Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications of Skeletal Muscle Extracellular Matrix Remodeling in Metabolic Disorders: Diabetes Perspective

The extracellular matrix (ECM) provides a scaffold for cells, controlling biological processes and providing structural as well as mechanical support to surrounding cells. Disruption of ECM homeostasis results in several pathological conditions. Skeletal muscle ECM is a complex network comprising collagens, proteoglycans, glycoproteins, and elastin. Recent therapeutic approaches targeting ECM remodeling have been extensively deliberated. Various ECM components are typically found to be augmented in the skeletal muscle of obese and/or diabetic humans. Skeletal muscle ECM remodeling is thought to be a feature of the pathogenic milieu allied with metabolic dysregulation, obesity, and eventual diabetes. This narrative review explores the current understanding of key components of skeletal muscle ECM and their specific roles in the regulation of metabolic diseases. Additionally, we discuss muscle-specific integrins and their role in the regulation of insulin sensitivity. A better understanding of the importance of skeletal muscle ECM remodeling, integrin signaling, and other factors that regulate insulin activity may help in the development of novel therapeutics for managing diabetes and other metabolic disorders.
Thromboembolic Risk of C1 Esterase Inhibitors: A Systematic Review on Current Evidence

ABSTRACT Introduction The exact risk of developing a thromboembolic event (TEE) while using complement 1 esterase inhibitors (C1-INHs) is currently undetermined for patients with hereditary angioedema (HAE). This systematic review aimed to define the potential risk of TEEs from these agents. Areas covered This evaluation covers publications examining or mentioning the risk of TEEs in association with C1-INHs. A systematic literature search was conducted utilizing PubMed, Scopus, and ProQuest. This review utilized search results through January 2020 and followed the PRISMA recommendations for a systematic review. Articles not available in English and animal or in-vitro studies were excluded. For inclusion, studies had to be open-label, randomized-controlled, cross-sectional, or clinical observational studies. A total of 13 studies met inclusion criteria and yielded 1716 patients receiving at least one dose of C1-INH, though only 41 incidences of thrombosis were documented. Expert opinion Significant heterogeneity exists in the available literature concerning both study design and the reporting of data; therefore, interpretation of thrombotic risk is difficult. TEEs are rarely reported in the literature, and they seem unlikely to occur in patients without underlying risk factors. Important risk factors include those found in the prescribing information of C1-INHs.
Detection and genotyping of bovine leukemia virus (BLV) in Vietnamese cattle

Bovine leukemia virus (BLV) belongs to the genus, Deltaretrovirus of the family, Retroviridae and it is the causative agent of enzootic bovine leukosis. The prevalence of BLV in three provinces in the Red River Delta Region in the North of Vietnam, Hanoi, Vinhphuc and Bacninh was studied from April 2017 to June 2018. A total of 275 blood samples collected from cattle were used for serum isolation and DNA extraction. Of these samples, 266 sera were subjected to ELISA test for detecting antibody against BLV gp51 protein and 152 DNA samples were used to detect the 444 bp fragment corresponding to a part of the gp51 region of the env by nested PCR. The results showed that 16.5% (n=44) and 21.1% (n=32) of samples were positive for BLV gp51 antibody and BLV proviral DNA, respectively. Phylogenetic analysis of the partial (423 bp) and complete (913 bp) BLV env-gp51 gene indicated that Vietnamese strains were clustered into genotypes 1, 6 and 10 (G1, G6 and G10). Of those genotypes, G1 genotype was dominant; G6 strains were designated as G6e and G6f subgenotypes; the existence of genotype 10 was confirmed for the first time in Vietnam. The present study provides important information regarding the prevalence of BLV infection and genetic characteristics of BLV strains identified in Vietnam, contributing to promote the establishment of disease control and eradication strategies in Vietnam.
Genome-wide prediction for complex traits under the presence of dominance effects in simulated populations using GBLUP and machine learning methods.

