bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferences About Drug Safety in Phase III Trials in Oncology: Examples From Advanced Prostate Cancer
Authors: Drago Joshua Z , Gönen Mithat , Thanarajasingam Gita , Sacks Chana A , Morris Michael J , Kantoff Philip W , Stopsack Konrad H 
Published: August 2020

Abstract

Background
Safety is a central consideration when choosing between multiple medications with similar efficacy. We aimed to evaluate whether adverse event (AE) profiles of 3 such drugs in advanced prostate cancer could be distinguished based on published literature.

Methods
We assessed consistency in AE reporting, AE risk in placebo arms, and methodology used for risk estimates and quantification of statistical uncertainty in randomized placebo-controlled phase III trials of apalutamide, enzalutamide, and darolutamide in advanced prostate cancer.

Results
Seven included clinical trials enrolled a total of 9215 participants (range = 1051-1715 per trial) across 3 prostate cancer disease states. Within disease states, baseline patient characteristics appeared similar between trials. Of 54 distinct AE types in total, only 3 (fatigue, hypertension, and seizure) were reported by all 7 trials. Absolute risks of AEs in the placebo arms differed systematically and more than twofold between trials, which was associated with visit frequency and resulted in different degrees of uncertainty in AE profiles between trials. No trial used inferential methodology to quantify statistical uncertainty in AE risks, but 6 of 7 trials drew overall conclusions. Two trials concluded that there was no elevated AE risk because of the intervention, including the trial of darolutamide, which had the greatest statistical uncertainty.

Conclusions
Rigorous comparison of drug safety was precluded by heterogeneity in AE reporting, variation in AE risks in the placebo arms, and lack of inferential statistical methodology, underscoring considerable opportunities to improve how AE data are collected, analyzed, and interpreted in oncology trials.
A novel BSD domain-containing transcription factor controls vegetative growth, leaf senescence, and fruit quality in tomato
Authors: Fan Youhong , Niu Xiangli , Huang Li , Gross Rachel , Lu Han , Hawkins Madigan , Yuan Yulin , Miao Min , Liu Yongsheng , Xiao Fangming 
Published: August 2020

Abstract
BSD (mammalian BTF2-like transcription factors, synapse-associated proteins, and DOS2-like proteins) is a conserved domain that exists in a variety of organisms, but its function has not been well studied. Here, we identified a novel BSD domain-containing protein (SlBSD1) in tomato (Solanum lycopersicum). Biochemical and microscopy assays indicated that SlBSD1 is a functional transcription factor that is predominantly localized in the nucleus. Loss-of-function and overexpression analyses suggested that SlBSD1 is a novel regulator of vegetative growth and leaf senescence in tomato. SlBSD1-knockdown (-KD) plants exhibited retarded vegetative growth and precocious leaf senescence, whereas SlBSD1-overexpression (-OX) plants displayed the opposite phenotypes. The negative role of SlBSD1 in leaf senescence was also supported by RNA-seq analysis comparing leaf tissues from SlBSD1-KD and wild-type plants. In addition, contents of soluble solids were altered in fruits in the SlBSD1-KD and SlBSD1-OX plants. Taken together, our data suggest that the novel transcription factor SlBSD1 plays important roles in controlling fruit quality and other physiological processes in tomato, including vegetative growth and leaf senescence.
Microvariability in AGNs: study of different statistical methods – II. Light curves from simulated images
Authors: Zibecchi L , Andruchow I , Cellone S A , Carpintero D D 
Published: August 2020

