Miracle-dz/UniFAR-FTUs huggingface dataset:
The association between hyperlipidemia, lipid-lowering drugs and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus

Aims Previous studies showed conflicting relationship between hyperlipidemia, lipid-lowering therapy and diabetic peripheral neuropathy (DPN). As most of these works emerges from the Western and Australian countries, our study aims to investigate whether hyperlipidemia or lipid-lowering therapy (LLT) is associated with DPN in Taiwanese patients with type 2 diabetes (T2D). Methods A cross-sectional, hospital-based observation study in adults with T2D was conducted from January to October 2013. DPN was screened using the Michigan Neuropathy Screening Instrument. Data were obtained at the time of enrollment, including medication usage, anthropometric measurements and laboratory examinations. Results 2,448 participants were enrolled, 524 (21.4%) of whom had DPN. Patients with DPN had significantly lower plasma total cholesterol (185.6 ± 38.6 vs 193.4 ± 42.3 mg/dL) and low-density lipoprotein cholesterol levels (114.6 ± 32.7 vs 119 ± 30.8 mg/dL). Multivariate analysis demonstrated that neither hyperlipidemia (adjusted OR (aOR), 0.81; 95% confidence interval (CI), 0.49–1.34) nor LLT (aOR, 1.10; 95% CI, 0.58–2.09) was associated with DPN. Subgroup analysis revealed that neither total cholesterol (aOR, 0.72; 95% CI, 0.2–2.62), low-density lipoprotein cholesterol levels (aOR, 0.75; 95% CI, 0.2–2.79), statin (aOR, 1.09; 95% CI, 0.59–2.03) nor fibrate (aOR, 1.73; 95% CI, 0.33–1.61) was associated with DPN. Conclusion Our results suggest that neither hyperlipidemia nor lipid-lowering medication was associated with DPN in adults with T2D. DPN is a multifactorial disease, and our findings indicate that lipid metabolism may play a minor role in its pathogenesis.
Deep Hashing Mutual Learning for Brain Network Classification

Recently, clinical phenotypic semantic information has begun to play an important role in some brain network classification methods based on deep learning. However, most current methods only consider the phenotypic semantic information of individual brain networks but ignore the potential phenotypic characteristics among group brain networks. To address this problem, we present a deep hashing mutual learning (DHML)-based brain network classification method. Specifically, we first design a separable CNN-based deep hashing learning to extract individual topological features of brain networks and map them into hash codes. Secondly, we construct a group brain network relationship graph based on the similarity of phenotypic semantic information, in which each node is a brain network, and the properties of the nodes are the individual features extracted in the previous step. Then, we adopt a GCN-based deep hashing learning to extract the group topological features of the brain network and map them to hash codes. Finally, the two deep hashing learning models perform mutual learning by measuring the distribution differences between the hash codes to achieve the interaction of individual and group features. The experimental results on the three commonly used brain atlases (AAL Atlas, Dosenbach160 Atlas, and CC200 Atlas) of the ABIDE I dataset show that our proposed DHML method achieves optimal classification performance compared with some state-of-the-art methods.
Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

Infection with certain cutaneous human papillomaviruses (HPV), in conjunction with chronic ultraviolet (UV) exposure, are the major cofactors of non‐melanoma skin cancer (NMSC), the most frequent cancer type worldwide. Cutaneous squamous cell carcinomas (SCCs) as well as tumors in general represent three‐dimensional entities determined by both temporal and spatial constraints. Whole tissue proteomics is a straightforward approach to understand tumorigenesis in better detail, but studies focusing on different progression states toward a dedifferentiated SCC phenotype on a spatial level are rare. Here, we applied an innovative proteomic workflow on formalin‐fixed, paraffin‐embedded (FFPE) epithelial tumors derived from the preclinical animal model Mastomys coucha. This rodent is naturally infected with its genuine cutaneous papillomavirus and closely mimics skin carcinogenesis in the context of cutaneous HPV infections in humans. We deciphered cellular networks by comparing diverse epithelial tissues with respect to their differentiation level and infection status. Our study reveals novel regulatory proteins and pathways associated with virus‐induced tumor initiation and progression of SCCs. This approach provides the basis to better comprehend the multistep process of skin carcinogenesis.
Time-resolved proteomic analyses of senescence highlight metabolic rewiring of mitochondria

