bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adapting an Interdisciplinary Learning Health System Framework for Academic Health Centers: A Scoping Review
Authors: Anderson Jami L. , Mugavero Michael J. , Ivankova Nataliya V. , Reamey Rebecca A. , Varley Allyson L. , Samuel Shekwonya E. , Cherrington Andrea L. 
Published: June 2022

PurposeLearning health systems (LHSs), defined as a systematic process for aligning science, informatics, and clinical practice to integrate providers, researchers, and patients as active participants in an evidence-based care continuum, can provide an ideal environment for academic health centers to rapidly adopt evidence-based guidelines and translate research into practice. However, few LHS frameworks are specifically adapted for academic health centers. The authors wanted to identify the definitions, components, and other features of LHSs to develop an interdisciplinary LHS framework for use within academic health centers.MethodThe authors conducted a scoping review of the literature to identify definitions, components, and other features of LHSs that are useful to academic health centers. In January 2021, they searched PubMed, Academic Search Premier, and Scopus databases and identified English-language, peer-reviewed articles pertaining to LHS, LHS frameworks, organization, components, and models. Since the phraselearning health systemis relatively new terminology, they conducted a supplemental review with alternative phrases, includingembedded researchandcoordinatedorcollaborative research network. They used the Knowledge to Action (KTA) Framework to integrate the generation and flow of research into practice.ResultsThe primary review retrieved 719 articles and the supplemental review retrieved 209; of these, 49 articles were retained to synthesize common definitions, components, and other features of LHS frameworks. Seven structural components of LHSs were identified: organization and collaborations, performance, ethics and security, scientific approaches, data, information technology, and patient outcomes. An adapted interdisciplinary LHS framework was developed that incorporated research and learning engines derived from the KTA and adaptations of common components and other features within the reviewed articles to fit the interests of providers, researchers, and patients within academic health centers.ConclusionsThe adapted LHS framework can be used as a dynamic foundation for development and organization of interdisciplinary LHSs within academic health centers.
A comparison of pain, fatigue, and function between post–COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study
Authors: Haider Saman , Janowski Adam J. , Lesnak Joseph B. , Hayashi Kazuhiro , Dailey Dana L. , Chimenti Ruth , Frey-Law Laura A. , Sluka Kathleen A. , Berardi Giovanni 
Published: June 2022

Abstract
A growing number of individuals report prolonged symptoms following acute Coronavirus-19 (COVID-19) infection, known as post–COVID-19 condition (post-COVID-19). While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these individuals, despite initial reports of a clinical phenotype similar to fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME). This study aimed to characterize multiple symptom domains in individuals reporting post–COVID-19 and compare its clinical phenotype with those with FMS and CFS. A total of 707 individuals with a single or comorbid diagnosis of post–COVID-19, FMS, and/or CFS completed multiple surveys assessing self-reported pain, fatigue, physical and cognitive function, catastrophizing, kinesiophobia, anxiety, depression, dyspnea, and sleep quality. In all 3 diagnoses, elevated pain, fatigue, anxiety, depression, catastrophizing, and kinesiophobia were reported. Physical and cognitive function were similarly impacted among individuals with post-COVID-19, FMS, and CFS; however, individuals with post-COVID-19 reported lower pain and fatigue than FMS and CFS. The comorbid diagnosis of post-COVID-19 with FMS and/or CFS further exacerbated pain, fatigue, and psychological domains when compared with post-COVID-19 alone. In summary, individuals with post-COVID-19 report a symptom phenotype similar to FMS and CFS, negatively impacting cognitive and physical function, but with less severe pain and fatigue overall. These findings may help direct future investigations of the benefit of a biopsychosocial approach to the clinical management of post-COVID-19.
Mining database and verification of PIK3CB as a marker predicting prognosis and immune infiltration in renal clear cell carcinoma
Authors: Ye Jianzhong , Zeng Tao 
Published: June 2022

Abstract

Background:
Kidney renal clear cell carcinoma (KIRC) was the most prevalent malignancy of urinary system. Phosphatidylinositol 3-kinase pathway exerted a vital function in tumor proliferation, invasion, and survival by integrating extracellular growth signals.

Methods:
The expression and clinical significance of PIK3CB in KIRC was explored using bioinformatics analysis. And qRT-PCR was performed to verify our results.

