bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated With Emergency Department Health Professionals' Attitudes Toward Family Presence During Adult Resuscitation in 9 Greek Hospitals
Authors: Bellali Thalia , Manomenidis Georgios , Platis Charalampos , Kourtidou Eleni , Galanis Petros 
Published: July 2020

Background
Different cultural context results in variability in health professionals' attitude toward family presence in the emergency department (ED) during resuscitation. Knowledge about emergency department health professionals' (EDHPs') attitude toward family presence during resuscitation (FPDR) in Greece can contribute to the understanding of cultural and value-related obstacles and opportunities to implement this practice. It would be useful for Greek health professionals when they have to care for citizens from other countries in which guidelines for FPDR exist to understand their difference in behavior and reaction and be more tolerant.

Objectives
To explore Greek EDHPs' experiences, concerns, and benefits regarding FPDR and determine the contributing factors that are associated with their positive or negative attitude about the process.

Methods
A convenience sample of 305 health professionals working in the ED of 9 general hospitals of the National Healthcare System in northern Greece participated in a cross-sectional study (response rate, 87.6%).

Results
Positive experience of FPDR was encountered in 65.9% of EDHPs. Only 2.3% reported that they work in EDs where FPDR is allowed. Hospital regional location, previous positive experience of FPDR, and competency in supporting family members during FPDR were independently associated with a positive attitude toward FPDR.

Conclusions
Greek EDHPs are not ready to accept FPDR practice. The establishment of formal policy similarly to resuscitation guidelines and family-centered training courses are needed to mitigate negative beliefs. Attempts to enhance positive attitude should include educational interventions providing knowledge on the benefits of FPDR.
Age-Based Percentiles of Measured Mean Arterial Pressure in Pediatric Patients in a Hospital Setting
Authors: Roberts Joan S. , Yanay Ofer , Barry Dwight 
Published: July 2020

Objectives:
To develop and validate age-specific percentile curves of measured mean arterial pressure for children in a hospital setting.

Design:
Retrospective observational study of electronic records.

Setting:
Tertiary care, freestanding pediatric hospital in Seattle, WA.

Patients:
Nonpremature children, birth to 18 years old, evaluated in the emergency room, or admitted to either acute care or critical care units.

Interventions:
Oscillometric blood pressure data collected from February 2012 to June 2016 were examined for documentation of systolic, diastolic, and mean arterial pressure values. Quantile curves were developed using restricted cubic splines and validated with two sets of patient data. The effects of birth sex and behavioral state on the curves were examined. The frequency of values less than 5th percentile for mean arterial pressure within a population was compared with four published criteria for hypotension.

Measurements and Main Results:
Eighty-five–thousand two-hundred ninety-eight patients (47% female) provided 2,385,122 mean arterial pressure readings to develop and validate age-based distributions to create percentile curves and a reference table. The behavior state of patients affected the curves, with disturbed behavior state more prevalent in toddler-aged patients. There was no clinical difference between females and males within age brackets. Mean arterial pressure quantiles identified additional hypotensive episodes as compared with systolic blood pressure thresholds and predicted mean arterial pressure values. Code and data available at: https://osf.io/upqtv/.

Conclusions:
This is the first study reporting age-specific quantiles of measured mean arterial pressure in children in a hospital setting. The percentile curves may guide care in illnesses when perfusion pressure is critical and serve as parameter for bedside and electronic record-based response to clinical change. Future work to correlate threshold mean arterial pressure values with outcomes would be feasible based on quantile curves.
Rapid Diagnostic Tests for Meningitis and Encephalitis—BioFire
Authors: Fleischer Eduardo , Aronson Paul L. 
Published: July 2020

Abstract
Meningitis and encephalitis (ME) are important causes of morbidity and mortality worldwide. Patients suspected of having ME are often hospitalized and started on empiric antimicrobial treatment, because of the potential adverse consequences of delaying the diagnosis or treatment. Multiplexed polymerase chain reaction panels are one of several rapid diagnostic technologies that have the potential to overcome some of the limitations of conventional diagnostic methods for ME. The BioFire FilmArray Meningitis/Encephalitis Panel was the first Food and Drug Administration–cleared multiplex polymerase chain reaction for the evaluation of cerebrospinal fluid samples, able to identify 14 organisms in a single test reaction. This newer rapid diagnostic tool has an overall high sensitivity and specificity for the diagnosis of ME with a fast turnaround time and has the potential to improve resource utilization for patients presenting with suspicion of ME. However, further research is needed to determine its optimal use in the evaluation of patients with suspected ME.
The final step of 40S ribosomal subunit maturation is controlled by a dual key lock
Authors: Plassart Laura , Shayan Ramtin , Montellese Christian , Rinaldi Dana , Larburu Natacha , Pichereaux Carole , Lebaron Simon , O’Donohue Marie-Françoise , Kutay Ulrike , Marcoux Julien , Gleizes Pierre-Emmanuel , Plisson-Chastang Célia 
Published: July 2020

