bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole blood resuscitation restores intestinal perfusion and influences gut microbiome diversity
Authors: Yracheta Jaclyn , Muraoka Wayne , Wu Xiaowu , Burmeister David , Darlington Daniel , Zhao David , Lai Zhao , Sayyadioskoie Shannon , Cap Andrew P. , Bynum James , Nicholson Susannah E. 
Published: August 2021

OBJECTIVE
Gut dysbiosis, an imbalance in the gut microbiome, occurs after trauma, which may be ameliorated with transfusion. We hypothesized that gut hypoperfusion following trauma causes dysbiosis and that whole blood (WB) resuscitation mitigates these effects.

METHODS
Anesthetized rats underwent sham (S; laparotomy only, n = 6); multiple injuries (T; laparotomy, liver and skeletal muscle crush injuries, and femur fracture, n = 5); multiple injuries and 40% hemorrhage (H; n = 7); and multiple injuries, hemorrhage, and WB resuscitation (R; n = 7), which was given as 20% estimated blood volume from donor rats 1 hour posttrauma. Baseline cecal mesenteric tissue oxygen (O2) concentration was measured following laparotomy and at 1 hour and 2 hours posttrauma. Fecal samples were collected preinjury and at euthanasia (2 hours). 16S rRNA sequencing was performed on purified DNA, and diversity and phylogeny were analyzed with QIIME (Knight Lab, La Jolla, CA; Caporaso Lab, Flagstaff, AZ) using the Greengenes 16S rRNA database (operational taxonomic units; 97% similarity). α and β diversities were estimated using observed species metrics. Permutational analysis of variance was performed for overall significance.

RESULTS
In H rats, an average decline of 36% ± 3.6% was seen in the mesenteric O2 concentration at 1 hour without improvement by 2 hours postinjury, which was reversed following resuscitation at 2 hours postinjury (4.1% ± 3.1% difference from baseline). There was no change in tissue O2 concentration in the S or T rats. β Diversity differed among groups for all measured indices except Bray-Curtis, with the spatial median of the S and R rats more similar compared with S and H rats (p < 0.05). While there was no difference in α diversity found among the groups, indices were significantly correlated with mesenteric O2 concentration. Members of the family Enterobacteriaceae were significantly enriched in only 2 hours.

CONCLUSION
Mesenteric perfusion after trauma and hemorrhage is restored with WB resuscitation, which influences β diversity of the gut microbiome. Whole blood resuscitation may also mitigate the effects of hemorrhage on intestinal dysbiosis, thereby influencing outcomes.
Effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in Balb/c mice after sciatic nerve injury
Authors: Sun Huiyan , Li Qiang , Zhang Limin , Su Zhiyong , Li Jinlong , Cao Jian 
Published: August 2021

Objective
To investigate the effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in mice with sciatic nerve injury, and to explore the relationship between PSD-95 protein and myelin regeneration after nerve myelin injury.

Methods
One hundred twenty-seven male adult Balb/c mice were selected and randomly divided into high, medium and low 7,8-dihydroxycoumarin dose groups and blank control group. Anastomosis was then carried out for the amputated right sciatic nerve, and intraperitoneal injection of 7,8-dihydroxycoumarin was applied postoperatively. At weeks 1, 2, 4 and 8 after surgery, nervous tissues from the injury side were taken for immunohistochemical Luxol Fast Blue staining, so as to observe the morphological changes of the locally injured nerve myelin. Meanwhile, PSD-95 mRNA and protein expression were determined using real-time PCR and western blotting.

Results
The nerve myelin recovery in injury side of mice at all time points showed a definite dose-effect relationship with the dose of 7,8-dihydroxycoumarin. Moreover, 7,8-dihydroxycoumarin could inhibit the PSD-95 mRNA level and protein expression. At the same time, there was a dose-effect of the inhibition.

Conclusions
7,8-Dihydroxycoumarin can affect nerve recovery in mice with sciatic nerve injury, which shows a definite dose–effect relationship with its dose. Besides, PSD-95 protein expression can suppress the regeneration of the injured nerve myelin.
Dynamic changes in c-Fos and NF-κB gene expression and Ca, Fe, Cu, Zn and Mg content due to brain injury in irradiated rats
Authors: Xu Chao , Tu Yu , Zhou Juying , Xu Xiaoting , Qin Songbing , Wang Lili 
Published: August 2021

Background
This study aims to investigate the dynamic changes of c-Fos and NF-κB expression, and to evaluate the Ca, Fe, Cu, Zn and Mg content of hippocampal tissues in rat brains injured by 20 Gy of electron beam irradiation.