Time-resolved proteomic analyses of senescent fibroblasts reveal that nearly 40% of the analyzed mitochondrial proteome have changed upon induction of senescence. Our study highlights the rewiring of mitochondrial metabolism as a central feature among all changes in mitochondrial pathways of senescent cells. Mitochondrial dysfunction and cellular senescence are hallmarks of aging. However, the relationship between these two phenomena remains incompletely understood. In this study, we investigated the rewiring of mitochondria upon development of the senescent state in human IMR90 fibroblasts. Determining the bioenergetic activities and abundance of mitochondria, we demonstrate that senescent cells accumulate mitochondria with reduced OXPHOS activity, resulting in an overall increase of mitochondrial activities in senescent cells. Time-resolved proteomic analyses revealed extensive reprogramming of the mitochondrial proteome upon senescence development and allowed the identification of metabolic pathways that are rewired with different kinetics upon establishment of the senescent state. Among the early responding pathways, the degradation of branched-chain amino acid was increased, whereas the one carbon folate metabolism was decreased. Late-responding pathways include lipid metabolism and mitochondrial translation. These signatures were confirmed by metabolic flux analyses, highlighting metabolic rewiring as a central feature of mitochondria in cellular senescence. Together, our data provide a comprehensive view on the changes in mitochondrial proteome in senescent cells and reveal how the mitochondrial metabolism is rewired in senescent cells.
Assessment of imidacloprid induced genotoxicity in Pethia conchonius (Rosy barb), a common freshwater fish of India

Abstract Imidacloprid is one of the highly efficient, globally used neonicotinoid groups of insecticides. The indiscriminate use of imidacloprid is contaminating large water bodies affecting not only the target organisms but also non-target organisms including fish. The present study aimed to assess the extent of nuclear DNA damage by imidacloprid in Pethia conchonius a freshwater fish in India using comet and micronucleus assays. The LC50 value of imidacloprid was estimated to be 227.33 mg L−1. Based on the LC50-96 h value, three sub-lethal concentrations of imidacloprid, SLC I −18.94 mg L−1, SLC II −28.41 mg L−1 and SLC III −56.83 mg L−1 were used to detect its genotoxic effect at DNA and cellular level. The imidacloprid exposed fishes exhibited higher DNA damage and nuclear abnormalities (p < 0.05) than the control. The %head DNA, %tail DNA, tail length and the frequency of micronuclei with other nuclear abnormalities like blebbed and notched nuclei were significantly higher than the control in a time and concentration-dependent manner. The DNA damage parameters such as %head DNA (29.107 ± 1.843), %tail DNA (70.893 ± 1.843), tail length (361.431 ± 8.455) micronucleus (1.300 ± 0.019), notched (0.844 ± 0.011) and blebbed (0.811 ± 0.011) nuclei were found to be highest for SLC III (56.83 mg L−1) at 96 h. The findings indicate that IMI is highly genotoxic in fish and other vertebrates leading to mutagenic/clastogenic effects. The study will be helpful in optimization of the imidacloprid use.
Autophagy prevents early proinflammatory responses and neutrophil recruitment during Mycobacterium tuberculosis infection without affecting pathogen burden in macrophages

The immune response to Mycobacterium tuberculosis infection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models during M. tuberculosis infection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival during M. tuberculosis infection; however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment during M. tuberculosis infection, we used different mouse strains that conditionally delete Atg5 in specific cell types. We found that ATG5 is required in CD11c+ cells (lung macrophages and dendritic cells) to control the production of proinflammatory cytokines and chemokines during M. tuberculosis infection, which would otherwise promote neutrophil recruitment. This role for ATG5 is autophagy dependent, but independent of mitophagy, LC3-associated phagocytosis, and inflammasome activation, which are the most well-characterized ways that autophagy proteins regulate inflammation. In addition to the increased proinflammatory cytokine production from macrophages during M. tuberculosis infection, loss of ATG5 in innate immune cells also results in an early induction of TH17 responses. Despite prior published in vitro cell culture experiments supporting a role for autophagy in controlling M. tuberculosis replication in macrophages, the effects of autophagy on inflammatory responses occur without changes in M. tuberculosis burden in macrophages. These findings reveal new roles for autophagy proteins in lung resident macrophages and dendritic cells that are required to suppress inflammatory responses that are associated with poor control of M. tuberculosis infection.
Nonsymmetric coupling of boundary elements and ultraweak finite elements and DPG method with optimal test functions