ABSTRACTPreventing premature interaction of preribosomes with the translation apparatus is essential to translation accuracy. Hence, the final maturation step releasing functional 40S ribosomal subunits, namely processing of the 18S ribosomal RNA 3’ end, is safeguarded by protein DIM2, which both interacts with the endoribonuclease NOB1 and masks the rRNA cleavage site. To elucidate the control mechanism that unlocks NOB1 activity, we performed cryo-EM analysis of late human pre-40S particles purified using a catalytically-inactive form of ATPase RIO1. These structures, together with in vivo and in vitro functional analyses, support a model in which ATP-loaded RIO1 cooperates with ribosomal protein RPS26/eS26 to displace DIM2 from the 18S rRNA 3’ end, thereby triggering final cleavage by NOB1; release of ADP then leads to RIO1 dissociation from the 40S subunit. This dual key lock mechanism requiring RIO1 and RPS26 guarantees the precise timing of pre-40S particle conversion into translation-competent ribosomal subunits.
Mucin-type O-glycosylation Landscapes of SARS-CoV-2 Spike Proteins
Authors: Zhang Yong , Zhao Wanjun , Mao Yonghong , Chen Yaohui , Zhu Jingqiang , Hu Liqiang , Gong Meng , Cheng Jingqiu , Yang Hao 
Published: July 2020

ABSTRACTThe densely glycosylated spike (S) proteins that are highly exposed on the surface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitate viral attachment, entry, and membrane fusion. We have previously reported all the 22N-glycosites and site-specificN-glycans in the S protein protomer. Herein, we report the comprehensive and precise site-specific O-glycosylation landscapes of SARS-CoV-2 S proteins, which were characterized using high-resolution mass spectrometry. Following digestion using trypsin and trypsin/Glu-C, and de-N-glycosylation using PNGase F, we determined the mucin-type (GalNAc-type) O-glycosylation pattern of S proteins, including unambiguousO-glycosites and the 6 most commonO-glycans occupying them, via Byonic identification and manual validation. Finally, 43O-glycosites were identified in the insect cell-expressed S protein. Most glycosites were modified by non-sialylatedO-glycans such as HexNAc(1) and HexNAc(1)Hex(1). In contrast, 30O-glycosites were identified in the human cell-expressed S protein S1 subunit. Most glycosites were modified by sialylatedO-glycans such as HexNAc(1)Hex(1)NeuAc(1) and HexNAc(1)Hex(1)NeuAc(2). Our results are the first to reveal that the SARS-CoV-2 S protein is a mucin-type glycoprotein; clusteredO-glycans often occur in the N- and the C-termini of the S protein, and theO-glycosite andO-glycan compositions vary with the host cell type. These site-specific O-glycosylation landscapes of the SARS-CoV-2 S protein are expected to provide novel insights into the viral binding mechanism and present a strategy for the development of vaccines and targeted drugs.
Whole genome sequencing based differentiation between re-infection and relapse in Indian patients with tuberculosis recurrence, with and without HIV co-infection
Authors: Shanmugam Sivakumar , Bachmann Nathan L , Martinez Elena , Menon Ranjeeta , Narendran Gopalan , Narayanan Sujantha , Tripathy Srikanth , Devi K R Uma , Sawleshwarkar Shailendra , Marais Ben , Sintchenko Vitali 
Published: July 2020

