bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicompartmental trauma alters bone marrow erythroblastic islands
Authors: Kelly Lauren S. , Munley Jennifer A. , Pons Erick E. , Coldwell Preston S. , Kannan Kolenkode B. , Efron Philip A. , Mohr Alicia M. 
Published: January 2023

BACKGROUND
Trauma is associated with widespread inflammation, neuroendocrine activation, and an inadequate bone marrow response to anemia. During late-stage erythropoiesis, erythroid progenitors/erythroblasts form clusters on the surface of specialized bone marrow macrophages where they are supported through terminal differentiation and enucleation. We hypothesized that these erythroblastic islands (EBIs) are adversely impacted by severe trauma.

METHODS
Male Sprague-Dawley rats (n = 8/group) were subjected to either multiple injuries (PT) (lung contusion, hemorrhagic shock, cecectomy, and bifemoral pseudofractures), PT plus 2 hours of daily chronic restraint stress (PT/CS), or naive controls. Bone marrow was harvested on days 2 and 7. Nuclear-stained, enriched bone marrow EBIs were fixed and stained for CD71, VCAM-1, and CD163, and confocal images were obtained at 20 times magnification. Numbers of erythroid cells/EBI and ratio of reticulocytes/EBI were counted by a blinded observer. Differences were compared using analysis of variance, with significance defined as p < 0.05.

RESULTS
PT and PT/CS had significantly reduced numbers of erythroid cells per EBI on day 2 when compared with naive (PT: 5.9 ± 1.0 cells [p < 0.05], PT/CS: 6.8 ± 0.8 cells [p < 0.05] vs. naive: 8.5 ± 0.8 cells). On day 7, the number of erythroid cells/EBI increased following PT (8.3 ± 0.4 cells) but remained reduced following PT/CS (5.9 ± 0.5 cells [p < 0.05]). This correlated with an increased proportion of reticulocytes/EBI on day 7 following PT, which was not present following PT/CS (PT: 54% [p < 0.05] vs. PT/CS: 28%).

CONCLUSION
Late-stage erythropoiesis was altered following multicompartmental PT early after injury, and these alterations persisted with the addition of daily chronic stress. Alterations in EBI structure and function after severe trauma and critical illness may serve as a promising new area of study to improve mechanistic understanding of persistent anemia after trauma.
Institutional outcomes of blunt liver and splenic injury in the Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium era
Authors: Stewart Shai , Fraser James A. , Rentea Rebecca M. , Aguayo Pablo , Juang David , Fraser Jason D. , Snyder Charles L. , Hendrickson Richard J. , St. Peter Shawn D. , Oyetunji Tolulope A. 
Published: January 2023

BACKGROUND
The Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium practice management guideline was created to standardize management of blunt liver or spleen injury across pediatric trauma centers. We describe our outcomes since guideline adoption at our institution and hypothesize that blunt liver or spleen injury may be managed more expeditiously than currently reported without compromising safety.

METHODS
A retrospective cohort study was conducted on patients younger than 18 years presenting with blunt liver and/or splenic injuries from March 2016 to March 2021 at one participating center.

RESULTS
A total of 199 patients were included. There were no clinically relevant differences for age, body mass index, or sex among the cohort. Isolated splenic injuries (n = 91 [46%]) and motor vehicle collisions (n = 82 [41%]) were the most common injury and mechanism, respectively. The overall median length of stay (LOS) was 1.2 days (interquartile range, 0.45–3.3 days). Intensive care unit utilization was 23% (n = 46). There was no statistically significant difference in median LOS among patients with isolated solid organ injuries, regardless of injury grade. There were no readmissions associated with non-operative management.

