Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of temperature and ethanol on the kinetics of proanthocyanidin adsorption in model wine systems.

The kinetics, quantitative and qualitative effects of grape proanthocyanidin (PA) adsorption to grape skin-derived cell wall material (CWM) were investigated in five different temperature-ethanol conditions. Progress curves for each condition were constructed by monitoring the decrease in concentration of PA solutions after exposure to CWM over 720 minutes. Adsorption isotherms were constructed for each condition, and a Langmuir equation model was applied to each via regression analysis. Compositional changes in the PA solutions after exposure to CWM were determined using phloroglucinolysis and gel permeation chromatography (GPC). A negative correlation between PA adsorption and both temperature and ethanol concentration was found. Progress curves suggested that both temperature and ethanol affect the equilibration rate of the adsorption reactions. Additionally, equilibration rates for lower temperature and ethanol concentration conditions were found to be much longer than previously reported, taking up to 720 minutes. Phloroglucinolysis results showed no discernable correlation between temperature or ethanol concentration and %galloylation or %gallo units of adsorbed compounds. Analyses by phloroglucinolysis and GPC indicate a preferential adsorption of larger molecular weight PA's under all conditions, though no discernable impact on PA composition was detected. Additionally, findings suggest that both temperature and ethanol concentration impact the percent reduction in molar mass of the PA solution. Data from this study was ultimately utilized to develop a computational model for predicting phenolic extraction during red wine fermentations.
Self-Perceived Health Status and Sense of Coherence in Children With Type 1 Diabetes in the West Bank, Palestine

Introduction: Self-perceived health status and sense of coherence (SOC) are essential constructs for capturing health outcomes in children with type 1 diabetes (T1D). This study measured self-perceived health status and SOC in children with T1D and compared them with a healthy reference group in West Bank, Palestine. Methodology: One hundred children with T1D aged 8 to 18 years and 300 healthy children completed PedsQL 4.0 Generic Core Scales and SOC-13 in a cross-sectional descriptive study. Results: All children reported acceptable self-perceived health status and low degree of SOC. In the diabetes group, high degree of SOC was associated with better self-perceived health status and more optimal metabolic control. Males in the diabetes group reported higher self-perceived health status than females. Discussion: The unstable political situation in Palestine may threaten SOC in children in general. Health professionals can monitor self-perceived health status and SOC to evaluate interventions aiming to improve glycemic control.
Clinical Impact of RANK Signalling in Ovarian Cancer

Ovarian cancer (OC) is a gynaecological malignancy with poor clinical outcome and limited treatment options. The receptor activator of nuclear factor-κB (RANK) pathway, activated by RANK ligand (RANKL), critically controls bone metabolism, tumourigenesis and tumour immune responses. Denosumab, a monocloncal RANKL antibody, exerts tumour-suppressive effects in mice and humans. Here, we investigated the relevance of RANK signalling in OC. RANK, RANKL and OPG expression in 192 epithelial OC tissues was compared to expression in 35 non-malignant control tissues and related to clinico-pathological characteristics. Findings were validated in a cohort of 563 OC patients from The Cancer Genome Atlas (TCGA). The expression of RANK, RANKL and OPG was studied in four OC cell lines and the impact of RANK ligation or blockade on OC cell proliferation was determined. RANK, RANKL and OPG were expressed in epithelial and stromal cells in OC. RANKL expression was elevated in OC tissue, particularly in BRCA1/2 mutated tumours. High RANKL expression independently predicted reduced progression-free (PFS, p = 0.017) and overall survival (OS, p = 0.007), which could be validated in the TCGA cohort (PFS, p = 0.022; OS, p = 0.046, respectively). Expression of RANK and OPG in OC cells was induced by inflammatory cytokines IL-1β and TNFα. Neither recombinant RANK ligation nor denosumab treatment affected OC cell proliferation. Our study independently links RANKL expression with poor clinical outcome in two unrelated OC cohorts. These findings implicate RANK signalling in the immunopathogenesis of OC and warrant clinical trials with denosumab in OC.
The Use of Data Mining Methods for the Prediction of Dementia: Evidence From the English Longitudinal Study of Aging

Dementia in older age is a major health concern with the increase in the aging population. Preventive measures to prevent or delay dementia symptoms are of utmost importance. In this study, a large and wide variety of factors from multiple domains were investigated using a large nationally representative sample of older people from the English Longitudinal Study of Ageing. Seven machine learning algorithms were implemented to build predictive models for performance comparison. A simple model ensemble approach was used to combine the prediction results of individual base models to further improve predictive power. A series of important factors in each domain area were identified. The findings from this study provide new evidence on factors that are associated with the dementia in later life. This information will help our understanding of potential risk factors for dementia and identify warning signs of the early stages of dementia. Longitudinal research is required to establish which factors may be causative and which factors may be a consequence of dementia.
A trap mutant reveals the physiological client spectrum of TRC40

