Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations between continuous glucose monitoring-derived metrics and diabetic retinopathy and albuminuria in patients with type 2 diabetes

Introduction Preventing the development and progression of diabetic microvascular complications through optimal blood glucose control remains an important challenge. Whether metrics based on continuous glucose monitoring are useful for the management of diabetic microvascular complications is not entirely clear. Research design and methods This is an exploratory analysis of an ongoing prospective, multicenter, 5-year follow-up observational study. Study participants included 999 outpatients with type 2 diabetes who underwent continuous glucose monitoring at baseline. Associations between continuous glucose monitoring-derived metrics and the severity of diabetic retinopathy or albuminuria were investigated using multivariable proportional odds models. Results The overall prevalence of diabetic retinopathy was 22.2%. Multivariate analysis with proportional odds models demonstrated that continuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy, even after adjusting for various possible risk factors. However, significant relationships were not observed after adjusting for hemoglobin A1c (HbA1c) levels. The prevalence of microalbuminuria and macroalbuminuria was 20.3% and 6.7%, respectively. Similarly, multivariate analysis demonstrated that those metrics are significantly associated with the severity of albuminuria. These relationships remained significant even after further adjusting for HbA1c levels. Conclusions Continuous glucose monitoring-derived metrics related to intraday and interday glucose variability are significantly associated with the severity of diabetic retinopathy or albuminuria in patients with type 2 diabetes. Thus, evaluating these metrics might possibly be useful for risk assessment of diabetic microvascular complications. Trial registration number UMIN000032325.
Extracellular histones are a target in myocardial ischaemia–reperfusion injury

Abstract Aims Acute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). Histones have been described as important Danger Associated Molecular Proteins (DAMPs) in sepsis. The objective of this study was to establish whether extracellular histone release contributes to myocardial infarction. Methods and results Isolated, perfused rat hearts were subject to I/R. Nucleosomes and histone-H4 release was detected early during reperfusion. Sodium-β-O-Methyl cellobioside sulfate (mCBS), a newly developed histone-neutralizing compound, significantly reduced infarct size whilst also reducing the detectable levels of histones. Histones were directly toxic to primary adult rat cardiomyocytes in vitro. This was prevented by mCBS or HIPe, a recently described, histone-H4 neutralizing peptide, but not by an inhibitor of TLR4, a receptor previously reported to be involved in DAMP-mediated cytotoxicity. Furthermore, TLR4-reporter HEK293 cells revealed that cytotoxicity of histone H4 was independent of TLR4 and NF-κB. In an in vivo rat model of I/R, HIPe significantly reduced infarct size. Conclusion Histones released from the myocardium are cytotoxic to cardiomyocytes, via a TLR4-independent mechanism. The targeting of extracellular histones provides a novel opportunity to limit cardiomyocyte death during I/R injury of the myocardium.
Nucleoprotein‐enriched diet enhances protein synthesis pathway and satellite cell activation via ERK1/2 phosphorylation in unloaded rat muscles

What is the central question of this study? The purpose of this study was to determine whether the nucleotides in a nucleoprotein‐enriched diet could ameliorate the unloading‐associated decrease in soleus muscle mass and fibre size. What is the main finding and its importance? The results indicate that the nucleotides in the nucleoprotein‐enriched diet could ameliorate the unloading‐associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy.
Asymmetric Autoamplification in the Oxidative Kinetic Resolution of Secondary Benzylic Alcohols Catalyzed by Manganese Complexes

