bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neck pain care pathways and costs: association with the type of initial contact health care provider. A retrospective cohort study
Authors: Elton David , Zhang Meng 
Published: July 2022

AbstractBackgroundFor individuals with neck pain (NP) the type of health care provider (HCP) initially contacted and subsequent services used are less well understood than for low back pain (LBP). The purpose of this retrospective observational study of administrative data was to examine the association between type of HCP initially contacted by individuals with NP, service utilization, and total episode cost.MethodsA US national sample of NP episodes completed in 2017-2019 was analyzed. Separate analyses of a combined surgical and non-surgical (pooled) sample and a non-surgical sample were performed. Seventeen types of HCP initially contacted by an individual with NP was the primary independent variable. Dependent measures included rate and timing of use of fourteen types of health care services and total episode cost. A mixed effects model applied to pooled and non-surgical samples was used to test the association between initial contact HCP, total episode cost and rate of prescription opioid and NSAID use for NP.ResultsThe study included 323,348 continuously insured individuals aged 18 years and older with 390,992 complete episodes of NP involving 321,538 HCPs and incurring $472,399,064 in expenditures. 53.0% of episodes had initial contact with a primary care or specialist HCP, with these episodes associated with higher rates of imaging, pharmaceutical, and interventional services. 40.4% of episodes had initial contact with a non-prescribing HCP, with these episodes associated with higher rates of non-pharmaceutical services. Chiropractors (DC) were the most common type of HCP initially contacted (38.5% of episodes) and were associated with the lowest adjusted total episode cost. Results were consistent for individuals experiencing single or multiple episodes during the study period.ConclusionsThis study of a large US cohort of commercially insured individuals with NP helps fill a knowledge gap regarding NP care pathway attributes. Like LBP, the treatment of NP is highly variable with the initial HCP selected by an individual with NP associated with differences in services received and episode cost. Initial contact with a non-prescribing HCP was associated with lower rates of imaging, pharmacology, and interventional services.
Forms of support and experiencing maltreatment and disrespect during childbirth at a health facility: a self-reported cross-sectional study in Ghana
Authors: Asare Agnes , Tabong Philip Teg-Nefaah 
Published: July 2022

AbstractProviding support to women and encouraging women to deliver in health facility settings (skilled delivery) is one strategy to improve maternal health outcomes in developing countries. However, fear of maltreatment and disrespect during labour and delivery, have been reported as barriers to facility delivery. This study was therefore conducted to assess postnatal women’s self-reported experience and type of maltreatment and disrespect during delivery. Using a cross sectional study design, 313 women were randomly selected from the three health facilities located in the La-Nkwantenang-Madina Municipality in the Greater Accra region. The data was analysed using STATA 15. Bivariable data analysis using Pearson’s Chi-square was used to determine the association between socio-demographic characteristics, reproductive history and experience of maltreatment. Logistic regression analysis was done to determine the strengths of association. More than half (54.3%) of the postnatal women were encouraged to have support persons during labour and delivery. About 75.7% reported experiencing some form of maltreatment and disrespect. About a fifth (19.8%, n=62) of the women experienced physical abuse, 9.3% (n=29) experienced undignified care, 7.7% (n=24) of the women were detained or confined against their will, and 60.4% (n=189) indicated they did not receive consented care. The study concludes that maltreatment and disrespect during labour is widespread. Expanding health facilities may not achieve desired skilled or facility-based delivery without improving the birth experience of women.
CSF metabolites associated with biomarkers of Alzheimer’s disease pathology
Authors: Dong Ruocheng , Lu Qiongshi , Kang Hyunseung , Suridjan Ivonne , Kollmorgen Gwendlyn , Wild Norbert , Deming Yuetiva , Van Hulle Carol A. , Anderson Rozalyn M. , Zetterberg Henrik , Blennow Kaj , Carlsson Cynthia M. , Asthana Sanjay , Johnson Sterling C. , Engelman Corinne D. 
Published: July 2022

AbstractINTRODUCTIONMetabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer’s disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease.METHODSThe relative abundance of untargeted metabolites was assessed in 161 individuals. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study.RESULTSMWAS results showed several significantly associated metabolites for all the biomarkers except Aβ42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid β (Aβ40), α-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for Aβ40 and α-synuclein.DISCUSSIONThis study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.
Mendelian randomization confirms the role of Y-chromosome loss in Alzheimer’s Disease etiopathogenesis in males
Authors: García-González Pablo , de Rojas Itziar , Moreno-Grau Sonia , Montrreal Laura , Puerta Raquel , Alarcón-Martín Emilio , Quintela Inés , Orellana Adela , Andrade Victor , Adami Pamela Martino , Heilmann-Heimbach Stefanie , Gomez-Garre Pilar , Teresa Periñán María , Alvarez Ignacio , Diez-Fairen Monica , Nuñez Llaves Raul , Olivé Roig Claudia , Garcia-Ribas Guillermo , Menéndez-González Manuel , Martínez Carmen , Aguilar Miquel , Buongiorno Mariateresa , Franco-Macías Emilio , Saez Maria Eugenia , Cano Amanda , Bullido Maria , Real Luis , Rodríguez-Rodríguez Eloy , Royo Jose , Álvarez Victoria , Pastor Pau , Piñol-Ripoll Gerard , Mir Pablo , Lara Miguel Calero , Padilla Miguel Medina , Sánchez-Juan Pascual , Carracedo Angel , Valero Sergi , Hernandez Isabel , Tàrraga Lluis , Ramirez Alfredo , Boada Mercé , Ruiz Agustín 
Published: July 2022

ABSTRACTMosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event occurring exclusively in men and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomization to construct an age-independent polygenic risk score of mLOY (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per SD unit (p=4.22·10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in males with mild cognitive impairment (HR=1.23; p=0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group. The male-specificity of the observed effects suggests that these associations of mLOY with AD are caused by the inherent loss of the Y chromosome, and not by the increased genomic instability underlying mLOY risk. Additionally, we found that blood mLOY phenotype was associated with increased CSF levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis. Furthermore, we encourage researchers to use this mloy-PRS instrument to find unbiased associations between mLOY and ageing-related diseases.
Assessing Etiologic Heterogeneity for Multinomial Outcome with Two-Phase Outcome-Dependent Sampling Design
Authors: Reifeis Sarah A. , Hudgens Michael G. , Troester Melissa A. , Love Michael I. 
Published: July 2022

AbstractEtiologic heterogeneity occurs when distinct sets of events or exposures give rise to different subtypes of disease. Inference about subtype-specific exposure effects from two-phase outcome-dependent sampling data requires adjustment for both confounding and the sampling design. Common approaches to inference for these effects do not necessarily appropriately adjust for these sources of bias, or allow for formal comparisons of effects across different subtypes. Herein, using inverse probability weighting (IPW) to fit a multinomial model is shown to yield valid inference with this sampling design for subtype-specific exposure effects and contrasts thereof. The IPW approach is compared to common regression-based methods for assessing exposure effect heterogeneity using simulations. The methods are applied to estimate subtype-specific effects of various exposures on breast cancer risk in the Carolina Breast Cancer Study.
Changes in mobility patterns during the COVID-19 pandemic in Zambia: implications for the effectiveness of NPIs in Sub-Saharan Africa
Authors: Loisate Stacie , Mutembo Simon , Arambepola Rohan , Makungo Kabondo , Kabalo Elliot N , Sinyange Nyambe B. , Kapata Nathan , Liwewe Mazyanga , Silumezi Andrew , Chongwe Gershom , Kostandova Natalya , Truelove Shaun , Wesolowski Amy 
Published: July 2022

