bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTEGRAL/IBIS 17-yr hard X-ray all-sky survey
Authors: Krivonos Roman A , Sazonov Sergey Yu , Kuznetsova Ekaterina A , Lutovinov Alexander A , Mereminskiy Ilya A , Tsygankov Sergey S 
Published: December 2021

ABSTRACT
The International Gamma-Ray Astrophysics Laboratory (INTEGRAL), launched in 2002, continues its successful work in observing the sky at energies E &gt; 20 keV. The legacy of the mission already includes a large number of discovered or previously poorly studied hard X-ray sources. The growing INTEGRAL archive allows one to conduct an all-sky survey including a number of deep extragalactic fields and the deepest ever hard X-ray survey of the Galaxy. Taking advantage of the data gathered over 17 yr with the IBIS coded-mask telescope of INTEGRAL, we conducted survey of hard X-ray sources, providing flux information from 17 to 290 keV. The catalogue includes 929 objects, 890 of which exceed a detection threshold of 4.5σ and the rest are detected at 4.0σ–4.5σ and belong to known catalogued hard X-ray sources. Among the identified sources of known or suspected nature, 376 are associated with the Galaxy and Magellanic clouds, including 145 low-mass and 115 high-mass X-ray binaries, 79 cataclysmic variables, and 37 of other types; and 440 are extragalactic, including 429 active galactic nuclei (AGNs), 2 ultra-luminous sources, 1 supernova (AT2018cow), and 8 galaxy clusters. 113 sources remain unclassified. 46 objects are detected in the hard X-ray band for the first time. The LogN-LogS distribution of 356 non-blazar AGNs is measured down to a flux of 2 × 10−12 erg s−1 cm−2 and can be described by a power law with a slope of 1.44 ± 0.09 and normalization 8 × 10−3 deg−2 at 10−11 erg s−1 cm−2. The LogN-LogS distribution of unclassified sources indicates that the majority of them are of extragalactic origin.
The impact of black hole feedback on the UV luminosity and stellar mass assembly of high-redshift galaxies
Authors: Piana Olmo , Dayal Pratika , Choudhury Tirthankar Roy 
Published: December 2021

ABSTRACT
We employ the Delphi semi-analytical model to study the impact of black hole growth on high-redshift galaxies, both in terms of the observed ultraviolet (UV) luminosity and of the star formation rate. To do this, first, we assess the contribution of active galactic nuclei (AGN) to the total galaxy UV luminosity as a function of stellar mass and redshift. We find that for MUV ≲ −24 mag and z ≈ 5−6, the galaxies for which the black hole UV luminosity outshines the stellar UV emission become the majority, and we estimate their duty cycle. Secondly, we study the evolution of the AGN and stellar luminosity functions (LFs), finding that it is driven both by changes in their characteristic luminosities (i.e. evolution of the intrinsic brightness of galaxies) and in their normalizations (i.e. evolution of the number densities of galaxies), depending on the luminosity range considered. Finally, we follow the mass assembly history for three different halo mass bins, finding that the magnitude of AGN-driven outflows depends on the host halo mass. We show that AGN feedback is most effective when the energy emitted by the accreting black hole is approximately $1{{\ \rm per\ cent}}$ of the halo binding energy, and that this condition is met in galaxies in haloes with $M_\mathrm{h} \sim 10^{11.75} \, {\rm \rm M_\odot }$ at z = 4. In such cases, AGN feedback can drive outflows that are up to 100 times more energetic than supernovae-driven outflows, and the star formation rate is a factor of 3 lower than for galaxies of the same mass without black hole activity.
Phylogeography Reveals Association between Swine Trade and the Spread of Porcine Epidemic Diarrhea Virus in China and across the World
Authors: He Wan-Ting , Bollen Nena , Xu Yi , Zhao Jin , Dellicour Simon , Yan Ziqing , Gong Wenjie , Zhang Cheng , Zhang Letian , Lu Meng , Lai Alexander , Suchard Marc A , Ji Xiang , Tu Changchun , Lemey Philippe , Baele Guy , Su Shuo 
Published: December 2021

