Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutral Diclofenac Causes Remarkable Changes in Phosphatidylcholine Bilayers: Relevance for Gastric Toxicity Mechanisms

The main objective of this study was to clarify the topical mechanisms underlying diclofenac-induced gastric toxicity by considering for the first time both ionization states of this nonsteroidal anti-inflammatory drug. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes were the model system chosen to mimic the protective phospholipid layers of the gastric mucosa and to describe the interactions with diclofenac, considering the pH gradient found in the gastric mucosa (3 < pH < 7.4). Complementary experimental techniques were combined to evaluate the drug’s affinity for DMPC bilayers, as well as to assess the drug’s effects on the structural properties of the phospholipid bilayer. The diclofenac-DMPC interactions were clearly dependent on the drug’s ionization state. Neutral diclofenac displayed greater affinity for DMPC bilayers than anionic diclofenac. Moreover, the protonated/neutral form of the drug induced more pronounced and/or distinct alterations in the structure of the DMPC bilayer than the deprotonated/ionized form, considering similar membrane concentrations. Therefore, neutral diclofenac-induced changes in the structural properties of the external phospholipid layers of the gastric mucosa may constitute an additional toxicity mechanism of this worldwide-used drug, which shall be considered for the development of safer therapeutic strategies. SIGNIFICANCE STATEMENT Neutral or anionic diclofenac exerted distinct alterations in phosphatidylcholine bilayers, which are used in this work as models for the protective phospholipid layers of the gastric mucosa. Remarkable changes were induced by neutral diclofenac in the structural properties of the phospholipid bilayer, suggesting that both ionized and neutral states of nonsteroidal anti-inflammatory drugs must be considered to clarify their mechanisms of toxicity and to ultimately develop safer anti-inflammatory drugs.
Is student loan debt good or bad for full-time employment upon graduation from college?

Student loan debt represents an important phenomenon in the United States, as around 61% of bachelor's degree recipients graduate with a debt of over $28,100. Although studies emphasize that holding student loan debt delays the transition to adulthood in terms of marriage and home ownership, little is known about its impact on employment and this limited research offers, at best, equivocal evidence. The current study draws from Conservation of Resources theory to argue that student loan debt acts as a major financial stressor for new labor market entrants during job search. Using archival data from 1,248 graduating seniors from 4 geographically diverse universities in the United States collected in the context of a prospective study design, we found evidence for 2 countervailing mechanisms through which student loan debt may influence full-time employment upon graduation. On the one hand, college students who had student loan debt were more likely to experience financial strain, and subsequently more job search strain, which was negatively related to college seniors' odds of securing full-time employment upon graduation. On the other hand, this financial strain was also positively related to students' work hours while in the last semester of college, which was positively related to their odds of securing full-time employment upon graduation. Further mediation tests revealed that only the 3-stage indirect effect through job search strain (i.e., student loan debt → financial strain → job search strain → full-time employment) was statistically significant. The theoretical and practical implications of these findings are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Analysis of Heterozygous BRCA1 5382ins Founder Mutation in a Cohort of Egyptian Breast Cancer Female Patients Using Pyrosequencing Technique

Background: Up to half of the heritable mutations in breast cancer (BC) are attributed to BRCA1 and BRCA2 genes. The mutation prevalence is variable based on ethnicity and may be influenced by founder mutations. The aim of this pilot study is to determine for the first time, the prevalence of BRCA1 5382insC founder mutation in a cohort of Egyptian familial breast cancer patients (FBC). Methods: Female patients were selected to have familial type of breast cancer. Twenty healthy females were included as a control group. Peripheral blood samples were withdrawn from all studied females and were analyzed for BRCA1 5382insC founder mutation detection using pyrosequencing technique. Results: Eighty Egyptian FBC females were eligible to be enrolled in the study with a mean age of 48.31 ± 10.97years. We found a BRCA1 5382insC mutation carrier frequency of 5% of total studied FBC patients (4 out of 80 patients) with 95% confidence interval (1.61-12.99). There was a high statistical significant difference between carriers and non-carriers concerning the number of affected family members by BC, (p=0.001). Conclusion: BRCA1 5382insC founder mutation is not uncommon among Egyptian FBC females. The carrier frequency is comparable to that reported worldwide; however it is lower than those from previous Egyptian studies using different molecular techniques. The strong association between the mutation and the number of affected family members suggest wider screening of the mutation among high risk families using the reliable pyrosequencing technique.
Vitamin D Pathway and Other Related Polymorphisms and Risk of Prostate Cancer: Results from the Prostate Cancer Prevention Trial