Materials and methods
A single dose of 5 MeV is administered to the whole brains of rats to establish animal model of radiation-induced brain injury (RBI). Hematoxylin and eosin staining is performed to observe the pathological changes in brain microvascular endothelial cells. Quantitative reverse transcription-PCR and western blotting assays are utilized to test c-Fos and NF-κB gene expression levels in brain tissue. Inductively coupled plasma-atomic emission spectrometry is leveraged to detect the Ca, Fe, Cu, Zn and Mg contents of the hippocampi.

Results
The c-Fos and NF-κB gene expression levels in protective group are lower than those in the irradiated group after MgSO4 treatment. In the irradiated group, Ca content at several time points and Fe content on days 1, 3 and 7 are higher than those in the blank group. Additionally, in the irradiated group, Cu and Zn contents on days 1, 7, 14 and 60 are less than those in the blank group.

Conclusion
In RBI model, adding Mg2+ may relieve RBI. The protective mechanisms of Mg2+ in the hippocampi from a variety of brain activity indicators including the c-Fos and NF-κB genes.
Performance and safety of induced sputum procedure in young children in Malawi: a prospective study
Authors: Nyangulu Wongani WN , Thole Herbert HT , Chikhoza Angella AC , Msakwiza Mike MM , Nyirenda James JN , Chisala Mphatso MC , Iroh Tam Pui-Ying P-YIT 
Published: August 2021

AbstractBackgroundCollecting sputum specimens are a challenge in infants and young children. We assessed performance and safety of induced sputum (IS) collection in this population, embedded in a prospective study evaluating respiratory cryptosporidiosis in Malawian children with diarrheal disease.MethodsWe assessed sputum quality and correlation with detection of cryptosporidium, and evaluated safety and adverse events in 162 children.ResultsAmong 159 stool specimens tested, 34 (21%, 95% CI 15.0 – 28%) were positive for Cryptosporidium spp. There were160 IS and 161 nasopharyngeal (NP) specimens collected. The majority of IS specimens 122/147 (83%) were clear in appearance, and 132/147 (90%) were of good quality. Among the respiratory specimens tested, 10 (6.3%, 95% CI 2.5 - 10) IS and 4 (3% (95% CI 0 – 5)) NP were positive for Cryptosporidium spp. When stool cryptosporidium PCR was the gold standard, IS PCR sensitivity was higher (29 %, 95% CI 22 – 37) compared to NP PCR (12%, 95% CI 7 – 17) for detection of Cryptosporidium spp. One (0.4%) adverse event occurred, a drop in oxygen saturations at 30-minute post procedure evaluation. Consciousness – level, median respiratory rate and oxygen saturations were unchanged, before or after IS.ConclusionsIS provides good quality specimens, is more sensitive than NP specimens for diagnosis of respiratory cryptosporidiosis, and collection can be done safely in children hospitalized with diarrheal disease.
A systematic review of the impact of the Alpha and Gamma variants of concern on hospitalization and symptomatic rates of SARS-CoV-2
Authors: Schroeder Alexandra , MacLeod Matthew R. 
Published: August 2021

AbstractThe hospitalization and symptomatic rates of Severe Acute Respiratory Syndrome Coronavirus Disease 2019 (SARS-CoV-2) are key epidemiological parameters affecting risk analyses conducted for the Canadian Armed Forces (CAF) during the Coronavirus Disease-19 (COVID-19) pandemic. As one of the criteria of a variant of concern (VOC) is that it affects disease severity, the authors sought to understand whether the Alpha and Gamma VOCs are significantly different in these two parameters than the original wildtype of SARS-CoV-2, the most prevalent in relevant areas of Canada as of study initiation. Searches for studies were conducted in Scopus and PubMed, and located through following citations and receiving studies from daily literature scans. For the hospitalization outcome, effect ratios relative to original wildtype were included. For the symptomatic ratio, the ratio itself for each variant was used. Analysis of age-related effects was of particular value, as CAF members are primarily adults under the age of 60. The firmest conclusion of this review is that the Alpha VOC comes with a higher relative risk of hospitalization compared to the original wildtype, most likely above 1.4, while unlikely to be above 2, with the balance of evidence being that the relative risk is not significantly modified by age. The evidence for Gamma is more limited, but the odds ratio may be above 2, and potentially much greater than that, especially for those 20-39 years of age. For both VOCs reports on symptomatic ratio differed on whether there was an effect, as well as its potential direction.
Genome Wide Analysis Across Alzheimer’s Disease Endophenotypes: Main Effects and Stage Specific Interactions
Authors: Jacobson Tanner Y. , Nho Kwangsik , Risacher Shannon L. , Gao Sujuan , Shen Li , Foroud Tatiana , Saykin Andrew J. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2021

