bluuebunny/crossref_metadata_2025_split huggingface dataset:
FMNL2 interacts with cerebrovascular risk factors to alter Alzheimer’s disease risk
Authors: Raghavan Neha S. , Sariya Sanjeev , Lee Annie J. , Gao Yizhe , Reyes-Dumeyer Dolly , De Jager Philip L. , Bennett David A. , Menon Vilas , Lantigua Rafael A. , Kukull Walter A. , Brickman Adam M. , Manly Jennifer J , Gutierrez Jose , Vardarajan Badri N. , Tosto Giuseppe , Mayeux Richard 
Published: September 2020

AbstractINTRODUCTIONLate-onset Alzheimer’s disease (AD) frequently co-occurs with cerebrovascular disease. We hypothesized that interactions between genes and cerebrovascular risk factors (CVRFs) contribute to AD risk.METHODSParticipants age 65 years or older from five multi-ethnic cohorts (N=14,669) were included in genome-wide association meta-analyses for AD including an interaction factor for a CVRF score created from body mass index, hypertension, heart disease, and diabetes. Significant gene level results were substantiated using neuropathological and gene expression data.RESULTSAt the gene-level, FMNL2 interacted with the CVRF score to significantly modify AD risk (p= 7.7×10-7). A SNP within FRMD4B, rs1498837, was nominally significant (p=7.95×10-7). Increased FMNL2 expression was significantly associated with brain infarcts and AD.DISCUSSIONFMNL2 is highly expressed in the brain and has been associated with ischemic stroke and failures in endosomal trafficking, a major pathway in AD pathology. The results highlight an interaction between FMNL2 and CVRFs on AD susceptibility.
Assessing the effectiveness of animal therapy on alleviation of anxiety in pre-school children
Authors: Tahan Mohammad , Sadeghifar Azam , Ahangri Elahe 
Published: September 2020

AbstractIntroductionThe purpose of this study was to assess the effectiveness of animal therapy in alleviation of anxiety in pre-school children.MethodThe study was carried out as a quasi-experimental study with pre-test and post-test design and control group. The study population consisted of 33 anxious 5-7years old children (participated in a welfare anxiety screening plan held by Counseling Center, Tehran-Iran) between 2018 and 2019. The participants took part in the study voluntarily.The subjects were randomly divided into experimental and control groups (10 in each group). The experimental group was exposed to 8 sessions of animal therapy. The research instrument was Spence Preschool Anxiety Scale (Parent Form) and the data were analyzed on SPSS 21 software.ResultsThe results showed that animal therapy had a significant effect on general anxiety score after adjusting for post-test scores (f= 32.49 and p= 0.001) with the effect equal to 0.70. In addition, the effect of animal therapy on anxiety of separation (f= 5.63, p= 0.03), generalized anxiety disorder (f= 8.56, p= 0.01), social phobia (f= 14.58, p= 0.002) and specific anxiety (f= 11.63, p= 0.005) was significant with effects equal to 0.30, 0.40, 0.53, and 0.47, respectively. The results also showed that the effect of animal therapy on obsession was not significant (p>0.05).ConclusionTherefore, it can be concluded that Animal therapy is effective in alleviating anxiety in children.
Olfactory impairment is related to tau pathology and neuroinflammation in Alzheimer’s disease
Authors: Klein Julia , Yan Xinyu , Johnson Aubrey , Tomljanovic Zeljko , Zou James , Polly Krista , Honig Lawrence S. , Brickman Adam M. , Stern Yaakov , Devanand D.P. , Lee Seonjoo , Kreisl William C. 
Published: September 2020

ABSTRACTBackgroundOlfactory impairment is evident in Alzheimer’s disease (AD), however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood.ObjectiveTo determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation.MethodsParticipants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET and fifty-three underwent 11C-PBR28 PET to measure tau pathology and neuroinflammation, respectively. Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau) and β-amyloid (Aβ42).ResultsLow UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex and posterior cingulate cortex (p < 0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01).ConclusionsOlfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.NCT Registration Numbers:NCT03373604; NCT02831283
First “snap-shot” meta-analysis to estimate the prevalence of serum antibodies to SARS-CoV-2 in humans
Authors: Rostami Ali , Sepidarkish Mahdi , Leeflang Mariska , Riahi Seyed Mohammad , Shiadeh Malihe Nourollahpour , Esfandyari Sahar , Mokdad Ali H , Hotez Peter J. , Gasser Robin B. 
Published: September 2020