The aim of this study was to compare the predictive performance of the Genomic Best Linear Unbiased Predictor (GBLUP) and machine learning methods (Random Forest - RF, Support Vector Machine - SVM and Artificial Neural Network - ANN) in simulated populations presenting different levels of dominance effects. Simulated genome comprised 50k single nucleotide polymorphism (SNP) and 300 QTL (Quantitative Trait Loci), both biallelic and randomly distributed across 29 autosomes. A total of six traits were simulated considering different values for the narrow and broad-sense heritability. In the purely additive scenario with low heritability (h2 = 0.10), the predictive ability obtained using GBLUP was slightly higher than the other methods whereas ANN provided the highest accuracies for scenarios with moderate heritability (h2 = 0.30). The accuracies of dominance deviations predictions varied from 0.180 to 0.350 in GBLUP extended for dominance effects (GBLUP-D), from 0.06 to 0.185 in RF and they were null using the ANN and SVM methods. Although RF has presented higher accuracies for total genetic effect predictions, the MSE (Mean-squared error) values in such a model were worse than those observed for GBLUP-D in scenarios with large additive and dominance variances. When applied to pre-screen important regions, the RF approach detected QTL with high additive and/or dominance effects. Among machine learning methods, only the RF was capable to cover implicitly dominance effects without increasing the number of covariates in the model, resulting in higher accuracies for the total genetic and phenotypic values as the dominance ratio increases. Nevertheless, whether the interest is to infer directly on dominance effects, GBLUP-D could be a more suitable method.
Standardization of rehabilitation program for post-apoplectic limb spasm treated by Tongjing Tiaoxing tuina and scalp acupuncture with physical therapy

Abstract Background: Tong Jing Tiao Xing tuina (TJTX) is a Chinese massage method. Excising with scalp acupuncture (ESA) is a treatment combining scalp electroacupuncture with physical therapy (PT), and yinao fujian formula (YNFJ) is a Chinese oral herbal granule medicine. The combination of the 3 methods is called the “Zhishen Tiaoxing” (ZSTX) rehabilitation program, which is used as an alternative of limb spasm after stroke. There is little available evidence demonstrating its safety and efficacy. Methods: This will be a subject-blind, randomized controlled trial conducted in 3 medical centers. It will strictly follow the Standards for Reporting Interventions in Clinical Trials of Acupuncture, 2010. We will recruit 316 patients with limb spasm after stroke, 200 from the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China, 80 from the Second Affiliated Hospital of Heilongjiang University of Chinese medicine, Harbin, China, and 36 from Huashan Hospital of Fudan University, Shanghai, China. A block randomization sequence stratified by centers will be generated using SAS Version 9.2 software (SAS Institute, Cary, NC, USA), which was performed at the Guangdong Provincial Hospital of Chinese Medicine's Key Unit of Methodology in Clinical Research. The treatment group is treated with TJTX (once a day), ESA (once a day), and oral YNFJ (twice a day). The control group will be treated with PT. Two groups of patients will be treated 5 sessions a week for 4 weeks, and there will be 6-month follow-up. The outcome evaluators will be blinded to patient grouping. The primary outcome will be modified Ashworth scales. The secondary outcome indexes will be the simplified Fugl–Meyer assessment scale, surface electromyogram root mean square value, modified Barthel index, stroke-specific quality of life scale, health scale of traditional Chinese medicine, visual analogue scale (VAS), and the Hamilton depression scale. Discussion: The Randomized Controlled Trial (RCT) mainly aim to evaluate the effectiveness and safety of traditional Chinese medicine rehabilitation program, by comparing the treatment of ZSTX with the PT for the treatment of limb spasm after stroke. Trial registration: Chinese Clinical Trial Registry: ChiCTR 1900024255. Registered on July 3, 2019.
Novel recombinant Mce-truncated protein based ELISA for the diagnosis of Mycobacterium avium subsp. paratuberculosis infection in domestic livestock