Herein, chiral Mn–aminopyridine complexes have been shown to catalyze the oxidation of alkylarenes to enantiomerically enriched 1‐arylalkanols with hydrogen peroxide. The observed enantiomeric excess values result from the direct enantioselective benzylic C−H hydroxylation, accompanied by stereoconvergent oxidative kinetic resolution of the resulting alcohol. Testing several (S,S)‐bipyrrolidine derived Mn complexes has revealed a novel catalyst (6) that exhibits the best kinetic resolution in the series (krel up to 8.8), along with sufficient reactivity and efficiency (>1000 catalytic turnovers). The mechanistic study of the Mn‐mediated alcohol oxidation witnesses electrophilic active species (ρ=−1.2), with rate‐limiting H abstraction (kH/kD=2.2), followed by oxygen rebound and dehydration of the resulting gem‐diol to form the ketone. Intriguingly, while for the resolution of the relatively bulky 1,2‐diphenylethanol, krel is virtually constant throughout the reaction, for less bulky alcohols, krel increases with increasing conversion, in line with the rising optical purity of the 1‐arylalkanol. The latter participates in the oxidation as an auxiliary ligand, assisting the chiral recognition. This effect is related to the previously described asymmetric autocatalysis and asymmetric autoinduction, but is not identical with either of those, with the differences being discussed. To unambiguously identify this effect, the term asymmetric autoamplification (chiral autoamplification) is proposed.
Silicene/ZnI2 van der Waals heterostructure: tunable structural and electronic properties

By utilizing ab initio density functional theory, the structural and electronic properties of novel silicene/ZnI2 heterobilayers (HBLs) were investigated. Constructing HBLs with ZnI2 in different stacking configurations leads to direct bandgap opening of silicene at K point, which ranges from 138.2 to 201.2 meV. By analyzing the projected density of states and charge density distribution, we found that the predicted HBLs conserve the electronic properties of silicene and ZnI2 can serve as a decent substrate. The tunability of electronic properties can be achieved by enforcing biaxial strain and by varying interlayer distance where bandgap can get as low as zero to as high as 318.8 meV and 290.7 meV, respectively depending on the stacking patterns. Maintenance of the remarkable features of silicene, high mobility of charge carriers, and fine-tuning of bandgap pave the way to construct new nanoelectronic devices using these novel silicene/ZnI2 HBLs.
Distortions to the passage of time during England’s second national lockdown: A role for depression

In attempts to control the spread of the Covid-19 virus, many governments have resorted to imposing national lockdowns on their citizens. Previous research has demonstrated the passage of time becomes distorted for many people during these lockdowns. To date, research has only examined how time was experienced early in initial lockdowns. The current study examined whether distortions to the passage of time were also present later into the global pandemic. An online questionnaire was used to collect passage of time judgments for the day, week and 8 month period since the first UK lockdown. In addition, measures of affect, social satisfaction, task-load, compliance and health status were also recorded. The results show that over 80% of people reported experiencing distortion to the passage of time during the second English lockdown in comparison with normal. Depression, satisfaction with social interaction and shielding status were found to be significant predictors of temporal distortion. A slower passage of time was associated with greater depression, shielding and greater dissatisfaction with social interactions. Feeling like it was longer than 8 months since the UK’s first lockdown was associated with greater depression, increased dissatisfaction with social interaction and greater change of life as a result of lockdown. The results suggest that distortions to the passage of time are an enduring feature of lockdown life and that different factors predict temporal experience during different points in lockdown.
Parents’ Attitudes Toward School Students’ Overuse of Smartphones and Its Detrimental Health Impacts: Qualitative Study

Background Parents’ awareness of the risks of the overuse of smartphones (SPs) among their children and parents’ attitudes toward this societal phenomenon are crucial factors to consider when investigating the causes and effects of, as well as interventions to control, this public health issue. Objective This study aimed to explore the awareness and attitudes of parents regarding SP overuse among their children and the detrimental impacts associated with it. Methods The qualitative method of semistructured face-to-face interviews was used to collect data from fathers and mothers of children aged 6-18 years from all 6 educational/governorate regions in the governmental sector in Kuwait. Results A total of 120 parents agreed to participate in the study; there were more female (75/120, 62.5%) than male (45/120, 37.5%) respondents. Almost all of the participants (118/120, 98.3%) were aware that the overuse of SPs could lead to their children becoming addicted to the devices; they were also aware that there could be side effects on their children’s health (117/120, 97.5%). Although the participants, mostly the mothers, supervised their children’s use of SPs closely (106/120, 88.3%), the majority could not control their children’s length of time using SPs, as the children considered this a deprivation of their rights. Eye-related problems, headaches, and anger were the most common side effects experienced by the children. Conclusions Although the parents were aware of the detrimental impacts of SP overuse, the majority could not control the length of time their children spent using the devices. It was found that strong social bonds among family members play a large role in controlling the use of SPs. A number of solutions for families and the government to combat the overuse of SPs are suggested.
Estimating COVID-19 cases in Makkah region of Saudi Arabia: Space-time ARIMA modeling

