bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Features and Outcomes of Coronavirus Disease 2019 Among People With Human Immunodeficiency Virus in the United States: A Multicenter Study From a Large Global Health Research Network (TriNetX)
Authors: Yendewa George A , Perez Jaime Abraham , Schlick Kayla , Tribout Heather , McComsey Grace A 
Published: June 2021

Abstract

Background
Human immunodeficiency virus infection (HIV) is a presumed risk factor for severe coronavirus disease 2019 (COVID-19), yet little is known about COVID-19 outcomes in people with HIV (PWH).

Methods
We used the TriNetX database to compare COVID-19 outcomes of PWH and HIV-negative controls aged ≥18 years who sought care in 44 healthcare centers in the United States from January 1 to December 1, 2020. Outcomes of interest were rates of hospitalization (composite of inpatient non-intensive care [ICU] and ICU admissions), mechanical ventilation, severe disease (ICU admission or death), and 30-day mortality.

Results
Of 297 194 confirmed COVID-19 cases, 1638 (0.6%) were HIV-infected, with &gt;83% on antiretroviral therapy (ART) and 48% virally suppressed. Overall, PWH were more commonly younger, male, African American or Hispanic, had more comorbidities, were more symptomatic, and had elevated procalcitonin and interleukin 6. Mortality at 30 days was comparable between the 2 groups (2.9% vs 2.3%, P = .123); however, PWH had higher rates hospitalization (16.5% vs 7.6%, P &lt; .001), ICU admissions (4.2% vs 2.3%, P &lt; .001), and mechanical ventilation (2.4% vs 1.6%, P &lt; .005). Among PWH, hospitalization was independently associated with male gender, being African American, integrase inhibitor use, and low CD4 count; whereas severe disease was predicted by older age (adjusted odds ratio [aOR], 8.33; 95% confidence interval [CI], 1.06–50.00; P = .044) and CD4 &lt;200 cells/mm3 (aOR, 8.33; 95% CI, 1.06–50.00; P = .044).

Conclusions
People with HIV had higher rates of poor COVID-19 outcomes but were not more at risk of death than their non-HIV-infected counterparts. Older age and low CD4 count predicted adverse outcomes.
Climate change adaptation to extreme heat: a global systematic review of implemented action
Authors: Turek-Hankins Lynée L , Coughlan de Perez Erin , Scarpa Giulia , Ruiz-Diaz Raquel , Schwerdtle Patricia Nayna , Joe Elphin Tom , Galappaththi Eranga K , French Emma M , Austin Stephanie E , Singh Chandni , Siña Mariella , Siders A R , van Aalst Maarten K , Templeman Sienna , Nunbogu Abraham M , Berrang-Ford Lea , Agrawal Tanvi ,   the Global Adaptation Mapping Initiative team, Mach Katharine J 
Published: June 2021

Abstract
Extreme heat events impact people and ecosystems across the globe, and they are becoming more frequent and intense in a warming climate. Responses to heat span sectors and geographic boundaries. Prior research has documented technologies or options that can be deployed to manage extreme heat and examples of how individuals, communities, governments and other stakeholder groups are adapting to heat. However, a comprehensive understanding of the current state of implemented heat adaptations—where, why, how and to what extent they are occurring—has not been established. Here, we combine data from the Global Adaptation Mapping Initiative with a heat-specific systematic review to analyze the global extent and diversity of documented heat adaptation actions (n = 301 peer-reviewed articles). Data from 98 countries suggest that documented heat adaptations fundamentally differ by geographic region and national income. In high-income, developed countries, heat is overwhelmingly treated as a health issue, particularly in urban areas. However, in low- and middle-income, developing countries, heat adaptations focus on agricultural and livelihood-based impacts, primarily considering heat as a compound hazard with drought and other hydrological hazards. 63% of the heat-adaptation articles feature individuals or communities autonomously adapting, highlighting how responses to date have largely consisted of coping strategies. The current global status of responses to intensifying extreme heat, largely autonomous and incremental yet widespread, establishes a foundation for informed decision-making as heat impacts around the world continue to increase.
Effects of encapsulated cinnamaldehyde on growth performance, intestinal digestive and absorptive functions, meat quality and gut microbiota in broiler chickens
Authors: Yang Chongwu , Diarra Moussa S , Choi Janghan , Rodas-Gonzalez Argenis , Lepp Dion , Liu Shangxi , Lu Peng , Mogire Marion , Gong Joshua , Wang Qi , Yang Chengbo 
Published: June 2021

