Miracle-dz/UniFAR-FTUs huggingface dataset:
Subtle signatures of seeps: Record of groundwater in a Dryland, DK, Olduvai Gorge, Tanzania

Few proxies exist to identify aridity in the depositional record, although drylands cover ca 30% of the modern continental surface. New exposures in a siliciclastic and carbonate sequence in an arid to hyperarid basin at Olduvai Gorge, Tanzania provide a unique multi‐proxy record of a 1·85 Ma landscape that was exploited by early humans. The 2 m thick sequence of clastics and carbonates that are exposed along a 450 m outcrop records climate change over a single precession (dry‐wet‐dry) cycle. Siliciclastic data (sedimentary structures, grain size, mineralogy) and biological data are combined with data for a 10 to 35 cm thick limestone (stable isotopes, elemental geochemistry, petrography) to generate a depositional facies model for a site DK (Douglass Korongo) on this dry rift basin landscape. This site was situated on a low gradient, distal portion of a volcaniclastic alluvial fan. The clastics are intercalated distal alluvial fan sandy silts and lake clays that accumulated in a low energy environment. Groundwater discharge and the alkaline springs and seeps during wet‐to‐dry change in climate made a freshwater carbonate‐rich environment. Bedded lithofacies (a lime mudstone with fossils) were deposited in shallow standing (spring‐fed) pools, while nodular lithofacies with calcite spherulites indicate permanently saturated ground (seeps). Both environments experienced similar diagenesis, that is, the precipitation of authigenic barite from supersaturated groundwater, desiccation and pedogenesis, and late‐stage calcite precipitation. Compositional and isotopic data suggest that a fresh groundwater‐fed system was available to early humans even during dry intervals of the precession cycle.
Gray and White Matter Voxel-Based Morphometry of Alzheimer’s Disease With and Without Significant Cerebrovascular Pathologies

Alzheimer’s disease (AD) is the most common type of dementia, and AD individuals often present significant cerebrovascular disease (CVD) symptomology. AD with significant levels of CVD is frequently labeled mixed dementia (or sometimes AD-CVD), and the differentiation of these two neuropathologies (AD, AD-CVD) from each other is challenging, especially at early stages. In this study, we compared the gray matter (GM) and white matter (WM) volumes in AD (n = 83) and AD-CVD (n = 37) individuals compared with those of cognitively healthy controls (n = 85) using voxel-based morphometry (VBM) of their MRI scans. The control individuals, matched for age and sex with our two dementia groups, were taken from the ADNI. The VBM analysis showed widespread patterns of significantly lower GM and WM volume in both dementia groups compared to the control group (P < .05, family-wise error corrected). While comparing with AD-CVD, the AD group mainly demonstrated a trend of lower volumes in the GM of the left putamen and right hippocampus and WM of the right thalamus (uncorrected P < .005 with cluster threshold, K = 10). The AD-CVD group relative to AD tended to present lower GM and WM volumes, mainly in the cerebellar lobules and right brainstem regions, respectively (uncorrected P < .005 with cluster threshold, K = 10). Although finding a discriminatory feature in structural MRI data between AD and AD-CVD neuropathologies is challenging, these results provide preliminary evidence that demands further investigation in a larger sample size.
Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats

Astrocyte morphology affects function, including the regulation of glutamatergic signaling. This morphology changes dynamically in response to the environment. However, how early life manipulations alter adult cortical astrocyte morphology is underexplored. Our lab uses brief postnatal resource scarcity, the limited bedding and nesting (LBN) manipulation, in rats. We previously found that LBN promotes later resilience to adult addiction-related behaviors, reducing impulsivity, risky decision-making, and morphine self-administration. These behaviors rely on glutamatergic transmission in the medial orbitofrontal (mOFC) and medial prefrontal (mPFC) cortex. Here we tested whether LBN changed astrocyte morphology in the mOFC and mPFC of adult rats using a novel viral approach that, unlike traditional markers, fully labels astrocytes. Prior exposure to LBN causes an increase in the surface area and volume of astrocytes in the mOFC and mPFC of adult males and females relative to control-raised rats. We next used bulk RNA sequencing of OFC tissue to assess transcriptional changes that could increase astrocyte size in LBN rats. LBN caused mainly sex-specific changes in differentially expressed genes. However, Park7, which encodes for the protein DJ-1 that alters astrocyte morphology, was increased by LBN across sex. Pathway analysis revealed that OFC glutamatergic signaling is altered by LBN in males and females, but the gene changes in that pathway differed across sex. This may represent a convergent sex difference where glutamatergic signaling, which affects astrocyte morphology, is altered by LBN via sex-specific mechanisms. Collectively, these studies highlight that astrocytes may be an important cell type that mediates the effect of early resource scarcity on adult brain function.
IBRtools: An R package for calculating integrated biomarker indexes

