Miracle-dz/UniFAR-FTUs huggingface dataset:
Visuomotor performance at high altitude in COPD patients. Randomized placebo-controlled trial of acetazolamide

Introduction: We evaluated whether exposure to high altitude impairs visuomotor learning in lowlanders with chronic obstructive pulmonary disease (COPD) and whether this can be prevented by acetazolamide treatment. Methods: 45 patients with COPD, living <800 m, FEV1 ≥40 to <80%predicted, were randomized to acetazolamide (375 mg/d) or placebo, administered 24h before and during a 2-day stay in a clinic at 3100 m. Visuomotor performance was evaluated with a validated, computer-assisted test (Motor-Task-Manager) at 760 m above sea level (baseline, before starting the study drug), within 4h after arrival at 3100 m and in the morning after one night at 3100 m. Main outcome was the directional error (DE) of cursor movements controlled by the participant via mouse on a computer screen during a target tracking task. Effects of high altitude and acetazolamide on DE during an adaptation phase, immediate recall and post-sleep recall were evaluated by regression analyses. www.ClinicalTrials. gov NCT03165890. Results: In 22 patients receiving placebo, DE at 3100 m increased during adaptation by mean 2.5°, 95%CI 2.2° to 2.7° (p < 0.001), during immediate recall by 5.3°, 4.6° to 6.1° (p < 0.001), and post-sleep recall by 5.8°, 5.0 to 6.7° (p < 0.001), vs. corresponding values at 760 m. In 23 participants receiving acetazolamide, corresponding DE were reduced by −0.3° (−0.6° to 0.1°, p = 0.120), −2.7° (−3.7° to −1.6°, p < 0.001) and −3.1° (−4.3° to −2.0°, p < 0.001), compared to placebo at 3100 m. Conclusion: Lowlanders with COPD travelling to 3100 m experienced altitude-induced impairments in immediate and post-sleep recall of a visuomotor task. Preventive acetazolamide treatment mitigated these undesirable effects.
Drivers of rainfall trends in and around Mainland Southeast Asia

Observational rain gauge/satellite and reanalysis datasets since the 1950s are evaluated for trends in mean and extreme rainfall in and around Mainland Southeast Asia (MSEA). Rain gauge data indicate strong increases exceeding 50% in both annual mean precipitation and various extreme precipitation indices over Vietnam and the northwestern part of the peninsula since 1979. The remote influence of ENSO may partially explain the recent precipitation trend toward a more intense regional hydrological cycle, in response to predominant La Niña states over recent decades. Increasing precipitation in MSEA is also associated with increased monsoon intensity in southeast Asia and a northward shift of the monsoon activity center toward MSEA over 1979–2018. Warming-driven evaporation increases were obtained over the adjacent seas typically feeding precipitation over MSEA associated with a shift toward predominantly positive phases of the two major natural climate variability modes of the tropical Indian Ocean, namely the Indian Ocean Dipole and the Indian Ocean Basin Mode. A moisture budget analysis using ERA5 re-analysis data showed increasing oceanic moisture transports along the typical winter and summer moisture pathways toward the MSEA. However, results show that during summer the major part of increased moisture from the oceanic moisture sources ends up as precipitation over the oceanic regions adjacent to MSEA with ERA5 not being able to produce the observed positive trends in summer continental precipitation. On the other hand, ERA5 reveals pronounced increases in winter precipitation over the MSEA, in accordance with rain-gauge data, associated with strongly increasing transport of moisture originated from the western tropical Pacific and the South China Sea.
Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma

Background Immunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified. Methods In this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models. Results The 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis. Conclusion In conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.
Editorial: Protein phosphorylation and dephosphorylation in plant-microbe interactions

COPYRIGHT © 2022 Su, Lu, Staal and Ludwików. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Protein phosphorylation and dephosphorylation in plant-microbe interactions
An improved convolutional neural network for convenient rail damage detection

The long-term operation of a railroad usually leads to defects in its rails, axles, fasteners, etc. These problems directly affect the safety of the rail system. Therefore, it is important to ensure the health of key railroad structures. In this paper, a deep learning-based rail damage identification method is established by analyzing the rail vibration signals collected with piezoelectric ceramic pads. The multiple features of vibration signals are combined and then reconstructed into grayscale maps as the inputs of the model. The key information of the grayscale maps is extracted using neural networks. The idea of pre-convolution is used to solve the problem that the model pays more attention to certain features due to the different input sizes and the implied weights of the features. Finally, the performance of the three convolutional neural networks (CNN) in rail damage detection is evaluated and compared. The results show that the CNN with pre-convolution and Residual structure has better recognition for the presence of rail damage than other methods.
The correlation between economic fluctuation, workforce employment and health expenditure in the BRICS countries

