bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic Force Generation in an Isometric Binary Mechanical System: A Thermodynamic Model of Muscle Force Generation
Authors: Murthy Vidya , Baker Josh E. 
Published: September 2023

ABSTRACTWith implications for both clean energy technologies and human health, models of muscle contraction provide insights into the inner workings of one of the most energy-efficient engines on the planet and into the modifications to that engine that lead to human diseases. However, only scientific methods can provide these insights. A binary mechanical model is a recently developed thermodynamic model of muscle contraction that implies a novel entropic kinetic formalism, provides a solution to a paradox that has perplexed scientists for over a century, and accounts for many mechanical and energetic aspects of muscle contraction. Here we use this model to perform discrete state chemical simulations of isometric force generation under different conditions and show explicitly that force generating kinetics are bounded by thermodynamic equations, that four phases of force generation occur as four separate thermodynamic processes, and that periodic force generation emerges with amplitudes and periodicities that bifurcate between constant and stochastic values through mechanisms easily understood relative to ideal thermodynamic processes. We discuss these results relative to experimental observations of spontaneous oscillatory contractions (SPOCs) in muscle and periodic force generation in small myosin ensembles.Significance StatementMost models of muscle contraction to date are based on the obsolete 17th century scientific philosophy that the force of the system is determined by the force of the molecules in that system. A new thermodynamic model of muscle provides a completely different interpretation of muscle mechanics and chemistry, implies a novel thermodynamic kinetic formalism, and has solved a paradigm that has intrigued scientists for over a century. Here, we use this model to simulate muscle force generation and show that force generating kinetics are constrained by thermodynamic equations that provide a clear mechanism for the periodic force generation that emerges from these stochastic simulations.
Four Phases of a Force Transient Emerge from a Binary Mechanical System
Authors: Baker Josh E. 
Published: September 2023

ABSTRACTModels of muscle contraction are important for guiding drug discovery, drug validation, and clinical decision-making with the goal of improving human health. Models of muscle contraction are also key to discovering clean energy technologies from one of the most efficient and clean-burning machines on the planet. However, these important goals can only be met through muscle models that are based on science. Most every model and mechanism (e.g., a molecular power stroke) of muscle contraction described in the literature to date is based on a corpuscular mechanic philosophy that has been challenged by science for over two decades. A thermodynamic model and mechanisms (e.g., a molecular switch) of muscle contraction is supported by science but has not yet been tested against experimental data. Here, I show that following a rapid perturbation to the free energy of a thermodynamic muscle system, a transient force response emerges with four phases, each corresponding to a different clearly-defined thermodynamic (not molecular) process. I compare these four phases to those observed in two classic muscle transient experiments. The observed consistency between model and data implies that the simplest possible model of muscle contraction (a binary mechanical system) accurately describes muscle contraction.
Within Thermal Scales: The Kinetic and Energetic Pull of Chemical Entropy
Authors: Baker Josh E. 
Published: September 2023

ABSTRACTBiological systems are fundamentally containers of thermally fluctuating atoms that through unknown mechanisms are structurally layered across many thermal scales from atoms to amino acids to primary, secondary, and tertiary structures to functional proteins to functional macromolecular assemblies and up. Understanding how the irreversible kinetics (i.e., the arrow of time) of biological systems emerge from the equilibrium kinetics of constituent structures defined on smaller thermal scales is central to describing biological function. Muscle’s irreversible power stroke – with its mechanochemistry defined on both the thermal scale of muscle and the thermal scale of myosin motors – provides a clear solution to this problem.Individual myosin motors function as reversible force-generating switches induced by actin binding and gated by the release of inorganic phosphate, Pi. As shown in a companion article, whenNindividual switches thermally scale up to an ensemble ofNswitches in muscle, the entropy of a binary system of switches is created. We have shown in muscle that a change in state of this binary system of switches entropically drives actin-myosin binding (the switch) and muscle’s irreversible power stroke, and that this simple two-state model accurately accounts for most key aspects of muscle contraction. Extending this observation beyond muscle, here I show that the chemical kinetics of an ensemble ofNmolecules differs fundamentally from a conventional chemical analysis ofNindividual molecules, describing irreversible chemical reactions as being pulled into the future by the a priori defined entropy of a binary system rather than being pushed forward by the physical occupancy of chemical states (e.g., mass action).
GIA: A genome interval arithmetic toolkit for high performance interval set operations
Authors: Teyssier Noam , Kampmann Martin , Goodarzi Hani 
Published: September 2023

