bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Long COVID-19, its Severity, and the Need for Immediate Attention: Analysis of Clinical Trials and Twitter data
Authors: Bhattacharyya Arinjita , Seth Anand , Rai Shesh 
Published: September 2022

AbstractThe coronavirus disease 2019 (COVID-19) has been declared a pandemic since March 2020 by the World Health Organisation (WHO). The infection pathway follows symptoms of fever, cough, shortness of breath, dyspnea, and severe cases that lead to hospitalization, emergency life support, and even death. Identifying the disease progression and predicting patient outcomes early, precisely predicting the possibility of long-term adverse events through effective modeling, and use of real-world data such as longitudinal clinical trial data, electronic health records data, and health insurance data are of immense importance to effective treatment, resource allocation, and prevention of severe adverse events (SAE) of grades four or five.The main goal of the study is threefold. Firstly, we raise awareness about the different clinical trials that are being conducted concurrently on Long covid-19, and how these are beneficial. Secondly, we analyze the recent tweets on Long haul covid-19 and give an overview of the sentiments of the opinion of the people. Finally, we analyze the sentiment scores and find if they are associated with the demographics of the tweeters via a negative binomial regression model.The trials were selected with long Covid-19 available in ClinicalTrials.Gov. Also, the tweets obtained with the term #long covid-19 consisted of 8436 tweets. We utilized the NRC Emotion Lexicon method for sentiment analysis is a list of English words and their associations with eight basic emotions (anger, fear, anticipation, trust, surprise, sadness, joy, and disgust) and two sentiments (negative and positive) (11). We obtained a matrix of sentiment scores, as well as retweet counts and favorite counts which were analyzed. We regressed the retweet counts and the favorite counts with the sentiment scores and find if they are associated with the emotions and sentiments of the tweeters via a negative binomial regression model since the outcome variable is count data.Our results find that there are two types of clinical trials (a total of 298) being conducted 1)observational and b) interventional. The details about enrollment, time to completion, clinical trial phases, etc., are discussed. Sentiment analysis with the NRC method of the tweets shows that there are both positive and negative sentiments. The retweet counts and favorite counts are associated with the sentiments and emotions such as disgust, joy, sadness, surprise, trust, negative, positive, etc.Finally, to conclude we need resources, and further research needs to be conducted in this area of long Covid-19.
Home-based High Intensity Functional Strength Training (HIFST) for Older Adults: A Protocol for a Pilot Randomized Controlled Trial and Qualitative Description of an Exercise Program to Prevent Functional Decline after an Injury
Authors: Morgan Ashley , Tang Ada , Heisz Jennifer , Thabane Lehana , Richardson Julie 
Published: September 2022

ABSTRACTBackgroundSlip, trips, and falls are a common cause of injury in older adults; limiting physical activity participation and mobility task performance. These injuries may result in preclinical mobility limitation (PCML), a period in which individuals report modifications but not difficulty in mobility tasks. Individuals with PCML are at risk of functional decline which can be prevented with exercise. High-intensity functional strength training (HIFST) involves short intervals of ‘hard’ interspersed with ‘easy’ exercise that may be a time efficient strategy to improve functioning for older adults experiencing PCML.ObjectiveThis protocol outlines the rationale, methods, and planned analyses for a pilot randomized controlled trial and qualitative description (QD) to investigate the feasibility, preliminary effects, and acceptability of a home-based 12-week HIFST intervention for community-dwelling older adults (≥ 55 years) with PCML who have had an injury from a slip, trip, or fall.MethodsTwenty-four participants (target) will be randomized into a 12-week home-based HIFST or lower extremity stretching intervention. Feasibility will be determined using criteria for adherence, recruitment, retention, and safety and results will be presented using descriptive statistics. Preliminary effects on physical functioning, cognitive functioning, enjoyment, and harms will be assessed and presented as mean between-group differences with 95% confidence intervals. HIFST participants will be recruited for follow-up interviews using QD methodology to investigate the acceptability of the intervention. The results of this pilot trial will provide essential information for future research regarding the process, resources, and scientific merit of conducting home-based high-intensity exercise in a post-injury older adult population.Trial RegistrationNCT05266911
A case-control study based on the National Health and Nutrition Examination Survey to evaluate the effects of human papilloma virus on bone health in women
Authors: Li Xiang , Jiao Guangjun , Chen Yunzhen 
Published: September 2022

