bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of advanced glycation end products on bone properties in chronic kidney disease
Authors: Damrath John G. , Creecy Amy , Wallace Joseph M. , Moe Sharon M. 
Published: April 2021

Purpose of review
Chronic kidney disease (CKD) affects over 15% of Americans and results in an increased risk of skeletal fractures and fracture-related mortality. However, there remain great challenges in estimating fracture risk in CKD patients, as conventional metrics such as bone density assess bone quantity without accounting for the material quality of the bone tissue. The purpose of this review is to highlight the detrimental effects of advanced glycation end products (AGEs) on the structural and mechanical properties of bone, and to demonstrate the importance of including bone quality when assessing fracture risk in CKD patients.

Recent findings
Increased oxidative stress and inflammation drive the production of AGEs in CKD patients that form nonenzymatic crosslinks between type I collagen fibrils in the bone matrix. Nonenzymatic crosslinks stiffen and embrittle the bone, reducing its ability to absorb energy and resist fracture. Clinical measurement of AGEs is typically indirect and fails to distinguish the identity and properties of the various AGEs.

Summary
Accounting for the impact of AGEs on the skeleton in CKD patients may improve our estimation of overall bone quality, fracture risk, and treatments to improve both bone quantity and quality by reducing AGEs in patients with CKD merit investigation in order to improve our understanding of the etiology of increased fracture risk.
Urine Output Calculated Using Actual Body Weight May Result in Overestimation of Acute Kidney Injury for Obese Patients
Authors: Jiang Jun , Zhang Jing , Liu Ye , Xu Dongxue , Peng Zhiyong 
Published: April 2021

ABSTRACT

Goal:
The derived hourly urine output (UO) indexed by body weight is one of the major criteria for the diagnosis of acute kidney injury (AKI). However, it is unclear whether actual body weight (ABW) or ideal body weight (IBW) should be used. This study aims to explore whether UO calculation based on ABW might lead to overestimation of AKI.

Method:
AKI patients identified in the Medical Information Mart for Intensive Care III database by different components of the Kidney Disease Improving Global Outcomes guidelines and different definitions of body weight were retrospectively studied. Hospital and 90-day mortality were compared to decide whether different patient groups had the same outcome.

Results:
In the cohort of 14,725 patients, AKI was identified in 4,298 (29.19%) and 3,060 (20.78%) patients respectively when ABW or IBW was used (P < 0.01). Multivariate logistic regression revealed that AKI patients identified by UO calculated from ABW had similar hospital and 90-day mortality to that of patients with no evidence of AKI. Whereas AKI patients identified by serum creatinine changes, or those identified by both ABW and IBW, had twice higher the risks of hospital death and about 1.5 times higher the risks of 90-day death compared with thoese with no evidence of AKI. Results were confirmed in two separate sensitivity analyses where patients whose admission creatinine levels were within the normal reference ranges and patients identified as sepsis were studied.

Conclusions:
Calculating hourly body weight normalized UO using ABW may lead to underestimation of UO and overestimation of AKI.
Vagus Nerve Stimulation Protects Enterocyte Glycocalyx After Hemorrhagic Shock Via the Cholinergic Anti-Inflammatory Pathway
Authors: Wu Juan , Yin Yushuang , Qin Mingzhe , Li Kun , Liu Fang , Zhou Xiang , Song Xiaoyang , Li Bixi 
Published: April 2021

ABSTRACT

Introduction:
Electrical vagal nerve stimulation is known to decrease gut permeability and alleviate gut injury caused by traumatic hemorrhagic shock. However, the specific mechanism of action remains unclear. Glycocalyx, located on the surface of the intestinal epithelium, is associated with the buildup of the intestinal barrier. Therefore, the goal of our study was to explore whether vagal nerve stimulation affects enterocyte glycocalyx, gut permeability, gut injury, and remote lung injury.

Materials and methods:
Male Sprague Dawley rats were anesthetized and their cervical nerves were exposed. The rats underwent traumatic hemorrhagic shock (with maintenance of mean arterial pressure of 30–35 mmHg for 60 min) with fluid resuscitation. Vagal nerve stimulation was added to two cohorts of animals before fluid resuscitation, and one of them was injected with methyllycaconitine to block the cholinergic anti-inflammatory pathway. Intestinal epithelial glycocalyx was detected using immunofluorescence. Intestinal permeability, the degree of gut and lung injury, and inflammation factors were also assessed.

Results:
Vagal nerve stimulation alleviated the damage to the intestinal epithelial glycocalyx and decreased intestinal permeability by 43% compared with the shock/resuscitation phase (P < 0.05). Methyllycaconitine partly eliminated the effects of vagal nerve stimulation on the intestinal epithelial glycocalyx (P < 0.05). Vagal nerve stimulation protected against traumatic hemorrhagic shock/fluid resuscitation-induced gut and lung injury, and some inflammatory factor levels in the gut and lung tissue were downregulated after vagal nerve stimulation (P < 0.05).