Results:
PIK3CB was downregulated at mRNA and protein level in KIRC. KIRC patients with low PIK3CB expression indicated a worse overall survival, progression free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the predicted calibration plots for 1-year, 3-year, and 5-year OS probabilities showed good agreement compared with the actual OS of KIRC patients. Validation research demonstrated a downregulation of PIK3CB in KIRC tissues and a poor overall survival in KIRC patients with low PIK3CB expression. Furthermore, Cox regression analysis revealed that PIK3CB expression was an independent prognostic factor for KIRC. PIK3CB expression showed positive correlation with the abundance of immune cells. Moreover, enrichment analysis revealed that PIK3CB and associated genes were mainly associated with RNA splicing and JAK-STAT signaling pathway.

Conclusion:
Our study suggested that PIK3CB was a potential biomarker for prognosis and correlated with immune infiltrates in KIRC.
Unusual manifestations of adrenal insufficiency
Authors: Hsu Chia-Chen , Lin Hong-Da , Huang Chung-Yen , Chiang Yi-Lun 
Published: June 2022

Abstract

Rationale:
Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease.

Patient concerns:
A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache.

Diagnoses:
Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2 cm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy.

Interventions:
Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly.

Outcomes:
His symptoms and laboratory data recovered after the operation and medical treatment.

Lessons:
This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.
Percutaneous vertebroplasty in osteoporotic vertebral compression fracture with huge spinal epidural hematoma
Authors: Wang Huafeng , Lin Fengfei , Liang Guiqing , Lin Yuhan 
Published: June 2022

Abstract

Rationale:
Osteoporotic vertebral compression fracture (OVCF) accompanying huge spinal epidural hematoma (SEH) is fairly rare. The aim of this report is to investigate the management strategies and treatment outcomes of OVCF accompanying SEH.

Patient concerns:
An 89-year-old female patient was admitted to hospital because of severe back pain and numbness of both lower limbs after a slight fall. The magnetic resonance imaging examination of the patient showed a fresh compression fracture at L2 accompanying a large dorsal SEH which extended from the T12 to L3 and deformed the spinal cord.

Diagnosis:
The patient was diagnosed with OVCF accompanying SEH.

Interventions:
Given mild neurologic deficits, the hematoma was not treated, and the patient underwent percutaneous vertebroplasty (PVP) only.

Outcomes:
After the procedure, immediate pain relief was achieved and the numbness of both lower limbs disappeared 3 days later. Three months after the procedure, the follow-up magnetic resonance imaging revealed a complete resolution of the hematoma.

Lessons:
OVCF accompanying SEH is fairly rare, and the exact pathophysiological mechanisms are still not clear. In selected patients without or with only slight neurologic symptoms, it is reasonable to perform PVP alone in OVCF accompanying SEH. Moreover, intravertebral stability after PVP might have played a role in spontaneous resolution of SEH.
Income and Race-Ethnicity Disparities in Medical Care Utilization and Expenditures in the United States, 2017-2019
Authors: Wetzler Harry , Cobb Herbert 
Published: June 2022

ABSTRACTBackgroundThe COVID-19 pandemic has focused attention on race and income disparities in SARS-CoV-2 mortality and morbidity. Much less attention has been paid to other socioeconomic factors including income.ObjectiveThe goal of this study was to compare disparities in medical care utilization and related expenditures associated with income to those associated with race and ethnicity in the US for those aged 0 to 64 for four categories of medical services: hospital, emergency room, ambulatory care, and prescription medications.MethodsWe used Medical Expenditure Panel Survey data for years 2017 through 2019. For each of the four medical services, there were three measures. First was the percentage of those aged 0-64 with or without utilization and expenditures. Due to statistical issues related to zero values for utilization and expenditures, the second and third measures were average utilization and expenditures only for those with both utilization and expenditures. Disparities by income and race-ethnicity were measured by calculating the percent difference between the group with the lowest utilization or expenditures and the group with the highest utilization or expenditures.ResultsFor 9 of the 12 separate differences the income differences exceed the corresponding race-ethnicity difference and the income differences are generally much greater in magnitude. Within the income comparisons, those on Medicaid had the greatest utilization in 7 of the 8 comparisons. The High Income group had greatest expenditures for 3 of the 4 medical services. Non-Hispanic Whites had the greatest utilization and expenditures for 9 of the 12 measures and Hispanics had the least utilization and expenditures for 9 of the 12 measures.ConclusionsThese results indicate that income inequalities are more strongly associated with medical care utilization and expenditures than race-ethnicity among those aged 0-64. Although more research should focus on income related health disparities in the United States, it is time to recognize that sound health policy must include reducing socioeconomic inequalities, especially those related to income.
Recessive and sex-dependent genetic effects in primary hypertension
Authors: Zucker Roei , Linial Michal 
Published: June 2022

