Miracle-dz/UniFAR-FTUs huggingface dataset:
Soluble epoxide hydrolase is an endogenous regulator of obesity-induced intestinal barrier dysfunction and bacterial translocation

Significance Defective intestinal barrier function and enhanced lipopolysaccharide (LPS)/bacterial translocation is a key pathogenic factor in many human diseases, including obesity. To date, the molecular mechanisms leading to intestinal barrier defects are not well understood, and there are no available therapeutic approaches to target intestinal barrier function. Here we show that soluble epoxide hydrolase (sEH) could be a novel therapeutic target of obesity-induced intestinal barrier dysfunction and LPS/bacterial translocation, and that sEH inhibitors, which have been evaluated in human clinical trials targeting other disorders, could be promising agents for prevention or treatment. Intestinal barrier dysfunction, which leads to translocation of bacteria or toxic bacterial products from the gut into bloodstream and results in systemic inflammation, is a key pathogenic factor in many human diseases. However, the molecular mechanisms leading to intestinal barrier defects are not well understood, and there are currently no available therapeutic approaches to target intestinal barrier function. Here we show that soluble epoxide hydrolase (sEH) is an endogenous regulator of obesity-induced intestinal barrier dysfunction. We find that sEH is overexpressed in the colons of obese mice. In addition, pharmacologic inhibition or genetic ablation of sEH abolishes obesity-induced gut leakage, translocation of endotoxin lipopolysaccharide or bacteria, and bacterial invasion-induced adipose inflammation. Furthermore, systematic treatment with sEH-produced lipid metabolites, dihydroxyeicosatrienoic acids, induces bacterial translocation and colonic inflammation in mice. The actions of sEH are mediated by gut bacteria-dependent mechanisms, since inhibition or genetic ablation of sEH fails to attenuate obesity-induced gut leakage and adipose inflammation in mice lacking gut bacteria. Overall, these results support that sEH is a potential therapeutic target for obesity-induced intestinal barrier dysfunction, and that sEH inhibitors, which have been evaluated in human clinical trials targeting other human disorders, could be promising agents for prevention and/or treatment.
Psoralen Derivatives with Enhanced Potency

Psoralen is a furocoumarin natural product that intercalates within DNA and forms covalent adducts when activated by ultraviolet radiation. It is well known that this property contributes to psoralen’s clinical efficacy in several disease contexts, which include vitiligo, psoriasis, graft‐versus‐host disease and cutaneous T‐cell lymphoma. Given the therapeutic relevance of psoralen and its derivatives, we attempted to synthesize psoralens with even greater potency. In this study, we report a library of 73 novel psoralens, the largest collection of its kind. When screened for the ability to reduce cell proliferation, we identified two derivatives even more cytotoxic than 4′‐aminomethyl‐4,5′,8‐trimethylpsoralen (AMT), one of the most potent psoralens identified to date. Using MALDI‐TOF MS, we studied the DNA adduct formation for a subset of novel psoralens and found that in most cases enhanced DNA binding correlated well with cytotoxicity. Generally, our most potent derivatives contain positively charged substituents, which we believe increase DNA affinity and enhance psoralen intercalation. Thus, we provide a rational approach to guide efforts toward further optimizing psoralens to fully capitalize on this drug class’ therapeutic potential. Finally, the structure–activity insights we have gained shed light on several opportunities to study currently underappreciated aspects of psoralen’s mechanism.
The Pharmacokinetic–Pharmacodynamic (PKPD) Relationships of AZD3229, a Novel and Selective Inhibitor of KIT, in a Range of Mouse Xenograft Models of GIST

