bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childbearing Decisions in Residency: A Multicenter Survey of Female Residents
Authors: Stack Shobha W. , Jagsi Reshma , Biermann J. Sybil , Lundberg Gina P. , Law Karen L. , Milne Caroline K. , Williams Sigrid G. , Burton Tracy C. , Larison Cindy L. , Best Jennifer A. 
Published: June 2020

Purpose
To characterize how female residents make decisions about childbearing, factors associated with the decision to delay childbearing, and satisfaction with these decisions.

Method
In 2017, the authors sent a voluntary, anonymous survey to 1,537 female residents enrolled across 78 graduate medical education programs, consisting of 25 unique specialties, at 6 U.S. academic medical centers. Survey items included personal, partner, and institutional characteristics, whether the respondent was delaying childbearing during residency, and the respondent’s satisfaction with this decision.

Results
The survey response rate was 52% (n = 804). Among the 447 (56%) respondents who were married or partnered, 274 (61%) were delaying childbearing. Residents delaying childbearing were significantly more likely to be younger (P < .001), not currently a parent (P < .001), in a specialty with an uncontrollable lifestyle (P = .001), or in a large program (P = .004). Among self-reported reasons for delaying childbearing, which were not mutually exclusive, the majority cited a busy work schedule (n = 255; 93%) and desire not to extend residency training (n = 145; 53%). Many cited lack of access to childcare (n = 126; 46%), financial concerns (n = 116; 42%), fear of burdening colleagues (n = 96; 35%), and concern for pregnancy complications (n = 74; 27%). Only 38% (n = 103) of respondents delaying childbearing were satisfied with this decision, with satisfaction decreasing with increasing age.

Conclusions
Decisions to delay childbearing are more common in certain specialties, and many residents who delay childbearing are not satisfied with that decision. These findings suggest that greater attention is needed overall, and particularly in certain specialties, to promote policies and cultures that both anticipate and normalize parenthood in residency, thus minimizing the conflict between biological and professional choices for female residents.
Risk Factors for Developing Severe Acute Kidney Injury in Adult Patients With Refractory Postcardiotomy Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation
Authors: Lepère Victoria , Duceau Baptiste , Lebreton Guillaume , Bombled Camille , Dujardin Olivier , Boccara Lucile , Charfeddine Ahmed , Amour Julien , Hajage David , Bouglé Adrien 
Published: June 2020

Objectives:
Postcardiotomy cardiogenic shock occurs in 2–6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients.

Design:
Retrospective observational cohort study between January 2013 and December 2016.

Setting:
An 18-bed surgical ICU in a university hospital.

Patients:
A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients.

Interventions:
None.

Measurements and Main Results:
The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3–16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31–6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01–1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02–1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001–1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006–1.018]; p < 0.001) on the day of implantation.

Conclusions:
Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.
Physical, Mental, and Cognitive Health Status of ICU Survivors Before ICU Admission: A Cohort Study
Authors: Geense Wytske W. , van den Boogaard Mark , Peters Marco A. A. , Simons Koen S. , Ewalds Esther , Vermeulen Hester , van der Hoeven Johannes G. , Zegers Marieke 
Published: June 2020

Objectives:
Although patient’s health status before ICU admission is the most important predictor for long-term outcomes, it is often not taken into account, potentially overestimating the attributable effects of critical illness. Studies that did assess the pre-ICU health status often included specific patient groups or assessed one specific health domain. Our aim was to explore patient’s physical, mental, and cognitive functioning, as well as their quality of life before ICU admission.

Design:
Baseline data were used from the longitudinal prospective MONITOR-IC cohort study.

Setting:
ICUs of four Dutch hospitals.

Patients:
Adult ICU survivors (n = 2,467) admitted between July 2016 and December 2018.

Interventions:
None.

