bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRE1α/XBP1 pathway expression is impaired in pediatric cholestatic liver disease explants
Authors: Kriegermeier Alyssa , Hyon Angela , LeCuyer Brian , Hubchak Susan , Liu Xiaoying , Green Richard M. 
Published: March 2022

AbstractBackground/AimsCholestatic liver diseases (CLD) are the leading indication for pediatric liver transplantation. Increased intrahepatic bile acid concentrations cause endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) is activated to maintain homeostasis. UPR dysregulation, including the inositol-requiring enzyme 1α/X-box protein 1 (IRE1α/XBP1) pathway, is associated with several adult liver diseases. We evaluated hepatic UPR expression in pediatric patients with end-stage CLD and hypothesize that an inability to appropriately activate the hepatic IRE1α/XBP1 pathway is associated with the pathogenesis of CLD.MethodsWe evaluated 34 human liver explants. Cohorts included: pediatric CLD (Alagille, ALGS, and progressive familial intrahepatic cholestasis, PFIC), pediatric non-cholestatic liver disease controls (autoimmune hepatitis, AIH), adult CLD, and normal controls. We performed RNA-seq, quantitative PCR, and western blotting to measure expression differences of the hepatic UPR and other signaling pathways.ResultsMetascape pathway analysis demonstrated that the KEGG ‘protein processing in ER’ pathway was downregulated in pediatric CLD compared to normal controls. Pediatric CLD had decreased hepatic IRE1α/XBP1 pathway gene expression and decreased protein expression of p-IRE1α compared to normal controls. These CLD changes were not disease-specific to ALGS or PFIC. IRE1α/XBP1 pathway gene expression was decreased in pediatric CLD compared to AIH disease controls.ConclusionPediatric CLD explants have decreased gene and protein expression of the protective IRE1α/XBP1 pathway and down-regulated KEGG protein processing in the ER pathways. IRE1α/XBP1 pathway expression differences occur when compared to both normal and non-cholestatic disease controls. Attenuated expression of the IRE1α/XBP1 pathway is associated with cholestatic diseases and could be targeted to treat pediatric CLD.
Implicit sensorimotor adaptation is preserved in Parkinson’s Disease
Authors: Tsay Jonathan S. , Najafi Tara , Schuck Lauren , Wang Tianhe , Ivry Richard B. 
Published: March 2022

AbstractOur ability to enact successful goal-directed actions involves multiple learning processes. Among these processes, implicit motor adaptation ensures that the sensorimotor system remains finely tuned in response to changes in the body and environment. Whether Parkinson’s Disease (PD) impacts implicit motor adaptation remains a contentious area of research: whereas multiple reports show impaired performance in this population, many others show intact performance. While there are a range of methodological differences across studies, one critical issue is that performance in many of the studies may reflect a combination of implicit adaptation and strategic re-aiming. Here, we revisited this controversy using a visuomotor task designed to isolate implicit adaptation. In two experiments, we found that adaptation in response to a wide range of visual perturbations (3° - 45°) was similar in PD and matched control participants. Moreover, in a meta-analysis of previously published work, we found that the mean effect size contrasting PD and controls across 16 experiments was not significant. Together, these analyses indicate that implicit adaptation is preserved in PD, offering a fresh perspective on the role of the basal ganglia in sensorimotor learning.Significance statementAmong multiple motor learning processes, implicit adaptation ensures that our motor system remains exquisitely calibrated. Whether Parkinson’s disease affects implicit motor adaptation has been a point of controversy. We revisited this issue using a visuomotor task designed to isolate implicit adaptation and found that individuals with PD and matched controls showed indistinguishable performance. A meta-analysis based on data from 16 previous experiments yielded a similar null result, strongly supporting the notion that implicit adaptation is preserved in PD.
The impact of COVID-19 non-pharmaceutical interventions on future respiratory syncytial virus transmission in South Africa
Authors: Bents Samantha , Viboud Cécile , Grenfell Bryan , Hogan Alexandra , Tempia Stefano , Gottberg Anne von , Moyes Jocelyn , Walaza Sibongile , Cohen Cheryl , Baker Rachel 
Published: March 2022