The novel coronavirus COVID-19 is spreading across the globe. By 30 Sep 2020, the World Health Organization (WHO) announced that the number of cases worldwide had reached 34 million with more than one million deaths. The Kingdom of Saudi Arabia (KSA) registered the first case of COVID-19 on 2 Mar 2020. Since then, the number of infections has been increasing gradually on a daily basis. On 20 Sep 2020, the KSA reported 334,605 cases, with 319,154 recoveries and 4,768 deaths. The KSA has taken several measures to control the spread of COVID-19, especially during the Umrah and Hajj events of 1441, including stopping Umrah and performing this year’s Hajj in reduced numbers from within the Kingdom, and imposing a curfew on the cities of the Kingdom from 23 Mar to 28 May 2020. In this article, two statistical models were used to measure the impact of the curfew on the spread of COVID-19 in KSA. The two models are Autoregressive Integrated Moving Average (ARIMA) model and Spatial Time-Autoregressive Integrated Moving Average (STARIMA) model. We used the data obtained from 31 May to 11 October 2020 to assess the model of STARIMA for the COVID-19 confirmation cases in (Makkah, Jeddah, and Taif) in KSA. The results show that STARIMA models are more reliable in forecasting future epidemics of COVID-19 than ARIMA models. We demonstrated the preference of STARIMA models over ARIMA models during the period in which the curfew was lifted.
Maternal exposure to low doses of bisphenol A affects learning and memory in male rat offspring with abnormal N-methyl-d-aspartate receptors in the hippocampus

Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to induce learning and memory deficits. However, the mechanisms have not been fully elucidated. Growing evidence has suggested that N-methyl-d-aspartate receptors (NMDARs) are involved in cognitive impairments. In this study, BPA was administered to female Sprague–Dawley rats (six per dose group) at concentrations of 0 (control), 4, 40, and 400 μg/kg·body weight/day from gestation day 1 through lactation day 21. Spatial learning was evaluated using the Morris water maze on postnatal day 22. Expression levels of NMDARs were determined using real-time polymerase chain reaction and Western blot. The results showed that male offspring exposed to BPA exhibited increased latency in reaching the platform and reduced time in the target quadrant, and the number of crossing the platform was less, as compared with the control group. The mRNA and protein expression levels of NMDARs in the hippocampus were significantly downregulated when compared with the control group of male offspring. The data showed that maternal exposure to BPA at low dosage can cause cognitive deficits in male rat offspring, probably due to a decrease in NMDARs in the hippocampus.
Antioxidant‐modulated cytotoxicity of silver nanoparticles

The properties of silver nanoparticles (AgNPs) synthesized using compounds exhibiting biological activity seem to constitute an interesting issue worthy of examination. In these studies, two types of AgNPs were synthesized by a chemical reduction method using well‐known antioxidants: gallic acid (GA) and ascorbic acid (AA). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the AgNPs were spherical. The average size was equal to 26 ± 6 nm and 20 ± 7 nm in the case of ascorbic acid‐silver nanoparticles (AAgNPs) and gallic acid‐silver nanoparticles (GAAgNPs), respectively. Surface‐enhanced Raman spectroscopy (SERS) confirmed that the AgNPs were not stabilized by pure forms of applied antioxidants. Changes in mitochondrial activity and secretion of inflammatory and apoptosis mediators after the exposure of human promyelocytic (HL‐60) and histiocytic lymphoma (U‐937) cells to the AgNPs were studied to determine the impact of stabilizing layers on nanoparticle toxicity. The GAAgNPs were found to be more toxic for the cells than the AAgNPs. Their toxicity was manifested by a strong reduction in mitochondrial activity and induction of the secretion of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and caspase‐9. The addition of pure antioxidants to the AgNP suspensions was found to influence their toxicity. There was a significant positive effect in the case of the mixture of AA with AAgNPs and GA with GAAgNPs. The results obtained suggest that the presence of stabilizing agents adsorbed on the surface of AgNPs is the main factor in shaping their toxicity. Nevertheless, the toxic effect can be also tuned by the introduction of free antioxidant molecules to the AgNP suspensions.
Anti-inflammatory chemoprevention attenuates the phenotype in a mouse model of esophageal adenocarcinoma.