Johne’s disease (JD) is an infectious wasting condition of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) in domestic livestock of every country that has been investigated. Controlling JD is problematic due to the lack of sensitive, specific, efficient, and cost-effective diagnostic tests. A major challenge in the development of diagnostics like ELISA is the selection of an ideal antigen/(s) that is pathogen-specific and allows sensitive recognition. Therefore, the purpose of this study was to identify and use Mce-truncated protein-based ELISA assay for the diagnosis of MAP infection with high sensitivity and specificity. In silico epitope prediction by epitope mapping throughout the whole length of MAP2191 protein revealed that C-terminal portion of this protein presented potential T- and B-cell epitopes. Therefore, a novel Mce-truncated protein encoded by the selected region of MAP2191 gene was expressed, purified with Ni-NTA gel matrix and confirmed by SDS PAGE and western blot. A profiling ELISA assay was developed to evaluate sera from MAP infected and non-infected ruminant species for antibodies against Mce-truncated protein to infer the immunogenicity of this protein in the host. Using this Mce protein-based ELISA, 251 goats, 53 sheep, 117 buffaloes, and 33 cattle serum samples were screened and 49.4, 51.0, 69.2, and 54.6% animals, respectively, were found positive. Comparing with i-ELISA, the new Mce-based ELISA kit showed a relatively higher specificity but suffered from slightly reduced sensitivity. Mce-based ELISA excluded apparently false positive results of i-ELISA. Mce protein was found to be antigenic and Mce-ELISA test could be employed as a diagnostic test for JD in domestic livestock in view of the a relatively higher specificity and accuracy. The antigenic potential of Mce antigen can also be exploited for the development of a new vaccine for the control of MAP infection.
Accuracy of blood-pressure monitors owned by patients with hypertension (ACCU-RATE study): a cross-sectional, observational study in central England

Background Home blood-pressure (BP) monitoring is recommended in guidelines and is increasingly popular with patients and health professionals, but the accuracy of patients’ own monitors in real-world use is not known. Aim To assess the accuracy of home BP monitors used by people with hypertension, and to investigate factors affecting accuracy. Design and setting Cross-sectional, observational study in urban and suburban settings in central England. Method Patients (n = 6891) on the hypertension register at seven practices in the West Midlands, England, were surveyed to ascertain whether they owned a BP monitor and wanted it tested. Monitor accuracy was compared with a calibrated reference device at 50 mmHg intervals between 0–280/300 mmHg (static pressure test); a difference from the reference monitor of +/−3 mmHg at any interval was considered a failure. Cuff performance was also assessed. Results were analysed by frequency of use, length of time in service, make and model, monitor validation status, purchase price, and any previous testing. Results In total, 251 (76%, 95% confidence interval [95% CI] = 71 to 80%) of 331 tested devices passed all tests (monitors and cuffs), and 86% (CI] = 82 to 90%) passed the static pressure test; deficiencies were, primarily, because of monitors overestimating BP. A total of 40% of testable monitors were not validated. The pass rate on the static pressure test was greater in validated monitors (96%, 95% CI = 94 to 98%) versus unvalidated monitors (64%, 95% CI = 58 to 69%), those retailing for >£10 (90%, 95% CI = 86 to 94%), those retailing for ≤£10 (66%, 95% CI = 51 to 80%), those in use for ≤4 years (95%, 95% CI = 91 to 98%), and those in use for >4 years (74%, 95% CI = 67 to 82%). All in all, 12% of cuffs failed. Conclusion Patients’ own BP monitor failure rate was similar to that demonstrated in studies performed in professional settings, although cuff failure was more frequent. Clinicians can be confident of the accuracy of patients’ own BP monitors if the devices are validated and ≤4 years old.
Using a citizens’ jury approach to determine a good nutrition resource for pregnant women

Abstract Objective: The development of user-friendly nutrition resources for pregnant women seldom involves end-users. This qualitative study used a citizens’ jury approach to determine if our modification of a longstanding, frequently used dietitian-informed diet and diabetes booklet was deemed to be a good healthy eating resource for pregnant women. Design: Midwives recruited thirteen first-time pregnant women not requiring specialist obstetric care or specialist dietetic advice for any reason. Participants were sent a copy of the modified healthy eating in pregnancy booklet prior to ‘jury day’. Five women were unable to attend the citizens’ jury citing reasons such as early labour. At the jury, five experts presented evidence. Participants adjourned, with an independent facilitator, to ‘deliberate’ as to whether the resource was suitable or not. The verdict was presented, and subsequent discussion was audio-recorded, transcribed and inductively content analysed. Setting: Southland, New Zealand. Participants: Pregnant women aged 19–35 years (n 8), of whom half had a household income <$NZ30 000. Results: The verdict was ‘Yes’; the resource was good. Three themes were derived: communication of health information, resource content and harm reduction in pregnancy. Based on these data, ways to enhance the quality and usability of the booklet were evident. Conclusions: Citizens’ juries can be used to obtain an independent assessment by end-users of health resources. Our modified diet and diabetes booklet was considered suitable for providing healthy eating advice to pregnant women. Inclusion of end-users’ perspectives is critical for end-user relevant content, comprehension and resource credibility.
Predicting COVID-19 Incidence Using Anosmia and Other COVID-19 Symptomatology: Preliminary Analysis Using Google and Twitter