ABSTRACT
In a previous paper, we studied two statistical methods used to analyse the variability of active galactic nuclei (AGNs): the C and F statistics. Applying them to observed differential light curves (DLCs) of 39 AGNs, we found that, even though the C criterion cannot be considered as an actual statistical test, it could still be a useful parameter to detect variability, whereas F is a good detector of non-variability. In order to test these results under controlled input conditions, so that the different error sources could be individually evaluated, we generated a series of synthetic DLCs simulating astronomical images with different atmospheric conditions, such as cloud cover, seeing or sky brightness, as well as several types of intrinsic variability of the AGN, all with a specific instrumental configuration. Having obtained light curves for each case, we applied both statistics to them in order to test their reliability. We found that a weight factor should always be used with these indices. The F-test has a tendency to classify noisy non-variable curves as variable (i.e. false positives), although it is reliable and robust to correctly classify non-variable curves. In contrast, although the C index tends to give false negatives, we found that whenever the C index indicates a source to be variable, it effectively is. Finally, light curves with low amplitude variabilities are more likely to be affected by changes in atmospheric conditions.
The completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: GLAM-QPM mock galaxy catalogues for the emission line galaxy sample
Authors: Lin Sicheng , Tinker Jeremy L , Klypin Anatoly , Prada Francisco , Blanton Michael R , Comparat Johan , Dawson Kyle S , de Mattia Arnaud , du Mas des Bourboux Hélion , Percival Will J , Raichoor Anand , Rossi Graziano , Smith Alex , Zhao Cheng 
Published: August 2020

ABSTRACT
We present 2000 mock galaxy catalogues for the analysis of baryon acoustic oscillations (BAOs) in the Emission Line Galaxy (ELG) sample of the extended Baryon Oscillation Spectroscopic Survey Data Release 16 (eBOSS DR16). Each mock catalogue has a number density of $6.7 \times 10^{-4} h^3 \rm Mpc^{-3}$, covering a redshift range from 0.6 to 1.1. The mocks are calibrated to small-scale eBOSS ELG clustering measurements at scales of $\lesssim 30\, h^{-1}$Mpc. The mock catalogues are generated using a combination of GaLAxy Mocks (GLAM) simulations and the quick particle-mesh (QPM) method. GLAM simulations are used to generate the density field, which is then assigned dark matter haloes using the QPM method. Haloes are populated with galaxies using a halo occupation distribution. The resulting mocks match the survey geometry and selection function of the data, and have slightly higher number density that allows room for systematic analysis. The large-scale clustering of mocks at the BAO scale is consistent with data and we present the correlation matrix of the mocks.
CoV3D: a database of high resolution coronavirus protein structures
Authors: Gowthaman Ragul , Guest Johnathan D , Yin Rui , Adolf-Bryfogle Jared , Schief William R , Pierce Brian G 
Published: August 2020

AbstractSARS-CoV-2, the etiologic agent of COVID-19, exemplifies the general threat to global health posed by coronaviruses. The urgent need for effective vaccines and therapies is leading to a rapid rise in the number of high resolution structures of SARS-CoV-2 proteins that collectively reveal a map of virus vulnerabilities. To assist structure-based design of vaccines and therapeutics against SARS-CoV-2 and other coronaviruses, we have developed CoV3D, a database and resource for coronavirus protein structures, which is updated on a weekly basis. CoV3D provides users with comprehensive sets of structures of coronavirus proteins and their complexes with antibodies, receptors, and small molecules. Integrated molecular viewers allow users to visualize structures of the spike glycoprotein, which is the major target of neutralizing antibodies and vaccine design efforts, as well as sets of spike-antibody complexes, spike sequence variability, and known polymorphisms. In order to aid structure-based design and analysis of the spike glycoprotein, CoV3D permits visualization and download of spike structures with modeled N-glycosylation at known glycan sites, and contains structure-based classification of spike conformations, generated by unsupervised clustering. CoV3D can serve the research community as a centralized reference and resource for spike and other coronavirus protein structures, and is available at: https://cov3d.ibbr.umd.edu.
Trends in Legionnaires’ Disease-Associated Hospitalizations, United States, 2006–2010
Authors: Mudali Gayathri , Kilgore Paul E , Salim Abdulbaset , McElmurry Shawn P , Zervos Marcus 
Published: August 2020

Abstract

Background
Legionella pneumophila is a waterborne cause of both healthcare-associated and community-acquired pneumonia. Legionella pneumophila serogroup 1 is responsible for 80% of infections. There is currently limited published disease burden data on Legionnaires’ disease-associated hospitalization in the United States.