Abstract
Essential oils are potential antimicrobial alternatives and their applications in animal feeds are limited due to their fast absorption in the upper gastrointestinal tract. This study investigated the effects of encapsulated cinnamaldehyde (CIN) at 50 mg/kg or 100 mg/kg on the growth performance, organ weights, meat quality, intestinal morphology, jejunal gene expression, nutrient digestibility, and ileal and cecal microbiota. A total of 320 male day-old broiler Cobb-500 chicks were randomly allocated to four treatments with eight pens per treatment (10 birds per pen): 1) basal diet (negative control, NC); 2) basal diet supplemented with 30 mg/kg avilamycin premix (positive control, PC); 3) basal diet with 50 mg/kg encapsulated CIN (EOL); 4) basal diet with 100 mg/kg encapsulated CIN (EOH). Despite birds fed EOH tended to increase (P = 0.05) meat pH at 24 h, all pH values were normal. Similar to PC group, meats from birds fed EOL and EOH showed a reduced (P &lt; 0.05) Warner–Bratzler force shear (WBFS) compared to the NC group. The highest villus to crypt ratios (VH/CD; P &lt; 0.05) were observed in broilers fed either EOL or EOH, with an average of 14.67% and 15.13% in the duodenum and 15.13% and 13.58% in the jejunum, respectively. For jejunal gene expressions, only six out of the 11 studied genes showed statistically significant differences among the dietary treatments. Gene expressions of cationic amino acid transporter 1 (CAT-1) and neutral amino acid transporter 1 (B0AT-1) were upregulated in EOH-fed birds compared to PC and NC-fed birds (P &lt; 0.05), respectively; while the expression of proliferating cell nuclear antigen (PCNA) was downregulated in EOL-fed birds when compared to NC birds (P &lt; 0.05). Nonetheless, the expressions of cadherin 1 (CDH-1), zonula occludens 1 (ZO-1), and maltase-glucoamylase (MG) were all upregulated (P &lt; 0.05) in EOH-fed birds compared to PC-fed birds. The apparent ileal digestibility (AID) of dry matter, crude protein, crude fat and of all 18 tested amino acids increased in EOL-fed birds (P &lt; 0.01). Additionally, relative abundances (%) of ileal Proteobacteria decreased, while ileal and cecal Lactobacillus increased in EOH-fed birds (P &lt; 0.05). In conclusion, dietary encapsulated CIN improved meat quality and gut health by reducing meat WBFS, increasing VH/CD in intestines, jejunal gene expressions, AID of nutrients and beneficial ileal and cecal microbiota composition.
Antigenic minimalism of SARS-CoV-2 is linked to surges in COVID-19 community transmission and vaccine breakthrough infections
Authors: Venkatakrishnan A.J. , Anand Praveen , Lenehan Patrick , Ghosh Pritha , Suratekar Rohit , Siroha Abhishek , Chowdhury Dibyendu Roy , O’Horo John C. , Yao Joseph D. , Pritt Bobbi S. , Norgan Andrew , Hurt Ryan T. , Badley Andrew D. , Halamka John D. , Soundararajan Venky 
Published: June 2021