Objective To determine the relative correlations of Twitter and Google Search user trends concerning smell loss with daily coronavirus disease 2019 (COVID-19) incidence in the United States, compared to other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. To describe the effect of mass media communications on Twitter and Google Search user trends. Study Design Retrospective observational study. Setting United States. Subjects and Methods Google Search and “tweet” frequency concerning COVID-19, smell, and nonsmell symptoms of COVID-19 generated between January 1 and April 8, 2020, were collected using Google Trends and Crimson Hexagon, respectively. Spearman coefficients linking each of these user trends to COVID-19 incidence were compared. Correlations obtained after excluding a short timeframe (March 22 to March 24) corresponding to the publication of a widely read lay media publication reporting anosmia as a symptom of infection was performed for comparative analysis. Results Google searches and tweets concerning all nonsmell symptoms (0.744 and 0.761, respectively) and COVID-19 (0.899 and 0.848) are more strongly correlated with disease incidence than smell loss (0.564 and 0.539). Twitter users tweeting about smell loss during the study period were more likely to be female (52%) than users tweeting about COVID-19 more generally (47%). Tweet and Google Search frequency pertaining to smell loss increased significantly (>2.5 standard deviations) following a widely read media publication linking smell loss and SARS-CoV-2 infection. Conclusions Google Search and tweet frequency regarding fever and shortness of breath are more robust indicators of COVID-19 incidence than anosmia. Mass media communications represent important confounders that should be considered in future analyses.
Research on the Ecology of Water Mites (Acari : Hydracarina ) in North-East of Algeria (Wetland Complex of El-Kala National Park)

An analysis of eight physical and chemical parameters was realized to determine the influence of species on the biodiversity of water mites. A total of 292 water mites belonging to 9 species were collected from the two lakes (Tonga and Oubeira), El-mellah lagoon, and Goureate pool from November 2007 to November 2009. Despite this importance, the Hydracarina have not been well investigated or documented in northern Algeria or elsewhere in Africa. To expand current knowledge of the Hydracarina in Algeria, we examined water mites biodiversity and physical and chemical characteristics of mites habitats in 4 locations of the wetland complex in the North-East of Algeria. We found 9 species belonging to 5 families The species dominants (dominance>5%) were Eylais hamata (24%), Piona alpicola (22%), Arrenurus novus (13%), Eylais sp. (12%), Piona nodata (10%), Arrenurus batillifer (10%) and (dominance ˂5%) were Hydrochoreutes intermedius (4.5%), Diplodontus sp. (3.5%), Hydrachna globosa (3.4%) distributed among our sample sites, and were able to determine significant differences in physical and chemical parameters among the sites as
Energy-Optimal Latency-Constrained Application Offloading in Mobile-Edge Computing

Mobile-edge computation offloading (MECO) is a promising emerging technology for battery savings in mobile devices (MD) and/or in latency reduction in the execution of applications by (either total or partial) offloading highly demanding applications from MDs to nearby servers such as base stations. In this paper, we provide an offloading strategy for the joint optimization of the communication and computational resources by considering the blue trade-off between energy consumption and latency. The strategy is formulated as the solution to an optimization problem that minimizes the total energy consumption while satisfying the execution delay limit (or deadline). In the solution, the optimal transmission power and rate and the optimal fraction of the task to be offloaded are analytically derived to meet the optimization objective. We further establish the conditions under which the binary decisions (full-offloading and no offloading) are optimal. We also explore how such system parameters as the latency constraint, task complexity, and local computing power affect the offloading strategy. Finally, the simulation results demonstrate the behavior of the proposed strategy and verify its energy efficiency.
The host range of three biotypes of Dactylopius tomentosus (Lamarck) (Hemiptera: Dactylopiidae) and their potential as biological control agents of Cylindropuntia spp. (Cactaceae) in Australia