CONCLUSION
The Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium guideline fosters high rates of nonoperative management with low intensive care unit utilization and LOS while demonstrating safety in implementation, irrespective of injury grade.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Targeting of Th17-related cytokines in patients with Darier Disease
Authors: Ettinger Monika , Burner Teresa , Sharma Anshu , Chang Yun-Tsan , Lackner Angelika , Prompsy Pacôme , Pospischil Isabella , Traxler Judith , Wahl Gerald , Altrichter Sabine , Tsai Yi-Chien , Varkhande Suraj R. , Schoeftner Leonie C. , Iselin Christoph , Gratz Iris K. , Kimeswenger Susanne , Guenova Emmanuella , Hoetzenecker Wolfram 
Published: January 2023

AbstractDarier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. DD patients often have skin involvement characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. Using gene and protein expression profiling assays, we demonstrate enhanced expression of Th-17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We prove that targeting the IL-23/-17 axis in DD with monoclonal antibodies is an effective and safe therapy for DD patients, leading to significant clinical improvement. As DD is a chronic, relapsing disease, our findings provide new options for the long-term management of skin inflammation in patients with DD.
Microdiversity of the Vaginal Microbiome is Associated with Preterm Birth
Authors: Liao Jingqiu , Shenhav Liat , Urban Julia A. , Serrano Myrna , Zhu Bin , Buck Gregory A. , Korem Tal 
Published: January 2023

AbstractPreterm birth (PTB) is the leading cause of neonatal morbidity and mortality. The vaginal microbiome has been associated with PTB, yet the mechanisms underlying this association are not fully understood. Understanding microbial genetic adaptations to selective pressures, especially those related to the host, may yield new insights into these associations. To this end, we analyzed metagenomic data from 705 vaginal samples collected longitudinally during pregnancy from 40 women who delivered preterm spontaneously and 135 term controls from the Multi-Omic Microbiome Study-Pregnancy Initiative (MOMS-PI1). We find that the vaginal microbiome of pregnancies that ended preterm exhibits unique genetic profiles. It is more genetically diverse at the species level, a result which we validate in an additional cohort, and harbors a higher richness and diversity of antimicrobial resistance genes, likely promoted by transduction. Interestingly, we find thatGardnerellaspecies, a group of central vaginal pathobionts, are driving this higher genetic diversity, particularly during the first half of the pregnancy. We further present evidence thatGardnerellaspp. undergoes more frequent recombination and stronger purifying selection in genes involved in lipid metabolism. Overall, our results reveal novel associations between the vaginal microbiome and PTB using population genetics analyses, and suggest that evolutionary processes acting on the vaginal microbiome may play a vital role in adverse pregnancy outcomes such as preterm birth.
Learning fast and fine-grained detection of amyloid neuropathologies from coarse-grained expert labels
Authors: Wong Daniel R. , Magaki Shino D. , Vinters Harry V. , Yong William H. , Monuki Edwin S. , Williams Christopher K. , Martini Alessandra C. , DeCarli Charles , Khacherian Chris , Graff John P. , Dugger Brittany N. , Keiser Michael J. 
Published: January 2023

AbstractPrecise, scalable, and quantitative evaluation of whole slide images is crucial in neuropathology. We release a deep learning model for rapid object detection and precise information on the identification, locality, and counts of cored plaques and cerebral amyloid angiopathies (CAAs). We trained this object detector using a repurposed image-tile dataset without any human-drawn bounding boxes. We evaluated the detector on a new manually-annotated dataset of whole slide images (WSIs) from three institutions, four staining procedures, and four human experts. The detector matched the cohort of neuropathology experts, achieving 0.64 (model) vs. 0.64 (cohort) average precision (AP) for cored plaques and 0.75 vs. 0.51 AP for CAAs at a 0.5 IOU threshold. It provided count and locality predictions that correlated with gold-standard CERAD-like WSI scoring (p=0.07± 0.10). The openly-available model can quickly score WSIs in minutes without a GPU on a standard workstation.
Compensatory adaptation does not fully alleviate the costs associated with rifampicin resistance and occurs predominantly through off-target mutations
Authors: Cohen Yasmin , Rozen Gydeon A , Pennings Pleuni S , Katz Sophia , Hershberg Ruth 
Published: January 2023

