bluuebunny/crossref_metadata_2025_split huggingface dataset:
Awareness of HIV Preexposure Prophylaxis Among People at Risk for HIV: Results From the 2017–2019 National Survey of Family Growth
Authors: Keddem Shimrit , Dichter Melissa E. , Hamilton Alison B. , Chhatre Sumedha , Sonalkar Sarita 
Published: June 2021

Background
Although daily preexposure prophylaxis (PrEP) is now widely accepted as a safe and effective method for reducing the risk of HIV in high-risk groups, uptake has been slow. The goal of this analysis was to identify factors associated with PrEP awareness among individuals at risk for HIV.

Methods
This investigation analyzed data from the Centers for Disease Control and Prevention nationally representative survey, National Survey of Family Growth, for the years 2017 to 2019. Logistic regression was used to explore the relationship between PrEP awareness and demographics, HIV risk factors, and provider HIV risk screening.

Results
Only 37% of survey respondents with an increased risk of HIV were aware of PrEP. Several segments of the at-risk population had lower odds of being aware of PrEP, including heterosexual women, heterosexual men, individuals younger than 20 years, and individuals with lower levels of education. Those who participate in sex in exchange for money or drugs had significantly lower odds of being aware of PrEP. In comparison, PrEP awareness was significantly higher among nonheterosexual men and both men and women whose partners were HIV positive. Lastly, those who had been screened by a provider for HIV risk had significantly higher odds of being aware of PrEP.

Conclusions
This research supports the need for policies and programs to increase awareness of PrEP, especially among certain segments of the population at increased risk for HIV.
Effects of Orthoses on Standing Postural Control and Muscle Activity in Children With Cerebral Palsy
Authors: Leonard Rebecca , Sweeney Jane , Damiano Diane , Bjornson Kristie , Ries Julie 
Published: June 2021

Purpose:
This exploratory study assessed postural control and muscle activity in children with cerebral palsy while standing barefoot (BF), in prescribed ankle-foot orthoses (AFOs) and in distal control orthoses (DCOs), which stabilized foot-ankle and deliberately aligned the shank.

Methods:
This within-subject study evaluated 10 participants, Gross Motor Functional Classification System level III, across the 3 ankle-foot conditions in: (1) static standing duration and (2) modified Clinical Test of Sensory Interaction on Balance with electromyography (EMG) on 7 muscles.

Results:
Participants had significantly decreased center of gravity (COG) velocity sway in DCO versus BF and AFO, decreased loss of balance (LOB), and increased standing for DCO versus BF. DCO had minimal effect on EMG activity.

Conclusions:
DCO provided significant stabilizing effects on COG sway velocity, standing duration, and LOB. DCO may be effective in balance training. It is unclear whether benefit was derived from stabilization of the ankle joint, the resultant shank alignment, or both.
Police transport of firearm-injured patients—more often and more injured
Authors: Maher Zoё , Beard Jessica H. , Dauer Elizabeth , Carroll Madeleine , Forman Steven , Topper Gena V. , Pathak Abhijit , Santora Thomas A. , Sjoholm Lars Ola , Zhao Huaqing , Goldberg Amy J. 
Published: June 2021

BACKGROUND
Police transport (PT) of penetrating trauma patients decreases the time between injury and trauma center arrival. Our study objective was to characterize trends in the rate of PT and its impact on mortality. We hypothesized that PT is increasing and that these patients are more injured.

METHODS
We conducted a single-center, retrospective cohort study of adult (≥18 years) patients presenting with gunshot wounds (GSWs) to a level 1 center from 2012 to 2018. Patients transported by police or ambulance (emergency medical service [EMS]) were included. The association between mode of transport (PT vs. EMS) and mortality was evaluated using χ2, t tests, Mann-Whitney U tests, and logistic regression.

