bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of Automated Data-adaptive Propensity Score Method for Confounding by Indication in Comparative Effectiveness Study in Real World Medicare and Registry Data
Authors: Kumamaru Hiraku , Jalbert Jessica J. , Nguyen Louis L. , Williams Lauren A , Miyata Hiroaki , Setoguchi Soko 
Published: April 2021

ABSTRACTBackgroundConfounding by indication is a serious threat to comparative studies using real world data. We assessed the utility of automated data-adaptive analytic approach for confounding adjustment when both claims and clinical registry data are available.MethodsWe used a comparative study example of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) in 2005-2008 when CAS was only indicated for patients with high surgical risk. We included Medicare beneficiaries linked to the Society for Vascular Surgery’s Vascular Registry >65 years old undergoing CAS/CEA. We compared hazard ratios (HRs) for death while adjusting for confounding by combining various 1) Propensity score (PS) modeling strategies (investigator-specified [IS-PS] vs. automated data-adaptive [ada-PS]); 2) data sources (claims-only, registry-only and claims-plus-registry); and 3) PS adjustment approaches (matching vs. quintiles-adjustment with/without trimming). An HR of 1.0 was a benchmark effect estimate based on CREST trial.ResultsThe cohort included 1,999 CAS and 3,255 CEA patients (mean age 76). CAS patients were more likely symptomatic and at high surgical risk, and experienced higher mortality (crude HR=1.82 for CAS vs. CEA). HRs from PS-quintile adjustment without trimming were 1.48 and 1.52 for claims-only IS-PS and ada-PS, 1.51 and 1.42 for registry-only IS-PS and ada-PS, and 1.34 and 1.23 for claims-plus-registry IS-PS and ada-PS, respectively. Estimates from other PS adjustment approaches showed similar patterns.ConclusionsIn a comparative effectiveness study of CAS vs. CEA with severe confounding by indication, ada-PS performed better than IS-PS in general, but both claims and registry data were needed to adequately control for bias.
The demographic and geographic impact of the COVID pandemic in Bulgaria and Eastern Europe in 2020
Authors: Rangachev Antoni , Marinov Georgi K. , Mladenov Mladen 
Published: April 2021

AbstractBackgroundThe COVID-19 pandemic followed a unique trajectory in Eastern Europe compared to other heavily affected regions, with most countries there only experiencing a major surge of cases and deaths towards the end of 2020 after a relatively uneventful first half of the year. However, the consequences of that surge have not received as much attention as the situation in Western countries. Bulgaria, even though it has been one of the most heavily affected countries, has been one of those neglected cases.MethodsWe use mortality and mobility data from Eurostat, official governmental and other sources to examine the development and impact of the COVID-19 pandemic in Bulgaria and other European countries.ResultsWe find a very high level of excess mortality in Eastern European countries measured by several metrics including excess mortality rate (EMR), P-scores and potential years of life lost. By the last metric Eastern Europe emerges as the hardest hit region by the pandemic in Europe in 2020. With a record EMR at ∼0.25% and a strikingly large and mostly unique to it mortality rate in the working age demographics, Bulgaria emerges as one of the most affected countries in Eastern Europe. The high excess mortality in Bulgaria correlates with insufficient intensity of testing and with delayed imposition of “lockdown” measures. We also find major geographic and demographic disparities within the country, with considerably lower mortality observed in major cities relative to more remote areas (likely due to disparities in the availability of medical resources). Analysis of the course of the epidemic revealed that individual mobility measures were predictive of the eventual decline in cases and deaths. However, while mobility declined as a result of the imposition of a lockdown, it already trended downwards before such measures were introduced, which resulted in a reduction of deaths independent of the effect of restrictions.ConclusionsLarge excess mortality and high numbers of potential years of life lost are observed as a result of the COVID pandemic in Bulgaria, as well as in several other countries in Eastern Europe. Significant delays in the imposition of stringent mobility-reducing measures combined with a lack of medical resources likely caused a substantial loss of life, including in the working age population.
Postoperative morbidity after liver resection- A Systemic review, meta-analysis, and metaregression of factors affecting them
Authors: Vasavada Bhavin , Patel Hardik 
Published: April 2021

