bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of Transmission Potential During Nonsevere COVID-19 Illness
Authors: Shrestha Nabin K , Marco Canosa Francisco , Nowacki Amy S , Procop Gary W , Vogel Sherilynn , Fraser Thomas G , Erzurum Serpil C , Terpeluk Paul , Gordon Steven M 
Published: June 2020

Abstract

Background
Patients recovering from coronavirus disease 2019 (COVID-19) often continue to test positive for the causative virus by polymerase chain reaction (PCR) even after clinical recovery, thereby complicating return-to-work plans. The purpose of this study was to evaluate transmission potential of COVID-19 by examining viral load with respect to time.

Methods
Health care personnel (HCP) at Cleveland Clinic diagnosed with COVID-19, who recovered without needing hospitalization, were identified. Threshold cycles (Ct) for positive PCR tests were obtained and viral loads calculated. The association of viral load with days since symptom onset was examined in a multivariable regression model, which was reduced by stepwise backward selection to only keep variables significant at a level of .05. Viral loads by day since symptom onset were predicted using the model and transmission potential evaluated by examination of a viral load-time curve.

Results
Over 6 weeks, 230 HCP had 528 tests performed. Viral loads declined by orders of magnitude within a few days of symptom onset. The only variable significantly associated with viral load was time since onset of symptoms. Of the area under the curve (AUC) spanning symptom onset to 30 days, 96.9% lay within the first 7 days, and 99.7% within 10 days. Findings were very similar when validated using split-sample and 10-fold cross-validation.

Conclusions
Among patients with nonsevere COVID-19, viral loads in upper respiratory specimens peak by 2 or 3 days from symptom onset and decrease rapidly thereafter. The vast majority of the viral load-time AUC lies within 10 days of symptom onset.
SARS-CoV-2 Infection in Healthcare Personnel With High-risk Occupational Exposure: Evaluation of 7-Day Exclusion From Work Policy
Authors: Maltezou Helena C , Dedoukou Xanthi , Tseroni Maria , Tsonou Paraskevi , Raftopoulos Vasilios , Papadima Kalliopi , Mouratidou Elisavet , Poufta Sophia , Panagiotakopoulos George , Hatzigeorgiou Dimitrios , Sipsas Nikolaos 
Published: June 2020

Abstract

Background
As of late February 2020, Greece has been experiencing the coronavirus disease 2019 (COVID-19) epidemic. Healthcare personnel (HCP) were disproportionately affected, accounting for ~10% of notified cases. Exclusion from work for 7 days was recommended for HCP with high-risk occupational exposure. Our aim was to evaluate the 7-day exclusion from work policy for HCP with high-risk exposure.

Methods
HCP with a history of occupational exposure to COVID-19 were notified to the Hellenic National Public Health Organization, regardless of their exposure risk category. Exposed HCP were followed for 14 days after last exposure.

Results
We prospectively studied 3398 occupationally exposed HCP; nursing personnel accounted for most exposures (n = 1705; 50.2%). Of the 3398 exposed HCP, 1599 (47.1%) were classified as low-risk, 765 (22.5%) as moderate-risk, and 1031 (30.4%) as high-risk exposures. Sixty-six (1.9%) HCP developed COVID-19 at a mean of 3.65 (range: 0–17) days postexposure. Of the 66 HCP with COVID-19, 46, 7, and 13 had a history of high-, moderate- or low-risk exposure (4.5%, 0.9%, and 0.8% of all high-, moderate-, and low-risk exposures, respectively). Hospitalization and absenteeism were more prevalent among HCP with high-risk exposure. A logistic regression analysis showed that the following variables were significantly associated with an increased risk for the onset of COVID-19: male, administrative personnel, underlying disease, and high-risk exposure.

Conclusions
HCP with high-risk occupational exposure to COVID-19 had increased probability of serious morbidity, healthcare seeking, hospitalization, and absenteeism. Our findings justify the 7-day exclusion from work policy for HCP with high-risk exposure.
Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results
Authors: Budoff Matthew J , Muhlestein Joseph B , Bhatt Deepak L , Le Pa Viet T , May Heidi T , Shaikh Kashif , Shekar Chandana , Kinninger April , Lakshmanan Suvasini , Roy Sion K , Tayek John , Nelson John R 
Published: June 2020

Abstract

Aims
Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients.