AbstractIn response to the COVID-19 pandemic, the South African government employed various nonpharmaceutical interventions (NPIs) in order to reduce the spread of SARS-CoV-2. In addition to mitigating transmission of SARS-CoV-2, these public health measures have also functioned in slowing the spread of other endemic respiratory pathogens. Surveillance data from South Africa indicates low circulation of respiratory syncytial virus (RSV) throughout the 2020-2021 Southern Hemisphere winter seasons. Here we fit age-structured epidemiological models to national surveillance data to predict the 2022 RSV outbreak following two suppressed seasons. We project a 32% increase in the peak number of monthly hospitalizations among infants ≤ 2 years, with older infants (6-23 month olds) experiencing a larger portion of severe disease burden than typical. Our results suggest that hospital system readiness should be prepared for an intense RSV season in early 2022.
Response to COVID-19 booster vaccinations in seronegative people with MS
Authors: Tallantyre Emma C , Scurr Martin J , Vickaryous Nicola , Richards Aidan , Anderson Valerie , Baker David , Chance Randy , Evangelou Nikos , George Katila , Giovannoni Gavin , Harding Katharine E , Hibbert Aimee , Ingram Gillian , Jolles Stephen , Jones Meleri , Kang Angray S , Loveless Samantha , Moat Stuart J , Robertson Neil P , Rios Francesca , Schmierer Klaus , Willis Mark , Godkin Andrew , Dobson Ruth 
Published: March 2022

AbstractBackgroundUncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course.MethodsPwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/-venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test.ResultsOf 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3.ConclusionsApproximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.Key messagesWhat is already knownThe benefits of COVID vaccination are well described. It is unknown whether there is additional benefit afforded from a third COVID-19 vaccination in those people who have failed to mount a serological response to their initial vaccine course.What this study addsApproximately one third of people with MS in our study, all of whom had failed to response to initial vaccine course, developed anti-spike antibodies following a third COVID-19 vaccine. Two-thirds of participants had T cell response to vaccination. No people taking fingolimod appeared to mount a T cell response to vaccination.How this study might influence practiceThese findings highlight potential benefits of booster vaccinations to a substantial proportion of immunosuppressed people who have failed to respond to initial vaccination course. The clinical correlates of antibody and T-cell responses to COVID-19 remain uncertain but they are almost certainly associated with milder subsequent disease in the general population.
Maternal diet and gut microbiota influence predisposition to cardiovascular disease in the offspring
Authors: Jama Hamdi , Dona Malathi S.I. , Dinakis Evany , Nakai Michael , Paterson Madeleine R. , Shihata Waled , Krstevski Crisdion , Cohen Charles. D. , Weeks Kate L. , Farrugia Gabriella E. , Johnson Chad , Salimova Ekaterina , Donner Daniel , Kiriazis Helen , Kaipananickal Harikrishnan , Okabe Jun , Anderson Dovile , Creek Darren J. , Mackay Charles R. , El-Osta Assam , Pinto Alexander R. , Kaye David M. , Marques Francine Z 
Published: March 2022

AbstractCardiovascular disease is one of the most significant causes of death globally, especially in regions where unhealthy diets are prevalent and dietary fibre intake is low.1,2 Fibre, particularly prebiotic types that feed gut microbes, is essential for maintaining healthy gut microbial ecosystems.3 One assumption has been that cardiovascular health relates directly to lifestyle choices in adult life. Here, we show in mice that some of these benefits operate from the prenatal stage and relate to the diet and gut microbiome of the mother. Intake of fibre during pregnancy shaped the mothers’ gut microbiome, which had a lasting founding effect on the offspring’s microbial composition and function. Maternal fibre intake during pregnancy significantly changed the cardiac cellular and molecular landscape in the offspring, protecting them against the development of cardiac hypertrophy, remodelling, and inflammation. These suggest a role for foetal exposure to maternal-derived gut microbial metabolites, which are known to cross the placenta and drive epigenetic changes. Maternal fibre intake led to foetal epigenetic reprogramming of the atrial natriuretic peptide gene (Nppa), protective against heart failure. These results underscore the importance of dietary intake and the gut microbiome of the mother during pregnancy for cardiovascular disease in the offspring.
Environmental DNA sequencing data from algal blooms in Lake Erie using Oxford Nanopore MinION
Authors: Koeppel Alexander F. , Goodrum Will , Steffen Morgan , Wurch Louie , Turner Stephen D. 
Published: March 2022

AbstractHarmful Algal Blooms (HABs) pose a significant and increasing risk, both to human health and to the Blue Economy. Genomics approaches to early detection promise to help mitigate these risks. We have developed and prototyped HABSSED (HAB Surveillance by Sequencing of Environmental DNA), a portable, reliable, rapid, low-cost pipeline for detecting HABs in the field using 3rd generation sequencing with the Oxford Nanopore MinION device. We demonstrated the efficacy of our approach by sequencing existing samples collected from a National Oceanic and Atmospheric Administration (NOAA) Great Lakes Environmental Research Laboratory (GLERL) on Lake Erie. We sequenced environmental DNA (eDNA) from samples drawn before, during, and after a Microcystis bloom, and estimate the abundanced of HAB-associated taxa. While sequencing results showed some evidence of human and E. coli contamination, we find that the abundance of Mycrocystis and other HAB-associated orgnisms significantly differs between pre- and post-bloom environments. Here we describe the publicly available sequencing data that was generated as part of this research, which is available in the Sequence Read Archive (SRA) under accession number PRJNA812770.
Graph-based algorithms for phase-type distributions
Authors: Røikjer Tobias , Hobolth Asger , Munch Kasper 
Published: March 2022