Barrett´s Esophagus (BE) is the main known precursor condition of Esophageal Adenocarcinoma (EAC). BE is defined by the presence of metaplasia above the normal squamous columnar junction and has mainly been attributed to gastroesophageal reflux disease (GERD) and chronic reflux esophagitis. Thus, the rising incidence of EAC in the Western world is likely mediated by chronic esophageal inflammation, secondary to GERD in combination with environmental risk factors such as a Western diet and obesity. However, (at present) risk prediction tools and endoscopic surveillance have shown limited effectiveness. Chemoprevention as an adjunctive approach remains an attractive option to reduce the incidence of neoplastic disease. Here, we investigate the feasibility of chemopreventive approaches in BE and EAC via inhibition of inflammatory signaling in a transgenic mouse model of BE and EAC (L2-IL1B mice), with accelerated tumor formation on a high fat diet (HFD). L2-IL1B mice were treated with the IL-1 receptor antagonist Anakinra and the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin or Sulindac. Interleukin-1b antagonism reduced tumor progression in L2-IL1B mice with or without a HFD, while both NSAIDs were effective chemoprevention agents in the accelerated HFD fed L2-IL1B mouse model. Sulindac treatment also resulted in a marked change in the immune profile of L2-IL-1B mice. In summary, anti-inflammatory treatment of HFD-treated L2-IL1B mice acted protectively on disease progression. These results from a mouse model of BE support results from clinical trials that suggest that anti-inflammatory medication may be effective in the chemoprevention of EAC.
Body Composition Changes in Children during Treatment for Moderate Acute Malnutrition: Findings from a 4-Arm Cluster-Randomized Trial in Sierra Leone

ABSTRACT Background Measures that better describe “healthy” and sustainable recovery during nutritional treatment of children with moderate acute malnutrition (MAM) are needed. Objectives We compared changes to body composition among children receiving 1 of 4 specialized nutritious food (SNFs) during treatment of MAM and by recovery and relapse outcomes. Methods The study was nested within a prospective, cluster-randomized, community-based, cost-effectiveness trial assessing 4 SNFs to treat children aged 6–59 mo with MAM [midupper arm circumference (MUAC) ≥11.5 cm and <12.5 cm without bipedal edema] in Sierra Leone. Biweekly SNF rations (1 of 3 fortified-blended foods or a lipid-based nutrient supplement) were given until children recovered (MUAC ≥12.5 cm), or up to 7 rations (∼12 wk). Deuterium dilution was used to estimate fat-free mass (FFM) and fat mass (FM) at enrollment and after 4 wk of treatment to ensure similar treatment exposure among the participants. Another MUAC measurement was performed among recovered children 4 wk after program exit to determine whether recovery was sustained. ANOVA, paired t tests, and linear regression models were used to determine significant differences in changes from baseline to 4 wk. Results Among 312 analyzed participants, mean baseline weight comprised ∼80% FFM; mean weight gained after 4 wk comprised ∼82% FFM. Changes in FM and FFM among 4 SNFs were similar. Children who recovered gained more weight (241%), FFM (179%), and weight-for-height z score (0.44 compared with 0) compared with those who did not recover; sustainers gained 150% more weight. FM gains were positive among recovered children and sustainers, as well as negative among those who did not recover or sustain recovery, but not significantly different. Conclusions Four SNFs had similar effects on body composition in children after 4 wk of treatment for MAM, showing a healthy pattern of weight gain, the majority being FFM. Differential responses to treatment underscore a need for further research to provide targets for healthy, sustainable recovery. This trial was registered at clinicaltrials.gov as NCT03146897.
Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila

Reduced activity of the insulin/IGF signalling network increases health during ageing in multiple species. Diverse and tissue-specific mechanisms drive the health improvement. Here, we performed tissue-specific transcriptional and proteomic profiling of long-lived Drosophila dilp2-3,5 mutants, and identified tissue-specific regulation of >3600 transcripts and >3700 proteins. Most expression changes were regulated post-transcriptionally in the fat body, and only in mutants infected with the endosymbiotic bacteria, Wolbachia pipientis, which increases their lifespan. Bioinformatic analysis identified reduced co-translational ER targeting of secreted and membrane-associated proteins and increased DNA damage/repair response proteins. Accordingly, age-related DNA damage and genome instability were lower in fat body of the mutant, and overexpression of a minichromosome maintenance protein subunit extended lifespan. Proteins involved in carbohydrate metabolism showed altered expression in the mutant intestine, and gut-specific overexpression of a lysosomal mannosidase increased autophagy, gut homeostasis, and lifespan. These processes are candidates for combatting ageing-related decline in other organisms.
Deep-learning based repurposing of FDA-approved drugs against Candida albicans dihydrofolate reductase and molecular dynamics study

Abstract Candida albicans causes the fatal fungal bloodstream infection in humans called Candidiasis. Most of the Candida species are resistant to the antifungals used to treat them. Drug-resistant C. albicans poses very serious public health issues. To overcome this, the development of effective drugs with novel mechanism(s) of action is requisite. Drug repurposing is considered a viable alternative approach to overcome the above issue. In the present study, we have attempted to identify drugs that could target the essential enzyme, dihydrofolate reductase of C. albicans (CaDHFR) to find out potent and selective antifungal antifolates. FDA-approved-drug-library from the Selleck database containing 1930 drugs was screened against CaDHFR using deep-learning, molecular docking, X-score and similarity search methods. The screened compounds showing better binding with CaDHFR were subjected to molecular dynamics simulation (MDS). The results of post-MDS analysis like RMSD, RMSF, RG, SASA, the number of hydrogen bonds and PCA suggest that Paritaprevir, Lumacaftor and Rifampin can make good interaction with CaDHFR. Furthermore, analysis of binding free energy corroborated the stability of interactions as they had binding energy of −114.91 kJ mol−1, −79.22 kJ mol−1 and −78.52 kJ mol−1 for Paritaprevir, Lumacaftor and Rifampin respectively as compared to the reference (−63.10 kJ mol−1). From the results, we conclude that these drugs have great potential to inhibit CaDHFR and would add to the drug discovery against candidiasis, and hence these drugs for repurposing should be explored further. Graphical Abstract Communicated by Ramaswamy H. Sarma
ACE2, TMPRSS2, and L-SIGN Expression in Placentae From HIV-Positive Pregnancies Exposed to Antiretroviral Therapy—Implications for SARS-CoV-2 Placental Infection

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding receptor ACE2 and the spike protein priming protease TMPRSS2 are coexpressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART). Methods We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2, and L-SIGN by quantitative polymerase chain reaction in 105 placentae: 45 from pregnant women with HIV (WHIV) on protease inhibitor (PI)-based ART, 17 from WHIV on non-PI–based ART, and 43 from HIV-uninfected women. Results ACE2 levels were lower, while L-SIGN levels were higher, in placentae from WHIV on PI-based ART compared to those on non-PI–based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses. Conclusions We identified pregnant women of black race and WHIV on PI-based ART to have relatively lower expression of placental ACE2 than those of white race and HIV-uninfected women. This may potentially contribute to altered susceptibility to COVID-19 in these women, favorably by reduced viral entry or detrimentally by loss of ACE2 protection against hyperinflammation.