Miracle-dz/UniFAR-FTUs huggingface dataset:
AF-CBT for Families Experiencing Physical Aggression or Abuse Served by the Mental Health or Child Welfare System: An Effectiveness Trial

The Partnerships for Families project is a randomized clinical trial to evaluate the effectiveness of Alternatives for Families: A Cognitive Behavioral Therapy (AF-CBT), an evidence-based treatment (EBT) for families who are at risk of or have histories of child physical abuse. Across 10 agencies whose programs were supported by referrals from the mental health or child welfare system, individual providers were randomized to receive AF-CBT training (n = 90) in a 6-month learning community or treatment as usual (TAU; n = 92) which provided trainings per agency routine. We recruited families served by providers in the AF-CBT (n = 122) and TAU (n = 73) conditions and collected multiple outcomes at up to four time points (0, 6, 12, and 18 months). Using univariate tests and growth curve models, the analyses revealed that AF-CBT (vs. TAU) showed improvements in both service systems (e.g., abuse risk, family dysfunction) or one service system (e.g., threats of force, child to parent minor assault), with some outcomes showing no improvement (e.g., parental anger). These findings are discussed in relation to AF-CBT, service system, provider, and family characteristics, and training/dissemination methods that affect the delivery of an EBT for this population in community settings.
The mesentery: an ADME perspective on a ‘new’ organ

Abstract With the inclusion of mesentery, the total number of human organs has recently increased by one. The mesentery was formerly construed to be a complex, discontinuous anatomical structure simply serving as a support for organs in abdominal cavity. However, recent research has established the mesentery to be a far more simple and unfragmented organ. Newly emerging information on the mesentery has challenged some older pathophysiological concepts. This review briefly discusses the anatomy of the mesentery, historical perspective on the mesentery, embryology, drug metabolizing enzymes and transporters of the mesentery, and the mesentery’s role in diseases. The possible impact of the mesentery on absorption, distribution, metabolism, and excretion (ADME) is also discussed.
Real life Egyptian experience of Daclatasvir plus Sofosbuvir with Ribavirin in naïve difficult to treat HCV patients.

Background Chronic infection with Hepatitis C virus (HCV) is considered as a major cause for developing liver cirrhosis and hepatocellular carcinoma. A new era in HCV treatment is ongoing using direct acting antiviral activity (DAA). The first approved DAA drug was Sofosbuvir which has a high tolerability and preferable pharmacokinetic profile. Another recently developed drug is Daclatasvir a first-in-class HCV NS5A replication complex inhibitor. Both drugs are administered orally once daily and have potent antiviral activity with wide genotypic coverage. Methods In the outpatient clinic, one hundred and fifty naïve difficult to treat chronic HCV patients were recruited from Tropical Medicine Department at Fayoum public hospital. A combination of Daclatasvir (60 mg) and Sofosbuvir (400 mg) (DCV/SOF) has been administered for those patients once daily with Ribavirin (1200 mg or 1000 mg based on patients' weight on two divided doses) over a period of 12 weeks. All patients have been followed up for clinical, laboratory assessment and HCV PCR to detect the efficacy and safety of the therapy. Results Sustained Virologic Response rate (SVR12) was achieved in the vast majority of patients (90.67%). Cirrhotic patients showed lower SVR compared to non-cirrhotic patients (88.89% vs 90.91%, respectively). Around half of the patients (49.33%) developed adverse events (AEs) during treatment. The most common AEs were headache, fatigue and abdominal pain Conclusion The available evidence seems to suggest that combination therapy of (DCV/SOF with RBV) in the treatment of chronic HCV genotype IV naïve difficult to treat patients either cirrhotic or non-cirrhotic is safe and effective. Monitoring for clinical and laboratory hepatic parameters was the basis for these findings.
Clinical Profile of HLA B-27-Associated Uveitis Patients in a Tertiary Care Eye Hospital in Eastern India

ABSTRACT Purpose: To analyse clinical profile of the patients with HLA B 27- associated uveitis in a tertiary care eye hospital in Eastern India Method: Retrospective analysis of 61 eyes of 43 patients with HLA B27- associated uveitis between 2015 and 2016. Result: We observed a male predominance (67%), and more unilateral involvement (58%) in our patients. The mean age of presentation was 44.7 ±11.7 years. Significant vitritis and macular edema were noted in 14 and 7 eyes respectively. In addition to topical therapy, oral steroid was required in 49% patients and 58% patients were treated with methotrexate. Five patients (12%) required biologicals. There was improvement in BCVA at final follow-up (p<0.001). Conclusion: Compared to the existing literature, the current study observed relatively high age of presentation and frequent posterior segment involvement with less systemic association.
ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

