Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.
Overcoming establishment thresholds for peat mosses in human‐made bog pools

Abstract Globally, peatlands have been affected by drainage and peat extraction, with adverse effects on their functioning and services. To restore peat‐forming vegetation, drained bogs are being rewetted on a large scale. Although this practice results in higher groundwater levels, unfortunately it often creates deep lakes in parts where peat was extracted to greater depths than the surroundings. Revegetation of these deeper waters by peat mosses appears to be challenging due to strong abiotic feedbacks that keep these systems in an undesired bare state. In this study, we theoretically explore if a floating peat mat and an open human‐made bog lake can be considered two alternative stable states using a simple model, and experimentally test in the field whether stable states are present, and whether a state shift can be accomplished using floating biodegradable structures that mimic buoyant peat. We transplanted two peat moss species into these structures (pioneer sp. Sphagnum cuspidatum and later‐successional sp. S. palustre) with and without additional organic substrate. Our model suggests that these open human‐made bog lakes and floating peat mats can indeed be regarded as alternative stable states. Natural recovery by spontaneous peat moss growth, i.e., a state shift from open water to floating mats, is only possible when the water table is sufficiently shallow to avoid light limitation (<0.29 m at our site). Our experiment revealed that alternative stable states are present and that the floating structures facilitated the growth of pioneer S. cuspidatum and vascular plants. Organic substrate addition particularly facilitated vascular plant growth, which correlated to higher moss height. The structures remained too wet for the late‐successional species S. palustre. We conclude that open water and floating peat mats in human‐made bog lakes can be considered two alternative stable states, and that temporary floating establishment structures can induce a state shift from the open water state to peat‐forming vegetation state. These findings imply that for successful restoration, there is a clear water depth threshold to enable peat moss growth and there is no need for addition of large amounts of donor‐peat substrate. Correct species selection for restoration is crucial for success.
Caffeine content and antioxidant activity of various brews of specialty grade coffee.

BACKGROUND The aim of the study was to evaluate the caffeine level and antioxidant activity of brews of specialty grade coffee compared to popular coffee brands. METHODS Ten types of coffee were used, including 7 specialty Arabica, 1 Robusta and 2 popular cheap coffee brands. For caffeine determination, HPLC analysis and the spectrophotometric method were used as reference. The total polyphenol content and antioxidant capacity (DPPH and FRAP methods) were evaluated. For two selected high-quality coffees, the influence of the brewing method on the antioxidant activity and caffeine content in the brews was assayed. RESULTS Regarding the caffeine content, differences between specialty coffee brews and popular products were not found, and an average level amounted to 56 and 40 mg/ml, respectively. In contrast, the antioxidant capacity of specialty coffee brews was significantly higher than for popular ones, independently of the test used. The highest scavenging ability and total phenolic content was found for S3 specialty coffee (46.15% of DPPH inhibition and 58.7 mg GAE/ml, respectively), whereas the lowest was found for popular coffee (about 35% of DPPH inhibition and about 41 mg/GAE/ml). For two selected high-quality coffees, the influence of the brewing method on the antioxidant activity and caffeine content in the brews was tested. It was found that the use of a dripper (overflow brewing method) provides the brew with the best antioxidant properties but with moderate caffeine levels. CONCLUSIONS It was found that 'specialty' quality coffees do not differ from popular brands in terms of caffeine content, but significantly outweigh them in terms of antioxidant activity. This property can be beneficial in the case of a high consumption of coffee, due to antiradical protective effects without the risk of caffeine overdose.
Sensitive screening of synthetic cannabinoids using liquid chromatography quadrupole time-of-flight mass spectrometry after solid phase extraction.

Analysis of synthetic cannabinoids still pose a challenge for many institutions due to the number of available substances and the constantly changing drug market. Both new and well-known substances keep appearing and disappearing on the market, making it hard to adapt analytical methods in a timely manner. In this study, we developed a qualitative screening approach for synthetic cannabinoids and their metabolites by means of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Samples were measured in data-dependent auto-MS/MS mode and identified by fragment spectra, retention time and accurate mass. Two established solid phase extractions were compared using fortified serum and urine samples. Mixes of 199 synthetic cannabinoids and 110 metabolites were used in 1 ng/mL and 10 ng/mL concentrations. Up to 93 % of synthetic cannabinoids and 74 % of metabolites were detected in fortified 1 ng/mL samples. From February 2018 to October 2020, we analyzed 1492 cases, of which 73 cases were positive for synthetic cannabinoids or metabolites. 5F-MDMB-PICA, 4F-MDMB-BINACA, MDMB-4en-PINACA and 4F-MDMB-BICA were most frequently detected. Hydrolysis metabolites were detected in many blood samples, providing a longer detection window. Quantification was conducted via liquid chromatography triple quadrupole mass spectrometry after liquid-liquid extraction. Concentrations were mostly close to 1 ng/mL in blood samples. LC-QTOF-MS was able to detect substances above trace quantities (< 0.1 ng/mL) in most cases, therefore fulfilling its purpose as a sensitive general screening approach. Expansion of the screening library was uncomplicated and enables future additions for up to thousands of targets.
Comparison of myoglobin clearance in three types of blood purification modalities

