bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling population III stars for seminumerical simulations
Authors: Tanaka Toshiyuki , Hasegawa Kenji 
Published: January 2021

ABSTRACT
Theoretically modelling the 21-cm signals caused by Population III stars (Pop III stars) is the key to extracting fruitful information on Pop III stars from current and forthcoming 21-cm observations. In this work, we develop a new module of Pop III stars in which the escape fractions of ionizing photons and Lyman–Werner (LW) photons, photoheating by UV radiation, and LW feedback are consistently incorporated. By implementing the module into a public 21-cm seminumerical simulation code, 21cmfast, we demonstrate 21-cm signal calculations, neglecting X-ray heating and focusing on the high redshifts when we assume that the formation of Pop III stars dominates that of other populations. What we find is that the contribution from Pop III stars to cosmic reionization significantly depends on the treatment of the escape fraction. With our escape fraction model, Pop III stars hardly contribute to reionization because less massive haloes, whose escape fraction are high, cannot host Pop III stars due to LW feedback. On the other hand, massive minihaloes contribute to reionization with the conventional constant escape fraction. We also find that UV photoheating has non-negligible impact on the 21-cm global signal and the 21-cm power spectrum if the ionization fraction of the Universe is higher than roughly 1 per cent. In this case, the strength of the 21-cm global signal depends on the photoheating efficiency and thus on the Pop III star mass. We conclude that detailed modelling of Pop III stars is imperative to predict 21-cm observables accurately for future observations.
A genome-wide strategy to identify causes and consequences of retrotransposon expression finds activation by BRCA1 in ovarian cancer
Authors: Alkailani Maisa , Palidwor Gareth , Poulin Ariane , Mohan Raghav , Pepin David , Vanderhyden Barbara , Gibbings Derrick 
Published: January 2021

AbstractIt is challenging to identify the causes and consequences of retrotransposon expression in human disease due to the hundreds of active genomic copies and their poor conservation across species. We profiled genomic insertions of retrotransposons in ovarian cancer. In addition, in ovarian and breast cancer we analyzed RNAs exhibiting Bayesian correlation with retrotransposon RNA to identify causes and consequences of retrotransposon expression. This strategy finds divergent inflammatory responses associated with retrotransposon expression in ovarian and breast cancer and identifies new factors inducing expression of endogenous retrotransposons including anti-viral responses and the common tumor suppressor BRCA1. In cell lines, mouse ovarian epithelial cells and patient-derived tumor spheroids, BRCA1 promotes accumulation of retrotransposon RNA. BRCA1 promotes transcription of active families of retrotransposons and their insertion into the genome. Intriguingly, elevated retrotransposon expression predicts survival in ovarian cancer patients. Retrotransposons are part of a complex regulatory network in ovarian cancer including BRCA1 that contributes to patient survival. The described strategy can be used to identify the regulators and impacts of retrotransposons in various contexts of biology and disease in humans.
Water transport to the core–mantle boundary
Authors: Walter Michael J 
Published: January 2021

Abstract
Water is transported to Earth's interior in lithospheric slabs at subduction zones. Shallow dehydration fuels hydrous island arc magmatism but some water is transported deeper in cool slab mantle. Further dehydration at ∼700 km may limit deeper transport but hydrated phases in slab crust have considerable capacity for transporting water to the core-mantle boundary. Quantifying how much remains the challenge.
Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam for the Treatment of Multidrug-Resistant Gram-Negative Infections
Authors: Wilson Geneva M , Fitzpatrick Margaret , Walding Kyle , Gonzalez Beverly , Schweizer Marin L , Suda Katie J , Evans Charlesnika T 
Published: January 2021

AbstractCeftolozane-tazobactam (C/T), ceftazidime-avibactam (C/A), and meropenem/vaborbactam (M/V) are new beta-lactam/beta-lactamase combination antibiotics commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections. This review reports the clinical success rates for C/T, C/A, and M/V. PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for publications detailing the use of C/T, C/A, and M/V. A meta-analysis determined the pooled effectiveness of C/T, C/A, and M/V. The literature search returned 1950 publications; 29 publications representing 1620 patients were retained. Pneumonia was the predominant infection type (49.8%). MDRPA was the major pathogen treated (65.3%). The pooled clinical success rate was 73.3% (95% CI, 68.9%–77.5%). C/T, C/A, or M/V resistance was reported in 8.9% of the population. These antibiotics had a high clinical success rate in patients with complicated infections and limited treatment options. Larger studies comparing C/T, C/A, and M/V against other antibiotic regimens are needed.
SARS-CoV-2 Seroconversion and Viral Clearance in Patients Hospitalized With COVID-19: Viral Load Predicts Antibody Response
Authors: Masiá Mar , Telenti Guillermo , Fernández Marta , García José A , Agulló Vanesa , Padilla Sergio , García-Abellán Javier , Guillén Lucía , Mascarell Paula , Asenjo José C , Gutiérrez Félix 
Published: January 2021

