Miracle-dz/UniFAR-FTUs huggingface dataset:
GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β cell regeneration

GLP-1 receptor agonists, widely used to treat diabetes, are converted to human β cell regenerative drugs by adding a DYRK1A inhibitor. Best buddies for β cells Regeneration of insulin-producing pancreatic β cells is a key therapeutic strategy for diabetes. Previous efforts to stimulate β cell proliferation through combined inhibition of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) and TGFβ/SMAD signaling have had restricted clinical development due to their combined action on human cell types other than β cells. Ackeifi et al. show that glucagon-like peptide-1 receptor agonists partner with DYRK1A inhibitors to stimulate proliferation of functional β cells in cadaveric human pancreatic islets, with a relatively β cell–specific effect. Streptozocin-induced diabetic mice transplanted with human islets showed improved insulin secretion and glycemic control after in vivo combination treatment. Glucagon-like peptide-1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 inhibitors are widely prescribed diabetes drugs due to their ability to stimulate insulin secretion from remaining β cells and to reduce caloric intake. Unfortunately, they fail to increase human β cell proliferation. Small-molecule inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) are able to induce adult human β cell proliferation, but rates are modest (~2%), and their specificity to β cells is limited. Here, we provide evidence that combining any member of the GLP1R agonist class with any member of the DYRK1A inhibitor class induces a synergistic increase in human β cell replication (5 to 6%) accompanied by an actual increase in numbers of human β cells. GLP1R agonist–DYRK1A inhibitor synergy required combined inhibition of DYRK1A and an increase in cAMP and did not lead to β cell dedifferentiation. These beneficial effects on proliferation were seen in both normal human β cells and β cells derived from individuals with type 2 diabetes. The ability of the GLP1R agonist–DYRK1A inhibitor combination to enhance human β cell proliferation, human insulin secretion, and blood glucose control extended in vivo to studies of human islets transplanted into euglycemic and streptozotocin-diabetic immunodeficient mice. No adverse events were observed in the mouse studies during a 1-week period. Because of the relative β cell specificity of GLP1R agonists, the combination provides an improved, although not complete, degree of human β cell specificity.
Effects of whole body vibration training combined with blood flow restriction on muscle adaptation

Abstract This study investigated the effects of whole body vibration (WBV) training combined with blood flow restriction (BFR) on muscle fitness. Twenty physically inactive adults were randomly assigned to a WBV + BFR group (8 men and 2 women) and a WBV group (8 men and 2 women). The participants in the WBV group were subjected to 10 sets of intermittent WBV exercise 20 min/day, 3 days/week, for 8 weeks. The participants in the WBV + BFR group received the same WBV treatment, but the proximal portion of their thighs was compressed using inflatable cuffs. Dual-energy X-ray absorptiometry estimated thigh muscle mass, one repetition maximal (1RM) leg press, and muscle endurance were measured before and after the training programme. The results indicated that thigh muscle mass significantly increased (3%) after the 8-week training period only in the WBV + BFR group. Meanwhile, 1RM leg press and muscle endurance significantly increased in both groups after training (p < 0.05). Analysis of covariance revealed that the increase in 1RM leg press and muscle endurance was significantly higher (p < 0.05) in the WBV + BFR group than the WBV group (leg press: 11.1%. vs. 4.37%; muscle endurance: 48.84% vs. 15.19%, respectively). In conclusion, exposure to regular WBV + BFR training can increase thigh muscle mass, maximal strength, and muscle endurance compared with exposure to WBV training alone. WBV + BFR training appears to be a feasible strategy for improving muscle mass, strength, and endurance in previously untrained participants.
Personality Factors and Sick Leave Days. Evidence from a Nationally Representative Longitudinal Study in Germany.

Background: The question of whether employees’ sickness absence from the workplace depends on personality has been researched. Existing evidence mostly stems from cross-sectional studies, mainly showing that personality factors were not associated with the number of sick leave days, except for neuroticism, which was positively associated with sick leave days. Based on the above, it remains an under researched question whether intraindividual changes in personality factors are associated with changes in sick leave days. Thus, based on a nationally representative sample, the current study aimed to investigate the relationship between personality factors and sick leave days longitudinally based on a nationally representative sample of individuals in Germany. Methods: The present study used data from the German Socio-Economic Panel (GSOEP), a longitudinal survey of private households in Germany. Information from the years 2005, 2009, 2013 were used. The Big Five Inventory-GSOEP (BFI-S) was used to measure personality. Sick leave days in the preceding year were recorded. Poisson fixed effects regressions were used. Results: Adjusting for potential confounders, regressions showed that increases in neuroticism were associated with increased sick leave days. The longitudinal association between extraversion and sick leave days was marginally significant (p < 0.10). Other personality factors were not significantly associated with sick leave days. In addition, sick leave days increased with worsening self-rated health, presence of severe disability and increasing age. Conclusions: The findings of the current study highlight the association between neuroticism and sick leave days longitudinally. Further research is required to elucidate the underlying mechanisms.
Association Between Body Mass Index and Dental Caries in a Turkish Subpopulation of Adults: A Cross-Sectional Study.