Measurements and Main Results:
Patients, or their proxy, rated their level of frailty (Clinical Frailty Scale), fatigue (Checklist Individual Strength-8), anxiety and depression (Hospital Anxiety and Depression Scale), cognitive functioning (Cognitive Failure Questionnaire-14), and quality of life (Short Form-36) before ICU admission. Unplanned patients rated their pre-ICU health status retrospectively after ICU admission. Before ICU admission, 13% of all patients was frail, 65% suffered from fatigue, 28% and 26% from symptoms of anxiety and depression, respectively, and 6% from cognitive problems. Unplanned patients were significantly more frail and depressed. Patients with a poor pre-ICU health status were more often likely to be female, older, lower educated, divorced or widowed, living in a healthcare facility, and suffering from a chronic condition.

Conclusions:
In an era with increasing attention for health problems after ICU admission, the results of this study indicate that a part of the ICU survivors already experience serious impairments in their physical, mental, and cognitive functioning before ICU admission. Substantial differences were seen between patient subgroups. These findings underline the importance of accounting for pre-ICU health status when studying long-term outcomes.
Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress
Authors: Rajgarhia Ayan , Ayyasola Kameshwar , Zaghloul Nahla , Da Re Jorge M. Lopez , Miller Edmund J. , Ahmed Mohamed 
Published: June 2020

AbstractBackgroundChronic hypoxic stress induces epigenetic modifications in cardiac fibroblasts, such as inactivation of tumor suppressor genes (RASSF1A), and activation of kinases (ERK1/2). The effects of the antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), on these epigenetic changes has not been fully explored.ObjectivesTo define the effect of EC-SOD overexpression on cardiac fibrosis induced by chronic hypoxia.MethodsWild type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG) were housed in hypoxia (10% O2) for 21 days. Right ventricular tissue was studied for cardiac fibrosis markers using RT-PCR and Western Blot analyses. Downstream effects were studied, for both RASSF-1 expression and methylation and its relation to ERK1/2, usingin-vivo&in-vitromodelsResultsThere were significant increases in markers of cardiac fibrosis : Collagen 1, Alpha Smooth Muscle Actin (ASMA) and SNAIL, in the WT hypoxic animals as compared to the TG hypoxic group (p< 0.05). Expression of DNA methylation enzymes (DNMT 1,2) was significantly increased in the WT hypoxic mice as compared to the hypoxic TG mice (p<0.001). RASSF1A expression was significantly lower and ERK1/2 was significantly higher in hypoxia WT compared to the hypoxic TG group (p<0.05). Use of SiRNA to block RASSF1A gene expression in murine cardiac fibroblast tissue culture led to increased fibroblast proliferation (p<0.05). Methylation of RASSF1A promoter region showed a significant reduction in the TG hypoxic group compared to the WT hypoxic group (0.59 vs 0.75 respectively).ConclusionsEC-SOD significantly attenuates RASSF1A gene methylation, and plays a pivotal role cardiac fibrosis induced by hypoxia.
ENHANCEMENT OF PARVALBUMIN INTERNEURON-MEDIATED NEUROTRANSMISSION IN THE RETROSPLENIAL CORTEX OF ADOLESCENT MICE FOLLOWING THIRD TRIMESTER-EQUIVALENT ETHANOL EXPOSURE
Authors: Bird Clark W. , Chavez Glenna J. , Barber Megan J. , Valenzuela C. Fernando 
Published: June 2020