In this paper, we use the Fourier ARDL method (data from 2000 to 2019) to examine whether there is a correlation between economic fluctuation, health expenditure, and employment rate among BRICS countries. Fourier ARDL's model, the same as Bootstrap ARDL model, is to test the long-term cointegration relationship of variables; when there is cointegration, it will test whether there is a causal relationship. When there is no cointegration, short-term Granger causality between variables is tested. Our study shows that, in the long-term, whether South Africa takes economic fluctuation, employment rate or health expenditure as the dependent variable, there is a cointegration relationship with the other two independent variables, but the causal relationship is not significant. In short-term Granger causality tests, the effects of economic fluctuation in Brazil, China, and South Africa on health expenditure lag significantly by one period. Economic fluctuation in Brazil, India and China had a negative effect on employment rate, while South Africa had a positive effect. Health expenditure in Russia and India has a negative effect on employment rate, while China has a positive effect. Employment rates in China and South Africa have a significant positive effect on economic fluctuation, while Russia has a negative effect. India's employment rate has a negative effect on health expenditure, while South Africa's has a positive effect. In short-term causality tests, different countries will exhibit different phenomena. Except for economic fluctuation, where health spending is positive, everything else is negatively correlated, and all of them are positive in South Africa. Finally, we make policy recommendations for the BRICS countries on economic fluctuation, employment rates, and health expenditure.
Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

During adolescence, internal and external factors contribute to engaging with alcohol binge drinking (ABD), putting at risk the neurodevelopment of brain regions crucial for emotional control and stress coping. This research assessed the prevalence of ABD in late adolescent students of Southern Italy and characterized their psychological profile and drinking motives. Translational effects of alcohol binge drinking in the animal model were also studied. Seven hundred and fifty-nine high school students of both sexes (aged 18–20) were recruited. Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), Drinking Motives Questionnaire-Revised Short Form, Millon Clinical Multiaxial Inventory-Third Ed., State-Trait Anxiety Inventory, Connor-Davidson Resilience Scale, and Basic Self-Esteem Scale identified alcohol habits, drinking motives, and psychopathological profile. Eighty-five percentage of the students drank alcohol and 28% of them engaged in ABD; AUDIT-C correlated with enhancement, coping, and conformity motives. ABD was related to a greater likelihood of presenting clinical syndromes and personality disorders, as well as low resilience and self-esteem. Thereafter, in the pre-clinical model, adolescent male rats were exposed to alcohol (3.5 g/kg) in an intermittent binge-like paradigm and tested during prolonged abstinence. Rats were evaluated for anxiety-like behavior, motivated behaviors, resilience, and stress response following a psychosocial challenge. Binge-like alcohol-exposed adolescent rats displayed high integrated z-score for social- and novelty-induced anxiety, altered motivation-driven output, decreased resilience, and a blunted HPA axis response to psychosocial stress, with respect to respective controls. Our data confirm that ABD is the chosen pattern of drinking in a significant percentage of high school students in Southern Italy, and highlights AUDIT-C score as a relevant parameter able to predict the occurrence of affective disturbances. The evidence from the preclinical model shows that ABD produces detrimental consequences in the adolescent rat brain, resulting in negative affect, emotional dysregulation, and aberrant stress response, pointing to decreasing excessive alcohol drinking as a primary goal for the global act for brain health.
QCD analysis of the ATLAS and CMS 
W±
 and 
Z
 cross-section measurements and implications for the strange sea density

In the present paper, the ATLAS inclusive W± and Z boson production data are analyzed together with the CMS inclusive W± and Z boson production data to investigate any possible tensions between the data sets and to determine the strange sea fraction, within the framework of a parton distribution function fit at next-to next-to-leading order in perturbative QCD.
The effect of serum IL-2 levels on the prognosis of primary biliary cholangitis-related liver failure and the preliminary exploration of its mechanism

Background In primary biliary cholangitis (PBC), the levels of serum IL-2 were involved in liver inflammation and immune changes. This study aimed to investigate the prognostic significance of serum IL-2 combined with total bilirubin (TBIL) in liver failure and cytokine changes during the disease. Methods A total of 160 PBC patients treated with UDCA were included. Parameters at admission were collected, and the COX regression model was used to predict independent risk factors associated with PBC disease progression. We identified the optimal cut-off values and prognosis effects of serum IL-2 and TBIL based on the time-dependent receiver operating characteristic (ROC) curve. We also analyzed the incidence of liver failure with Kaplan-Meier survival analysis. In addition, the changes of cytokines (mainly IL-2) in liver tissues and blood samples from 11 patients with end-stage PBC liver failure and five healthy controls were examined. Results Age, IL-2, ALB, γ-GT, ALP, TBIL, Hb, TBA, WBC, and PLT, as well as anti-Sp100, were found to be independent risk factors in PBC patients with liver failure. Patients with decreased serum IL-2 levels and increased TBIL levels have a significantly higher incidence of liver failure and a worse prognosis. Patients with advanced PBC liver failure after liver transplantation exhibited a significant decrease in levels of serum IL-2 and a relatively immunosuppressed status. Conclusions The combination of serum IL-2 and TBIL can be a predictor of the progression of liver failure in patients with primary biliary cholangitis, and it is likely to be related to the expression of GM-CSF and G-CSF.
Integrating peripheral blood and brain transcriptomics to identify immunological features associated with Alzheimer’s disease in mild cognitive impairment patients

