bluuebunny/crossref_metadata_2025_split huggingface dataset:
α4β2* Nicotinic Cholinergic Receptor Target Engagement in Parkinson Disease Gait-Balance Disorders
Authors: Albin Roger L. , Müller Martijn L.T.M. , Bohnen Nicolaas I. , Spino Cathie , Sarter Martin , Koeppe Robert A. , Szpara Ashley , Kim Kamin , Lustig Cindy , Dauer William T. 
Published: October 2020

AbstractObjectiveAttentional function deficits secondary to degeneration of brain cholinergic systems are significant contributors to gait-balance deficits in Parkinson disease (PD). As an initial step towards assessing if α4β2* nicotinic acetylcholine receptor (nAChR) stimulation improves attention and gait-balance function, we assessed target engagement of the α4β2* nAChR partial agonist varenicline.MethodsNon-demented PD participants with cholinergic deficits were identified with [18F]fluoroethoxybenzamicol positron emission tomography (PET). α4β2* nAChR occupancy after subacute oral varenicline treatment was measured with [18F]flubatine PET. With a dose selected from the receptor occupancy experiment, varenicline effects on gait, balance, and cognition were assessed in a double-masked placebo-controlled crossover study. Primary endpoints were normal pace gait speed and a measure of postural stability.ResultsAll varenicline doses (0.25 mg per day, 0.25 mg b.i.d., 0.5 mg b.i.d., and 1.0 mg b.i.d.) produced 60% - 70% receptor occupancy. We selected 0.5 mg po b.i.d for the crossover study. Thirty-three (of thirty-four) participants, completed the crossover study with excellent tolerability. Varenicline had no significant impact on the postural stability measure and caused slower normal pace gait speed. Varenicline narrowed the difference in normal pace gait speed between dual task and no dual task gait conditions, reduced dual task cost, and improved performance on a sustained attention test. We obtained identical conclusions in 28 participants in whom treatment compliance was confirmed by plasma varenicline measurements.InterpretationVarenicline occupied a significant fraction of α4β2* nicotinic acetylcholine receptors, was tolerated well, enhanced attentional function, and altered gait performance. These results are consistent with relevant target engagement. Varenicline or similar agents may be worth further evaluation for mitigation of gait and balance disorders in PD.
Presence Of Infection By Mycobacterium Avium Subsp. Paratuberculosis In The Blood Of Patients With Crohn’s Disease And Control Subjects Shown By Multiple Laboratory Culture And Antibody Methods
Authors: Kuenstner J. Todd , Potula Raghava , Bull Tim J. , Grant Irene R. , Foddai Antonio , Naser Saleh , Bach Horacio , Zhang Peilin , Yu Daohai , Lu Xiaoning , Shafran Ira 
Published: October 2020

AbstractMycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohn’s disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to assess the degree of viable culturable MAP bacteremia in humans, definite identification of the organisms cultured and to assess if CD patients have a significantly higher rate of MAP infection compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients, two patients with CD and concurrent ulcerative colitis (UC), 14 patients with UC only and 140 non-CD controls. Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with positive Phage assay (8/9) or MAP culture (1/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.
Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19: The PRIEST observational cohort study
Authors: Goodacre Steve , Thomas Ben , Sutton Laura , Bursnall Matthew , Lee Ellen , Bradburn Mike , Loban Amanda , Waterhouse Simon , Simmonds Richard , Biggs Katie , Marincowitz Carl , Schutter Jose , Connelly Sarah , Sheldon Elena , Hall Jamie , Young Emma , Bentley Andrew , Challen Kirsty , Fitzimmons Chris , Harris Tim , Lecky Fiona , Lee Andrew , Maconochie Ian , Walter Darren 
Published: October 2020