ABSTRACTPrenatal ethanol exposure causes a variety of cognitive deficits that have a persistent impact on quality of life, some of which may be explained by ethanol-induced alterations in interneuron function. Studies from several laboratories, including our own, have demonstrated that a single binge-like ethanol exposure during the equivalent to the third trimester of human pregnancy leads to acute apoptosis and long-term loss of interneurons in the rodent retrosplenial cortex (RSC). The RSC is interconnected with the hippocampus, thalamus, and other neocortical regions and plays distinct roles in visuospatial processing and storage, as well as retrieval of hippocampal-dependent episodic memories. Here we used slice electrophysiology to characterize the acute effects of ethanol on GABAergic neurotransmission in the RSC of neonatal mice, as well as the long-term effects of neonatal ethanol exposure on parvalbumin-interneuron mediated neurotransmission in adolescent mice. Mice were exposed to ethanol using vapor inhalation chambers. In postnatal day (P) 7 mouse pups, ethanol unexpectedly failed to potentiate GABAAreceptor-mediated synaptic transmission. Binge-like ethanol exposure of P7 mice expressing channel rhodopsin in parvalbumin-positive interneurons enhanced the peak amplitudes, asynchronous activity and total charge, while decreasing the rise-times of optically-evoked GABAAreceptor-mediated inhibitory postsynaptic currents in adolescent animals. These effects could partially explain the learning and memory deficits that have been documented in adolescent and young adult mice exposed to ethanol during the third trimester-equivalent developmental period.
High-Accuracy Multiplexed SARS-CoV-2 Antibody Assay with Avidity and Saliva Capability on a Nano-Plasmonic Platform
Authors: Liu Tiancheng , Hsiung Jessica , Zhao Su , Kost Jessica , Sreedhar Deepika , Olson Kjerstie , Keare Douglas , Roche John , Hanson Carl V. , Press Cynthia , Boggs John , Rodriguez-Soto Jorge P. , Montoya Jose G. , Tang Meijie , Dai Hongjie 
Published: June 2020

AbstractThe outbreak and rapid spread of SARS-CoV-2 virus has led to a dire global pandemic with millions of people infected and ~ 400,000 deaths thus far. Highly accurate detection of antibodies for COVID-19 is an indispensable part of the effort to combat the pandemic1,2. Here we developed two-plex antibody detection against SARS-CoV-2 spike proteins3(the S1 subunit and receptor binding domain RBD) in human serum and saliva on a near-infrared nano-plasmonic gold (pGOLD) platform4–8. By testing nearly 600 serum samples, pGOLD COVID-19 assay achieved ~ 99.78 % specificity for detecting both IgG and IgM with 100 % sensitivity in sera collected > 14 days post disease symptom onset, with zero cross-reactivity to other diseases. Two-plex correlation analysis revealed higher binding of serum IgM to RBD than to S1. IgG antibody avidity toward multiple antigens were measured, shedding light on antibody maturation in COVID-19 patients and affording a powerful tool for differentiating recent from remote infections and identifying re-infection by SARS-CoV-2. Just as important, due to high analytical sensitivity, the pGOLD COVID-19 assay detected minute amounts of antibodies in human saliva, offering the first non-invasive detection of SARS-CoV-2 antibodies.
Crystal structure of SARS-CoV-2 main protease in complex with a Chinese herb inhibitor shikonin
Authors: Li Jian , Zhou Xuelan , Zhang Yan , Zhong Fanglin , Lin Cheng , McCormick Peter J. , Jiang Feng , Zhou Huan , Wang Qisheng , Duan Jingjing , Zhang Jin 
Published: June 2020

AbstractMain protease (Mpro, also known as 3CLpro) has a major role in the replication of coronavirus life cycle and is one of the most important drug targets for anticoronavirus agents. Here we report the crystal structure of main protease of SARS-CoV-2 bound to a previously identified Chinese herb inhibitor shikonin at 2.45 angstrom resolution. Although the structure revealed here shares similar overall structure with other published structures, there are several key differences which highlight potential features that could be exploited. The catalytic dyad His41-Cys145 undergoes dramatic conformational changes, and the structure reveals an unusual arrangement of oxyanion loop stabilized by the substrate. Binding to shikonin and binding of covalent inhibitors show different binding modes, suggesting a diversity in inhibitor binding. As we learn more about different binding modes and their structure-function relationships, it is probable that we can design more effective and specific drugs with high potency that can serve as effect SARS-CoV-2 anti-viral agents.
Chloroplast acquisition without the gene transfer in kleptoplastic sea slugs,Plakobranchus ocellatus
Authors: Maeda Taro , Takahashi Shunichi , Yoshida Takao , Shimamura Shigeru , Takaki Yoshihiro , Nagai Yukiko , Toyoda Atsushi , Suzuki Yutaka , Arimoto Asuka , Ishii Hisaki , Satoh Noriyuki , Nishiyama Tomoaki , Hasebe Mitsuyasu , Maruyama Tadashi , Minagawa Jun , Obokata Junichi , Shigenobu Shuji 
Published: June 2020