AbstractThe raging COVID-19 pandemic in India and reports of “vaccine breakthrough infections” globally have raised alarm mandating the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 1.57 million SARS-CoV-2 genomes from 187 countries/territories and performed whole-genome viral sequencing from 53 COVID-19 patients, including 20 vaccine breakthrough infections. We identified 89 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a three-month window. Deletions in the Spike protein N-terminal domain (NTD) are highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 41.8, 95% CI: 6.36-1758, p-value = 7.7e-05). In the recent COVID-19 surge in India, an NTD deletion (ΔF157/R158) increased over 10-fold in prevalence from February 2021 (1.1%) to April 2021 (15%). During the recent surge in Chile, an NTD deletion (Δ246-253) increased rapidly over 30-fold in prevalence from January 2021 (0.86%) to April 2021 (33%). Strikingly, these simultaneously emerging deletions associated with surges in different parts of the world both occur at an antigenic supersite that is targeted by neutralizing antibodies. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences and identified deletions within this NTD antigenic supersite in a patient with vaccine breakthrough infection (Δ156-164) and other deletions from unvaccinated severe COVID-19 patients that could represent emerging deletion-prone regions. Overall, the expanding repertoire of Spike protein deletions throughout the pandemic and their association with case surges and vaccine breakthrough infections point to antigenic minimalism as an emerging evolutionary strategy for SARS-CoV-2 to evade immune responses. This study highlights the urgent need to sequence SARS-CoV-2 genomes at a larger scale globally and to mandate a public health policy for transparent reporting of relevant clinical annotations (e.g. vaccination status) in order to aid the development of comprehensive therapeutic strategies.
Parental plans to vaccinate children for COVID-19 in New York City
Authors: Teasdale Chloe A. , Borrell Luisa N. , Shen Yanhan , Kimball Spencer , Rinke Michael L. , Fleary Sasha A. , Nash Denis 
Published: June 2021

AbstractOnce COVID-19 vaccines are approved for children <12 years of age, high pediatric vaccination coverage will be needed to help minimize the public health threat from the SARS-CoV-2 epidemic. We conducted an online survey of 1,119 parents and caregivers of children ≤12 years in New York City from March 9 to April 11, 2021. Among parents surveyed, 61.9% reported plans to vaccinate their youngest child for COVID-19, 14.8% said they do not plan to vaccinate their child and 23.3% were unsure. Female and non-Hispanic Black parents were least likely to report plans to vaccinate their children. Safety, effectiveness and perceptions that children do not need vaccination were the primary reasons for vaccine hesitancy/resistance. Parents who have or will vaccinate themselves were significantly more likely to report they would vaccinate their children. Efforts to increase awareness about vaccine safety and education about the importance of vaccinating children are needed.
A Transcriptomic Severity Metric that Predicts Clinical Outcomes in Critically Ill Surgical Sepsis Patients
Authors: Brakenridge Scott C. , Starostik Petr , Ghita Gabriella , Midic Uros , Darden Dijoia , Fenner Brittany , Wacker James , Efron Philip A. , Liesenfeld Oliver , Sweeney Timothy E , Moldawer Lyle L. 
Published: June 2021

PurposePrognostic metrics for the rapid and accurate prediction of sepsis severity that could elicit a meaningful change in clinical practice are currently lacking. Here, we evaluated a whole blood, multiplex host mRNA expression metric, Inflammatix-Severity-2 (IMX-SEV-2), for identifying septic, hospitalized patients for 30-day mortality, development of chronic critical illness (CCI), discharge disposition, and/or secondary infections.MethodsThis is a retrospective, validation cohort analysis of a prospectively enrolled 335 patient study with surgical sepsis treated in the surgical intensive care unit. Whole blood collected in PAXgene®Blood RNA collection tubes at 24 hours post sepsis diagnosis was analyzed using a custom 29-mRNA classifier (IMX-SEV-2) in a CLIA-CAP-accredited diagnostic laboratory using the NanoString FLEX®profiler.ResultsAmong patients meeting Sepsis-3 criteria, the IMX-SEV-2 severity score was significantly better (p<0.05) at predicting secondary infections (AUROC 0.71) and adverse clinical outcomes (AUROC 0.75) than C-reactive protein (CRP), absolute lymphocyte counts (ALC), total white blood cell (WBC) count, age and Charlson comorbidity index (and better, albeit nonsignificantly, than IL-6 and APACHE II). Using multivariate logistic regression analysis, only combining the Charlson comorbidity index (AUROC 0.80) or APACHE II (AUROC 0.81) with the IMX-SEV-2 significantly improved prediction of adverse clinical outcomes, and combining with the Charlson comorbidity index for predicting 30-day mortality (AUROC 0.79).ConclusionsThe IMX-SEV-2 severity score was superior at predicting secondary infections and overall adverse clinical outcomes versus other common metrics. Importantly, combining a rapidly measured transcriptomic metric with clinical or physiologic indices has sufficient precision to optimize resource utilization and allow adjustments to patient management that may improve outcomes in surgical sepsis. Hospitalized patients who are septic and present with an elevated IMX-SEV2 severity score and pre-existing comorbidities would be strong candidates for clinical interventions aimed at reducing the risk of secondary infections and adverse clinical outcomes.
Social support, social strain and declines in verbal memory: 16-year follow-up of the English Longitudinal Study of Ageing cohort
Authors: Scholes Shaun , Liao Jing 
Published: June 2021