AbstractPhase-type distributions model the time until absorption in continuous or discrete-time Markov chains on a finite state space. The multivariate phase-type distributions have diverse and important applications by modeling rewards accumulated at visited states. However, even moderately sized state spaces make the traditional matrix-based equations computationally infeasible. State spaces of phase-type distributions are often large but sparse, with only a few transitions from a state. This sparseness makes a graph-based representation of the phase-type distribution more natural and efficient than the traditional matrix-based representation. In this paper, we develop graph-based algorithms for analyzing phase-type distributions. In addition to algorithms for state space construction, reward transformation, and moments calculation, we give algorithms for the marginal distribution functions of multivariate phase-type distributions and for the state probability vector of the underlying Markov chains of both time-homogeneous and time-inhomogeneous phase-type distributions. The algorithms are available as a numerically stable and memory-efficient open source software package written in C named ptdalgorithms. This library exposes all methods in the programming languages C and R. We compare the running time of ptdalgorithms to the fastest tools using a traditional matrix-based formulation. This comparison includes the computation of the probability distribution, which is usually computed by exponentiation of the sub-intensity or sub-transition matrix. We also compare time spent calculating the moments of (multivariate) phase-type distributions usually defined by inversion of the same matrices. The numerical results of our graph-based and traditional matrix-based methods are identical, and our graph-based algorithms are often orders of magnitudes faster. Finally, we demonstrate with a classic problem from population genetics how ptdalgorithms serves as a much faster, simpler, and completely general modeling alternative.
Associations between locus coeruleus MRI contrast and physiological responses to acute stress in younger and older adults
Authors: Bachman Shelby L. , Nashiro Kaoru , Yoo Hyunjoo , Wang Diana , Thayer Julian F. , Mather Mara 
Published: March 2022

AbstractAcute stress activates the brain’s locus coeruleus (LC)-noradrenaline system. Recent studies indicate that a magnetic resonance imaging (MRI)-based measure of LC structure is associated with better cognitive outcomes in later life. Yet despite the LC’s documented role in promoting physiological arousal during acute stress, no studies have examined whether MRI-assessed LC structure is related to arousal responses to acute stress. In this study, 102 younger and 51 older adults completed an acute stress induction task while we assessed multiple measures of physiological arousal (heart rate, breathing rate, systolic and diastolic blood pressure, sympathetic tone, and heart rate variability, HRV). We used turbo spin echo MRI scans to quantify LC MRI contrast as a measure of LC structure. We applied univariate and multivariate approaches to assess how LC MRI contrast was associated with arousal at rest and during acute stress reactivity and recovery. In older participants, having higher caudal LC MRI contrast was associated with greater stress-related increases in systolic blood pressure and decreases in HRV, as well as lower HRV during recovery from acute stress. These results suggest that having higher caudal LC MRI contrast in older adulthood is associated with more pronounced physiological responses to acute stress. Further work is needed to confirm these patterns in larger samples of older adults.
Gram-negative Antimicrobial spectrum of Ulmus pumila
Authors: Schafer Josh , Puga Troy B. , Miller Sha’Rai T. , Agbedanu Prince N. 
Published: March 2022