AbstractBackgroundCOVID-19 is arguably the number-one public health concern worldwide, and efforts are now escalating to control its spread.ObjectiveIn this study, we undertake a meta-analysis to estimate the global and regional anti-SARS-CoV-2 seroprevalence rates in humans and assess whether seroprevalence associates with geographical, climatic and socio-demographic factors.Data sourcesWe systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv for peer-reviewed articles or preprints (up to 14 August 2020).Study eligibility criteriaPopulation-based studies describing prevalence of anti-SARS-CoV-2 serum antibodies in general people.Participantsgeneral people who were tested for prevalence of anti-SARS-CoV-2 serum antibodies.InterventionsThere were no interventions.MethodsWe used random-effects model to estimate pooled seroprevalence, and then extrapolated these findings to the global population (for 2020). Sub-group and meta-regression analyses explored potential sources of heterogeneity in the data and relationships between seroprevalence and socio-demographic, geographical and climatic factors.ResultsIn total, 47 serological studies involving 399,265 people from 23 countries met the inclusion criteria. The pooled seroprevalence of SARS-CoV-2 in general people was estimated at 3.38% (95% CI, 3.05%–3.72%; 15,879/399,265). On a regional basis, we determined seroprevalence estimates of 5.27% (3.97–6.57%) in Northern Europe; 4.41% (2.20–6.61%) in Southern Europe; 4.41% (3.03– 5.79%) in North America; 3.17% (1.96–4.38%) in Western Europe; 2.02% (1.56–2.49%) in the Eastern Asia; and 1.45% (0.95–1.94%) in South America. Extrapolating to the 2020 world population, we estimated that 263,565,606 individuals had been exposed or infected with SARS-CoV-2 at the first wave of the pandemic. A significantly higher seroprevalence was related to higher income levels and human development indices, higher geographical latitudes and lower mean environmental temperatures.InterpretationThis study reinforces that SARS-CoV-2 infection is a very rapidly-spreading communicable disease and calls for routine surveys to constantly monitor temporal changes in seroprevalence around the globe.
Outcome of SARS-CoV-2 infection linked to MAIT cell activation and cytotoxicity: evidence for an IL-18 dependent mechanism
Authors: Flament H. , Rouland M. , Beaudoin L. , Toubal A. , Bertrand L. , Lebourgeois S. , Gouda Z. , Rousseau C. , Soulard P. , Hurtado-Nedelec M. , Luce S. , Bailly K. , Andrieu M. , Boitard C. , Vallet-Pichard A. , Gautier JF. , Ajzenberg N. , Terrier B. , Pene F. , Ghosn J. , Yazdanpanah Y. , Visseaux B. , Descamps D. , Timsit JF. , Monteiro R.C. , Lehuen A. 
Published: September 2020

AbstractImmune system dysfunction is paramount in Coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in a cohort of 182 patients including patients at various stages of disease activity. A profound decrease of MAIT cell counts in blood of critically ill patients was observed. These cells showed a strongly activated and cytotoxic phenotype that positively correlated with circulating pro-inflammatory cytokines, notably IL-18. MAIT cell alterations markedly correlated with disease severity and patient mortality. SARS-CoV-2-infected macrophages activated MAIT cells in a cytokine-dependent manner involving an IFNα-dependent early phase and an IL-18-induced later phase. Therefore, altered MAIT cell phenotypes represent valuable biomarkers of disease severity and their therapeutic manipulation might prevent the inflammatory phase involved in COVID-19 aggravation.
Could Deficiencies in South African Data Be the Explanation for Its Early SARS-CoV-2 Peak?
Authors: Childs S. J. 
Published: September 2020