Abstract

Background
The interdependencies of viral replication and the host immune response in patients with coronavirus disease 2019 (COVID-19) remain to be defined. We investigated the viral determinants of antibody response, the predictors of nonseroconversion, and the role of antibodies on viral dynamics.

Methods
This was a prospective study in patients hospitalized with COVID-19 that was microbiologically confirmed by real-time polymerase chain reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies (total and S-IgG/N-IgG), respectively.

Results
Of 132 patients included, 99 (75%) showed positive antibody titers after a median (Q1–Q3) of 11 (8–14) days. The median (Q1–Q3) follow-up was 74.5 (63.0–87.0) days. In an adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load (P = .009) and positively with time to viral clearance (P = .004). Adjusted predictors of S-IgG levels were time to viral clearance (P &lt; .001), bilateral lung infiltrates on admission (P = .011), and the time-dependent SARS-CoV-2 RNA (P &lt; .001) and SARS-CoV-2 RNA area under the curve (P = .001). Thirty-three (25%) patients showed undetectable antibody titers. Patients who did not seroconvert had higher cycle threshold values of RT-PCR (38.0 vs 28.0; P &lt; .001), had shorter time to viral clearance (3.0 vs 41.0; P &lt; .001), and were more likely to have SARS-CoV-2 only detected on fecal samples (P &lt; .001). Nonseroconvertors had also lower levels of blood inflammatory biomarkers on admission and lower disease severity.

Conclusions
Viral replication determines the magnitude of antibody response to SARS-CoV-2, which, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.
Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study
Authors: Isfordink Cas J , van de Laar Thijs J W , Rebers Sjoerd P H , Wessels Els , Molenkamp Richard , Knoester Marjolein , Baak Bert C , van Nieuwkoop Cees , van Hoek Bart , Brakenhoff Sylvia M , Blokzijl Hans , Arends Joop E , van der Valk Marc , Schinkel Janke ,   HepNed Study Group, Willemse Sophie , Erken Robin , Bomers Marije , Ramsoekh Dewkoemar , Amsterdam U M C , de Knegt Rob , de Man Rob , Rijnders Bart , Erasmus M C , van Soest Hanneke , Haaglanden M C , Koek Ger , Posthouwer Dirk , Koc Ozgür , Maastricht U M C , Burger David , van Dijk Marleen , Drenth Joost , von den Hoff Daan , Radboud U M C , Brouwer Johannes , de Graaf Gasthuis Reinier , Boland Greet , van Erpecum Karel , Utrecht U M C 
Published: January 2021

Abstract

Background
The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands.

Methods
We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation.

Results
We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3–infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS.

Conclusions
The DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.
The Clinical Course of COVID-19 in the Outpatient Setting: A Prospective Cohort Study
Authors: Blair Paul W , Brown Diane M , Jang Minyoung , Antar Annukka A R , Keruly Jeanne C , Bachu Vismaya S , Townsend Jennifer L , Tornheim Jeffrey A , Keller Sara C , Sauer Lauren , Thomas David L , Manabe Yukari C ,   Ambulatory COVID Study Team, Cox Andrea L , Heaney Chris D , Klein Sabra L , Mehta Shruti H , Mostafa Heba , Pekosz Andy S , Pisanic Nora , Smith L Leigh , Armstrong Derek T , Azamfirei Razvan , Barnaba Brittany , Charles Curtisha , Church Taylor , Dai Weiwei , Fuchs Joelle , Ganesan Abhinaya , Hardick Justin , Holden Jeffrey , Johnstone Jaylynn R , Kruczynski Kate , Kusemiju Oyinkansola , Lambrou Anastasia , Li Lucy , Littlefield Kirsten , Montana Manuela Plazas , Park Han-Sol , Payton Christine B , Popper Caroline , Prizzi Michelle , Reuland Carolyn J , Sewell Thelio , Tuchler Amanda , Ursin Rebecca L , Walch Samantha N 
Published: January 2021