Vitamin D may influence prostate cancer risk, but evidence is inconsistent. We conducted a nested case–control study in the Prostate Cancer Prevention Trial (PCPT). Cases (n = 1,128) and controls (n = 1,205) were frequency matched on age, first-degree relative with prostate cancer, and PCPT treatment arm (finasteride/placebo); African-Americans were oversampled and case/control status was biopsy confirmed. We selected 21 SNPs in vitamin D–related genes (VDR, GC, C10orf88, CYP2R1, CYP24A1, CYP27B1, DHCR7, and NADSYN1) to test genotype and genotype–treatment interactions in relation to prostate cancer. We also tested mean serum 25(OH)D differences by minor allele distributions and tested for serum 25(OH)D–genotype interactions in relation to prostate cancer risk. Log-additive genetic models (Bonferroni-corrected within genes) adjusted for age, body mass index, PSA, and family history of prostate cancer revealed a significant interaction between treatment arm and GC/rs222016 (finasteride OR = 1.37, placebo OR = 0.85; Pinteraction < 0.05), GC/rs222014 (finasteride OR = 1.36, placebo OR = 0.85; Pinteraction < 0.05), and CYP27B1/rs703842 (finasteride OR = 0.76, placebo OR = 1.10; Pinteraction < 0.05) among Caucasians, and C10orf88/rs6599638 (finasteride OR = 4.68, placebo OR = 1.39; Pinteraction < 0.05) among African-Americans. VDR/rs1544410 and CYP27B1/rs703842 had significant treatment interactions for high-grade disease among Caucasians (finasteride OR = 0.81, placebo OR = 1.40; Pinteraction < 0.05 and finasteride OR = 0.70, placebo OR = 1.28; Pinteraction < 0.05, respectively). Vitamin D–related SNPs influenced serum 25(OH)D, but gene-serum 25(OH)D effect modification for prostate cancer was marginally observed only for CYP24A1/rs2248359. In conclusion, evidence that vitamin D–related genes or gene-serum 25(OH)D associations influence prostate cancer risk is modest. We found some evidence for gene–finasteride interaction effects for prostate cancer in Caucasians and African-Americans. Results suggest only minimal associations of vitamin D with total or high-grade prostate cancer.
Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials

Background It has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument’s poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depression Rating-Scale (MADRS). Methods and findings We conducted a meta-analysis based on the comprehensive dataset of acute antidepressant trials provided by Cipriani et al. We included all placebo-controlled trials that reported continuous outcomes based on either the HDRS 17-item version or the MADRS. We computed standardised mean difference effect size estimates and raw score drug-placebo differences to evaluate thresholds for clinician-rated minimal improvements (clinical significance). We selected 109 trials (n = 32,399) that assessed the HDRS-17 and 28 trials (n = 11,705) that assessed the MADRS. The summary estimate (effect size) for the HDRS-17 was 0.27 (0.23 to 0.30) compared to 0.30 (0.22 to 0.38) for the MADRS. The effect size difference between HDRS-17 and MADRS was thus only 0.03 and not statistically significant according to both subgroup analysis (p = 0.47) and meta-regression (p = 0.44). Drug-placebo raw score difference was 2.07 (1.76 to 2.37) points on the HDRS-17 (threshold for minimal improvement: 7 points according to clinician-rating and 4 points according to patient-rating) and 2.99 (2.24 to 3.74) points on the MADRS (threshold for minimal improvement: 8 points according to clinician-rating and 5 points according to patient-rating). Conclusions Overall there was no meaningful difference between the HDRS-17 and the MADRS. These findings suggest that previous meta-analyses that were mostly based on the HDRS did not underestimate the drugs’ true treatment effect as assessed with MADRS, the preferred outcome rating scale. Moreover, the drug-placebo differences in raw scores suggest that treatment effects are indeed marginally small and with questionable importance for the average patient.
Abstract S2-02: The impact of adjuvant denosumab on disease-free survival: Results from 3,425 postmenopausal patients of the ABCSG-18 trial

