of gene regulatory networks in specific cells. We demonstrate our proposed methodology is superior to the state-of-the-art algorithms in accurately recovering genome-wide functional interactions, whether from synthetic or empirical data. We optimized our algorithm for GPU-based implementation thereby further enhancing the utility of our proposed methodology in comparison to the ten benchmarked methods.
Global diversity of enterococci and description of 18 novel species
Authors: Schwartzman Julia A. , Lebreton Francois , Salamzade Rauf , Martin Melissa J. , Schaufler Katharina , Urhan Aysun , Abeel Thomas , Camargo Ilana L.B.C , Sgardioli Bruna F. , Prichula Janira , Frazzon Ana Paula Guedes , Tyne Daria Van , Treinish Gregg , Innis Charles J. , Wagenaar Jaap A. , Whipple Ryan M. , Manson Abigail L. , Earl Ashlee M. , Gilmore Michael S. 
Published: May 2023

ABSTRACTEnterococci are commensal gut microbes of most land animals. They diversified over hundreds of millions of years adapting to evolving hosts and host diets. Of over 60 known enterococcal species,Enterococcus faecalisandE. faeciumuniquely emerged in the antibiotic era among leading causes of multidrug resistant hospital-associated infection. The basis for the association of particular enterococcal species with a host is largely unknown. To begin deciphering enterococcal species traits that drive host association, and to assess the pool ofEnterococcus-adapted genes from which known facile gene exchangers such asE. faecalisandE. faeciummay draw, we collected 886 enterococcal strains from nearly 1,000 specimens representing widely diverse hosts, ecologies and geographies. This provided data on the global occurrence and host associations of known species, identifying 18 new species in the process expanding genus diversity by >25%. The novel species harbor diverse genes associated with toxins, detoxification, and resource acquisition.E. faecalisandE. faeciumwere isolated from a wide diversity of hosts highlighting their generalist properties, whereas most other species exhibited more restricted distributions indicative of specialized host associations. The expanded species diversity permitted theEnterococcusgenus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades as well as genes associated with range expansion, such as B-vitamin biosynthesis and flagellar motility. Collectively, this work provides an unprecedentedly broad and deep view of the genusEnterococcus, potential threats to human health, and new insights into its evolution.SIGNIFICANCEEnterococci, host-associated microbes that are now leading drug-resistant hospital pathogens, arose as animals colonized land over 400 million years ago. To globally assess the diversity of enterococci now associated with land animals, we collected 886 enterococcal specimens from a wide range of geographies and ecologies, ranging from urban environments to remote areas generally inaccessible to humans. Species determination and genome analysis revealed host associations from generalists to specialists, and identified 18 new species, increasing the genus by over 25%. This added diversity provided greater resolution of the genus clade structure, identifying new features associated with species radiations. Moreover, the high rate of new species discovery shows that tremendous genetic diversity in Enterococcus remains to be discovered.
Antigenic mapping of the hemagglutinin of the H9 subtype influenza A viruses using sera from Japanese quail (Coturnix c. japonica)
Authors: Carnaccini Silvia , Cáceres C. Joaquín , Gay L. Claire , Ferreri Lucas M. , Skepner Eugene , Burke David F. , Brown Ian H. , Geiger Ginger , Obadan Adebimpe , Rajao Daniela S. , Lewis Nicola S. , Perez Daniel R. 
Published: May 2023

ABSTRACTInfluenza A viruses (FLUAV) of the H9N2 subtype are zoonotic pathogens that cause significant economic damage to the poultry industry. Vaccination to prevent and control H9N2 infections in poultry is widely employed in the Middle East and Asia. We used phylogenetics and antigenic analysis to study the antigenic properties of the H9 hemagglutinin (HA) using sera produced in Japanese quail (Coturnix c. japonica). Consensus HA1 sequences were generated to capture antigenic diversity among isolates. We constructed chimeric H9N2 viruses containing the HA1 of each consensus sequence on a constant isogenic backbone. The resulting viruses were used to generate antisera from quail, a common and significant minor poultry species whose anti-HA response profiles remain poorly defined. Antigenic maps were generated by plotting the cross-hemagglutination inhibition (HI) data from the panel of quail sera against the chimeric constructs and 51 H9 field isolates. The chimeric antigens were divided into four different antigenic profiles (cyan, blue, orange, and red). Site-directed mutagenesis analysis showed 9 amino acid positions of antigenic relevance. Substitutions at amino acid positions 149, 150, and 180 (H9 HA numbering) had relatively significant impact on HI activity using quail sera. Substitutions E180A and R131K/E180A led to the most significant antigenic change transitions. This study provides insights into the antigenic profile of H9 FLUAVs, with important implications for understanding antigenic drift and improving vaccine development for use in minor poultry species.IMPORTANCEDetermining the relevant amino acids involved in antigenic drift on the surface protein hemagglutinin (HA) is critical to understand influenza virus evolution and efficient assessment of vaccine strains relative to current circulating strains. We used antigenic cartography to generate an antigenic map of the H9 HA using sera produced in one of the most relevant minor poultry species, Japanese quail. Key antigenic positions were identified and tested to confirm their impact on the antigenic profile. This work provides a better understanding of the antigenic diversity of the H9 HA as it relates to reactivity to quail sera and will facilitate a rational approach for selecting more efficacious vaccines against poultry-origin H9 influenza viruses in minor poultry species.
When is an auxotroph not an auxotroph: how budding yeast lackingMET17collectively overcome their metabolic defect
Authors: Sonal  , Yuan Alex E. , Yang Xueqin , Shou Wenying 
Published: May 2023