Abstract
The ongoing SARS (severe acute respiratory syndrome)-CoV (coronavirus)-2 pandemic has exposed major gaps in our knowledge on the origin, ecology, evolution, and spread of animal coronaviruses. Porcine epidemic diarrhea virus (PEDV) is a member of the genus Alphacoronavirus in the family Coronaviridae that may have originated from bats and leads to significant hazards and widespread epidemics in the swine population. The role of local and global trade of live swine and swine-related products in disseminating PEDV remains unclear, especially in developing countries with complex swine production systems. Here, we undertake an in-depth phylogeographic analysis of PEDV sequence data (including 247 newly sequenced samples) and employ an extension of this inference framework that enables formally testing the contribution of a range of predictor variables to the geographic spread of PEDV. Within China, the provinces of Guangdong and Henan were identified as primary hubs for the spread of PEDV, for which we estimate live swine trade to play a very important role. On a global scale, the United States and China maintain the highest number of PEDV lineages. We estimate that, after an initial introduction out of China, the United States acted as an important source of PEDV introductions into Japan, Korea, China, and Mexico. Live swine trade also explains the dispersal of PEDV on a global scale. Given the increasingly global trade of live swine, our findings have important implications for designing prevention and containment measures to combat a wide range of livestock coronaviruses.
SpeciesRax: A Tool for Maximum Likelihood Species Tree Inference from Gene Family Trees under Duplication, Transfer, and Loss
Authors: Morel Benoit , Schade Paul , Lutteropp Sarah , Williams Tom A , Szöllősi Gergely J , Stamatakis Alexandros 
Published: December 2021

Abstract
Species tree inference from gene family trees is becoming increasingly popular because it can account for discordance between the species tree and the corresponding gene family trees. In particular, methods that can account for multiple-copy gene families exhibit potential to leverage paralogy as informative signal. At present, there does not exist any widely adopted inference method for this purpose. Here, we present SpeciesRax, the first maximum likelihood method that can infer a rooted species tree from a set of gene family trees and can account for gene duplication, loss, and transfer events. By explicitly modeling events by which gene trees can depart from the species tree, SpeciesRax leverages the phylogenetic rooting signal in gene trees. SpeciesRax infers species tree branch lengths in units of expected substitutions per site and branch support values via paralogy-aware quartets extracted from the gene family trees. Using both empirical and simulated data sets we show that SpeciesRax is at least as accurate as the best competing methods while being one order of magnitude faster on large data sets at the same time. We used SpeciesRax to infer a biologically plausible rooted phylogeny of the vertebrates comprising 188 species from 31,612 gene families in 1 h using 40 cores. SpeciesRax is available under GNU GPL at https://github.com/BenoitMorel/GeneRax and on BioConda.
Characterization of the SARS-CoV-2 ExoN (nsp14ExoN–nsp10) complex: implications for its role in viral genome stability and inhibitor identification
Authors: Baddock Hannah T , Brolih Sanja , Yosaatmadja Yuliana , Ratnaweera Malitha , Bielinski Marcin , Swift Lonnie P , Cruz-Migoni Abimael , Fan Haitian , Keown Jeremy R , Walker Alexander P , Morris Garrett M , Grimes Jonathan M , Fodor Ervin , Schofield Christopher J , Gileadi Opher , McHugh Peter J 
Published: December 2021

AbstractThe SARS-CoV-2 coronavirus is the causal agent of the current global pandemic. SARS-CoV-2 belongs to an order, Nidovirales, with very large RNA genomes. It is proposed that the fidelity of coronavirus (CoV) genome replication is aided by an RNA nuclease complex, comprising the non-structural proteins 14 and 10 (nsp14–nsp10), an attractive target for antiviral inhibition. Our results validate reports that the SARS-CoV-2 nsp14–nsp10 complex has RNase activity. Detailed functional characterization reveals nsp14–nsp10 is a versatile nuclease capable of digesting a wide variety of RNA structures, including those with a blocked 3′-terminus. Consistent with a role in maintaining viral genome integrity during replication, we find that nsp14–nsp10 activity is enhanced by the viral RNA-dependent RNA polymerase complex (RdRp) consisting of nsp12–nsp7–nsp8 (nsp12–7–8) and demonstrate that this stimulation is mediated by nsp8. We propose that the role of nsp14–nsp10 in maintaining replication fidelity goes beyond classical proofreading by purging the nascent replicating RNA strand of a range of potentially replication-terminating aberrations. Using our developed assays, we identify drug and drug-like molecules that inhibit nsp14–nsp10, including the known SARS-CoV-2 major protease (Mpro) inhibitor ebselen and the HIV integrase inhibitor raltegravir, revealing the potential for multifunctional inhibitors in COVID-19 treatment.
Prospective biomarker study in newly diagnosed glioblastoma: Cyto-C clinical trial
Authors: Griguer Corinne E , Oliva Claudia R , Coffey Christopher S , Cudkowicz Merit E , Conwit Robin A , Gudjonsdottir Anna L , Ecklund Dixie J , Fedler Janel K , Neill-Hudson Tina M , Nabors Louis B , Benge Melanie , Hackney James R , Chase Marianne , Leonard Timothy P , Patel Toral , Colman Howard , de la Fuente Macarena , Chaudhary Rekha , Marder Karen , Kreisl Teri , Mohile Nimish , Chheda Milan G , McNeill Katharine , Kumthekar Priya , Dogan Aclan , Drappatz Jan , Puduvalli Vinay , Kowalska Agnes , Graber Jerome , Gerstner Elizabeth , Clark Stephen , Salacz Michael , Markert James 
Published: December 2021

Abstract

Background
Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of MGMT promoter methylation status.