AbstractObjectivesWe aimed to derive and validate a triage tool, based on clinical assessment alone, for predicting adverse outcome in acutely ill adults with suspected COVID-19 infection.MethodsWe undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. The primary outcome was death or organ support (respiratory, cardiovascular, or renal) by record review at 30 days. We split the cohort into derivation and validation sets, developed a clinical score based on the coefficients from multivariable analysis using the derivation set, and the estimated discriminant performance using the validation set.ResultsWe analysed 11773 derivation and 9118 validation cases. Multivariable analysis identified that age, sex, respiratory rate, systolic blood pressure, oxygen saturation/inspired oxygen ratio, performance status, consciousness, history of renal impairment, and respiratory distress were retained in analyses restricted to the ten or fewer predictors. We used findings from multivariable analysis and clinical judgement to develop a score based on the NEWS2 score, age, sex, and performance status. This had a c-statistic of 0.80 (95% confidence interval 0.79-0.81) in the validation cohort and predicted adverse outcome with sensitivity 0.98 (0.97-0.98) and specificity 0.34 (0.34-0.35) for scores above four points.ConclusionA clinical score based on NEWS2, age, sex, and performance status predicts adverse outcome with good discrimination in adults with suspected COVID-19 and can be used to support decision-making in emergency care.RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533
Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
Authors: Wagner Robert , Heni Martin , Tabak Adam G. , Machann Jürgen , Schick Fritz , Randrianarisoa Elko , de Angelis Martin Hrabě , Birkenfeld Andreas L. , Stefan Norbert , Peter Andreas , Häring Hans-Ulrich , Fritsche Andreas 
Published: October 2020

AbstractThe state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is it predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI measured body fat distribution, liver fat content, and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have immanent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.
SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations
Authors: Richmond Craig S. , Sabin Arick P. , Jobe Dean A. , Lovrich Steven D. , Kenny Paraic A. 
Published: October 2020

ABSTRACTCollege reopening decisions during the SARS-CoV-2 pandemic represent a trade-off between competing risks to students, faculty and staff, and college finances. Additionally, risks taken in reopening colleges can impose significant burdens on individuals living in surrounding communities. Many colleges that reopened for in-person instruction have reported frequent SARS-CoV-2 outbreaks. La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing of SARS-CoV-2 cases in La Crosse during that period found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. Eight sampled genomes represented two independent transmission events into two skilled nursing facilities, resulting in two fatalities. Our study highlights the very significant risks imposed by college administrator reopening decisions, not just on college-associated populations, but on vulnerable individuals in surrounding communities.
The alternative complement pathway is activated in protoporphyria patients during sun exposure
Authors: Granata Francesca , Duca Lorena , Brancaleoni Valentina , Fustinoni Silvia , De Luca Giacomo , Motta Irene , Graziadei Giovanna , Di Pierro Elena 
Published: October 2020

ABSTRACTThe homeostasis of tissues in chronic disease is an important function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells.Protoporphyria (PP) is a rare disease that causes photosensitivity at the visible light due to the accumulation of Protoporphyrin-IX in the dermis. The aim of this study was to deep the knowledge about the involvement of AP in PP photoreaction.Global radiation and UV data were provided from regional agency of environmental protection (ARPA). Properdin, Factor H (FH) and C5 levels were assessed in the serum collected during winter and summer from 19 PP patients and 13 controls..Properdin in winter and summer reflected a positive increase compared to controls. The values in summer were higher than winter. The C5 results were altered only in summer. The outcome was reversed for FH: in the winter, it was higher compared to the summer. A positive correlation was reported between properdin and C3 in summer; a negative tendency between Factor B (FB) and FH was detected.This study substantiated the differential involvement of AP depending on the increase in light exposure during the season, which was demonstrated with ARPA data. The enhanced systemic response could justify the malaise sensation of patients after long light exposure and can be exploited to elucidate the new therapeutic approach.
Rapid detection of SARS-CoV-2 antibodies in oral fluids
Authors: MacMullan Melanie A. , Chellamuthu Prithvi , Mades Aubree , Das Sudipta , Turner Fred , Slepnev Vladimir I , Ibrayeva Albina 
Published: October 2020

AbstractCurrent commercially available methods for reliably detecting antibodies against SARS-CoV-2 remain expensive and inaccessible due to the need for whole blood collection by highly trained phlebotomists using personal protective equipment (PPE). We evaluated an antibody detection approach utilizing the OraSure® Technologies’ Oral Antibody Collection Device (OACD) and their proprietary SARS-CoV-2 total antibody detection enzyme-linked immunosorbent assay (ELISA). We found that the OraSure® test for total antibody detection in oral fluid had comparable sensitivity and specificity to serum-based ELISAs while presenting a more affordable and accessible system with the potential for self-collection.
COVID-19 vaccination rate and protection attitudes can determine the best prioritisation strategy to reduce fatalities
Authors: Rodríguez Jorge , Patón Mauricio , Acuña Juan M 
Published: October 2020