RESULTS
Of 2,007 patients, there were 1,357 PT patients and 650 EMS patients. Overall in-hospital mortality was 23.7%. The rate of GSW patients arriving by PT increased from 48.9% to 78.5% over the study period (p < 0.001). Compared with EMS patients, PT patients were sicker on presentation with lower initial systolic blood pressure (98 vs. 110, p < 0.001), higher Injury Severity Score (median [interquartile range], 10 [2–75] vs. 9 [1–17]; p < 0.001) and more bullet wounds (3.5 vs. 2.9, p < 0.001). Police-transported patients more frequently underwent resuscitative thoracotomy (19.2% vs. 10.0%, p < 0.001) and immediate surgical exploration (31.3% vs. 22.6%, p < 0.001). There was no difference in adjusted in-hospital mortality between transport groups. Of patients surviving to discharge, PT patients had higher Injury Severity Score (9.6 vs. 8.3, p = 0.004) and lower systolic blood pressure on arrival (126 vs. 130, p = 0.013) than EMS patients.

CONCLUSION
Police transport of GSW patients is increasing at our urban level 1 center. Compared with EMS patients, PT patients are more severely injured but have similar in-hospital mortality. Further study is necessary to understand the impact of PT on outcomes in specific subsets in penetrating trauma patients.

LEVEL OF EVIDENCE
Epidemiological, level III.
Prehospital end-tidal carbon dioxide predicts hemorrhagic shock upon emergency department arrival
Authors: Bulger Natalie , Harrington Brenna , Krieger Josh , Latimer Andrew , Arbabi Saman , Counts Catherine R. , Sayre Michael , Maynard Charles , Bulger Eileen M. 
Published: June 2021

BACKGROUND
In addition to reflecting gas exchange within the lungs, end-tidal carbon dioxide (ETCO2) also reflects cardiac output based on CO2 delivery to the pulmonary parenchyma. We hypothesized that low prehospital ETCO2 values would be predictive of hemorrhagic shock in intubated trauma patients.

METHODS
A retrospective observational study of adult trauma patients intubated in the prehospital setting and transported to a single Level I trauma center from 2016 to 2019. Continuous prehospital ETCO2 data were linked with patient care registries. We developed a novel analytic approach that allows for reflection of prehospital ETCO2 over the entire prehospital course of care. The primary outcome was hemorrhagic shock on emergency department (ED) presentation, defined as either initial ED systolic blood pressure of 90 mm Hg or less or initial Shock Index (SI) > 0.9, and transfusion of at least one unit of blood product during their ED stay. Prehospital ETCO2 less than 25 mm Hg was evaluated for predictive value of hemorrhagic shock.

RESULTS
Three hundred and seven patients (82% men, 34% penetrating injury, 42% in hemorrhagic shock on ED arrival, 27% mortality) were included in the study. Patients in hemorrhagic shock had lower median ETCO2 values (26.5 mm Hg vs. 32.5 mm Hg; p < 0.001) than those not in hemorrhagic shock. Patients with prehospital ETCO2 less than 25 mm Hg were 3.0 times (adjusted odds ratio = 3.0; 95% confidence interval, 1.1–7.9) more likely to be in hemorrhagic shock upon ED arrival than patients with ETCO2 ≥ 25 mm Hg.

CONCLUSION
Intubated patients with hemorrhagic shock upon ED arrival had significantly lower prehospital ETCO2 values. Incorporating ETCO2 assessment into prehospital care for trauma patients could support decisions regarding prehospital blood transfusion, and triage to higher-level trauma centers, and trauma team activation.

LEVEL OF EVIDENCE
Prognostic, level III.
A Combined microRNA and Chemokine Profile in Urine to Identify Rejection After Kidney Transplantation
Authors: Gielis Els M. , Anholts Jacqueline D.H. , van Beelen Els , Haasnoot Geert W. , De Fijter Hans W. , Bajema Ingeborg , Heidt Sebastiaan , van de Vrie Mathijs , Hilbrands Luuk B. , Mallat Marko J.K. , Ledeganck Kristien J. , Claas Frans H.J. , Eikmans Michael 
Published: June 2021

Background.
There is an unmet need for noninvasive tools for diagnosis of rejection after kidney transplantation. The aim of this study was to determine the discriminative value of a combined cellular and molecular biomarker platform in urine for the detection of rejection.