AbstractBackgroundGlobally, both human papillomavirus (HPV) infection and osteoporosis (OP) are more prevalent in women than in men. It remains unclear whether HPV has an impact on bone health.MethodsThis case-control study was based on data from the National Health and Nutrition Examination Survey (NHANES). Comparable datasets were created via the nearest neighbor propensity score matching (PSM) method (1:2). The Welch two-sample t test was used to analyze the association between HPV infection and bone mineral density (BMD). Restricted cubic spline (RCS) and Kendall’s tau-b tests were used to explore the effect of HPV infection type on BMD.ResultsBMDs in the legs and lumbar spine were lower in subjects infected with HPV than in uninfected subjects. RCS analysis showed that the larger the number of cooccurring HPV types in a woman, the lower the BMD was. In addition, four HPV types were negatively associated with leg BMD, and 14 HPV types were negatively associated with lumbar spine BMD. HPV types 53, 59, and 89 had effects on both leg and lumbar spine BMDs.ConclusionsHPV infection was associated with a decrease in BMD. Appropriately designed trials can help determine whether interventions to prevent HPV infection will have a protective effect on BMD.FundingThis research was not supported by any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study
Authors: Zhou Xiaofeng , Kelly Scott P. , Liang Caihua , Li Ling , Shen Rongjun , Leister-Tebbe Heidi K. , Terra Steven G. , Gaffney Michael , Russo Leo 
Published: September 2022

AbstractObjectivesThe aim of this analysis was to describe nirmatrelvir/ritonavir real-world effectiveness in preventing hospitalization among high-risk US COVID-19 patients during SARS-CoV-2 Omicron predominance.DesignAn ongoing population-based cohort study with retrospective and prospective collection of electronic healthcare data in the United States.MethodsData for this analysis were collected from the US Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset during December 22, 2021−June 8, 2022. Key eligibility criteria for inclusion in the database analysis were ≥12-years-old; positive SARS-CoV-2 test, COVID-19 diagnosis, or nirmatrelvir/ritonavir prescription; and high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching (PSM). Immortal time bias was addressed.Outcome measuresHospitalization rates within 30 (primary analysis) or 15 (sensitivity analysis) days from COVID-19 diagnosis overall and within subgroups were evaluated.ResultsBefore PSM, the nirmatrelvir/ritonavir group (n=2811) was less racially diverse, older, and had higher COVID-19 vaccination rates and a greater number of comorbidities than the non-nirmatrelvir/ritonavir group (n=194,542). Baseline characteristics were well balanced across groups (n=2808 and n=10,849, respectively) after PSM. Incidence of hospitalization (95% CI) within 30 days was 1.21% (0.84%−1.69%) for the nirmatrelvir/ritonavir group and 6.94% (6.03%−7.94%) for the non-nirmatrelvir/ritonavir group, with a hazard ratio (95% CI) of 0.16 (0.11−0.22; 84% relative risk reduction). Incidence within 15 days was 0.78% (0.49%−1.18%) for the nirmatrelvir/ritonavir group and 6.54% (5.65%−7.52%) for the non-nirmatrelvir/ritonavir group; hazard ratio 0.11 (0.07−0.17; 89% relative risk reduction). Nirmatrelvir/ritonavir was effective in African American patients (hazard ratio, 0.35 [0.15−0.83]; 65% relative risk reduction). Relative risk reductions were comparable with overall results across ages and among vaccinated patients.ConclusionsReal-world nirmatrelvir/ritonavir effectiveness against hospitalization during the Omicron era supports EPIC-HR efficacy among high-risk patients. Future research should confirm these early real-world results and address limitations.
Sorting of droplets at kHz rates using absorbance activated acoustic sorting
Authors: Richter Esther S. , Link Andreas , McGrath John S. , Sparrow Raymond W. , Gantz Maximilian , Medcalf Elliot J. , Hollfelder Florian , Franke Thomas 
Published: September 2022