AbstractObjectiveEstimate differences in the rate of decline in verbal memory by levels of perceived relationship quality among community-dwelling adults.ParticipantsIn the English Longitudinal Study of Ageing (ELSA), n = 10,109 participants aged 50-89 years were assessed at wave 1 (baseline: 2002-03) and followed-up over 16 years to wave 9 (2017-18).MethodsVerbal memory was assessed biennially by tests of immediate and delayed word-recall. Positive and negative aspects of perceived relationship quality (social support and strain, respectively) were measured by relationship type (spouse; children; extended family members; friends). Random effects within-between (REWB) modelling was used to separate between- and within-person effects. Associations were estimated between levels of social support/strain and (i) baseline levels of memory (main effects), and (ii) the 2-year decline in memory (interaction with time).ResultsLongitudinal associations were most prominent for men, specific to relationship type, and showed between-rather than within-person effects. Among men, higher spousal strain was associated with faster decline in memory (βbetween-effect×time= -0.043; 95% CI: -0.084, -0.002; p = 0.039), whilst greater support from children was associated with slower decline (βbetween-effect×time= 0.020; 95% CI: 0.002, 0.039; p = 0.033). Men with higher levels of strain from friends had lower baseline memory (βbetween-effect= -0.382; 95% CI: -0.627, -0.137; p = 0.002) and showed faster decline (βbetween-effect×time= -0.047; 95% CI: -0.095, 0.000; p = 0.051).ConclusionsDifferences between persons in levels of social support and social strain were modestly associated with the rate of memory decline, especially among men. Our findings can inform future research studies and intervention strategies designed to maximise the potential of social relations to promote healthy cognitive ageing.
A Randomised Crossover Trial: Exploring the Dose-Response effect Of Carbohydrate restriction on glycaemia in people with type 2 diabetes (D-ROC2)
Authors: Ozairi Ebaa Al , Abdul-Ghani Muhammad , Oliver Nick , Whitcher Brandon , Awadi Reem Al , Samad Abeer El , Taghadom Etab , Al-Kandari Jumana , Guess Nicola 
Published: June 2021

ABSTRACTAimsThe role of carbohydrate restriction in the management of glycaemia in type 2 diabetes (T2D) has been a subject of immense debate and controversy partly due to low-carbohydrate trials being confounded by multiple factors including degree of calorie restriction, dietary protein content, and by no clear definition of a low-carbohydrate diet. The current study sought to provide insight into the relationship between carbohydrate restriction and glycaemia by testing the effect of varying doses of carbohydrate on continuous glucose concentrations within a range of intakes defined as low-carbohydrate while controlling for confounding factors.MethodsThis was a randomised crossover trial in participants with T2D testing 5 different 6-day eucaloric, isocaloric dietary treatments with varying carbohydrate contents (10%, 15%, 20%, 25%, and 30% kcal). Diets were kept isocaloric by exchanging %kcal from carbohydrate with predominantly unsaturated fat, keeping protein constant at 15% kcal. Daily self-weighing was employed to ensure participants maintained their weight throughout each treatment arm. Between dietary treatments, participants underwent a washout period of at least 7 days and were advised to maintain their habitual diet. Glycemic control was assessed using a continuous glucose monitoring device that was placed while the participant was on their normal diet, and was worn for the 6 days of each treatment.Results12 participants completed the study. There were no differences in 24-hour and postprandial sensor glucose concentrations between the 30%kcal and 10%kcal doses (7.4 ± 1.1mmol/L vs 7.6 ± 1.4mmol/L (P=0.28) and 8.0 ± 1.4mmol/L vs 8.3 ± 1.3mmol/L (P=0.28) respectively). In our exploratory analyses we did not find any dose-response relationship between carbohydrate intake and glycaemia. A small amount of weight loss occurred in each treatment arm (range: 0.4 to 1.1kg over the 6 days) but adjusting for these differences did not influence the primary or secondary outcomes.ConclusionsModest changes in dietary carbohydrate content in the absence of weight loss while keeping dietary protein intake constant do not appear to influence glucose concentrations in people with T2D.Trial RegistrationISRCTN 11067343.
Association between discrimination stress and suicidality in preadolescent children
Authors: Argabright Stirling T. , Visoki Elina , Moore Tyler M. , Ryan Dallas T. , DiDomenico Grace E. , Njoroge Wanjiku F.M. , Taylor Jerome H. , Guloksuz Sinan , Gur Ruben C. , Gur Raquel E. , Benton Tami D. , Barzilay Ran 
Published: June 2021

