Miracle-dz/UniFAR-FTUs huggingface dataset:
Study on the accessibility and affordability of 50 drugs in Wuhan based on the WHO/HAI standardization method

Objective To understand the availability and affordability of essential drugs in Wuhan since the implementation of the national essential medicine system, and to provide a basis for the subsequent formulation and improvement of related policies. Methods Using the standard survey method jointly developed by the WHO and Health Action International (HAI), a sample of 50 essential drugs was selected to investigate and evaluate their availability and affordability in public medical and health institutions and social retail pharmacies in Wuhan, using six diseases with high clinical morbidity as the targets. Results The availability of the original drug and the lowest-priced generic drug in public hospitals is 26.4 and 42.47% respectively, and that in retail pharmacies is 26.8 and 54.4% respectively. The median price ratio of the original drug and the lowest-priced generic drug is 28.71 and 2.23 respectively in public hospitals, and 29.24 and 3.59 respectively in retail pharmacies; In addition to individual drugs, such as omeprazole, others are affordable. The availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs. Conclusion The availability of essential drugs in public hospitals in Wuhan is lower than that in social retail pharmacies, and the availability of the lowest-priced generic drugs is much higher than that of original drugs. The price of the original drug is much higher than the international reference price; The price of medicines in public hospitals is lower than that in retail pharmacies;the overall condition of affordability is good, but there is a big gap between the affordability levels of original drugs and generic drugs, and the affordability of original drugs is relatively poor. It is recommended to adjust the relevant policies according to the actual situation of Wuhan city itself, moderately ensure the supply of original drugs, improve the price transparency of retail pharmacies, and ensure that the basic drug needs of the public are met.
Automated, high-accuracy classification of textured microstructures using a convolutional neural network

Crystallographic texture is an important descriptor of material properties but requires time-intensive electron backscatter diffraction (EBSD) for identifying grain orientations. While some metrics such as grain size or grain aspect ratio can distinguish textured microstructures from untextured microstructures after significant grain growth, such morphological differences are not always visually observable. This paper explores the use of deep learning to classify experimentally measured textured microstructures without knowledge of crystallographic orientation. A deep convolutional neural network is used to extract high-order morphological features from binary images to distinguish textured microstructures from untextured microstructures. The convolutional neural network results are compared with a statistical Kolmogorov–Smirnov tests with traditional morphological metrics for describing microstructures. Results show that the convolutional neural network achieves a significantly improved classification accuracy, particularly at early stages of grain growth, highlighting the capability of deep learning to identify the subtle morphological patterns resulting from texture. The results demonstrate the potential of a convolutional neural network as a tool for reliable and automated microstructure classification with minimal preprocessing.
PI(4,5)P2-dependent and -independent roles of PI4P in the control of hormone secretion by pituitary cells

Plasma membrane and organelle membranes are home to seven phosphoinositides, an important class of low-abundance anionic signaling lipids that contribute to cellular functions by recruiting cytoplasmic proteins or interacting with the cytoplasmic domains of membrane proteins. Here, we briefly review the functions of three phosphoinositides, PI4P, PI(4,5)P2, and PI(3,4,5)P3, in cellular signaling and exocytosis, focusing on hormone-producing pituitary cells. PI(4,5)P2, acting as a substrate for phospholipase C, plays a key role in the control of pituitary cell functions, including hormone synthesis and secretion. PI(4,5)P2 also acts as a substrate for class I PI3-kinases, leading to the generation of two intracellular messengers, PI(3,4,5)P3 and PI(3,4)P2, which act through their intracellular effectors, including Akt. PI(4,5)P2 can also influence the release of pituitary hormones acting as an intact lipid to regulate ion channel gating and concomitant calcium signaling, as well as the exocytic pathway. Recent findings also show that PI4P is not only a precursor of PI(4,5)P2, but also a key signaling molecule in many cell types, including pituitary cells, where it controls hormone secretion in a PI(4,5)P2-independent manner.
Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation

Introduction Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity. Cohorts To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses – in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other. Results We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation – in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03. Discussion Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.
Human alveolar macrophage metabolism is compromised during Mycobacterium tuberculosis infection