AbstractBackgroundThe unprecedented rapid development of vaccines against the SARS-CoV-2 virus creates in itself a new challenge for governments and health authorities: the effective vaccination of large numbers of people in a short time and, possibly, with shortage of vaccine doses. To whom vaccinate first and in what sequence, if any at all, to avoid the most fatalities remains an open question.MethodsA compartmental model considering age-related groups was developed to evaluate and compare vaccine distribution strategies in terms of the total avoidable fatalities. Population groups are established based on relevant differences in mortality (due to e.g. their age) and risk-related traits (such as their behaviour and number of daily person-to-person interactions). Vaccination distribution strategies were evaluated for different vaccine effectiveness levels, population coverage and vaccination rate using data mainly from Spain.FindingsOur results show that, if children could also be included in the vaccination, a rollout by priority to groups with the highest number of daily person-to-person interactions can achieve large reductions in total fatalities. This is due to the importance of the avoided subsequent infections inflicted on the rest of the population by highly interactive individuals. If children are excluded from the vaccination, the differences between priority strategies become smaller and appear highly depending on rollout rate, coverage and the levels of self-protection and awareness exercised by the population.InterpretationThese results are in possible contradiction with several published plans for COVID-19 vaccination and highlight the importance of conducting an open comprehensive and thorough analysis of this problem leaving behind possible preconceptions.
Implementing a Telemedicine Curriculum for Internal Medicine Residents during a Pandemic: The Cleveland Clinic Experience
Authors: Savage David J. , Gutierrez Omar , Montane Bryce , Singh Achintya Dinesh , Yudelevich Eric , Mahar Jamal , Brateanu Andrei , Khatri Lakshmi , Fleisher Catherine , Jolly Stacey 
Published: October 2020

AbstractIntroductionTelemedicine is an important element of healthcare. However, until the COVID-19 pandemic, training in telemedicine was not a substantial element of most residency programs. Social distancing measures changed this. The Cleveland Clinic Internal Medicine Residency Program (IMRP) is one of the largest programs in the United States, which made the task of developing and adopting an effective, expedited telemedicine curriculum challenging. Our goal was to implement a system for teaching telemedicine care skills and supervising the care provided by residents during virtual visits.MethodsThis study was started in April 2020. We developed and implemented a resident-led curriculum and training program for providing telemedicine care in less than five weeks. This entailed creating a formal training program for residents, creating a resource guide for the different video communication tools, and training preceptors to safely supervise care in this new paradigm. We also created an assessment instrument in our education evaluation system that allows residents to receive feedback on their performance during virtual appointments.ResultsOver 2000 virtual visits were performed by residents in a span of 10 weeks. Of 148 residents, 38% responded to the pre-participation survey. A majority had no prior telemedicine experience and expressed only slight comfort with the modality.DiscussionThrough collaboration with experienced residents and faculty, we expeditiously developed an enhancement to our ambulatory care curriculum to teach residents how to provide virtual care and help faculty with supervision. We share our insights on this experience for other residency programs to utilize.
Antimicrobial resistance surveillance: can we estimate resistance in bloodstream infections from other types of specimen?
Authors: Vihta Karina-Doris , Gordon Nicola Claire , Stoesser Nicole , Quan T. Phuong , Tyrrell Carina SB , Vongsouvath Manivanh , Ashley Elizabeth A , Chansamouth Vilada , Turner Paul , Ling Clare L , Eyre David , White Nicholas J , Crook Derrick , Peto Tim , Walker Ann Sarah 
Published: October 2020

SynopsisBackgroundAntimicrobial resistance (AMR) surveillance of bloodstream infections is challenging in low- and middle-income countries (LMICs), limited laboratory capacity preventing routine patient-level susceptibility testing. Other specimen types could provide an effective approach to surveillance.ObjectivesOur study aims to systematically evaluate the relationship between resistance prevalence in non-sterile sites and bloodstream infections.MethodsAssociations between resistance rates in Escherichia coli and Staphylococcus aureus isolates from blood and other specimens were estimated in Oxfordshire, UK, 1998-2018, comparing proportions resistant in each calendar year using time series cross-correlations and across drug-years. We repeated analysis across publicly-available data from four high-income and 12 middle-income countries, and in three hospitals/programmes in LMICs.Results8102 E. coli bloodstream infections, 322087 E. coli urinary tract infections, 6952 S. aureus bloodstream infections and 112074 S. aureus non-sterile site cultures were included from Oxfordshire. Resistance trends over time in blood versus other specimens were strongly correlated (maximum cross-correlation 0.51-0.99, strongest associations in the same year for 18/27 pathogen-drug combinations). Resistance prevalence was broadly congruent across drug-years for each species. 276/312 (88%) species-drug-years had resistance prevalence in other specimen types within ±10% of that blood isolates. Results were similar across multiple countries and hospitals/programmes in high/middle/low income-settings.ConclusionsResistance in bloodstream and less invasive infections are strongly related over time, suggesting the latter could be a surveillance tool for AMR in LMICs. These infection sites are easier to sample and cheaper to obtain the necessary numbers of susceptibility tests, providing more cost-effective evidence for decisions including empiric antibiotic recommendations.
Indolent Presentations of Leukemic Lung Disease in Acute Myeloid Leukemia
Authors: Kunitomo Yukiko , Lee Seohyuk , Avery Chace C. , Valda Toro Patricia L. , Cohen Avi J. , Ehtashimi-Afshar Solmaz , Kahn Peter A. , Siddon Alexa , Boddu Prajwal , Datta Rupak , Dela Cruz Charles S. , Gautam Samir 
Published: October 2020