Background: Adjuvant endocrine therapy compromises bone health in pre- and postmenopausal breast cancer (BC) patients. Bisphosphonates have been shown to prevent and counteract these side effects of endocrine therapy, and to improve disease-free and overall survival outcomes in postmenopausal (natural or induced) BC patients (EBCTCG meta-analysis, Lancet 2015). The aim of ABCSG-18 was to investigate the effects of adjuvant anti-RANK-ligand Denosumab on bone health and disease outcomes in postmenopausal patients with early hormone receptor+ (HR+) BC receiving AI treatment. Patients and Methods: 3,425 postmenopausal patients with HR+ BC receiving AI were recruited in 58 trial sites into this prospective, randomized, double-blind, placebo-controlled, phase-III trial. Patients were randomized 1:1 to either Denosumab 60mg or placebo q6mo s.c. Bone end point results showed that adjuvant denosumab significantly reduced clinical fractures (primary endpoint, HR=0.5, p Results: With a median follow-up of 4 years, 370 DFS events were recorded. 203 DFS events occurred in the placebo group, and 167 in the Denosumab group (HR 0.816, p=0.051). Subgroup analyses indicate that the Denosumab benefit (overall absolute 2.1% at 5 years) may be particularly driven by tumors larger than 2cm (HR=0.66, p=0.016), ductal breast cancer histology type (HR=0.79, p=0.048), and tumors with both ER and PR positive (HR=0.75, p=0.013). Summary and conclusion: Adjuvant Denosumab 60mg q6mo s.c. improves disease-free survival of HR+ breast cancer patients receiving aromatase inhibitors. Numerically, this benefit of adjuvant Denosumab is at least comparable to the DFS-benefit of adjuvant bisphosphonates. Bases on these results and the previously reported dramatic reduction of fractures, adjuvant Denosumab should be offered to all postmenopausal HR+ breast cancer patients on AI. Citation Format: Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF, On behalf of the Austrian Breast and Colorectal Cancer Study Group. The impact of adjuvant denosumab on disease-free survival: Results from 3,425 postmenopausal patients of the ABCSG-18 trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S2-02.
The long-term impacts of preterm birth and associated morbidities on bone health in preschool children: a prospective cross-sectional study from Turkey

Abstract Objective To evaluate the impact of preterm birth on bone health in preschool children. Methods A total of 166 preschool children (aged 7–8 years) born preterm (n = 86, <37-week gestation) and at term (n = 80, ≥37 weeks of gestation) in our hospital were included in this prospective cross-sectional study. Data on antenatal, perinatal, and early postnatal characteristics and maternal obstetric history were obtained from medical records. Bone densitometry data including total bone mineral content (BMC), bone mineral density (BMD; total, lumbar, and femoral), z-scores, and bone loss were collected for each participant. Results Current height, weight, and BMI values were significantly lower in the preterm group (p < .001). Serum calcium, phosphorus and alkaline phosphatase (ALP) levels did not differ among groups, whereas VitD3 levels were significantly higher in the preterm group (p = .039). The mean total BMC, total BMD, lumbar (L2–L4) BMD, femur BMD, total z-score, and L2–L4 z-score values were significantly lower for the preterm group, whereas the total, lumbar, and femoral bone loss were significantly higher (p < .001), regardless of the severity of prematurity. Intraventricular hemorrhage (IVH) and retinopathy were significantly associated with lower total BMC (p = .004, p = .012, respectively). Fortified breastfeeding was associated with lumbar bone loss (p = .043), and formula feeding was associated with both femur and lumbar bone loss (p = .006, p = .012, respectively). Conclusions Our findings revealed long-term adverse effects of preterm birth on bone health, with significantly lower anthropometric values (weight, height, and BMI), lower scores for total BMC, BMD (total, lumbar, femoral), and z-scores (total, femur), along with higher bone loss (total, lumbar, femoral) and higher rates of osteopenia and osteoporosis in preschool children born preterm (whether moderate or very preterm) compared with those born at term. Exclusive breastfeeding appears to reduce the likelihood of long-term bone loss in preterm infants
The Cost of the “July Effect” in Microsurgery

