Miracle-dz/UniFAR-FTUs huggingface dataset:
The paradoxical response to short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease

Background There are a few studies about paradoxical bronchodilator response (BDR), which means a decrease in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after short-acting bronchodilator administration in patients with chronic obstructive pulmonary disease (COPD). We evaluated the effect of paradoxical BDR on the clinical outcomes of COPD patients in South Korea. Methods We analyzed the KOrea COpd Subgroup Study team (KOCOSS) cohort data in South Korea between January 2012 and December 2017. BDR was defined as at least a 12% and 200-mL reduction in FEV1 or FVC after bronchodilator administration. Results A total of 1,991 patients were included in this study. A paradoxical BDR was noted in 57 (2.9%) patients and was independently associated with worse dyspnea and poor quality of life. High C-reactive protein (CRP) levels were associated with a paradoxical BDR (OR, 1.05; 95% CI, 1.01–1.09; P=0.003). However, paradoxical BDR was not associated with severe acute exacerbations. Pre-bronchodilator FEV1 (L) showed a higher area under the curve (AUC) for predicting severe acute exacerbations than the post-bronchodilator FEV1 (L) in the paradoxical BDR group (0.788 vs. 0.752). Conclusion A paradoxical reduction of FEV1 or FVC after bronchodilator administration may be associated with chronic inflammation in the airway and independently associated with worse respiratory symptoms and poor quality of life.
Seasonal and long-term consequences of esca on grapevine stem xylem integrity.

Hydraulic failure has been extensively studied during drought-induced plant dieback, but its role in plant-pathogen interactions is under debate. During esca, a grapevine (Vitis vinifera) disease, symptomatic leaves are prone to irreversible hydraulic dysfunctions but little is known about the hydraulic integrity of perennial organs over the short- and long-term. We investigated the effects of esca on stem hydraulic integrity in naturally infected plants within a single season and across season(s). We coupled direct (ks) and indirect (kth) hydraulic conductivity measurements, and tylose and vascular pathogen detection with in vivo X-ray microtomography visualizations. We found xylem occlusions (tyloses), and subsequent loss of stem ks, in all of the shoots with severe symptoms (apoplexy) and in more than 60% of the shoots with moderate symptoms (tiger-stripe), and no tyloses in shoots that were currently asymptomatic. In vivo stem observations demonstrated that tyloses were observed only when leaf symptoms appeared, and resulted in more than 50% PLC in 40% of symptomatic stems, unrelated to symptom age. The impact of esca on xylem integrity was only seasonal and no long-term impact of disease history was recorded. Our study demonstrated how and to what extent a vascular disease such as esca, affecting xylem integrity, could amplify plant mortality by hydraulic failure.
Integrated Enzyme‐Based Biofuel Cells–A Review

Enzyme‐based biofuel cells provide versatile means to generate electrical power from biomass or biofuel substrates, and to use biological fluids as fuel‐sources for the electrical activation of implantable electronic medical devices, or prosthetic aids. This review addresses recent advances for assembling biofuel cells based on integrated, electrically contacted thin film‐modified enzyme electrodes. Different methods to electrically communicate the enzymes associated with the anodes/cathodes of the biofuel cell elements are presented. These include: (i) The reconstitution of apo‐enzymes on relay‐cofactor monolayers assembled on electrodes, or the crosslinking of cofactor‐enzyme affinity complexes assembled on electrodes. (ii) The immobilisation of enzymes in redox‐active hydrogels associated with electrodes. (iii) The use of nano‐elements, such as carbon nanotubes, for the electrical contacting of the enzyme electrodes comprising the biofuel cells. All three methods are implemented for the electrical contacting of oxidases and dehydrogenases with electrodes acting as anodes of biofuel cells, and for the electrical wiring of bilirubin oxidase, cytochrome oxidase, and laccase with electrodes, that yield the cathode units of the biofuel cells. Different methods to control the biofuel cells, operation by external stimuli are discussed, including the application of external magnetic fields, and the electrochemical switching of the biofuel cell operation.
Immediate self-information is prioritized over expanded self-information across temporal, social, spatial, and probability domains