AbstractThe SARS-CoV-2 pandemic peaked very early in comparison to the thresholds predicted by an analysis of prior lockdown regimes. The most convenient explanation is that some, external factor changed the value of the basic reproduction number, r0; and there certainly are arguments for this. Other factors could, nonetheless, have played a role. This research attempts to reconcile the observed peak with the thresholds predicted by lockdown regimes similar to the one in force at the time. It contemplates the effect of two, different, hypothetical errors in the data: The first is that the true level of infection has been underestimated by a multiplicative factor, while the second is that of an imperceptible, pre-existing, immune fraction of the population. While it is shown that it certainly is possible to manufacture the perception of an early peak as extreme as the one observed, solely by way of these two phenomena, the values need to be fairly high. The phenomena would not, by any measure, be insignificant. It also remains an inescapable fact that the early peak in infections coincided with a fairly profound change in r0; in all the contemplated scenarios of data-deficiency.
Adenoma detection rate in fecal immunochemical test positive colonoscopies: a population-based observational study
Authors: Denis Bernard , Gendre Isabelle , Tuzin Nicolas , Guignard Anne , Perrin Philippe , Rahmi Gabriel 
Published: September 2020

AbstractBackground and aimsNeoplasia-related indicators, such as adenoma detection rate (ADR), are a priority in the quality improvement process for colonoscopy. Our aim was to assess and compare different detection and characterization indicators in fecal occult blood test (FOBT)-positive colonoscopies, to analyze the factors influencing their variance, and to propose benchmarks.MethodsRetrospective analysis of prospectively collected data from all colonoscopies performed between 2007 and 2019 after a positive guaiac-based FOBT or a fecal immunochemical test (FIT) in the population-based colorectal cancer (CRC) screening program conducted in Alsace, part of the French national program. Detection indicators included ADR, NewADR (including proximal serrated lesions), mean number of adenomas per colonoscopy, and proximal serrated lesion detection rate. Characterization indicators included non-neoplastic polyp detection rate.ResultsOverall, 13.455 FIT-positive colonoscopies were performed by 116 endoscopists. The overall ADR was 57.6% (95%CI 56.8-58.5). For each 10 μg/g increase in fecal hemoglobin concentration, a 2% increase in ADR was observed. Endoscopists whose ADR was ≥55% were high detectors for all neoplasia, including proximal serrated lesions and number of adenomas. The non-neoplastic polyp detection rate was 39.5% in highest detectors (ADR >70%), significantly higher than in lower detectors (21.4%) (p<0.001). There was a strong correlation between detection and characterization indicators, e.g. between proximal serrated lesion and non-neoplastic polyp detection rates (Pearson = 0.73; p<0.01).ConclusionsA single indicator, NewADR, including proximal serrated lesions, is enough to assess the neoplasia yield of colonoscopy provided the target standard is raised between 55% and 70% in FIT-positive colonoscopies (65-80% in men, 45-60% in women).
Early Prediction of Sepsis in the ICU using Machine Learning: A Systematic Review
Authors: Moor Michael , Rieck Bastian , Horn Max , Jutzeler Catherine R. , Borgwardt Karsten 
Published: September 2020