ABSTRACTAssimilation of sulfur is vital to all organisms. InS. cerevisiae, inorganic sulfate is first reduced to sulfide, which is then reacted to an organic carbon backbone by the Met17 enzyme. The resulting homocysteine can then be converted to all other essential organosulfurs such as methionine, cysteine, and glutathione. This pathway has been known for nearly half a century, andmet17mutants have long been classified as organosulfur auxotrophs which are unable to grow on sulfate as the sole sulfur source. Surprisingly, we found thatmet17Δ could grow on sulfate, albeit only at sufficiently high cell densities. We show that the accumulation of hydrogen sulfide gas underpins this density-dependent growth ofmet17Δ on sulfate, and that the locusYLL058W(HSU1) enablesmet17Δ cells to assimilate hydrogen sulfide. Hsu1 protein is induced during sulfur starvation and under exposure to high sulfide in wildtype cells, suggesting multiple functions of this gene. In a mathematical model, the low efficiency of sulfide assimilation inmet17Δ can explain the observed density-dependent growth ofmet17Δ on sulfate. Thus, having uncovered and explained the paradoxical growth of a commonly used “auxotroph”, our findings may impact the design of future studies in yeast genetics, metabolism, and volatile-mediated microbial interactions.
The role of Smarcad1 in retroviral repression in mouse embryonic stem cells
Authors: Bren Igor , Strauss Carmit , Schlesinger Sharon 
Published: May 2023

AbstractBackgroundMoloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3. However, the role of Trim28, H3.3, and Smarcad1 in MLV repression in ESCs still needs to be fully understood.ResultsIn this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states.ConclusionsOverall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.Take homeDepletion of Smarcad1 impairs retroviral repression.Smarcad1 is necessary for proper recruitment of Trim28 and H3.3 deposition.Depleting Smarcad1 and Trim28 results in enhanced derepression of the MLV provirus.
Molecular mechanisms underlying the formation of larval green color and camouflage patterns in swallowtail butterfly,Papilio memnon
Authors: Liu Liang , Komata Shinya , Wu Kai , Kojima Tetsuya , Fujiwara Haruhiko 
Published: May 2023

AbstractInsects have various strategies like mimicry or camouflage to avoid predation. Swallowtail butterfly larvae switch from a black and white pattern mimicking bird droppings to a green camouflage pattern in the fifth (final) instar. This larval pattern switch is regulated during the juvenile hormone (JH)-sensitive period, when JH titer declines rapidly, andclawless(cll),abdominal-A(abd-A), andAbdominal-B(Abd-B) function during this period. However, the molecular mechanism behind the background green color, a crucial aspect of the camouflage pattern, remains poorly understood. Here, we usedPapilio memnon, which switches to the camouflage pattern in the fifth instar but is greenish from the third instar, to investigate the mechanism of camouflage pattern formation, particularly the larval green coloration.Through RNA sequencing, we found thatBBPs forming a gene cluster are upregulated in the green regions ofP. memnonlarvae during the fourth instar, whereasP. xuthuslarvae, which have not yet turned green, showed minimalBBPs expression. WhenBBP1andBBP2, which were particularly highly expressed, were knocked down by RNAi, there was a phenotypic change in green to yellow in both fourth and fifth instar larvae. Expression analysis and knockdown experiments were conducted also forJHBP, which had been previously reported, and confirmed that it is involved in the synthesis of yellow pigment. Furthermore, knockdown ofUbxresulted in no phenotypic change in fourth instar larvae, but in fifth instar larvae, the eyespots pattern characteristic of the camouflage pattern almost entirely disappeared, suggesting thatUbxis also functional only during JH-sensitive period.Our results indicate that the switch from mimetic to camouflage patterns resulted from the function ofcll,abd-A,Abd-B, andUbxprepatterning genes during the JH-sensitive period. And the increased expression ofBBPs andJHBPs, independent of the JH-sensitive period, contributed to the development of green coloration.
High Ambient Temperature in Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia
Authors: Rogne Tormod , Wang Rong , Wang Pin , Deziel Nicole C. , Metayer Catherine , Wiemels Joseph L. , Chen Kai , Warren Joshua L. , Ma Xiaomei 
Published: May 2023

ABSTRACTBackgroundHigh ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, the incidence is increasing, and in the United States it disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood ALL.MethodsWe used data from California birth records (1982-2015) and California Cancer Registry (1988-2015) to identify ALL cases diagnosed <14 years and 50 times as many controls matched by sex, race/ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. Association between ambient temperature and ALL was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy) and constructed an alternatively matched dataset for exposure contrast by seasonality.FindingsOur study included 6,258 ALL cases and 307,579 controls. The peak association between ambient temperature and risk of ALL was observed in gestational week 8, where a 5 °C increase was associated with an odds ratio of 1.09 (95% confidence interval 1.04-1.14) and 1.05 (95% confidence interval 1.00-1.11) among Latino and non-Latino White children, respectively. The sensitivity analyses supported this.InterpretationOur findings suggest an association between high ambient temperature in early pregnancy and risk of childhood ALL. Further replication and investigation of mechanistic pathways may inform mitigation strategies.