People construct self-representation beyond the experiential self and the self-concept can expand to interpersonal as well as intrapersonal dimensions. The cognitive ability to project oneself onto expanded selves in different time points and places plays a crucial role in planning and decision-making situations. However, no research to date has shown evidence explaining the early mechanism of how processing the experiential self-information differs from processing the expanded self-information across temporal, social, spatial, and probability domains. We report novel effects showing a systematic information prioritization toward the experiential selves (i.e., the self that is now, here, and with highest certainty) compared to the expanded selves (i.e., the self that is in the future, at a distant location, and with lower certainty; Experiments 1a, 2, and 3). Implicit prioritization biases lasted over time (Experiment 1b; i.e., 4 months) indicating a trait-like more than a state-like measure of individual differences. Different biases, however, did not consistently correlate with each other (Experiments 1a to 3) suggesting separate underlying mechanisms. We discuss potential links to the basic structure of self-representation and individual differences for implications.
Coexistence of Bipolar and Unipolar Switching of Cu and Oxygen Vacancy Nanofilaments in Cu/TaOx/Pt Resistive Devices

Switching of a resistive Cu/TaOx/Pt device can be based on the formation of two types of nanofilament in the same device: Cu and oxygen vacancy conductive filaments, depending on the polarity of switching voltage. Cu/TaOx/Pt device can be switched in bipolar and unipolar regimes. The two types of conduction can be distinguished by different values of the resistance temperature coefficient. Both positive and negative voltages can reset the device when sufficient Joule heating is produced. The negative set voltages for oxygen vacancy filaments show higher absolute values than those for the Cu filaments. The unique fourfold switching property of a
放Identification of serum biomarkers to predict pemetrexed/platinum chemotherapy efficacy for advanced lung adenocarcinoma patients by data-independent acquisition (DIA) mass spectrometry analysis with parallel reaction monitoring (PRM) verification

Background Pemetrexed/platinum chemotherapy has been the standard chemotherapy regimen for lung adenocarcinoma patients, but the efficacy varies considerably. Methods To discover new serum biomarkers to predict the efficacy of pemetrexed/platinum chemotherapy, we analyzed 20 serum samples from advanced lung adenocarcinoma patients who received pemetrexed/platinum chemotherapy with the data-independent acquisition (DIA) quantitative mass spectrometry (MS). Results The 20 patients were categorized as “good response” [12 patients achieving partial response (PR)] and “poor response” [8 patients with progressive disease (PD)] groups. Altogether 23 significantly different expressed proteins were identified, which had relative ratios higher than 1.2 or lower than –0.83, with 7 proteins having an area under the curve (AUC) above 0.8. To further validate the DIA results, we used the parallel reaction monitoring (PRM) method to examine 16 candidate serum biomarkers in the study cohort of 20 patients and another cohort of 22 advanced lung adenocarcinoma patients (16 PR and 6 PD). Quantitative validation using PRM correlated well with the DIA results, and 10 promising proteins exhibited a similar up- or downregulation. It is worth noting that glutathione peroxidase 3 (GPX3) exhibits significant upregulation in the poor response group compared with the good response group, which was validated by both DIA and PRM methods. Conclusions Our study confirmed that combined DIA MS and PRM approaches were effective in identifying serum predictive biomarkers for advanced lung adenocarcinoma patients. Further studies are needed to explore the potential biological mechanism underlying these biomarkers.
Biomonitoring of workers employed in a titanium dioxide production plant: Use of buccal micronucleus cytome assay as noninvasive biomarker to evaluate genotoxic and cytotoxic effects