ABSTRACT The transmembrane recognition complex (TRC) pathway targets tail-anchored (TA) proteins to the membrane of the endoplasmic reticulum (ER). While many TA proteins are known to be able to use this pathway, it is essential for the targeting of only a few. Here, we uncover a large number of TA proteins that engage with TRC40 when other targeting machineries are fully operational. We use a dominant-negative ATPase-impaired mutant of TRC40 in which aspartate 74 was replaced by a glutamate residue to trap TA proteins in the cytoplasm. Manipulation of the hydrophobic TA-binding groove in TRC40 (also known as ASNA1) reduces interaction with most, but not all, substrates suggesting that co-purification may also reflect interactions unrelated to precursor protein targeting. We confirm known TRC40 substrates and identify many additional TA proteins interacting with TRC40. By using the trap approach in combination with quantitative mass spectrometry, we show that Golgi-resident TA proteins such as the golgins golgin-84, CASP and giantin as well as the vesicle-associated membrane-protein-associated proteins VAPA and VAPB interact with TRC40. Thus, our results provide new avenues to assess the essential role of TRC40 in metazoan organisms. This article has an associated First Person interview with the first author of the paper. Summary: A strategy to decipher which tail-anchored proteins do (as opposed to can or must) use the TRC pathway in intact cells generates a comprehensive list of human TRC40 clients.
Fascial nomenclature: Update on related consensus process

The term fascia is increasingly used not only by anatomists but also by other professionals and authors in different health‐oriented fields. This goes along with an inconsistent usage of the term, in which many different tissues are included by different authors causing an increasing amount of confusion. The Fascia Research Society acted to address this issue by establishing a Fascia Nomenclature Committee (FNC) with the purpose of clarifying the terminology relating to fascia. This committee conducted an elaborate Delphi process to foster a structured consensus debate among different experts in the field. This process led to two distinct terminology recommendations from the FNC, defining the terms “a fascia” and “the fascial system. ” This article reports on the process behind this proposed terminology as well as the implications for inclusion and exclusion of different tissue types to these definitions. Clin. Anat. 32:929–933, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.
Impact of Percent Body Fat on All-Cause Mortality among Adequate Dialysis Patients with and without Insulin Resistance: A Multi-Center Prospective Cohort Study

The association between body fat and mortality in hemodialysis patients remains controversial. We examined the effect of percent body fat (PBF) on all-cause mortality among adequate hemodialysis patients with and without insulin resistance (IR). A prospective cohort study was conducted on 365 adequate hemodialysis patients (equilibrated Kt/V ≥ 1.2) from seven hospitals. Patients’ characteristics and clinical and biochemical parameters were assessed at baseline between September 2013 and April 2017. Patients were followed up for all-cause mortality until April 2018. The median value of homeostatic model assessment (HOMA-IR) was used to classify IR. Cox proportional hazard models were utilized to examine predictors of all-cause mortality. During 1.4 (1.0–3.2) years of follow-up, 46 patients died. In patients with IR (HOMA-IR ≥ 5.18), PBF was significantly higher in the survival group than in the death group (31.3 ± 9.0 vs. 25.4 ± 8.2, p = 0.005). After controlling for confounding factors, PBF was significantly associated with lower risk for all-cause mortality in patients with IR (hazard ratio, 0.94; 95% confidence interval, 0.89–1.00; p = 0.033). The association was not observed in patients without IR. In conclusion, percent body fat shows a protective effect on survival in hemodialysis patients with IR.
The Influence of Microfungi on the Mycelial Growth of Ectomycorrhizal Fungus Tricholoma matsutake

Pine mushroom (Tricholoma matsutake) is one of the most valued ectomycorrhizal fungi in Asia because of its unique pine-like aroma; however, due to exceptionally slow growth of its mycelia in artificial conditions, its cultivation has been largely deemed as not possible. Previous studies have shown that some bacteria and a few Trichoderma species associated with pine mushroom promoted the growth of T. matsutake isolate, but this effect is relatively unexplored. In this study, we investigated the diversity of microfungi in the fairy ring of T. matsutake and their effect on the growth of T. matsutake isolate. From 184 fungal isolates, 28 species were identified based on suitable molecular markers. Penicillium was most frequently observed (16 species), followed by Trichoderma (4 species). Five Zygomycota species showed a high promoting effect on the growth of T. matsutake while the effects of ascomycetes were mixed. The microfungi that promote the growth of T. matsutake can be useful for forest nursery and artificial cultivation of T. matsutake.
Changes in rapid HIV treatment initiation after national “treat all” policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis

Background Most countries have formally adopted the World Health Organization’s 2015 recommendation of universal HIV treatment (“treat all”). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts. Methods and findings We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI −2.9 to 3.8; p = 0.804) and Uganda (−4.2 pp, 95% CI −9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16–24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all. Conclusions Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.
Sympathetic innervation of the interscapular brown adipose tissue in mouse