AbstractDifferentiation between relapse and reinfection in cases with tuberculosis (TB) recurrence has important implications for public health, especially in patients with human immunodeficiency virus (HIV) co-infection. Forty-one pairedM. tuberculosisisolates collected from 20 HIV-positive and 21 HIV-negative patients, who experienced TB recurrence after previous successful treatment, were subjected to whole genome sequencing (WGS) in addition to spoligotyping and mycobacterial interspersed repeat unit (MIRU) typing. Comparison ofM. tuberculosisgenomes indicated that 95% of TB recurrences in the HIV-negative cohort were due to relapse, while the majority of TB recurrences (75%) in the HIV-positive cohort was due to re-infection (P=0.0001). Drug resistance conferring mutations were documented in four pairs (9%) of isolates associated with relapse. The high contribution of re-infection to TB among HIV patients warrants further study to explore risk factors for TB exposure in the community.
Critical Mobility, a practical criterion and early indicator for regional COVID-19 resurgence
Authors: Freitag Marcus O. , Schmude Johannes , Siebenschuh Carlo , Stolovitzky Gustavo , Hamann Hendrik F. , Lu Siyuan 
Published: July 2020

AbstractThe sharp reduction of human mobility in March 2020, as observed by anonymized cellphone data, has played an important role in thwarting a runaway COVID-19 pandemic. As the world is reopening, the risks of new flare-ups are rising. We report a data-driven approach, grounded in strong correlation between mobility and growth in COVID-19 cases two weeks later, to establish a spatial-temporal model of “critical mobility” maps that separate relatively safe mobility levels from dangerous ones. The normalized difference between the current and critical mobility has predictive power for case trajectories during the “opening-up” phases. For instance, actual mobility has risen above critical mobility in many southern US counties by the end of May, foreshadowing the latest virus resurgence. Encouragingly, critical mobility has been rising throughout the USA, likely due to face mask-wearing and social distancing measures. However, critical mobility is still well below pre-COVID mobility levels in most of the country suggesting continued mobility-reduction is still necessary.
Impact of low-frequency coding variants on human facial shape
Authors: Liu Dongjing , Alhazmi Nora , Matthews Harold , Lee Myoung Keun , Li Jiarui , Hecht Jacqueline T. , Wehby George L. , Moreno Lina M. , Heike Carrie L. , Roosenboom Jasmien , Feingold Eleanor , Marazita Mary L. , Claes Peter , Liao Eric C. , Weinberg Seth M. , Shaffer John R. 
Published: July 2020

AbstractThe contribution of low-frequency variants to the genetic architecture of normal-range facial traits is unknown. We studied the influence of low-frequency coding variants (MAF < 1%) on multi-dimensional facial shape phenotypes in 2329 healthy Europeans. We used MultiSKAT o scan the exome for face-associated low-frequency variants in a gene-based manner. Seven genes (AR, CARS2, FTSJ1, HFE, LTB4R, TELO2, NECTIN1) were significantly associated with shape variation of the cheek, chin, nose and mouth areas. These genes displayed a wide range of phenotypic effects, with some impacting the full face and others affecting localized regions. The missense variant rs142863092 inNECTIN1had a significant effect on chin morphology, and was predicted bioinformatically to be deleterious.NECTIN1is an established craniofacial gene that underlies a human syndrome that includes a mandibular phenotype. We further showed thatnectin1amutations can affect zebrafish craniofacial development, with the size and shape of the mandibular cartilage altered in mutant animals. These Findings highlighted the role of low-frequency coding variants in normal-range facial variation.
Genomic prediction for malting quality traits in practical barley breeding programs
Authors: Sarup Pernille , Edriss Vahid , Kristensen Nanna Hellum , Jensen Jens Due , Orabi Jihad , Jahoor Ahmed , Jensen Just 
Published: July 2020

AbstractGenomic prediction can be advantageous in barley breeding for traits such as yield and malting quality to increase selection accuracy and minimize expensive phenotyping. In this paper, we investigate the possibilities of genomic selection for malting quality traits using a limited training population. The size of the training population is an important factor in determining the prediction accuracy of a trait. We investigated the potential for genomic prediction of malting quality within breeding cycles with leave one out (LOO) cross-validation, and across breeding cycles with leave set out (LSO) cross-validation. In addition, we investigated the effect of training population size on prediction accuracy by random two, four, and ten-fold cross-validation. The material used in this study was a population of 1329 spring barley lines from four breeding cycles. We found medium to high narrow sense heritabilities of the malting traits (0.31 to 0.65). Accuracies of predicting breeding values from LOO tests ranged from 0.6 to 0.9 making it worth the effort to use genomic prediction within breeding cycles. Accuracies from LSO tests ranged from 0.39 to 0.70 showing that genomic prediction across the breeding cycles were possible as well. Accuracy of prediction increased when the size of the training population increased. Therefore, prediction accuracy might be increased both within and across breeding cycle by increasing size of the training population
PTPN11/SHP2 negatively regulates growth in breast epithelial cells: implications on tumorigenesis
Authors: Chakladar Madhumita , Nair Madhumathy G , Prabhu Jyothi S , Sridhar T S , Kelkar Devaki , Kulkarni Madhura , Shashidhara LS 
Published: July 2020