AbstractAim of the studyThis systemic review and meta-analysis aimed to analyze post-operative morbidity after liver resection, and also study various factors associated with mortality via metaregression analysis.Material and MethodsPubMed, Cochrane Library, Embase, google scholar, web of science with keywords like ‘liver resection”; “mortality”;” hepatectomy”. Weighted percentage post-operative morbidities were analyzed. Meta-analysis and meta-regression were done by the DerSimonian-Liard random effect model. Heterogeneity was assessed using the Higgins I2 test. Publication bias was assessed using a funnel plot. Funnel plot asymmetry was evaluated by Egger’s test. Morbidity was defined as any postoperative morbidity mentioned.ResultsA total of 46 studies was included in the final analysis. Total 45771 patients underwent liver resections. 16111 patients experienced complications during the postoperative period. Weighted post-operative morbidity was 30.2% (95 % C.I. 24.8-35.7%). Heterogeneity was high with I2 99.46% and p-value <0.01. On univariate analysis, major liver resections were significantly associated with heterogeneity. (p=0.024). However, residual heterogeneity was still high with I2 98.62%, p<0.001. So, multifactor metaregression analysis major hepatectomy (p<0.001), Open hepatectomy (p=0.001), cirrhotic liver (p=0.002), age (p<0.001), blood loss (p<0.001), and colorectal metastasis (p<0.001) independently associated with postoperative morbidity. Residual heterogeneity was moderate I2= 39.9% and nonsignificant p=0.189.ConclusionLiver resection is associated with high postoperative morbidity and various factors like major hepatectomy, Open hepatectomy, cirrhotic liver, blood loss, and colorectal metastasis were associated with morbidity and responsible for heterogeneity across the studies.
Machine Learning based COVID-19 Diagnosis from Blood Tests with Robustness to Domain Shifts
Authors: Roland Theresa , Böck Carl , Tschoellitsch Thomas , Maletzky Alexander , Hochreiter Sepp , Meier Jens , Klambauer Günter 
Published: April 2021

AbstractWe investigate machine learning models that identify COVID-19 positive patients and estimate the mortality risk based on routinely acquired blood tests in a hospital setting. However, during pandemics or new outbreaks, disease and testing characteristics change, thus we face domain shifts. Domain shifts can be caused, e.g., by changes in the disease prevalence (spreading or tested population), by refined RT-PCR testing procedures (taking samples, laboratory), or by virus mutations. Therefore, machine learning models for diagnosing COVID-19 or other diseases may not be reliable and degrade in performance over time. To countermand this effect, we propose methods that first identify domain shifts and then reverse their negative effects on the model performance. Frequent re-training and reassessment, as well as stronger weighting of more recent samples, keeps model performance and credibility at a high level over time. Our diagnosis models are constructed and tested on large-scale data sets, steadily adapt to observed domain shifts, and maintain high ROC AUC values along pandemics.
Living Shorelines Achieve Functional Equivalence to Natural Fringe Marshes across Multiple Ecological Metrics
Authors: Isdell Robert E. , Bilkovic Donna Marie , Guthrie Amanda G. , Mitchell Molly M. , Chambers Randolph M. , Leu Matthias , Hershner Carlton 
Published: April 2021

ABSTRACTNature-based features provide a welcome class of adaptations to promote ecological resilience in the face of climate change. Along coastlines, living shorelines are among the preferred adaptation strategies to both reduce erosion and provide ecological functions. As an alternative to shoreline armoring, living shorelines are viewed favorably among coastal managers, wetlands boards, and some private property owners, but they have yet to undergo a thorough examination of how their levels of ecosystem functions compare to their closest natural counterpart: fringing marshes. Here, we provide a synthesis of results from a multi-year, large-spatial-scale study in which we compared numerous ecological metrics measured in thirteen pairs of living shorelines and natural fringing marshes throughout coastal Virginia, USA. Overall, we found that living shorelines were functionally equivalent to natural marshes in nearly all measured aspects, except for a lag in sediment composition. These data support the prioritization of living shorelines as a coastal adaptation strategy.
Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
Authors: Lam Suzanne , Hérard Anne-Sophie , Boluda Susana , Petit Fanny , Eddarkaoui Sabiha , Cambon Karine ,   The Brainbank Neuro-CEB Neuropathology Network, Picq Jean-Luc , Buée Luc , Duyckaerts Charles , Haïk Stéphane , Dhenain Marc 
Published: April 2021

AbstractAlzheimer’s disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaquesi.e.tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the current study, human AD brain extracts (ADbe) and control-brain extracts (Ctrlbe) were infused in the hippocampus of Aβ plaque-bearing APPswe/PS1dE9mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. ADbeinoculation induced memory deficit. It increased deposition of Aβ plaques close to the inoculation site. Tau pathology was also induced in ADbe-inoculated mice. Neuropil threads and neurofibrillary tangles occurred next to the inoculation site and spread to connected regions notably the perirhinal/entorhinal cortex. Neuritic plaque pathology was detected in both ADbe- and Ctrlbe- inoculated animals but ADbeinoculation increased the severity close and at distance of the inoculation site. Finally, ADbeinoculation reduced synaptic density close to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not of other tau lesions or Aβ lesions, which suggests that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load.Graphical abstract
New distributional opportunities with niche innovation in Eurasian snowfinches
Authors: Cobos Marlon E , Cheng Yalin , Song Gang , Lei Fumin , Peterson A. Townsend 
Published: April 2021