Myoglobin, which can cause acute kidney injury, has a relatively high molecular weight and is poorly cleared by diffusion. We compared and examined myoglobin clearance by changing the blood purification membrane and modality in patients with a myoglobin blood concentration ≥ 1000 ng/ml. We retrospectively analyzed three patient groups based on the following three types of continuous hemofiltration (CHF): AN69ST membrane, polymethylmethacrylate (PMMA) membrane, and high‐flow hemodiafiltration (HDF) with increased dialysate flow rate using the PMMA membrane. There was no significant difference in clearance in CHF between AN69ST and PMMA membranes. However, the high‐flow HDF group showed the highest myoglobin clearance (p = 0.003). In the PMMA membrane, changing the treatment modality to high‐flow HDF increased clearance above the theoretical value, possibly due to internal filtration. To remove myoglobin by kidney replacement therapy from patients with hypermyoglobinemia, a modality such as high‐flow HDF would be desirable.
Mycobacterium tuberculosis Phe-tRNA synthetase: structural insights into tRNA recognition and aminoacylation

Abstract Tuberculosis, caused by Mycobacterium tuberculosis, responsible for ∼1.5 million fatalities in 2018, is the deadliest infectious disease. Global spread of multidrug resistant strains is a public health threat, requiring new treatments. Aminoacyl-tRNA synthetases are plausible candidates as potential drug targets, because they play an essential role in translating the DNA code into protein sequence by attaching a specific amino acid to their cognate tRNAs. We report structures of M. tuberculosis Phe-tRNA synthetase complexed with an unmodified tRNAPhe transcript and either L-Phe or a nonhydrolyzable phenylalanine adenylate analog. High-resolution models reveal details of two modes of tRNA interaction with the enzyme: an initial recognition via indirect readout of anticodon stem-loop and aminoacylation ready state involving interactions of the 3′ end of tRNAPhe with the adenylate site. For the first time, we observe the protein gate controlling access to the active site and detailed geometry of the acyl donor and tRNA acceptor consistent with accepted mechanism. We biochemically validated the inhibitory potency of the adenylate analog and provide the most complete view of the Phe-tRNA synthetase/tRNAPhe system to date. The presented topography of amino adenylate-binding and editing sites at different stages of tRNA binding to the enzyme provide insights for the rational design of anti-tuberculosis drugs.
Different Sensitivity of action potential generation to the rate of depolarization in vagal afferent A-fiber versus C-fiber neurons.

The vagal afferent nerves innervate the visceral organs and convey sensory information from the internal environment to the central nervous system. A better understanding of the mechanisms controlling the activation of vagal afferent neurons bears physiological and pathological significance. Although it is generally believed that the magnitude and the rising rate of membrane depolarization are both critical for the action potential generation, no direct or quantitative evidence has been documented so far for the sensitivity of vagal afferent neuron activation to the rate of depolarization and for its underlying ionic mechanisms. Here, by measuring the response of mouse nodose neurons to the suprathreshold current stimuli of varying rising rates, the slowest depolarization capable of evoking action potentials, the rate-of-depolarization threshold (dV/dtthreshold), was determined and found to be ~20 fold higher in the A-fiber neurons compared to the C-fiber neurons classified based on the capsaicin responsiveness and characteristics of action potential waveforms. Moreover, although the dV/dtthreshold varied substantially among individual neurons it was not different in any one neuron in response to different intensities of current stimuli. Finally, inhibition of low-threshold activated D-type potassium current (IK.D) by α-dendrotoxin or low concentration of 4-aminopyrydine nearly abrogated the sensitivity of action potential generation to the depolarization rate. Thus, the depolarization rate is an important independent factor contributing to the control of action potential discharge, which is particularly effective in the vagal afferent A-fiber neurons. The IK.D channel may regulate the excitability of vagal sensory neurons by setting the dV/dtthreshold for action potential discharge.
3D morphometric study of domestic fowl glomerulus—A scanning electron microscope study of vascular corrosion casts

