bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of implementing objective diagnostic verification of asthma in the United States
Authors: Yaghoubi Mohsen , Adibi Amin , Zafari Zafar , FitzGerald J Mark , Aaron Shawn D. , Johnson Kate M. , Sadatsafavi Mohsen 
Published: November 2019

AbstractBackgroundAsthma diagnosis in the community is often made without objective testing.ObjectiveThe aim of this study was to evaluate the cost-effectiveness of implementing a stepwise objective diagnostic verification algorithm among patients with community-diagnosed asthma in the United States (US).MethodsWe developed a probabilistic time-in-state cohort model that compared a stepwise asthma verification algorithm based on spirometry and methacholine challenge test against the current standard of care over 20 years. Model input parameters were informed from the literature and with original data analyses when required. The target population was US adults (≥15 y/o) with physician-diagnosed asthma. The final outcomes were costs (in 2018 $) and quality-adjusted life years (QALYs), discounted at 3% annually. Deterministic and probabilistic analyses were undertaken to examine the effect of alternative assumptions and uncertainty in model parameters on the results.ResultsIn a simulated cohort of 10,000 adults with diagnosed asthma, the stepwise algorithm resulted in the removal of diagnosis in 3,366. This was projected to be associated with savings of $36.26 million in direct costs and a gain of 4,049.28 QALYs over 20 years. Extrapolating these results to the US population indicated an undiscounted potential savings of $56.48 billion over 20 years. Results were robust against alternative assumptions and plausible changes in values of input parameters.ConclusionImplementation of a simple diagnostic testing algorithm to verify asthma diagnosis might result in substantial savings and improvement in patients’ quality of life.Key MessagesCompared with current standards of practice, the implementation of an asthma verification algorithm among US adults with diagnosed asthma can be associated with reduction in costs and gain in quality of life.There is substantial room for improving patient care and outcomes through promoting objective asthma diagnosis.Capsule summaryAsthma ‘overdiagnosis’ is common among US adults. An objective, stepwise verification algorithm for re-evaluation of asthma diagnosis can result in substantial savings in costs and improvements in quality of life.
Projected Impact of Concurrently Available Long-Acting Injectable and Daily-Oral HIV Pre-Exposure Prophylaxis: A Mathematical Model
Authors: Maloney Kevin M. , Guillou Adrien Le , Driggers Robert A. , Sarkar Supriya , Anderson Emeli J. , Malik Amyn A. , Jenness Samuel M. 
Published: November 2019

ABSTRACTBackgroundLong-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) is reportedly efficacious, although full trial results have not been published. We used a dynamic network model of HIV transmission among men who have sex with men (MSM) to assess the population impact of LAI-PrEP when available concurrently with daily-oral (DO) PrEP.MethodsThe reference model represents the current HIV epidemiology and DO-PrEP coverage (15% among indicated) among MSM in the southeastern US. Primary analyses investigated varied PrEP uptake and proportion selecting LAI-PrEP. Secondary analyses evaluated uncertainty in pharmacokinetic efficacy and LAI-PrEP persistence relative to DO-PrEP.ResultsCompared to the reference scenario, if 50% chose LAI-PrEP, 4.3% (95% SI: −7.3%, 14.5%) of infections would be averted over 10 years. LAI-PrEP impact is slightly greater than the DO-PrEP only regimen based on assumptions of higher adherence and partial protection after discontinuation. If the total PrEP initiation rate doubled, 17.1% (95% SI: 6.7%, 26.4%) of infections would be averted. The highest population-level impact occurred when LAI-PrEP uptake and persistence improved.ConclusionsIf LAI-PrEP replaces DO-PrEP, its availability will modestly improve the population impact. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage, or if persistence is greater for LAI-PrEP.SummaryLong-acting injectable pre-exposure prophylaxis (LAI-PrEP) will modestly decrease HIV incidence if it replaces daily-oral PrEP use among men who have sex with men. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage.
Global and Historical Distribution ofClostridioides difficilein the Human Diet (1981-2019): Systematic Review and Meta-Analysis of 21886 Samples Reveal Sources of Heterogeneity, High-Risk Foods, and Unexpected Higher Prevalence Towards the Tropic
Authors: Rodriguez-Palacios Alexander , Mo Kevin Q , Shah Bhavan U. , Msuya Joan , Bijedic Nina , Deshpande Abhishek , Ilic Sanja 
Published: November 2019