AbstractBackgroundOutpatient coronavirus disease 2019 (COVID-19) has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a prospective cohort study.MethodsOutpatient adults with positive reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited by phone between April 21 and July 23, 2020, after receiving outpatient or emergency department testing within a large health network in Maryland, United States. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28, and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial and logistic regression.ResultsAmong 118 SARS-CoV-2-infected outpatients, the median age (interquartile range [IQR]) was 56.0 (50.0–63.0) years, and 50 (42.4%) were male. Among individuals in the first week of illness (n = 61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median (IQR) of 20 (13–38) days from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiver operating characteristics curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (95% CI, 0.73–0.99).ConclusionsSymptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.
Sleep walking copepods? Calanus diapausing in hypoxic waters adjust their vertical position during winter
Authors: Kaartvedt Stein , Røstad Anders , Titelman Josefin 
Published: January 2021

Abstract
While hypoxia is generally associated with negative connotations, some animals may also take advantage of reduced oxygen concentrations. However, the dynamics of such processes for zooplankton are poorly understood. We made continuous acoustic studies of Calanus helgolandicus overwintering in hypoxic waters (Oslofjorden, Norway). Their apparent minimum oxygen tolerance was 0.2–0.3 mL O2 L−1 at 8°C. The copepods adjusted their vertical distribution in concert with the upward progression of hypoxia as oxygen contents declined in the course of winter. The hypoxic overwintering habitat largely excluded potential predators and mortality appeared low in early winter. As the copepod distribution shallowed in phase with declining oxygen contents at depth, mortality increased. In contrast to recent predictions, C. helgolandicus had sufficient energy reserves to sustain long-term overwintering. Termination of the overwintering phase in spring was gradual but appeared to accelerate during the development of the spring bloom. Enhanced oceanic deoxygenation with climate change may affect seasonally migrating copepods in unpredictable ways.
Beta interferons as immunotherapy in multiple sclerosis: a new outlook on a classic drug during the COVID-19 pandemic
Authors: Dumitrescu L , Papathanasiou A , Coclitu C , Constantinescu C S , Popescu B O , Tanasescu R 
Published: January 2021

Abstract
Beta interferons (IFN-β) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-β preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of ‘smart’ autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-β. Here, we present the IFN-β-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-β in the treatment of COVID-19 is also briefly discussed.
Methamphetamine and sleep impairments: neurobehavioral correlates and molecular mechanisms
Authors: Vrajová Monika , Šlamberová Romana , Hoschl Cyril , Ovsepian Saak V 
Published: January 2021

Abstract
Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have been on a rapid rise, with growing detrimental effects on mental and physical health, and devastating psychosocial impact pressing for intervention. Among the unwanted effects of methamphetamine, acute and long-term sleep impairments are of major concern, posing a significant therapeutic challenge, and a cause of addiction relapse. Unraveling mechanisms and functional correlates of methamphetamine-related sleep and circadian disruption are, therefore, of key relevance to translational and clinical psychiatry. In this article, we review the mounting evidence for the acute and long-term impairements of sleep–wake behavior and circadian activity caused by single or recurring methamphetamine usage and withdrawal. Factors contributing to the severity of sleep loss and related cognitive deficit, with risks of relapse are discussed. Key molecular players mediating methamphetamine-induced dopamine release and neuromodulation are considered, with wake-promoting effects in mesolimbic circuits. The effects on various sleep phases and related changes in dopamine levels in selected subcortical structures are reviewed and compared to other psychostimulants with similar action mechanisms. A critical appraisal is presented of the therapeutic use of modafinil, countering sleep, and circadian rhythm impairments. Finally, emerging knowledge gaps and methodical limitations are highlighted along with the areas for future research and therapeutic translation.
Association of objectively measured sleep with frailty and 5-year mortality in community-dwelling older adults
Authors: Guida Jennifer L , Alfini Alfonso J , Gallicchio Lisa , Spira Adam P , Caporaso Neil E , Green Paige A 
Published: January 2021

Abstract

Study Objectives
To determine whether actigraphy-measured sleep was independently associated with risk of frailty and mortality over a 5-year period among older adults.