AbstractThis study explores the evolutionary history of ecological niche characters in the Eurasian snowfinch lineage. Specifically, we use new analytical approaches to reconstruct ecological niche evolution, taking uncertainty in knowledge of the ecological niche limits into account. We found an overall pattern of niche conservatism in relation to both temperature and precipitation characteristics of niches, but for one dramatic niche evolution event, inMontifringilla nivalis. Interestingly, this species is also that which has by far the broadest geographic distribution among snowfinches. We conclude that an evolutionary change in niche characteristics perhaps withinM. nivalis(i.e., present in some and not all of its populations) made possible the broad, westward range expansion of that species, thus changing the distributional potential of the snowfinch lineage dramatically.
Characterising contact in disease outbreaks via a network model of spatial-temporal proximity
Authors: Myall Ashleigh , Peach Robert L. , Wan Yu , Mookerjee Siddharth , Jauneikaite Elita , Bolt Frankie , Price James , Davies Frances , Weiße Andrea Y. , Holmes Alison , Barahona Mauricio 
Published: April 2021

ABSTRACTContact tracing is a key tool in epidemiology to identify and control outbreaks of infectious diseases. Existing contact tracing methodologies produce contact maps of individuals based on a binary definition of contact which can be hampered by missing data and indirect contacts. Here, we present a Spatial-temporal Epidemiological Proximity (StEP) model to recover contact maps in disease outbreaks based on movement data. The StEP model accounts for imperfect data by considering probabilistic contacts between individuals based on spatial-temporal proximity of their movement trajectories, creating a robust movement network despite possible missing data and unseen transmission routes. Using real-world data we showcase the potential of StEP for contact tracing with outbreaks of multidrug-resistant bacteria and COVID-19 in a large hospital group in London, UK. In addition to the core structure of contacts that can be recovered using traditional methods of contact tracing, the StEP model reveals missing contacts that connect seemingly separate outbreaks. Comparison with genomic data further confirmed that these recovered contacts indeed improve characterisation of disease transmission and so highlights how the StEP framework can inform effective strategies of infection control and prevention.
Statistical Design and Analysis of Diagnostic Tests for Mutating Viruses
Authors: Han Yang , Sun Yujia , Hsu Jason C. , House Thomas , Gent Nick , Hall Ian 
Published: April 2021

AbstractAs the SARS-CoV-2 virus mutates, mutations harboured in patients become increasingly diverse. Patients classified into two strains may have overlapping non-variant-defining mutations.Mutation calling by sequencing is relative to a reference genome. As SARS-CoV-2 mutates, tracking emerging mutant strains may become increasingly problematic if the reference genome remains Wuhan-Hu-1, because the comparison then becomes indirect: current dominant strain relative to Wuhan-Hu-1 versus emerging strain relative to Wuhan-Hu-1.The original Thermo Fisher’s TaqPath PCR test, on which the UK has standardized national testing of SARS-CoV-2 primarily, targets Wuhan-Hu-1. PCR targets appear readily updated, as TaqPath 2.0 now targets both currently known and future SARS-CoV-2 mutations, probing the N gene and ORF1ab but not the S gene, with 8 probes instead of the original 3 probes. Going forward, our statistical method can more directly compare current wildtype versus emerging mutants, since our new method can use any pair of probes updated to probe the current wildtype and anticipated mutations.The fact that patients harbour mixtures of mutations allows our statistical methods to potentially catch emerging mutants. Given a PCR test which targets the current dominant strain (current wildtype), our statistical method can potentially directly differentiate the current wildtype from an emerging strain.
Metabolic and muscle-derived serum biomarkers define CHCHD10-linked late-onset spinal muscular atrophy
Authors: Järvilehto Julius , Harjuhaahto Sandra , Palu Edouard , Auranen Mari , Kvist Jouni , Zetterberg Henrik , Koskivuori Johanna , Lehtonen Marko , Saukkonen Anna Maija , Jokela Manu , Ylikallio Emil , Tyynismaa Henna 
Published: April 2021