AbstractClostridioides difficile(CD) is a spore-forming bacterium that causes life-threatening intestinal infections in humans. Although formerly regarded as exclusively nosocomial, there is increasing genomic evidence that person-to-person transmission accounts for only <25% of cases, supporting the culture-based hypothesis that foods may be routine sources of CD-spore ingestion in humans.To synthesize the evidence on the risk of CD exposure via foods, we conducted a systematic review and meta-analysis of studies reporting the culture prevalence of CD in foods between January 1981 and November 2019. Meta-analyses, risk-ratio estimates, and meta-regression were used to estimate weighed-prevalence across studies and food types to identify laboratory and geographical sources of heterogeneity.In total, 21,886 food samples were tested for CD between 1981 and 2019 (232 food-sample-sets; 79 studies; 25 countries). Culture methodology, sample size and type, region, and latitude were significant sources of heterogeneity (p<0.05). Although non-strictly-anaerobic methods were reported in some studies, and we confirmed experimentally that improper anaerobiosis of media/sample-handling affects CD recovery in agar (Fisher, p<0.01), most studies (>72%) employed the same (one-of-six) culture strategy. Because the prevalence was also meta-analytically similar across six culture strategies reported, all studies were integrated using three meta-analytical methods. At the study level (n=79), the four-decade global cumulative-prevalence of CD in the human diet was 4.1% (95%CI=-3.71, 11.91). At the food-set level (n=232), the weighted prevalence ranged between 4.5% (95%CI=3-6%; all studies) and 8% (95%CI=7-8%; only CD-positive-studies). Risk-ratio ranking and meta-regression showed that milk was the least likely source of CD, while seafood, leafy green vegetables, pork, and poultry carried higher risks (p<0.05). Across regions, the risk of CD in foods for foodborne exposure reproducibly decreased with Earth latitude (p<0.001).In conclusion, CD in the human diet is a global nonrandom-source of foodborne exposure that occurs independently of laboratory culture methods, across regions, and at variable level depending on food type and latitude. The latitudinal trend (high CD-food-prevalence towards tropic) is unexpectedly inverse to the epidemiological observations of CD-infections in humans (frequent in temperate regions). Findings suggests the plausible hypothesis that ecologically-richer microbiomes in the tropic might protect against intestinal CD colonization/infections despite CD ingestion.
Incidence and Prevalence of Hidradenitis Suppurativa: A Systematic Review and Meta-analysis
Authors: Gill N. , Gniadecki R. 
Published: November 2019

AbstractBackgroundHidradenitis is a chronic relapsing follicular occlusive disease with a widely variable reported prevalence. The exact prevalence and incidence of HS is unknown.ObjectivesTo perform a systematic review and meta-analysis of the published literature to estimate the global incidence and prevalence of HS.MethodsLiterature searches were performed on Medline, Embase, and Pubmed to identify studies reporting incidence and/or prevalence of HS. Pooled estimates of prevalence and incidence were calculated with a meta-analysis of proportions.ResultsIn total, 12 studies were included (Australia, Brazil, Denmark, France, Germany, Ireland, Israel, UK, USA) comprising a total population of 53,805,690. Eleven studies reported prevalence. The pooled proportion of individuals in the general population with HS was 0.36% (95% CI 0.21 - 0.56). Self-reported HS gave a higher prevalence estimate than clinician-diagnosed HS. HS is more prevalent in women. Average annual incidence of HS was 28.5 cases/100,000 (95% CI 26.8 – 30.1).ConclusionsWe estimated the global prevalence of HS to be 0.36% with 3:2 female predominance and average annual incidence to be 28.5 cases/100,000.
Antimicrobial resistance trends from a hospital and diagnostic facility in Lahore, Pakistan: A five-year retrospective analysis (2014-2018)
Authors: Ching Carly , Nizamuddin Summiya , Rasheed Farah , Seager R.J. , Litvak Felix , Sultan Faisal , Zaman Muhammad 
Published: November 2019