AbstractBackgroundPatients with active acute myelogenous leukemia (AML) are at risk for leukemic infiltration (LI) into the lung and acute tumor lysis pneumopathy (ATLP) following chemotherapy. Fulminant presentations of these leukemic lung diseases are well-described, but indolent forms have not yet been studied. Therefore, we sought to elucidate the clinical features of mild-to-moderate LI and ATLP.MethodsA retrospective cohort analysis was performed on 51 hospitalized patients with AML, circulating blast count ≥3%, non-critical illness, and receipt of bronchoscopy between 2015-2019. Diagnoses of LI and ATLP were made via retrospective chart review by a multidisciplinary team of physicians.Results19 cases of leukemic lung disease were identified: 14 with LI and 5 with ATLP. The clinical presentations closely resembled pneumonia, with the majority demonstrating respiratory symptoms (63%), hypoxemia (63%), fever (84%), and pulmonary opacities (100%). All patients were presumptively diagnosed with infection, leading to an average of 18 days of broad-spectrum antibiotic therapy and multiple instances of delayed chemotherapy in treatment candidates. Although most patients were near the end-of-life (90% died within 1 year), transitions to comfort care were infrequent (25%) and hospitalizations were protracted (median 25 days).ConclusionsLI and ATLP are common yet under-recognized pulmonary complications in patients with active AML. When presenting indolently, these conditions are difficult to distinguish from lung infection, leading to missed diagnosis, inappropriate antibiosis, chemotherapy deferrals, and prolonged hospitalizations. Greater awareness and consensus definitions of LI and ATLP are therefore needed to improve care of this population.
The ADEPT Study, A Comparative Study of Dentists’ Ability to Detect Enamel-only Proximal Caries in Bitewing Radiographs With and Without the use of AssistDent® Artificial Intelligence Software
Authors: Devlin Hugh , Williams Tomos , Graham Jim , Ashley Martin 
Published: October 2020

AbstractIntroductionReversal of enamel-only proximal caries by non-invasive treatments is important in preventive dentistry. However, detecting such caries using bitewing radiography is difficult, and the subtle patterns are often missed by dental practitioners.AimsTo investigate whether the ability of dentists to detect enamel-only proximal caries is enhanced by the use of AssistDent® Artificial Intelligence (AI) software.Materials and MethodsIn the ADEPT (AssistDent Enamel-only Proximal caries assessmenT) study, twenty-three dentists were randomly divided into a control arm, without AI assistance, and an experimental arm in which AI assistance provided on-screen prompts indicating potential enamel-only proximal caries. All participants analysed a set of 24 bitewings in which an expert panel had previously identified 65 enamel-only carious lesions and 241 healthy proximal surfaces.ResultsThe control group found 44.3% of the caries, whereas the experimental group found 75.8%. The experimental group incorrectly identified caries in 14.6% of the healthy surfaces compared to 3.7% in the control group. The increase in sensitivity of 71% and decrease in specificity of 11% are statistically significant (p<0.01).ConclusionsAssistDent® Artificial Intelligence software significantly improves dentists’ ability to detect enamel-only proximal caries and could be considered as a tool to support preventive dentistry in general practice.Key PointsEnamel-only proximal caries are often missed by dentists when examining bitewing radiographs.The use of AssistDent® Artificial Intelligence software results in a 71% increase in ability to detect enamel-only proximal caries accompanied by a 11% decrease in specificity.Artificial Intelligence software could be considered as a tool to support preventive dentistry in general practice.