bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation on How Dynamic Effective Connectivity Patterns Encode the Fluctuating Pain Intensity in Chronic Migraine
Authors: Bassez Iege , Van de Steen Frederik , Hackl Sophie , Jahn Pauline , Mayr Astrid , Marinazzo Daniele , Schulz Enrico 
Published: February 2022

ABSTRACTChronic migraine is characterised by persistent headaches for more than 15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 minutes). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients.The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.
Persistent horizontal and vertical, MR-induced nystagmus in resting state Human Connectome Project data
Authors: Go Cammille C , Taskin Huseyin O , Ahmadi Seyed-Ahmad , Frazzetta Giulia , Cutler Laura , Malhotra Saguna , Morgan Jessica IW , Flanagin Virginia L , Aguirre Geoffrey K 
Published: February 2022

AbstractObjectiveStrong magnetic fields from magnetic resonance (MR) scanners induce a Lorentz force that contributes to vertigo and persistent nystagmus. Prior studies have reported a predominantly horizontal direction for healthy subjects in a 7 Tesla (T) MR scanner, with slow phase velocity (SPV) dependent on head orientation. Less is known about vestibular signal behavior for subjects in a weaker, 3T magnetic field, the standard strength used in the Human Connectome Project (HCP). The purpose of this study is to characterize the form and magnitude of nystagmus induced at 3T.MethodsForty-two subjects were studied after being introduced head-first, supine into a Siemens Prisma 3T scanner. Eye movements were recorded in four separate acquisitions over 20 minutes. A biometric eye model was fit to the recordings to derive rotational eye position and then SPV. An anatomical template of the semi-circular canals was fit to the T2 anatomical image from each subject, and used to derive the angle of the B0 magnetic field with respect to the vestibular apparatus.ResultsRecordings from 37 subjects yielded valid measures of eye movements. The population-mean SPV ± SD for the horizontal component was −1.38 ± 1.27 deg/sec, and vertical component was −0.93 ± 1.44 deg/sec, corresponding to drift movement in the rightward and downward direction. Although there was substantial inter-subject variability, persistent nystagmus was present in half of subjects with no significant adaptation over the 20 minute scanning period. The amplitude of vertical drift was correlated with the roll angle of the vestibular system, with a non-zero vertical SPV present at a 0 degree roll.InterpretationNon-habituating vestibular signals of varying amplitude are present in resting state data collected at 3T.
Structural and functional alterations of neuromuscular synapses in a mouse model of ACTA1 congenital myopathy
Authors: Liu Yun , Lin Weichun 
Published: February 2022

AbstractMutations in skeletal muscle α-actin (Acta1) cause a variety of myopathies. In a mouse model of congenital myopathy, heterozygous Acta1 (H40Y) knock-in (Acta1+/Ki) mice exhibit features of human nemaline myopathy, including premature lethality, severe muscle weakness, reduced mobility, and the presence of nemaline rods in muscle fibers. In this study, we investigated the structure and function of the neuromuscular junction (NMJ) in the Acta1+/Ki mice. We found marked impairments in NMJ structure in the mutant mice, including fragmented endplates and nerve terminals, reduced density of acetylcholine receptors (AChRs) on endplate membranes, reduced nerve occupancy at endplates, and increased numbers of muscle fiber subsynaptic nuclei. We compared the NMJs in three different types of muscles – the extensor digitorum longus (EDL, composed of fast-twitch muscle fibers), soleus (Sol, enriched in slow-twitch fibers) and the triangularis sterni muscle (TS, a mixed fiber type muscle). Among these three types of muscles, EDL was affected to the greatest extent, suggesting that fast-twitch fibers may be most susceptible to NMJ fragmentation in Acta1+/Ki nemaline myopathy.Electrophysiological analysis of mutant NMJs showed a reduced quantal size (reduced mEPP amplitude), increased mEPP frequency, and increased quantal content, but normal EPP amplitude compared to wild type (WT) NMJs. The results suggest that affected synapses may have undergone homeostatic compensation to maintain normal levels of neurotransmitter release. In addition, paired-pulse facilitation was reduced and synaptic depression under repetitive nerve stimulation was enhanced, indicating shortterm synaptic plasticity was compromised in the mutant mice.Key pointsMice heterozygous for an Acta1 (H40Y) knock-in mutation exhibit clinical features of human nemaline myopathy. We report structural and functional alterations of neuromuscular synapses in these mutant mice. The NMJ impairments include endplate fragmentation, reduced endplate nerve occupancy, and increased numbers of subsynaptic nuclei in muscle fibers.Neuromuscular synaptic transmission was compromised – demonstrating both increased quantal content and changes in short-term synaptic plasticity.Increases in spontaneous neurotransmitter release and quantal content suggest homeostatic compensation of synapses to maintain normal transmitter release in the mutant NMJs.
Uncertainty Quantification in Variable Selection for Genetic Fine-Mapping using Bayesian Neural Networks
Authors: Cheng Wei , Ramachandran Sohini , Crawford Lorin 
Published: February 2022