AbstractSome sea slugs sequester chloroplasts from algal food in their intestinal cells and photosynthesize for months. This phenomenon, kleptoplasty, poses a question of how the chloroplast retains its activity without the algal nucleus. There have been debates on the horizontal transfer of algal genes to the animal nucleus. To settle the arguments, this study reported the genome of a kleptoplastic sea slugPlakobranchus ocellatusand found no evidence of photosynthetic genes encoded on the nucleus. Nevertheless, it was confirmed that light illumination prolongs the life of mollusk under starvation. These data presented a paradigm that a complex adaptive trait, as typified by photosynthesis, can be transferred between eukaryotic kingdoms by a unique organelle transmission without nuclear gene transfer. Our phylogenomic analysis showed that genes for proteolysis and immunity undergo gene expansion and are up-regulated in chloroplast-enriched tissue, suggesting that these molluskan genes are involved in the DNA-independent phenotype acquisition.
Detection of SARS-CoV-2 RNA by multiplex RT-qPCR
Authors: Kudo Eriko , Israelow Benjamin , Vogels Chantal B.F. , Lu Peiwen , Wyllie Anne L. , Tokuyama Maria , Venkataraman Arvind , Brackney Doug E , Ott Isabel M. , Petrone Mary E. , Earnest Rebecca , Lapidus Sarah , Muenker M. Catherine , Moore Adam J. , Casanovas-Massana Arnau ,   Yale IMPACT Research Team, Omer Saad B. , Cruz Charles S. Dela , Farhadian Shelli F. , Ko Albert I. , Grubaugh Nathan D. , Iwasaki Akiko 
Published: June 2020

AbstractThe current RT-qPCR assay recommended for SARS-CoV-2 testing in the United States requires analysis of three genomic targets per sample: two viral and one host. To simplify testing and reduce the volume of required reagents, we developed a multiplex RT-qPCR assay to detect SARS-CoV-2 in a single reaction. We used existing N1, N2, and RP primer and probe sets by the CDC, but substituted fluorophores to allow multiplexing of the assay. The cycle threshold (Ct) values of our multiplex RT-qPCR were comparable to those obtained by the singleplex assay adapted for research purposes. Low copies (>500 copies / reaction) of SARS-CoV-2 RNA were consistently detected by the multiplex RT-qPCR. Our novel multiplex RT-qPCR improves upon current singleplex diagnostics by saving reagents, costs, time and labor.
Single cell transcriptomic profiling identifies molecular phenotypes of newborn human lung cells
Authors: Bhattacharya Soumyaroop , Myers Jacquelyn L. , Baker Cameron , Guo Minzhe , Danopoulos Soula , Myers Jason R. , Bandyopadhyay Gautam , Romas Stephen , Huyck Heidie L. , Misra Ravi S. , Dutra Jennifer , Holden-Wiltse Jeanne , McDavid Andrew , Ashton John M. , Alam Denise Al , Potter S. Steven , Whitsett Jeffrey A. , Xu Yan , Pryhuber Gloria S. , Mariani Thomas J. 
Published: June 2020

