Miracle-dz/UniFAR-FTUs huggingface dataset:
International waist circumference percentile cut-offs for central obesity in children and adolescents aged 6-18 years.

CONTEXT No universal waist circumference (WC) percentile cut-offs used have been proposed for screening central obesity in children and adolescents. OBJECTIVE To develop international WC percentile cut-offs for children and adolescents with normal weight based on data from eight countries in different regions and examine the relation with cardiovascular risk. DESIGN AND SETTING We used pooled data on WC in 113,453 children and adolescents (males, 50.2%) aged 4-20 years from eight countries in different regions (Bulgaria, China, Iran, Korea, Malaysia, Poland, Seychelles, and Switzerland). We calculated WC percentile cut-offs in samples including or excluding children with obesity, overweight or underweight. WC percentiles were generated using the general additive model for location scale and shape (GAMLSS). We also estimated the predictive power of the WC 90th percentile cut-offs to predict cardiovascular risk using receiver operator characteristics curve analysis based on data from three countries that had available data (China, Iran and Korea). We also examined which WC percentiles connected with WC cut-offs for central obesity in adults (at age of 18 years). MAIN OUTCOME MEASURE WC measured based on recommendation by the World Health Organization. RESULTS We validated the performance of the age- and sex- specific 90th percentile WC cut-offs calculated in children and adolescents (6-18 years of age) with normal weight (excluding youth with obesity, overweight or underweight) by linking it with cardiovascular risk (AUC: 0.69 for boys; 0.63 for girls). In addition, WC percentile among normal weight children linked relatively well with established WC cut-offs for central obesity in adults (e.g., AUC in US adolescents: 0.71 for boys; 0.68 for girls). CONCLUSION The international WC cut-offs developed in this study could be useful to screen central obesity in children and adolescents aged 6-18 years and allow direct comparison of WC distributions between populations and over time.
Separation of the epitopes in a multi-epitope chimera: Helical or flexible linkers?

BACKGROUND The engineered chimeric peptides including functional multi-epitope structures fused by various peptide linkers are widely applied in biotechnological research to improve the expression level and biological activity of chimera. OBJECTIVE The aim of our study was to evaluate the effect of helical and flexible linkers on solubility, expression level and folding of multi-epitope chimera containing four epitopes of human T lymphotropic virus type 1 (HTLV-1). METHODS For this purpose, the chimera sequences connected by the helical or flexible linker were inserted into different plasmid vectors and expressed in E. coli strains. The expressed products were analyzed using SDS-PAGE and Western blot techniques. Additionally, the molecular modeling study of the chimera with helical or flexible linker was performed using iterative threading assembly refinement (I-TASSER) to attain their three-dimensional structures. RESULTS Comparison of the chimera expression indicated that the insertion of a flexible (GGGGS)3 linker among chimera epitopes could significantly enhance the level of expression, whereas, the low-level of chimera expression was observed for chimera containing the contiguous helical (EAAAK)5 linker. According to the results of sequence alignment and plasmid stability test, the structure and function of a consecutive helical linker among chimera epitopes were similar to porins as the outer-membrane pore-forming proteins. The molecular modeling results confirmed our experimental study. CONCLUSION This investigation illustrated the key role of linker design in determining the expression level of multi-epitope chimera and conformational folding.
Sarcopenia in COPD: a systematic review and meta-analysis

COPD is associated with a progressive loss of muscle mass and function. However, there is an unmet need to define and standardise methods to estimate the prevalence of sarcopenia in COPD patients. We performed a systematic review and meta-analysis of the prevalence of this extrapulmonary manifestation in COPD patients. We searched Embase, Medline (Ovid), CINAHL (EBSCO), Web of Science, Scopus and Google Scholar for studies published up to January 17, 2019, assessing sarcopenia in COPD patients based on low muscle mass and decreased muscle function. Interventional studies, in vitro experiments, protocols or reviews and meta-analyses were excluded. We estimated heterogeneity (I2) and assessed significance (Q) using a Chi-squared test for estimates obtained from random-effects models. 4465 articles were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 62 full-text articles. Finally, 10 articles (n=2565 COPD patients) were included in this systematic review and meta-analyses. Overall, the prevalence of sarcopenia in patients with COPD was 21.6% (95% CI 14.6–30.9%, I2=94%), ranging from 8% in population-based to 21% in clinic-based studies, and 63% in COPD patients residing in nursing homes. Sarcopenia is frequently observed in COPD patients, with varying prevalence across population settings. Sarcopenia in COPD should be assessed using standardised tests and cut-off points from sarcopenia consensus criteria for clinical practice and international comparisons. We confirmed a high prevalence of sarcopenia in COPD patients, with varying prevalence across population settings. We recommend adhering to the sarcopenia consensus criteria to systematically evaluate the muscle health of COPD patients. http://bit.ly/2KA6weh
Does whole-body electrical muscle stimulation combined with strength training promote morphofunctional alterations?