Background Immune system dysfunction has been proven to be an important pathological event in Alzheimer’s disease (AD). Mild cognitive impairment (MCI), as a transitional stage between normal cognitive function and AD, was an important research object for the screening of early diagnostic markers and therapeutic targets for AD. However, systematic assessment of peripheral immune system changes in MCI patients and consistent analysis with that in the CNS were still lacking. Methods Peripheral blood transcriptome data from the AddNeuroMed Cohort (n = 711) was used as a training dataset to assess the abundance of 24 immune cells through ImmuCellAI and to identify MCI-related immune signaling pathways and hub genes. The expression level of the immune hub gene was validated in peripheral blood (n = 587) and brain tissue (78 entorhinal cortex, 140 hippocampi, 91 temporal cortex, and 232 frontal cortex) validation datasets. Finally, reliable immune hub genes were applied for Gene Set Enrichment Analysis and correlation analysis of AD pathological characteristics. Results MCI patients have early changes in the abundance of various types of immune cells in peripheral blood, accompanied by significant changes in NF-kB, TNF, JAK-STAT, and MAPK signaling pathways. Five hub immune-related differentially expressed genes (NFKBIA, CD4, RELA, CASP3, and HSP90AA1) were screened by the cytoHubba plugin in Cytoscape and the least absolute shrinkage and selection operator (LASSO) regression. Their expression levels were significantly correlated with infiltration score and the abundance of monocytes, natural killer cells, Th2 T cells, T follicular helper cells, and cytotoxic T cells. After validation with independent datasets derived from peripheral blood and brain, RELA and HSP90AA1 were identified as two reliable immune hub genes in MCI patients and had consistent changes in AD. The Gene Set Enrichment Analysis (GSEA) showed that their expression levels were closely associated with Alzheimer’s disease, JAK-STAT, calcium signaling pathway, etc. In addition, the expression level of RELA was positively correlated with β- and γ-secretase activity and Braak stage. The expression level of HSP90AA1 was negatively correlated with α- and β-secretase activity. Conclusion Immune system dysfunction was an early event in AD. It provides a new target for the early diagnosis and treatment of AD.
Gut microbiome modulation mediated by probiotics: Positive impact on growth and health status of Labeo rohita

The current study was targeted to determine the effect of probiotics on the growth, physiology, and gut microbiology of Labeo rohita fingerlings. One hundred and twenty fishes were divided into four dietary groups, each in triplicate for a feeding trial of 90 days. These treatments included T0 (control, basal diet) used as the reference, and three probiotic-supplemented diets represented as Tbc (Bacillus cereus), Tgc (Geotrichum candidum), and Tmc (B. cereus and G. candidum). The probiotics were supplemented at a level of 1 × 109 CFU/g feed. Fishes nurtured on probiotic-added diet showed significantly high physiological improvement (p < 0.05) in terms of growth, feed utilization capacity, hematological profile, and digestive enzymes as compared to control. The fish were subjected to a challenge test after a 90-day feeding trial. The Tmc exhibited maximum fish growth when challenged by Staphylococcus aureus and showed fish survival when compared to control, in which fish mortality was examined. Fish gut microbial composition was modulated by probiotic treatments, especially in Tgc and Tmc as compared to control. The absence of opportunistic pathogens such as Staphylococcus saprophyticus and Sporobolomyces lactosus and detection of lower levels of Trichosporon and Cryptococcus in treated groups indicate the gut modulation driven by applied probiotics. The G. candidum QAUGC01 was retrieved in yeast metagenomics data, which might be due to the production of polyamines by them that facilitated adherence and consequent persistence. In conclusion, it can be suggested that the probiotic-supplemented diet could enhance fish growth and feed efficiency through community modulation and digestive enzymes, which could be a milestone in local aquaculture.
Effects of simulated acid rain on rhizosphere microorganisms of invasive Alternanthera philoxeroides and native Alternanthera sessilis