We aimed to evaluate whether TiO2 production process induces genotoxic and cytotoxic effects on the first target organ of inhalable particles by a sensitive and noninvasive biomarker of effect. Final aim was to find a useful and suitable tool to assess and manage the risk of TiO2 occupational exposure. We enrolled 40 workers employed in TiO2 production, 5 office workers, and 18 external controls. Buccal micronucleus cytome assay (BMCyt assay) was applied because it allows to evaluate micronucleus (MN), nuclear buds (NB), and broken eggs (BE) indicating the presence of chromosomal instability and gene amplification and binucleated cells (BIN), karyolytic cells (KL), and condensed chromatin (CC) indicating cytokinesis defect or arrest, cell death and apoptosis respectively. We characterized the exposure measuring inhalable and respirable particles by personal monitoring. BMCyt‐assay showed in exposed workers compared with external controls a higher value of MN frequency (2.57 vs. 0.05‰, p < .001) and MN positivity, evaluated as percentage of subjects with MN frequency higher than a 1.5‰ cut‐off value (52.5 vs. 0%). We also found in exposed workers higher frequency of BE + NB (2.41 vs. 0.22‰, p = .002), BIN (9.45 vs. 8.44‰, p = .047) and CC (1.80 vs. 0.21, p = .001) than in controls. Moreover, we found a relationship between personal monitoring results and presence of MN and other cellular anomalies. This study demonstrates induction of genotoxic and cytotoxic effects on buccal cells of workers involved in TiO2 production, suggesting the suitability of BMCyt assay as tool for risk assessment and management of TiO2 exposure.
Nutrition status mediates the association between cognitive decline and sarcopenia

In this study, we investigated whether nutrition status mediates the relationship between cognitive decline and sarcopenia. Sarcopenia was assessed in 4023 community-dwelling older adults from West China using the AWGS 2014 diagnostic criteria. Cognitive function and nutrition status were assessed using the 10-item Short Portable Mental Status Questionnaire (SPMSQ) and Mini Nutrition Assessment-Short Form (MNA-SF) scale, respectively. Mediation model regression analysis demonstrated that nutrition status was negatively associated with sarcopenia (β = -0.521; 95% CI: -0.583 to -0.459). The indirect effects of cognitive decline on sarcopenia were significant after adjusting for age, sex, and ethnicity (β = 0.015; 95% CI: 0.012 to 0.017), but the direct effects of cognitive decline on sarcopenia were not statistically significant after adding nutrition status as a parameter in the mediation model analysis (β = -0.001; 95% CI: -0.008 to 0.005). Structural equation model (SEM) framework pathway analysis confirmed the association between nutrition status, cognitive decline, and sarcopenia. These findings demonstrate that the negative effects of cognitive decline on sarcopenia were mediated by nutrition status. We therefore postulate that maintaining a good nutrition status delays the negative effects of cognitive decline on sarcopenia in older adults.
Impacts of Microbial based Therapy on Growth Performance, Intestinal Health, Carcass Traits and Economic Efficiency of Clostridium perfringens‐Infected Cobb and Arbor Acres Broilers

Abstract The poultry farms need a safe and effective alternative for antibiotics that can counteract the negative impacts of necrotic enteritis (NE), which causes severe mortalities and economic losses. The current study was aimed to examine the influence of antibiotic (Flagymox) and the microbial‐based administration on carcass traits in Clostridium (C.) perfringens‐infected Cobb and Arbor Acres broilers. A total number of 360 Cobb and Arbor Acres broiler chicks (180 numbers per breed) were allocated to four groups; negative control group (without any treatments); positive control group (administration of C. perfringens at the rate of 1 × 109cfu/bird via crop gavage twice daily from day 16 to 18 post‐hatch); C. perfringens challenge plus antibiotic (Flagymox®) group, and Clostridium perfringens challenge plus microbial‐based treatment (Big‐lactoα®) group. The results indicated that the Flagymox and Big‐lactoα treated Cobb breed group achieved a significant increase in their body weight (BW) than the positive control group at the third week post‐infection. Also, the Arbor Acres breed gained significantly higher weight compared to the Cobb breed at the third week. Total weight gain (TWG) from 0 to the fifth week in the Cobb and Arbor Acres breeds were higher in the groups treated with Flagymox and Big‐lactoα compared to the birds challenged with C. perfringens without any treatment, thus, increasing the total return (TR) in the treated groups. Economic efficiency showed no significant differences (p < .05) between the treatment groups of both the breeds. Although the treatment cost of Flagymox is higher than the microbial‐based treatment (0.86 versus 0.35 LE), there were no mortalities reported in the microbial‐based groups in both the breeds resulting in significantly low losses compared to the Flagymox treated groups. The groups treated with the microbial‐based products in both breeds were superior in dressing percentage (75.16 and 77.06% for Cobb and Arbor Acres, respectively) compared to that of the other groups. In conclusion, microbial‐based therapy improved the growth rate, carcass traits, survival rate, and economic efficiency in necrotic enteritis induced in Cobb and Arbor Acres broilers.
Efficacy of onabotulinumtoxinA in the treatment of unipolar major depression: Systematic review, meta-analysis and meta-regression analyses of double-blind randomised controlled trials