Methods and results
EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40–115 mg/dL, and persistently high triglyceride levels (135–499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (−1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use.

Conclusion
EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial.

ClinicalTrials. govIdentifier
NCT029226027.
Class switching and high-affinity immunoglobulin G production by B cells is dispensable for the development of hypertension in mice
Authors: Chen Yuhan , Dale Bethany L , Alexander Matthew R , Xiao Liang , Ao Mingfang , Pandey Arvind K , Smart Charles D , Davis Gwendolyn K , Madhur Meena S 
Published: June 2020

Abstract

Aims
Elevated serum immunoglobulins have been associated with experimental and human hypertension for decades but whether immunoglobulins and B cells play a causal role in hypertension pathology is unclear. In this study, we sought to determine the role of B cells and high-affinity class-switched immunoglobulins on hypertension and hypertensive end-organ damage to determine if they might represent viable therapeutic targets for this disease.

Methods and results
We purified serum immunoglobulin G (IgG) from mice exposed to vehicle or angiotensin (Ang) II to induce hypertension and adoptively transferred these to wild type (WT) recipient mice receiving a subpressor dose of Ang II. We found that transfer of IgG from hypertensive animals does not affect blood pressure, endothelial function, renal inflammation, albuminuria, or T cell-derived cytokine production compared with transfer of IgG from vehicle infused animals. As an alternative approach to investigate the role of high-affinity, class-switched immunoglobulins, we studied mice with genetic deletion of activation-induced deaminase (Aicda−/−). These mice have elevated levels of IgM but virtual absence of class-switched immunoglobulins such as IgG subclasses and IgA. Neither male nor female Aicda−/− mice were protected from Ang II-induced hypertension and renal/vascular damage. To determine if IgM or non-immunoglobulin-dependent innate functions of B cells play a role in hypertension, we studied mice with severe global B-cell deficiency due to deletion of the membrane exon of the IgM heavy chain (µMT−/−). µMT−/− mice were also not protected from hypertension or end-organ damage induced by Ang II infusion or deoxycorticosterone acetate-salt treatment.

Conclusions
These results suggest that B cells and serum immunoglobulins do not play a causal role in hypertension pathology.
Early glycaemic changes after initiation of oral antidiabetic medication and risk of major adverse cardiovascular events: results from a large primary care population of patients with type 2 diabetes
Authors: Ghouse Jonas , Blanche Paul , Skov Morten W , Lind Bent , Vaag Allan , Kanters Jørgen K , Svendsen Jesper H , Køber Lars , Olesen Morten S , Gerds Thomas A , Holst Anders G , Nielsen Jonas B 
Published: June 2020

Abstract

Aims
To determine the risk of major adverse cardiovascular events (MACE) and death, associated with an early large and rapid decline in glycated haemoglobin (HbA1C) following first time initiation of an oral antidiabetic drug (OAD).

Methods and results
We included 10 518 primary care patients with type 2 diabetes, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.5–4.5 months after OAD initiation), divided by the time between the two measurements. The decline was reported in mmol/mol change per 3 months in HbA1C and categorized by the median decline into levels of steep [≥9 mmol/mol (≥0.8%)] and flat decline [&lt;9 mmol/mol per 3 months (&lt;0.8%)]. Pre-treatment HbA1C was categorized by the median, into levels of low (48–62 mmol/mol) and high (&gt;62 mmol/mol). Multiple Cox regression was used to study the effect of decline (steep vs. flat) on the outcome hazard rates separately for patients with low and high pre-treatment HbA1C. Analyses were adjusted for age, sex, traditional cardiovascular risk factors, severe comorbidities, and concomitant medication treatment. During a median follow-up time of 7.7 years, 1625 developed MACE and 2323 died. We found that a steep decline vs. a flat decline was significantly associated with a decreased hazard for MACE, both in individuals with high [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.69–0.94; P = 0.005] and low pre-treatment HbA1C (HR 0.79; 95% CI 0.66–0.96; P = 0.015). The hazard of MACE was more pronounced on the short-term vs. long-term in individuals with high pre-treatment HbA1C. We found no significant association between combinations of pre-treatment HbA1C and decline categories and hazard of all-cause mortality. However, a combination of a low pre-treatment HbA1C and steep decline was associated with increased 1-year mortality (HR 1.52; 95% CI 1.00–2.29; P = 0.048) and hypoglycaemia (HR 1.82; 95% CI 1.11–2.98; P = 0.017).