AbstractDroplet microfluidics allows one to address the ever-increasing demand to screen large libraries of biological samples. Absorbance spectroscopy complements the golden standard of fluorescence detection by label free target identification and providing more quantifiable data. However, this is limited by speed and sensitivity. In this paper we increase the speed of sorting by including acoustofluidics, achieving sorting rates of target droplets of 1 kHz. We improved the devices design for detection of absorbance using fibre-based interrogation of samples with integrated lenses in the microfluidic PDMS device for focusing and collimation of light. This optical improvement reduces the scattering and refraction artefacts, improving the signal quality and sensitivity. The novel design allows us to overcome limitations based on dielectrophoresis sorting, such as droplet size dependency, material and dielectric properties of samples. Our acoustic activated absorbance sorter removes the need for offset dyes or matching oils and sorts about a magnitude faster than current absorbance sorter.
Metabolons, quinary structure, and domain motion: enzyme choreography in the cytoplasm
Authors: Samuel Russell Premila P. , Rickard Meredith M. , Pogorelov Taras V. , Gruebele Martin 
Published: September 2022

AbstractHow do enzymes form metabolons inside cells? To answer that question, we created an all-atom model of a section of the human cytoplasm and simulated it for over 30 microseconds. Among other proteins, nucleic acids, and metabolites, the model contains three successive members of the glycolytic cycle: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), and phosphoglycerate mutase (PGM). These enzymes interact to form transient, but long-lived, multi-enzyme complexes with characteristic lifetimes in the 1 to 5 μs range, thus modeling the functional metabolon structures that facilitate compartmentalization of metabolic pathways and substrate channeling in cell. We analyze the quinary structure between enzymes down to the formation of specific hydrogen-bonded interactions between side chains, together with the movement, in concert, of water molecules in or out between interacting amino acids to mediate contact formation and dissolution. We also observed large-scale enzymatic domain motion that has been proposed to convert between substrate-accessible and catalytically functional states: a direct hinge-bending motion of up to 28° changes the relative orientation of the N- and C-terminal domains of PGK, causing the initially open, and presumably inactive, conformation of PGK to sample both “semi-closed” and “closed” conformations. Although classical molecular dynamics (MD) cannot simulate enzymatic activity, closed structures are the functionally active forms of PGK, and their equilibrium with open structures opens the door for future quantum mechanics/molecular mechanics (QM/MM) and other reactive simulations of the cytoplasm.
Modeling communication and switching nonlinear dynamics in multi-region neural activity
Authors: Karniol-Tambour Orren , Zoltowski David M. , Diamanti E. Mika , Pinto Lucas , Tank David W. , Brody Carlos D. , Pillow Jonathan W. 
Published: September 2022

AbstractUnderstanding how multiple brain regions interact to produce behavior is a major challenge in systems neuroscience, with many regions causally implicated in common tasks such as sensory processing and decision making. However, a precise description of interactions between regions remains an open problem. Moreover, neural dynamics are nonlinear, non-stationary, and can vary dramatically across sessions, days, and animals. Here, we propose multi-region, switching dynamical systems (MR-SDS), a probabilistic model of multiple latent interacting systems that evolve with switching nonlinear dynamics and communication between regions. MR-SDS includes directed interactions between brain regions, allowing for estimation of state-dependent communication signals, and accounts for sensory inputs effects, history effects, and heterogeneity across days and animals. We show that our model accurately recovers latent trajectories, vector fields underlying switching nonlinear dynamics, and cross-region communication profiles in two simulations. We then apply our method to two large-scale, multi-region neural datasets involving mouse decision making. The first includes hundreds of neurons per region, recorded simultaneously at single-cell-resolution across 3 distant cortical regions. The second is a mesoscale widefield dataset of 8 adjacent cortical regions imaged across both hemispheres. On these multi-region datasets, our model outperforms existing piece-wise linear multi-region models and reveals multiple distinct dynamical states and a rich set of cross-region communication profiles.
In vitroIsolation ofTreponema pallidumsubsp.pallidumfrom Fresh and Frozen Needle Aspirates of Primary Experimental Syphilis Lesions
Authors: Tantalo Lauren C. , Molini Barbara J. , Bose Mahashweta , Klausner Jeffrey D. , Giacani Lorenzo 
Published: September 2022