AbstractObjectiveObserving antimicrobial resistance (AMR) trends is critical to identify emerging pathogens and potential disease outbreaks. Determining these trends also allows for policy evaluations and development of interventions. We performed a retrospective analysis of microbiological testing results from a hospital and diagnostic facility in Lahore, Pakistan that represents country-wide sampling. Within this analysis, data was disaggregated by nationality, as it has been suggested that migration increases the burden of AMR. We sought to determine any trends in AMR among populations, which are often at-risk, while contributing to AMR surveillance in Pakistan, which currently does not have a national surveillance network.MethodsRetrospective analysis of antimicrobial susceptibility records from 2014 to 2018 from Shaukat Khanum Memorial Cancer Hospital & Research Centre (SKMCH&RC) in Lahore, Pakistan was performed. All positive microbiological cultures from patients was analyzed to assess antibiotic resistance rates of the most common bacterial isolates and incidence of ESKAPE pathogens and emerging outbreaks among adults and children.ResultsFor all years, data for a total of 12,702 and 78,130 bacterial and fungal isolates from children and adults, respectively, with Pakistani nationality were analyzed. For all years, data for 597 and 2470 bacterial and fungal isolates for children and adults, respectively, with Afghan nationality were analyzed. AMR rates largely did not vary between populations, but rather followed similar trends. AMR rates also largely agreed with the World Health Organization Global Antimicrobial Surveillance System results for Pakistan.ConclusionPakistan requires increased AMR surveillance to identify emerging resistance infections and outbreaks.
Temperature-related disasters in Europe – a cross-sectional analysis of the emergency events database from a pediatric perspective
Authors: Brennenstuhl Heiko , Will Manuel , Ries Elias , Mechler Konstantin , Garbade Sven , Ries Markus 
Published: November 2019

AbstractThis study investigates patterns of extreme temperature-related events in Europe and its significance for the public health, with a focus on the vulnerable pediatric population. A generalized additive model of average surface temperature development for the European countries is described and discussed with an in-depth analysis of the influence of temperature on evolutional and behavioral aspects.MethodsExtreme temperature related events are recorded in the publicly available epidemiological database of Emergency Events (EM-DAT). A comparative and descriptive statistical analysis of this data was conducted with a focus on (prospective) records from 1988 onwards. Average surface temperature data was provided by the World Bank’s Climate Change Knowledge Portal. The criteria for strengthening the reporting of observational studies in epidemiology (STROBE) were respected.ResultsWithin EM-DAT, extreme temperature-related disasters in Europe were categorized as either heat waves, drought, forest or land fires, or cold waves and severe winter conditions, accordingly. The most frequent type of event recorded were cold waves (36.2%). However, cold waves and severe winter conditions only accounted for about 6,460 casualties (4.4%), while heat waves were responsible for a total of 137,533 casualties (95.1%). During the prospective observational period of the EM-DAT database, heat waves in 2003, 2006, 2010, and 2015, claimed a total of 119,760 casualties. These most severe heatwaves were geographically distributed over Russia (2010), as well as France, Italy, Spain, and Germany, each in 2003. Accordingly, analysis of temperature data revealed an increasing average surface temperature for all assessed European countries, correlating with in an increasing frequency of extreme temperature-related events.ConclusionThis study shows that according to EM-DAT data extreme temperatures are an increasingly important public health threat to the European population as the average European surface temperatures are rising. Although cold waves are more frequently reported in EM-DAT, heat waves are the major cause for temperature-related casualties. Therefore, we conclude that evolutional and cultural resilience against cold and drought is significantly higher than it is against heat. Our results project that the frequency, duration and intensity of heat waves will further increase due to current climatic changes and become a more prevalent problem for future generations. Hence, we propose an emergency plan to inform the public and authorities about measurements to be taken in such extreme heat conditions to overcome the prevailing lack of information available to the public.
Aberrant effective connectivity is associated with positive symptoms in first-episode schizophrenia
Authors: Dietz Martin J. , Zhou Yuan , Veddum Lotte , Frith Christopher D. , Bliksted Vibeke F. 
Published: November 2019