PURPOSE To evaluate the relationship between decayed, missing and filled teeth (DMFT index) and body mass index (BMI) in a Turkish population of adults aged 20-30 years who did not have any chronic diseases. MATERIALS AND METHODS This study was conducted on a total of 394 patients. DMFT index was used to define the number of teeth with decays, teeth with fillings, and missing teeth. The body weight and height of the study participants were measured with a digital scale and height rod. BMI was calculated by dividing the body weight by the square root of the height. One-way analysis of variance (ANOVA) and Bonferroni tests were used to compare three or more groups and to compare two groups, respectively. The statistical significance level was evaluated at p < 0.05. RESULTS Differences in DMFT index among BMI groups was found to be statistically significant (p = 0.001; p < 0.01). DMFT index was significantly higher in the obese group than in the normal-weight group (p = 0.001) and overweight group (p = 0.001). No statistically significant differences were found between DMFT indices of study participants of normal weight and those who were overweight (p > 0.05). CONCLUSION Positive correlation was observed between obesity and DMFT index. Coadministration of obesity prevention programmes and preventive oral health programmes can improve public health to a better point.
High rates of fat oxidation are maintained after the sleep low approach despite delayed carbohydrate feeding during exercise

Abstract Training with low carbohydrate availability enhances endurance training adaptations but training volume may be compromised. We explored whole-body metabolism and performance with delayed carbohydrate feeding during exercise undertaken following acute sleep-low training. We hypothesised this strategy would not suppress fat oxidation and would maintain exercise performance. The study involved three experimental trials and included 9 men and 1 woman (⩒O2peak = 58.8 ± 5.5 mL kg−1 min−1). Each trial started in the afternoon with an exhaustive cycling protocol. The following morning 1-h of steady-state cycling (SS) was followed by a time trial (TT). Carbohydrates (CHO) were not ingested in recovery from exhaustive exercise or during next day exercise in the Placebo trial (PLA); CHO were not ingested during recovery but were fed (15 g every ∼15-min) from 30-min into SS and continued during the TT in the delayed feeding trial (DELAY); CHO were provided during recovery (1.2 g/kg/h for 7 h) and next day exercise (as in DELAY) in a third condition (CHO). Exercise metabolism was assessed using indirect calorimetry and blood sampling. Fat oxidation rates during SS were similar in PLA (0.83 ± 0.17 g/min) and DELAY (0.78 ± 0.14 g/min) (p > 0.05) and higher than CHO (0.57 ± 0.27 g/min) (p < 0.05). There were no significant differences in TT performance (49.1 ± 10.7, 43.4 ± 7.6, 41.0 ± 7.9 min in PLA, DELAY and CHO, respectively; p > 0.05). Delayed carbohydrate feeding could be a strategy to maintain high-fat oxidation rates typically associated with exercise undertaken after the sleep-low approach to training but the acute performance effects remain inconclusive.
Dietary Grape Pomace Supplementation in Dairy Cows: Effect on Nutritional Quality of Milk and Its Derived Dairy Products

Grape pomace (GP) is the main solid by-product of winemaking and represents a rich source of potent bioactive compounds which could display a wide range of beneficial effects in human health for their association with reduced risk of several chronic diseases. Several studies have proposed the use of GP as a macro-ingredient to obtain economically worthwhile animal feedstuffs naturally enriched by polyphenols and dietary fibers. Moreover, the research carried out in this field in the last two decades evidences the ability of GP to induce beneficial effects in cow milk and its derived dairy products. First of all, a general increase in concentration of polyunsaturated fatty acids (PUFA) was observed, and this could be considered the reflection of the high content of these compounds in the by-product. Furthermore, an improvement in the oxidative stability of dairy products was observed, presumably as a direct consequence of the high content of bioactive compounds in GP that are credited with high and well-characterized antioxidant functions. Last but not least, particularly in ripened cheeses, volatile compounds (VOCs) were identified, arising both from lipolytic and proteolytic processes and commonly associated with pleasant aromatic notes. In conclusion, the GP introduction in the diet of lactating cows made it possible to obtain dairy products characterized by improved nutritional properties and high health functionality. Furthermore, the presumable improvement of organoleptic properties seems to be effective in contributing to an increase in the consumer acceptability of the novel products. This review aims to evaluate the effect of the dietary GP supplementation on the quality of milk and dairy products deriving from lactating dairy cows.
Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