Interleukin‐33 (IL‐33) and its receptor, ST2, are implicated in bone remodeling. The lack of estrogen after menopause results in an accelerated bone loss. Here we investigated the role of ST2 in the bone loss induced by estrogen deficiency. ST2‐deficient mice (ST2−/−) and their littermates (wildtype [WT]) were ovariectomized (OVX), while ovary‐intact mice were used as controls. Bone sites were analyzed by microcomputed tomography, histomorphometry, and quantitative real‐time polymerase chain reaction (qPCR). Deletion of IL‐33 or ST2 resulted in a similar bone loss in the femur and maxilla. Ovariectomy in WT mice caused bone loss in the same areas. The lack of ST2 in OVX mice did not alter bone remodeling in the femur but prevented bone loss in the maxilla. Consistently, ovariectomy increased the IL‐33 messenger RNA (mRNA) levels in the maxilla but not in the femur. Under mechanical stimulation, ovariectomy and ST2 deletion independently increased bone remodeling induced by orthodontic tooth movement, which was also associated with a greater number of osteoclasts and a reduced number of osteoblasts in the maxillary bone. ST2−/− OVX mice, however, displayed twice as many osteoblasts as that of WT OVX mice. Ovariectomy and ST2 deletion differently altered the cytokine mRNA levels in the maxilla. Remarkably, interleukin‐10 expression was decreased in both WT OVX and ST2−/− mice, and this reduction was completely restored in ST2−/− OVX mice. The results demonstrate that estrogen and IL33/ST2 independently protect against bone loss. However, the ovariectomy‐induced bone loss is IL‐33/ST2‐dependent in the maxilla but not in the femur, indicating a bimodal and site‐specific role of ST2 in bone remodeling.
Improving UN Intelligence through Civil–Military Collaboration: Lessons from the Joint Mission Analysis Centres

Fearing a loss of sovereignty, UN member states have historically been hesitant to provide the UN with an intelligence-collection mandate. The increased size, length and complexity of peacekeeping operations, compounded by severe security threats to UN personnel, make a stronger UN intelligence capability in the field increasingly necessary. The article examines the contribution of the UN's Joint Mission Analysis Centre (JMAC) to UN intelligence capabilities and concludes that, in larger missions in particular, the multidisciplinary JMAC structure has delivered valuable intelligence to senior mission management. Nevertheless, in all missions improved information-sharing procedures are necessary to ensure that the JMAC is able to fulfil its intelligence mandate.
Women’s role in male circumcision promotion in Rakai, Uganda

ABSTRACT Medical male circumcision (MMC) has expanded in sub-Saharan Africa, yet uptake remains sub-optimal. We sought to understand women’s perceptions of and influence on MMC in Rakai, Uganda. We conducted in-depth interviews with 27 women in fishing and trading communities, including women married to circumcised and uncircumcised men, single women, and sex workers. Data analysis followed a team-based framework approach. All female participants preferred circumcised men because of perceived reduced HIV and sexually transmitted infection (STI) risk, improved penile hygiene, and increased sexual pleasure. Perceived negative aspects included abstinence during wound healing, potentially increased male sexual risk behaviors, fear of being blamed for HIV acquisition, and economic insecurity due to time off work. Participants felt women could persuade their partners to be circumcised, accompany them to the clinic, refuse sex with uncircumcised men, and participate in community MMC activities. Findings support women’s important role in MMC acceptance.
Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients

Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case–control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real‐time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non‐remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.
Gene Signature of Proliferating Human Pancreatic &agr; Cells

Pancreatic α cells proliferate at a low rate, and little is known about the control of this process. Here we report the characterization of human α cells by large-scale, single-cell RNA sequencing coupled with pseudotime ordering. We identified two large subpopulations and a smaller cluster of proliferating α cells with increased expression of genes involved in cell-cycle regulation. The proliferating α cells were differentiated, had normal levels of GCG expression, and showed no signs of cellular stress. Proliferating α cells were detected in both the G1S and G2M phases of the cell cycle. Human α cells proliferate at a fivefold higher rate than human β cells and express lower levels of the cell-cycle inhibitors CDKN1A and CDKN1C. Collectively, this study provides the gene signatures of human α cells and the genes involved in their cell division. The lower expression of two cell-cycle inhibitors in human α cells could account for their higher rate of proliferation compared with their insulin-producing counterparts.
Effect of 12 wk of resistant starch supplementation on cardiometabolic risk factors in adults with prediabetes: a randomized controlled trial.