Methods
This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed GBM who were to undergo surgical resection and would be candidates for standard of care. The primary end point was overall survival (OS) time, and the secondary end point was progression-free survival (PFS) time. Tumor CcO activity and MGMT promoter methylation status were assayed in a centralized laboratory.

Results
OS and PFS did not differ by high or low tumor CcO activity, and the prognostic validity of MGMT promoter methylation was confirmed. Notably, a planned exploratory analysis suggested that the combination of low CcO activity and MGMT promoter methylation in tumors may be predictive of long-term survival.

Conclusions
Tumor CcO activity alone was not confirmed as a prognostic marker in GBM patients. However, the combination of low CcO activity and methylated MGMT promoter may reveal a subgroup of GBM patients with improved long-term survival that warrants further evaluation. Our work also demonstrates the importance of performing large, multi-institutional, prospective studies to validate biomarkers. We also discuss lessons learned in assembling such studies.
Long working hours, depression and suicidality among OB/GYNs in Japan
Authors: Ishikawa M 
Published: December 2021

Abstract

Background
There is abundant evidence linking long working hours among physicians with adverse health effects; however, most studies have focused on medical residents. In Japan, obstetrician/gynaecologists (OB/GYNs) work the longest hours, yet no studies have investigated potential relationships between excessive overtime and depression and suicidal ideation within this population.

Aims
To investigate the relationship between long working hours and depression and suicidal ideation among OB/GYNs in Japan.

Methods
We administered a survey questionnaire to OB/GYNs and received 919 valid responses. Multivariate logistic regression was performed with depression and suicidal ideation as the outcome variables and number of working hours per week, gender, age, marital status, hospital type and geographical area type as the explanatory variables.

Results
Sixteen per cent of the participants were depressed, and 3% reported suicidal ideation. Working 100 or more hours per week increased the odds for both depression and suicidal ideation [odds ratio (OR): 2.08 (95% confidence interval {CI}: 1.07–4.05, P = 0.03); and OR: 7.03 (95% CI: 1.95–25.38, P &lt; 0.001), respectively].

Conclusions
The results suggest that the Japanese Government should vigorously promote physicians’ work-style reform, so that a lowered upper limit of overtime hours will be enforced from 2024 to improve physicians’ health and patients’ safety.
Depression prevention in healthcare workers during the COVID-19 pandemic
Authors: Takada H , Ae R , Ogawa M , Kagomoto T 
Published: December 2021

AbstractBackgroundFew studies have assessed depression in healthcare workers (HCWs) in Japan owing to the coronavirus disease 2019 (COVID-19) pandemic, and no studies have proposed effective interventions to help support their mental health.AimsTo test the hypothesis that enhancing access to mental healthcare professionals helps to improve HCWs’ mental health.MethodsThis cross-sectional study assessed depressive symptoms in HCWs at three hospitals in Osaka prefecture between May and July, 2020. The survey obtained information on HCWs’ mental state and related situations/perceptions. Multivariable logistic regression analysis was performed to identify factors associated with depressive symptoms.ResultsOf the 3291 eligible HCWs, 1269 (39%) completed the survey. Of all HCWs, 87 (7%) were physicians, and 700 (55%) were nurses. A total of 181 (14%) HCWs had moderate-to-severe symptoms of depression. Being a frontline worker was not significantly associated with depressive symptoms (odds ratio: 0.86 [95% confidence intervals: 0.54–1.37], P = 0.50). The unwillingness to consult with anyone was significantly associated with more severe depressive symptoms (1.70 [1.10–2.63], P &lt; 0.01). HCWs who had no opportunity to confide in family/friends (1.66 [1.10–2.52], P &lt; 0.01) or colleagues/supervisors (3.19 [2.22–4.58], P &lt; 0.001) were significantly more likely to have depressive symptoms.ConclusionsBeing a frontline HCW in a Japanese hospital treating patients with COVID-19 was not significantly associated with having depressive symptoms. The study highlights that encouraging daily communication with close persons (family, friends, colleagues and supervisors), rather than improving access to mental health professionals, might help to prevent depression in HCWs during the COVID-19 pandemic.
Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection
Authors: Zasowski Evan J , Trinh Trang D , Claeys Kimberly C , Lagnf Abdalhamid M , Bhatia Sahil , Klinker Kenneth P , Veve Michael P , Estrada Sandy J , Johns Scott T , Sawyer Adam J , Huang Vanthida , LaFrance Brandi , Levine Donald P , Kaye Keith S , Davis Susan L , Rybak Michael J 
Published: December 2021

Abstract

Background
Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin.