AbstractIn this paper, we propose a new approach for variable selection using a collection of Bayesian neural networks with a focus on quantifying uncertainty over which variables are selected. Motivated by fine-mapping applications in statistical genetics, we refer to our framework as an “ensemble of single-effect neural networks” (ESNN) which generalizes the “sum of single-effects” regression framework by both accounting for nonlinear structure in genotypic data (e.g., dominance effects) and having the capability to model discrete phenotypes (e.g., case-control studies). Through extensive simulations, we demonstrate our method’s ability to produce calibrated posterior summaries such as credible sets and posterior inclusion probabilities, particularly for traits with genetic architectures that have significant proportions of non-additive variation driven by correlated variants. Lastly, we use real data to demonstrate that the ESNN framework improves upon the state-of-the-art for identifying true effect variables underlying various complex traits.
Automatic Generation of Interactive Multidimensional Phase Portraits
Authors: Ogunsan Oluwateniayo O. , Lobo Daniel 
Published: February 2022

AbstractMathematical models formally and precisely represent biological mechanisms with complex dynamics. To understand the possible behaviors of such systems, phase portrait diagrams can be used to visualize their overall global dynamics across a domain. However, producing these phase portrait diagrams is a laborious process reserved to mathematical experts. Here, we developed a computational methodology to automatically generate phase portrait diagrams to study biological dynamical systems based on ordinary differential equations. The method only needs as input the variables and equations describing a multidimensional biological system and it automatically outputs for each pair of dependent variables a complete phase portrait diagram, including the critical points and their stability, the nullclines of the system, and a vector space of the trajectories. Crucially, the portraits generated are interactive, and the user can move the visualized planar slice, change parameters with sliders, and add trajectories in the phase and time domains, after which the diagrams are updated in real time. The method is available as a user-friendly graphical interface or can be accessed programmatically with aMathematicapackage. The generated portraits and particular views can be saved as computable notebooks preserving the interactive functionality, an approach that can be adopted for reproducible science and interactive pedagogical materials. The method, code, and examples are freely-available athttps://lobolab.umbc.edu/autoportrait.
The effect of carbamazepine on bone structure and strength in control and Osteogenesis Imperfecta (Col1a2+/p.G610C) mice
Authors: Blank Martha , McGregor Narelle E , Rowley Lynn , Kung Louise HW , Crimeen-Irwin Blessing , Poulton Ingrid J , Walker Emma C , Gooi Jonathan H , Lamande Shireen R. , Sims Natalie A , Bateman John F. 
Published: February 2022

AbstractThe inherited brittle bone disease osteogenesis imperfecta (OI) is commonly caused byCOL1A1andCOL1A2mutations that disrupt the collagen I triple helix. This causes intracellular endoplasmic reticulum (ER) retention of the misfolded collagen and can result in a pathological ER stress response. A therapeutic approach to reduce this toxic mutant load could be to stimulate mutant collagen degradation by manipulating autophagy and/or ER-associated degradation. Since carbamazepine (CBZ) both stimulates autophagy of misfolded collagen X and improves skeletal pathology in a metaphyseal chondrodysplasia model, we tested the effect of CBZ on bone structure and strength in 3 week-old male OICol1a2+/p.G610Cand control mice. Treatment for 3 or 6 weeks with CBZ, at the dose effective in metaphyseal chondrodysplasia, provided no therapeutic benefit toCol1a2+/p.G610Cmouse bone structure, strength, or composition, measured by micro-computed tomography, three point bending tests and Fourier-transform infrared microspectroscopy. In control mice however, CBZ treatment for 6 weeks impaired femur growth and led to lower femoral cortical and trabecular bone mass. These data, showing the negative impact of CBZ treatment on the developing mouse bones, raise important issues which must be considered in any human clinical applications of CBZ in growing individuals.
Time-lagged Flux in the Transition Path Ensemble: Flux Maximization and Relation to Transition Path Theory
Authors: Li Wenjin 
Published: February 2022

