Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative effects of human-equivalent low, moderate, and high dose oral prednisone intake on autoimmunity and glucocorticoid-related toxicity in a murine model of environmental-triggered lupus

Autoimmune diseases can be triggered by environmental toxicants such as crystalline silica dust (cSiO2). Here, we characterized the dose-dependent immunomodulation and toxicity of the glucocorticoid (GC) prednisone in a preclinical model that emulates onset and progression of cSiO2-triggered lupus. Two cohorts of 6-wk-old female NZBWF1 mice were fed either control AIN-93G diet or one of three AIN-93G diets containing prednisone at 5, 15, or 50 mg/kg diet which span human equivalent oral doses (HED) currently considered to be low (PL; 5 mg/d HED), moderate (PM; 14 mg/d HED), or high (PH; 46 mg/d HED), respectively. At 8 wk of age, mice were intranasally instilled with either saline vehicle or 1 mg cSiO2 once weekly for 4 wk. The experimental plan was to 1) terminate one cohort of mice (n=8/group) 14 wk after the last cSiO2 instillation for pathology and autoimmunity assessment and 2) to maintain a second cohort (n=9/group) to monitor glomerulonephritis development and survival. Mean blood concentrations of prednisone’s principal active metabolite, prednisolone, in mice fed PL, PM, and PH diets were 27, 105, 151 ng/ml, respectively, which are consistent with levels observed in human blood ≤ 12 h after single bolus treatments with equivalent prednisone doses. Results from the first cohort revealed that consumption of PM, but not PL diet, significantly reduced cSiO2-induced pulmonary ectopic lymphoid structure formation, nuclear-specific AAb production, inflammation/autoimmune gene expression in the lung and kidney, splenomegaly, and glomerulonephritis in the kidney. Relative to GC-associated toxicity, PM diet, but not PL diet, elicited muscle wasting, but these diets did not affect bone density or cause glucosuria. Importantly, neither PM nor PL diet improved latency of cSiO2-accelerated death. PH-fed mice in both cohorts displayed robust GC-associated toxicity including body weight loss, reduced muscle mass, and extensive glucosuria 7 wk after the final cSiO2 instillation requiring their early removal from the study. Taken together, our results demonstrate that while moderate doses of prednisone can reduce important pathological endpoints of cSiO2-induced autoimmunity in lupus-prone mice, such as upstream ectopic lymphoid structure formation, these ameliorative effects come with unwanted GC toxicity, and, crucially, none of these three doses extended survival time.
Problematic smartphone use is associated with differences in static and dynamic brain functional connectivity in young adults

Introduction This study aimed to investigate the possible associations between problematic smartphone use and brain functions in terms of both static and dynamic functional connectivity patterns. Materials and methods Resting-state functional magnetic resonance imaging data were scanned from 53 young healthy adults, all of whom completed the Short Version of the Smartphone Addiction Scale (SAS-SV) to assess their problematic smartphone use severity. Both static and dynamic functional brain network measures were evaluated for each participant. The brain network measures were correlated the SAS-SV scores, and compared between participants with and without a problematic smartphone use after adjusting for sex, age, education, and head motion. Results Two participants were excluded because of excessive head motion, and 56.9% (29/51) of the final analyzed participants were found to have a problematic smartphone use (SAS-SV scores ≥ 31 for males and ≥ 33 for females, as proposed in prior research). At the global network level, the SAS-SV score was found to be significantly positively correlated with the global efficiency and local efficiency of static brain networks, and negatively correlated with the temporal variability using the dynamic brain network model. Large-scale subnetwork analyses indicated that a higher SAS-SV score was significantly associated with higher strengths of static functional connectivity within the frontoparietal and cinguloopercular subnetworks, as well as a lower temporal variability of dynamic functional connectivity patterns within the attention subnetwork. However, no significant differences were found when directly comparing between the groups of participants with and without a problematic smartphone use. Conclusion Our results suggested that problematic smartphone use is associated with differences in both the static and dynamic brain network organizations in young adults. These findings may help to identify at-risk population for smartphone addiction and guide targeted interventions for further research. Nevertheless, it might be necessary to confirm our findings in a larger sample, and to investigate if a more applicable SAS-SV cutoff point is required for defining problematic smartphone use in young Chinese adults nowadays.
Mixed growth of Salix species can promote phosphate-solubilizing bacteria in the roots and rhizosphere