Conclusion
A combination of a high pre-treatment HbA1C and a steep decline in HbA1C was associated with a decreased short-term risk of MACE. A low pre-treatment HbA1C and a steep decline was associated with a long-term reduced risk of MACE, but a short-term increased risk of death and hypoglycaemia.
Challenges and strategies for ELF-aware teacher development
Authors: Choi Koun , Liu Yongcan 
Published: June 2020

Abstract
Teachers play a crucial role in the implementation of an English as a lingua franca (ELF) perspective in the classroom. However, little research has been conducted on what challenges teachers might encounter and what types of support are needed to teach English from an ELF perspective. This study thus explores the experiences of seven primary teachers enrolled in a teacher development programme designed to support their attempts to teach from an ELF perspective in South Korea. Drawing on in-depth interview data, the paper provides detailed accounts of the challenges and strategies for developing ELF-aware teachers. The main challenges encountered included a lack of the pedagogical skills required to implement planned lessons, the paucity of relevant instructional materials, and parents’ strong preference for Standard English. It is possible, however, that these challenges could be addressed by creating opportunities for guided reflection, peer collaboration, and effective communication. Implications for future ELF-aware teacher development programmes are also discussed.
Complementary effectiveness of carotid sinus massage and tilt testing for the diagnosis of reflex syncope in patients older than 40 years: a cohort study
Authors: Brignole Michele , Kessisoglu Federica , Croci Francesco , Solano Alberto , Donateo Paolo , Maggi Roberto , Solari Diana , Bertolone Cristina , Fontana Daniele , Oddone Daniele , Rivasi Giulia , Rafanelli Martina , Casini Niccolò , Ungar Andrea 
Published: June 2020

Abstract

Aims
Indications, methodology, and diagnostic criteria for carotid sinus massage (CSM) and tilt testing (TT) have been standardized by the 2018 Guidelines on Syncope of the European Society of Cardiology. Aim of this study was to assess their effectiveness in a large cohort which reflects the performance under ‘real-world’ conditions.

Methods and results
We analysed all patients who had undergone CSM and TT in the years 2003–2019 for suspected reflex syncope. Carotid sinus massage was performed according to the ‘Method of Symptoms’. Tilt testing was performed according to the ‘Italian protocol’ which consists of a passive phase followed by a sublingual nitroglycerine phase. For both tests, positive test was defined as reproduction of spontaneous symptoms in the presence of bradycardia and/or hypotension. Among 3293 patients (mean age 73 ± 12 years, 48% males), 2019 (61%) had at least one test positive. A bradycardic phenotype was found in 420 patients (13%); of these, 60% were identified by CSM, 37% by TT, and 3% had both test positive. A hypotensive phenotype was found in 1733 patients (53%); of these, 98% were identified by TT and 2% had both TT and CSM positive.