Abstract Multibiomarker studies are useful to evaluate the early warning signs of environmental degradation, and their unified responses are often assessed through two common indexes, Integrated Biomarker Response (IBR) and Integrated Biological Responses version 2 (IBRv2). The R package IBRtools allows users to calculate both IBR and IBRv2 while simultaneously incorporating all the biomarkers under evaluation. The package includes functions for calculating the indexes IBR and IBRv2 and obtaining their standardized values, as well a function for radar chart creation and three example datasets. Here we describe the main algorithms involved in IBR and IBRv2 calculations, a description of the novel package and illustrate a workflow using data examples available on the package to guide the user on how to accurately acquire the values for either the IBR index or the IBRv2 index. The IBRtools package provides a user‐friendly platform for R users to obtain IBR index and IBRv2 values, making it straightforward even for large datasets.
MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder

Background Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive. Aims To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression. Methods Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression. Results The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity. Conclusions Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.
Telemedicine models of care: A retrospective review of telehealth in a Melbourne outpatient chronic wound service in 2021

Abstract To review the application of telehealth guidelines developed by Bondini et al for clinicians to determine patient suitability for telehealth in an outpatient Chronic Wound Service, including the proportion of patients suitable for telehealth, type and mode of telehealth encounters. Retrospective, random convenience sample of patients attending the Chronic Wound Service in 2021. Fifty‐six patients were included, most with leg/foot wounds (93%), median age 74 [54–84], 64% male. Four patients at admission and 19 patients at review met criteria for telehealth. Six percent of encounters were telehealth; phone‐only (82%), unscheduled nursing reviews (77%) in patients with healing wounds. Thirty patients (54%) received at least one telehealth encounter. Telehealth occurred 35.6 days later in the admission than face‐to‐face encounters (p < 0.05, 95% CI 14.9–56.3). There was a significant relationship between patients receiving telehealth and meeting telehealth suitability criteria on reviews ( X 2 (1) = 19.6*, p < 0.001). Eighteen percent of patients required wound‐related hospitalisation during their outpatient admission. Telehealth guidelines identified patients suitable for telehealth, although the proportion of patients was small. Telehealth was mostly utilised for nurse‐led telephone calls in patients with improving wounds. Future research into use of telephone review for clinical standards of wound care is warranted.
Performance of machine translators in translating French medical research abstracts to English: A comparative study of DeepL, Google Translate, and CUBBITT

Background Non-English speaking researchers may find it difficult to write articles in English and may be tempted to use machine translators (MTs) to facilitate their task. We compared the performance of DeepL, Google Translate, and CUBBITT for the translation of abstracts from French to English. Methods We selected ten abstracts published in 2021 in two high-impact bilingual medical journals (CMAJ and Canadian Family Physician) and used nine metrics of Recall-Oriented Understudy for Gisting Evaluation (ROUGE-1 recall/precision/F1-score, ROUGE-2 recall/precision/F1-score, and ROUGE-L recall/precision/F1-score) to evaluate the accuracy of the translation (scores ranging from zero to one [= maximum]). We also used the fluency score assigned by ten raters to evaluate the stylistic quality of the translation (ranging from ten [= incomprehensible] to fifty [= flawless English]). We used Kruskal-Wallis tests to compare the medians between the three MTs. For the human evaluation, we also examined the original English text. Results Differences in medians were not statistically significant for the nine metrics of ROUGE (medians: min-max = 0.5246–0.7392 for DeepL, 0.4634–0.7200 for Google Translate, 0.4815–0.7316 for CUBBITT, all p-values > 0.10). For the human evaluation, CUBBITT tended to score higher than DeepL, Google Translate, and the original English text (median = 43 for CUBBITT, vs. 39, 38, and 40, respectively, p-value = 0.003). Conclusion The three MTs performed similarly when tested with ROUGE, but CUBBITT was slightly better than the other two using human evaluation. Although we only included abstracts and did not evaluate the time required for post-editing, we believe that French-speaking researchers could use DeepL, Google Translate, or CUBBITT when writing articles in English.
Real‐world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia

Abstract Background The first‐generation BTK inhibitor ibrutinib is a standard‐of‐care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation. Methods This study used 2013–2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL. Results The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow‐up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient‐months for all discontinuers and 32.9 per 1000 patient‐months for non‐discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient‐months compared with non‐discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6). Conclusion In this first real‐world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib‐related AEs and/or new treatments to improve real‐world outcomes in patients with CLL.
Exploring the role of sex in the association of late chronotype on cardiorespiratory fitness

Abstract Circadian rhythms differ between young adult males and females. For example, males tend to be later chronotypes, preferring later timing of sleep and activity, than females. Likewise, there are sex differences in body composition and cardiorespiratory fitness. Few studies have investigated the association between circadian rhythms, cardiorespiratory fitness, and body composition. We sought to determine whether chronotype and circadian phase were associated with cardiorespiratory fitness, body composition, and anthropometric measures in sedentary males and females. Fifty‐nine adults participated in the study. Circadian phase and chronotype were measured using dim light melatonin onset (DLMO) and the Morningness–Eveningness Questionnaire (MEQ) score. We used peak oxygen uptake (VO2peak) results from a maximal graded exercise test to assess cardiorespiratory fitness. Body composition, BMI, and circumferences were collected as markers of adiposity. We observed a sex difference in the association between DLMO and VO2peak. For males, a later DLMO was associated with a lower VO2peak. VO2peak did not vary based on DLMO in females. Later circadian phase was also associated with increased body fat percentage, fat mass index, and abdominal circumference in males, but not females. Collectively, these results suggest that males who are later chronotypes may be at risk of obesity and low cardiorespiratory fitness.
“Non-Eloquent” brain regions predict neuropsychological outcome in tumor patients undergoing awake craniotomy

Supratotal resection of primary brain tumors is being advocated especially when involving “non-eloquent” tissue. However, there is extensive neuropsychological data implicating functions critical to higher cognition in areas considered “non-eloquent” by most surgeons. The goal of the study was to determine pre-surgical brain regions that would be predictive of cognitive outcome at 4–6 months post-surgery. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer-v6.0 image analysis suite. Linear regression models were used to regress cortical volumes from both hemispheres, against the total cognitive z-score to determine the relationship between brain structure and broad cognitive functioning while controlling for age, sex, and total segmented brain volume. We identified 62 consecutive patients who underwent planned awake resections of primary (n = 55, 88%) and metastatic at the University of New Mexico Hospital between 2015 and 2019. Of those, 42 (23 males, 25 left hemispheric lesions) had complete pre and post-op neuropsychological data available and were included in this study. Overall, total neuropsychological functioning was somewhat worse (p = 0.09) at post-operative neuropsychological outcome (Mean = -.20) than at baseline (Mean = .00). Patients with radiation following resection (n = 32) performed marginally worse (p = .036). We found that several discrete brain volumes obtained pre-surgery predicted neuropsychological outcome post-resection. For the total sample, these volumes included: left fusiform, right lateral orbital frontal, right post central, and right paracentral regions. Regardless of lesion lateralization, volumes within the right frontal lobe, and specifically right orbitofrontal cortex, predicted neuropsychological difference scores. The current study highlights the gaps in our current understanding of brain eloquence. We hypothesize that the volume of tissue within the right lateral orbital frontal lobe represents important cognitive reserve capacity in patients undergoing tumor surgery. Our data also cautions the neurosurgeon when considering supratotal resections of tumors that do not extend into areas considered “non-eloquent” by current standards.
Prediction performance of scoring systems after out-of-hospital cardiac arrest: A systematic review and meta-analysis

