bluuebunny/crossref_metadata_2025_split huggingface dataset:
SeroTracker-RoB: a decision rule-based algorithm for reproducible risk of bias assessment of seroprevalence studies
Authors: Bobrovitz Niklas , Noël Kim , Li Zihan , Cao Christian , Deveaux Gabriel , Selemon Anabel , Clifton David A. , Yanes-Lane Mercedes , Yan Tingting , Arora Rahul K. 
Published: November 2021

ABSTRACTBackgroundRisk of bias (RoB) assessments are a core element of evidence synthesis but can be time consuming and subjective. We aimed to develop a decision rule-based algorithm for RoB assessment of seroprevalence studies.MethodsWe developed the SeroTracker-RoB algorithm. The algorithm derives seven objective and two subjective critical appraisal items from the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence studies and implements decision rules that determine study risk of bias based on the items. Decision rules were validated using the SeroTracker seroprevalence study database, which included non-algorithmic RoB judgements from two reviewers. We quantified efficiency as the mean difference in time for the algorithmic and non-algorithmic assessments of 80 randomly selected articles, coverage as the proportion of studies where the decision rules yielded an assessment, and reliability using intraclass correlations comparing algorithmic and non-algorithmic assessments for 2,070 articles.ResultsA set of decision rules with 61 branches was developed using responses to the nine critical appraisal items. The algorithmic approach was faster than non-algorithmic assessment (mean reduction 2.32 minutes [SD 1.09] per article), classified 100% (n=2,070) of studies, and had good reliability compared to non-algorithmic assessment (ICC 0.77, 95% CI 0.74-0.80). We built the SeroTracker-RoB Excel Tool which embeds this algorithm for use by other researchers.ConclusionsThe SeroTracker-RoB decision-rule based algorithm was faster than non-algorithmic assessment with complete coverage and good reliability. This algorithm enabled rapid, transparent, and reproducible RoB evaluations of seroprevalence studies and may support evidence synthesis efforts during future disease outbreaks. This decision rule-based approach could be applied to other types of prevalence studies.
Enhancing Cognitive Restructuring with Concurrent fMRI-guided Neurostimulation for Emotional Dysregulation: A Randomized Controlled Trial
Authors: Neacsiu Andrada D. , Beynel Lysianne , Graner John L. , Szabo Steven T. , Appelbaum Lawrence G. , Smoski Moria J. , LaBar Kevin S. 
Published: November 2021

AbstractBackgroundTransdiagnostic clinical emotional dysregulation is a key component of psychopathology and offers an avenue to address multiple disorders with one transdiagnostic treatment. In the current study, we pilot a one-time intervention that combines cognitive restructuring (CR) with repetitive transcranial magnetic stimulation (rTMS), targeted using functional magnetic resonance imaging (fMRI).MethodsThirty-seven clinical adults with high emotional dysregulation were enrolled in this randomized, double-blind, placebo-controlled trial. fMRI was collected as participants were reminded of lifetime stressors and asked to downregulate their distress using CR tactics. fMRI BOLD data were analyzed to identify the cluster of voxels within the left dorsolateral prefrontal cortex (dlPFC) with the highest activation when participants attempted to downregulate, versus passively remember, distressing memories. Participants underwent active or sham rTMS (10 Hz) over the target while practicing CR following autobiographical emotional induction.ResultsReceiving active versus sham rTMS led to significantly higher high frequency heart rate variability during regulation, lower regulation duration, and higher likelihood to use CR during the week following the intervention. There were no differences between conditions when administering neurostimulation without CR compared to sham. Participants in the sham versus active condition experienced less distress the week after the intervention. There were no differences between conditions at the one-month follow up.ConclusionThis study demonstrated that combining active rTMS with emotion regulation training significantly enhances emotion regulation and augments the impact of training for as long as a week. These findings are a promising step towards a combined intervention for transdiagnostic emotion dysregulation.
Integrated multi-omics data analysis identifies a novel genetics-risk gene ofIRF4associated with prognosis of oral cavity cancer
Authors: Lv Yan , Huang Yukuang , Xu Xuejun , Wang Zhiwei , Yu Yanfang , Ma Yunlong , Wu Mengjie 
Published: November 2021