OBJECTIVES: The aim of this study was to evaluate the effects of 8 weeks of strength training (ST) combined with whole-body electrical stimulation (EMS) on morphofunctional adaptations in active individuals. METHODS: Fifty-eight volunteers were randomly distributed into the following groups: an untrained control (UN) group (n=16), an ST group (n=21) or an ST combined with EMS (ST+EMS) group (n=21). Both intervention groups (the ST and ST+EMS groups) performed 3 exercises (biceps curl, back squats and high-pulley tricep extensions) twice a week for 8 weeks. The subjects performed 3 sets of 8 to 12 maximum repetitions (MRs) with a 90-second rest duration between sets. The ST+EMS group performed the resistance training exercises wearing a whole-body suit that provided electrical stimulation at frequencies between 80-85 Hz, with a continuously bipolar impulse duration and pulse breadth of 350 µs. The intensity for each muscle group was controlled by Borg’s category ratio (CR)-10 scale; the intensity started at 5-6 and eventually reached 7-8. One-repetition maximum strength (1RM) and muscle thickness (MT) were measured before and after the training intervention. MT was evaluated in the biceps brachii (BB), triceps brachii (TB), and vastus lateralis (VL). RESULTS: No differences (p>0.05) were found between the ST and ST+EMS groups. Improvements (p<0.05) in the absolute values of the morphofunctional parameters after the training protocol were observed. Significant differences were found between both the intervention groups and the UN group (p<0.05). The ST+EMS group presented high percentage changes (p<0.05) in muscular strength for the 1RMsquat (43.2%, ES=1.64) and the MT of the BB (21.6%, ES=1.21) compared to the ST (20.5%, ES=1.43, 11.9%, ES=0.77) group. CONCLUSIONS: Our data suggest that the combination of ST+EMS may promote alterations in muscle strength and MT in healthy active subjects.
Targeting redox heterogeneity to counteract drug tolerance in replicating Mycobacterium tuberculosis

Chloroquine resets the redox physiology of Mycobacterium tuberculosis to potentiate the efficacy of antibiotics in vivo. Antibiotic redox-based redux Phagosomal pH and redox heterogeneity in Mycobacterium tuberculosis (Mtb) can promote tolerance of the bacterium to antibiotics. Mishra et al. found that the approved antimalarial drug chloroquine inhibited this acidification and resulted in altered redox metabolism and improved susceptibility of Mtb to first-line antituberculosis drugs, particularly isoniazid, in infected macrophages in vitro. Coadministration of chloroquine improved isoniazid treatment outcomes in both mouse and guinea pig models of Mtb infection. This work suggests the repurposing of chloroquine to potentiate and possibly shorten antibiotic treatment of tuberculosis. The capacity of Mycobacterium tuberculosis (Mtb) to tolerate multiple antibiotics represents a major problem in tuberculosis (TB) management. Heterogeneity in Mtb populations is one of the factors that drives antibiotic tolerance during infection. However, the mechanisms underpinning this variation in bacterial population remain poorly understood. Here, we show that phagosomal acidification alters the redox physiology of Mtb to generate a population of replicating bacteria that display drug tolerance during infection. RNA sequencing of this redox-altered population revealed the involvement of iron-sulfur (Fe-S) cluster biogenesis, hydrogen sulfide (H2S) gas, and drug efflux pumps in antibiotic tolerance. The fraction of the pH- and redox-dependent tolerant population increased when Mtb infected macrophages with actively replicating HIV-1, suggesting that redox heterogeneity could contribute to high rates of TB therapy failure during HIV-TB coinfection. Pharmacological inhibition of phagosomal acidification by the antimalarial drug chloroquine (CQ) eradicated drug-tolerant Mtb, ameliorated lung pathology, and reduced postchemotherapeutic relapse in in vivo models. The pharmacological profile of CQ (Cmax and AUClast) exhibited no major drug-drug interaction when coadministered with first line anti-TB drugs in mice. Our data establish a link between phagosomal pH, redox metabolism, and drug tolerance in replicating Mtb and suggest repositioning of CQ to shorten TB therapy and achieve a relapse-free cure.
Evaluating The Effectiveness Of Telephone Triage For Priority Emergency Ambulance Dispatch