AbstractTransition path ensemble is of special interest in reaction coordinate identification as it consists of reactive trajectories that start from the reactant state and end in the product one. As a theoretical framework for describing the transition path ensemble, the transition path theory has been introduced more than ten years ago and so far its applications have been only illustrated in several low-dimensional systems. Given the transition path ensemble, expressions for calculating flux, current (a vector field), and principal curve are derived here in the space of collective variables from the transition path theory and they are applicable to time-series obtained from molecular dynamics simulations of high-dimensional systems, i.e., the position coordinates as a function of time in the transition path ensemble. The connection of the transition path theory is made to a density-weighted average flux, a quantity proposed in a previous work to appraise the relevance of a coordinate to the reaction coordinate [W. Li, J. Chem. Phys. 156, 054117 (2022)]. Most importantly, as an extension of the existing quantities, time-lagged quantities such as flux and current are also proposed. The main insights and objects provided by these time-lagged quantities are illustrated in the application to the alanine peptide in vacuum.
Cross-neutralizing activity against Omicron could be obtained in SARS-CoV-2 convalescent patients who received two doses of mRNA vaccination
Authors: Kurahashi Yukiya , Furukawa Koichi , Sutandhio Silvia , Tjan Lidya Handayani , Iwata Sachiyo , Sano Shigeru , Tohma Yoshiki , Ohkita Hiroyuki , Nakamura Sachiko , Nishimura Mitsuhiro , Arii Jun , Kiriu Tatsunori , Yamamoto Masatsugu , Nagano Tatsuya , Nishimura Yoshihiro , Mori Yasuko 
Published: February 2022

AbstractThe SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n=23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Surprisingly and interestingly, after the second vaccination, the subjects’ neutralizing antibody titers including that against Omicron all became seropositive, and significant fold-increases (21.1–52.0) were seen regardless of the subjects’ disease severity. Our findings thus demonstrate that at least two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.
Inflammatory and immune markers in HIV-infected older adults on long-term antiretroviral therapy: persistent elevation of sCD14 and of proinflammatory effector memory T cells
Authors: Watanabe Makiko , Jergovic Mladen , Davidson Lisa , LaFleur Bonnie J. , Castaneda Yvonne , Martinez Carmine , Smithey Megan J. , Stowe Raymond P. , Haddad Elias K. , Nikolich-Žugich Janko 
Published: February 2022

SUMMARYHIV-positive patients whose viral loads are successfully controlled by active antiretroviral therapy (ART) show no clinical signs of AIDS. However, their lifespan is shorter compared to individuals with no HIV infection and they prematurely exhibit a multitude of chronic diseases typically associated with advanced age. It was hypothesized that immune system aging may correlate with, and provide useful biomarkers for, this premature loss of healthspan in HIV+ subjects. Here, we tested whether the immune correlates of aging, including cell numbers and phenotypes, inflammatory status and control of human cytomegalovirus (hCMV) in HIV-positive subjects on long-term successful ART (HIV+) may reveal increased “immunological age” compared to healthy, age-matched cohort (HC) in participants between 50 and 69 years of age. Specifically, we expected that younger HIV+ subjects may immunologically resemble older individuals without HIV. We found no evidence to support this hypothesis. While T cells from HIV+ participants displayed different expression of several differentiation and/or inhibitory/exhaustion markers in different T cell subpopulations, aging by a decade did not pronounce these changes. Similarly, while the HIV+ participants exhibited higher T cell responses and elevated inflammatory marker levels in plasma, indicative of chronic inflammation, this trait was not age-sensitive. We did find differences in immune control of hCMV, and, more importantly, a sustained elevation of sCD14 and of proinflammatory CD4 and CD8 T cell responses across age groups, pointing towards uncontrolled inflammation as a factor in reduced healthspan in successfully treated older HIV+ patients.
Psychological Distress and Metabolomic Markers: A Systematic Review
Authors: Zhu Yiwen , Jha Shaili C. , Shutta Katherine H. , Huang Tianyi , Balasubramanian Raji , Clish Clary B. , Hankinson Susan E. , Kubzansky Laura D. 
Published: February 2022

AbstractPsychological distress is a multifactorial construct that refers to non-specific symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), or stress more generally. A systematic review of metabolomic markers associated with distress has the potential to reveal underlying molecular mechanisms linking distress to adverse health outcomes. The current systematic review extends prior reviews of clinical depressive disorders by synthesizing 39 existing studies that examined metabolomic markers for PTSD, anxiety disorders, and subclinical psychological distress in biological specimens. Most studies were based on small sets of pre-selected candidate metabolites, with few metabolites overlapping between studies. Vast heterogeneity was observed in study design and inconsistent patterns of association emerged between distress and metabolites. To gain a more robust understanding of distress and its metabolomic signatures, future research should include 1) large, population-based samples and longitudinal assessments, 2) replication and validation in diverse populations, 3) and agnostic metabolomic strategies profiling hundreds of targeted and nontargeted metabolites. Addressing these research priorities will improve the scope and reproducibility of future metabolomic studies of psychological distress.HighlightsLiterature on metabolomic markers of distress beyond clinical depression is scarceMost existing studies were candidate based and had little overlap of targetsVast heterogeneity exists in methods and patterns of findings from studies reviewedCritical gaps in sample selection, study design, and methods need to be addressed
Joint modeling of survival and backwards recurrence outcomes: an analysis of factors associated with fertility treatment
Authors: Guo Siyuan , Zhang Jiajia , McLain Alexander C. 
Published: February 2022