AbstractThe manner in which costs associated with antibiotic resistance mutations are alleviated through the acquisition of compensatory mutations has bearing on the dynamics of resistance accumulation and spread as well as on our more general understanding of the persistence of adaptive genotypes. Here, we combine evolutionary experiments, fitness analyses, and whole genome sequencing to examine the way compensation to alleviate costs associated with rifampicin resistance is achieved, both when resistance is fixed and when initial majorities of resistant cells are grown alongside susceptible cells. We found compensatory mutations to occur across all examined populations. However, compensation never fully alleviates the initial costs of resistance. In contrast to prevalent assumptions, compensatory mutations mostly occurred outside of the RNA polymerase core enzyme, which serves as the target of rifampicin. The target size for compensatory mutations appears to be high, as great variation exists in compensatory mutations, even within a single population. At the same time, the pathways of compensation are quite convergent, meaning that, across independent populations, we often observe compensatory mutations in the same loci and sometimes even observe the precise same compensatory mutations across populations.
Effects ofMAPTrs17649553 on Structural Network Integrity and Verbal Memory in Parkinson’s Disease
Authors: Chen Zhichun , Wu Bin , Li Guanglu , Zhou Liche , Zhang Lina , Liu Jun 
Published: January 2023

AbstractBackgroundCurrently, over 90 genetic loci have been found to be associated with Parkinson’s disease (PD) in genome-wide association studies, nevertheless, the effects of these genetic variants on the clinical features and brain structure of PD patients are largely unknown.ObjectiveThis study investigated the effects of microtubule-associated protein tau (MAPT), rs17649553 (C>T), a genetic variant associated with reduced PD risk, on the functional and structural networks of PD patients.MethodsTotally 83 PD subjects from Parkinson’s Progression Markers Initiative database were included for this study. They all received structural and functional magnetic resonance imaging and whole exome sequencing. The effects ofMAPTrs17649553 on brain structural and functional networks were systematically assessed.ResultsMAPTrs17649553 T allele was associated with better verbal memory in PD patients. In addition,MAPTrs17649553 significantly reshaped the topology of gray matter covariance network and white matter network but not that of functional network. Both the network metrics in gray matter covariance network and white matter network were correlated with verbal memory, however, the mediation analysis showed that it was the small-worldness topology in white matter network that mediated the effects ofMAPTrs17649553 on verbal memory.ConclusionIn sum, we proposed thatMAPTrs17649553 T allele was associated with superior structural network topology and better verbal memory in PD. Future studies are needed to determine the role ofMAPTrs17649553 in PD initiation and progression.
Adverse childhood trauma and reoccurrence of illness impact the gut microbiome, which affects suicidal behaviors and the phenome of major depression: towards enterotypic-phenotypes
Authors: Maes Michael , Vasupanrajit Asara , Jirakran Ketsupar , Klomkliew Pavit , Chanchaem Prangwalai , Tunvirachaisakul Chavit , Plaimas Kitiporn , Suratanee Apichat , Payungporn Sunchai 
Published: January 2023

AbstractThe first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours and cognitive deficits; the effects of adverse childhood experiences (ACE) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc).We determined isometric log-ratio abundances or prevalence of gut microbiome phyla, genera, and species by analyzing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing.Six microbiome taxa accounted for 36% of the variance in the depression phenome, namelyHungatellaandFusicatenibacter(positive associations) andButyricicoccus, Clostridium, Parabacteroides merdae, andDesulfovibrio piger(inverse association). This profile (labeled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to suicidal behaviours. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, andRomboutsia were positively associated, whileProteobacteriaandClostridium sensu strictowere negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current suicidal behaviours.In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and suicidal behaviours, and possibly for the prevention of future episodes.
The fitness consequences of wildlife conservation translocations: a meta-analysis
Authors: Gross Iwo P. , Wilson Alan E. , Wolak Matthew E. 
Published: January 2023