AbstractThe COVID-19 pandemic has impacted many facets of human behavior, including human mobility partially driven by the implementation of non-pharmaceutical interventions (NPIs) such as stay at home orders, travel restrictions, and workplace and school closures. Given the importance of human mobility in the transmission of SARS-CoV-2, there have been an increase in analyses of mobility data to understand the COVID-19 pandemic to date. However, despite an abundance of these analyses, few have focused on Sub-Saharan Africa (SSA). Here, we use mobile phone calling data to provide a spatially refined analysis of sub-national human mobility patterns during the COVID-19 pandemic from March 2020-July 2021 in Zambia. Overall, among highly trafficked intra-province routes, mobility decreased up to 52% from March-May 2020 compared to baseline, which was also the time period of the strictest NPIs. However, despite dips in mobility during the first wave of COVID-19 cases, mobility returned to baseline levels and did not drop again suggesting COVID-19 cases did not influence mobility in subsequent waves.
Characterization and Preclinical Treatment of Rotational Force-Induced Brain Injury
Authors: Umfress Alan , Chakraborti Ayanabha , Sudarsana Devi Suma Priya , Adams Raegan , Epstein Daniel , Massicano Adriana , Sorace Anna , Singh Sarbjit , Hossian M. Iqbal , Andrabi Shaida A. , Crossman David K. , Kumar Nilesh , Mukhtar M. Shahid , Simpson Claire , Abell Kathryn , Stokes Matthew , Wiederhold Thorsten , Rosen Charles , Luo Huiyang , Lu Hongbing , Natarajan Amarnath , Bibb James A. 
Published: July 2022

ABSTRACTMillions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks to months after injury and impede neurological recovery. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of rotational head trauma in rodents and extensively characterized the pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant cyclin dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. Finally, we utilize Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.
Exploring Phylogenetic Classification and Further Applications of Codon Usage Frequencies
Authors: Hallee Logan 
Published: July 2022

AbstractCodons are the repeats of three nucleic acids in genetic material read during translation. 64 total codons exist at different frequencies known to vary between organisms. Codon usage frequencies (CUFs) have recently been used for phylogenetic classification at different discrimination levels. However, the accuracy of phylogenetic classification and applications of this predictive power are not fully elucidated in the current literature. The goal of this project was two-fold: 1.) To increase the accuracy and depth of phylogenetic classification models using CUFs in literature. 2.) To explore the potential application of identifying open reading frames (ORFs) with CUFs. To increase the accuracy of classification models GridSearchCV, TensorFlow, and keras were used to design an improved Artificial Neural Network than the relevant example in the literature. Commonly used predictors were explored in an ensemble format that performs even better than the improved neural network. To explore a more discriminatory and phylogenetically deep classification K Means was used to look at possible clustering structures in the CUF data. To identify ORFs the codon frequencies of each potential ORF are compared to the frequencies of an organism of choice with a multinomial goodness-of-fit test. With correct optimization, these tests can reject possible ORFs with high confidence. In addition to these goals, the codons were ranked in terms of importance for classification with lasso regression and random forests feature ranking. This not only highlights exciting biology related to tRNA concentrations and the variance thereof, but is also helpful for optimizing the statistical tests for ORF identification.
Assessing extracellular vesicles in human biofluids using flow-based analyzers
Authors: Krzyzaniak Olga , Wai Yim Kevin Ho , Al Hrout Ala’a , Peacock Ben , Chahwan Richard 
Published: July 2022