AbstractMotivationThis study addresses the pressing need for efficient interval techniques in processing vast genomic datasets, such as those generated by ChIP-seq, RNA-seq, and whole-genome sequencing. Intervals are critical in characterizing biological features, necessitating streamlined interval manipulation for meaningful insights. Existing tools often struggle with memory and runtime requirements when managing extensive genomic region arithmetic.ResultsThe study introduces GIA (Genomic Interval Arithmetic) and BEDRS, a novel command-line tool and a rust library that significantly enhance the performance of genomic interval analysis. GIA outperforms existing tools like BEDOPS, BEDTools, and GenomicRanges by a factor of 2x to 20x across a range of operations. These advances enable researchers to perform genomic interval operations more efficiently, drastically reducing computational time and resource requirements in high-throughput genomic sequencing analysis.Availability and Implementation-https://github.com/noamteyssier/gia-https://github.com/noamteyssier/bedrs
Reference Sequence Browser: An R application with a user-friendly GUI to rapidly query sequence databases
Authors: Ramesh Sriram , Rapp Samuel , Tapias Gomez Jorge , Levine Benjamin , Tapias-Gomez Daniel , Chung Dickson , Truong Zia 
Published: September 2023

AbstractLand managers, researchers, and regulators increasingly utilize environmental DNA (eDNA) techniques to monitor species richness, presence, and absence. In order to properly develop a biological assay for eDNA metabarcoding or quantitative PCR, scientists must be able to find not only reference sequences (previously identified sequences in a genomics database) that match their target taxa but also reference sequences that match non-target taxa. Determining which taxa have publicly available sequences in a time-efficient and accurate manner currently requires computational skills to search, manipulate, and parse multiple unconnected DNA sequence databases.Our team iteratively designed a Graphic User Interface (GUI) Shiny application called the Reference Sequence Browser (RSB) that provides users efficient and intuitive access to multiple genetic databases regardless of computer programming expertise. The application returns the number of publicly accessible barcode markers per organism in the NCBI Nucleotide, BOLD, or CALeDNA CRUX Metabarcoding Reference Databases. Depending on the database, we offer various search filters such as min and max sequence length or country of origin. Users can then download the FASTA/GenBank files from the RSB web tool, view statistics about the data, and explore results to determine details about the availability or absence of reference sequences.
Short-term statin treatment reduces, and long-term statin treatment abolishes chronic vascular injury by radiation therapy
Authors: Ait-Aissa Karima , Guo Xutong , Klemmensen Madelyn , Leng Linette N. , Koval Olha M. , Grumbach Isabella M. 
Published: September 2023

ABSTRACTBackgroundThe incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease.ObjectivesDetermine if irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared to long-term administration.MethodsC57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy x-ray head-and-neck irradiation. Subsequently, they received pravastatin either for one additional day or for one year. Carotid arteries were tested for vascular reactivity and altered gene expression one year after irradiation.ResultsTreatment with pravastatin for 24 hours reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction after IR. It reduced the expression of some markers associated with inflammation and oxidative stress and modulated that of subunits of the voltage and Ca2+activated K+(BK) channel in the carotid artery one year after irradiation. Treatment with pravastatin for one year completely reversed the changes caused by irradiation.ConclusionsIn mice, short-term administration of pravastatin is sufficient to reduce chronic vascular injury after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.
Genetic networks suggest Asperger’s Syndrome as a distinct subtype of Autism Spectrum Conditions
Authors: Dmytriw Adam A. , Naveed Sadiq , Ghozy Sherief , Morsy Sara 
Published: September 2023