Microvascularization of domestic fowl kidneys was studied using scanning electron microscopy (SEM) of vascular corrosion casts (VCCs). Two types of nephrons, mammalian‐type (MT) and reptilian‐type (RT) nephrons and their glomerular structure were analysed quantitatively by 3D morphometry. A significant difference in shape and size between the MT and RT glomeruli was found. The mean diameter of the RT glomeruli was about 56 µm, while that of MT glomeruli was significantly larger, namely about 80 µm. The afferent arterioles in mammalian‐type glomeruli usually bifurcated into two lobular branches and formed a complex glomerular capillary network with numerous loops. Reptilian‐type glomeruli consisted of a single capillary forming few loops and leaving the glomerulus as efferent arteriole. Diameters of afferent and efferent arteriolar replicas were similar in all three kidney divisions of MT and RT nephrons. The absence of the interconnecting branches between the MT nephron capillaries at the gross inspection suggests that the mammalian‐type nephron glomeruli, although more complex than the reptilian type, are not equivalent to those in mammalian kidneys.
Symptoms of Depression and Anxiety in Patients With Type 2 Diabetes in a Canadian Outpatient Cardiac Rehabilitation Program

Supplemental Digital Content is Available in the Text. A retrospective analysis was conducted in 6746 patients who completed cardiac rehabilitation (CR). There was no association between diabetes status and depression before or after CR. Patients with diabetes were more likely to report moderate-to-severe anxiety after completing CR. Younger patients with diabetes who currently smoke or recently quit may require additional management of anxiety symptoms during CR. Purpose: The objective of this study was to determine whether type 2 diabetes status is associated with an increased likelihood of depressed mood and anxiety in patients attending cardiac rehabilitation (CR) and to explore predictors of depression and anxiety after CR completion in patients with diabetes. Methods: A retrospective analysis was conducted in patients who completed a 12-wk CR program between 2002 and 2016. Patients were classified as reporting normal-to-mild or moderate-to-severe symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale (HADS). Logistic regression models were used to compare predictors of depression and anxiety prior to CR enrollment and investigate predictors of post-CR HADS scores among a subset of patients with diabetes. Results: Data from 6746 patients (mean age 61 ± 11 yr, 18% female, 18% with diabetes) were analyzed. After controlling for known predictors of depression, patients with diabetes were not more likely to report moderate-to-severe levels of depression prior to or after completing CR. In patients with diabetes, younger age predicted moderate-to-severe depression post-CR (OR = 0.95: 95% CI, 0.93-0.98). Patients with diabetes were also more likely to report moderate-to-severe levels of anxiety after completing CR (OR = 1.45: 95% CI, 1.02-2.07). Younger age (OR = 0.93: 95% CI, 0.88-0.97) and smoking status (OR = 3.3: 95% CI, 1.15-7.06) predicted moderate-to-severe post-CR anxiety in patients with diabetes. Conclusions: Patients with diabetes, particularly younger patients who currently smoke or recently quit, are more likely to report having anxiety following CR. These patients may therefore require additional management of anxiety symptoms during CR. Larger studies of CR patients with diabetes and more variable depression and anxiety levels are needed.
circUBAP2 exacerbates malignant capabilities of NSCLC by targeting KLF4 through miR-3182 modulation

Chemo-resistance and refractoriness remain challenges for Non-small cell lung cancer (NSCLC) patients and the underlying molecular mechanisms haven’t been fully explained. In this study, we investigated the influence of circUBAP2 on the NSCLC tumor cells. This study might provide novel therapeutic targets for NSCLC treatment. Clinical samples and NSCLC cell lines were used to investigate circUBAP2 expressions and their impact on tumor cell chemo-resistance. CCK8 and transwell assays were conducted to explore the differences of NSCLC tumor proliferation and migration capabilities affected by circUBAP2. Dual-luciferase reporter gene assay was performed to explore the detailed molecular mechanism of circUBAP2 regulation network. circUBAP2 exhibited significantly elevated average level in our clinical samples of NSCLC, compared with normal tissues. CircUBAP2 level was positively correlated with disease stage and metastatic status. circUBAP2 significantly enhanced the migration, proliferation and chemo-resistance of NSCLC cell lines. Further experiments indicated that circUBAP2 promoted malignant biological behavior of NSCLC tumor cells by targeting KLF4 through modulating miR-3182 expression. Our study demonstrated for the first time that circUBAP2 played an important role exacerbating malignant capabilities of NSCLC. circUBAP2-miR3182-KLF4 regulative network demonstrated in this study could be a novel therapeutic target for future NSCLC treatment.
Trials and Tribulations: mHealth Clinical Trials in the COVID-19 Pandemic