AbstractBackgroundSepsis is among the leading causes of death in intensive care units (ICU) world-wide and its recognition, particularly in the early stages of the disease, remains a medical challenge. The advent of an affluence of available digital health data has created a setting in which machine learning can be used for digital biomarker discovery, with the ultimate goal to advance the early recognition of sepsis.ObjectiveTo systematically review and evaluate studies employing machine learning for the prediction of sepsis in the ICU.Data sourcesUsing Embase, Google Scholar, PubMed/Medline, Scopus, and Web of Science, we systematically searched the existing literature for machine learning-driven sepsis onset prediction for patients in the ICU.Study eligibility criteriaAll peer-reviewed articles using machine learning for the prediction of sepsis onset in adult ICU patients were included. Studies focusing on patient populations outside the ICU were excluded.Study appraisal and synthesis methodsA systematic review was performed according to the PRISMA guidelines. Moreover, a quality assessment of all eligible studies was performed.ResultsOut of 974 identified articles, 22 and 21 met the criteria to be included in the systematic review and quality assessment, respectively. A multitude of machine learning algorithms were applied to refine the early prediction of sepsis. The quality of the studies ranged from “poor” (satisfying ≤ 40% of the quality criteria) to “very good” (satisfying ≥ 90% of the quality criteria). The majority of the studies (n= 19, 86.4%) employed an offline training scenario combined with a horizon evaluation, while two studies implemented an online scenario (n= 2, 9.1%). The massive inter-study heterogeneity in terms of model development, sepsis definition, prediction time windows, and outcomes precluded a meta-analysis. Last, only 2 studies provided publicly-accessible source code and data sources fostering reproducibility.LimitationsArticles were only eligible for inclusion when employing machine learning algorithms for the prediction of sepsis onset in the ICU. This restriction led to the exclusion of studies focusing on the prediction of septic shock, sepsis-related mortality, and patient populations outside the ICU.Conclusions and key findingsA growing number of studies employs machine learning to optimise the early prediction of sepsis through digital biomarker discovery. This review, however, highlights several shortcomings of the current approaches, including low comparability and reproducibility. Finally, we gather recommendations how these challenges can be addressed before deploying these models in prospective analyses.Systematic review registration numberCRD42020200133
Hydroxicloroquine for Pre-Exposure Prophylaxis for SARS-COV-2
Authors: de la Iglesia Jaime López , Fernández Naiara Cubelos , Flores Roi Naveiro , Gómez Marina Montoro , González de Haro Francisco Javier , González María Ajenjo , Vicente Estefanía Tobal , Gil de Gómez María Lamuedra , Guisado María Teresa Nuevo , Gómez Isabel Torio , Andrada Ana Peñalver , Cao Nuria Martínez , Figaredo Paula González , García Carlos Robles , Machón Lidia Anastasia Alvarado , Alcalde Ángeles Lafont , Rilo José Cesáreo Naveiro 
Published: September 2020

ABSTRACTSARS-CoV-2 infection has a high transmission level. At the present time there is not a specific treatment approved but it is known that, in vitro, chloroquine and hydroxychloroquine can inhibit the coronavirus.Objectiveverifying if patients with autoimmune diseases that are on treatment with HCQ have less incidence and severity on COVID-19.Material and methodsthis is a retrospective cohort study. The exposed cohort was formed by individuals with autoimmune diseases with HCQ treatment. The control cohort was randomly selected using the Health Card database. To deal with confounding variables and evaluate the effect of HCQ on the incidence and severity of SARS-CoV-2 infection, propensity score matching was used. Risk difference and paired percentage difference between exposed and non-exposed groups was estimated.Results919 individuals formed the exposed cohort and 1351 the control cohort. After matching, there were 690 patients on each group. During the time of the study, in the exposed group there were 42 (6.1%) individuals with suspected COVID-19, 12(1.7%) with confirmed COVID-19 and 3(0.4%) were hospitalized. In the control group there were 30(4.3%) individuals with suspected COVID-19, 13(1.9%) with confirmed COVID-19 and 2(0.3%) were hospitalized. The risk difference between each cohort was: 0.017(−0.05-0.04) for suspected COVID-19; -0.014(−0.015-0.012) for confirmed COVID-19 and 0.001(−0.007-0.007) for hospitalized patients. There were not significant differences.Conclusionthere is no difference neither on the incidence nor on the severity of COVID-19 between patients with autoimmune diseases with HCQ treatment and patients that do not take HCQ.
Evaluating the design and implementation of an adapted Plan-Do-Study-Act (PDSA) approach to improve health system bottlenecks in Nigeria
Authors: Eboreime Ejemai Amaize , Olawepo John Olajide , Banke-Thomas Aduragbemi , Ramaswamy Rohit 
Published: September 2020