AbstractBackgroundThe Diagnostic and Statistical Manual of Mental Disorders (DSM-V) issued new diagnostic criteria for autism spectrum conditions (ASC) which excluded cases of Asperger’s syndrome (AS) and pervasive developmental disorder not otherwise specified (PDD-NOS). This negatively affected the support received by those affected. In this study, we explored if AS can be considered a subtype of autism.MethodsWe explored if AS is considered a subtype of autism through gene network analysis. We analysed the GEO microarray data of 170 autism patients, then, used a weighted gene co-expression network (WGCNA) pipeline. We explored whether these modules share the same expression patterns across autism subtypes. The study had 170 patients grouped into three groups: AS, autism, and PDD-NOS.ResultsTwenty-one genetic modules were constructed for autism spectrum conditions. However, only AS had a significant downregulation in one of the modules. The module genes were significantly involved in the regulation of proteolysis, catabolic process, and NF-kappaB signalling. Pathway analysis showed the association of these genes with RIPK1-mediated necrosis and regulation of necroptotic cell death. Brain enrichment analysis showed a spatiotemporal distribution. There was significant gene enrichment in the prefrontal cortex during infancy and childhood then it changes in adulthood to be more abundant in the cingulum bundle, and corpus callosum.ConclusionsOur results suggest AS can be a distinct subtype of ASD, showing a similar gene expression pattern. Spatiotemporal distribution of the module genes in different brain regions explains the high functionality in individuals with AS.
Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study
Authors: Lam Yin Ting , Papon Jean-François , Alexandru Mihaela , Anagiotos Andreas , Armengot Miguel , Boon Mieke , Burgess Andrea , Calmes Doriane , Crowley Suzanne , Dheyauldeen Sinan Ahmed. D. , Emiralioglu Nagehan , Erdem Eralp Ela , van Gogh Christine , Gokdemir Yasemin , Haarman Eric G. , Harris Amanda , Hayn Isolde , Ismail-Koch Hasnaa , Karadag Bülent , Kempeneers Céline , Kieninger Elisabeth , Kim Sookyung , Lorent Natalie , Ozcelik Ugur , Pioch Charlotte , Raidt Johanna , Reula Ana , Roehmel Jobst , Sperstad Kennelly Synne , Yiallouros Panayiotis , Goutaki Myrofora 
Published: September 2023

AbstractIntroductionNearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study.MethodsWe included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (CRS)—defined using patient-reported information and examination findings—with reported sputum production and shortness of breath—using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of CRS and FEV1, accounting for relevant factors.ResultsWe included 457 patients [median age: 15; interquartile range (IQR) 10–24; 54% males]. Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.29–3.54], and CRS (OR 2.3; 95% CI 1.57–3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2; 95% CI 1.20–4.09) and hearing (OR 2.0; 95% CI 1.10–3.64) problems and CRS (OR 2.1; 95% CI 1.48–3.07). We did not find any association between CRS and FEV1.ConclusionReported upper airway symptoms and signs of CRS associated with reported pulmonary symptoms; however, not with lung function. Our results emphasise assessing and managing upper and lower respiratory disease as a common, interdependent entity among patients with PCD.
Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age
Authors: Terebuh Pauline , Olaker Veronica R. , Kendall Ellen K. , Kaelber David C. , Xu Rong , Davis Pamela B. 
Published: September 2023

ABSTRACTObjectiveBeginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities.DesignWe conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations.ResultsCompared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections.ConclusionThese results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare (∼1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver.What is already known on this topicClusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent.What this study addsSARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases.How this study might affect research, practice or policyDespite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.
The impact of motor, non-motor, and social aspects on the sexual health of men living with Parkinson’s disease
Authors: Antunes Souza Bruno Rafael , Costa Nóbrega Kátia Cirilo , de Almeida da Silva Bruno Eron , Gonçalves Raissa Amorim , Martins Thalyta Silva , Santos Geovanna Ferreira , Frazão Andre Helene , Roque Antonio Carlos , da Silva Nascimento Isaíra Almeida Pereira , Pimentel Piemonte Maria Elisa 
Published: September 2023