Methods
In this study, we estimated the annual incidence of Legionnaires’ disease-associated hospitalizations in United States and identified demographic, temporal, and regional characteristics of individuals hospitalized for Legionnaires’ disease. A retrospective study was conducted using the National Hospital Discharge Survey (NHDS) data from 2006 to 2010. The NHDS is a nationally representative US survey, which includes estimates of inpatient stays in short-stay hospitals in the United States, excluding federal, military, and Veterans Administration hospitals. All discharges assigned with the Legionnaires’ disease International Classification of Diseases 9th Clinical Modification discharge diagnostic code (482.84) were included in this study.

Results
We observed the annual incidence and number of Legionnaires’ disease-associated hospitalizations (per 100 000 population) in the United States by year, age, sex, race, and region. Over a 5-year period, 14 574 individuals experienced Legionnaires’ disease-associated hospitalizations in the United States The annual population-adjusted incidence (per 100 000 population) of Legionnaires’ disease-associated hospitalizations was 5.37 (95% confidence interval [CI], 5.12–5.64) in 2006, 7.06 (95% CI, 6.80–7.40) in 2007, 8.77 (95% CI, 8.44–9.11) in 2008, 17.07 (95% CI, 16.62–17.54) in 2009, and 9.66 (95% CI, 9.32–10.01) in 2010. A summer peak of Legionnaires’ disease-associated hospitalizations occurred from June through September in 2006, 2007, 2008, and 2010.

Conclusions
Legionnaires’ disease-associated hospitalizations significantly increased over the 5-year study period. The increasing disease burden of Legionnaires’ disease suggests that large segments of the US population are at risk for exposure to this waterborne pathogen.
Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations With 24-Month Growth and Neurodevelopment
Authors: Moraka Natasha O , Moyo Sikhulile , Smith Christiana , Ibrahim Maryanne , Mayondi Gloria , Leidner Jean , Powis Kathleen M , Cassidy Adam R , Kammerer Betsy , Ajibola Gbolahan , Williams Paige L , Weinberg Adriana , Musonda Rosemary , Shapiro Roger , Gaseitsiwe Simani , Lockman Shahin 
Published: August 2020

Abstract

Background
We sought to identify predictors of child cytomegalovirus (CMV) infection overall and by maternal HIV status and to assess associations of child CMV status with growth and neurodevelopmental outcomes at 24 months of age in Botswana.

Methods
Data and samples were used from the Botswana-based observational Tshipidi study (2010–2014), enrolling pregnant women living with and without HIV and following their infants through 2 years of age. Child plasma samples were tested at 18 months of age for anti-CMV immunoglobulin G (IgG). Associations were assessed between detectable anti-CMV IgG and growth (using the World Health Organization Child Growth Standards) and neurodevelopment (using the Bayley Scales of Infant and Toddler Development III and the Developmental Milestones Checklist) at 24 months of age.

Results
Of 317 children, 215 (68%) had detectable anti-CMV IgG at 18 months of age. Comparatively, 83% (n = 178) of HIV-unexposed uninfected (HUU) children had positive CMV serology vs 47% (n = 139) of HIV-exposed uninfected (HEU) children (P &lt; .01); 100% of HUU vs 10.5% of HEU children breastfed. Child CMV infection was not associated with weight-for-age, weight-for-length, or length-for-age z-scores at 24 months. In HUU children, CMV infection was associated with smaller head circumference (P &lt; .01). No difference was observed by child CMV status in any neurodevelopmental domain at 24 months.

Conclusions
We observed high CMV seropositivity in 18-month-old children in Botswana, with higher seropositivity among breastfed (HUU) children. Positive CMV serostatus was not associated with 24-month child growth or neurodevelopmental outcomes, with the exception of smaller head circumference among HUU CMV-positive children.
Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia
Authors: Son Hyo-Ju , Cho Eun Been , Bae Moonsuk , Lee Seung Cheol , Sung Heungsup , Kim Mi-Na , Jung Jiwon , Kim Min Jae , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Kim Yang Soo , Chong Yong Pil 
Published: August 2020

Abstract

Background
Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia.

Methods
Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing.

