bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole Blood Resuscitation and Association with Survival in Injured Patients with an Elevated Probability of Mortality
Authors: Sperry Jason L , Cotton Bryan A , Luther James F , Cannon Jeremy W , Schreiber Martin A , Moore Ernest E , Namias Nicholas , Minei Joseph P , Wisniewski Stephen R , Guyette Frank X ,   the Shock, Whole Blood, and Assessment of Traumatic Brain Injury (SWAT) Study Group
Published: April 2023

BACKGROUND:
Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation.

STUDY DESIGN:
A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors.

RESULTS:
A total of 1,051 patients in hemorrhagic shock met all enrollment criteria. The cohort was severely injured with >70% of patients requiring massive transfusion. After propensity adjustment, no significant 4-hour mortality difference across LTOWB and component patients was found (relative risk [RR] 0.90, 95% CI 0.59 to 1.39, p = 0.64). Similarly, no adjusted mortality differences were demonstrated at 24 hours or 28 days for the enrolled cohort. When patients with an elevated prehospital probability of mortality were analyzed, LTOWB resuscitation was independently associated with a 48% lower risk of 4-hour mortality (relative risk [RR] 0.52, 95% CI 0.32 to 0.87, p = 0.01) and a 30% lower risk of 28-day mortality (RR 0.70, 95% CI 0.51 to 0.96, p = 0.03).

CONCLUSIONS:
Early LTOWB resuscitation is safe but not independently associated with survival for the overall enrolled population. When patients were selected with an elevated probability of mortality based on prehospital injury characteristics, LTOWB was independently associated with a lower risk of mortality starting at 4 hours after arrival through 28 days after injury.
PROFILE AND TRAINING ON GENDER IDENTITY AMONG HEALTH PROFESSIONALS IN THE CAETÉ REGION IN THE EASTERN AMAZON
Authors: Barbosa Pedro Renan Nascimento , Fernandes Roseane do Socorro da Silva Matos , Nunes Erica Feio Carneiro , Rodrigues Cibele Nazaré Câmara 
Published: April 2023

ABSTRACTBackgroundThe National Policy on Integral Health of Lesbians, Gays, Bisexuals, Transvestites, and Transsexuals (PNSILGBT+) aims to eliminate discrimination and institutional prejudice in public health services, with emphasis on training and enabling professionals to assist in the care of this population. However, for transsexuals and transvestites, this access continues to be neglected.AimTo determine the profile of health professionals, their academic-professional training in health, and their knowledge about the specificities of gender identity.MethodsThis is a cross-sectional, observational, quantitative survey conducted with health professionals working in the Caeté Region. Data were collected using a semi-structured questionnaire, which was applied online via Google Forms in the period from March 2021 to August 2021.OutcomesEpidemiological profile, academic education, area of practice, and knowledge about gender identity were predictors for the descriptive analysis.ResultsThe sample consisted of 73 participants: 82.19% female, 100% cisgender, with a mean age of 32.37±7.80 years, and the majority self-declared as Catholic (65.75%). The largest number of health professionals were in Nursing (34.24%), practicing in Tertiary Care (50.68%), with an average time of service of 6.24±6.30 years. The volunteers reported that they did not understand the difference between cisgender and transgender people (57.53%), admitting that they had not received any training on gender identity or the healthcare of Lesbians, Gays, Bisexuals, Transvestites, and Transsexuals (LGBT)+ people (79.45%). However, 87.67% understood the importance of training on this subject for the healthcare of this population.Clinical ImplicationsThis study demonstrates the need for continued trainings on gender identity, health and care of the LGBT+ population, with a focus on transgender people, to eliminate institutional bias.Strengths and limitationsThe research was based on the search for professionals’ knowledge about gender identity, even in healthcare in a region in the interior of the Amazon, however it did not reach the preterit sample n, but it was important for the debate between the professionals reached and the institutions and their managers.ConclusionThe academic training and professional development of health professionals are still lacking when it comes to the theme studied; a fundamental point needed to comply with the National Curricular Guidelines (NCDs) for courses in health, National Policy for Professional Development, and in particular, the PNSILGBT+.
Effectiveness of mHealth Interventions for Blood Pressure Control among Vulnerable Populations: A Systematic Review
Authors: Azar Kristen M.J. , Zoken Yael , Cooper-DeHoff Rhonda M. , Fontil Valy , Madelaine F. Modrow , Nasrallah Catherine , Pletcher Mark J. 
Published: April 2023

AbstractSocial determinants of health and sociodemographic differences place some individuals at higher risk for hypertension leading to persisting disparities. While mobile health (mHealth) offers a promising approach to facilitate blood pressure (BP) management, it remains unclear which interventions are most effective for addressing disparities in hypertension control. We reviewed the current literature to examine whether mHealth interventions for BP control are effective in improving BP control in populations vulnerable to disparities in hypertension. We conducted a systematic review using multiple databases from January 1, 2009 through December 31, 2020. For inclusion, participants must have elevated blood pressure and belong to a sociodemographic group with known disparities in hypertension. We also tracked specific characteristics of each intervention. Out of the eight articles that met our eligibility criteria for inclusion, five were published in 2018 to 2020. Only four demonstrated a significant reduction in BP and all those interventions incorporated care teams. Despite some evidence of the effectiveness of mHealth interventions for improving BP control among vulnerable groups, more effective interventions are needed, and the quality of studies is overall low. Further research is needed to find the most effective ways to engage diverse communities with mHealth solutions to improve BP control.
A critical role for PLCG1 in RAS activation by BCR-ABL1 and FLT3-ITD
Authors: Szeto May Yee , Mase Anjeli , Kulhanek Kayla , Banerjee Saikat , Rubio Ignacio , Roose Jeroen , Shah Neil 
Published: April 2023

AbstractMyeloid leukemias are frequently associated with pathologically activating mutations in tyrosine kinases [BCR-ABL1 in chronic myeloid leukemia (CML); FLT3 juxtamembrane internal tandem duplication (ITD) mutations, FLT3 and KIT activation loop mutations in acute myeloid leukemia (AML)]. Mutations in these kinases activate RAS, which initiates multiple downstream signaling pathways that regulate cell proliferation, differentiation, and apoptosis. The mechanisms whereby RAS is activated by these kinases is incompletely understood, and a better understanding of the molecular mediators involved in RAS activation may uncover new therapeutic strategies. Here we identify a biologically and therapeutically important novel mechanism whereby BCR-ABL1 and FLT3-ITD activate the critical downstream effector RAS in part through phospholipase C gamma-1 (PLCG1). PLCG1 knockout decreases proliferation of CML and FLT3-ITD-expressing AML cells, reduces RAS nucleotide exchange factor activity, and increases sensitivity of CML cells to BCR-ABL1 tyrosine kinase inhibitors (TKIs). Collectively, these studies suggest that PLCG1 inhibition may augment clinical responses to BCR-ABL1 and FLT3 TKIs in CML and AML.
Survey of rice (Oryza sativaL.) production ecosystems in northern Ghana confirms low risk of exposure to potential toxic elements from local grain consumption
Authors: Adomako Eureka E. A. , Aboagye-Ghunney Kow , Owusu Prince 
Published: April 2023