AbstractSchizophrenia is a tenacious psychiatric disorder thought to result from synaptic dysfunction. While symptomatology is traditionally divided into positive and negative symptoms, abnormal social cognition is now recognized a key component of schizophrenia. Nonetheless, we are still lacking a mechanistic understanding of how aberrant synaptic connectivity is expressed in schizophrenia during social perception and how it relates to positive and negative symptomatology. We used fMRI and dynamic causal modelling (DCM) to test for abnormalities in synaptic efficacy in twenty-four patients with first-episode schizophrenia (FES) compared to twenty-five matched controls performing the Human Connectome Project (HCP) social cognition paradigm. Patients had not received regular therapeutic antipsychotics, but were not completely drug naïve. Our data reveal an increase in excitatory feedforward connectivity from motion-sensitive V5 to posterior superior temporal sulcus (pSTS) in patients compared to matched controls. At the same time, were less accurate than controls in judging social stimuli from non-social stimuli. Crucially, patients with a higher degree of positive symptoms had more disinhibition within pSTS, a region computationally involved in Theory of Mind. We interpret these within a predictive coding framework where increased feedforward connectivity may encode aberrant prediction errors from V5 to hierarchically higher pSTS and local disinhibition within pSTS may reflect aberrant encoding of the precision of cortical representations about social stimuli.
Stereotactic arrhythmia radioablation for refractory scar-related ventricular tachycardia
Authors: Gianni Carola , Rivera Douglas , Burkhardt J David , Pollard Brad , Gardner Edward , Maguire Patrick , Zei Paul C , Natale Andrea , Al-Ahmad Amin 
Published: November 2019

AbstractBackgroundStereotactic radiosurgery is a form of radiotherapy that is performed in a single session and focuses high-dose ionizing radiation beams from a collimated radiation source to a small, localized area of the body. Recently, stereotactic radiosurgery has been applied to arrhythmias (stereotactic arrhythmia radioablation - STAR), with promising results reported in patients with refractory, scar-related ventricular tachycardia (VT), a cohort with known high morbidity and mortality.ObjectiveHerein, we describe our experience with the use of CyberKnife, a frameless image-guided linear accelerator stereotactic radiosurgery system, in conjunction with CardioPlan, a cardiac specific radiotherapy planning software, to treat patients with scar-related VT, detailing its early and mid-to long-term results.MethodsThis is a pilot, prospective study of patients undergoing STAR for refractory VT. The anatomical target for radioablation was defined based on the clinical VT morphology, electroanatomical mapping, and study-specific pre-procedural imaging with cardiac computed tomography. The target volume delineated with the aid of CardioPlan was treated with a prescription radiation dose of 25 Gy delivered in a single fraction by CyberKnife in an outpatient setting. Ventricular arrhythmias and radiation-related adverse events were monitored at follow-up to determine STAR efficacy and safety.ResultsFive patients (100 % male, 63 ± 12 years old, 80 % ischemic cardiomyopathy, left ventricular ejection fraction 34 ± 15 %) with refractory VT underwent STAR between January and June 2018. Radioablation was delivered in 82 ± 11 minutes without acute complications. During a mean follow-up of 12 ± 2 months, all patients experienced clinically significant mid-to late-term ventricular arrhythmia recurrence; two patients died of complications associated with their advanced heart failure. There were no clinical or imaging evidence of radiation necrosis or other radiation-induced complications in the organs at risk surrounding the scar targeted by radioablation.ConclusionDespite good initial results, STAR did not result in effective ventricular arrhythmia control in the long term in a selected, high-risk population of patients with scar-related VT. The safety profile was confirmed to be favorable, with no radiation-related complications observed during follow-up. Further studies are needed to explain these disappointing results.
Genetic risk of cholangiocarcinoma is linked to the autophagy gene ATG7
Authors: Greer Stephanie U. , Ogmundsdottir Margret H. , Chen Jiamin , Lau Billy T. , Delacruz Richard Glenn C. , Sandoval Imelda T. , Kristjansdottir Sigrun , Jones David A. , Haslem Derrick S. , Romero Robin , Fulde Gail , Bell John M. , Jonasson Jon G. , Steingrimsson Eirikur , Ji Hanlee P. , Nadauld Lincoln D. 
Published: November 2019