The host range of two newly imported biotypes of Dactylopius tomentosus and their potential as biological control agents of Cylindropuntia spp. were investigated. A third biotype (‘imbricata’) of D. tomentosus previously released in Australia to control C. imbricata was also screened to determine if it will feed on other species of Cylindropuntia occurring in Australia. Efficacy trials were conducted to evaluate the ability of the biotypes to retard the growth or kill those plant species supporting development of four or more individuals in the host test trials. The host range of the three biotypes of D. tomentosus was restricted to the genus Cylindropuntia. However, the biotypes showed varying degrees of specificity within this genus. The ‘imbricata’ biotype was the only biotype to develop on Australian C. rosea provenances, albeit with a range of developmental success on all C. rosea provenances tested. The Spanish provenance supported the highest development success followed by Grawin (NSW), Lorne Station (NSW) while the least preferred was the Mexican provenance. The ‘rosea’ and ‘cholla’ biotypes were unsuitable candidates to control C. rosea in Australia. However, the efficacy trials showed that the ‘cholla’ biotype had a high impact on four of the eight naturalised Cylindropuntia species in Australia. This biotype established rapidly and the sustained feeding of one fecund female and her progeny killed potted plants of C. imbricata and C. fulgida at week 18. This biotype has the potential to be an effective agent against C. fulgida, C. imbricata, C. kleiniae and C. tunicata and, as a consequence, an application seeking its release in Australia has been lodged.
NADPH-Independent Inactivation of CYP2B6 and NADPH-Dependent Inactivation of CYP3A4/5 by PBD: Potential Implication for Assessing Covalent Modulators for Time-Dependent Inhibition

Pyrrolo[2,1-c][1,4]benzodiazepine dimer (PBD) has shown broad antitumor properties and potential as a therapeutic agent for cancers. During a routine drug-drug interaction assessment, it was found that PBD is a reversible inhibitor of CYP2C8 (IC50 = 1.1 µM) but not CYP1A2, 2B6, 2C9, 2C19, 2D6, or 3A4/5. Additionally, PBD is a classic time-dependent inhibition (TDI) of CYP3A4/5, with >30-fold shift in IC50 after a preincubation with NADPH. All other CYPs tested did not show evidence for TDI, but potent inhibition of CYP2B6 (IC50 = 1.5 µM) was observed after a preincubation with or without (w/wo) NADPH, which was an unexpected observation given the fact that no inhibition was observed in the direct inhibition assay. No other CYP isoforms were susceptible to this apparent non-NADPH–dependent inhibition, suggesting that PBD may selectively inactivate CYP2B6 without metabolic activation. The washing of the human liver microsome pellet after incubation with PBD did not fully recover CYP2B6 activity, indicating that PBD is covalently bound to CYP2B6, leading to inactivation of the enzyme. To further investigate the mechanism of NADPH-independent inhibition, the IC50 shift was determined for several PBD analogs, and it was found that the compounds without both reactive imines did not show NADPH-independent inhibition of CYP2B6, implying that NADPH-independent inactivation was likely caused by direct covalent binding of PBD to the enzyme in a highly structure-specific manner. These data clearly highlight the need to assess direct and time-dependent inhibition w/wo NADPH to adequately characterize the in vitro CYP inhibitory properties of drug candidates with reactive moieties. SIGNIFICANCE STATEMENT We described a very unique in vitro CYP inhibition profile of pyrrolo[2,1-c][1,4]benzodiazepine dimer as a potent reversible CYP2C8 inhibitor, an NADPH-dependent CYP3A4/5 time-dependent inhibition (TDI) inhibitor, and an NADPH-independent CYP2B6 TDI inhibitor, and inhibition of CYPs occurs through three distinct mechanisms: reversible drug-enzyme binding, enzyme inactivation via bioactivation, and enzyme inactivation by covalent binding via chemical reactions. Our results suggest that, for compounds with reactive functional moieties, false positives can be reported when the conventional TDI assay is utilized.