AbstractThe increase in methods focused on various types of survival outcomes has allowed practitioners to analyze data that are difficult or expensive to prospectively observe. Still, there are populations that are challenging to study. For example, obtaining a representative sample of couples attempting to become pregnant is difficult due to the dynamic nature of the population. This has led to an increase in the use of cross-sectional designs yielding backwards recurrent survival outcomes. In this paper, we consider the analysis of a survival outcome where subjects are observed if they are at-risk for a separate dependent survival outcome. The motivation for this problem is to determine which factors are associated with time-to-fertility-treatment (TTFT) among women currently attempting pregnancy in a cross-sectional sample. We propose appending a marginal accelerated failure time (AFT) model on TTFT with a conditional model on time-to-pregnancy (TTP) given TTFT to account for their dependence and avoid biases. We address challenges that arise due to the censoring of TTFT and the resulting increased computational complexity. The performance is validated via comprehensive simulation studies. We apply our approach to data from the National Survey of Family Growth to estimate the association insurance type has on TTFT, and estimate the impact of fertility treatment on TTP.
The effect of job strain and worksite social support on reported side effects of COVID-19 vaccine: a prospective study of employees in Japan
Authors: Sasaki Natsu , Kuroda Reiko , Tsuno Kanami , Imamura Kotaro , Kawakami Norito 
Published: February 2022

AbstractObjectivesThis prospective study aimed to examine the association of job demands, job control, and the lack of supervisor and coworker support with side effects after receiving COVID-19 vaccination in a sample of employees in Japan.MethodsThe data were retrieved from an online panel of full-time employees (E- COCO- J). The analysis included participants who were employed and were not vaccinated at baseline (June 2021) but received vaccination at a four-month follow-up (October 2021). An 11-item scale measured the side effects of COVID-19 vaccines. Four types of psychosocial working conditions (i.e., job demands, job control, and supervisor and coworker support) were measured using the Brief Job Stress Questionnaire (BJSQ). Multiple linear regression analyses were conducted to examine the relationship between the psychosocial working conditions and side effects of COVID-19 vaccines, adjusting for gender, age, educational attainment, marital status, occupation, chronic disease, dose of vaccination, anxiety from potential side effects of vaccines, fear and worry about COVID-19, and psychological distress at baseline.ResultsOverall, 747 employees were included in the analysis. The average number of side effects was 3.78 (SD=2.19): Arm pain (81.1%), fatigues (64.1%), muscle pains (63.3%), and fever (37.5 degrees Celsius +) (53.5%) were reported more frequently. Coworker support score was significantly and negatively associated with the numbers of side effects (standardized β=-0.122, p=0.017). Women, young age, second time vaccination, and high psychological distress were significantly associated with several side effects.ConclusionsEmployees with low coworker support may be more likely to have side effects after COVID-19 vaccinations. The findings of this study could inform employees with low coworker support that increasing workplace support may reduce the side effects.Highlights⍰The effect of poor psychosocial working conditions on side effects after COVID-19 vaccinations was unknown.⍰Poor coworker support at baseline was significantly associated with increased side effects after COVID-19 vaccinations.⍰Informing workers with low coworker support about the findings may help them prepare for the side effect and motivate them to improve coworker support to reduce side effects.
Individuals with Metabolic Syndrome show altered fecal lipidomic profiles with no signs of intestinal inflammation or increased intestinal permeability: a pilot study
Authors: Coleman Mia J. , Espino Luis M. , Lebensohn Hernan , Zimkute Marija V. , Yaghooti Negar , Ling Christina L. , Gross Jessica M. , Listwan Natalia , Cano Sandra , Garcia Vanessa , Lovato Debbie M. , Tigert Susan L. , Jones Drew , Gullapalli Rama R. , Rakov Neal E. , Perez Euriko G. Torrazza , Castillo Eliseo F. 
Published: February 2022

ABSTRACTMetabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low HDL cholesterol, hyperglycemia, hypertension or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS with the goal to evaluate for any signs of underlying gut inflammation, increased intestinal permeability, and alterations in host-microbiota metabolism as assessed by fecal metabolites. No signs of intestinal inflammation or increased intestinal permeability were observed in MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. An although our MetS cohort showed no signs of intestinal inflammation they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels, and decreasing HDL cholesterol levels. Taken together, our main results show MetS subjects show major alterations in fecal lipid profiles suggesting alterations in intestinal host-microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.