Background/Objective Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung cancer cell lines. Methods Expression levels of CB1, CB2, EGFR, CDH1, CDH2 and VIM were evaluated by quantitative reverse transcription-polymerase chain reaction. THC and CBD (10–100 μM), individually or in combination (1:1 ratio), were used for in vitro assays. Cell proliferation was determined by BrdU incorporation assay. Morphological changes in the cells were visualized by phase-contrast and fluorescence microscopy. Migration was studied by scratch recolonization induced by 20 ng/ml epidermal growth factor (EGF). Results The tumor samples were classified according to the level of expression of CB1, CB2, or both. Patients with high expression levels of CB1, CB2, and CB1/CB2 showed increased survival reaching significance for CB1 and CB1/CB2 (p = 0.035 and 0.025, respectively). Both cannabinoid agonists inhibited the proliferation and expression of EGFR in lung cancer cells, and CBD potentiated the effect of THC. THC and CBD alone or in combination restored the epithelial phenotype, as evidenced by increased expression of CDH1 and reduced expression of CDH2 and VIM, as well as by fluorescence analysis of cellular cytoskeleton. Finally, both cannabinoids reduced the in vitro migration of the three lung cancer cells lines used. Conclusions The expression levels of CB1 and CB2 have a potential use as markers of survival in patients with NSCLC. THC and CBD inhibited the proliferation and expression of EGFR in the lung cancer cells studied. Finally, the THC/CBD combination restored the epithelial phenotype in vitro.
Factors Impacting on Development and Implementation of Training Programs for Health Professionals to Deliver Brief Interventions, with a Focus on Programs Developed for Indigenous Clients: A Literature Review

This paper reviews the literature on evaluations of brief intervention training programs for health professionals which address one or more lifestyle factors of chronic disease to identify factors impacting on development and implementation of programs. A search was conducted of the literature evaluating brief intervention training programs from 2000–2019 in the databases: Medline, CINAHL, Psychinfo, Academic Premier, Science Direct, Ovid (Including EMBASE and Healthstar), Web of Science and Informit. The content analysis and data extraction were aligned to the domains in the Consolidated Framework for Implementation Research (CFIR) to assist in the narrative synthesis. The search identified eight evaluations of programs targeting multiple risk factors, and 17 targeting single risk factors. The behavioural risk factor most commonly addressed was smoking, followed by alcohol and drug use. Programs consisted of face-to-face workshops and/or online or distance learning methods. Facilitators included availability of sustainable funding, adapting the program to suit the organisation’s structural characteristics and adoption of the intervention into routine client care. For Indigenous programs, the use of culturally appropriate images and language, consultation with Indigenous communities, and development of resources specific to the communities targeted were important considerations.
Obesity Reduces Maternal Blood Triglyceride Concentrations by Reducing Angiopoietin-Like Protein 4 Expression in Mice

To ensure fetal lipid supply, maternal blood triglyceride (TG) concentrations are robustly elevated during pregnancy. Interestingly, a lower increase in maternal blood TG concentrations has been observed in some obese mothers. We have shown that high-fat (HF) feeding during pregnancy significantly reduces maternal blood TG levels. Therefore, we performed this study to investigate if and how obesity alters maternal blood TG levels. Maternal obesity was established by prepregnant HF (ppHF) feeding, which avoided the dietary effect during pregnancy. We found not only that maternal blood TG concentrations in ppHF dams were remarkably lower than in control dams but also that the TG peak occurred earlier during gestation. Hepatic TG production and intestinal TG absorption were unchanged in ppHF dams, but systemic lipoprotein lipase (LPL) activity was increased, suggesting that increased blood TG clearance contributes to the decreased blood TG concentrations in ppHF dams. Although significantly higher levels of UCP1 protein were observed in interscapular brown adipose tissue (iBAT) of ppHF dams, Ucp1 gene deletion did not restore blood TG concentrations in ppHF dams. Expression of the angiopoietin-like protein 4 (ANGPTL4), a potent endogenous LPL inhibitor, was significantly increased during pregnancy. However, the pregnancy-induced elevation of blood TG was almost abolished in Angptl4−/− dams. Compared with control dams, Angptl4 mRNA levels were significantly lower in iBAT, gonadal white adipose tissue, and livers of ppHF dams. Importantly, ectopic overexpression of ANGPTL4 restored maternal blood TG concentrations in ppHF dams. Together, these results indicate that ANGPTL4 plays a vital role in increasing maternal blood TG concentrations during pregnancy. Obesity impairs the rise of maternal blood TG concentrations by reducing ANGPTL4 expression in mice.
1000 Families Study, a UK multiwave cohort investigating the well-being of families of children with intellectual disabilities: cohort profile