Background Type 2 resistant starch (RS2) has been shown to improve glycemic control and some cardiovascular endpoints in rodent and human studies. Objective The aim of this study was to perform one of the first randomized clinical trials in adults with prediabetes and one of the longest trials to test whether RS2 can improve cardiometabolic health. Design 68 overweight [body mass index (BMI) ≥27 kg/m2] adults aged 35-75 y with prediabetes were randomized to consume 45 g/d of high-amylose maize (RS2) or an isocaloric amount of the rapidly digestible starch amylopectin (control) for 12 wk. At baseline and postintervention, ectopic fat depots (visceral adipose tissue, intrahepatic lipids, and intramyocellular lipids) were measured by magnetic resonance imaging/spectroscopy, energy metabolism by respiratory chamber, and carbohydrate metabolism by glycated hemoglobin (HbA1c), an intravenous glucose tolerance test, and a meal tolerance test. Cardiovascular risk factors-serum lipids, blood pressure, heart rate, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, and tumor necrosis factor [TNF]-α)-were also measured. The primary endpoints were insulin sensitivity, insulin secretion, ectopic fat, and markers of inflammation. Data were primarily analyzed as treatment effects via a linear mixed model both with and without the addition of covariates. Results Relative to the control group, RS2 lowered HbA1c by a clinically insignificant 0.1 ± 0.2% (Δ = -1 ± 2 mmol/mol; P = 0.05) but did not affect insulin secretion, insulin sensitivity, the disposition index, or glucose or insulin areas under the curve relative to baseline (P ≥ 0.23). RS2 decreased heart rate by 5 ± 9 beats/min (P = 0.02) and TNF-α concentrations by 2.1 ± 2.7 pg/mL (P = 0.004), relative to the control group. Ectopic fat, energy expenditure, substrate oxidation, and all other cardiovascular risk factors were unaffected (P ≥ 0.06). Conclusions 12 wk of supplementation with resistant starch reduced the inflammatory marker TNF-α and heart rate, but it did not significantly improve glycemic control and other cardiovascular disease risk factors, in adults with prediabetes. This trial was registered at clinicaltrials.gov as NCT01708694.
The effect of time on cognitive impairments after non-traumatic subarachnoid haemorrhage and after traumatic brain injury

ABSTRACT Objectives: To compare the effect of time on cognitive impairments after Subarachnoid Haemorrhage and Traumatic Brain Injury and explore associations with baseline variables and global function. Methods: Patients with a Glasgow Coma Scale score of 3–13, were assessed at 3, 6 and 12 months post injury by use of BNIS for cognitive impairment, RLAS-R to categorise cognitive and behavioural function, Barthel Index to assess performance of daily living, HADS to screen for depression and anxiety, and EuroQoL-5D, LiSat-11 and Glasgow Outcome Scale Extended to assess global function. Results: BNIS T-scores did not differ significantly between groups and the proportion of patients with cognitive impairments was not significantly different at any time point. Cognition improved significantly between all time points in both groups except from 6 to 12 months after TBI. Generalised estimating equation showed non-significant signs of slower recovery of BNIS T-scores over time after SAH. Acute GCS scores were associated with BNIS T-scores after TBI but not after SAH. At 12 months, similar proportions of patients with SAH and TBI had good outcome. Conclusions: Cognitive improvements after SAH and TBI exhibit similarities and correlate with global function. GCS scores are associated with outcome after TBI but not after SAH.
Preliminary evaluation of plasticizer and BPA in Tunisian cosmetics and investigation of hazards on human skin cells

ABSTRACT In this study, 18 plasticizer (phthalates, adipates, sebacates, and others) and BPA residues in some cosmetic samples collected from Tunisian market are evaluated by micro-matrix solid-phase dispersion combined with GC-MS. In parallel, the impact of these molecules and the cosmetics in the human epithelial cell lines is investigated. The cytotoxic activity of cosmetic extracts is evaluated in vitro against B16 and Hep-2 human skin cell lines using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. This study shows that the tested cosmetic products could constitute a hazard to the consumer health and wellness and that strict safety analysis on cosmetic products needs to be carried out before they are marketed.
In vivo tracking of intravenously injected mesenchymal stem cells in an Alzheimer’s animal model

Purpose: The purpose of this study was to investigate how intravenously injected bone marrow-derived mesenchymal stem cells (BMSCs) are distributed in the body of an Alzheimer’s disease (AD) animal model. Methods: Stem cells were collected from bone marrow of mice and labeled with Indium-111 (111In). The 111In-labeled BMSCs were infused intravenously into 3×Tg-AD mice in the AD group and non-transgenic mice (B6129SF2/J) as controls. Biodistribution was evaluated with a gamma counter and gamma camera 24 and 48 h after injecting the stem cells. Results: A gamma count of the brain showed a higher distribution of labeled cells in the AD model than in the control group at 24 (p = .0004) and 48 h (p = .0016) after injection of the BMSCs. Similar results were observed by gamma camera imaging (i.e., brain uptake in the AD model was significantly higher than that in the control group). Among the other organs, uptake by the spleen was the highest in both groups. More BMSCs were found in the lungs of the control group than in those of the AD group. Conclusions: These results suggest that more intravenously infused BMSCs reached the brain in the AD model than in the control group, but the numbers of stem cells reaching the brain was very small.
A membrane fusion protein, Ykt6, regulates epithelial cell migration via microRNA-mediated suppression of Junctional Adhesion Molecule A