AbstractBackgroundOral cavity cancer (OCC) is one of the most common carcinoma diseases. Recent genome-wide association studies (GWAS) have reported numerous genetic variants associated with OCC susceptibility. However, the regulatory mechanisms of these genetic variants underlying OCC remain largely unclear.ObjectiveThis study aimed to identify OCC-related genetics risk genes contributing to the prognosis of OCC.MethodsBy combining GWAS summary statistics (N = 4,151) with expression quantitative trait loci (eQTL) across 49 different tissues from the GTEx database, we performed an integrative genomics analysis to uncover novel risk genes associated with OCC. By leveraging various computational methods based on multi-omics data, risk genes were prioritized as promising candidate genes for drug repurposing in OCC.ResultsUsing two independent computational algorithms, we found that 14 risk genes whose genetics-modulated expressions showed a notable association with OCC. Among them, nine genes were newly identified, such asIRF4(P = 2.5×10-9and P = 1.06×10-4), TNS3(P = 1.44×10-6and P = 4.45×10-3), ZFP90(P = 2.37×10-6and P = 2.93×10-4), andDRD2(P = 2.0×10-5and P = 6.12×10-3).These 14 genes were significantly overrepresented in several cancer-related terms, and 10 of 14 genes were enriched in 10 potential druggable gene categories. Based on differential gene expression analysis, the majority of these genes (71.43%) showed remarkable differential expressions between OCC patients and paracancerous controls. Integration of multi-omics-based evidence from genetics, eQTL, and gene expression, we identified that the novel risk gene ofIRF4exhibited the highest ranked risk score for OCC. Survival analysis showed that dysregulation ofIRF4expression was significantly associated with cancer patients outcomes (P = 8.1×10-5).ConclusionsIn summary, we prioritized 14 OCC-associated genes with nine novel risk genes, especially theIRF4gene, which provides a drug repurposing resource to develop therapeutic drugs for oral cancer.
Causal Inference and COVID-19 Nursing Home Patients: Identifying Factors That Reduced Mortality Risk
Authors: Ahmed Amina , Goldberg Robert , Swiader Joseph , Wintrob Zachary A.P. , Yilmaz Margaret 
Published: November 2021

AbstractLess than 1% of the US population lives in long-term care facilities, yet this subset of the population accounts for 22% of total COVID-19 related deaths.1 Because of a lack of experimental evidence to treat COVID-19, analysis of real-world data to identify causal relationships between treatments/policies to mortality and morbidity among high-risk individuals is critical. We applied causal inference (CI) analysis to longitudinal patient-level health data of 4,091 long-term care high-risk patients with COVID-19 to determine if any actions or therapies delivered from January to August of 2020 reduced COVID-19 patient mortality rates during this period.Causal inference findings determined that certain supportive care interventions caused reduced mortality rates for nursing home residents regardless of severity of disease (as measured by oxygen saturation level, presence of pneumonia and organ failure), comorbidities or social determinants of health such as race, age, and weight.2 While we do not address the biological mechanisms associated with specific medical interventions and their impact on mortality, this analysis suggests methods to validate and optimize treatment protocols using domain knowledge and causal inference analysis of real-world data across patient populations and care settings.
Failure of Concentric Regulatory Zones to Halt the Spread of COVID-19 in South Brooklyn, New York: October-November 2020
Authors: Harris Jeffrey E. 
Published: November 2021