Pulmonary macrophages have two distinct ontogenies: long-lived embryonically-seeded alveolar macrophages (AM) and bone marrow-derived macrophages (BMDM). Here, we show that after infection with a virulent strain of Mycobacterium tuberculosis (H37Rv), primary murine AM exhibit a unique transcriptomic signature characterized by metabolic reprogramming distinct from conventional BMDM. In contrast to BMDM, AM failed to shift from oxidative phosphorylation (OXPHOS) to glycolysis and consequently were unable to control infection with an avirulent strain (H37Ra). Importantly, healthy human AM infected with H37Ra equally demonstrated diminished energetics, recapitulating our observation in the murine model system. However, the results from seahorse showed that the shift towards glycolysis in both AM and BMDM was inhibited by H37Rv. We further demonstrated that pharmacological (e.g. metformin or the iron chelator desferrioxamine) reprogramming of AM towards glycolysis reduced necrosis and enhanced AM capacity to control H37Rv growth. Together, our results indicate that the unique bioenergetics of AM renders these cells a perfect target for Mtb survival and that metabolic reprogramming may be a viable host targeted therapy against TB.
Effects of direct oral anticoagulants vs. vitamin K antagonists on acute kidney injury in patients with atrial fibrillation: A systematic review

Background Patients with atrial fibrillation (AF) are routinely prescribed oral anticoagulants to prevent thromboembolism. Concerns regarding the efficacy and safety of oral anticoagulants, such as vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs), arise for patients with non-valvular atrial fibrillation (NVAF) because of their widespread use in clinical practice. Even though there have been an abundance of studies on this topic, it is still not clear if DOAC users with NVAF have a lower risk of acute kidney injury (AKI) than warfarin users. Methods and results We conducted electronic searches in PubMed, Embase, and the Cochrane Library to identify relevant studies for this systematic review. We included randomized clinical trials and observational studies that reported on the incidence rate, hazard ratio (HR), and 95% confidence interval (95% CI) of AKI in patients using oral anticoagulants. This systemic review included six observational studies and four randomized clinical trials (RCT). The overall results showed that DOACs were associated with a lower AKI risk than warfarin. However, for NVAF patients with severe renal dysfunction, DOACs may not have a reduced risk of AKI compared to warfarin. Conclusion The overall results suggest that, except for edoxaban, patients using DOACs may experience a reduced risk of AKI. However, it is uncertain whether this is also the case for patients with severe renal dysfunction. Further research is needed to confirm the effect of DOACs on this population.
Effects of “Taking the Waist as the Axis” Therapy on trunk postural control disorder after stroke: A randomized controlled trial

Background Sufficient attention to trunk rehabilitation after stroke is still lacking. Loss of trunk selective activity is considered to be the leading cause of trunk postural control disorder after stroke. “Taking the Waist as the Axis” Therapy (WAT) was developed as a combination of the concept of “Taking the Waist as the Axis” from Tai Chi and the rehabilitation of trunk dysfunction after stroke. The present clinical trial examined and assessed the effects of WAT on stroke patients. Methods A total of 43 stroke hemiplegic patients with trunk postural control disorder, whose Trunk Impairment Scale (TIS) scoring between 8 and 18, participated in the present study and were allocated randomly to the experimental (n = 23) or control groups (n = 20). The experimental group received WAT plus conventional therapy, and the control group received “Trunk Selective Activity” Therapy (TSAT) plus conventional therapy. Both groups received treatment once daily and 5 times per week for 3 weeks. The Trunk Impairment Scale (TIS), Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), change of Intra-abdominal Pressure (IAP), static balance ability assessment, rapid ventilation lung function test and the Modified Barthel Index (MBI) were evaluated before and after intervention for both groups. Results The experimental group was superior to the control group in TIS [4 (2, 5) vs. 3 (1.25, 4), p = 0.030], change of IAP [−3 (−8, −1.33) vs. −0.02 (−3.08, 6), p = 0.011], FMA-upper extremity [10 (6, 18) vs. 1 (0, 3), p = 0.002], FMA-lower extremity [2 (1, 4) vs. 1 (0, 2), p = 0.009] and FMA [14 (7, 21) vs. 2 (0.25, 3.75), p = 0.001]. Within experimental group, forced vital capacity (FVC) [81.35 (63.30, 94.88) vs. 91.75 (79.40, 97.90), p = 0.02] was significantly improved. Conclusion WAT was an effective trunk treatment after stroke, which significantly improved the patients’ trunk posture control ability, motor function and forced vital capacity. However, the results still need to be interpreted with caution for the intervention only lasted for 3 weeks.
The Nonpotentiality of Active-Region Coronae and the Dynamics of the Photospheric Magnetic Field