Conclusion
The overall diagnostic yield of the tests in patients &gt;40-year-old with suspected reflex syncope was 61%. Both CSM and TT are useful for identifying those patients with a bradycardic phenotype, whereas CSM has a limited value for identifying the hypotensive phenotype. Since the overlap of responses between tests is minimal, both CSM and TT should be performed in every patient over 40 years receiving investigation for unexplained but possible reflex syncope.
Polyphasic taxonomic analysis of Nitratireductor arenosus sp. nov., isolated from sea sand
Authors: Baek Jihye , Kim Jong-Hwa , Jeong Jiseon , Yoon Jung-Hoon , Sukhoom Ampaitip , Kim Wonyong 
Published: June 2020

ABSTRACT
A novel proteobacterial bacterium, designated strain CAU 1489T, was isolated from Jeju Island, Republic of Korea. Cells were strictly anaerobic, Gram stain-negative, cream-pigmented, non-spore-forming, motile and short rod-shaped. Strain CAU 1489T exhibited the highest 16S rRNA gene sequence similarity (98.2%) to Nitratireductor mangrovi SY7T. Multilocus sequence analysis of 16S rRNA and four housekeeping genes (rpoB, rpoC, gyrB and dnaK) indicated that CAU 1489T represents a distinct branch within Nitratireductor. The whole genome was 4.8 Mb with a G + C content of 64.7 mol%, including protein-coding genes related to the function terms amino acids and derivatives, nucleotides and nucleosides, protein metabolism, carbohydrates and cofactors, vitamins, prosthetic groups and pigments. The major fatty acids were 11-methyl C18:1ω7c, cyclo- C19:0ω8c, iso-C17:0 and summed feature 8 (C18:1ω6c and/or C18:1ω7c), and the predominant respiratory quinone was Q-10. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and two unidentified phospholipids. Digital DNA–DNA hybridization and average nucleotide identity values were 19.4–22.0% and 72.4–79.1%, respectively. On the basis of taxonomic characterization, strain CAU 1489T constitutes a novel species, for which the name Nitratireductor arenosus sp. nov. is proposed. The type strain is CAU 1489T ( = KCTC 62997T = NBRC 113694T).
Ubiquity and functional uniformity in CO2 concentrating mechanisms in multiple phyla of Bacteria is suggested by a diversity and prevalence of genes encoding candidate dissolved inorganic carbon transporters
Authors: Scott Kathleen M , Harmer Tara L , Gemmell Bradford J , Kramer Andrew M , Sutter Markus , Kerfeld Cheryl A , Barber Kourtney S , Bari Saaurav , Boling Joshua W , Campbell Cassandra P , Gallard-Gongora Javier F , Jackson Jessica K , Lobos Aldo , Mounger Jeannie M , Radulovic Peter W , Sanson Jacqueline M , Schmid Sarah , Takieddine Candice , Warlick Kiley F , Whittaker Robert 
Published: June 2020

ABSTRACT
Autotrophic microorganisms catalyze the entry of dissolved inorganic carbon (DIC; = CO2 + HCO3− + CO32−) into the biological component of the global carbon cycle, despite dramatic differences in DIC abundance and composition in their sometimes extreme environments. “Cyanobacteria” are known to have CO2 concentrating mechanisms (CCMs) to facilitate growth under low CO2 conditions. These CCMs consist of carboxysomes, containing enzymes ribulose 1,5-bisphosphate oxygenase and carbonic anhydrase, partnered to DIC transporters. CCMs and their DIC transporters have been studied in a handful of other prokaryotes, but it was not known how common CCMs were beyond “Cyanobacteria”. Since it had previously been noted that genes encoding potential transporters were found neighboring carboxysome loci, α-carboxysome loci were gathered from bacterial genomes, and potential transporter genes neighboring these loci are described here. Members of transporter families whose members all transport DIC (CHC, MDT and Sbt) were common in these neighborhoods, as were members of the SulP transporter family, many of which transport DIC. 109 of 115 taxa with carboxysome loci have some form of DIC transporter encoded in their genomes, suggesting that CCMs consisting of carboxysomes and DIC transporters are widespread not only among “Cyanobacteria”, but also among members of “Proteobacteria” and “Actinobacteria”.
Multiple Invasions of Visitor, a DD41D Family of Tc1/mariner Transposons, throughout the Evolution of Vertebrates
Authors: Shen Dan , Gao Bo , Miskey Csaba , Chen Cai , Sang Yatong , Zong Wencheng , Wang Saisai , Wang Yali , Wang Xiaoyan , Ivics Zoltán , Song Chengyi 
Published: June 2020