Phosphorus (P) is an essential plant nutrient that can limit plant growth due to low availability in the soil. P-solubilizing bacteria in the roots and rhizosphere increase the P use efficiency of plants. This study addressed the impact of plant species, the level of plant association with bacteria (rhizosphere or root endophyte) and environmental factors (e.g., seasons, soil properties) on the abundance and diversity of P-solubilizing bacteria in short-rotation coppices (SRC) of willows (Salix spp.) for biomass production. Two willow species (S. dasycladoscv. Loden and S. schwerinii × S. viminalis cv. Tora) grown in mono-and mixed culture plots were examined for the abundance and diversity of bacteria in the root endosphere and rhizosphere during two seasons (fall and spring) in central Sweden and northern Germany. Soil properties, such as pH and available P and N, had a significant effect on the structure of the bacterial community. Microbiome analysis and culture-based methods revealed a higher diversity of rhizospheric bacteria than endophytic bacteria. The P-solubilizing bacterial isolates belonged mainly to Proteobacteria (85%), Actinobacteria (6%) and Firmicutes (9%). Pseudomonas was the most frequently isolated cultivable bacterial genus from both the root endosphere and the rhizosphere. The remaining cultivable bacterial isolates belonged to the phyla Actinobacteria and Firmicutes. In conclusion, site-specific soil conditions and the level of plant association with bacteria were the main factors shaping the bacterial communities in the willow SRCs. In particular, the concentration of available P along with the total nitrogen in the soil controlled the total bacterial diversity in willow SRCs. A lower number of endophytic and rhizospheric bacteria was observed in Loden willow species compared to that of Tora and the mix of the two, indicating that mixed growth of Salix species promotes P-solubilizing bacterial diversity and abundance. Therefore, a mixed plant design was presented as a management option to increase the P availability for Salix in SRCs. This design should be tested for further species mixtures.
Factors influencing clinicians' willingness to use an AI-based clinical decision support system

Background Given the opportunities created by artificial intelligence (AI) based decision support systems in healthcare, the vital question is whether clinicians are willing to use this technology as an integral part of clinical workflow. Purpose This study leverages validated questions to formulate an online survey and consequently explore cognitive human factors influencing clinicians' intention to use an AI-based Blood Utilization Calculator (BUC), an AI system embedded in the electronic health record that delivers data-driven personalized recommendations for the number of packed red blood cells to transfuse for a given patient. Method A purposeful sampling strategy was used to exclusively include BUC users who are clinicians in a university hospital in Wisconsin. We recruited 119 BUC users who completed the entire survey. We leveraged structural equation modeling to capture the direct and indirect effects of “AI Perception” and “Expectancy” on clinicians' Intention to use the technology when mediated by “Perceived Risk”. Results The findings indicate a significant negative relationship concerning the direct impact of AI's perception on BUC Risk (ß = −0.23, p < 0.001). Similarly, Expectancy had a significant negative effect on Risk (ß = −0.49, p < 0.001). We also noted a significant negative impact of Risk on the Intent to use BUC (ß = −0.34, p < 0.001). Regarding the indirect effect of Expectancy on the Intent to Use BUC, the findings show a significant positive impact mediated by Risk (ß = 0.17, p = 0.004). The study noted a significant positive and indirect effect of AI Perception on the Intent to Use BUC when mediated by risk (ß = 0.08, p = 0.027). Overall, this study demonstrated the influences of expectancy, perceived risk, and perception of AI on clinicians' intent to use BUC (an AI system). AI developers need to emphasize the benefits of AI technology, ensure ease of use (effort expectancy), clarify the system's potential (performance expectancy), and minimize the risk perceptions by improving the overall design. Conclusion Identifying the factors that determine clinicians' intent to use AI-based decision support systems can help improve technology adoption and use in the healthcare domain. Enhanced and safe adoption of AI can uplift the overall care process and help standardize clinical decisions and procedures. An improved AI adoption in healthcare will help clinicians share their everyday clinical workload and make critical decisions.
Outcomes of critically ill coronavirus disease 2019 patients requiring kidney replacement therapy: A retrospective cohort study