ABSTRACTCholangiocarcinoma is an aggressive cancer originating from the bile duct. Although cholangiocarcinoma does occur in families, to date no specific causative gene has been identified. We identified ATG7 as a cancer susceptibility gene using a joint genetic analysis of an extended pedigree with familial cholangiocarcinoma in combination with a population genetic association study. Affected family members had a germline mutation (c.2000C>T [p.Arg659*]) in the autophagy related gene, ATG7, and all of the affected individuals had cholangiocarcinoma tumors harboring somatic genomic deletions of ATG7. From a population genetic study, we identified a germline polymorphism of ATG7 (c.1591C>G [p.Asp522Glu]) associated with increased risk of cholangiocarcinoma. The autophagy substrate p62 demonstrated a higher accumulation in tumors of p.Asp522Glu carriers compared with non-carriers indicating defective autophagy. To determine whether the germline ATG7 mutation had functional consequences, we developed an ATG7-deficient cholangiocyte cell line, derived from human bile duct, to test for autophagy-mediated lipidation activity. The germline mutation from the familial cholangiocarcinoma demonstrated a lack of lipidation activity compared to the wildtype ATG7. Moreover, in zebrafish embryos depleted of atg7, a reproducible necrotic head phenotype was rescued by injection of wildtype ATG7 but not mutant ATG7. Our findings point to ATG7 as a causative genetic risk factor for cholangiocarcinoma and implicate autophagy as a novel cancer driver mechanism.
Simultaneous fluorescence imaging of tilted focal planes at two depths in thick neural tissue: Implementation with remote focus in a widefield electrophysiological microscope
Authors: Lagarde Bruno , Russell Noah , Esposito Elric , Desban Laura , Wyart Claire , Ogden David 
Published: November 2019

AbstractWide-field imaging conventionally results in a single image plane oriented perpendicular to the optical axis. However, in brain slice or in vivo recording, neuronal or circuit morphologies lie in arbitrarily tilted planes. Consequently the spatiotemporal advantages of wide-field non-scanned imaging are lost because of the time required for stepwise focal readjustments to view an entire neuron or network. We describe an application of remote focus that views simultaneously two planes separated by up to 100 µm, each with variable tilt from the conventional image plane. This permits fluorescence detection of ion fluxes or membrane potential across neuronal compartments and their correlation with electrical activity. Further, two fluorophores can be viewed simultaneously in each plane.We show (i) neuronal images tilted to optimise simultaneous aquisition of somatic, dendritic and axonal compartments; (ii) networks viewed simultaneously at 2 depths separated by up to 100 µm, (iii) widefield imaging at 30 Hz of Gcamp5 fluorescence during spontaneous spiking in motoneuron layers of zebrafish spinal cord separated by 30-40 microns.
To dereplicate or not to dereplicate?
Authors: Evans Jacob T. , Denef Vincent J. 
Published: November 2019

AbstractOur ability to reconstruct genomes from metagenomic datasets has rapidly evolved over the past decade, leading to publications presenting 1,000s, and even more than 100,000 metagenome-assembled genomes (MAGs) from 1,000s of samples. While this wealth of genomic data is critical to expand our understanding of microbial diversity, evolution, and ecology, various issues have been observed in some of these datasets that risk obfuscating scientific inquiry. In this perspective we focus on the issue of identical or highly similar genomes assembled from independent datasets. While obtaining multiple genomic representatives for a species is highly valuable, multiple copies of the same or highly similar genomes complicates downstream analysis. We analyzed data from recent studies to show the levels of redundancy within these datasets, the highly variable performance of commonly used dereplication tools, and to point to existing approaches to account and leverage repeated sampling of the same/similar populations.