Acid rain not only has serious harm to the environment, but also has the same threat to plants, but the invasive plant Alternanthera philoxeroides still grows well compared to the native plant Alternanthera sessilis under acid rain stress. However, the underlying mechanism of resistance to the acid rain environment in invasive Alternanthera philoxeroides remains unclear. In the current study, we comparatively analyzed the plant physiological characteristics, soil physicochemical properties, and rhizosphere microbial communities of invasive A. philoxeroides and native A. sessilis under different pH condition. The simulated acid rain had a significant inhibitory effect on the morphological and physiological traits of A. philoxeroides and A. sessilis and reduced the soil nutrient content. However, A. philoxeroides was more tolerant of acid rain. Compared with CK, simulated acid rain treatment at pH 2.5 significantly increased the Chao1, ACE, and Shannon indexes of A. philoxeroides microorganisms. Under simulated acid rain treatment at pH 2.5, the fungal flora Chao1, ACE and Shannon index were significantly higher than those of CK by 14.5%, 12.4%, and 30.4%, respectively. The dominant bacterial phyla of soil bacteria were Proteobacteria, Actinobacteria, Bacteroidota, Actinobacteria, Firmicutes, Myxococcota, Chloroflexi, Patescibacteria, Gemmatimonadota, Verrucomicrobiota, and Armatimonadota. The dominant fungi were Ascomycota, Basidiomycota, Rozellomycota, and Olpidiomycota. The bacterial and fungal diversity and structure of A. philoxeroides and A. sessilis showed the greatest difference between the pH 2.5 treatment and CK. Redundancy analysis showed that electrical conductivity (EC) and total phosphorus (TP) were the main factors changing the bacterial communities, and available phosphorus (AP), organic matter (OM), EC, and pH were the main factors changing the fungal communities. This study contributes to the microbial community structure of the invasive plant A. philoxeroides and provides a theoretical basis for studying the invasion mechanism of invasive plants under acid rain.
Hepatic overexpression of protein targeting to glycogen attenuates obesity and improves hyperglycemia in db/db mice

Increased liver glycogen content has been shown to reduce food intake, attenuate obesity, and improve glucose tolerance in a mouse model of high-fat diet (HFD)-induced obesity. Here we studied the contribution of liver glycogen to the regulation of obesity and glucose metabolism in a model of type 2 diabetes and obesity, namely the db/db mouse. To this end, we crossed db/db mice with animals overexpressing protein targeting to glycogen (PTG) in the liver to generate db/db mice with increased liver glycogen content (db/db-PTG). Hepatic PTG overexpression reduced food intake and fat weight and attenuated obesity and hyperglycemia in db/db mice. Db/db-PTG mice showed similar energy expenditure and physical activity to db/db mice. PTG overexpression reduced liver phosphoenolpyruvate carboxykinase (PEPCK) protein levels and repressed hepatic glucose production in db/db mice. Moreover, increased liver glycogen elevated hepatic ATP content in these animals. However, lipid metabolism was not modified by PTG overexpression. In conclusion, increased liver glycogen content ameliorates the diabetic and obesity phenotype in db/db mice.
Bacillus subtilis KLBMPGC81 suppresses appressorium-mediated plant infection by altering the cell wall integrity signaling pathway and multiple cell biological processes in Magnaporthe oryzae

Magnaporthe oryzae is one of the most destructive crop pathogens in the world, causing huge losses in rice harvest every year. Bacillus subtilis is a potential biocontrol agent that has been explored in many crop systems because it is a potent producer of bioactive compounds. However, the mechanisms by which these agents control rice blasts are not fully understood. We show that B. subtilis KLBMPGC81 (KC81) and its supernatant (SUP) have high antimicrobial activity against M. oryzae strain Guy11. To better exploit KC81 as a biocontrol agent, the mechanism by which KC81 suppresses rice blast pathogens was investigated. This study shows that KC81 SUP is effective in controlling rice blast disease. The SUP has a significant effect on suppressing the growth of M. oryzae and appressorium-mediated plant infection. KC81 SUP compromises cell wall integrity, microtubules and actin cytoskeleton, mitosis, and autophagy, all of which are required for M. oryzae growth, appressorium development, and host infection. We further show that the SUP reduces the activity of the cyclin-dependent kinase Cdc2 by enhancing the phosphorylation of Cdc2 Tyr 15, thereby impairing mitosis in M. oryzae cells. SUP induces the cell wall sensor MoWsc1 to activate the cell wall integrity pathway and Mps1 and Pmk1 mitogen-activated protein kinases. Taken together, our findings reveal that KC81 is an effective fungicide that suppresses M. oryzae growth, appressorium formation, and host infection by abnormally activating the cell wall integrity pathway, disrupting the cytoskeleton, mitosis, and autophagy.