Introduction Ongoing changes in post resuscitation medicine and society create a range of ethical challenges for clinicians. Withdrawal of life-sustaining treatment is a very sensitive, complex decision to be made by the treatment team and the relatives together. According to the guidelines, prognostication after cardiopulmonary resuscitation should be based on a combination of clinical examination, biomarkers, imaging, and electrophysiological testing. Several prognostic scores exist to predict neurological and mortality outcome in post-cardiac arrest patients. We aimed to perform a meta-analysis and systematic review of current scoring systems used after out-of-hospital cardiac arrest (OHCA). Materials and methods Our systematic search was conducted in four databases: Medline, Embase, Central and Scopus on 24th April 2023. The patient population consisted of successfully resuscitated adult patients after OHCA. We included all prognostic scoring systems in our analysis suitable to estimate neurologic function as the primary outcome and mortality as the secondary outcome. For each score and outcome, we collected the AUC (area under curve) values and their CIs (confidence iterval) and performed a random-effects meta-analysis to obtain pooled AUC estimates with 95% CI. To visualize the trade-off between sensitivity and specificity achieved using different thresholds, we created the Summary Receiver Operating Characteristic (SROC) curves. Results 24,479 records were identified, 51 of which met the selection criteria and were included in the qualitative analysis. Of these, 24 studies were included in the quantitative synthesis. The performance of CAHP (Cardiac Arrest Hospital Prognosis) (0.876 [0.853–0.898]) and OHCA (0.840 [0.824–0.856]) was good to predict neurological outcome at hospital discharge, and TTM (Targeted Temperature Management) (0.880 [0.844–0.916]), CAHP (0.843 [0.771–0.915]) and OHCA (0.811 [0.759–0.863]) scores predicted good the 6-month neurological outcome. We were able to confirm the superiority of the CAHP score especially in the high specificity range based on our sensitivity and specificity analysis. Conclusion Based on our results CAHP is the most accurate scoring system for predicting the neurological outcome at hospital discharge and is a bit less accurate than TTM score for the 6-month outcome. We recommend the use of the CAHP scoring system in everyday clinical practice not only because of its accuracy and the best performance concerning specificity but also because of the rapid and easy availability of the necessary clinical data for the calculation.
The efficacy of sacral foam dressing in preventing sacral pressure injury: A systematic review and meta‐analysis

Abstract Purpose We aim to evaluate the efficacy of sacral foam dressings in preventing sacral pressure injury. Methods The PubMed, Embase and Web of Science databases were searched for relevant publications until October 2023. All studies evaluating the efficacy of sacral foam dressings in preventing sacral pressure injury were included. We calculated pooled risk ratio (RR) with 95% confidence intervals (CIs) for binary outcomes. The Cochrane's Risk of Bias Tool were used to evaluate the quality of studies. Results A total of 9 randomized controlled studies with 3972 patients were included in this analysis. Sacral pressure injury rate was significantly lower in the sacral foam dressing group compared with the standard care group (RR: 0.37, 95% CI: 0.17–0.82). Furthermore, the rate of ≥stage II sacral pressure injury was also significantly reduced (RR: 0.56, 95% CI: 0.37–0.83), along with a lower blanching erythema rate (RR: 0.64, 95% CI: 0.42–0.97). No obvious publication bias was observed in the funnel plot (Egger's p values = 0.91). Conclusions Sacral foam dressing significantly reduced the incidence of sacral pressure injuries, including those of stage II or higher, and blanching erythema when compared to standard care without sacral foam dressing. However, the results should be interpreted with cautious because of the observed heterogeneity and the diverse patient population. Further larger, well‐designed randomized control studies are needed.
Tissue‐specific expression differences in Ras‐related GTP‐binding proteins in male rats

Abstract The protein kinase Mechanistic Target of Rapamycin (mTOR) in Complex 1 (mTORC1) is regulated in part by the Ras‐related GTP‐binding proteins (Rag GTPases). Rag GTPases form a heterodimeric complex consisting of either RagA or RagB associated with either RagC or RagD and act to localize mTORC1 to the lysosomal membrane. Until recently, RagA and RagB were thought to be functionally redundant, as were RagC and RagD. However, recent research suggests that the various isoforms differentially activate mTORC1. Here, the mRNA expression and protein abundance of the Rag GTPases was compared across male rat skeletal muscle, heart, liver, kidney, and brain. Whereas mRNA expression of RagA was higher than RagB in nearly all tissues studied, RagB protein abundance was higher than RagA in all tissues besides skeletal muscle. RagC mRNA expression was more abundant or equal to RagD mRNA, and RagD protein was more abundant than RagC protein in all tissues. Moreover, the proportion of RagB in the short isoform was greater than the long in liver, whereas the opposite was true in brain. These results serve to further elucidate Rag GTPase expression and offer potential explanations for the differential responses to amino acids that are observed in different tissues.
smdi: an R package to perform structural missing data investigations on partially observed confounders in real-world evidence studies

Abstract Objectives Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We aimed to develop a toolkit to streamline missing data diagnostics to guide choice of analytic approaches based on meeting necessary assumptions. Materials and methods We developed the smdi (structural missing data investigations) R package based on results of a previous simulation study which considered structural assumptions of common missing data mechanisms in EHR. Results smdi enables users to run principled missing data investigations on partially observed confounders and implement functions to visualize, describe, and infer potential missingness patterns and mechanisms based on observed data. Conclusions The smdi R package is freely available on CRAN and can provide valuable insights into underlying missingness patterns and mechanisms and thereby help improve the robustness of real-world evidence studies.