Abstract
Although the DD41D (named as Visitor, VS) family of Tc1/mariner transposons was discovered in Arthropods and Mollusca, the evolution profile of this family is still largely unknown. We found that VS is widespread in the animal kingdom, including 140 species of 18 orders in invertebrates and 30 species of 12 orders in vertebrates, and one land plant species. Our data revealed multiple horizontal transfer events in both invertebrates and vertebrates and invasion into multiple lineages of mammals, including Chiroptera (seven species), Dasyuromorphia/Marsupialia (one species), Didelphimorphia/Marsupialia (one species), Diprotodontia/Marsupialia (two species), and Primates (one species). Phylogenetic analysis revealed a close relationship of VSs to DD37D/maT and DD34D/mariner and confirmed that VSs with the DD40D signature identified previously are not a distinct family but originated from DD41D/VS. Age analysis revealed that the most recent invasion of VSs was found in ray-finned fishes and a toad, followed by relatively young invasions in bats and marsupials, whereas VSs in mammals, jawless fishes, and lizards were mainly represented by ancient copies, suggesting old age. Phylogenetic analyses and comparison of pairwise distances between VSs and recombination-activating gene 1 (RAG1) support horizontal transfer events of VSs in vertebrates. The intact VSs from bats were nonfunctional as determined by the transposition activity assay. Some vertebrate lineages and species were identified as the hot hosts of Tc1/mariner transposons. Overall, our study presents the evolution profile of VSs and suggests that VSs play roles in diversifying and shaping the genomes of diverse animal lineages.
The ACE (Albumin, CRP and Endoscopy) Index in Acute Colitis: A Simple Clinical Index on Admission that Predicts Outcome in Patients With Acute Ulcerative Colitis
Authors: Grant Rebecca K , Jones Gareth-Rhys , Plevris Nikolas , Lynch Ruairi W , Jenkinson Philip W , Lees Charlie W , Manship Thomas A , Jagger Fiona A M , Brindle William M , Shivakumar Mrithula , Satsangi Jack , Arnott Ian D R 
Published: June 2020

Abstract

Background
Intravenous (IV) steroids remain the first-line treatment for patients with acute ulcerative colitis (UC). However, 30% of patients do not respond to steroids, requiring second-line therapy and/or surgery. There are no existing indices that allow physicians to predict steroid nonresponse at admission. We aimed to determine if admission biochemical and endoscopic values could predict response to IV steroids.

Methods
All admissions for acute UC (ICD-10 K51) between November 1, 2011, and October 31, 2016 were identified. Case note review confirmed diagnosis; clinical, endoscopic, and laboratory data were collected. Steroid response was defined as discharge home with no further therapy for active UC. Nonresponse was defined as requirement for second-line therapy or surgery. Univariate and binary logistic regression analyses were employed to identify factors associated with steroid nonresponse.

Results
Two hundred and thirty-five acute UC admissions were identified, comprising both acute severe and acute nonsevere UC; 155 of the 235 patients (66.0%) responded to steroids. Admission C-reactive protein (CRP) (P = 0.009, odds ratio [OR] 1.006), albumin (P &lt; 0.001, OR 0.894) and endoscopic severity (P &lt; 0.001, OR 3.166) differed significantly between responders and nonresponders. A simple UC severity score (area under the curve [AUC] 0.754, P &lt; 0.001) was derived from these variables; 78.1% (25 of 32) of patients with concurrent CRP ≥50 mg/L, albumin ≤30 g/L, and increased endoscopic severity (severe on physician’s global assessment) (maximum score = 3) did not respond to IV steroids (positive predictive value [PPV] 78.1%, negative predictive value [NPV] 87.1%).

Conclusions
More than three quarters of patients scoring 3 (albumin ≤30 g/L, CRP ≥50 mg/L, and increased endoscopic severity) did not respond to IV steroids. This combination of parameters (ACE) identifies on admission a high-risk population who may benefit from earlier second-line medical treatment or surgical intervention.