ABSTRACTExtracellular vesicles (EVs) are increasingly being analyzed by flow cytometry. Yet, their miniscule size and low refractive index, causes the scatter intensity of most EVs to fall below the detection limit of most flow cytometers. A new class of devices, known as spectral flow analyzers, are becoming standards in cell phenotyping studies. Largely, due to their unique capacity of detecting a vast panel of markers with higher sensitivity for light scatter detection. Another class of devices, known as nano-analyzers, provides high resolution detection of sub-micron sized particles. Here, we aim to compare the EVs phenotyping performance between the Aurora (Cytek) spectral cell analyzer and the NanoFCM (nFCM) nanoflow analyzer. These two devices were specifically chosen given their lead in becoming gold standards in their respective fields. Immune cell-derived EVs remain poorly characterized despite their clinical potentials. We therefore, used B- and T- cell line-derived EVs and donor-matched human biofluid-derived EVs from serum, urine, and saliva in combination with a panel of established immune markers for this comparative study. A comparative evaluation of both cytometry platforms was performed, discussing their potential and suitability for different applications. We found that nFCM can accurately i) analyze small EVs (40 to 200 nm) matching the size accuracy of electron microscopy; ii) measure concentration of single EV particle per volume; iii) identify underrepresented EV marker subsets; and iv) provide co-localization of EV surface markers. We could also show that human sample biofluids have unique EV marker signatures that could have future clinical relevance.
Incorporating Prior Genomic Dose-Response Data to Support the Benchmark Dose Estimation of Toxicogenomics
Authors: Ji Chao , Shao Kan 
Published: July 2022

AbstractChemical risk assessment is an important tool to evaluate the toxicity of chemicals in the environment, and high throughput toxicogenomics plays an increasingly important role in risk assessment. In toxicogenomics, dose-response analysis for each gene is a data-limited situation, and thus parameter and benchmark dose (BMD) estimations typically have large uncertainty. To solve this problem, an informative prior by synthesizing toxicological information is integrated into the Bayesian benchmark dose modeling system (BBMD), a leading web-based toxicogenomics analysis application. We analyzed 276,126 toxicogenomics dose-response datasets and obtained plausible estimation of informative priors for seven commonly used continuous dose-response models. The effects of informative priors are investigated at the individual probe and pathway levels. Simulation studies based on six “true” models generated from typical genomic dose-response shapes show a significant decrease in uncertainty and an increase in accuracy of BMD estimates for most scenarios with informative priors than the counterpart with uninformative priors. The case study on the pathway analysis indicates that informative priors slightly improve the correlation between the pathway-based point of departure and apical point of departure. Overall, our study provides a practical strategy to incorporate existing toxicogenomic information as priors to improve the quality of chemical risk assessment.Graphic abstract
Changes in brain structure and function in a multisport cohort of retired female and male athletes, many years after suffering a concussion. The ICHIRF-BRAIN Study
Authors: Turner Michael , Belli Antonio , Castellani Rudolph J. , McCrory Paul 
Published: July 2022

AbstractMild traumatic brain injury is widely regarded as a misnomer: it is globally a major cause of disability and is hypothesized as a potential causal factor in subsequent neurodegeneration. Commonly arising in sport, mounting evidence of varying degrees of cognitive impairment in retired athletes exposed to repeated concussions motivates close examination of its cumulative effects on the brain. Studying a cohort of 125 retired athletes with a mean of 11 reported concussions and 36 matched controls with none, here we evaluated whole-brain volumetric and subcortical morphological effects with Bayesian regression models and functional connectivity effects with network-based statistics. Estimates of potential cognitive impact were derived from meta-analytic functional mapping based on 13,459 imaging studies. Across the array of brain structural and functional effects identified, regions significantly lower in volume in the concussed group included, in order of greatest effect size, the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger within the athlete group included, in order of greatest effect size, the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial segment to the postcentral gyrus (all significant with 95% Bayesian credible interval). Subcortical morphology analysis corroborated these findings, revealing a significant, age-independent relationship between inward deformation of the hippocampus and the number of concussions sustained (corrected-p<0.0001). Functional connectivity analyses revealed a distinct brain network with significantly increased edge strength in the athlete cohort comprising 150 nodes and 400 edges (corrected-p=0.02), with the highest degree nodes including the pre-central and post-central gyri and right insula. The functional communities of the greatest eigenvector centralities corresponded to motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with increasing bouts of concussion, which included disengagement of the frontal pole, superior frontal, and middle frontal gyri (p=0.04). Aligned to meta-analytic neuroimaging data, the observed changes suggest possible functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. That such changes are observed many years after retirement from impact sport suggests strong repetition effects and/or underpinning genetic selection factors. These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury.