bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial, gender, and psychosocial disparities in viral suppression trends among people receiving coordinated HIV care in Los Angeles County
Authors: Li Michael J. , Chau Brendon , Garland Wendy H. , Oksuzyan Sona , Weiss Robert E. , Takada Sae , Kao Uyen , Lee Sung-Jae , Shoptaw Steven J. 
Published: April 2023

Objective:
To longitudinally evaluate differences in HIV viral suppression (< 200 c/mL) by intersections of race/ethnicity, gender, and psychosocial issues in people with HIV in the Los Angeles County Medical Care Coordination Program.

Design:
We analyzed 187,830 viral load measurements over 10,184 people with HIV enrolled in the Medical Care Coordination Program between January 1, 2013 and March 1, 2020.
Methods: We fit Bayesian logistic hierarchical random effects models to test interactions between gender, race/ethnicity, and a psychosocial acuity score on viral suppression over time from 1 year prior to program enrollment to 24 months after enrollment.

Results:
The probability of viral suppression declined prior to enrollment, then increased and stabilized by 6 months after enrollment. Black/African American patients with low and moderate psychosocial acuity scores did not achieve the same increase in percentage of viral suppression as those in other racial/ethnic groups. Transgender women with high psychosocial acuity scores took longer (about 1 year) to achieve the same percentage of viral suppression as clients of other gender identities.

Conclusions:
Some racial/ethnic and gender disparities in viral suppression persisted after enrollment in the Los Angeles County Medical Care Coordination Program while accounting for psychosocial acuity score, which may be explained by factors not assessed in the program.
N-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis
Authors: Jia Degong , Guo Shanshan , Jia Zhixing , Gao Zhengjie , You Kun , Gong Jianping , Li Shengwei 
Published: April 2023

Background.
N-acetylcysteine (NAC) is a potentially effective drug for treating ischemia–reperfusion injury in transplanted livers, but its effect remains controversial.

Methods.
A systematic review and meta-analysis of relevant clinical trials published and registered in the Cochrane Library, MEDLINE, EMBASE, ClinicalTrial.gov, WHO ICTRP, etc, before March 20, 2022 were conducted and registered with PROSPERO (CRD42022315996). Data were pooled using a random effects model or a fixed effects model based on the amount of heterogeneity.

Results.
Thirteen studies with 1121 participants, 550 of whom received NAC, were included. Compared with the control, NAC significantly reduced the incidence of primary graft nonfunction (relative risk [RR], 0.27; 95% confidence interval [CI], 0.08-0.96), the incidence of postoperative complications (RR, 0.52; 95% CI, 0.41-0.67), the peak postoperative aspartate transferase level (mean difference [MD], −267.52; 95% CI, −345.35 to −189.68), and the peak alanine transferase level (MD, −293.29; 95% CI, −370.39 to −216.20). NAC also improved 2-y (RR, 1.18; 95% CI, 1.01-1.38) graft survival rate. However, NAC increased the intraoperative cryoprecipitate (MD, 0.94; 95% CI, 0.42-1.46) and red blood cell (MD, 0.67; 95% CI, 0.15-1.19) requirements. Moreover, NAC was administered in various modes in these studies, including to the donor, recipient, or both. Subgroup analysis and network meta-analysis showed that NAC administration to recipients could play a more significant role than the other 2 administration modes.

Conclusions.
Our study supports the protective effect of NAC against LT-induced ischemia–reperfusion injury and shows better clinical outcomes of NAC administration to recipients.
Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study
Authors: Tingle Samuel J. , Bramley Rebecca , Goodfellow Michael , Thompson Emily R. , McPherson Stuart , White Steve A. , Wilson Colin H. 
Published: April 2023

Background.
Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor “liver blood tests” on transplant outcomes.

Methods.
This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016–2019); adjusted regressions models were used to assess the effect of donor “liver blood tests” on outcomes.

Results.
A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044).

Conclusions.
Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.
Time to Whole Blood Transfusion in Hemorrhaging Civilian Trauma Patients: There Is Always Room for Improvement
Authors: Hosseinpour Hamidreza , Magnotti Louis J , Bhogadi Sai Krishna , Anand Tanya , El-Qawaqzeh Khaled , Ditillo Michael , Colosimo Christina , Spencer Audrey , Nelson Adam , Joseph Bellal 
Published: April 2023

BACKGROUND:Whole blood (WB) is becoming the preferred product for the resuscitation of hemorrhaging trauma patients. However, there is a lack of data on the optimum timing of receiving WB. We aimed to assess the effect of time to WB transfusion on the outcomes of trauma patients.STUDY DESIGN:The American College of Surgeons TQIP 2017 to 2019 database was analyzed. Adult trauma patients who received at least 1 unit of WB within the first 2 hours of admission were included. Patients were stratified by time to first unit of WB transfusion (first 30 minutes, second 30 minutes, and second hour). Primary outcomes were 24-hour and in-hospital mortality, adjusting for potential confounders.RESULTS:A total of 1,952 patients were identified. Mean age and systolic blood pressure were 42 ± 18 years and 101 ± 35 mmHg, respectively. Median Injury Severity Score was 17 [10 to 26], and all groups had comparable injury severities (p = 0.27). Overall, 24-hour and in-hospital mortality rates were 14% and 19%, respectively. Transfusion of WB after 30 minutes was progressively associated with increased adjusted odds of 24-hour mortality (second 30 minutes: adjusted odds ratio [aOR] 2.07, p=0.015; second hour: aOR 2.39, p=0.010) and in-hospital mortality (second 30 minutes: aOR 1.79, p=0.025; second hour: aOR 1.98, p=0.018). On subanalysis of patients with an admission shock index >1, every 30-minute delay in WB transfusion was associated with higher odds of 24-hour (aOR 1.23, p = 0.019) and in-hospital (aOR 1.18, p = 0.033) mortality.CONCLUSIONS:Every minute delay in WB transfusion is associated with a 2% increase in odds of 24-hour and in-hospital mortality among hemorrhaging trauma patients. WB should be readily available and easily accessible in the trauma bay for the early resuscitation of hemorrhaging patients.
Changing Epidemiology of Haemophilus influenzae carriage among Children in Lombok Island, Indonesia
Authors: Putri Nina Dwi , Salsabila Korrie , Prayitno Ari , Aprianti Shindy Claudya , Paramaiswari Wisiva Tofriska , Krisna Made Ananda , Safari Dodi 
Published: April 2023

The Haemophilus influenzae serotype b (Hib) conjugate vaccine routine immunization program has been implemented for almost a decade, but there is a limited surveillance of H. influenzae carriage in Indonesia. H. influenzae was isolated from nasopharyngeal swab specimens from healthy children in Lombok Island, West Nusa Tenggara, Indonesia in 2018-2019. Serotyping was performed using quantitative polymerase chain reaction. Among 96 young children in Lombok Island, we identified H. influenzae from 40 out of 96 NP swab specimens (41.6%). We found 39 non-typeable H. influenzae (NTHi) and 1 serotype b isolate.
Ultra-Rare Genetic Variation in Relapsing Polychondritis: A Whole-Exome Sequencing Study
Authors: Luo Yiming , Ferrada Marcela A. , Sikora Keith A. , Rankin Cameron , Alessi Hugh , Kastner Daniel L. , Deng Zuoming , Zhang Mengqi , Merkel Peter A. , Kraus Virginia B. , Allen Andrew S. , Grayson Peter C. 
Published: April 2023

AbstractObjectiveRelapsing polychondritis (RP) is a systemic inflammatory disease of unknown etiology. The study objective was to examine the contribution of rare genetic variations in RP.MethodsWe performed a case-control exome-wide rare variant association analysis including 66 unrelated European American RP cases and 2923 healthy controls. Gene-level collapsing analysis was performed using Firth’s logistics regression. Pathway analysis was performed on an exploratory basis with three different methods: Gene Set Enrichment Analysis (GSEA), sequence kernel association test (SKAT) and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and healthy controls using enzyme-linked immunosorbent assay (ELISA).ResultsIn the collapsing analysis, RP was associated with higher burden of ultra-rare damaging variants in theDCBLD2gene (7.6% vs 0.1%, unadjusted odds ratio = 79.8, p = 2.93 x 10-7). Patients with RP and ultra-rare damaging variants inDCBLD2had a higher prevalence of cardiovascular manifestations. Plasma DCBLD2 protein levels were significantly higher in RP than healthy controls (5.9 vs 2.3, p < 0.001). Pathway analysis showed statistically significant enrichment of genes in the tumor necrosis factor (TNF) signaling pathway driven by rare damaging variants inRELB,RELAandRELusing higher criticism test weighted by degree and eigenvector centrality.ConclusionsThis study identified specific rare variants inDCBLD2as putative genetic risk factors for RP. Genetic variation within the TNF pathway is also potentially associated with development of RP. These findings should be validated in additional patients with RP and supported by future functional experiments.
Clinical Performance of BD Veritor™ Assay Across SARS-CoV-2 Variants
Authors: Eckert Karen , Gutierrez Sebastian , Knight Brittany , Cooper Lauren 
Published: April 2023

ABSTRACTBackgroundDifferent rates of morbidity, mortality, transmission, and immune escape are associated with various strains of the SARS-CoV-2 virus. With the emergence of new strains during seasonal outbreaks, ensuring that antigen-based immunoassays can detect SARS-CoV-2 infections across identified circulating viral variants is a crucial component of infection control efforts.ObjectiveTo validate the performance of the BD Veritor System for Rapid Detection of SARS-CoV-2 Assay (BD Veritor assay) to detect SARS-CoV-2 across variants of concern (VOC) and variants of interest (VOI).MethodsUsing the Illumina NextSeq 2000 Sequencer, viral sequencing was performed on prospectively collected, then frozen, SARS-CoV-2 RT-PCR positive nasal swabs stored in universal transport media (UTM). Specimens from symptomatic and asymptomatic individuals were included in the study. Using the information obtained from the sequencing analysis, the performance of the BD Veritor System assay was evaluated against the highly sensitive molecular RT-PCR Quidel Lyra SARS-CoV-2 assay for each variant.ResultsThe resulting PPA was 97.4% (95% CI: 86.8, 99.5) for detection of SARS-CoV-2 across all variants identified by Next Generation Sequencing (i.e., WHO-labeled variants Alpha, Delta, Gamma, Iota, Lambda, as well as two other non-labeled variants), with a 100% PPA for five of the six variant labels identified.ConclusionThe results demonstrate the robust performance of the BD Veritor assay in detecting SARS-CoV-2 in clinical nasal specimens in selected variants. As new variants emerge, additional studies will be beneficial to ensure the sustained performance of SARS-CoV-2 assays.
scRNA-seq revealed the special IG H&L V(D)J allelic inclusion rearrangement and the high proportion dual BCR expressing B cells
Authors: Zhu Lanwei , Peng Qi , Wu Yingjie , Yao Xinsheng 
Published: April 2023

abstractSince the first report of V (D) J “ allelic exclusion/inclusion”and” dual BCR “in 1961, despite continuous new discoveries, the proportion and source mechanism of dual BCR under physiological conditions have been puzzling immuologists.This study takes advantage of the single cell V (D) J sequencing technology, which can perfectly match the heavy and light chains of BCR at the level of a single B cell, and obtain the full length mRNA sequence of the CDR3 region. By analyzing the pairing of functional IGH and IGL chains in single B cell from human and mouse bone marrow and peripheral blood, it was found that dual BCR B cells exhibit stable and high levels of expression.Among them, human bone marrow and peripheral blood contain about 10% dual (or multiple) BCR B cells, and mouse peripheral blood and bone marrow memory B cells contain about 20% dual (or multiple) BCR B cells. At the same time, we innovatively found that in each research sample of humans and mice, there are three (or more) functional rearrangements (mRNA level) of a single chain in a single B cell. By analyzing the position, direction and other compositional characteristics of the V(D)J gene family, we found that at least two(or more) of them are derived from over two(or more) specific allelic inclusion rearrangements of a single chromosome.(mRNA molecular level evidence).The results of this article provides new insights, new methods and modeling references for evaluating the proportion, molecular characteristics and source mechanisms of dual BCR B cells, as well as potential significance of allelic inclusion (exclusion escape) of V(D)J rearrangement.
Severe cirrhosis is associated with increased surgical mortality and morbidities in patients with hip fractures: a propensity-score matched analysis using a large inpatient database
Authors: Hamada Osamu , Shin Jung-ho , Tsutsumi Takahiko , Tsunemitsu Ayako , Sasaki Noriko , Kunisawa Susumu , Fushimi Kiyohide , Imanaka Yuichi 
Published: April 2023

AbstractObjectiveThe aim of this study was to compare postoperative mortality and morbidities in patients with hip fractures undergoing surgery by Child-Pugh classes.Summary Background DataAdvanced cirrhosis is associated with increased mortality in several types of surgery, but the impact of severity of cirrhosis on postoperative outcomes in patients with hip fractures remain unclear.MethodsWe analyzed data of patients with hip fracture within a large inpatient database. We performed three sets of 1:1 propensity-score matching for four groups: cases without cirrhosis, and Child-Pugh classes A, B and C. We compared in-hospital mortality, length of stay, hospitalization fee, rate of 30-day readmission and complications in the following three pairs: cases without cirrhosis vs Child-Pugh class A, Child-Pugh class A vs B, and Child-Pugh class B vs C.ResultsAmong 833,648 eligible cases, propensity-score matching created 1,065 pairs between cases without cirrhosis vs Child-Pugh class A, 1,012 pairs between Child-Pugh class A vs B, and 489 pairs between Child-Pugh class B vs C. In-hospital mortality did not differ between cases with cirrhosis and those with Child-Pugh A classification (1.69% vs 1.41%; RD -0.28%; 95% CI: -1.34%–0.78%). In-hospital mortality was significantly higher in patients with Child-Pugh B classification than in those with A classification (1.48% vs 5.93%; RD 4.45%; 95% CI: 2.79%–6.10%), and in those with Child-Pugh C classification compared with those with B classification (6.34% vs 28.43%; RD 22.09%; 95% CI: 17.54%–26.63%). Among cases with cirrhosis, those in more severe Child-Pugh classes had longer length of stay, higher hospitalization fees and higher ratio of complications, such as acute liver failure, upper gastrointestinal bleeding and sepsis.ConclusionsOur results could help to identify patients at high-risk of postoperative mortality and morbidity among those with both hip fracture and cirrhosis. Patients with Child-Pugh C classification may benefit from discussions about nonsurgical management, goals of care, and overall prognosis.Mini-abstractWe conducted propensity-score matched analysis to examine mortality of groups of patients with hip fractures in a national patient database according to degree of severity of cirrhosis. Patients with higher Child-Pugh class of cirrhosis was shown to be associated with higher mortality.
Resource allocation strategies for insecticide-treated bed nets to achieve malaria eradication
Authors: Schmit Nora , Topazian Hillary M , Pianella Matteo , Charles Giovanni D , Winskill Peter , White Michael T , Hauck Katharina , Ghani Azra C 
Published: April 2023

ABSTRACTBackgroundLarge reductions in the global malaria burden have been achieved in the last decades, but plateauing funding poses a challenge for progressing towards the ultimate goal of malaria eradication. We aimed to determine the optimal strategy to allocate global resources to achieve this goal.MethodsUsing previously published mathematical models ofPlasmodium falciparumandPlasmodium vivaxtransmission incorporating insecticide-treated nets (ITNs) as an illustrative intervention, we sought to identify the global funding allocation that maximized impact under defined objectives and across a range of global funding budgets.ResultsWe found that the optimal strategy for case reduction closely mirrored an allocation framework that prioritizes funding for high-transmission settings, resulting in total case reductions of 76% (optimal strategy) and 66% (prioritizing high-transmission settings) at intermediate budget levels. Allocation strategies that had the greatest impact on case reductions were associated with lesser near-term impacts on the global population at risk, highlighting a trade-off between reducing burden and “shrinking the map” through a focus on near-elimination settings. The optimal funding distribution prioritized high ITN coverage in high-transmission settings endemic forP. falciparumonly, while maintaining lower levels in low-transmission settings. However, at high budgets, 62% of funding was targeted to low-transmission settings co-endemic forP. falciparumandP. vivax.ConclusionsThese results support current global strategies to prioritize funding to high-burdenP. falciparum-endemic settings in sub-Saharan Africa to minimize clinical malaria burden and progress towards elimination but highlight competing goals of reducing the global population at risk and addressing the burden ofP. vivax.
Amyloplast sedimentation repolarizes LAZYs to achieve gravity sensing in plants
Authors: Chen Jiayue , Yu Renbo , Li Na , Deng Zhaoguo , Zhang Xinxin , Zhao Yaran , Qu Chengfu , Yuan Yanfang , Pan Zhexian , Zhou Yangyang , Li Kunlun , Wang Jiajun , Chen Zhiren , Wang Xiaoyi , Wang Xiaolian , Dong Juan , Deng Xing Wang , Chen Haodong 
Published: April 2023

SUMMARYGravity controls directional growth of plants, and the classical starch-statolith hypothesis proposed more than a century ago postulates that amyloplast sedimentation in specialized cells initiates gravity sensing, but the molecular mechanism remains mysterious. Here, we report that gravistimulation by reorientation triggers the Mitogen-Activated Protein Kinase (MAPK) signaling-mediated phosphorylation of LAZY proteins, the key regulators of gravitropism accumulated more on the lower side of the plasma membrane in columella cells in regular growthArabidopsis. Phosphorylation of LAZY increases its interaction with several TOC proteins on the surface of amyloplasts, facilitating the translocation of LAZY proteins from the plasma membrane to the amyloplasts. Amyloplast sedimentation subsequently guides LAZY to relocate to the new lower side of the plasma membrane in columella cells, where LAZY induces asymmetrical auxin distribution and differential growth. Together, this study provides a molecular interpretation for the starch-statolith hypothesis: the organelle movement-triggered molecular polarity formation.
RORψt+CD4+T cells promote IL-23R-mediated neuronal cell apoptosis in the central nervous system
Authors: Sonar Sandip Ashok , Metei Thoihen Heikrujam , Inamdar Shrirang , Lenka Nibedita , Lal Girdhari 
Published: April 2023

AbstractTranscription factors T-bet and RORψt play a crucial role in neuronal autoimmunity, and mice deficient in these two factors do not develop experimental autoimmune encephalomyelitis (EAE). The independent role of T-bet and RORψt in the pathogenesis of EAE and how they help induce apoptosis of neurons in the central nervous system (CNS) during neuronal autoimmunity is unclear. In the present study, we showed that myelin oligodendrocyte glycoprotein (MOG35-55) peptide-specific Th1 cells deficient in RORψt could cross BBB but fail to induce apoptosis of neurons and EAE. Pathogenic Th17 cell-derived cytokines GM-CSF, TNF-α, IL-17A, and IL-21 significantly increase the surface expression of IL-23R on neuronal cells. Furthermore, we showed that, in EAE, neurons in the brain and spinal cord express IL-23R. IL-23-IL-23R signaling in neuronal cells caused phosphorylation of STAT3 (Ser727 and Tyr705) and induced cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1) molecules in an IL-23R-dependent manner and caused apoptosis. Thus, we provided a mechanism where we showed that T-bet is required to recruit pathogenic Th17 cells and RORψt expression to drive the apoptosis of IL-23R+neurons in the CNS and cause EAE. Understanding detailed molecular mechanisms will help to design better strategies to control neuroinflammation and autoimmunity.GRAPHICAL ABSTRACTOne Sentence SummaryIL-23-IL-23R signaling promotes apoptosis of CNS neurons.