Methods.
First, microRNA (miR) molecules were screened in transplant biopsies and urine sediments of patients with acute rejection and patients without rejection and stable graft function. Second, the expression of 15 selected miRs was quantified in an independent set of 115 urine sediments of patients with rejection and 55 urine sediments of patients without histological signs of rejection on protocol biopsy. Additionally, CXCL-9 and CXCL-10 protein levels were quantified in the urine supernatant.

Results.
Levels of miR-155-5p (5.7-fold), miR-126-3p (4.2-fold), miR-21-5p (3.7-fold), miR-25-3p (2.5-fold), and miR-615-3p (0.4-fold) were significantly different between rejection and no-rejection urine sediments. CXCL-9 and CXCL-10 levels were significantly elevated in urine from recipients with rejection. In a multivariable model (sensitivity: 89.1%, specificity: 75.6%, area under the curve: 0.94, P < 0.001), miR-155-5p, miR-615-3p, and CXCL-9 levels were independent predictors of rejection. Stratified 10-fold cross validation of the model resulted in an area under the curve of 0.92.

Conclusions.
A combined urinary microRNA and chemokine profile discriminates kidney transplant rejection from stable graft conditions.
Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics
Authors: Dyson Louise , Hill Edward M. , Moore Sam , Curran-Sebastian Jacob , Tildesley Michael J. , Lythgoe Katrina A , House Thomas , Pellis Lorenzo , Keeling Matt J. 
Published: June 2021

AbstractViral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.
Immunity to SARS-CoV-2 persists 9 months post-symptoms with an altered T cell phenotype compared to influenza A virus-specific memory
Authors: Law Jaclyn C. , Girard Melanie , Chao Gary Y. C. , Ward Lesley A. , Isho Baweleta , Rathod Bhavisha , Colwill Karen , Li Zhijie , Rini James M. , Yue Feng Yun , Mubareka Samira , McGeer Allison J. , Ostrowski Mario A. , Gommerman Jennifer L. , Gingras Anne-Claude , Watts Tania H. 
Published: June 2021

AbstractSARS-CoV-2 induces T cell, B cell and antibody responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. Here we followed T cell and antibody responses in 24 mainly non-hospitalized SARS-CoV-2 recovered subjects at two time points (median of 45- and 145-days post-symptom onset). Antibody responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-S and anti-RBD IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. Based on intracellular cytokine production or proliferation, CD4+T cell responses to SARS-CoV-2 were detected in all subjects, decaying with a half-life of 5-6 months for S-specific IL-2-producing cells. CD4+responses were largely of the T helper 1 phenotype, but with a lower ratio of IFN-γ: IL-2 producing cells and a lower frequency of CD8+:CD4+T cells compared to influenza A virus-(IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ: IL-2 and IFN-γ: IL-6 and an altered cytotoxic profile for S- and N-specific compared to IAV-specific responses. These data suggest that the memory T-cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxic profile compared to long term memory to IAV within the same subjects.One Sentence SummaryImmunity to SARS-CoV-2 in a cohort of patients, mainly with mild COVID-19 disease, persists to 9 months with an altered T cell cytokine and cytotoxicity profile compared to influenza A virus-specific memory T cells from the same subjects.
SARS-CoV-2 B.1.617 Indian variants: are electrostatic potential changes responsible for a higher transmission rate?
Authors: Pascarella Stefano , Ciccozzi Massimo , Zella Davide , Bianchi Martina , Benetti Francesca , Broccolo Francesco , Cauda Roberto , Caruso Arnaldo , Angeletti Silvia , Giovanetti Marta , Cassone Antonio 
Published: June 2021

