Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin prevents PFKFB3-related aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts by regulating AMPK/mTOR pathway

Aerobic glycolysis has been shown to contribute to the abnormal activation of lung fibroblasts with excessive collagen deposition in lipopolysaccharide (LPS)-induced pulmonary fibrosis. Targeting aerobic glycolysis in lung fibroblasts might therefore be considered as a promising therapeutic approach for LPS-induced pulmonary fibrosis. In the present study, the aim was to investigate whether metformin, a widely used agent for treating type 2 diabetes, could alleviate LPS-induced lung fibroblast collagen synthesis and its potential underlying mechanisms. Different concentrations of metformin were used to treat the human lung fibroblast MRC-5 cells after LPS challenge. Indicators of aerobic glycolysis in MRC-5 cells were detected by measuring glucose consumption and lactate levels in culture medium in addition to lactate dehydrogenase activity in cellular lysates. The glucose consumption, lactate levels and the lactate dehydrogenase activity were measured respectively using colorimetric/fluorometric and ELISA kits. The effects of metformin in AMP-activated protein kinase (AMPK) activation was assessed by mitochondrial complex I activity kits. Collagen I, α-smooth muscle actin (α-SMA) and collagen III were used as markers of collagen synthesis, which was measured using western blotting, whereas phosphorylated (p-) AMPK, AMPK, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and mTOR were detected by western blotting. Metformin significantly decreased mitochondrial complex I activity and upregulated the expression of p-AMPK/AMPK protein in a concentration-dependent manner. Furthermore, the aerobic glycolysis mediated by PFKFB3 and collagen synthesis in LPS-treated MRC-5 cells was gradually inhibited with increasing concentrations of metformin. However, this inhibitory role of metformin on PFKFB3-meditaed aerobic glycolysis and collagen synthesis was prevented by treatments with 3BDO and compound C, which are specific mTOR activator and AMPK inhibitor, respectively. Taken together, the findings from this study suggested that metformin may prevent PFKFB3-associated aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts via regulating the AMPK/mTOR pathway.
Manganese Toxicity Development in Muskmelons as Influenced by Nitrogen Form

Muskmelon (Cucumis melo L.) ‘Harvest Queen’ seedlings were grown in sand culture at 2, 15, or 30 ppm Mn with 3 different N treatments to evaluate the effects of N form on growth, composition, and development of Mn toxicity. Nitrogen treatments consisted of NO3, NH4, and NH4 shifted to NO3 at 5 days, when Mn toxicity symptoms began to show on NO3-treated plants. Muskmelons produced the most growth with N supplied as NO3, least growth with NH4, and intermediate growth with the NH4-to-NO3 shift treatment. Plants grown with NO3-N at 15 or 30 ppm of Mn had restricted growth, developed Mn toxicity symptoms 5 days after the start of Mn treatments, and had a Mn composition of over 1500 ppm in dry shoot tissue. With NH4 the Mn treatments had no effect on growth, no Mn toxicity symptoms developed, and Mn composition of shoot tissue was <800 ppm. Shifting plants from NH4 to NO3-N resulted in the development of Mn toxicity symptoms and tissue Mn composition over 1500 ppm within 4 days after the shift.
Nattokinase atherothrombotic prevention study: A randomized controlled trial.

BACKGROUND Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.
Interpretation of the Changing the Band Gap of Al2O3 Depending on Its Crystalline Form: Connection with Different Local Symmetries

The valence and conduction bands of am- and γ-Al2O3 films grown by the atomic layer deposition technique were studied simultaneously in identical experimental conditions using high-resolution near -edge X-ray absorption fine structure and soft X-ray photoelectron spectroscopy. The valence band maximum was found to be centered at 3.64 ± 0.04 eV for am-Al2O3 and 3.47 ± 0.04 eV for γ-Al2O3. The band gap of Al2O3 was determined to be 7.0 ± 0.1 and 7.6 ± 0.1 eV for measured am- and γ-Al2O3, respectively. The main role in changing the band gap belongs to a shift of the bottom of conduction band depending on Al2O3 crystalline form. The position of the bottom of the conduction band is governed by the charge transfer from Al atom to the oxygen that depends strongly on the Al atom coordination symmetries. A strong p–d hybridization allowed for Td symmetry but forbidden for Oh symmetry plays the decisive role in the formation of the bottom of the conduction band.
Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats

Background/aim This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats. Materials and methods Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (p < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group. Conclusion These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.
Identifying electronic-sport athletes’ sleep-wake cycle characteristics

ABSTRACT Organized electronic-sport competitions (e-Sport) is related to several health problems, including sleep disorders. The objective of this study was to evaluate the characteristics of the sleep-wake cycle of League of Legends (LoL) athletes during their pre-training, training, pre-competition, and competition routines. Twenty male elite LoL players completed the questionnaires related to sleep pattern (Pittsburgh Sleep Quality Index), sleepiness (Epworth Sleepiness Scale), and chronotype (Morningness–Eveningness Questionnaire), and they wore an actigraph for 7 days. Pre-training and pre-competition assessments were carried out by questionnaires (n = 20) and training and competition assessments by actigraph (n = 16). The chronotype that most Eathletes presented was a moderately evening type. They presented a poor sleep quality and were borderline for excessive daytime sleepiness. Sleep onset and offset times were significantly prolonged during the competition condition (t = 2.11, p < .05; t = 2.51, p < .05). Correlations showed a relationship between PSQI and Sleepiness in the pre-training and pre-competition conditions (r = 0.50, p = .02) and chronotype with sleep onset (r = 0.61, p = .01), total sleep time (r = 0.55, p = .02), and time awake (r = 0.49, p = .04) in the competition condition. Linear regression analysis indicated associations between the PSQI and sleepiness (25%; p = .02) during pre-training and pre-competition. During the competition there were associations between chronotype and sleep onset (37%; p = .01), chronotype and time awake (24%; p = .04), and chronotype and TST (30%; p = .02). In general, the findings support the conclusion that LoL athletes presented an altered sleep pattern during their training routines.
Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults with Obesity While Dieting.

BACKGROUND Obesity exacerbates age-related effects on body composition, physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting obese older adults is unknown. METHODS In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait-speed, and knee strength by dynamometry. RESULTS IMAT and VAT decreased more in COMB than AEX and REX groups (IMAT; -41% vs. -28% and -23% and VAT: -36% vs. -19% and -21%; p=.003 to .01); IMAT and VAT decreased in all groups more than control (CON) (between-group p<.001). ISI increased more in COMB than AEX and REX groups (86% vs. 50% and 39%; p=.005 to .03). PPT improved more in COMB than AEX and REX groups, while VO2peak improved more in COMB and AEX than REX group (all p<.05). Knee strength improved more in COMB and REX than AEX group (all p<.05). Changes in IMAT and VAT correlated with PPT (r=-.28 and -.39), VO2peak (r=-.49 and -.52), gait-speed (r=-.25 and -.36), and ISI (r=-.49 and -.52) (all p<.05). CONCLUSIONS Weight loss plus combination aerobic and resistance exercise was most effective in improving ectopic fat deposition and physical and metabolic function in older adults with obesity.
Do Athlete and Coach Performance Perfectionism Predict Athlete Burnout?

ABSTRACT Research has illustrated that athlete perfectionism predicts athlete burnout. The present study sought to build on existing research in two ways. First, we provide the first test of the relationship between performance perfectionism and athlete burnout. That is, whether the degree to which athlete’s expect their own or others’ sport performances to be perfect, predicts burnout. Second, we broaden the examination of the perfectionism-burnout relationship to include coaches by testing the incremental predictive ability of perceptions of coach other-oriented performance perfectionism (the degree to which coaches were perceived to expect perfect performances from others). A sample of 190 competitive adult athletes (M age = 20.54) completed measures of their own performance perfectionism (self-oriented, socially prescribed, and other-oriented performance perfectionism), perceived coach other-oriented performance perfectionism, and burnout symptoms. Regression analyses indicated that both athlete self-oriented and socially prescribed performance perfectionism positively predicted athlete burnout. In addition, after controlling for all dimensions of athlete performance perfectionism, perceived coach other-oriented performance perfectionism positively predicted athlete burnout. The findings suggest that, in addition to their own perfectionism, when athletes perceive their coaches to be more perfectionistic towards others, they are more likely to experience burnout.
Discriminative Utility of Transcranial Magnetic Stimulation-Derived Markers of Cortical Excitability for Transient Ischemic Attack