Abstract The existence of the “July effect,” or the idea that the new academic year intrinsically has an increased complication rate is evaluated in microsurgical free tissue transfer procedures. The National Surgical Quality Improvement Program registry was queried for all free flap procedures performed between 2005 and 2016 (n = 3405). Cases were grouped as having occurred in the first academic quarter (Q1: July 1–September 30) or fourth quarter (Q4: April 1–June 30). Demographical data and complications were compared using univariate χ2 analysis, multivariate logistic regression was used to control for confounding variables, and inpatient stay and operating cost estimates were created. Of a total of 1722 cases, 905 were performed in the first academic quarter and 817 were performed in the fourth academic quarter. There was no significant difference between Q1 and Q4 in readmission rate (P = 0.378) or reoperation rate (P = 0.730). Patients in Q1 had significantly longer operative times (P = 0.001) and length of stay (P = 0.002) compared with those in Q4. In addition, cost of inpatient stay and operating costs associated with each free flap were significantly increased in Q1 compared with Q4 (P = 0.029; P = 0.001). The total cost per quarter for free flaps was also significantly more expensive in Q1 vs Q4, with the highest average difference in cost of $350,010.64 (P = 0.001). Having surgery early in the academic year does not put patients at any increased risk for major complications but is associated with increased operating time, length of stay, and total cost.
Mothering in the Context of Mental Disorder: Effect of Caregiving Load on Maternal Health in a Predominantly Hispanic Sample

Background: Mothering in the context of mental disorders presents with multiple challenges. However, this phenomenon is poorly understood: It is not known how child caregiving affects the health of their mothers. Aims: The purpose of this study was to examine associations between child caregiving load and health indicators in mothers receiving outpatient behavioral health services for mental or substance use disorders. Method: A total of 172 mothers (80% Hispanic/Latina) completed surveys on their mental and physical health, and children’s behaviors and medical problems. Child caregiving load consisted of number of children living with the mother, and presence of children’s internalizing, externalizing, or medical problems. Results: Child caregiving load had significantly positive associations with mother’s psychological distress, fatigue, pain, and body mass index. Child internalizing and medical problems were associated with mothers’ poor health status. Conclusions: Hispanics/Latinos experience health disparities, and Hispanic/Latina mothers who are already at risk due to their mental disorders experience an additional health burden associated with caring for children with emotional or health problems. Psychiatric and mental health nurse practitioners should assess child caregiving impact on mothers with mental disorders and seek to mitigate their caregiving burden and maintain their health. Further research is needed to clarify child characteristics and the mechanisms associated with maternal caregiver burden, suboptimal self-care, and adverse health outcomes. Structural Ecosystems Therapy for women in Recovery (SET-R) study/Healthy Home; Clinical Trial ID NCT02702193
Call the On-Call: a study of student learning on an interprofessional training ward