Emergency telephone calls (108) for an ambulance are usually dealt with "first come first served". We have devised and assessed criteria that the ambulance dispatch might use to prioritize responses. The data were collected retrospectively on consecutive patients presenting to an accident and emergency (A and E) department after a 108 emergency call. An unblinded researcher abstracted data including age, time, caller, location, reason for the call and A and E diagnosis and each case was examined for ten pre-determined criteria necessitating an immediate ambulance response - namely cardiac arrest, chest pain, shortness of breath, altered mental status / seizures, abdominal / loin pain at age >65 years, fresh haemetemesis, fall from >2 meters, penetrating injuries and major burns. 567 patients were recruited, of which 57% were males with a median age of 45 years. 434 calls came from by standers or patients themselves, 30 from general practioners, 83 from other hospitals and 20 from the police. 51% patients were admitted. 43% met at least one of the above mentioned criteria. Most patients did not meet the criteria for an immediate ambulance dispatch.
Are people-centred mental health services acceptable and feasible in Timor-Leste? A qualitative study.

People-centred mental healthcare is an influential concept for health system strengthening and sustainable development that has been developed and promoted primarily in Western contexts. It characterizes service users, families and communities as active participants in health system development. However, we have limited understanding of how well people-centred mental healthcare aligns with the multiplicity of peoples, cultures, languages and contexts in low- and middle-income countries (LMICs). Timor-Leste, a lower-middle income country in South-East Asia, is in the process of strengthening its National Mental Health Strategy 2018-22 to align with people-centred mental healthcare. To support the implementation of this Strategy, this study investigated the acceptability and feasibility of people-centred mental health services in Timor-Leste. In-depth semi-structured individual (n = 57) and group interviews (n = 15 groups) were conducted with 85 adults (≥18 years). Participants were service users, families, decision-makers, service providers and members of civil society and multilateral organizations across national and sub-national sites. Government and non-government mental health and social care was also observed. Framework analysis was used to analyse interview transcripts and observation notes. The study found that the ecology of mental healthcare in Timor-Leste is family-centred and that government mental health services are largely biomedically oriented. It identified the following major challenges for people-centred mental health services in Timor-Leste: different sociocultural perceptions of (in)dividual personhood, including a diminished status of people with mental illness; challenges in negotiating individual and family needs; a reliance on and demand for biomedical interventions; and barriers to health service access and availability. Opportunities for people-centred mental healthcare are better available within the social and disability sectors, which focus on social inclusion, human rights and peer support. Accounting for local cultural knowledge and understandings will strengthen design and implementation of people-centred mental healthcare in LMIC settings.
Empagliflozin and Dapagliflozin Reduce ROS Generation and Restore NO Bioavailability in Tumor Necrosis Factor α-Stimulated Human Coronary Arterial Endothelial Cells.