AbstractRationaleWhile animal model studies have extensively defined mechanisms controlling cell diversity in the developing mammalian lung, the limited data available from late stage human lung development represents a significant knowledge gap. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung.MethodsSingle cell RNA sequencing generated transcriptional profiles of 5500 cells obtained from two one-day old human lungs (born at gestational ages of 39 and 31 weeks) from the LungMAP Human Tissue Core Biorepository at the University of Rochester. Frozen single cell isolates were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Single cell sequence data from 32000 postnatal day 1, 3, 7 and 10 mouse lung (n = 2 at each time point) cells generated by the LungMAP Research Center at Cincinnati Children’s Hospital and Medical Center, using Dropseq platform, was integrated with the human data. In situ hybridization was used to confirm the spatial location of cellular phenotypes.ResultsTranscriptional interrogation of donor newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, and immune cells and signature genes for each of these populations were identified. Computational integration of newborn human and postnatal mouse lung development cellular transcriptomes facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the human and mouse cellular transcriptomes also demonstrated cell type-specific differences in developmental states of the newborn human lung cells. In particular, matrix fibroblasts could be separated into those representative of younger cells (n=393), or older cells (n=158).This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of development. Our results indicate that integrated single cell RNA profiling of human and mouse lung will help identify common and species-specific mechanisms of lung development and respiratory disease.
Longitudinal Saliva Omics Responses to Immune Perturbation: A Case Study
Authors: Mias George I. , Singh Vikas Vikram , Rogers Lavida R.K. , Xue Shuyue , Zheng Minzhang , Domanskyi Sergii , Kanada Masamitsu , Piermarocchi Carlo , He Jin 
Published: June 2020

ABSTRACTSaliva omics, a rapidly developing field for non-invasive diagnostics, may be utilized for monitoring very young or elderly populations, as well as individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over 100 timepoints, over three periods involving: (i) hourly sampling over 24 hours without intervention, (ii) hourly sampling over 24 hours including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (iii) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome were profiled, and salivary extracellular vesicles were derived, from which small-RNA sequencing was used to determine RNA, miRNA, piRNA and bacterial RNA components. The two 24-hour periods were used in a paired analysis to reveal vaccination responses. Temporal trends were classified and collective behavior revealed broad immune-responses captured in saliva, both at the innate as well as the adaptive response time frames.
Time Course of COVID-19 epidemic in Algeria: Retrospective estimate of the actual burden
Authors: Hamidouche Mohamed , Belmessabih Nassira 
Published: June 2020

AbstractSince December 2019, the five continents have been incrementally invaded by SARS-CoV-2. Africa is the last and least affected to date. However, Algeria is among the first countries affected since February 25, 2020. In order to benefit from its experience in the least affected countries, this study aims to describe the epidemic’s current situation and then retrospectively estimate its real burden.As a first part of the study, we described the epidemic’s indicators as; the cumulative and daily reported cases and deaths, and we computed the R0 evolution. Secondly, we used the New York City cases-fatality rate standardized by Algerian age structure, to retrospectively estimate the actual burden.We found that reported cases are in a clear diminution, but, the epidemic epicentre is moving from Blida to other cities. We noted a clear peak in daily cases-fatality from March 30, to April 17, 2020, Fig. 3, due to underestimating the actual infections of the first 25 days. Since May 8, 2020, the daily R0 is around one, Fig. 4. Moreover, we noticed 31% reduction of its mean value from 1,41 to 0,97 between the last two months. The Algerian Age-Standardized Infection Fatality Rate we found is 0,88%. Based on that, we demonstrated that only 1,5% of actual infections were detected and reported before March 30, and 20% after March 31, Fig. 5. Therefore, the actual infections burden is currently five times higher than reported. At the end, we found that at least 0,2 % of the population have been infected until May 27. Consequently, the acquired herd immunity to date is therefore not sufficient to avoid a second wave.We believe that, the under estimation of the epidemic’s actual burden is probably due to the lack of testing capacities, however, all the indicators show that the situation is currently controlled. This requires more vigilance for the next weeks during the gradual easing of the preventive measures.