ABSTRACT Interprofessional training wards are designed to train students’ team and communication competences. Such wards are generally highly valued clinical placements by undergraduate students; however, evidence in the literature suggests that medical students experience a lack of profession-specific tasks on these wards. Moreover, students lack structured training in the complexities of everyday communication where different health professions rarely are present together in stable teams. This paper reviews one strategy to train students in interprofessional communication while letting students perform profession-specific tasks. A qualitative study with ethnographically-collected data was conducted among three interprofessional student teams over three two-week periods, mixing field observations (75 h), interviews (n = 16), and field notes (45 pages). The findings show that students gained insights into new aspects of their professional roles and an appreciation of clear and open interprofessional communication over the telephone. Learning was facilitated through being confronted with new situations and discussing these experiences with each other over time. Call the On-Call as a pedagogic activity provided not just medical students, but also nursing students with new types of profession-specific tasks on the interprofessional training ward.
The regional environment and firms’ commitment to innovation: empirical evidence from Spain

ABSTRACT Using panel data for Spanish firms, this paper examines the role of firms’ regional knowledge environment for commitment to innovation of innovation active firms. The empirical results show that a stronger regional knowledge environment increases the likelihood that an innovator engages continuously in R&D as opposed to occasionally. This positive relationship with the regional knowledge environment is robust and significant in manufacturing and specifically for small firms and for technology-intensive firms.
Apherusa glacialis throughout the Arctic

ERIN H. KUNISCH*, BODIL A. BLUHM, MALIN DAASE, ROLF GRADINGER, HAAKON HOP, IGOR A. MELNIKOV, ØYSTEIN VARPE AND JØRGEN BERGE department of arctic and marine biology, faculty of biosciences, fisheries and economics, uit the arctic university of norway, po box 6050 langnes, n-9037, tromsø, norway, norwegian polar institute, fram centre, po box 6606, n-9296, tromsø, norway, p.p. shirshov institute of oceanology, ioras, 36 nakhimovskiy pr. , moscow 117997, russia, the university centre in svalbard (unis), po box 156, 9171 longyearbyen, norway, norwegian institute for nature research, po box 5685, torgarden, no-7485 trondheim, norway, and the norwegian university of science and technology (ntnu), no-7491 trondheim, norway
Supporting Stimulation Needs in Dementia Care through Wall-Sized Displays

Beside reminiscing, the increasing cognitive decline in dementia can also be addressed through sensory stimulation allowing the immediate, nonverbal engagement with the world through one's senses. Much HCI work has prioritized cognitive stimulation for reminiscing or personhood often on small screens, while less research has explored sensory stimulation like the one enabled by large displays. We describe a year-long deployment in a residential care home of a wall-sized display, and explored its domestication through 24 contextual interviews. Findings indicate strong engagement and attachment to the display which has inspired four psychosocial interventions using online generic content. We discuss the value of these findings for personhood through residents' exercise of choices, the tension between generic/personal content and its public/private use, the importance of participatory research approach to domestication, and the infrastructure-based prototype, illustrated by the DementiaWall and its generative quality.
The Growth Optimization of Pak Choy (Brassica rapa L. var. chinensis) in Household-Scale Aquaponics System

The growth of Pak Choy (Brassica rapa var. chinensis) using nutrients from catfish “Sangkuriang” (Clarias gariepinus) wastes was investigated in the household scale aquaponics systems by comparing the growth parameters value among the grow beds . The growth parameter of Pak Choy was fresh weight, leaf number, and leaf area. Meanwhile, catfish growth parameters were body weight and length, and feed conversion ratio (FCR). The experiments were arranged in a Completely Randomized Design (CRD) with 4 treatments and 3 replications . The data were analyzed using Analysis of Variance (Anova) followed by Duncan Multiple Range Test (DMRT) at 95% level of significant The result of the study showed that there were not significantly different in the growth parameter of Pak Choy among the grow beds in the vertical system. However, those in grow beds “A” were significantly higher than the rest of the grow beds in the horizontal aquaponics system. In general, all the growth parameter of Pak Choy in the vertical system was higher than in the horizontal one, although, it was not statistically significantly different . Nevertheless, the horizontal aquaponics system gave better results in the body weight and FCR of catfish.