AbstractLineage B.1.617+, also known as G/452R.V3, is a recently described SARS-CoV-2 variant under investigation (VUI) firstly identified in October 2020 in India. As of May 2021, three sublineages labelled as B.1.617.1, B.1.617.2 and B.1.617.3 have been already identified, and their potential impact on the current pandemic is being studied. This variant has 13 amino acid changes, three in its spike protein, which are currently of particular concern: E484Q, L452R and P681R. Here we report a major effect of the mutations characterizing this lineage, represented by a marked alteration of the surface electrostatic potential (EP) of the Receptor Binding Domain (RBD) of the spike protein. Enhanced RBD-EP is particularly noticeable in the B.1.617.2 sublineage, which shows multiple replacements of neutral or negatively-charged amino acids with positively-charged amino acids. We here hypothesize that this EP change can favor the interaction between the B.1.617+RBD and the negatively-charged ACE2 thus conferring a potential increase in the virus transmission.
Regulation of brain aging by neutral sphingomyelinase 2
Authors: Zhu Zhihui , Quadri Zainuddin , Crivelli Simone M. , Elsherbini Ahmed , Zhang Liping , Tripathi Priyanka , Qin Haiyan , Roush Emily , Spassieva Stefka D. , Nikolova-Karakashian Mariana , McClintock Timothy S. , Bieberich Erhard 
Published: June 2021

AbstractWe have shown that deficiency of neutral sphingomyelinase 2 (nSMase2), an enzyme generating the sphingolipid ceramide, improves memory in adult mice. Here, we performed sphingolipid and RNA-seq analyses on the cortex from 10 month-old nSMase2-deficient (fro/fro) and heterozygous (+/fro) mice. fro/fro cortex showed reduced levels of ceramide, particularly in astrocytes. Differentially abundant transcripts included several functionally related groups, with decreases in mitochondrial oxidative phosphorylation and astrocyte activation transcripts, while axon guidance and synaptic transmission transcripts were increased, indicating a role of nSMase2 in oxidative stress, astrocyte activation, and cognition. Experimentally induced oxidative stress decreased the level of glutathione (GSH), an endogenous inhibitor of nSMase2, and increased immunolabeling for ceramide in primary +/fro astrocytes, but not in fro/fro astrocytes. β-galactosidase activity was lower in 5-weeks old fro/fro astrocytes, indicating delayed senescence due to nSMase2 deficiency. In fro/fro cortex, levels of the senescence markers C3b and p27, and the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α were reduced, concurrent with 2-fold decreased phosphorylation of their downstream target, protein kinase Stat3. RNA and protein levels of the ionotropic glutamate receptor subunit 2b (Grin2b or NR2B) were increased by 2-fold, an effect known to enhance cognition. This was consistent with 3.5-fold reduced levels of exosomes carrying miR-223-3p, a micro-RNA downregulating Grin2b. In summary, our data show that nSMase2 deficiency prevents oxidative stress-induced elevation of ceramide and secretion of exosomes by astrocytes that suppress neuronal function, indicating a role of nSMase2 in the regulation of neuroinflammation and cognition during brain aging.Significance statementOxidative stress is associated with brain aging and cognitive decline. The underlying mechanism how oxidative stress impairs brain function is still not clear. We provide evidence that oxidative stress increases ceramide in astrocytes, which is prevented by deficiency of nSMase2, an enzyme that is activated by oxidative stress and generates ceramide from sphingomyelin. Mass spectrometric and transciptomic (RNA-seq) analyses show that in middle aged (10-month old) mouse cortex, nSMase2 deficiency reduces ceramide and increases expression of genes important for synaptic transmission and cognition. Therefore, our data show that oxidative stress-induced activation of nSMase2 and generation of ceramide is significant for cognitive decline during aging.
Country-wide genomic surveillance of SARS-CoV-2 strains
Authors: Kalia Kishan , Saberwal Gayatri , Sharma Gaurav 
Published: June 2021

AbstractGenomic surveillance has enabled the identification of several SARS-CoV-2 variants, allowing the formulation of appropriate public health policies. However, surveillance could be made more effective. We have determined that the time taken from strain collection to genome submission for over 1.7 million SARS-CoV-2 strains available at GISAID. We find that strain-wise, time lag in this process ranges from one day to over a year. Country-wise, the UK has taken a median of 16 days (for 417,287 genomes), India took 57 days (for 15,614 genomes), whereas Qatar spent 289 days (for 2298 genomes). We strongly emphasize that along with increasing the number of genomes of COVID-19 positive cases sequenced, their accelerated submission to GISAID should also be strongly encouraged and facilitated. This will enable researchers across the globe to track the spreading of variants in a timely manner; analyse their biology, epidemiology, and re-emerging infections; and define effective public health policies.
ECCsplorer: a pipeline to detect extrachromosomal circular DNA (eccDNA) from next-generation sequencing data
Authors: Mann Ludwig , Seibt Kathrin M. , Weber Beatrice , Heitkam Tony 
Published: June 2021