AbstractWe relied on reports of confirmed case incidence and test positivity, along with data on the movements of devices with location-tracking software, to evaluate a novel scheme of three concentric regulatory zones introduced by then New York Governor Cuomo to address an outbreak of COVID-19 in South Brooklyn in the fall of 2020. The regulatory scheme imposed differential controls on access to eating places, schools, houses of worship, large gatherings and other businesses within the three zones, but without restrictions on mobility. Within the central red zone, COVID-19 incidence temporarily declined from 131.2 per 100,000 population during the week ending October 3 to 62.5 per 100,000 by the week ending October 31, but then rebounded to 153.6 per 100,000 by the week ending November 28. Within the intermediate orange and peripheral yellow zones combined, incidence steadily rose from 28.8 per 100,000 during the week ending October 3 to 109.9 per 100,000 by the week ending November 28. Data on device visits to pairs of eating establishments straddling the red-orange boundary confirmed compliance with access controls. More general analysis of device movements showed stable patterns of mobility between and beyond zones unaffected by the Governor’s orders. A geospatial regression model of COVID-19 incidence in relation to device movements across zip code tabulation areas identified a cluster of five high-mobility ZCTAs with estimated reproduction number 1.91 (95% confidence interval, 1.27-2.55). In the highly populous area of South Brooklyn, controls on access alone, without restrictions on mobility, were inadequate to halt an advancing COVID-19 outbreak.
Very high relative seroprevalence of anti-SARS-CoV-2 antibodies among communities in Bangui, Central African Republic
Authors: Manirakiza Alexandre , Malaka Christian , Yambiyo Brice Martial , Diemer Saint-Calver Henri , Longo Jean de Dieu , Namseneï Joella , Coti-Reckoundji Cathy Sandra Gomelle , Bouhouda Modeste , Darnycka Belizaire Marie Roseline , Roungou Jean Baptiste , Komas Narcisse Patrice , Grésenguet Gérard , Vernet Guy , Vernet Marie-Astrid , Nakoune Emmanuel 
Published: November 2021

AbstractBackgroundLarge-scale population-based seroprevalence studies of SARS-CoV-2 are essential to characterize the cumulative incidence of SARS-CoV-2 infection and to extrapolate the prevalence of presumptive immunity at the population level.ObjectiveThe objective of our survey was to estimate the cumulative population immunity for COVID-19 and to identify individual characteristics associated with a positive serostatus.MethodThis was a clustered cross-sectional study conducted from July 12 to August 20, 2021, in households in the city of Bangui, the capital of the Central African Republic. Information regarding demographic characteristics (age, gender, and place of residence), comorbidities (chronic diseases) was collected. A venous blood sample was obtained for each participant to determine the level of total anti-SARS-CoV-2 antibodies using a WANTAI SARS-CoV-2 Ab ELISA kit.ResultsAll up, 799 participants were surveyed. The average age was 27 years, and 45·8% of the respondents were male (sex ratio: 0.8). The overall proportion of respondents with a positive serostatus was 74·1%. Participants over 20 years of age were twice as likely to have a positive serostatus, with an OR of 2.· ·2 (95% CI: [1·6, 3·1]).InterpretationThe results of this survey revealed a high cumulative level of immunity in Bangui, thus indicating a significant degree of spread of SARS-CoV-2 in the population. The public health implications of this high level of immunity to SARS-CoV-2, particularly on its variants burden, remain to be determined.FundingThis study was funded by the French Ministry for Europe and Foreign Affairs through the REPAIR COVID-19-Africa project coordinated by the Pasteur International Network association.
Interpretation of mendelian randomization using one measure of an exposure that varies over time
Authors: Morris Tim T , Heron Jon , Sanderson Eleanor , Smith George Davey , Tilling Kate 
Published: November 2021