BACKGROUND/AIMS Heart failure is characterized by chronic low-grade vascular inflammation, which in itself can lead to endothelial dysfunction. Clinical trials showed reductions in heart failure-related hospitalizations of type 2 diabetic patients using sodium glucose co-transporter 2 inhibitors (SGLT2i's). Whether and how SGLT2i's directly affect the endothelium under inflammatory conditions is not completely understood. The aim of the study was to investigate whether the SGLT2i Empagliflozin (EMPA) and Dapagliflozin (DAPA) reduce tumor necrosis factor α (TNFα) induced endothelial inflammation in vitro. METHODS Human coronary arterial endothelial cells (HCAECs) and human umbilical vein endothelial cells (HUVECs) were (pre-)incubated with 1 µM EMPA or DAPA and subsequently exposed to 10 ng/ml TNFα. ROS and NO were measured using live cell imaging. Target proteins were either determined by infrared western blotting or fluorescence activated cell sorting (FACS). The connection between Cav-1 and eNOS was determined by co-immunoprecipitation. RESULTS Nitric oxide (NO) bioavailability was reduced by TNFα and both EMPA and DAPA restored NO levels in TNFα-stimulated HCAECs. Intracellular ROS was increased by TNFα, and this increase was completely abolished by EMPA and DAPA in HCAECs by means of live cell imaging. eNOS signaling was significantly disturbed after 24 h when cells were exposed to TNFα for 24h, yet the presence of both SGLT2is did not prevent this disruption. TNFα-induced enhanced permeability at t=24h was unaffected in HUVECs by EMPA. Similarly, adhesion molecule expression (VCAM-1 and ICAM-1) was elevated after 4h TNFα (1.5-5.5 fold increase of VCAM-1 and 4-12 fold increase of ICAM-1) but were unaffected by EMPA and DAPA in both cell types. Although we detected expression of SGLT2 protein levels, the fact that we could not silence this expression by means of siRNA and the mRNA levels of SGLT2 were not detectable in HCAECs, suggests aspecificity or our SGLT2 antibody and absence of SGLT2 in our cells. CONCLUSION These data suggest that EMPA and DAPA rather restore NO bioavailability by inhibiting ROS generation than by affecting eNOS expression or signaling, barrier function and adhesion molecules expression in TNFα-induced endothelial cells. Furthermore, the observed effects cannot be ascribed to the inhibition of SGLT2 in endothelial cells.
Computational fluid dynamics simulation of changes in the morphology and airflow dynamics of the upper airways in OSAHS patients after treatment with oral appliances

Objectives To explore the changes of morphology and internal airflow in upper airways (UA) after the use of oral appliances (OAs) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS), and investigate the mechanisms by which OAs function as a therapy for OSAHS. Methods Eight OSAHS patients (all male, aged 37–58, mean age 46.25) underwent CT scans before and after OA use. Then, computational fluid dynamics(CFD) models were built on the base of the CT scans using Mimics and ANSYS ICEM CFD software. The internal airflow of the upper airways was simulated using ANSYS-FLUENT and the results were analyzed using ANSYS-CFD-Post. The data were analyzed to identify the most important changes of biomechanical properties between patients with and without OA intervention. Upper airway morphology and the internal airflow changes were compared using t-tests and Spearman correlation coefficient analysis. Results The narrowest area of upper airways was found to be located in the lower bound of velopharynx, where the volume and pressure were statistically significantly increased (P<0.05) and the air velocity was statistically significantly decreased (P<0.05) in the presence of the OA(P<0.05). After wearing OA, pharyngeal resistance was significantly decreased (P<0.05), from 290.63 to 186.25Pa/L, and the airflow resistance of the pharynx has reduced by 35.9%. Conclusion The enlargement of the upper airway after wearing the OA changed its airflow dynamics, which decreased the negative pressure and resistance in narrow areas of the upper airways. Thus, the collapsibility of the upper airways was reduced and patency was sustained.
Ancestry Estimation Using Cranial and Postcranial Macromorphoscopic Traits

Ancestry estimation methods using macromorphoscopic (MMS) traits commonly focus exclusively on cranial morphology. The objective of this study was to demonstrate the value of postcranial MMS traits, highlighting a combined cranial/postcranial trait approach to ancestry estimation using quadratic discriminant function and a variety of machine learning classification models including artificial neural networks (aNN), random forest models, and support vector machine. Eight cranial and eleven postcranial MMS traits were collected from the Terry and Bass Skeletal Collections (American Black = 81; American White = 173). Our classification models using cranial and postcranial traits correctly classified 88–92% of the sample, improving classification accuracies by nearly fifteen percent over models relying exclusively on cranial data. These same results demonstrate the importance of a multivariate statistical framework incorporating cranial and postcranial data and the nearly unlimited potential of machine learning models to improve the accuracy of ancestry estimates over traditional methods of analysis. To facilitate implementation in casework, one of the more robust models (aNN) is incorporated into a web‐based application, ComboMaMD Analytical, to facilitate cranial and postcranial MMS traits analysis for ancestry estimation.
Relationship between serum iohexol clearance, serum SDMA concentration, and serum creatinine concentration in non‐azotemic dogs