We propose and analyze a numerical method to solve an elliptic transmission problem in full space. The method consists of a variational formulation involving standard boundary integral operators on the coupling interface and an ultraweak finite element formulation on the interior. To be precise, it is a nonsymmetric coupling as developed in [3], but with an ultraweak finite element part as used in [2]. To guarantee the discrete inf-sup condition, we discretize the whole system with optimal test functions. In this way, we obtain quasi-optimality of the method in the so-called energy norm. In order to relate the energy norm to usual Sobolev norms, we use recent results regarding the nonsymmetric coupling of finite elements and boundary elements on polygonal interfaces, cf. [1,4].
MEDICAL AND SOCIAL ANALYSIS OF PATIENTS WHO DIED OF SARS-COV-2 IN THE SPECIALIZED INFECTIOUS DEPARTMENT OF THE CITY OF SUMY DURING THE FIRST WAVE OF THE EPIDEMIC.

OBJECTIVE The aim of the article is to analyze demographic indicators, clinical symptoms, concomitant pathology, and the course of acute respiratory viral infection (ARVI) caused by SARS-CoV-2 in patients with a fatal outcome of the disease. PATIENTS AND METHODS Materials and methods: To achieve the goal, a statistical method, an analytical method, and a method of retrospective analysis of the medical histories of patients with fatal cases who were hospitalized with a diagnosis of ARVI caused by SARS-CoV-2 were used. RESULTS Results: Mortality among patients who were hospitalized with a diagnosis of ARVI caused by SARS-CoV-2 was 8.18 ± 2.17%. Among them, 62% were male and 38% were female. Cardiovascular pathology took first place in the structure of concomitant pathology of all age groups and accounted for 76%. Oncological diseases accounted for 62%, gastrointestinal diseases - 54%, endocrine diseases - 38%, and respiratory system diseases 23% of the total number of patients with fatal cases. CONCLUSION Conclusions: Mortality from coronavirus infection in the period March - July 2020 among the male population was 62%, of which 13% - from the age group 18-45 years, 38% - from the age group 46-64 years, and 50% - patients 65 years old and older. Among the female population, the mortality rate was 38%, of which 20% were women in the age group 46-64% and 80% were 65 years and older. The presence of no-hospital polysegmental pneumonia as a complication of ARVI caused by SARS-CoV-2 was 62% among all age groups of the studied patients with fatal cases.
The Detection of Acute Risk of Self-injury Project: Protocol for an Ecological Momentary Assessment Study Among Individuals Seeking Treatment

Background Nonsuicidal self-injury (NSSI) is a major mental health concern. Despite increased research efforts on establishing the prevalence and correlates of the presence and severity of NSSI, we still lack basic knowledge of the course, predictors, and relationship of NSSI with other self-damaging behaviors in daily life. Such information will be helpful for better informing mental health professionals and allocating treatment resources. The DAILY (Detection of Acute rIsk of seLf-injurY) project will address these gaps among individuals seeking treatment. Objective This protocol paper presents the DAILY project’s aims, design, and materials used. The primary objectives are to advance understanding of (1) the short-term course and contexts of elevated risk for NSSI thoughts, urges, and behavior; (2) the transition from NSSI thoughts and urges to NSSI behavior; and (3) the association of NSSI with disordered eating, substance use, and suicidal thoughts and behaviors. A secondary aim is to evaluate the perspectives of individuals seeking treatment and mental health professionals regarding the feasibility, scope, and utility of digital self-monitoring and interventions that target NSSI in daily life. Methods The DAILY project is funded by the Research Foundation Flanders (Belgium). Data collection involves 3 phases: a baseline assessment (phase 1), 28 days of ecological momentary assessment (EMA) followed by a clinical session and feedback survey (phase 2), and 2 follow-up surveys and an optional interview (phase 3). The EMA protocol consists of regular EMA surveys (6 times per day), additional burst EMA surveys spaced at a higher frequency when experiencing intense NSSI urges (3 surveys within 30 minutes), and event registrations of NSSI behavior. The primary outcomes are NSSI thoughts, NSSI urges, self-efficacy to resist NSSI, and NSSI behavior, with disordered eating (restrictive eating, binge eating, and purging), substance use (binge drinking and smoking cannabis), and suicidal thoughts and behaviors surveyed as secondary outcomes. The assessed predictors include emotions, cognitions, contextual information, and social appraisals. Results We will recruit approximately 120 individuals seeking treatment aged 15 to 39 years from mental health services across the Flanders region of Belgium. Recruitment began in June 2021 and data collection is anticipated to conclude in August 2023. Conclusions The findings of the DAILY project will provide a detailed characterization of the short-term course and patterns of risk for NSSI and advance understanding of how, why, and when NSSI and other self-damaging behaviors unfold among individuals seeking treatment. This will inform clinical practice and provide the scientific building blocks for novel intervention approaches outside of the therapy room that support people who self-injure in real time. International Registered Report Identifier (IRRID) DERR1-10.2196/46244
Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index