The recent discovery of significant brown fat depots in adult humans has revived discussion of exploiting brown fat thermogenesis in the control of energy balance and body weight. The sympathetic nervous system (SNS) has a key role in the activation of brown fat and functional mapping of its components will be crucial for the development of specific neuromodulation techniques. The mouse is an important species used for molecular genetic modulations, but its small size is not ideal for anatomical dissections, thus brown fat innervation studies are mostly available in larger rodents such as rats and hamsters. Here, we use pseudorabies virus retrograde tracing, whole tissue clearing, and confocal/light sheet microscopy to show the location of pre‐ and postganglionic neurons selectively innervating the interscapular brown adipose tissue (iBAT) in the mouse. Using iDISCO whole tissue clearing, we identified iBAT projecting postganglionic neurons in the caudal parts of the ipsilateral fused stellate/T1, as well as the T2−T5 sympathetic chain ganglia and preganglionic neurons between levels T2 and T6 of the ipsilateral spinal cord. The methodology enabled high‐resolution imaging and 3D rendering of the specific SNS innervation of iBAT and will be helpful to discern peripheral nervous system innervation of other organs and tissues.
Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art

Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from milk thistle (Silybum marianum) seeds, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, although clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.
PRagMatic Pediatric Trial of Balanced versus nOrmaL Saline FlUid in Sepsis: the PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study.

BACKGROUND Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock. METHODS Open-label pragmatic randomized controlled trial (RCT) at a single academic children's hospital from January - August 2018. Eligible patients were >6 months to <18 years-old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration. RESULTS Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median crystalloid fluid volume received during the intervention window was 107 (IQR 60, 155) mL/kg and 98 (IQR 63, 128) mL/kg in the LR and NS arms, respectively (p=0.50). Patients randomized to LR received a median of only 20% (IQR 13, 32) of all study fluid as NS compared to 99% (IQR 64,100%) of study fluid as NS in the NS arm (absolute difference 79%, 95% CI 48,85). CONCLUSIONS A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock. This article is protected by copyright. All rights reserved.
Phosphoinositides modulate the voltage dependence of two-pore channel 3

Among the three two-pore channels (TPCs), TPC1 and TPC2 are selectively activated by PI(3,5)P2, while TPC3 has been considered not to respond to any PIP2s. Shimomura and Kubo find that TPC3 responds to both PI(3,5)P2 and PI(3,4)P2, but not to PI(4,5)P2.
Sexual harassment and assault among university students in Norway: a cross-sectional prevalence study

Objective The aim of the current study was to provide estimates of both overall and specific forms of sexual harassment among male and female college and university students. Design and setting Data stem from a recent national student health survey from 2018 for higher education in Norway (the SHoT study (Students’ Health and Wellbeing Study)). Participants 50 054 full-time students (69.1% women) aged 18–35 years participated, yielding a response rate of 31%. Main outcome measure Sexual harassment was defined according to Norwegian legal regulations, and was assessed by self-report on seven items covering verbal, non-verbal and physical sexual harassment. We also collected data on the timeframe and frequency of the sexual harassment, in addition to the formal position of the perpetrator of the harassment. Results Lifetime sexual harassment was reported by 24.2% (women 31.3%, men 8.0%), while 16.7% (women 21.6%, men 5.7%) reported having been sexually harassed within the past year. The most common forms of lifetime (ever having experienced) sexual harassments were ‘sexual expressions, suggestions or comments about your body’ and ‘unwanted touching, hugging or kissing’ (both 15.4%), while rape and rape attempt were reported by 3.4% and 2.1%, respectively. Exposure to all forms of past-year sexual harassments was significantly more common among women and the youngest age cohorts. Fellow students committed the past-year sexual harassment in 18%–29% of the instances, while a university staff member was reported to have committed the harassment in 0.6%–4.6% of cases. Conclusion Given the potential consequences suffered by those exposed to sexual harassment and assault, both the institutions and student welfare organisations should intensify their efforts to put the theme on the agenda and provide both legal and health services to victims of sexual harassment. The low response rate means that care should be taken in interpreting and generalising the findings to the whole student population.
Identification of Marek’s Disease Virus VP22 Tegument Protein Domains Essential for Virus Cell-to-Cell Spread, Nuclear Localization, Histone Association and Cell-Cycle Arrest

VP22 is a major tegument protein of alphaherpesviruses encoded by the UL49 gene. Two properties of VP22 were discovered by studying Marek’s disease virus (MDV), the Mardivirus prototype; it has a major role in virus cell-to-cell spread and in cell cycle modulation. This 249 AA-long protein contains three regions including a conserved central domain. To decipher the functional VP22 domains and their relationships, we generated three series of recombinant MDV genomes harboring a modified UL49 gene and assessed their effect on virus spread. Mutated VP22 were also tested for their ability to arrest the cell cycle, subcellular location and histones copurification after overexpression in cells. We demonstrated that the N-terminus of VP22 associated with its central domain is essential for virus spread and cell cycle modulation. Strikingly, we demonstrated that AAs 174-190 of MDV VP22 containing the end of a putative extended alpha-3 helix are essential for both functions and that AAs 159–162 located in the putative beta-strand of the central domain are mandatory for cell cycle modulation. Despite being non-essential, the 59 C-terminal AAs play a role in virus spread efficiency. Interestingly, a positive correlation was observed between cell cycle modulation and VP22 histones association, but none with MDV spread.