AbstractBackgroundSexual health (SH) is influenced by several biological, mental, and social factors which may be negatively impacted by PD. Despite its prevalence and relevance for quality of life, the factors that affect the SH in men with Parkinson’s disease (MwPD) are still poorly understood, and research in this area is scarce.AimTo investigate the impact of motor, non-motor, and social aspects on the SH in MwPD.MethodWe conducted a cross-sectional study of 80 men (mean age 53.55±10.8) in stages 1-3 of disease progression according to Hoehn and Yahr classification (H&Y), who reported to have sexual activity. The following data were collected for each person (used tests/scales indicated within parentheses and defined in glossary): (1) demographic information and global cognitive capacity (T-MoCA); (2) non-motor aspects of daily life experiences (MDS-UPDRS, part I); (3) motor aspects of daily life experiences (MDS-UPDRS, part II); (4) fatigue (FSS); (5) self-esteem (RSES); (6) sleep disorder (PDSS); (7) couple relationship quality (DAS); (8) depressive signals (BDI); (8) short-term sexual health by International Index of Erectile Function (IIFE); and (9) long-term sexual health by Sexual Quotient-Male (SQ-M).ResultsOur results suggest that the quality of marital relationships predicts short-term SH, motor disability level predicts erectile dysfunction, and depression predicts long-term SH in MwPD. Age, disease onset, disease duration, Levodopa dosage, and non-motor symptoms, excluding depression, were not correlated with SH.ConclusionOur findings confirm that multidimensional factors can affect the SH of MwPD and emphasize that only a multi-professional team can offer proper care to improve SH in MwPD.
Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021–June 2022
Authors: Sumner Kelsey M. , Yadav Ruchi , Noble Emma K. , Sandford Ryan , Joshi Devyani , Tartof Sara Y. , Wernli Karen J. , Martin Emily T. , Gaglani Manjusha , Zimmerman Richard K. , Talbot H. Keipp , Grijalva Carlos G. , Chung Jessie R. , Rogier Eric , Coughlin Melissa M. , Flannery Brendan 
Published: September 2023

ABSTRACTBackgroundWe assessed the association between antibody concentration ≤5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative studyMethodsFrom October 2021─June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti- SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1–adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure.ResultsA total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS- CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95%CI:690─981) among COVID-19 case- patients versus 1,189 BAU/mL (95%CI:1,050─1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections.ConclusionHigher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.
Associations between depression symptom burden and delirium risk: a prospective cohort study
Authors: Gaba Arlen , Li Peng , Zheng Xi , Gao Chenlu , Ruixue Cai , Hu Kun , Gao Lei 
Published: September 2023

AbstractBACKGROUND AND OBJECTIVESDelirium and depression are increasingly common in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer’s disease (AD), functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older individuals during hospitalization.RESEARCH DESIGN AND METHODS319,141 UK biobank participants between 2006-2010 (mean 58y [range 37-74, SD=8], 54% female) reported frequency (0-3) of four depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks, and aggregated into a depressive symptom burden score (0-12). New-onset delirium was obtained from hospitalization records during 12y median follow-up. 40,451 (mean age 57±8; range 40-74y) had repeat assessment on average 8y after their first. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium during hospitalization.RESULTS5,753 (15 per 1000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1-2, hazards ratio, HR=1.16, [95% confidence interval 1.08–1.25],p<0.001), modest (scores 3-5, 1.30 [1.19–1.43],p<0.001) and severe (scores ≥ 5, 1.38 [1.24–1.55],p<0.001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across hospitalization settings (e.g., surgical, medical, or critical care) and specialty (e.g., neuropsychiatric, cardiorespiratory or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03–1.88],p=0.03) independent of baseline depression burden. The association was strongest in those over 65y at baseline (pfor interaction <0.001).DISCUSSION AND IMPLICATIONSDepression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may be warranted for delirium prevention.