AbstractPurposeThis study explores the antimicrobial spectrum of Ulmus pumila by screening commonly infectious gram-negative bacteria for susceptibility. Currently, many gram-negative bacteria are developing resistance to recommended antibiotic therapies used in clinical practice. It is imperative that we continue to explore new antimicrobial compounds in order to help combat the global health issue of antibiotic resistance.Method3g of freshly harvested leaves and flower samples of Ulmus pumila were extracted in 15 ml of 95% ethanol. The mixture was filtered to remove the debris and sterile blank discs were soaked in the clear filtrate (samples) or the extraction solvent (as background controls) for 20 minutes. Glycerol stocks of bacteria were scaled in LB broth and Muller Hinton agar was prepared with 38g of agar in a liter of water. A 100-microliter suspension of the scaled bacteria was diluted with 9 ml of 1% saline solution and 100 microliters of this saline dilution was plated. Sterile paper discs that were infused with extracts (samples) or vehicle control (95% ethanol) were placed on the freshly plated bacterial plates and incubated at 37 degree Celsius overnight. Zones of inhibition were recorded as a measure of antibacterial activity.ResultUlmus pumila demonstrated antimicrobial activity against the following gram-negative bacteria: E. coli (16 mm mean zone of clearing), P. vulgaris (15 mm mean zone of clearing), E. cloacae (20.5 mm mean zone of clearing), and K. pneumoniae (16 mm mean zone of clearing).ConclusionUlmus pumila displayed antimicrobial activity against various species of gram-negative bacteria including E. coli, P. vulgaris, K. pneumonaie, and E. cloacae. Ulmus pumila has also previously demonstrated activity against some species of gram-positive bacteria. By this discovery, Ulmus pumila has the potential to serve as a broad-spectrum antimicrobial agent with activity against both gram-positive and gram-negative bacteria.
Effectiveness of Community-Based Rehabilitation (CBR) centres for improving physical fitness for community-dwelling older adults: a systematic review protocol
Authors: Xin Wei , Xu Dan , Dou Zulin , Jacques Angela , Umbella Josephine , Hill Anne-Marie 
Published: March 2022

AbstractIntroductionThe increasing ageing population has become a substantial challenge for both health care and social services in many Asian countries. There is a high incidence of chronic diseases and comorbidities in older populations, leading to impairments and functional disability. Functional disability may result in loss of independence, reduced quality of life and increased care needs. Community-based rehabilitation (CBR) aims to promote equality of opportunity and improve the social inclusion of individuals living with disability. CBR also provides rehabilitation to improve physical, mental, and social outcomes. However, there is limited evidence regarding the effectiveness of CBR for improving older adults’ physical fitness. The aim of this systematic review is to synthesise the evidence for the effectiveness of interventions delivered by CBR centres on physical fitness of community-dwelling older adults in Asian countries.Methods and analysisA search on four English databases (CINAHL, Medline, Scopus and Proquest) and two Chinese databases (China National Knowledge Internet and Wanfang Database) will be conducted, from inception to 15 November 2021. Both English and Chinese publications will be included. Experimental and quasi-experimental studies using any type of control group will be included. The primary outcomes are physical fitness (capacity to perform activities and tasks). Secondary outcomes are performance of activities of daily living and health-related quality of life. The quality of all included studies will be assessed using the Joanna Briggs Institute (JBI) standardised critical appraisal tools. Two reviewers will independently complete study screening, selection, quality appraisal, and data extraction. Quantitative data where possible will be pooled in statistical meta-analysis. All statistical analyses will be performed using Review Manager (Rev Man) V.5.3 software.Ethics and disseminationEthical approval is not required for this review. The findings of this review will be disseminated electronically through a peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42021292088Strengths and limitationsFindings and evidence in this review will be summarised and graded using the Grading of Recommendations, Assessment, Development and Evaluation Pro (GRADEPro) approach.A comprehensive literature search using both English and Chinese language databases will be conducted.Studies included in the review may measure different outcomes which may limit pooling in meta-analysis.Differences in populations and interventions delivered in the included studies may result in high levels of heterogeneity, leading to less certainty about the recommendations from the review.
A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits
Authors: Farrell Scott F. , Kho Pik-Fang , Lundberg Mischa , Campos Adrián I. , Rentería Miguel E. , de Zoete Rutger M. J. , Sterling Michele , Ngo Trung Thanh , Cuéllar-Partida Gabriel 
Published: March 2022

AbstractThe multifactorial nature of chronic pain with its numerous comorbidities presents a formidable challenge in disentangling their aetiology. Here, we performed genome-wide association studies of eight regional chronic pain types using UK Biobank data (N=4,037–79,089 cases; N=239,125 controls), followed by bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine (respectively) their genetic correlations and genetic causal proportion (GCP) parameters with 1,492 other complex traits. We report evidence of a shared genetic signature across common chronic pain types as their genetic correlations and GCP parameter directions were broadly consistent across a wide array of biopsychosocial traits. Across 5,942 significant genetic correlations, 570 trait pairs could be explained by a causal association (|GCP| > 0.6; 5% false discovery rate), including 82 traits affected by pain while 488 contributed to an increased risk of chronic pain such as certain somatic pathologies (e.g., musculoskeletal), psychiatric traits (e.g., depression), socioeconomic factors (e.g., occupation) and medical comorbidities (e.g., cardiovascular disease). This data-driven study has demonstrated a novel & efficient strategy for identifying genetically supported risk & protective traits to enhance the design of interventional trials targeting underlying causal factors and help accelerate the development of more effective treatments with broader clinical utility.