ABSTRACTIntroductionGenetic association analysis of key Alzheimer’s disease (AD) endophenotypes may provide insight into molecular mechanisms and genetic contributions.MethodsMajor AD endophenotypes based on the A/T/N (Amyloid-β, Tau, and Neurodegeneration) biomarkers and cognitive performance were selected from Alzheimer’s Disease Neuroimaging Initiative (ADNI) in up to 1,565 subjects. Genome-wide association analysis of quantitative phenotypes was performed using a main SNP effect and a SNP by Diagnosis interaction (SNPxDX) model to identify stage specific genetic effects.ResultsSixteen novel or replicated loci were identified in the main effect model, with six (SRSF10, MAPT, XKR3, KIAA1671, ZNF826P, and LOC100507506) meeting study significance thresholds with the A/T/N biomarkers. The SNPxDX model identified three study significant genetic loci (BACH2, EP300, PACRG-AS1) associated with a neuroprotective effect in later AD stage endophenotypes.DiscussionAn endophenotype approach identified novel genetic associations and new insights into the associations that may otherwise be missed using conventional case-control models.
Associations of Telemedicine vs. In-Person Ambulatory Care Visits on Cancellation Rates and 30-Day Follow-Up Hospitalizations and Emergency Department Visits
Authors: Kubes Julianne N. , Graetz Ilana , Wiley Zanthia , Franks Nicole , Kulshreshtha Ambar 
Published: August 2021

AbstractImportanceStudies have shown that telemedicine use in specific conditions can promote continuity of care, decreases healthcare costs, and can potentially improve clinical outcomes. The COVID-19 pandemic forced many healthcare systems to expand access for patients using telemedicine, but little is known about cancellation frequencies in telemedicine vs. in-person appointments and its impact on clinical outcomes.ObjectiveCompare ambulatory clinic cancellation rates, 30-day inpatient hospitalizations rates, and 30-day emergency department visit rates between in-person and video telemedicine appointments, and examine differences in cancellation rates by age, race/ethnicity, gender, and insurance.DesignA retrospective cohort study.SettingThe largest academic healthcare system in the state of Georgia with ambulatory clinics in urban, suburban and rural settings.ParticipantsAdults scheduled for an ambulatory clinic appointment from June 2020 to December 2020 were included. Each appointment was identified as either a video telemedicine or in-person clinic appointment. Demographics including age, race, ethnicity, gender, primary insurance, and comorbidities were extracted from the electronic medical record.Main Outcomes and MeasuresThe primary process outcome was ambulatory clinic cancellation rates. The primary clinical outcomes were 30-day hospitalization rates and 30-day emergency department visit rates. Multivariable logistic regression was used to assess differences in the clinical outcomes between appointment types.ResultsA total of 1,652,623 ambulatory clinic appointments were scheduled during the study period. Ambulatory appointment cancellations rates were significantly lower among telemedicine appointments compared to in-person appointments (20.5% vs. 31.0%, p <.001). Cancellation rates were significantly lower for telemedicine appointments than in-person appointments regardless of gender, age, race, ethnicity, primary insurance, or specialty (p <.05 for all sub-groups). Telemedicine appointments was associated with lower 30-day hospitalization rates compared to in-person appointments (2.1% vs. 2.8%; aOR: 0.72, 95% CI: 0.71 to 0.74). There was no difference in 30-day emergency department visit rates between telemedicine and in-person appointment patients (2.6% vs. 2.6%: aOR: 1.00, 95% CI: 0.98 to 1.02)Conclusions and RelevanceOur findings suggest that there are fewer barriers to attending an ambulatory care visit via telemedicine relative than in-person. Moreover, using telemedicine was not associated with any more frequent adverse clinical events compared with in-person visits.
Lessons Learned From the Implementation of a Participant-Collected, Mail-Based SARS-CoV-2 Serological Survey in Massachusetts, USA
Authors: Cramer Estee Y. , Snyder Teah , Ravenhurst Johanna , Lover Andrew A. 
Published: August 2021

AbstractThe rapid spread of SARS-CoV-2 is largely driven by pre-symptomatic or mildly symptomatic individuals who transmit the virus. Serological tests to identify antibodies against SARS-CoV-2 are an important tool to characterize subclinical infection exposure, which is critical in determining transmission trajectories and consequent population immunity. During the summer of 2020, a mail-based serological survey with self-collected dried blood spot (DBS) samples was implemented among university affiliates and their household members in Massachusetts, USA. Described here are some of the challenges faced and novel procedures used during the implementation of this study to assess the prevalence of SARS-CoV-2 antibodies amid the global pandemic. Important challenges included remote and contact-minimized participant recruitment, limited availability of commodities and laboratory capacity, a potentially biased sample population, and policy changes impacting the distribution of clinical results to study participants. Methods used to surmount these challenges and lessons learned are presented to inform similar studies. Key lessons relate to the acceptability and feasibility of DBS sampling, supply requirements, the logistics of packing and shipping packages, data linkages to enrolled household members, and the utility of having an on-call nurse available for participant concerns during sample collection.Future studies might consider additional recruitment techniques such as conducting studies during academic semesters when recruiting in a university setting, partnerships with supply and shipping specialists, and using a stratified sampling approach to minimize potential biases in recruitment. This study design highlights the feasibility and acceptability of self-collected bio-samples and has broad applicability for other serological surveys for a range of pathogens.
Worldwide association of lifestyle related factors and COVID-19 mortality
Authors: Wang Jingzhou , Sato Toshiro , Sakuraba Atsushi 
Published: August 2021