AbstractExpanding local rice production to meet consumer demand is a priority action under the Government of Ghana’s Planting for Food and Jobs initiative. While studies on yield-enhancing interventions including seed improvement and fertilizer management abound, fewer studies focus on food safety issues such as the potential toxic element status of the production ecosystems. This study was, therefore, conducted to bridge the knowledge gap. Chemical analyses were conducted on water, soil and rice grain samples from rainfed upland, rainfed lowland and irrigated lowland rice ecosystems in the Northern and Upper East regions of the country. Statistical analysis of the data showed that soil and rice grain arsenic concentrations were significantly higher (P < 0.001) in the Upper East region. In the Northern region, mean cadmium concentration in rice grains from the irrigated lowland fields (0.023 ± 0.003 mg/kg) was significantly higher than in grains from the rainfed fields. All recorded concentrations of rice grain arsenic, cadmium and lead were, however, within permissible limits, indicating a low risk of dietary exposure. The observed differences in concentrations within and between regions suggest that soil texture and other geogenic factors could influence the potential toxic element status of the rice production ecosystems. Regular monitoring is, therefore, recommended to maintain the safety of Ghana’s locally produced rice for human consumption.
Genetically Determined Blood Pressure, Antihypertensive Drugs, and Genes with Clinical Outcome after Ischemic Stroke: Evidence from Mendelian Randomization
Authors: Liu Hanchen , Zhang Xiaoxi , Zhou Yu , Nguyen Thanh N. , Zhang Lei , Xing Pengfei , Li Zifu , Shen Hongjian , Zhang Yongxin , Hua Weilong , Xu Hongye , Zhu Xuan , Lei Chen , Zuo Qiao , Zhao Rui , Li Qiang , Dai Dongwei , Zhang Yongwei , Xu Yi , Huang Qinghai , Liu Jianmin , Yang Pengfei 
Published: April 2023

AbstractBackgroundObservational studies suggest a robust association between blood pressure (BP) and functional outcomes in ischemic stroke patients. We sought to identify novel associations of the genetic basis of 3-month functional outcome after ischemic stroke based on a Mendelian randomization (MR) framework.MethodsWe selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3- month favorable functional outcome defined as modified Rankin Scale (mRS) of 0-2. The secondary outcome was excellent 90-day outcome defined as mRS 0-1. The Cochran’s Q statistic in Inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses.ResultsGenetic predisposition to higher systolic and diastolic BP was associated with a lower probability of 3-month excellent functional outcome after ischemic stroke in univariable IVW MR analysis (OR=1.29, 95%CI 1.05-1.59,p=0.014; OR=1.27, 95%CI 1.07-1.51,p=0.006, respectively). Pulse pressure was associated with both excellent and favorable functional outcome (OR=1.05, 95%CI 1.02-1.08,p=0.002; OR=1.04, 95%CI 1.01-1.07,p=0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB), were significantly associated with improved favorable functional outcome (OR=0.76, 95%CI 0.62-0.94,p=0.009; OR=0.89, 95%CI 0.83-0.97,p=0.005). Proxies for β-blockers, angiotensin receptor blocker (ARB) and thiazides failed to show associations with functional outcome (p>0.05).ConclusionWe provide evidence for a potential association of genetic predisposition to higher BP with higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcome in ischemic stroke.
Single B cell transcriptomics identifies multiple isotypes of broadly neutralizing antibodies against flaviviruses
Authors: Lubow Jay , Levoir Lisa M. , Ralph Duncan K. , Belmont Laura , Contreras Maya , Cartwright-Acar Catiana H. , Kikawa Caroline , Kannan Shruthi , Davidson Edgar , Doranz Benjamin J. , Duran Veronica , Sanchez David ER. , Sanz Ana M. , Rosso Fernando , Einav Shirit , Matsen Frederick A. , Goo Leslie 
Published: April 2023

SUMMARYSequential dengue virus (DENV) infections often generate neutralizing antibodies against all four DENV serotypes and sometimes, Zika virus. Characterizing cross-flavivirus broadly neutralizing antibody (bnAb) responses can inform countermeasure strategies that avoid infection enhancement associated with non-neutralizing antibodies. Here, we used single cell transcriptomics to mine the bnAb repertoire following secondary DENV infection. We identified several new bnAbs with comparable or superior breadth and potency to known bnAbs, and with distinct recognition determinants. Unlike all known flavivirus bnAbs, which are IgG1, one newly identified cross-flavivirus bnAb (F25.S02) was derived from IgA1. Both IgG1 and IgA1 versions of F25.S02 and known bnAbs displayed neutralizing activity, but only IgG1 enhanced infection in monocytes expressing IgG and IgA Fc receptors. Moreover, IgG-mediated enhancement of infection was inhibited by IgA1 versions of bnAbs. We demonstrate a role for IgA in flavivirus infection and immunity with implications for vaccine and therapeutic strategies.
Occurrence-based diversity estimation reveals macroecological and conservation knowledge gaps for global woody plants
Authors: Kusumoto Buntarou , Chao Anne , Eiserhardt Wolf L. , Svenning Jens-Christian , Shiono Takayuki , Kubota Yasuhiro 
Published: April 2023