Background: OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression. This putative new antidepressant agent offers minimal systemic side effects and negligible risk of pharmacological interactions. We set out to examine the evidence for the use of onabotulinumtoxinA in major depression. Methods: A systematic search of the literature identified double-blind randomised controlled trials (RCTs) investigating the use of onabotulinumtoxinA in the treatment of major depression versus placebo. Data, reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), was combined in meta-analyses (PROSPERO registration ID: CRD42020183538). Results: The search identified five RCTs (four double-blind) comparing onabotulinumtoxinA to placebo. OnabotulinumtoxinA was more effective than placebo when administered within the 20–40 IU dose range in double-blind RCTs. The analysis was free of publication bias and significantly heterogeneous. Meta-regression analyses indicated that onabotulinumtoxinA was more efficacious in women and in higher doses in female patients and less effective with polypharmacy, especially when an increasing number of antidepressants were prescribed. The effectiveness of onabotulinumtoxinA was higher in more recently published double-blind RCTs. Conclusion: The meta-analysis supports the efficacy of the intervention with the results being highly heterogeneous across studies. In view of the heterogeneity of the findings and the significant moderators of benefit (sex, year of study completion and the interaction between sex and dose), more research is required to better understand the role of onabotulinumtoxinA in the treatment of depression.
Apolipoprotein E ϵ4 allele and neuropsychiatric symptoms among older adults in Central Africa (EPIDEMCA study)

Abstract Objectives: To evaluate the association between neuropsychiatric symptoms and apolipoprotein E (APOE) ϵ4 allele among older people in Central African Republic (CAR) and the Republic of Congo (ROC). Design: Multicenter population-based study following a two-phase design. Setting: From 2011 to 2012, rural and urban areas of CAR and ROC. Participants: People aged 65 and over. Measurements: Following screening using the Community Screening Interview for Dementia, participants with low cognitive scores (CSI-D ≤ 24.5) underwent clinical assessment. Dementia diagnosis followed the DSM-IV criteria and Peterson’s criteria were considered for Mild Cognitive Impairment (MCI). Neuropsychiatric symptoms were evaluated through the brief version of the Neuropsychiatric Inventory (NPI-Q). Blood samples were taken from all consenting participants before APOE genotyping was performed by polymerase chain reaction (PCR). Logistic regression models were used to evaluate the association between the APOE ϵ4 allele and neuropsychiatric symptoms. Results: Overall, 322 participants had complete information on both neuropsychiatric symptoms and APOE status. Median age was 75.0 years and 81.1% were female. Neuropsychiatric symptoms were reported by 192 participants (59.8%) and at least 1 APOE ϵ4 allele was present in 135 (41.9%). APOE ϵ4 allele was not significantly associated with neuropsychiatric symptoms but showed a trend toward a protective effect in some models. Conclusion: This study is the first one investigating the association between APOE ϵ4 and neuropsychiatric symptoms among older people in sub-Saharan Africa (SSA). Preliminary findings indicate that the APOE ϵ4 allele was not associated with neuropsychiatric symptoms. Further research seems, however, needed to investigate the protective trend found in this study.
A Novel Convolutional Neural Network for the Diagnosis and Classification of Rosacea: Usability Study