AbstractPTPN11/SHP2, a non-receptor protein tyrosine phosphatase is a prominent target of the receptor tyrosine kinase that participates in positive feedback signalling of the human epidermal growth factor receptors and helps in growth and migration. PTPN11/SHP2 is widely believed to be an oncoprotein, although it’s possible tumor-suppressor role is also reported. Our analysis of breast cancer metadata shows, PTPN11/SHP2 copy number loss in luminal A subtype is correlated to poor disease-specific survival and late-stage cancer at diagnosis. Analysis of the level 4 Reverse Phase Protein Array (RPPA) data available on the TCGA database resulted in positive correlations between the lower expression levels of constitutively active variant, the phospho-SHP2-Y542, of PTPN11/SHP2 and larger tumor size and lymph node positivity. We experimentally examined possible negative regulation of growth by PTPN11/SHP2 using MCF10A, a normal breast epithelial cell line. Knock-down of PTPN11/SHP2 resulted in increased cell migration, cell shape changes to mesenchymal morphology, and increased survival in cells treated with epirubicin, a DNA-damaging drug. However, it did not alter the rate of cell proliferation. It is possible that PTPN11/SHP2 might function as a tumor suppressor by potentiating proliferating cells with increased cell migration and resistance to apoptosis.Statement of SignificanceMolecules likePTPN11/SHP2, among many others that show dual specificity in tumorigenesis in the same tissue depending on the upstream signaling cues, present challenges in the field of targeted drug therapy. This study puts forth the importance of understanding the mechanism of one of the two outcomes and thereby helps better clinical management of a subgroup of cancer.
Exploration of theNeisseriaresistome reveals resistance mechanisms in commensals that may be acquired byN. gonorrhoeaethrough horizontal gene transfer
Authors: Fiore Michael A. , Raisman Jordan C. , Wong Narayan H. , Hudson André O. , Wadsworth Crista B. 
Published: July 2020

AbstractNon-pathogenicNeisseriahave repeatedly been demonstrated to transfer antibiotic resistance genes to their pathogenic relative,Neisseria gonorrhoeae.However, the resistance genotypes and subsequent phenotypes of non-pathogens within the genus have been studied and described less frequently. Here, we use Etests to characterize the minimum inhibitory concentrations (MICs) of a panel ofNeisseria(n=26) – including several commensal species – acquired from the CDC & FDA’s Antibiotic Resistance (AR) Isolate Bank to a suite of diverse antibiotics. We furthermore use whole genome sequencing and the Comprehensive Antibiotic Resistance Database (CARD) Resistance Gene Identifier (RGI) platform to predict possible causal resistance-encoding mutations. Within this panel, resistant isolates to all tested antimicrobials including penicillin (n=5/26), ceftriaxone (n=2/26), cefixime (n=3/26), tetracycline (n=10/26), azithromycin (n=11/26), and ciprofloxacin (n=4/26) were found. In total we identify 63 distinct mutations predicted by RGI to be involved in resistance. The presence of several of these mutations had clear associations with increases in MIC such as: DNA gyrase subunit A (gyrA) (S91F) and ciprofloxacin, tetracycline resistance protein (tetM) and 30S ribosomal protein S10 (rpsJ) (V57M) and tetracycline, and TEM-type β-lactamases and penicillin. However, mutations with strong associations to macrolide and cephalosporin resistance were not conclusive. This work serves as an initial exploration into the resistance-encoding mutations harbored by non-pathogenicNeisseria,which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired byN. gonorrhoeae.
miR-100-5p downregulates mTOR to suppress the proliferation, migration and invasion of prostate cancer cells
Authors: Li Su-Liang , Ye Yun , Wang Jian-Jun 
Published: July 2020