Background Coronavirus disease 2019 (COVID-19) has resulted in high hospitalization rates worldwide. Acute kidney injury (AKI) in patients hospitalized for COVID-19 is frequent and associated with disease severity and poor outcome. The aim of this study was to investigate the incidence of kidney replacement therapy (KRT) in critically ill patients with COVID-19 and its implication on outcome. Methods We retrospectively analyzed all COVID-19 patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf (Germany) between 1 March 2020 and 31 July 2021. Demographics, clinical parameters, type of organ support, length of intensive care unit (ICU) stay, mortality and severity scores were assessed. Results Three-hundred critically ill patients with COVID-19 were included. The median age of the study population was 61 (IQR 51–71) years and 66% (n = 198) were male. 73% (n = 219) of patients required invasive mechanical ventilation. Overall, 68% (n = 204) of patients suffered from acute respiratory distress syndrome and 30% (n = 91) required extracorporeal membrane oxygenation (ECMO). We found that 46% (n = 139) of patients required KRT. Septic shock (OR 11.818, 95% CI: 5.941–23.506, p < 0.001), higher simplified acute physiology scores (SAPS II) (OR 1.048, 95% CI: 1.014–1.084, p = 0.006) and vasopressor therapy (OR 5.475, 95% CI: 1.127–26.589, p = 0.035) were independently associated with the initiation of KRT. 61% (n = 85) of patients with and 18% (n = 29) without KRT died in the ICU (p < 0.001). Cox regression found that KRT was independently associated with mortality (HR 2.075, 95% CI: 1.342–3.208, p = 0.001) after adjusting for confounders. Conclusion Critically ill patients with COVID-19 are at high risk of acute kidney injury with about half of patients requiring KRT. The initiation of KRT was associated with high mortality.
The application of Tong-fu therapeutic method on ulcerative colitis: A systematic review and meta-analysis for efficacy and safety of rhubarb-based therapy

Background: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. Method: Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). Results: A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. Conclusion: Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1–13 weeks or 3 months via administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.
Prediction and prevention of preeclampsia by physicians in Brazil: An original study

Background Considering the worldwide importance of preeclampsia, especially in Brazil, the screening of pregnant women at greater risk of developing the disease and the application of preventive measures are essential. This study aimed to assess the medical performance in this context in Brazil. Methods A survey was developed to quantify the number of physicians who prescribe acetylsalicylic acid (ASA) and/or calcium for preeclampsia prevention. The survey was sent to all Brazilian obstetricians affiliated to the Brazilian Federation of OBGYN by email and WhatsApp. The survey remained opened for 6 months and included questions about the use of ASA and calcium, as well as about the use of a complementary test to predict preeclampsia. Results The sample consisted of 360 responding physicians and 100% coverage of responses from physicians from the five different regions of Brazil was obtained. The vast majority of respondents (94.72%) prescribe ASA to prevent preeclampsia, with 80.3% prescribing a dose of 100 mg/day. Calcium is prescribed by 83.9% of the respondents. The majority of the interviewed sample (58.6%) requests uterine artery Doppler imaging to predict preeclampsia and 31.7% do not request any additional test. When the analysis was performed by region, only the northern region differed from the other Brazilian regions regarding the use of ASA and calcium for preeclampsia prevention. While more than 90% of physicians in the other regions prescribe ASA, 40% in the northern region do not use it (p < 0.0001). Regarding calcium, 30% of physicians in northern Brazil do not use the drug for preeclampsia prevention, a percentage that also differs from the other regions where the medication is prescribed by 80 to 90% of physicians (p = 0.021). Conclusions The vast majority of Brazilian physicians prescribe low-dose aspirin and calcium carbonate to prevent preeclampsia in high-risk pregnant women. In addition to the identification of clinical risk factors, most doctors use Doppler of the uterine arteries as a predictive method. In the northern region of Brazil, physicians use aspirin and calcium less frequently for preventing preeclampsia compared to the rest of the country.
Increased expression of the RNA-binding protein Musashi-2 is associated with immune infiltration and predicts better outcomes in ccRCC patients