ABSTRACTBackgroundEssential hypertension is a polygenic disease that affects almost half of the adult population in the USA. It is a major risk factor for renal, cerebrovascular, and cardiovascular diseases. Previous studies used UK-Biobank (UKB) GWAS results for hypertension to create a polygenic risk score (PRS), with the top and bottom 5% of the PRS translating to a 4-fold difference in the estimated risk. The heritability of hypertension is estimated to be high (30–60%), yet the underlying mechanisms and the associated genes are largely unknown.MethodsIn this study, we used a gene-based method, the proteome-wide association study (PWAS), to detect associations mediated by the effects of variants on protein function. PWAS was applied to individuals of European ancestry from the UKB, with 74,090 cases of clinical diagnosis of essential (primary) hypertension (ICD-10, I10) and 200,734 controls. PWAS aggregates the signal from all variants affecting each coding gene and provides scores for dominant, recessive, and hybrid genetic heritability.ResultsPWAS identified 70 statistically significant associated genes (FDR-q-value <0.05) and 127 genes with a weaker threshold (FDR-q-value <0.1). The overlap with GWAS summary statistics (total 1,362 genes) is only partial, with 23 and 62 genes identified exclusively by PWAS from a total of 70 and 127 genes, respectively), among them 18% were assigned recessive inheritance. Furthermore, PWAS analysis, separately performed on females and males from UKB genotyping imputed data, revealed sex-dependent genetics. There are 22 genes unique in females, with only 2 in males. We identified 6 female-specific genes that were not identified by PWAS for the entire group (70 genes). Only one associated gene (SH2B3) is shared between the sexes. Many of the female-significant genes from PWAS are enriched in cellular immunity functions.ConclusionsWe conclude that hypertension displays sex-dependent genetics with an overlooked recessive inheritance, postulating that the underlying mechanism is substantially different for males and females. Studying hypertension by a gene-based association method improves interpretability and clinical utility.
Pregnancy during COVID-19: social contact patterns and vaccine coverage of pregnant women from CoMix in 19 European countries
Authors: Wong Kerry LM , Gimma Amy , Paixao Enny S ,   CoMix Europe Working Group, Faes Christel , Beutels Philippe , Hens Niel , Jarvis Christopher I , Edmunds W. John 
Published: June 2022

AbstractBackgroundEvidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries.MethodsIn each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the mean adjusted contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap.FindingsWe recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI=3.5-3.7) than non-pregnant women (4.0, 95%CI=3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period.COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women.InterpretationSocial contacts and vaccine uptake protect pregnant women and their newborn babies. Recognition of maternal social support need, and efforts to promote the safety and effectiveness of the COVID-19 vaccines during pregnancy are high priorities in this vulnerable group.
Of Problems and Opportunities – How to Treat and How to Not Treat Crystallographic Fragment-Screening Data
Authors: Weiss Manfred S. , Wollenhaupt Jan , Correy Galen J. , Fraser James S. , Heine Andreas , Klebe Gerhard , Krojer Tobias , Thunnissen Marjolein , Pearce Nicholas M. 
Published: June 2022

SUMMARYIn their recent commentary in Protein Science, Jaskolski et al. analyze three randomly picked diffraction data sets from fragment-screening group depositions from the PDB and, based on that, claim that such data are principally problematic. We demonstrate here that if such data are treated properly, none of the proclaimed criticisms persist.
The complexity of keratocyte migration in salmon explant cultures: initial results and future prospects
Authors: Opstad Ida S. , Wolfson Deanna L. , Ahluwalia Balpreet S. , Agarwal Krishna , Seternes Tore , Dalmo Roy A. 
Published: June 2022