Abstract Background Serum creatinine and symmetric dimethylarginine (SDMA) are used as surrogate markers of glomerular filtration rate (GFR) in clinical practice. Data pertaining to the correlations between GFR, SDMA, and serum creatinine in client‐owned dogs are limited. Objectives To describe the relationship between GFR, SDMA, and serum creatinine in a population of client‐owned dogs, and to compare clinical utility of SDMA to GFR estimation for detecting pre‐azotemic chronic kidney disease. Animals Medical records of 119 dogs that had GFR estimation performed via serum iohexol clearance between 2012 and 2017. Methods Prospective study using archived samples. GFR, SDMA, and serum creatinine results were reviewed and submitting practices contacted for outcome data. All dogs included in the study population were non‐azotemic. Correlations between GFR, SDMA, and serum creatinine were determined by regression analysis. Sensitivity, specificity, and positive and negative likelihood ratios of different cutoffs for SDMA and serum creatinine for detecting decreased GFR were calculated, using a 95% confidence interval. Results Serum creatinine and SDMA were moderately correlated with GFR (R2 = 0.52 and 0.27, respectively, P < .0001) and with each other (R2 = 0.33, P < .0001). SDMA >14 μg/dL was sensitive (90%) but nonspecific (50%) for detecting a ≥40% decrease in GFR. Optimal SDMA concentration cutoff for detecting a ≥40% GFR decrease was >18 μg/dL (sensitivity 90%, specificity 83%). Conclusions and Clinical Importance In non‐azotemic dogs being screened for decreased renal function, using a cutoff of >18 μg/dL rather than >14 μg/dL increases the specificity of SDMA, without compromising sensitivity.
Morin inhibits colorectal tumor growth through inhibition of NF-κB signaling pathway

Abstract Background: To explore the effects and underlying mechanisms of Morin in human colorectal cancer. Methods: Effects of Morin on proliferation of human colorectal cells in vitro were detected by MTT and colony formation assay. Effects of Morin on growth of colorectal tumors in vivo were examined using the xenograft tumor model. Production of inflammatory cytokines was evaluated by ELISA assay. Effects of Morin on p65-NFκB expression and activation in HCT-116 cells were determined by qRT-PCR and western blot. Effects of C/EBPβ-induced upregulation of p65-NFκB on the inhibitory effects of Morin in HCT-116 cells were evaluated by qRT-PCR, western blot and immunofluorescent staining analysis. Results: Morin inhibited cell proliferation of human colorectal cells in vitro and growth of colorectal tumors in vivo. Morin treatment suppressed TNF-α-induced p65-NFκB expression and activation as well as production of IL-6 and IL-8 in HTC-116 cells. The inhibitory effects of Morin were abrogated by C/EBPβ-induced upregulation of p65-NFκB. Morin had inhibitory effects on human colorectal cancer both in vitro and in vivo. Conclusion: The antitumor functions of Morin in human colorectal cancer cells might be partially due to inhibition of NF-κB signaling.
Novel Propargyl-linked Bisubstrate Analogs as Tight-binding Inhibitors for Nicotinamide N-Methyltransferase.

Nicotinamide N-methyltransferase (NNMT) catalyzes the methyl transfer from cofactor S-adenosylmethionine (SAM) to nicotinamide and other pyridine-containing compounds. NNMT is an important regulator for nicotinamide metabolism and methylation potential. Aberrant expression levels of NNMT have been implicated in cancer, metabolic and neurodegenerative diseases, which makes NNMT a potential therapeutic target. Therefore, potent and selective NNMT inhibitors can serve as valuable tools to investigate the roles of NNMT in its mediated diseases. Here, we applied a rational strategy to design and synthesize the tight-binding bisubstrate inhibitor LL320 through a novel propargyl linker. LL320 demonstrates a Ki value of 1.6±0.3 nM, which is the most potent inhibitor to date. The co-crystal structure of LL320 confirms its interaction with both the substrate and cofactor binding sites on NNMT. Importantly, this is the first example of using propargyl linker to construct potent methyltransferase inhibitors, which will expand our understanding of the transition state of methyl transfer.