Results
A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95–12.42; P = .001), septic shock (aOR, 4.72; 95% CI, 2.12–10.49; P &lt; .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05–6.16; P = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors.

Conclusions
Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.
Benjamin Stillingfleet’s Notes on Paradise Lost, Lost and Found
Authors: Sugimura N K 
Published: August 2020

Abstract
This essay reveals that the annotated copy of Richard Bentley’s edition of Paradise Lost (1732) with MS notes attributed to Benjamin Stillingfleet (1702–1771), now housed in the British Library, is not, as has been assumed for over 170 years, in Stillingfleet’s autograph hand. Drawing on book history, biography, and manuscripts in various archives, this essay tells a three-way story about Stillingfleet’s holograph annotations on Paradise Lost, their partial transcription in the Bentley edition, and a set of‘original’ manuscript notes on the epic that Stillingfleet made while in Geneva in the early 1740s. It recounts how a predominantly male socio-literary culture—in which private manuscripts circulated among friends and were lent to antiquarians and editors alike—preserved one set of Stillingfleet’s handwritten notes in his interleaved two-volume Tonson edition of Paradise Lost (1727), while a partial copy of those notes was made by Stillingfleet’s close friend, Thomas Dampier (d. 1777), dean of Ely, in his interleaved copy of Bentley’s edition. Although Stillingfleet’s original and earlier‘sketch’ of manuscript notes appears to have been lost, the remarkably rich set of autograph notes on Milton’s epic made by Stillingfleet in the Tonson volume tantalizingly suggests what Stillingfleet’s prospective edition might have looked like, and how it positioned itself against Bentley’s edition of 1732. Stillingfleet’s autograph notes therefore significantly help in better understanding not only Milton’s reception history in the eighteenth century, but also the role his epic played in the eighteenth-century debate between the Ancients and the Moderns in English Enlightenment culture.
Nonrapid eye movement sleep electroencephalographic oscillations in idiopathic rapid eye movement sleep behavior disorder: a study of sleep spindles and slow oscillations
Authors: Sunwoo Jun-Sang , Cha Kwang Su , Byun Jung-Ick , Jun Jin-Sun , Kim Tae-Joon , Shin Jung-Won , Lee Soon-Tae , Jung Keun-Hwa , Park Kyung-Il , Chu Kon , Kim Manho , Lee Sang Kun , Kim Han-Joon , Schenck Carlos H , Jung Ki-Young 
Published: August 2020

Abstract

Study Objectives
We investigated electroencephalographic (EEG) slow oscillations (SOs), sleep spindles (SSs), and their temporal coordination during nonrapid eye movement (NREM) sleep in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).

Methods
We analyzed 16 patients with video-polysomnography-confirmed iRBD (age, 65.4 ± 6.6 years; male, 87.5%) and 10 controls (age, 62.3 ± 7.5 years; male, 70%). SSs and SOs were automatically detected during stage N2 and N3. We analyzed their characteristics, including density, frequency, duration, and amplitude. We additionally identified SO-locked spindles and examined their phase distribution and phase locking with the corresponding SO. For inter-group comparisons, we used the independent samples t-test or Wilcoxon rank-sum test, as appropriate.

Results
The SOs of iRBD patients had significantly lower amplitude, longer duration (p = 0.005 for both), and shallower slope (p &lt; 0.001) than those of controls. The SS power of iRBD patients was significantly lower than that of controls (p = 0.002), although spindle density did not differ significantly. Furthermore, SO-locked spindles of iRBD patients prematurely occurred during the down-to-up-state transition of SOs, whereas those of controls occurred at the up-state peak of SOs (p = 0.009). The phase of SO-locked spindles showed a positive correlation with delayed recall subscores (p = 0.005) but not with tonic or phasic electromyography activity during REM sleep.