AbstractIncomplete sampling of species’ geographic distributions has challenged biogeographers for many years to precisely quantify global-scale biodiversity patterns. After correcting for the spatial inequality of sample completeness, we generated a global species diversity map for woody angiosperms (82,974 species, 13,959,780 occurrence records). The estimated diversity demonstrated non-linear latitudinal and longitudinal patterns that were potentially related to region-specific biogeographic factors including current climate, paleoclimate, and topographical factors, while energy availability was the most important predictor at a global level. We identified the areas with potentially high species richness and rarity, but poorly explored, unprotected, and threatened by deforestation: they are distributed mostly at low latitudes across central South America, central Africa, subtropical China, and Indomalayan islands. These priority areas for botanical exploration would help to efficiently fill spatial knowledge gaps for better describing the status of biodiversity and improve the effectiveness of the protected area network for global woody plant conservation.TeaserBias-corrected diversity map based on occurrence records sheds new light on global macroecology and conservation of woody angiosperms.
Time of day and genotype sensitivity adjust molecular responses to temperature stress in sorghum
Authors: Bonnot Titouan , Somayanda Impa , Jagadish S. V. Krishna , Nagel Dawn H 
Published: April 2023

AbstractSorghum is one of the four major C4 crops that are considered to be tolerant to environmental extremes. Sorghum shows distinct growth responses to temperature stress depending on the sensitivity of the genetic background. About half of the transcripts in sorghum exhibit diurnal rhythmic expressions emphasizing significant coordination with the environment. However, an understanding of how molecular dynamics contribute to genotype-specific stress responses in the context of the time of day is not known. We examined whether temperature stress and the time of day impact the gene expression dynamics in cold-sensitive and tolerant and heat-sensitive and tolerant sorghum genotypes. We found that time of day is highly influencing the temperature stress responses, which can be explained by the rhythmic expression of most thermo-responsive genes. This effect is more pronounced in thermo-tolerant genotypes, suggesting a stronger regulation of gene expression by the time of day and/or by the circadian clock. Genotypic differences were mostly observed on average gene expression levels, but we identified groups of genes regulated by temperature stress in a time-of-day and genotype-specific manner. These include transcriptional regulators and several members of the Ca2+-binding EF-hand protein family. We hypothesize that expression variation of these genes between genotypes may be responsible for contrasting sensitivities to temperature stress in tolerant vs susceptible sorghum varieties. These findings offer a new opportunity to selectively target specific genes in efforts to develop climate-resilient crops based on their time of day and genotype variation responses to temperature stress.
Functional similarity of non-coding regions is revealed in phylogenetic average motif score representations
Authors: Alam Aqsa , Duncan Andrew G , Mitchell Jennifer A , Moses Alan M 
Published: April 2023

AbstractHere we frame the cis-regulatory code (that connects the regulatory functions of non-coding regions, such as promoters and UTRs, to their DNA sequences) as a representation building problem. Representation learning has emerged as a new approach to understand function of DNA and proteins, by projecting sequences into high-dimensional feature spaces, where the features are learned from data by a neural network. Inspired by these approaches, we seek to define a feature space where non-coding regions with similar regulatory functions are nearby each other. As a first attempt, we engineered features based on matches to biochemically characterized regulatory motifs in the DNA sequences of non-coding regions. Remarkably, we found that functionally similar promoters and 3’ UTRs could be grouped together in a feature space defined by simple averages of the best match scores in (unaligned) orthologous non-coding regions, which we refer to as phylogenetic average motif scores. Perhaps most important, because this feature space is based on known motifs and not fit to any data, it is fully interpretable and not limited to any particular cell type or experimental context. We find that we can read off known regulatory relationships and evolutionary rewiring from visualizations of phylogenetic average motif score representations, and that predicted regulatory interactions based on neighbors in the feature space are borne out in transcription factor deletion experiments. Phylogenetic averages of match scores to known motifs is a baseline for representation learning applied to non-coding sequences, and may continue to improve as databases of motifs become more complete.
Sexually dimorphic dynamics of the microtubule network in medaka (Oryzias latipes) germ cells
Authors: Kikuchi Mariko , Yoshimoto Miyo , Ishikawa Tokiro , Kanda Yuto , Mori Kazutoshi , Nishimura Toshiya , Tanaka Minoru 
Published: April 2023