Background CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). Objective This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. Methods Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. Results The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02, .03 respectively). The frequency of genotype “aa” and its “a” allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the “AA” and: aa” genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). Conclusions According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management.
Stability of polymeric cationic niosomes and their plasmid DNA-based complexes as gene delivery carriers

Abstract This study aims to explore the stability of lipo-polymeric niosomes/niosome-based pCMS-EGFP complexes under different storage temperatures (25 °C, 4 °C, and −20 °C). To date, the question of nucleic acid-complex stability is one of the most vital issues in gene delivery applications. The need for stable vaccines during the COVID-19 pandemic has merely highlighted it. In the case of niosomes as gene carriers, the scientific literature still lacks comprehensive stability studies. In this study, the physicochemical features of niosomes/nioplexes in terms of size, surface charge, and polydispersity index (PDI), along with transfection efficiency, and cytotoxicity in NT2 cells were evaluated for 8 weeks. Compared to day 0, the physicochemical features of the niosomes stored at 25 °C and −20 °C changed dramatically in terms of size, zeta potential, and PDI, while remaining in reasonable values when stored at 4 °C. However, niosomes and nioplexes stored at 4 °C and −20 °C showed nearly stable transfection efficiency values, yet an obvious decrease at 25 °C. This article provides a proof of concept into the stability of polymeric cationic niosomes and their nioplexes as promising gene delivery vehicles. Moreover, it highlights the practical possibility of storing nioplexes at 4 °C for up to 2 months, as an alternative to niosomes, for gene delivery purposes. Graphical Abstract
Effect of flanged diffuser divergence angle on wind turbine: A numerical investigation

Power augmentation in a small-scale horizontal axis wind turbine, with its rotor encased in a flanged diffuser is explored. The power output of the wind turbine varies with changes in the diffuser design and the resulting back pressure. Reduction in this back pressure also results in early flow separation at the diffuser surface, which hinders turbine performance. The main aim of this study is to numerically investigate the local configuration of the wind turbine location inside the diffuser by varying diffuser angles and wind speeds. Therefore, shroud and flange were modeled and analyzed using the computational fluid dynamic (CFD) analyses and experiments were performed at two wind speeds 6 m/s and 8 m/s with and without the diffuser for model validation. The divergence angle of 4° was found to have no flow separation, thus maximizing flow rate. The proposed design shows wind speed improvement of up to 1.68 times compared to the baseline configuration. The corresponding optimum flange height was found to be 250 mm. However, increasing the divergence angle had a similar output. The dimensionless location of wind turbine was found to be between 0.45 and 0.5 for 2° and 4° divergence angle respectively. Furthermore, the maximum augmentation location varies with wind speed and diffuser’s divergence angle as described by dimensionless location of wind turbine, thus presenting a noteworthy contribution to the horizontal axis wind turbine area with the flanged diffuser.
The influence of social support, social affiliation and intrinsic motivation for increasing underserved youth’s physical activity: A social climate-based intervention study

ABSTRACT The purpose of this study was to investigate the influences of intrinsic motivation, social affiliation orientations and reciprocal social support for physical activity (PA) on underserved youths’ afterschool period moderate-to-vigorous (MVPA) changing trajectories across the 16-week Connect through PLAY intervention, a social-motivational climate intervention. A total of 113 youth (61.06% African American, 56.64% girls) provided full data. Youths’ intrinsic motivation, social affiliation orientations and social support were measured by youth responses to a set of surveys at baseline and post-intervention. Youths’ afterschool period MVPA was measured using data from 7-day ActiGraph accelerometer wear at baseline, midpoint and post-intervention. Hierarchical linear modelling analysis found that youth daily afterschool period (3pm−6pm) MVPA increased, on average, 37.94 min across the 16-week intervention. Increases in intrinsic motivation, social affiliation orientations and social support were positive predictors of youth afterschool MVPA changing trajectory. The findings clarify the contributions that a social-motivational climate intervention can have on youth afterschool period MVPA through increasing youth intrinsic motivation, social affiliation and reciprocal social support.