AbstractObjectiveUS youth suicide rates are increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality, hence there is a need to study stressors that disproportionately impact Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality) across races.MethodWe analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study® that included a large, diverse sample of US children (N=11,235, mean age 10.9 years, 20.2% Black) phenotyped for environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (towards non-US born individuals; sexual orientation-based; weight-based). Matched analyses contrasted effects of racial/ethnic discrimination and racial identity on suicidality.ResultsBlack youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively associated with suicidality, adjusting for other discrimination types (odds ratio [OR]=2.6, 95%CI=2.1-3.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk [RR]=2.7, 95%CI=2-3.5), while Black race was not (RR=0.9, 95%CI=0.7-1.2).ConclusionRacial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences.
Evolutionary transition of doublesex regulation in termites and cockroaches: from sex-specific splicing to male-specific transcription
Authors: Miyazaki Satoshi , Fujiwara Kokuto , Kai Keima , Masuoka Yudai , Gotoh Hiroki , Niimi Teruyuki , Hayashi Yoshinobu , Shigenobu Shuji , Maekawa Kiyoto 
Published: June 2021

AbstractThe sex determination gene doublesex (dsx), which encodes a transcription factor with two domains: oligomerisation domain 1 (OD1) and OD2, is conserved among insects. The sex-specific Dsx splicing isoforms regulate the transcription of target genes and trigger sex differentiation in all holometabolous insects examined to date. However, in some hemimetabolous insects, dsx is less conserved and not spliced sexually. Here, to elucidate evolutionary changes in dsx in the gene structure and its regulatory manner in termites, we searched genome and/or transcriptome databases for the OD1 and OD2 of dsx in six termite species and their sister group (woodroach). Molecular phylogenetic analysis identified OD1 sequences of termites and a woodroach clustered with dsx of holometabolous insects and regarded them as dsx orthologues. In the woodroach, a dsx orthologue containing OD2 was spliced sexually, as previously shown in other insects. However, OD2 were not found in all termite dsx orthologues. These orthologues were encoded by only a single exon in three termites with genome information; they were not alternatively spliced, but transcribed in a male-specific manner in two species examined. Evolution of dsx regulation from sex-specific splicing to male-specific transcription might be occurred at the early stage of social evolution in termites.
Spike mutation T403R allows bat coronavirus RaTG13 to use human ACE2
Authors: Zech Fabian , Schniertshauer Daniel , Jung Christoph , Herrmann Alexandra , Xie Qinya , Nchioua Rayhane , Bozzo Caterina Prelli , Volcic Meta , Koepke Lennart , Krüger Jana , Heller Sandra , Kleger Alexander , Jacob Timo , Conzelmann Karl-Klaus , Ensser Armin , Sparrer Konstantin M.J. , Kirchhoff Frank 
Published: June 2021

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 pandemic, most likely emerged from bats1. A prerequisite for this devastating zoonosis was the ability of the SARS-CoV-2 Spike (S) glycoprotein to use human angiotensin-converting enzyme 2 (ACE2) for viral entry. Although the S protein of the closest related bat virus, RaTG13, shows high similarity to the SARS-CoV-2 S protein it does not efficiently interact with the human ACE2 receptor2. Here, we show that a single T403R mutation allows the RaTG13 S to utilize the human ACE2 receptor for infection of human cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S significantly reduced ACE2-mediated virus infection. The S protein of SARS-CoV-1 that also uses human ACE2 also contains a positive residue (K) at this position, while the S proteins of CoVs utilizing other receptors vary at this location. Our results indicate that the presence of a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2. This finding could help to predict the zoonotic potential of animal coronaviruses.