AbstractOogenesis is the process through which ovarian germ cells enter meiosis and acquire essential characteristics of an egg, such as an increase in follicular size and deposition of maternal factors. In vertebrates, however, the pathways that initiate oogenic processes after germ cell sex determination remain elusive. Here we report a dome-shaped microtubule structure that is maintained during oogenesis. This structure is established in primordial germ cells and maintained in gonocytes and stem-type germ cells in afoxl3-independent manner.dmrt1is required for disruption of the dome structure in differentiating spermatogonia. In addition, the dome structure accumulates mitochondria and Golgi apparatus, and is replaced by the Balbiani body, an oocyte-specific aggregate producing animal-vegetal polarity, suggesting a role for this structure in organelle transfer and oocyte polarization. Our findings show the presence of a pathway regulating a sexually dimorphic microtubule network independent of germ cell feminization byfoxl3.Summary StatementA dome-shaped microtubule structure leading to oocyte polarity was identified in germ cells. Genetic pathways involved in the formation and destabilization of the structure during germ cell sex determination were clarified.
BCG Vaccination Policy, Natural Boosting and Pediatric Brain and CNS Tumor Incidences
Authors: Singh Samer , Diwakar Amita , Singh Rakesh K. 
Published: April 2023

AbstractBacille Calmette-Guérin (BCG) vaccination supposedly imparts and augments “trained immunity” that cross-protects against multiple unrelated pathogens and enhances general immune surveillance. Gradual reductions in tuberculosis burden over the last 3-5 decades have resulted in the withdrawal of BCG vaccination mandates from developed industrialized countries while reducing to a single neonatal shot in the rest. Concurrently, a steady increase in early childhood Brain and CNS (BCNS) tumors has occurred. Though immunological causes of pediatric BCNS cancer are suspected, the identification of a causal protective variable with an intervention potential has remained elusive. An examination of the countries with contrasting vaccination policies indicates significantly lower BCNS cancer incidence (per hundred-thousand) in countries following neonatal BCG inoculations (n=146)vs. non-BCG countries (n=33) [Mean: 1.26vs. 2.64; Median: 0.985vs. 2.8; IQR: 0.31–2.0vs. 2.4–3.2;P=<0.0001(two-tailed)]. Remarkably, naturalMycobacteriumspp. exposure likelihood is negatively correlated with pediatric BCNS cancer incidences in all affected countries [r(154): —0.6085,P=<0.0001]. Seemingly, neonatal BCG vaccination and natural “boosting” are associated with a 15-20-fold lower BCNS cancer incidence. We attempt to synthesize existing evidence implying the immunological basis of early childhood BCNS cancer incidences and briefly indicate possible causes that could have precluded objective analysis of the existing data in the past. A comprehensive evaluation of immune training as a potential protective variable through well-designed controlled clinical trials or registry-based studies as feasible may be warranted for its potential applications in reducing childhood BCNS cancer incidences.Statement of SignificancePotential causal protective variable for childhood Brain and other CNS (BCNS) tumors has eluded discovery. Neonatal BCG vaccination and boosting byMycobacterium tuberculosiscomplex exposure seem associated with over 15-20 times lower BCNS cancer incidences. Data suggests neonatal BCG vaccination followed by “boosting” may be preventive for early childhood BCNS cancer incidences.