ABSTRACTIsolation ofTreponema pallidumsubsp.pallidumstrains still relies on rabbit intratesticular inoculation of clinical samples. Here, we report an alternative isolation approach based on the inoculation of fresh and frozen needle aspirates of primary experimental lesions into culture plates suitable forin vitropropagation of the syphilis agent.SUMMARYWe report on a rabbit-freein vitroisolation approach for syphilis strains that can be easily adapted to clinical specimens.
Simple and rapid site-specific integration of multiple heterologous DNAs into the Escherichia coli chromosome
Authors: Riley Lauren A. , Payne Irenee C. , Tumen-Velasquez Melissa , Guss Adam M. 
Published: September 2022

ABSTRACTEscherichia coli is the most studied and well understood microorganism, but research in this system can still be limited by available genetic tools, including the ability to rapidly integrate multiple DNA constructs efficiently into the chromosome. Site-specific, large serine recombinases can be useful tools, catalyzing a single, unidirectional recombination event between two specific DNA sequences, attB and attP, without requiring host proteins for functionality. Using these recombinases, we have developed a system to integrate up to twelve genetic constructs sequentially and stably into in the E. coli chromosome. A cassette of attB sites was inserted into the chromosome and the corresponding recombinases were cloned onto temperature sensitive plasmids to mediate recombination between a non-replicating, attP- containing “cargo” plasmid and the corresponding attB site on the chromosome. The efficiency of DNA insertion into the E. coli chromosome was approximately 107 cfu/μg DNA for six of the recombinases when the competent cells already contained the recombinase-expressing plasmid and approximately 105 cfu/μg DNA or higher when the recombinase-expressing plasmid and “cargo” plasmid were co-transformed. The “cargo” plasmid contains ΦC31 recombination sites flanking the antibiotic gene, allowing for resistance markers to be removed and reused following transient expression of the ΦC31 recombinase. As an example of the utility of this system, eight DNA methyltransferases from Clostridium clariflavum 4-2a were inserted into the E. coli chromosome to methylate plasmid DNA for evasion of the C. clariflavum restriction systems, enabling the first demonstration of transformation of this cellulose-degrading species.ImportanceMore rapid genetic tools can help accelerate strain engineering, even in advanced hosts like Escherichia coli. Here, we adapt a suite of site-specific recombinases to enable simple, rapid, and highly efficient site-specific integration of heterologous DNA into the chromosome. This utility of this system was demonstrated by sequential insertion of eight DNA methyltransferases into the E. coli chromosome, allowing plasmid DNA to be protected from restriction in Clostridium clariflavum and enabling genetic transformation of this organism. This integration system should also be highly portable into non-model organisms.
Humoral and Cellular Immunogenicity and Safety of 3 Doses of CoronaVac and BNT162b2 in Young Children and Adolescents with Kidney Diseases
Authors: Leung Daniel , Chan Eugene Yu-hin , Mu Xiaofeng , Rosa Duque Jaime S , Cheng Samuel MS , Ho Fanny Tsz-wai , Tong Pak-chiu , Lai Wai-ming , Lee Matthew HL , Chim Stella , Tam Issan YS , Tsang Leo CH , Kwan Kelvin KH , Chung Yuet , Wong Howard HW , Lee Amos MT , Li Wing Yan , Sze Summer TK , Lam Jennifer HY , Lee Derek HL , Chan Sau Man , Tu Wenwei , Peiris Malik , Ma Alison Lap-tak , Lau Yu Lung 
Published: September 2022