AbstractBackgroundSeveral lifestyle related factors such as obesity and diabetes have been identified as risk factors for Coronavirus disease 2019 (COVID-19) mortality. The objective of this study was to examine the global association between lifestyle related factors and COVID-19 mortality using data from each individual country.MethodsThe association between prevalence of seven lifestyle related factors (overweight, insufficient physical activity, smoking, type 2 diabetes, hypertension, hyperlipidemia, and age over 65) and COVID-19 mortality was assessed by linear and multivariable regression among 186 countries. The cumulative effect of lifestyle related factors on COVID-19 mortality was assessed by dividing countries into four categories according to the number of lifestyle related factors in the upper half range and comparing the mean mortality between groups.ResultsIn linear regression, COVID-19 mortality was significantly associated with overweight, insufficient physical activity, hyperlipidemia, and age ≥65. In multivariable regression, overweight and age ≥65 demonstrated significant association with COVID-19 mortality (P = 0.0039, 0.0094). Countries with more risk factors demonstrated greater COVID-19 mortality (P for trend <0.001).ConclusionLifestyle related factors, especially overweight and elderly population, were associated with increased COVID-19 mortality on a global scale. Global effort to reduce burden of lifestyle related factors along with protection and vaccination of these susceptible groups may help reduce COVID-19 mortality.
Significant reduction in humoral immunity among healthcare workers and nursing home residents 6 months after COVID-19 BNT162b2 mRNA vaccination
Authors: Canaday David H. , Oyebanji Oladayo A. , Keresztesy Debbie , Payne Michael , Wilk Dennis , Carias Lenore , Aung Htin , Denis Kerri St. , Lam Evan C. , Rowley Christopher F. , Berry Sarah D. , Cameron Cheryl M. , Cameron Mark J. , Wilson Brigid , Balazs Alejandro B. , King Christopher L. , Gravenstein Stefan 
Published: August 2021

AbstractHigh COVID-19 mortality among nursing home (NH) residents led to their prioritization for SARS-CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents’ poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 84% over 6 months’ time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 70% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.
Comparison of Antibody Levels in Response to SARS-CoV-2 Infection and Vaccination Type in a Midwestern Cohort
Authors: Remy Laura , Tomomori-Sato Chieri , Conkright-Fincham Juliana , Wiedemann Leanne M. , Conaway Joan W. , Unruh Jay R. 
Published: August 2021

AbstractWe present preliminary data in an ongoing observational study reporting SARS-CoV-2 spike protein reactive antibody levels from a convenience cohort of over 250 individuals in Kansas City. We observe stable antibody levels over one year in individuals who recovered from COVID19 infection caused by SARS-CoV-2. By comparison, our data reveals even higher antibody levels from naïve individuals vaccinated with Pfizer or Moderna vaccines and slightly lower levels from Johnson & Johnson (J&J) recipients. For all vaccines, inoculation after recovery resulted in higher antibody levels than vaccination alone. Responses to Pfizer and Moderna vaccines decreased over time from high initial levels but at the time of publication remain higher than those for recovered or J&J recipients. Within our limited cohort we only see slight demographic trends including higher antibody levels in recovered female vs. male individuals. Booster doses and breakthrough infections both result in rapid increases in antibody levels.
Effectiveness of COVID-19 Vaccines among Incarcerated People in California State Prisons: A Retrospective Cohort Study
Authors: Chin Elizabeth T. , Leidner David , Zhang Yifan , Long Elizabeth , Prince Lea , Schrag Stephanie J. , Verani Jennifer R. , Wiegand Ryan E. , Alarid-Escudero Fernando , Goldhaber-Fiebert Jeremy D. , Studdert David M. , Andrews Jason R. , Salomon Joshua A. 
Published: August 2021

ABSTRACTBackgroundPrisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings.MethodsWe conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons.FindingsAmong 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64−82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88−99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62−82%] and 92% [95% CI, 74−98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58−80%] and 96% [95% CI, 67−99%]).ConclusionsConsistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population.FundingHorowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.