ABSTRACT Vesicle trafficking regulates epithelial cell migration by remodeling matrix adhesions and delivering signaling molecules to the migrating leading edge. Membrane fusion, which is driven by soluble N-ethylmaleimide-sensitive factor associated receptor (SNARE) proteins, is an essential step of vesicle trafficking. Mammalian SNAREs represent a large group of proteins, but few have been implicated in the regulation of cell migration. Ykt6 is a unique SNARE existing in equilibrium between active membrane-bound and inactive cytoplasmic pools, and mediating vesicle trafficking between different intracellular compartments. The biological functions of this protein remain poorly understood. In the present study, we found that Ykt6 acts as a negative regulator of migration and invasion of human prostate epithelial cells. Furthermore, Ykt6 regulates the integrity of epithelial adherens and tight junctions. The observed anti-migratory activity of Ykt6 is mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreases the cellular level of Junctional Adhesion Molecule (JAM) A. This decreased JAM-A expression limits the activity of Rap1 and Rac1 small GTPases, thereby attenuating cell spreading and motility. The described novel functions of Ykt6 could be essential for the regulation of epithelial barriers, epithelial repair, and metastatic dissemination of cancer cells.
Suppressed epithelial-mesenchymal transition and cancer stem cell properties mediate the anti-cancer effects of ethyl pyruvate via regulation of the AKT/nuclear factor-κB pathway in prostate cancer cells

Castration-resistant prostate cancer (CRPC) is a leading cause of mortality among cases of prostate cancer (PCa). Current treatment options for CRPC are limited. Ethyl pyruvate (EP), a lipophilic derivative of pyruvic acid, has been reported to have antitumor activities. In the present study, the efficacy of EP against PCa was investigated using two human PCa cell lines and a mouse xenograft tumor model. PC3 and CWR22RV1 cells were treated with EP, and cytotoxicity was evaluated via Cell Counting Kit-8 and colony formation assays, while cell cycle distribution was assessed by flow cytometry. Changes in cell migration and invasion caused by EP treatment were also evaluated with Transwell and wound healing assays, and changes in the expression of intracellular signaling pathway components were detected by western blotting. EP treatment reduced cell viability, induced G1 arrest, and activated the intrinsic apoptosis pathway. Additionally, the in vivo experiments revealed that EP administration markedly inhibited tumor growth. EP also reversed epithelial-mesenchymal transition and suppressed cancer stem cell properties in part through negative regulation of AKT/nuclear factor-κB signaling. These results indicate that EP has anticancer activity in vitro and in vivo, and is therefore a promising therapeutic agent for the treatment of PCa.
Programmed Death Ligand 1 Is a Negative Prognostic Marker in Recurrent Isocitrate Dehydrogenase-Wildtype Glioblastoma.

BACKGROUND Checkpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results. OBJECTIVE To validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification. METHODS Using tissue microarrays, we compared 5 PD-L1 monoclonal antibodies (n = 56) and validated expression (n = 183) using quantitative immunohistochemistry (IHC) and RNA in situ hybridization (RISH). Expression data from The Cancer Genome Atlas (TCGA) and published studies were compared with clinical outcome. Multiplexed immunophenotyping was used to identify PD-L1+ cell populations in post-treatment glioblastoma. RESULTS Using a 5% cut-off, PD-L1 expression was significantly associated with a poor prognosis in both histologically defined (n = 125, log-rank P < .001) and recurrent isocitrate dehydrogenase (IDH)-wildtype glioblastoma (n = 60, log-rank P = .015). PD-L1 remained a significant negative prognosticator in Cox regression analysis (hazard ratio: 1.96, P = .021). Analysis of TCGA data confirmed decreased overall survival in recurrent non-glioma CpG island methylator phenotype (G-CIMP) glioblastoma (n = 12, log-rank P = .023), but not in glioblastoma as a group (n = 444, log-rank P = .135). PD-L1 RISH showed a significant correlation with IHC (P < .0001). PD-L1 was observed in the proliferating perivascular stem cell and immune niche of post-treatment glioblastoma. CONCLUSION A 5% PD-L1 expression cut-off identified a subset of glioblastoma that is associated with a worse clinical outcome. This association remained significant within the newly defined IDH-wildtype classification. These findings could have implications for patient stratification in future clinical trials of PD-1/PD-L1 blockade.