Conclusions:
Vagal nerve stimulation could relieve traumatic hemorrhagic shock/fluid resuscitation-induced intestinal epithelial glycocalyx damage via the cholinergic anti-inflammatory pathway.
Update on neuroimaging in Alzheimer's disease
Authors: Sintini Irene , Whitwell Jennifer L. 
Published: April 2021

Purpose of review
The purpose of this review was to discuss the contribution of the most recent neuroimaging studies to our understanding of the mechanisms underlying Alzheimer's disease.

Recent findings
Studies have applied cross-sectional and longitudinal positron emission tomography (PET), structural and resting-state functional magnetic resonance imaging to primarily investigate (1) how Alzheimer's disease pathological hallmarks like tau and amyloid-beta build up and spread across the brain at different disease stage and in different disease phenotypes and (2) how the spreading of these proteins is related to atrophy, to neuronal network disruption and to neuroinflammation.

Summary
The findings of these studies offer insight on the mechanisms that drive the pathological and clinical progression of Alzheimer's disease, highlighting their multifactorial nature, which is a crucial aspect for the development of disease-modifying therapeutics and can be captured with multimodal imaging approaches.
The role of childrens’ vaccination for COVID-19 - Pareto-optimal allocations of vaccines
Authors: Gavish Nir , Katriel Guy 
Published: April 2021

The ultimate goal of COVID-19 vaccination campaigns is to enable the return of societies and economies to a state of normality. While vaccines have been approved for children of age 12 and older, there is an ongoing debate as to whether children should be vaccinated and at what priority, with very different policies being adopted in different countries. In this work, we use mathematical modeling and optimization to study the effect of vaccinating children on the epidemic spread. We consider Pareto-optimal allocations according to competing measures of number of infections and mortality, and systematically study the trade-offs among them. When some weight is given to the number of infections, we find that it is optimal to allocate vaccines to adolescents in age group 10-19, even when they are assumed to be less susceptible than adults. Additionally, we find that in a broad range of scenarios, optimal allocations of vaccines do not include vaccination of age-group 0-9.Author summaryOne of the acute questions public health experts and policymakers currently confront is whether children of age 12 and older, and eventually perhaps younger children, should be vaccinated against COVID-19, and at what priority. Different countries have adopted diverse policies on this issue, while others remain undecided. One of the key considerations in this debate is the impact of children’s vaccination on the epidemic spread. In this work, we use mathematical and computational methods to study this question in a systematic, quantitative way. We compute optimal vaccination allocations, under different criteria for optimality, both including and not including children. To explore tradeoffs among different goals, such as reducing number of infections and reducing mortality, we use the idea of Pareto optimization, which is novel in this field. Our results show that, under a wide range of conditions, optimal vaccine allocations include vaccination of age group 10-19, while the vaccination of age group 0-9 is of lower priority than the vaccination of other age group.
Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD
Authors: Goodman Matthew O , Cade Brian E , Shah Neomi , Huang Tianyi , Dashti Hassan S , Saxena Richa , Rutter Martin K , Libby Peter , Sofer Tamar , Redline Susan 
Published: April 2021

ABSTRACTBackgroundObstructive sleep apnea (OSA) and its features, such as chronic intermittent hypoxia (IH), may differentially affect specific molecular pathways and processes in the pathogenesis of coronary artery disease (CAD) and influence the subsequent risk and severity of CAD events. In particular, competing adverse (e.g. inflammatory) and protective (e.g. increased coronary collateral blood flow) mechanisms may operate, but remain poorly understood. We hypothesize that common genetic variation in selected molecular pathways influences the likelihood of CAD events differently in individuals with and without OSA, in a pathway-dependent manner.MethodsWe selected a cross-sectional sample of 471,877 participants from the UK Biobank, among whom we ascertained 4,974 to have OSA, 25,988 to have CAD, and 711 to have both. We calculated pathway-specific polygenic risk scores (PS-PRS) for CAD, based on 6.6 million common variants evaluated in the CARDIoGRAMplusC4D genome-wide association study (GWAS), annotated to specific genes and pathways using functional genomics databases. Based on prior evidence of involvement with IH and CAD, we tested PS-PRS for the HIF-1, VEGF, NFκB and TNF signaling pathways.ResultsIn a multivariable-adjusted logistic generalized additive model, elevated PS-PRSs for the KEGG VEGF pathway (39 genes) associated with protection for CAD in OSA (interaction odds ratio 0.86,p= 6E-04). By contrast, the genome-wide CAD PRS did not show evidence of statistical interaction with OSA.ConclusionsWe find evidence that pathway-specific genetic risk of CAD differs between individuals with and without OSA in a qualitatively pathway-dependent manner, consistent with the previously studied phenomena whereby features of OSA may have both positive and negative effects on CAD. These results provide evidence that gene-by-environment interaction influences CAD risk in certain pathways among people with OSA, an effect that is not well-captured by the genome-wide PRS. These results can be followed up to study how OSA interacts with genetic risk at the molecular level, and potentially to personalize OSA treatment and reduce CAD risk according to individual pathway-specific genetic risk profiles.
Host-pathogen dynamics in longitudinal clinical specimens from patients with COVID-19
Authors: Lin Michelle J. , Rachleff Victoria M. , Xie Hong , Shrestha Lasata , Lieberman Nicole A.P. , Peddu Vikas , Addetia Amin , Casto Amanda M. , Breit Nathan , Mathias Patrick C. , Huang Meei-Li , Jerome Keith R. , Greninger Alexander L. , Roychoudhury Pavitra 
Published: April 2021

AbstractBackgroundRapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolutionin vivo.Methods and findingsHere we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-PCR cycle threshold (Ct) of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals.ConclusionsThese results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.
Real-world experience with tofacitinib in ulcerative colitis - a systematic review and meta-analysis
Authors: Lucaciu L , Constantine-Cooke N , Plevris N , Siakavellas S , Derikx LAAP , Jones GR , Lees CW 
Published: April 2021

ABSTRACTBackground and aimsEvidence on the outcomes of tofacitinib therapy in real world ulcerative colitis (UC) patients is needed, as a number of these patients would not match the inclusion criteria for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe ulcerative colitis (UC) patients.MethodsWe searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30/05/2018 and 24/01/2021. Pooled induction (8-14 weeks) and maintenance (16-26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models.ResultsNine studies were included, comprising 830 patients, of which 81% were previously treated with anti-TNF and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% CI 41-60%) and 37% (26-45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31-50%) and 29% (23-36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%).ConclusionsTofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.WHAT YOU NEED TO KNOWBackgroundTofacitinib is the first Janus kinase inhibitor (JAKi) approved for the treatment of moderate to severe ulcerative colitis (UC). Real-world data is needed to understand clinical effectiveness of new therapies.FindingsClinical response rates were consistent with those reported by OCTAVE Induction trials, showing clinical efficacy similar in real-world and controlled clinical trial cohorts. There were no major safety concerns reported.Implications for patient careThe results of this meta-analysis confirm the effectiveness and acceptable safety profile of tofacitinib in a real-world, highly refractory UC population, and further support its use in clinical practice.
Real-world effectiveness of Ad26.COV2.S adenoviral vector vaccine for COVID-19
Authors: Corchado-Garcia Juan , Puyraimond-Zemmour David , Hughes Travis , Cristea-Platon Tudor , Lenehan Patrick , Pawlowski Colin , Bade Sairam , O’Horo John C. , Gores Gregory J. , Williams Amy W. , Badley Andrew D. , Halamka John , Virk Abinash , Swift Melanie D. , Wagner Tyler , Soundararajan Venky 
Published: April 2021

AbstractIn light of the massive and rapid vaccination campaign against COVID-19, continuous real-world effectiveness and safety assessment of the FDA-authorized vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes. In this study, we leveraged large-scale longitudinal curation of electronic health records (EHRs) from the multi-state Mayo Clinic health system (MN, AZ, FL, WN, IA). We compared the infection rate of 2,195 individuals who received a single dose of the Ad26.COV2.S vaccine from Johnson & Johnson (J&J) to the infection rate of 21,950 unvaccinated, propensity-matched individuals between February 27th and April 14th 2021. Of the 1,779 vaccinated individuals with at least two weeks of follow-up, only 3 (0.17%) tested positive for SARS-CoV-2 15 days or more after vaccination compared to 128 of 17,744 (0.72%) unvaccinated individuals (4.34 fold reduction rate). This corresponds to a vaccine effectiveness of 76.7% (95% CI: 30.3-95.3%) in preventing SARS-CoV-2 infection with onset at least two weeks after vaccination. This data is consistent with the clinical trial-reported efficacy of Ad26.COV2.S in preventing moderate to severe COVID-19 with onset at least 14 days after vaccine administration (66.9%; 95% CI: 59.0-73.4%). Due to the recent authorization of the Ad26.COV2.S vaccine, there are not yet enough hospitalizations, ICU admissions, or deaths within this cohort to robustly assess the effect of vaccination on COVID-19 severity, but these outcomes will be continually assessed in near-real-time with our platform. Collectively, this study provides further evidence that a single dose of Ad26.COV2.S is highly effective in preventing SARS-CoV-2 infection and reaffirms the urgent need to continue mass vaccination efforts globally.
Head and body dyskinesia during gait in tactical athletes with vestibular deficit following concussion
Authors: Fraser John J. , VanDehy Jacob , Bodell Dawn M. , Gottshall Kim R. , Sessoms Pinata H. 
Published: April 2021