ABSTRACTObjectiveTo characterize serum biomarkers in mitochondrial CHCHD10-linked spinal muscular atrophy Jokela type (SMAJ) for disease monitoring and for understanding of pathogenic mechanisms.MethodsWe collected serum samples from a cohort of 49 SMAJ patients, all carriers of the heterozygous c.197G>T p.G66V variant inCHCHD10. As controls, we used age- and sex-matched serum samples obtained from Helsinki Biobank. Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with Single molecule array (Simoa), and fibroblast growth factor 21 (FGF-21) and growth differentiation factor 15 (GDF-15) with enzyme-linked immunosorbent assay. For nontargeted serum metabolite profiling, samples were analyzed with liquid chromatography–high resolution mass spectrometry. Disease severity was evaluated retrospectively by calculating a symptom-based score.ResultsAxon degeneration marker NfL was unexpectedly not altered in the serum of SMAJ patients, whereas astrocytic activation marker GFAP was slightly decreased. Creatine kinase was elevated in most patients, in particular males. We identified six metabolites that were significantly altered in SMAJ patients’ serum compared to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine and succinate. Creatine correlated with disease severity. Altered pyruvate and succinate indicated a metabolic response to mitochondrial dysfunction, however, lactate or mitochondrial myopathy markers FGF-21 or GDF-15 were not changed.ConclusionsBiomarkers of muscle mass and damage are altered in SMAJ serum, indicating a role for skeletal muscle in disease pathogenesis in addition to neurogenic damage. Despite the minimal mitochondrial pathology in skeletal muscle, signs of a metabolic shift can be detected in the serum of SMAJ patients.
Improved diagnosis of SARS-CoV-2 by using Nucleoprotein and Spike protein fragment 2 in quantitative dual ELISA tests
Authors: Verissimo Carolina De M. , O’Brien Carol , López Corrales Jesús , Dorey Amber , Cwiklinski Krystyna , Lalor Richard , Doyle Jack M. , Field Stephen , Masterson Claire , Martinez Eduardo Ribes , Hughes Gerry , Bergin Colm , Walshe Kieran , McNicholas Bairbre , Laffey John G. , Dalton John P. , Kerr Colm , Doyle Sean 
Published: April 2021

SUMMARYThe novel Coronavirus, SARS-CoV-2, is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and Spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative ELISA assays that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive COVID-19 cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients that had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.
Evaluating and optimizing COVID-19 vaccination policies: a case study of Sweden
Authors: Sjödin Henrik , Rocklöv Joacim , Britton Tom 
Published: April 2021

AbstractWe evaluate the efficiency of vaccination scenarios for COVID-19 by analysing a data-driven mathematical model. Healthcare demand and incidence are investigated for different scenarios of transmission and vaccination schemes. Our results suggest that reducing the transmission rate affected by invading virus strains, seasonality and the level of prevention, is most important. Second to this is timely vaccine deliveries and expeditious vaccination management. Postponing vaccination of antibody-positive individuals reduces also the disease burden, and once risk groups have been vaccinated, it is best to continue vaccinating in a descending age order.
GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme
Authors: Sherpa Dawafuti , Chrustowicz Jakub , Qiao Shuai , Langlois Christine R. , Hehl Laura A. , Gottemukkala Karthik Varma , Hansen Fynn M. , Karayel Ozge , von Gronau Susanne , Prabu J. Rajan , Mann Matthias , Alpi Arno F. , Schulman Brenda A. 
Published: April 2021

SUMMARYTo achieve precise cellular regulation, E3 ubiquitin ligases must be configured to match substrate quaternary structures. Here, by studying the yeast GID complex, mutation of which isGlucose-InducedDegradation deficient, we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryo EM structures show that to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two otherwise functional GID E3s assemble into a 20-protein Chelator-GIDSR4, which resembles an organometallic supramolecular chelate. The Chelator-GIDSR4assembly avidly binds multiple Fbp1 degrons and positions Fbp1 so that its protomers are simultaneously ubiquitylated at lysines near its allosteric and substrate binding sites. Significantly, key structural and biochemical features -including capacity for supramolecular assembly - are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical and cell biological data, we propose that higher-order E3 ligase assembly generally underlies multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.
Invasive grass litter suppresses native species and promotes disease
Authors: Benitez Liliana , Kendig Amy E. , Adhikari Ashish , Clay Keith , Harmon Philip F. , Holt Robert D. , Goss Erica M. , Flory S. Luke 
Published: April 2021

AbstractPlant litter can alter ecosystems and promote plant invasions by changing resource acquisition, depositing toxins, and transmitting microorganisms to living plants. Transmission of microorganisms from invasive litter to live plants may gain importance as invasive plants accumulate pathogens over time since introduction. It is unclear, however, if invasive plant litter affects native plant communities by promoting disease.Microstegium vimineumis an invasive grass that suppresses native populations, in part through litter production, and has accumulated leaf spot diseases since its introduction to the U.S. In a greenhouse experiment, we evaluated howM. vimineumlitter and accumulated pathogens mediated resource competition with the native grassElymus virginicus. Resource competition reduced biomass of both species and liveM. vimineumincreased disease incidence on the native species.Microstegium vimineumlitter also promoted disease on the native species, suppressed establishment of both species, and reduced biomass ofM. vimineum. Nonetheless, interference competition from litter had a stronger negative effect on the native species, increasing the relative abundance ofM. vimineum. Altogether, invasive grass litter suppressed both species, ultimately favoring the invasive species in competition, and increased disease incidence on the native species.