AbstractBackgroundMendelian randomization (MR) is a powerful tool through which the causal effects of modifiable exposures on outcomes can be estimated from observational data. Most exposures vary throughout the life course, but MR is commonly applied to one measurement of an exposure (e.g., weight measured once between ages 40 and 60). It has been argued that MR provides biased causal effect estimates when applied to one measure of an exposure that varies over time.MethodsWe propose an approach that emphasises the liability that causes the entire exposure trajectory. We demonstrate this approach using simulations and an applied example.ResultsWe show that rather than estimating the direct or total causal effect of changing the exposure value at a given time, MR estimates the causal effect of changing the liability as induced by a specific genotype that gives rise to the exposure at that time. As such, results from MR conducted at different time points are expected to differ (unless the liability of exposure is constant over time), as we demonstrate by estimating the effect of BMI measured at different ages on systolic blood pressure.ConclusionsPractitioners should not interpret MR results as timepoint-specific direct or total causal effects, but as the effect of changing the liability that causes the entire exposure trajectory. Estimates of how the effects of a genetic variant on an exposure vary over time are needed to interpret timepoint-specific causal effects.
Glutamate-Weighted Magnetic Resonance Imaging (GluCEST) Detects Effects of Transcranial Magnetic Stimulation to the Motor Cortex
Authors: Cember Abigail T.J. , Deck Benjamin L. , Kelkar Apoorva , Faseyitan Olu , Zimmerman Jared P. , Erickson Brian , Elliott Mark A. , Coslett H. Branch , Hamilton Roy H. , Reddy Ravinder , Medaglia John D. 
Published: November 2021

AbstractTranscranial magnetic stimulation (TMS) is used in several FDA-approved treatments and, increasingly, to treat neurological disorders in off-label uses. However, the mechanism by which TMS causes physiological change is unclear, as are the origins of response variability in the general population. Ideally, objective in vivo biomarkers could shed light on these unknowns and eventually inform personalized interventions. Continuous theta burst stimulation (cTBS) is a form of TMS which has been observed to reduce motor evoked potentials (MEPs) for 60 minutes or longer post-stimulation, although the consistency of this effect and its mechanism continue to be under debate. Here, we use glutamate-weighted chemical exchange saturation transfer (gluCEST) magnetic resonance imaging (MRI) at ultra-high magnetic field (7T) to measure changes in glutamate concentration at the site of cTBS. We find that gluCEST signal in the ipsilateral hemisphere of the brain generally decreases in response to cTBS, whereas consistent changes were not detected in the contralateral or in subjects receiving a sham stimulation.One Sentence SummaryWe used glutamate-weighted Chemical Exchange Saturation Transfer (GluCEST) imaging to detect changes in glutamate contrast in the brains of young, healthy adults undergoing transcranial magnetic stimulation (TMS) to the motor cortex.
Neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses in patients with triple negative breast cancer
Authors: Zhang Xiuli , Goedegebuure S. Peter , Myers Nancy B. , Vickery Tammi , McLellan Michael D. , Gao Feng , Sturmoski Mark A. , Chen Michael Y. , Kim Samuel W. , Chen Ina , Davidson Jesse T , Sankpal Narendra V. , Hundal Jasreet , Li Lijin , Myles Stephanie , Suresh Rama , Ma Cynthia X. , Foluso Ademuyiwa , Wang-Gillam Andrea , Davies Sherri , Hagemann Ian , Mardis Elaine R. , Griffith Malachi , Miller Christopher A. , Hansen Ted H. , Fleming Timothy P. , Schreiber Robert D. , Gillanders William E. 
Published: November 2021