AbstractBackgroundPrevious studies have shown that miR-100-5p expression is abnormal in prostate cancer. However, the role and regulatory mechanism of miR-100-5p requires further investigation. Thus, the aim of this study was to observe the effects of miR-100-5p on the proliferation, migration and invasion of prostate cancer (PCa) cells and to explore the potential related regulatory mechanism.MethodsDifferential miRNA expression analysis was performed using next-generation sequencing (NGS) in the PCa cell line LNCaP and the normal prostatic epithelial cell line RWPE-1. The expression levels of miR-100-5pwere detected using real-time fluorescence quantitative PCR (qRT-PCR). LNCaP cells were transfected with NC-mimics or miR-100-5p mimics by using liposome transfection. Moreover, the CCK-8 proliferation assay, cell scratch assay and Transwell assay were used to detect the effects of miR-100-5p on cell proliferation, migration and invasion. In addition, the potential target gene of miR-100-5p was predicted, and the influence of miR-100-5p on the expression of mTOR mRNA by qRT-PCR and the expression of mTOR protein was detected by western blot and immunohistochemical staining.ResultsDifferential expression analysis of high-throughput sequencing data showed low expression of miR-100-5p in the PCa cell line LNCaP. It was further confirmed by qRT-PCR that the expression of miR-100-5p in LNCaP cells was significantly lower than that in RWPE-1 cells (P<0.01). miR-100-5p expression in LNCaP cells was markedly upregulated after transfection with miR-100-5p mimics (P<0.01), while cell proliferation, migration and invasion capacities were clearly reduced (P<0.01), and mTOR mRNA and protein expression was also substantially lowered (P<0.01). Finally, we further confirmed by immunohistochemical staining that miR-100-5p regulated the expression of mTOR.ConclusionmiR-100-5p is expressed at low levels in LNCaP cells, and it can suppress LNCaP cell proliferation, migration and invasion, the mechanism of which is related to downregulating the expression of mTOR.
RIP140 inhibits glycolysis-dependent proliferation of breast cancer cells by regulating GLUT3 expression through transcriptional crosstalk between hypoxia induced factor and p53
Authors: Jacquier Valentin , Gitenay Delphine , Fritsch Samuel , Bonnet Sandrine , Győrffy Balázs , Jalaguier Stéphan , Linares Laetitia K. , Cavaillès Vincent , Teyssier Catherine 
Published: July 2020

AbstractCancer cells with uncontrolled proliferation preferentially depend on glycolysis to grow, even in the presence of oxygen. The transcriptional co-regulator RIP140 represses the activity of transcription factors that drive cell proliferation and metabolism and plays a role in mammary tumorigenesis. Here we use cell proliferation and metabolic assays to demonstrate that RIP140-deficiency causes a glycolysis-dependent increase in breast tumor growth. We further demonstrate that RIP140 reduces the transcription of the glucose transporter GLUT3 gene, by inhibiting the transcriptional activity of hypoxia inducible factor HIF-2α in cooperation with p53. Interestingly, RIP140 expression was significantly associated with good prognosis only for breast cancer patients with tumors expressing low GLUT3, low HIF-2α and high p53, thus confirming the mechanism of RIP140 anti-tumor activity provided by our experimental data. Overall, our work establishes RIP140 as a critical modulator of the p53/HIF cross-talk to inhibit breast cancer cell glycolysis and proliferation.
Biochemical Patterns of Antibody Polyreactivity Revealed Through a Bioinformatics-Based Analysis of CDR Loops
Authors: Boughter Christopher T. , Borowska Marta T. , Guthmiller Jenna J. , Bendelac Albert , Wilson Patrick C. , Roux Benoit , Adams Erin J. 
Published: July 2020

AbstractAntibodies are critical components of adaptive immunity, binding with high affinity to pathogenic epitopes. Antibodies undergo rigorous selection to achieve this high affinity, yet some maintain an additional basal level of low affinity, broad reactivity to diverse epitopes, a phenomenon termed “polyreactivity”. While polyreactivity has been observed in antibodies isolated from various immunological niches, the biophysical properties that allow for promiscuity in a protein selected for high affinity binding to a single target remain unclear. Using a database of nearly 1,500 polyreactive and non-polyreactive antibody sequences, we created a bioinformatic pipeline to isolate key determinants of polyreactivity. These determinants, which include an increase in inter-loop crosstalk and a propensity for an “inoffensive” binding surface, are sufficient to generate a classifier able to identify polyreactive antibodies with over 75% accuracy. The framework from which this classifier was built is generalizable, and represents a powerful, automated pipeline for future immune repertoire analysis.