AbstractIntact skin is of uttermost importance for fish welfare. The fish skin provides an environmental barrier and protects against invading pathogens. However, both pathogens and physical insults cause skin wounds that are of major concern in modern fish farming. The behavior and interactions between keratocyte cells and sheets of cells are not well understood. The collective migration of keratocytes (skin epithelial cells) is of central importance for wound healing in fish. In this study, we aimed to elucidate the complex wound healing process in fish skin by studying in vitro cultures of these highly motile cells. Using explant cultures from farmed Atlantic salmon (Salmo salar) and differential interference contrast microscopy (DIC), we have captured the dynamics of sheets of cells from harvested fish scales and of individual cells interacting in the cell sheet vicinity. In addition to direct contact, the cells were observed to interact through long membrane tubes, turn, rotate, merge, and/or detach. Additionally, stationary cells and cells moving on top of the cell sheets were observed. Cell sheets approaching one another from different scales did not merge but dispersed.
Large errors increase the generalization of locomotor adaptation depending on the error direction
Authors: de Kam Digna , Staring Wouter , Mariscal Dulce M. , Torres-Oviedo Gelsy 
Published: June 2022

AbstractGeneralization in motor adaptation involves the transfer of movements beyond the adaptation context. We investigated the effect of size (large vs. small) and direction (unidirectional vs. bidirectional) of performance errors during adaptation on the generalization of walking patterns from a split-belt treadmill (training context) to overground (testing context). We hypothesized that unusual errors (i.e., large unidirectional or bidirectional errors) would serve as contextual cues limiting generalization. The size of unidirectional errors was modulated either implicitly (i.e., gradual vs. semi-abrupt split-belt perturbations) or explicitly (i.e., through instructed visual feedback). Bidirectional errors were induced by a sudden removal of the split-perturbation after a long adaptation period, resulting in errors in the opposite direction to those at the start of the adaptation period. Our findings did not support our hypothesis. We found that bidirectional, but not large, performance errors limited generalization across contexts, which could be mediated by two distinct mechanisms. On the one hand, bidirectional errors upon removal of the split-perturbation are also experienced when transitioning to overground walking. Thus, bidirectional errors may facilitate switching between distinct walking patterns, thereby limiting generalization. On the other hand, large unidirectional errors induce more motor adaptation, which might lead to more generalization.
Connectome-based predictive modeling of cognitive reserve using task-based functional connectivity
Authors: Boyle Rory , Connaughton Michael , McGlinchey Eimear , Knight Silvin P. , De Looze Céline , Carey Daniel , Stern Yaakov , Robertson Ian H. , Kenny Rose Anne , Whelan Robert 
Published: June 2022

AbstractCognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task-based fMRI data that could then be applied to independent resting-state data. Connectome-based predictive modeling with leave-one-out cross-validation was applied to predict a residual measure of cognitive reserve using task-based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). Three network-strength predicted cognitive reserve measures were generated that accurately predicted the residual measures of unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio-behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting-state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network-strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task-based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task-based functional connectivity can be applied to independent resting-state data.
Variable Number Tandem Repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG
Authors: Ding Yuan Chun , Adamson Aaron W. , Bakhtiari Mehrdad , Patrick Carmina , Park Jonghun , Laitman Yael , Weitzel Jeffrey N. , Bafna Vineet , Friedman Eitan , Neuhausen Susan L. 
Published: June 2022

AbstractDespite substantial efforts in identifying both rare and common variants affecting disease risk, in the majority of diseases, a large proportion of unexplained genetic risk remains. We propose that variable number tandem repeats (VNTRs) may explain a proportion of the missing genetic risk. Herein, we tested whether VNTRs are causal modifiers of breast cancer risk in 347 female carriers of BRCA1 185delAG, an important group given their high risk of developing breast cancer. We performed targeted-capture to sequence VNTRs, called genotypes with adVNTR, and tested the association of VNTRs and breast cancer risk using Cox regression models. Of 303 VNTRs that passed quality control checks, 4 VNTRs were significantly associated with risk to develop breast cancer at false discovery rate [FDR] < 0.05 and an additional 4 VNTRs had FDR < 0.25. After determining the specific risk alleles, there was a significantly earlier age at development of breast cancer in carriers of the risk genotypes compared to those without the risk genotypes for seven of eight VNTRs. Results from this first systematic study of VNTRs demonstrate that VNTRs may explain a proportion of the unexplained genetic risk for disease and have larger effects than SNPs.