RNA-binding proteins (RBPs) mainly contribute to abnormalities in posttranscriptional gene regulation. The RBP Musashi-2, an evolutionarily conserved protein, has been characterized as an oncoprotein in various tumors. However, the prognostic value and potential roles of Musashi-2 in clear cell renal cell carcinoma (ccRCC) have not yet been elucidated. In this study, we found that Musashi-2 was mainly expressed in the normal distal tubular cells and collecting duct cells of the kidneys, while its expression was significantly decreased in ccRCC. And higher expression levels of Musashi-2 indicated better overall survival (OS) in ccRCC. Furthermore, immunohistochemistry demonstrated that PD-L1 expression was negatively correlated with Musashi-2 expression, and Musashi-2 was found to be remarkably correlated with multiple immune cells and immune inhibitors, including CD8+ T cells, CD4+ T cells, regulatory T (Treg) cells, PDCD1, CTLA4, Foxp3, and LAG3. Functional enrichment analysis revealed that Musashi-2 might be involved in ccRCC metabolic reprogramming and immune infiltration and further predicted the therapeutic sensitivity of ccRCC. Taken together, Musashi-2 is a prognostic biomarker for ccRCC patients that may provide novel insights into individualized treatment strategies and guide effective immunotherapy.
Genetic architecture of Parkinson’s disease subtypes – Review of the literature

The heterogeneity of Parkinson’s disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundations of PD heterogeneity remain elusive. Genetic contributions to PD may be informative in understanding the underpinnings of PD subtypes. As such, recognizing genotype-phenotype associations may be crucial for successful gene therapy. We review the state of knowledge on the genetic architecture underlying PD subtypes, discussing the monogenic forms, as well as oligo- and polygenic risk factors associated with various PD subtypes. Based on our review, we argue for the unification of PD subtyping classifications, the dichotomy of studies on genetic factors and genetic modifiers of PD, and replication of results from previous studies.
Menopause and development of Alzheimer’s disease: Roles of neural glucose metabolism and Wnt signaling

Late onset Alzheimer´s disease (AD) is a neurodegenerative disease with gender differences in its onset and progression, being the prevalence predominant in women and at an earlier age than in men. The pathophysiology of the menopausal condition has been associated to this dementia, playing major roles regarding both endocrine and glucose metabolism changes, amongst other mechanisms. In the current review we address the role of estrogen deficiency in the processes involved in the development of AD, including amyloid precursor protein (APP) processing to form senile plaques, Tau phosphorylation forming neurofibrillary tangles, Wnt signaling and AD neuropathology, the role of glucose brain metabolism, Wnt signaling and glucose transport in the brain, and our research contribution to these topics.
Exploratory studies of oral and fecal microbiome in healthy human aging

Growing evidence has linked an altered host fecal microbiome composition with health status, common chronic diseases, and institutionalization in vulnerable older adults. However, fewer studies have described microbiome changes in healthy older adults without major confounding diseases or conditions, and the impact of aging on the microbiome across different body sites remains unknown. Using 16S ribosomal RNA gene sequencing, we reconstructed the composition of oral and fecal microbiomes in young (23–32; mean = 25 years old) and older (69–94; mean = 77 years old) healthy community-dwelling research subjects. In both body sites, we identified changes in minor bacterial operational taxonomic units (OTUs) between young and older subjects. However, the composition of the predominant bacterial species of the healthy older group in both microbiomes was not significantly different from that of the young cohort, which suggests that dominant bacterial species are relatively stable with healthy aging. In addition, the relative abundance of potentially pathogenic genera, such as Rothia and Mycoplasma, was enriched in the oral microbiome of the healthy older group relative to the young cohort. We also identified several OTUs with a prevalence above 40% and some were more common in young and others in healthy older adults. Differences with aging varied for oral and fecal samples, which suggests that members of the microbiome may be differentially affected by aging in a tissue-specific fashion. This is the first study to investigate both oral and fecal microbiomes in the context of human aging, and provides new insights into interactions between aging and the microbiome within two different clinically relevant sites.