ABSTRACT: Background: Several guidelines currently recommend acute diffusion weighted imaging (DWI) for the detection of ischemia in transient ischemic attack (TIA). However, DWI hyperintensities resolve early and only 30%–50% with clinically defined TIA show acute DWI positivity. A recent meta-analysis reported an unexplained 7-fold variation in DWI positivity in TIA across studies, concluding that DWI does not provide a consistent basis for defining ischemia. Intracortical excitability, measured using transcranial magnetic stimulation (TMS), has previously been shown to be altered after TIA and associated with ABCD2 scores; however, whether altered cortical excitability is associated with clinical and DWI-based definitions of TIA remains unclear. Methods: Individuals with TIA symptoms (N = 23; mean age = 61 ± 12) were prospectively recruited and underwent DWI and paired-pulse TMS. Multivariate linear regression was used to estimate associations between TMS-derived excitability thresholds, and clinical TIA diagnosis, and imaging-based evidence of cerebral ischemia (DWI positivity). Area under the curve (AUC) analyses was used to compare the discriminability of TMS-derived thresholds and clinical TIA diagnoses. Results: Thresholds for intracortical inhibition in the TIA-unaffected hemisphere were significantly associated with the clinical diagnosis of TIA. No associations between TMS-derived thresholds and DWI positivity were observed. TMS thresholds showed low-moderate discriminability and values differed by age (65+) and sex. Conclusions: In this small sample, TMS-derived markers of intracortical excitability were associated with clinical TIA diagnoses but not DWI positivity. Our results provide preliminary evidence for the potential discriminative utility of TMS for the diagnosis of TIA and highlight the need for future work in larger cohorts.
Safety and Efficacy of First-Line Pembrolizumab in Black Patients with Metastatic Non-Small-Cell Lung Cancer.

INTRODUCTION Pembrolizumab, an immune checkpoint inhibitor (ICI), has become an integral part of front-line treatment of metastatic non-small-cell lung cancer (NSCLC). However, pivotal trials had significant underrepresentation of Black patients (pts). Lack of sufficient evidence regarding safety and efficacy of ICIs among minority racial groups poses a challenge in delivery of optimal cancer directed care. METHODS We retrospectively reviewed pts with stage IV NSCLC treated with first-line pembrolizumab across three MedStar facilities between January 1st, 2014 and May 31st, 2019. Progression-free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using the Kaplan-Meier method. Immune-related adverse events (irAEs) were assessed according to CTCAE v5.0. RESULTS 136 pts were identified with 74 (54.4%) White, 53 (39%) Black, 2 (1.5%) Asian and 7 (5.1%) other racial groups. Median age in White pts was 70 years and 65 years in Black pts (p<0.01). There was no difference in median PFS (5.7 vs 5.9 months, p= 0.651) or OS (11.8 vs 12.4 months, p= 0.949) between White and Black pts. In the subset of patients whose tumors had high programmed death-ligand 1 (PD-L1) expression (≥ 50%), there was still no difference in efficacy by race. Median PFS (8.7 vs 3.9 months, p= 0.843) and OS (14.7 vs 11.3 months, p= 0.581) in White versus Black pts were not different. Incidence of irAEs in White versus Black pts was 24.3% and 22.6%, respectively (p=0.83). CONCLUSIONS We found no major differences in either safety or efficacy of first-line pembrolizumab between White and Black pts. Use of first-line pembrolizumab-based treatment in Black pts with stage IV NSCLC is safe and efficacious, based on these real-world data. IMPLICATIONS FOR PRACTICE Immunotherapy has revolutionized treatment of solid and hematological malignancies. There are certain populations of patients underrepresented in the original trials including minority racial groups, patients with autoimmune diseases and those with chronic viral illnesses. Our study focuses on Black patients with metastatic lung cancer who received pembrolizumab and concludes similar safety and response to treatment when compared to White patients. Black patients are an important demographic group in clinical practice often facing systemic healthcare disparities. Our study paves a path for future studies in underrepresented populations receiving immunotherapy across various malignancies.
The influence of preoperative biopsy on the surgical method in breast cancer patients: a single-center experience of 3,966 cases in China.