The magnetic field in the solar photosphere frequently carries strong electric currents, even though the global coronal configuration often resembles a potential field ringed by the heliospheric current sheet. To understand this, we compare TRACE EUV images of active-region coronae and potential-field source-surface extrapolations based on SOHO MDI magnetograms for 95 active regions. We conclude that significant nonpotentiality of the overall active-region coronal field occurs (1) when new flux has emerged within or very near a region within the last ~30 hr, resulting in complex polarity separation lines, or (2) when rapidly evolving, opposite-polarity concentrations are in contact at 4'' resolution. If these criteria are met by more than 15% of the region's flux, they correctly identify the (non) potentiality of active-region coronae in 88% of the cases. Flares are found to occur 2.4 times more frequently in active regions with nonpotential coronae than in near-potential regions, while their average X-ray peak flare brightness is 3.3 times higher. We suggest that the currents associated with coronal nonpotentiality have a characteristic growth and decay timescale of ~10-30 hr. We find that shear flows drive enhanced flaring or coronal nonpotentiality only if associated with complex and dynamic flux emergence within the above timescale. We discuss the implications of this finding for the modeling of the coronal-heliospheric coupling.
Immunomodulatory effects of complex probiotics on the immuno-suppressed mice induced by cyclophosphamide

Introduction Previous studies have reported the beneficial effects of Bifidobacterium animalis subsp. lactis XLTG11, Lacticaseibacillus casei Zhang, and Lactiplantibacillus plantarum P8, respectively. However, studies on the immunomodulatory enhancing effects of three complex probiotics have not been conducted. The aim of our study is to investigate the immunomodulatory effects of complex probiotics effect on the immunosuppressed mice induced by cyclophosphamide (CTX). Methods An immunocompromised mouse model was established by intraperitoneal injection of cyclophosphamide, which was gavage of different doses of complex probiotics and levamisole hydrochloride. The splenic and thymic indices, intestinal barrier, leukocyte and lymphocyte counts, percentage of splenic lymphocyte subpopulations, cytokine levels, and gut microbiota were determined. Results Results showed that the complex probiotics significantly elevated the spleen and thymus indices, increased the villi and crypt depth and the goblet cells. The leukocyte and lymphocyte counts and the percentage of splenic lymphocyte subpopulations in the CTX-treated mice were significantly elevated by the complex probiotics. In addition, the cytokines (IL-6, IL-10, IL-1β, and IFN-γ) were significantly increased after complex probiotic treatment. The complex probiotics restored the gut microbiota structure to the pattern of the control group by reducing the ratio of Firmicutes/Bacteroidetes and enhancing the relative abundances of specific microbiota that produced short-chain fatty acids. Discussion This study provides theoretical support for the immunity-enhancing function of the complex probiotics as well as a pharmacological basis for its further development and utilization.
Childhood adversity and educational attainment: Evidence from Zambia on the role of personality

Introduction We examine whether personality traits mediate the association between childhood adversity and educational attainment using longitudinal data from a cohort in Zambia. Methods We fit a structural equation model using data on three forms of childhood adversity—household poverty, stunting as a measure of chronic malnutrition, and death of a parent—and data on the “Big Five” personality traits and educational attainment assessed at 15 years of age. Results We find that childhood poverty and death of a parent are associated with lower openness to experience. Furthermore, openness to experience mediates 93% of the negative association between death of a parent and school enrollment and 19% of the negative association between childhood poverty and enrollment. Discussion Our findings reinforce a diverse and growing body of evidence linking childhood adversity to educational attainment while also placing it in a new light. Future work should continue to examine the biological and psychosocial pathways that determine openness to experience and other personality traits, as well as their role in shaping important life outcomes.
Effects of COVID-19 pandemic on mental health among frontline healthcare workers: A systematic review and meta-analysis