ABSTRACTConservation translocation is a common strategy to offset mounting rates of population declines through the transfer of captive-or wild-origin organisms into areas where conspecific populations are imperiled or completely extirpated. Translocations that supplement existing populations are referred to as reinforcements, and can be conducted using captive-origin animals (ex situreinforcements [ESR]) or wild-origin animals without any captive ancestry (in situreinforcement [ISR]). These programs have been criticized for low success rates and husbandry practices that produce individuals with genetic and performance deficits, but the post-release performance of captive-origin or wild-origin translocated groups has not been systematically reviewed to quantify success relative to wild-resident control groups. To assess the disparity in post-release performance of translocated organisms relative to wild-resident conspecifics and examine the association of performance disparity with organismal and methodological factors across studies, we conducted a systematic review and meta-analysis of 821 performance comparisons from 171 studies representing nine animal classes (101 species). We found that translocated organisms have 64% decreased odds of out-performing their wild-resident counterparts, supporting claims of systemic issues hampering conservation translocations. To help identify translocation practices that could maximize program success in the future, we further quantified the impact of broad organismal and methodological factors on the disparity between translocated and wild-resident conspecific performance. Pre-release animal enrichment significantly reduced performance disparities, whereas our results suggest no overall effects of taxonomic group, sex, captive generation time, or the type of fitness surrogate measured. This work is the most comprehensive systematic review to date of animal conservation translocations in which wild conspecifics were used as comparators, thereby facilitating an evaluation of the overall impact of this conservation strategy and identifying specific actions to increase success. Our review highlights the need for conservation managers to include both sympatric and allopatric wild-reference groups to ensure the post-release performance of translocated animals can be evaluated. Further, our analyses identify pre-release animal enrichment as a particular strategy for improving the outcomes of animal conservation translocations, and demonstrate how meta-analysis can be used to identify implementation choices that maximize translocated animal contributions to recipient population growth and viability.
Temporal physiological, transcriptomic and metabolomic analyses revealed molecular mechanism ofCanna indica’s response to Cr stress
Authors: Wei Zhao , Zhongbing Chen , Xiuqing Yang , Luying Sheng , Huan Mao , Sixi Zhu 
Published: January 2023

AbstractChromium (Cr) can interfere with plant gene expression, change the content of metabolites and affect plant growth. However, the molecular response mechanism of wetland plants at different time sequences under Cr stress has yet to be fully understood.The results showed that Cr stress increased the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX) and peroxidase (POD), the contents of glutathione (GSH), malondialdehyde (MDA), and oxygen free radical (ROS), and inhibited the biosynthesis of photosynthetic pigments, thus leading to changes in plant growth and biomass. that Cr stress mainly affected 12 metabolic pathways, involving 38 differentially expressed metabolites, including amino acids, phenylpropane, and flavonoids. A total of 16247 differentially expressed genes were identified, among which, at the early stage of stress,C. indicaresponds to Cr toxicity mainly through galactose, starch and sucrose metabolism. With the extension of stress time, plant hormone signal transduction and MAPK signaling pathway inC. indicain the treatment group were significantly affected. Finally, in the late stage of stress,C. indicaco-defuses Cr toxicity by activating its Glutathione metabolism and Phenylpropanoid biosynthesis. In conclusion, this study revealed the molecular response mechanism ofC. indicato Cr stress at different times through multi-omics methods.Graphical Abstract
Using a Topic Model to Map and Analyze a Large Curriculum
Authors: Takizawa Peter A 
Published: January 2023

AbstractA qualitative and quantitative understanding of curriculum content is critical for knowing whether it’s meeting its learning objectives. Curricula for medical education present challenges due to amount of content, the diversity of topics and the large number of contributing faculty. To create a manageable representation of the content in the pre-clerkship curriculum at Yale School of Medicine, a topic model was generated from all educational documents given to students during the pre-clerkship period. The model was used to quantitatively map content to school-wide competencies. The model measured how much of the curriculum addressed each topic and identified a new content area of interest, gender identity, whose coverage could be tracked over four years. The model also allowed quantitative measurement of integration of content within and between courses in the curriculum. The methods described here should be applicable to curricula in which texts can be extracted from materials.
Stochastic Transmission in Epidemiological Models
Authors: Albani Vinicius V.L. , Zubelli Jorge P. 
Published: January 2023

AbstractRecent empirical evidence suggests that the transmission coefficient in susceptible-exposed-infected-removed-like (SEIR-like) models evolves with time, presenting random patterns, and some stylized facts, such as mean-reversion and jumps. To address such observations we propose the use of jump-diffusion stochastic processes to parameterize the transmission coefficient in an SEIR-like model that accounts for death and time-dependent parameters. We provide a detailed theoretical analysis of the proposed model proving the existence and uniqueness of solutions as well as studying its asymptotic behavior. We also compare the proposed model with some variations possibly including jumps. The forecast performance of the considered models, using reported COVID-19 infections from New York City, is then tested in different scenarios, including major outbreaks. The proposed jump-diffusion model presented remarkably accurate out-of-sample predictions, even during larger forecasted periods.
Daily exposure to PM2.5and 1.5 million deaths: A time-stratified case-crossover analysis in the Mexico City Metropolitan Area
Authors: Gutiérrez-Avila Iván , Riojas-Rodríguez Horacio , Colicino Elena , Rush Johnathan , Tamayo-Ortiz Marcela , Borja-Aburto Víctor Hugo , Just Allan C. 
Published: January 2023

AbstractBackgroundSatellite-based PM2.5predictions are being used to advance exposure science and air-pollution epidemiology in developed countries; including emerging evidence about the impacts of PM2.5on acute health outcomes beyond the cardiovascular and respiratory systems, and the potential modifying effects from individual-level factors in these associations. Research on these topics is lacking in Latin America.MethodsWe used a time-stratified case-crossover study design with 1,479,950 non-accidental deaths from Mexico City Metropolitan Area for the period of 2004-2019. Daily 1x1 km PM2.5(median=23.4 μg/m3; IQR=13.6 μg/m3) estimates from our satellite-based regional model were employed for exposure assessment at the sub-municipality level. Associations between PM2.5with broad-category (organ-system) and cause-specific mortality outcomes were estimated with distributed lag conditional logistic models. We also fit models stratifying by potential individual-level effect modifiers including; age, sex, and individual SES-related characteristics namely: education, health insurance coverage, and job categories.ResultsPM2.5exposure was associated with higher total non-accidental, cardiovascular, cerebrovascular, respiratory, and digestive mortality. A 10-μg/m3PM2.5higher cumulative exposure over one week (lag06) was associated with higher cause-specific mortality outcomes including hypertensive disease [2.28% (95%CI: 0.26%–4.33%)], acute ischemic heart disease [1.61% (95%CI: 0.59%–2.64%)], other forms of heart disease [2.39% (95%CI: -0.35%–5.20%)], hemorrhagic stroke [3.63% (95%CI: 0.79%–6.55%)], influenza and pneumonia [4.91% (95%CI: 2.84%–7.02%)], chronic respiratory disease [2.49% (95%CI: 0.71%–4.31%)], diseases of the liver [1.85% (95%CI: 0.31%–3.41%)], and renal failure [3.48% (95%CI: 0.79%–6.24%)]. No differences in effect size of associations were observed between SES strata.ConclusionsExposure to PM2.5was associated with mortality outcomes beyond the cardiovascular and respiratory systems, including specific death-causes from the digestive and genitourinary systems, with no indications of effect modification by individual SES-related characteristics.