Background The National Surgical Adjuvant Breast and Bowel Project (NSABP) B32 trial reported that the detection rate of sentinel lymph nodes by core needle biopsy (CNB) is higher than that by segmental resection. However, there are few reports regarding the detection rate of sentinel lymph nodes by vacuum-assisted breast biopsy (VABB). Therefore, we analyzed the impact of preoperative biopsy methods on the surgical modes of 3,966 patients with breast cancer in our center. Methods In total, 3,966 female breast cancer patients [clinical tumor node metastasis (TNM) stage I-III] were enrolled in this study. Preoperative pathological diagnosis methods included fine needle aspiration (FNA) biopsy, CNB, excision biopsy, and VABB. According to the time of diagnosis. The data were analysis by chi square test, variance analysis and the Kaplan-Meier time series in SPSS 22.0. Results There was a decrease in the number of patients that underwent excision biopsy (7.3% to 2.7%) and intraoperative freezing (89.4% to 28.9%) over time, while CNB exhibited an increasing trend (1.6% to 55.3%). The positive rates of VABB, CNB, excision biopsy, and FNA were 99.5%, 97.1%, 97.9%, and 82.2%, respectively, and the false negative rates were 0%, 1.8%, 0.34%, and 8.9%, respectively. The overall breast-conserving rate was 36.7%, while the breast-conserving rate for VABB was 57.1%. The axillary sentinel lymph node biopsy rate of cN0 patients was 48.3%, and the intraoperative frozen group (36.7%) and excision biopsy group (39.5%) were lower than the CNB (57.1%) and VABB (77.9%) groups. Until December 2019, there were 350 cases with tumor recurrence or metastasis. The methods of biopsy were not correlated to the cumulative survival time. Conclusions Changes to the diagnosis and treatment of breast cancer has a profound impact on the method of tumor biopsy. VABB biopsy offers advantages such as accurate diagnosis, a greater volume of tissue taken at one time, minimally invasive and repeatable, and does not affect the surgical approach and prognosis of patients. It will gradually become the primary method of preoperative pathological evaluation of breast cancer.
Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes

Background Melatonin (MT) has been shown to protect against various cardiovascular diseases. However, the effect of MT on lipopolysaccharide (LPS)-induced myocardial injury is poorly understood. This study aims to evaluate the effects of MT on LPS-induced myocardial injury in vitro. Methods H9C2 cells were divided into a control group, MT group, LPS group, and MT + LPS group. The control group was treated with sterile saline solution, the LPS group received 8 µg/mL LPS for 24 h, MT + LPS cells were pretreated with 200 µmol/L MT for 2 h then with 8 µg/mL LPS for 24 h, and the MT group received only 200 µmol/L MT for 2 h. The CCK-8 assay and lactate dehydrogenase (LDH) activity assay were used to analyze cell viability and LDH release, respectively. Intracellular reactive oxygen species (ROS) and the rate of pyroptosis were measured using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and propidium iodide (PI) staining, respectively. The cell supernatants were used to measure the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1β by enzyme-linked immunosorbent assay (ELISA). The protein levels of iNOS, COX-2, NF-κB, p-NF-κB, NLRP3, caspase-1, and GSDMD were detected by western blot. Results MT pretreatment significantly improved LPS-induced myocardial injury by inhibiting inflammation and pyroptosis in H9C2 cells. Moreover, MT inhibited the activation of the NF-κB pathway, and reduced the expression of inflammation-related proteins (iNOS and COX-2), and pyroptosis-related proteins (NLRP3, caspase-1, and GSDMD). Conclusions Our data suggests that MT can alleviate LPS-induced myocardial injury, providing novel insights into the treatment of sepsis-induced myocardial dysfunction.
Clergy Wholeness Study: How Occupational Distress, Depression, and Social Support Inform the Health of Clergy

It has been shown that the rate of clergy occupational distress and depression is increasing. This study examines occupational distress, social support, mental health, and spiritual wholeness in Florida clergy. Clergy in our study sample exhibited higher rates of occupational distress than the national average. Significant connections were made between validated instruments used to assess mental health, clergy occupational distress, and social support. More research is needed to understand the potential causal effects.
SARS-CoV-2-Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women.

SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women On December 20, 2020, Israel initiated a national vaccination program against COVID-19. One prioritized group was health care workers, many of whom are breastfeeding women.1 Despite the fact that the vaccine trial did not include this population2 and no other vaccine-related safety data had been published, breastfeeding women belonging to risk groups were encouraged to receive the vaccine.3 The Centers for Disease Control and Prevention has also recommended that breastfeeding women belonging to vaccine-target groups be immunized.4 We investigated whether maternal immunization results in secretion of SARS-CoV-2 antibodies into breast milk and evaluated any potential adverse events among women and their infants.