Purpose The 1000 Families Study is a large, UK-based, cohort of families of children with intellectual disability (ID). The main use of the cohort data will be to describe and explore correlates of the well-being of families of children with ID, including parents and siblings, using cross-sectional and (eventually) longitudinal analyses. The present cohort profile intends to describe the achieved cohort. Participants Over 1000 families of UK children with ID aged between 4 and 15 years 11 months (total n=1184) have been recruited. The mean age of the cohort was 9.01 years old. The cohort includes more boys (61.8%) than girls (27.0%; missing 11.1%). Parents reported that 45.5% (n=539) of the children have autism. Most respondents were a female primary caregiver (84.9%), and 78.0% were the biological mother of the cohort child with ID. The largest ethnic group for primary caregivers was White British (78.5%), over half were married and living with their partner (53.3%) and 39.3% were educated to degree level. Findings to date Data were collected on family, parental and child well-being, as well as demographic information. Wave 1 data collection took place between November 2015 and January 2017, primarily through online questionnaires. Telephone interviews were also completed by 644 primary caregivers. Future plans Wave 2 data collection is ongoing and the research team will continue following up these families in subsequent waves, subject to funding availability. Results will be used to inform policy and practice on family and child well-being in families of children with ID. As this cohort profile aims to describe the cohort, future publications will explore relevant research questions and report key findings related to family well-being.
The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort

Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.2%) were assigned a genetic diagnosis, with variants in MYRF, TMEM98, MFRP, and PRSS56. Two of four PRSS56 families harbored the previously described c.1066dupC variant implicated in over half of all reported PRSS56 kindreds, with different surrounding haplotypes in each family suggesting a mutational hotspot. Individuals with a genetic diagnosis had shorter mean axial lengths and higher hyperopia than those without, with recessive forms associated with the most extreme phenotypes. These findings detail the genetic architecture of nanophthalmos and posterior microphthalmos in a cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.
Calculation of the initial DNA damage induced by alpha particles in comparison with protons and electrons using Geant4-DNA

Abstract Purpose: Interaction of ionizing radiations with cells leads to single- and double-strand breaks (SSBs and DSBs) as well as base lesions of DNA. Employing the Geant4-DNA toolkit, we simulated the transportation of primary alphas and secondary particles in liquid water to study the damage in the form of SSBs and DSBs. Materials and Methods: Simulations were performed in a spherical water medium, where we used a B-DNA model and classified the DNA damage and its complexity. We assumed that in a certain vicinity of the DNA volume, energy depositions of more than 17.5 eV or hydroxyl radicals with a chemical-reaction probability of 0.13 would lead to strand breaks. Results: The results of 2 to 20 MeV alpha particles showed that more than 65% of the energy-deposition cases within the DNA volume would result in a form of break. The frequency pattern of higher-complexity damage types appeared to peak at higher deposited energies. Conclusion: We observed a reasonable agreement in terms of trend and value between our DSB yield results and experimental data. The yield results, as function of LET, suggested independence from particle type and converge to some extent at large LET. This manifests the dominant contribution of secondary electrons.
Fluorinated vs. Zwitterionic-Polymer Grafted Surfaces for Adhesion Prevention of the Fungal Pathogen Candida albicans

Fluorinated (F6) and zwitterionic, as well as phosphorylcholine (MPC) and sulfobetaine (MSA), copolymers containing a low amount (1 and 5 mol%) of 3-(trimethoxysilyl)propyl methacrylate (PTMSi) were prepared and covalently grafted to glass slides by using the trimethoxysilyl groups as anchorage points. Glass-surface functionalization and polymer-film stability upon immersion in water were proven by contact angle and angle-resolved X-ray photoelectron spectroscopy (AR-XPS) measurements. Antifouling performance of the grafted films was assayed against the yeast Candida albicans, the most common Candida species, which causes over 80% of candidiasis. Results revealed that the F6 fluorinated, hydrophobic copolymers performed much better in reducing the adhesion of C. albicans, with respect to both corresponding zwitterionic, hydrophilic MPC and MSA counterparts, and were similar to the glass negative control, which is well-known to inhibit the adhesion of C. albicans. A composition-dependent activity was also found, with the films of copolymer with 99 mol% F6 fluorinated co-units performing best.