AbstractBackgroundThe Plan-Do-Study-Act (PDSA) cycle is fundamental to many quality improvement (QI) models. For the approach to be effective in the real-world, variants must align with standard elements of the PDSA at the design stage. The adapted design must also be implemented with fidelity. Gaps at the adaptation or implementation stages result in design and implementation failures respectively. Using Taylor’s framework, this study evaluates the alignment between theory, design and implementation of the DIVA (Diagnose-Intervene-Verify-Adjust) model, a PDSA variant adapted for Nigeria’s health system performance improvement.MethodsAn iterative consensus building approach was used to develop a scorecard evaluating new conceptual indices of design and implementation of QI interventions (design and implementation index, defects and gaps). The scorecard assigned quantitative scores that measured the extent to which the reported or documented design or implementation activity aligned with Taylor’s theoretical framework.ResultsDesign (adaptation) scores were across all standard features indicating that design was well adapted to the typical PDSA. Conversely, implementation fidelity scores were only optimal with two standard features: prediction-based test of change and the use of data over time. The other features, use of multiple iterative cycles and documentation, had implementation gaps of 17% and 50% respectively. This may imply that observed effectiveness deficits of DIVA may be attributable to implementation rather than design gaps.ConclusionsThe effectiveness of QI interventions depend of good contextual adaptation and implementation fidelity such that core features (theory and internal logic) must not be compromised. This study demonstrates how both adaptation and implementation are important for success of QI interventions. It also presents an approach for evaluating other QI models using Taylor’s PDSA assessment framework as a guide, which might serve to strengthen the theory behind future QI models, and provide guidance on their appropriate use.
Health and Economic Effects of COVID-19 control in Australia: Modelling and quantifying the payoffs of ‘hard’ versus ‘soft’ lockdown
Authors: Grafton R. Quentin , Parslow John , Kompas Tom , Glass Kathryn , Banks Emily , Lokuge Kamalini 
Published: September 2020

AbstractObjective(s)Australia requires high quality evidence to optimise likely health and economy outcomes to effectively manage the current resurgence of COVID-19. We hypothesise that the most stringent social distancing (SD) measures (100% of level in Australia in April 2020) deliver better public health and economy outcomes.Design‘Fit-for-purpose’ (individual-based and compartment) models were used to simulate the effects of different SD and detection strategies on Australian COVID-19 infections and the economy from March to July 2020. Public reported COVID-19 data were used to estimate model parameters.Main outcome measuresPublic health and economy outcomes for multiple social distancing levels were evaluated, assessing “hard” versus “soft” lockdowns, and for early versus later relaxation of social distancing. Outcomes included costs and the timing and magnitude of observed COVID-19 cases and cumulative deaths in Australia from March to June 2020.ResultsHigher levels of social distancing achieve zero community transmission with 100% probability and lower economy cost while low levels of social distancing result in uncontrolled outbreaks and higher economy costs. High social distancing total economy costs were $17.4B versus $41.2B for 0.7 social distancing. Early relaxation of suppression results in worse public health outcomes and higher economy costs.Conclusion(s)Better public health outcomes (reduced COVID-19 fatalities) arepositivelyassociated with lower economy costs and higher levels of social distancing; achieving zero community transmissionlowersboth public health and economy costs compared to allowing community transmission to continue; and early relaxation of social distancingincreasesboth public health and economy costs.SignificanceThe knownis that COVID-19 infections can be suppressed with social distancing (SD) measures of sufficient stringency and duration.The newis we find highest levels of SD (100% SD that prevailed in April 2020) generate much lower COVID-9 deaths; reduced SD days; increased economic activity; and much higher probability of elimination over a subsequent 12-month period than lower levels of SD.The implicationsare that greater levels of SD are preferred to lower SD because they deliver both better public health and lower economy costs.
Rapid Retreat of the Pacific Maritime Forest
Authors: Kral George , Putnam Melodie , Rupp David 
Published: September 2020

AbstractThe temperate maritime climate of the Pacific Northwest region of the United States supports the world’s tallest and most economically productive conifer forests. These forests are vital to local ecosystems and society, and climate perturbations are likely to adversely affect the services these forests provide. This study presents a simple, easily replicated methodology for assessing effects of climate change in these local forests, using species with differential climatic ranges as ecological barometers. A comparative analysis of warm-adapted and cool-adapted species co-occurring within a warming but otherwise climatically homogenous area near the southeast margin of the Pacific maritime forest reveals dramatic differences in tree health and mortality between these climatically differentiated species groups. Our results strongly suggest a rapid decline at the southeastern extent of the Pacific maritime temperate forest, and a need to immediately modify local land management practices to address this new reality.