Summary Introduction: Mobile phone-based interventions in cardiovascular disease are growing in popularity. A randomised control trial (RCT) for a novel smartphone app-based model of care, named TeleClinical Care - Cardiac (TCC-Cardiac), commenced in February 2019, targeted at patients being discharged after care for an acute coronary syndrome or episode of decompensated heart failure. The app was paired to a digital sphygmomanometer, weighing scale and a wearable fitness band, all loaned to the patient, and allowed clinicians to respond to abnormal readings. The onset of the COVID-19 pandemic necessitated several modifications to the trial in order to protect participants from potential exposure to infection. The use of TCC-Cardiac during the pandemic inspired the development of a similar model of care (TCC-COVID), targeted at patients being managed at home with a diagnosis of COVID-19. Methods: Recruitment for the TCC-Cardiac trial was terminated shortly after the World Health Organization announced COVID-19 as a global pandemic. Telephone follow-up was commenced, in order to protect patients from unnecessary exposure to hospital staff and patients. Equipment was returned or collected by a ‘no-contact’ method. The TCC-COVID app and model of care had similar functionality to the original TCC-Cardiac app. Participants were enrolled exclusively by remote methods. Oxygen saturation and pulse rate were measured by a pulse oximeter, and symptomatology measured by questionnaire. Measurement results were manually entered into the app and transmitted to an online server for medical staff to review. Results: A total of 164 patients were involved in the TCC-Cardiac trial, with 102 patients involved after the onset of the pandemic. There were no hospitalisations due to COVID-19 in this cohort. The study was successfully completed, with only three participants lost to follow-up. During the pandemic, 5 of 49 (10%) of patients in the intervention arm were readmitted compared to 12 of 53 (23%) in the control arm. Also, in this period, 28 of 29 (97%) of all clinically significant alerts received by the monitoring team were managed successfully in the outpatient setting, avoiding hospitalisation. Patients found the user experience largely positive, with the average rating for the app being 4.56 out of 5. 26 patients have currently been enrolled for TCC-COVID. Recruitment is ongoing. All patients have been safely and effectively monitored, with no major adverse clinical events or technical malfunctions. Patient satisfaction has been high. Conclusion: The TCC-Cardiac RCT was successfully completed despite the challenges posed by COVID-19. Use of the app had an added benefit during the pandemic as participants could be monitored safely from home. The model of care inspired the development of an app with similar functionality designed for use with patients diagnosed with COVID-19.
Reclassification of Catabacter hongkongensis as Christensenella hongkongensis comb. nov. based on whole genome analysis

The genera Catabacter (family Catabacteraceae) and Christensenella (family Christensenellaceae) are close relatives within the phylum Firmicutes. Members of these genera are strictly anaerobic, non-spore forming, short straight rods with diverse phenotypes. Phylogenetic analysis of 16S rRNA genes suggest that Catabacter splits Christensenella into a polyphyletic clade. In an effort to ensure that family/genus names represent monophyletic clades, we performed a whole-genome based analysis of the genomes available for the cultured representatives of these genera: four species of Christensenella and two strains of Catabacter hongkongensis. A concatenated alignment of 135 shared protein sequences indicates that C. hongkongensis is indeed nested within the Christensenella clade. Based on their evolutionary relationship, we propose the transfer of Catabacter hongkongensis to the new genus as Christensenella hongkongensis comb.nov.
Exercise and fruit/vegetable intake, and their associations with body weight status in university students.

BACKGROUND evidence suggests that exposure to risk factors related to excess body weight is more frequent in the second and third decades of life. Thus, one of the most propitious environments for the acquisition of habits that can inhibit overweight is the university. OBJECTIVE to identify the frequency of aerobic and strength exercises and of fruit/vegetable intake in university students, and subsequently establish associations between both health behaviors and excess body weight. METHODS the sample was comprised of 5,310 university students. An online questionnaire was used to collect the frequency of exercises and fruit/vegetable intake. The body mass index was used to define body weight status. The data were analyzed statistically by employing a bivariate analysis and binary logistic regression. RESULTS the practice of aerobic and strength exercises was reported by 80.4 % and 51.6 % of the sample, respectively. Only 13 % of the surveyed university students had an adequate fruit/vegetable intake. The proportion of excess body weight was 39.1 %, the condition being significantly higher in men. The risk for excess body weight identified in the university students who reported not consuming fruits/vegetables daily was two to three times higher than in their peers who reported an adequate intake (women: OR = 2.92 [95 % CI 2.07-4.12]; men: OR = 1.98 [95 % CI 1.41-3.02]). Exposure to the risk for excess body weight was progressively lower as the reported frequency of aerobic exercise became higher. CONCLUSION these findings suggest the need to promote initiatives aimed at the preparation and implementation of health education and promotion programs in the university context, through actions of guidance about exercise and food intake that may help to minimize the risks of onset and development of excess body weight.