ABSTRACTBackgroundVestibular deficit is common following concussion and may affect gait. The purpose of this study was to investigate differences in head and pelvic center of mass (COM) movement during gait in tactical athletes with and without concussion-related central vestibular impairment.Material & Methods24 patients with post-concussion vestibular impairment (20 males, 4 females; age: 31.7±7.9 years; BMI: 27.3±3.3) and 24 matched controls (20 males, 4 females; age: 31.8±6.4 years; BMI: 27.2±2.6) were included in the analyses. Three-dimensional head and pelvic COM displacement and velocities were collected at a 1.0 m/s standardized treadmill walking speed and assessed using Statistical Parametric Mapping t-tests. Maximum differences (dmax) between groups were reported for all significant kinematic findings.ResultsThe Vestibular group demonstrated significantly diminished anteroposterior head excursions (dmax=2.3 cm, p=0.02;) and slower anteroposterior (dmax=0.37 m/s, p=0.01), mediolateral (dmax=0.47 m/s, p=0.02) and vertical (dmax=0.26 m/s, p<0.001) velocities during terminal stance into pre-swing phases compared to the Control group. Vertical pelvic COM excursion was significantly increased in midstance (dmax=2.4 cm, p=0.03) and mediolaterally during pre-to initial-swing phases (dmax=7.5 cm, p<0.001) in the Vestibular group. In addition, Pelvic COM velocities of the Vestibular group were higher mediolaterally during midstance (dmax=0.19 m/s, p=0.02) and vertically during post-initial contact (dmax=0.14 m/s, p<0.001) and pre-swing (dmax=0.16 m/s, p<0.001) compared to the Control group.SignificanceThe Vestibular group demonstrated a more constrained head movement strategy during gait compared with Controls, a finding that is likely attributed to a neurological impairment of visual-vestibular-somatosensory integration.
Racial and ethnic disparities for SARS-CoV-2 positivity in the United States: a generalizing pandemic
Authors: Ferguson Jacqueline M. , Justice Amy C. , Osborne Thomas F. , Magid Hoda S. Abdel , Purnell Amanda L. , Rentsch Christopher T. 
Published: April 2021

AbstractThe coronavirus pandemic has disproportionally impacted racial and ethnic minority communities in the United States. These disparities may be changing over time as outbreaks occur in different communities. Using electronic health record data from the Department of Veterans Affairs, we estimated odds ratios, stratified by region and time period, for testing positive for SARS-CoV-2 among 951,408 individuals tested for SARS-CoV-2 between February 12, 2020 and February 12, 2021. Our study found racial and ethnic disparities for testing positive were most pronounced at the beginning of the pandemic and decreased over time. A key finding was that the disparity among Hispanic individuals attenuated but remained elevated over the entire study period. We identified variation in racial and ethnic disparities in SARS-CoV-2 positivity by time and region independent of underlying health status and other key factors in a nationwide cohort, which provides important insight for strategies to contain and prevent further outbreaks.
The causal effects of chronic air pollution on the intensity of COVID-19 disease: Some answers are blowing in the wind
Authors: Conte Marc N. , Gordon Matthew , Swartwood Nicole A. , Wilwerding Rachel , Yu Chu A. (Alex) 
Published: April 2021

AbstractThe threats posed by COVID-19 have catalyzed a search by researchers across multiple disciplines for policy-relevant findings about critical risk factors. We contribute to this effort by providing causal estimates of the link between increased chronic ambient pollutant concentrations and the intensity of COVID-19 disease, as measured by deaths and hospitalizations in New York City from March through August, 2020. Given concerns about unobservable characteristics that contribute to both ambient air pollutant concentrations and the impacts of COVID-19 disease, we instrument for pollutant concentrations using the time spent downwind of nearby highways and estimate key causal relationships using two-stage least squares models. The causal links between increases in concentrations of our traffic-related air pollutants (PM2.5, NO2, and NO) and COVID-19 deaths are much larger than the correlations presented in recent observational studies. We find that a 0.16 μg/m3 increase in average ambient PM2.5 concentration leads to an approximate 30% increase in COVID-19 deaths. This is the change in concentration associated with being downwind of a nearby highway. We see that this effect is mostly driven by residents with at least 75 years of age. In addition to emphasizing the importance of searching for causal relationships, our analysis highlights the value of increasing the density of pollution-monitoring networks and suggests potential benefits of further tightening of Clean Air Act amendments, as our estimated effects occur at concentrations well below thresholds set by the National Ambient Air Quality Standards.