ABSTRACTPURPOSECancer neoantigens are important targets of cancer immunotherapy. Neoantigen vaccines have the potential to induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes. To test the safety, feasibility and efficacy of this platform, we performed a phase 1 clinical trial in triple negative breast cancer patients with persistent disease following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence.EXPERIMENTAL DESIGNExpressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite was used to identify and prioritize cancer neoantigens. Neoantigen DNA vaccines were designed and manufactured in an academic GMP facility at Washington University School of Medicine. Neoantigen DNA vaccines were administered via electroporation following completion of standard of care therapy. Safety was measured by clinical and laboratory evaluation. Immune responses were assessed by ELISPOT, flow cytometry and TCR sequencing.RESULTS18 subjects received three doses of a personalized neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4-20). The vaccinations were well tolerated with limited adverse events, primarily related to injection site reactions. Neoantigen-specific immune responses were induced in 16/18 patients as measured by ELISPOT and flow cytometry. At a median follow-up of 36 months, progression-free survival was 87.5% (95% CI: 72.7-100%) in the cohort of vaccinated patients compared to 49% (95% CI: 36.4-65.9%) in a cohort of institutional historical control patients (p=0.011).CONCLUSIONSNeoantigen DNA vaccines are safe, feasible, and capable of inducing a neoantigen-specific immune response. There is preliminary evidence of improved disease-free survival compared to historical controls.
Effectiveness of Vaccination against Reported SARS-CoV-2 Infection in United States Coast Guard Personnel between May and August 2021: A Time-Series Analysis
Authors: Iskander John , Frost Jamie , Russell Sharon , Ahluwalia Jaspal , Ward Emily , Steiner Shane , Thomas Dana , Michaud Paul 
Published: November 2021

AbstractBackgroundThe United States Coast Guard (CG) began voluntary use of SARS-CoV-2 vaccines under an Emergency Use Authorization on December 16, 2020. Vaccination status is monitored through a service-wide immunization registry. Active Duty and Reserve (military) CG members are required to report any new positive test for COVID-19 to a centralized database.MethodsBetween May and August 2021, vaccination effectiveness (VE) against any new report of COVID-19 was calculated according to standard formulas, using registry immunization status of cases and monthly mid-point vaccine coverage data. CG members recorded as fully vaccinated with a two-dose vaccine were compared with those with any other vaccine status. Sub-analyses were also conducted according to geographic area (Atlantic vs Pacific), age, and type of vaccine received.ResultsEffectiveness of full vaccination reached a peak of 89.0% in June, then declined over the rest of the study period to 62.7% in August. In July and August, steeper declines in VE were seen in the Atlantic region. The rate of breakthrough infections remained under 1% in two-dose vaccine recipients, and did not differ between those who received the Moderna or Pfizer vaccines. No hospitalizations or deaths due to COVID-19 disease were recorded in fully vaccinated Coast Guard members.ConclusionCoincident with the national spread of the Delta variant of SARS-CoV-2, overall vaccine effectiveness among CG personnel decreased during the summer months of 2021, but continued to provide substantial protection, as well as full protection against the most serious outcomes. Policy initiatives and outreach intended to increase vaccine coverage within this and other military populations could extend the disease prevention benefits seen in this study.
Antibody titers before and after booster doses of SARS-CoV-2 mRNA vaccines in healthy adults
Authors: Demonbreun Alexis R. , Sancilio Amelia , Vaught Lauren A. , Reiser Nina L. , Pesce Lorenzo , McNally Elizabeth M. , McDade Thomas W. 
Published: November 2021

AbstractTwo-dose messenger RNA vaccines (BNT162b2/Pfizer and mRNA-1273/Moderna) against SARS-CoV-2 were rolled out in the US in December 2020, and provide protection against hospitalization and death from COVID-19 for at least six months. Breakthrough infections have increased with waning immunity and the spread of the B.1.617.2 (Delta) variant in summer 2021, prompting approval of boosters for all adults over 18. We measured anti-receptor binding domain (RBD) IgG and surrogate virus neutralization of the interaction between SARS-CoV-2 spike protein and the human angiotensin-converting enzyme (ACE2) receptor, before and after boosters in N=33 healthy adults. We document large antibody responses 6-10 days after booster, with antibody levels that exceed levels documented after natural infection with COVID-19, after two doses of vaccine, or after both natural infection and vaccination. Surrogate neutralization of B.1.617.2 is high but reduced in comparison with wild-type SARS-CoV-2. These data support the use of boosters to prevent breakthrough infections and suggest that antibody-mediated immunity may last longer than after the second vaccine dose.