ABSTRACTBackgroundPatients with kidney diseases are at risk of severe complications from COVID-19, yet little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases.MethodsWe investigated the immunogenicity and safety of an accelerated, 3-dose primary series of COVID-19 vaccines among 64 pediatric chronic kidney disease patients (mean age 12.2; 32 male) with or without immunosuppression, dialysis, or kidney transplant. CoronaVac was given to those aged <5 years, 0.1ml BNT162b2 to those aged 5-11 years, and 0.3ml BNT162b2 to those aged 11-18 years.ResultsAntibody responses including S-RBD IgG (90.9-100% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6-94.0%) were significantly elicited by 3 doses of any vaccine. T cell responses were also elicited. Weaker neutralization responses were observed among kidney transplant recipients and non-dialysis children receiving rituximab for glomerular diseases. Neutralization was reduced against Omicron BA.1 compared to wild-type (post-dose 3 sVNT% level; 84% vs 27.2%; p<0.0001). However, T cell response against Omicron BA.1 was preserved, which likely confer protection against severe COVID-19. Hybrid immunity was observed after vaccination in infected patients, as evidenced by higher Omicron BA.1 neutralization response among infected patients receiving 2 doses than those uninfected. Generally mild or moderate adverse reactions following vaccines were reported.ConclusionsOur findings support that an accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.TRIAL REGISTRATIONClinicaltrials.govNCT04800133SIGNIFICANCE STATEMENTLittle is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. This paper describes the antibody and T cell responses of 3 doses of CoronaVac or BNT162b2, the top 2 COVID-19 vaccines distributed worldwide, by an accelerated regimen in patients with kidney diseases aged 1-18 years. Antibody and T cell responses were significantly elicited by either vaccine. Neutralization was reduced against Omicron while T cell response was preserved, which likely confer protection against severe COVID-19. Rate of severe adverse reactions was low in the study. Results confirm that accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.
Polymer physics of structural evolution in synthetic yeast chromosomes
Authors: Stracquadanio Giovanni , Yang Kun , Boeke Jef D. , Koszul Romain , Bader Joel S. 
Published: September 2022

AbstractYeast SCRaMbLE is an experimental method using designed synthetic yeast chromosomes to generate combinatorial diversity through genome rearrangements. These events occur at designed loxPsym recombination sites through the activity of Cre recombinase. While the synthetic SCRaMbLE system was designed to explore minimal genomes and permit rapid genome evolution, the pattern of recombinations also reflects inherent properties of DNA looping required to coalesce pairs of loxPsym sites.Genomes of yeast strains generated by SCRaMbLE are analyzed here using a new statistical mechanics model, called the SCRaMbLE Polymer Interaction (SPI) model. SPI uses polymer physics to model recombinations, and implements efficient rejection sampling and histogram reweighting algorithms to conduct SCRaMbLE experiments in silico.Using SPI, we found that recombination events observed experimentally are consistent with a random walk scaling exponent ranging between 0.45 and 0.6, which spans values of 0.5 for a Gaussian polymer and 0.588 for a self-avoiding walk. SPI provides a highly accurate tool to study SCRaMbLE recombinations and massively parallel genome recombination experiments.
Functional interpretation, cataloging, and analysis of 1,341 known and new glucose-6-phosphate dehydrogenase variants
Authors: Geck Renee C. , Powell Nicholas R. , Dunham Maitreya J. 
Published: September 2022

ABSTRACTGlucose-6-Phosphate Dehydrogenase (G6PD) deficiency affects over 500 million individuals who can experience anemia in response to oxidative stressors such as certain foods and drugs. Recently, the World Health Organization (WHO) called for revisiting G6PD variant classification as a priority to implement genetic medicine in low- and middle-income countries. Towards this goal, we sought to collect reports of G6PD variants and provide interpretations. We identified 1,341 G6PD variants in population and clinical databases. Using the ACMG standards and guidelines for the interpretation of sequence variants, we provided interpretations for 268 variants, including 186 variants that were not reported or of uncertain significance in ClinVar, bringing the total number of variants with non-conflicting interpretations to 400. For 414 variants with functional or clinical data, we analyzed associations between activity, stability, and current classification systems, including the new 2022 WHO Classification. We corroborated known challenges with classification systems, including phenotypic variation, emphasizing the importance of comparing variant effects across patients and studies. Biobank data made available by All of Us illustrate the benefit of large-scale sequencing and phenotyping by adding additional support connecting variants to G6PD-deficient anemia. By leveraging available data and interpretation guidelines, we created a repository for information on G6PD variants and nearly doubled the number of variants with clinical interpretations. These tools enable better interpretation of G6PD variants for the implementation of genetic medicine.