Background Rosacea is a chronic inflammatory disease with variable clinical presentations, including transient flushing, fixed erythema, papules, pustules, and phymatous changes on the central face. Owing to the diversity in the clinical manifestations of rosacea, the lack of objective biochemical examinations, and nonspecificity in histopathological findings, accurate identification of rosacea is a big challenge. Artificial intelligence has emerged as a potential tool in the identification and evaluation of some skin diseases such as melanoma, basal cell carcinoma, and psoriasis. Objective The objective of our study was to utilize a convolutional neural network (CNN) to differentiate the clinical photos of patients with rosacea (taken from 3 different angles) from those of patients with other skin diseases such as acne, seborrheic dermatitis, and eczema that could be easily confused with rosacea. Methods In this study, 24,736 photos comprising of 18,647 photos of patients with rosacea and 6089 photos of patients with other skin diseases such as acne, facial seborrheic dermatitis, and eczema were included and analyzed by our CNN model based on ResNet-50. Results The CNN in our study achieved an overall accuracy and precision of 0.914 and 0.898, with an area under the receiver operating characteristic curve of 0.972 for the detection of rosacea. The accuracy of classifying 3 subtypes of rosacea, that is, erythematotelangiectatic rosacea, papulopustular rosacea, and phymatous rosacea was 83.9%, 74.3%, and 80.0%, respectively. Moreover, the accuracy and precision of our CNN to distinguish rosacea from acne reached 0.931 and 0.893, respectively. For the differentiation between rosacea, seborrheic dermatitis, and eczema, the overall accuracy of our CNN was 0.757 and the precision was 0.667. Finally, by comparing the CNN diagnosis with the diagnoses by dermatologists of different expertise levels, we found that our CNN system is capable of identifying rosacea with a performance superior to that of resident doctors or attending physicians and comparable to that of experienced dermatologists. Conclusions The findings of our study showed that by assessing clinical images, the CNN system in our study could identify rosacea with accuracy and precision comparable to that of an experienced dermatologist.
The 21st Century CURES Act in Pediatric Gastroenterology: Problems, Solutions, and Preliminary Guidance

ABSTRACT The information blocking (IB) prohibition component of the 21st Century CURES Act (21CCA) comes into effect April 5, 2021, which gives patients and their families near-instant access to almost all clinical notes, lab results, and health data. Exceptions to IB prohibition include risk of harm and patient privacy, but violations can be punished by a fine of up to $1,000,000.00. A committee of pediatric gastroenterologists reviewed the 21CCA regulation and compared local practice policies. Pediatric practitioners need to understand how age will affect local information release policies and to know which note types are released, paying special consideration to trainee notes and confidential information. Extraneous detail should be removed from notes, emotional labeling be avoided, and objective statements be made when referring to the care of other providers. Awareness of the 21CCA provides pediatric gastroenterologists with the opportunity to adapt their medical documentation practices to accommodate the new law.
SOX7 suppresses endothelial-to-mesenchymal transitions by enhancing VE-cadherin expression during outflow tract development.

The endothelial-to-mesenchymal transition (EndMT) is a critical process that occurs during the development of the outflow tract (OFT). Malformations of the OFT can lead to the occurrence of conotruncal defects (CTD). SOX7 duplication has been reported in patients with congenital CTD, but its specific role in OFT development remains poorly understood. To decipher this, histological analysis showed that SOX7 was regionally expressed in the endocardial endothelial cells and in the mesenchymal cells of the OFT, where EndMT occurs. Experiments, using invitro collagen gel culture system, revealed that SOX7 was a negative regulator of EndMT that inhibited endocardial cell migration and resulted in decreased number of mesenchymal cells. Forced expression of SOX7 in endothelial cells blocked further migration and improved the expression of the adhesion protein vascular endothelial (VE)-cadherin. Moreover, a VE-cadherin knockdown could partly reverse the SOX7-mediated repression of cell migration. Luciferase and electrophoretic mobility shift assays demonstrated that SOX7 up-regulated VE-cadherin by directly binding to the gene's promoter in endothelial cells. The coding exons and splicing regions of the SOX7 gene were also scanned in the 536 sporadic CTD patients and in 300 unaffected controls, which revealed four heterozygous SOX7 mutations. Luciferase assays revealed that two SOX7 variants weakened the transactivation of the VE-cadherin promoter. In conclusion, SOX7 inhibited EndMT during OFT development by directly upregulating the endothelial-specific adhesion molecule VE-cadherin. SOX7 mutations can lead to impaired EndMT by regulating VE-cadherin, which may give rise to the molecular mechanisms associated with SOX7 in CTD pathogenesis.