Background As some countries announced to remove Coronavirus Disease 2019 (COVID-19) border, it indicates that the COVID-19 may have entered its terminal stage. In this COVID-19 pandemic, the mental health of frontline healthcare workers (HCWs) experienced unprecedented challenges. However, the impact of the COVID-19 pandemic on mental health among frontline HCWs lacks a high-quality and long-term systematic review and meta-analysis. Methods We conducted a systematic review and meta-analysis according to PRISMA guidelines. The system searches EMBASE, MEDLINE, PsycINFO, Cochrane Library, ScienceNet, and ERIC. Analyze the mental health problems of frontline HCWs in different regions and periods, including insomnia, stress, anxiety and depression. This study was registered in PROSPERO under the number CRD42021253821. Results A total of 19 studies on the effects of COVID-19 pandemic on mental health among frontline HCWs were included in this study. The overall prevalence of insomnia was 42.9% (95% CI, 33.9–51.9%, I2 = 99.0%) extracted from data from 14 cross-sectional studies (n = 10 127), 1 cohort study (n = 4,804), and 1 randomized controlled trial (RCT; n = 482) in 10 countries. The overall prevalence of stress was 53.0% (95% CI, 41.1–64.9%, I2 = 78.3%) extracted from data from nine cross-sectional studies (n = 5,494) and 1 RCT study (n = 482) from eight countries. The overall prevalence of anxiety and depression was 43.0% (95% CI, 33.8–52.3%, I2 = 99.0%) and 44.6% (95% CI, 36.1–53.1%, I2 = 99.0%) extracted from data from 17 cross-sectional studies (n = 11,727), one cohort study (n = 4,804), and one RCT study (n = 482) from 12 countries. The prevalence of stress and depression was higher in 2020, while the prevalence of insomnia and anxiety was higher in 2021. The prevalence of mental health problems among physicians was higher than that of other frontline HCWs. The prevalence of mental health problems among frontline HCWs is higher in South America and lower in North America. Conclusions This systematic review and meta-analysis showed that the COVID-19 pandemic have significant effects on mental health among frontline HCWs. The overall prevalence of insomnia, stress, anxiety and depression among frontline HCWs is high. Therefore, the health policy-makers should pay attention to and respond to the mental health problems of frontline HCWs in the context of public health emergencies. Systematic review registration https://www.crd. york.ac. uk/PROSPERO/.
Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites

Background Lingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear. Methods Male Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman’s correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes. Results Four-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman’s correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes. Conclusion Lingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.
Identification of sugar transporter genes and their roles in the pathogenicity of Verticillium dahliae on cotton

Introduction Verticillium wilt (VW) caused by Verticillium dahliae is a soil-borne vascular fungal disease that severely affects cotton yield and fiber quality. Sugar metabolism plays an important role in the growth and pathogenicity of V. dahliae. However, limited information is known about the sugar transporter genes and their roles in the growth and pathogenicity of V. dahliae. Method In this study, genome-wide identification of sugar transporter genes in V. dahliae was conducted and the expression profiles of these genes in response to root exudates from cotton varieties susceptible or resistant to V. dahliae were investigated based on RNA-seq data. Tobacco Rattle Virus-based host-induced gene silencing (TRV-based HIGS) and artificial small interfering RNAs (asiRNAs) were applied to investigate the function of candidate genes involved in the growth and pathogenic process of V. dahliae. Results A total of 65 putative sugar transporter genes were identified and clustered into 8 Clades. Of the 65 sugar transporter genes, 9 were found to be induced only by root exudates from the susceptible variety, including VdST3 and VdST12 that were selected for further functional study. Silencing of VdST3 or VdST12 in host plants by TRV-based HIGS reduced fungal biomass and enhanced cotton resistance against V. dahliae. Additionally, silencing of VdST12 and VdST3 by feeding asiRNAs targeting VdST12 (asiR815 or asiR1436) and VdST3 (asiR201 or asiR1238) inhibited fungal growth, exhibiting significant reduction in hyphae and colony diameter, with a more significant effect observed for the asiRNAs targeting VdST12. The inhibitory effect of asiRNAs on the growth of V. dahliae was enhanced with the increasing concentration of asiRNAs. Silencing of VdST12 by feeding asiR815+asiR1436 significantly decreased the pathogenicity of V. dahliae. Discussion The results suggest that VdST3 and VdST12 are sugar transporter genes required for growth and pathogenicity of V. dahliae and that asiRNA is a valuable tool for functional characterization of V. dahliae genes.