Methods
We used data from Waves 2 (W2) and 3 (W3) (2010–2015) of the National Social Life, Health and Aging Project, a prospective cohort of community-dwelling older adults born between 1920 and 1947. One-third of W2 respondents were randomly selected to participate in a sleep study, of whom N = 727 consented and N = 615 were included in the analytic sample. Participants were instructed to wear a wrist actigraph for 72 h (2.93 ± 0.01 nights). Actigraphic sleep parameters were averaged across nights and included total sleep time, percent sleep, sleep fragmentation index, and wake after sleep onset. Subjective sleep was collected via questionnaire. Frailty was assessed using modified Fried Frailty Index. Vital status was ascertained at the time of the W3 interview. W3 frailty/mortality status was analyzed jointly with a four-level variable: robust, pre-frail, frail, and deceased. Associations were modeled per 10-unit increase.

Results
After controlling for baseline frailty (robust and pre-frail categories), age, sex, education, body mass index, and sleep time preference, a higher sleep fragmentation index was associated with frailty (OR = 1.70, 95% CI: 1.02–2.84) and mortality (OR = 2.12, 95% CI: 1.09–4.09). Greater wake after sleep onset (OR = 1.24, 95% CI: 1.02–1.50) and lower percent sleep (OR = 0.41, 95% CI: 0.17–0.97) were associated with mortality.

Conclusions
Among community-dwelling older adults, actigraphic sleep is associated with frailty and all-cause mortality over a 5-year period. Further investigation is warranted to elucidate the physiological mechanisms underlying these associations.
Identifying and characterizing longitudinal patterns of insomnia across the deployment cycle in active duty Army soldiers
Authors: Miller Katherine E , Ramsey Christine M , Boland Elaine M , Klingaman Elizabeth A , Gehrman Philip 
Published: January 2021

Abstract

Study Objectives
The present study characterized a sample of 4,667 Army soldiers based on their patterns of insomnia before, during, and after deployment, and explored pre-deployment factors predictive of these patterns.

Methods
Data were analyzed from the Army Study to Assess Risk and Resilience in Service members (STARRS)—Pre/Post Deployment Study (PPDS), using surveys that captured data approximately 1–2 months pre-deployment, and 3- and 9-month post-deployment from soldiers deployed to Afghanistan. Patterns of insomnia across time were examined. Theoretically derived variables linked to sleep disturbance were examined as predictors of the insomnia patterns.

Results
Five longitudinal patterns of insomnia characterized the majority of the sample: “No Insomnia” (no insomnia symptoms at any timepoint; 31%), “Deployment-related Insomnia” (no pre-deployment insomnia, developed insomnia symptoms during deployment and recovered; 40%), “Incident Insomnia” (development insomnia during or shortly after deployment that did not remit; 14%), “Chronic Insomnia” (insomnia both pre- and post-deployment; 11%), and “Other Insomnia” (reported insomnia at ≥1 timepoint, but no clear pattern across the deployment cycle; 4%). Several pre-deployment factors were predictive of insomnia trajectories, including lifetime major depressive episodes, traumatic brain injury history, posttraumatic stress disorder, and past year personal life stressors.

Conclusions
Distinct longitudinal patterns of insomnia were identified, with more than half of the sample reporting insomnia at some point in the deployment cycle. Identifying mental health conditions that are associated with different insomnia patterns prior to deployment can inform targeted interventions to reduce long-term sleep difficulty.
Implications of the COVID-19 pandemic in eliminating trachoma as a public health problem
Authors: Blumberg Seth , Borlase Anna , Prada Joaquin M , Solomon Anthony W , Emerson Paul , Hooper Pamela J , Deiner Michael S , Amoah Benjamin , Hollingsworth T Déirdre , Porco Travis C , Lietman Thomas M 
Published: January 2021

AbstractBackgroundProgress towards elimination of trachoma as a public health problem has been substantial, but the coronavirus disease 2019 (COVID-19) pandemic has disrupted community-based control efforts.MethodsWe use a susceptible-infected model to estimate the impact of delayed distribution of azithromycin treatment on the prevalence of active trachoma.ResultsWe identify three distinct scenarios for geographic districts depending on whether the basic reproduction number and the treatment-associated reproduction number are above or below a value of 1. We find that when the basic reproduction number is &lt;1, no significant delays in disease control will be caused. However, when the basic reproduction number is &gt;1, significant delays can occur. In most districts, 1 y of COVID-related delay can be mitigated by a single extra round of mass drug administration. However, supercritical districts require a new paradigm of infection control because the current strategies will not eliminate disease.ConclusionsIf the pandemic can motivate judicious, community-specific implementation of control strategies, global elimination of trachoma as a public health problem could be accelerated.