AbstractMotivationExtrachromosomal circular DNAs (eccDNAs) are ring-like DNA structures physically separated from the chromosomes with 100 bp to several megabasepairs in size. Apart from carrying tandemly repeated DNA, eccDNAs may also harbor extra copies of genes or recently activated transposable elements. As eccDNAs occur in all eukaryotes investigated so far and likely play roles in stress, cancer, and aging, they have been prime targets in recent research – with their investigation limited by the scarcity of computational tools.ResultsHere, we present the ECCsplorer, a bioinformatics pipeline to detect eccDNAs in any kind of organism or tissue using next-generation sequencing techniques. Following Illumina-sequencing of amplified circular DNA (circSeq), the ECCsplorer enables an easy and automated discovery of eccDNA candidates. The data analysis encompasses two major procedures: First, read mapping to the reference genome allows the detection of informative read distributions including high coverage, discordant mapping, and split reads. Second, reference-free comparison of read clusters from amplified eccDNA against control sample data reveals specifically enriched DNA circles. Both software parts can be run separately or jointly, depending on the individual aim or data availability. To illustrate the wide applicability of our approach, we analyzed semiartificial and published circSeq data from the model organisms H. sapiens and A. thaliana, and generated circSeq reads from the non-model crop B. vulgaris. We clearly identified eccDNA candidates from all datasets, with and without reference genomes. The ECCsplorer pipeline specifically detected mitochondrial mini-circles and retrotransposon activation, showcasing the ECCsplorer’s sensitivity and specificity. The derived eccDNA targets are valuable for a wide range of downstream investigations – from analysis of cancer-related eccDNAs over organelle genomics to identification of active transposable elements.Availability and implementationThe ECCsplorer pipeline is available on GitHub at https://github.com/crimBubble/ECCsplorer under the GNU license.ContactTony Heitkam (tony.heitkam@tu-dresden.de)Supplementary informationSupplementary data are available online.
Genomic Prediction of Strawberry Resistance to Postharvest Fruit Decay Caused by the Fungal PathogenBotrytis cinerea
Authors: Petrasch Stefan , Mesquida-Pesci Saskia D. , Pincot Dominique D.A. , Feldmann Mitchell J. , López Cindy M. , Famula Randi , Hardigan Michael A. , Cole Glenn S. , Knapp Steven J. , Blanco-Ulate Barbara 
Published: June 2021

ABSTRACTGray mold, a disease of strawberry (Fragaria×ananassa) caused by the ubiquitous necrotrophBotrytis cinerea, renders fruit unmarketable and causes economic losses in the postharvest supply chain. To explore the feasibility of selecting for increased resistance to gray mold, we undertook genetic and genomic prediction studies in strawberry populations segregating for fruit quality and shelf life traits hypothesized to pleiotropically affect susceptibility. As predicted, resistance to gray mold was heritable but quantitative genetically complex. While every individual was susceptible, the speed of symptom progression and severity differed. Narrow-sense heritability ranged from 0.38-0.71 for lesion diameter (LD) and 0.39-0.44 for speed of emergence of external mycelium (EM). Even though significant additive genetic variation was genome wide observed for LD and EM, the phenotypic ranges were comparatively narrow and genome-wide analyses did not identify any large effect loci. Genomic selection accuracy ranged from 0.28-0.59 for LD and 0.37-0.47 for EM. Additive genetic correlations between fruit quality and gray mold resistance traits were consistent with prevailing hypotheses: LD decreased as titratable acidity increased, whereas EM increased as soluble solid whole genome content decreased and firmness increased. We concluded that phenotypic and genomic selection could be regression effective for reducing LD and increasing EM, especially in long shelf life populations, but that a significant fraction of the genetic variation for resistance to gray mold was caused by the pleiotropic effects of fruit quality traits that differ among market and shelf life classes.