Conclusions
In this study, we found abnormal EEG oscillations during NREM sleep in patients with iRBD. The impaired temporal coupling between SOs and SSs may reflect early neurodegenerative changes in iRBD.
Metabolomic analysis coupled with extreme phenotype sampling identified that lysophosphatidylcholines are associated with multisite musculoskeletal pain
Authors: Liu Ming , Xie Zikun , Costello Christie A. , Zhang Weidong , Chen Liujun , Qi Dake , Furey Andrew , Randell Edward W. , Rahman Proton , Zhai Guangju 
Published: August 2020

Abstract
Musculoskeletal pain often occurs simultaneously at multiple anatomical sites. The aim of the study was to identify metabolic biomarkers for multisite musculoskeletal pain (MSMP) by metabolomics with an extreme phenotype sampling strategy. The study participants (n = 610) were derived from the Newfoundland Osteoarthritis Study. Musculoskeletal pain was assessed using a self-reported pain questionnaire where painful sites were circled on a manikin by participants and the total number of painful sites were calculated. Targeted metabolomic profiling on fasting plasma samples was performed using the Biocrates AbsoluteIDQ p180 kit. Plasma cytokine concentrations including tumor necrosis factor-α, interleukin-6, interleukin-1β, and macrophage migration inhibitory factor were assessed by enzyme-linked immunosorbent assay. Data on blood cholesterol profiles were retrieved from participants' medical records. Demographic, anthropological, and clinical information was self-reported. The number of reported painful sites ranged between 0 and 21. Two hundred and five participants were included in the analysis comprising 83 who had ≥7 painful sites and 122 who had ≤1 painful site. Women and younger people were more likely to have MSMP (P ≤ 0.02). Multisite musculoskeletal pain was associated with a higher risk of having incontinence, worse functional status and longer period of pain, and higher levels of low-density lipoprotein and non–high-density lipoprotein cholesterol (all P ≤ 0.03). Among the 186 metabolites measured, 2 lysophosphatidylcholines, 1 with 26 carbons with no double bond and 1 with 28 carbons with 1 double bond, were significantly and positively associated with MSMP after adjusting for multiple testing with the Bonferroni method (P ≤ 0.0001) and could be considered as novel metabolic markers for MSMP.
Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy
Authors: Donatini Gianluca , Marciniak Camille , Lenne Xavier , Clément Guillaume , Bruandet Amélie , Sebag Frédéric , Mirallié Eric , Mathonnet Muriel , Brunaud Laurent , Lifante Jean-Christophe , Tresallet Christophe , Ménégaux Fabrice , Theis Didier , Pattou François , Caiazzo Robert 
Published: August 2020

Background:
Surgical removal of hyperfunctional parathyroid gland is the definitive treatment for primary hyperparathyroidism (pHPT). Postoperative follow-up shows variability in persistent/recurrent disease rate throughout different centers.

Objective:
To evaluate the incidence of redo surgery after targeted parathyroidectomy for pHPT.

Methods:
We performed a nationwide retrospective cohort study on the “Programme de Medicalisation des Systemes d’Information,” the French administrative database that collects information on all healthcare facilities’ discharges. We extracted data from 2009 to 2018 for all patients who underwent parathyroidectomy for pHPT between January 2011 to December 2016. The primary outcome was the reoperation rate within 2 years since first surgery. Patients who had a first attempt of surgery within the previous 24 months, familial hyperparathyroidism, multiglandular disease, and renal failure were excluded. Results were adjusted according to sex and the Elixhauser Comorbidity Index. Operative volume thresholds to define high-volume centers were achieved by the Chi-Squared Automatic Interaction Detector method.

Results:
In the study period, 13,247 patients (median age 63, F/M=3.6) had a focused parathyroidectomy by open (88.7%) or endoscopic approach. Need of remedial surgery was 2.8% at 2 years. In multivariate analysis, factors predicting redo surgery were: cardiac history (P=0.008), obesity (P=0.048), endoscopic approach (P=0.005), and low-volume center (P<0.001). We evaluated that an annual caseload of 31 parathyroidectomies was the best threshold to discriminate high-volume centers and carries the lowest morbidity/failure rate.

Conclusion:
Although focused parathyroidectomy represents a standardized operation, cure rate is strongly associated with annual hospital caseload, type of procedure (endoscopic), and patients’ features (obesity, cardiac history). Patients with risk factors for redo surgery should be considered for an open surgery in a high-volume center.