Methods
Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied.

Results
Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001).

Conclusions
No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.
Fosfomycin vs Ertapenem for Outpatient Treatment of Complicated Urinary Tract Infections: A Multicenter, Retrospective Cohort Study
Authors: Wald-Dickler Noah , Lee Todd C , Tangpraphaphorn Soodtida , Butler-Wu Susan M , Wang Nina , Degener Tyler , Kan Carolyn , Phillips Matthew C , Cho Edward , Canamar Catherine , Holtom Paul , Spellberg Brad 
Published: December 2021

Abstract

Background
We sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs).

Methods
We conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis.

Results
We identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum β-lactamase–producing E. coli and Klebsiella pneumoniae, 80%–90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68–2.16), 0.84 (95% CI, 0.46–1.52), and 0.94 (95% CI, 0.52–1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day).

Conclusions
These results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI.
Association Between Foot Surgery Type and Subsequent Healing in Veterans With Moderate-to-Severe Diabetic Foot Infections
Authors: Kim Justin J , Littman Alyson J , Sorkin John D , Roghmann Mary-Claire 
Published: December 2021

AbstractBackgroundDiabetic foot infections are a common precursor to lower extremity amputations. The treatment of diabetic foot infections involves both medical and surgical management, of which limb-sparing surgeries are increasingly preferred over amputations at or above the ankle to preserve mobility and quality of life. The outcomes following these limb-sparing surgeries are not well described.MethodsThis was a single-center, retrospective cohort study of 90 Veterans with moderate-to-severe diabetic foot infections between 2017 and 2019 from the Veterans Affairs Maryland Health Care System. The exposure was foot surgery with bone resection (ie, toe amputation, metatarsal resection, transmetatarsal amputation) vs debridement alone. The outcome was healing within 1 year. We used log-binomial regression to assess the association between foot surgery type and healing, stratify by infection location, and evaluate potential confounding variables.ResultsThe cumulative incidence of healing after foot surgery with bone resection was greater than that following debridement (risk ratio [RR], 1.80 [95% confidence interval {CI}, 1.17–2.77]). This association was modified by infection location and greater for toe infections (RR, 4.52 [95% CI, 1.30–15.7]) than other foot infections (RR, 1.19 [95% CI, .69–2.02]). We found no evidence of confounding by comorbidities or infection severity.ConclusionsFor patients with toe infections, foot surgery with bone resection was associated with better healing than debridement alone. The multiple specialties caring for patients with diabetic foot infections need a stronger common knowledge base—from studies like this and future studies—to better counsel patients about their treatment and prognosis.
A dominant mutation in β-AMYLASE1 disrupts nighttime control of starch degradation in Arabidopsis leaves
Authors: Feike Doreen , Pike Marilyn , Gurrieri Libero , Graf Alexander , Smith Alison M 
Published: December 2021

Abstract
Arabidopsis (Arabidopsis thaliana) leaves possess a mechanism that couples the rate of nighttime starch degradation to the anticipated time of dawn, thus preventing premature exhaustion of starch and nighttime starvation. To shed light on the mechanism, we screened a mutagenized population of a starvation reporter line and isolated a mutant that starved prior to dawn. The mutant had accelerated starch degradation, and the rate was not adjusted to time of dawn. The mutation responsible led to a single amino acid change (S132N) in the starch degradation enzyme BETA-AMYLASE1 (BAM1; mutant allele named bam1-2D), resulting in a dominant, gain-of-function phenotype. Complete loss of BAM1 (in bam1-1) did not affect rates of starch degradation, while expression of BAM1(S132N) in bam1-1 recapitulated the accelerated starch degradation phenotype of bam1-2D. In vitro analysis of recombinant BAM1 and BAM1(S132N) proteins revealed no differences in kinetic or stability properties, but in leaf extracts, BAM1(S132N) apparently had a higher affinity than BAM1 for an established binding partner required for normal rates of starch degradation, LIKE SEX FOUR1 (LSF1). Genetic approaches showed that BAM1(S132N) itself is likely responsible for accelerated starch degradation in bam1-2D and that this activity requires LSF1. Analysis of plants expressing BAM1 with alanine or aspartate rather than serine at position 132 indicated that the gain-of-function phenotype is not related to phosphorylation status at this position. Our results strengthen the view that control of starch degradation in wild-type plants involves dynamic physical interactions of degradative enzymes and related proteins with a central role for complexes containing LSF1.