Purpose: The emergence of secondary mutations is a cause of resistance to current KIT inhibitors used in the treatment of patients with gastrointestinal stromal tumors (GIST). AZD3229 is a selective inhibitor of wild-type KIT and a wide spectrum of primary and secondary mutations seen in patients with GIST. The objective of this analysis is to establish the pharmacokinetic–pharmacodynamic (PKPD) relationship of AZD3229 in a range of mouse GIST tumor models harboring primary and secondary KIT mutations, and to benchmark AZD3229 against other KIT inhibitors. Experimental Design: A PKPD model was developed for AZD3229 linking plasma concentrations to inhibition of phosphorylated KIT using data generated from several in vivo preclinical tumor models, and in vitro data generated in a panel of Ba/F3 cell lines. Results: AZD3229 drives inhibition of phosphorylated KIT in an exposure-dependent manner, and optimal efficacy is observed when >90% inhibition of KIT phosphorylation is sustained over the dosing interval. Integrating the predicted human pharmacokinetics into the mouse PKPD model predicts that an oral twice daily human dose greater than 34 mg is required to ensure adequate coverage across the mutations investigated. Benchmarking shows that compared with standard-of-care KIT inhibitors, AZD3229 has the potential to deliver the required target coverage across a wider spectrum of primary or secondary mutations. Conclusions: We demonstrate that AZD3229 warrants clinical investigation as a new treatment for patients with GIST based on its ability to inhibit both ATP-binding and A-loop mutations of KIT at clinically relevant exposures.
Determinants of Therapeutic Alliance With People With Psychotic Disorders

Abstract Therapeutic alliance determines medical treatment adherence, the success of psychotherapy, and the effectiveness of care. This systematic review aims at better understanding its determinants. The electronic databases Pubmed, Cochrane Library, and Web of Science were searched, using combinations of terms relating to psychosis and therapeutic alliance. Studies were selected and data were extracted using a PRISMA statement. Forty-one studies were selected, including 20 cross-sectional studies, 10 cohort studies, five randomized controlled trials, four literature reviews, and two retrospective studies. The quality of therapeutic alliance correlates with clinical symptoms, insight, social and family support, the therapist's qualities, the availability of shared therapeutic decision making, and the types of hospitalization. Although current evidence needs to be completed with further studies, it is already clear that group and family psychoeducation, cognitive remediation, community-based psychiatric services, and shared therapeutic decision making are essential approaches in the management of patients with psychosis.
Glucose Homeostasis and the Metabolic Syndrome

Glucose Homeostasis and the Metabolic Syndrome Glucose homeostasis represents the outcome of a complex feedback system for maintaining glucose tolerance within rather narrow physiological limits. Aberrant glucose homeostasis contributes to a number of downstream effects, including insulin resistance. Insulin resistance occurs when muscle, fat, or liver does not appropriately use the insulin that is produced by the pancreas. As a result, more insulin is required to process the same amount of glucose, but with increasing insulin resistance, there are increasing levels of glucose in the circulation. Deviant glucose homeostasis, coupled with insulin resistance, results in both hyperglycemia and hyperinsulinemia, leading to risk of type 2 diabetes mellitus (T2DM). T2DM, obesity, and other factors that increase the risk of cardiovascular disease constitute an entity defined as the metabolic syndrome. Although multiple (but similar) versions of the metabolic syndrome have been described (ie, insulin resistance syndrome, Syndrome X), they all include measures of obesity, hypertension, T2DM, and dyslipidemia. Importantly, genetic factors play a critical role in glucose homeostasis (T2DM), insulin resistance, and the components of the metabolic syndrome. This article accompanies the ATVB in Focus: Metabolic Syndrome and Insulin Resistance: Mechanisms and Consequences series that was published in the August 2012 issue.
Fundoplication After Myotomy for Achalasia

To the Editor: I was interested in reading the article of W.O. Richards et al entitled “Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia” published in Annals of Surgery, Sept 2004. The authors studied the antireflux effect of Dor’s anterior fundoplication associated with Heller’s myotomy by means of a prospective randomized study in which a group of 21 patients underwent simple Heller procedure and another group of 22 patients underwent Heller plus Dor’s fundoplication. The conclusion was that pathologic gastroesophageal reflux (GER) occurred more significantly in the first group of patients. Nevertheless, the occurrence of pathologic GER after simple transabdominal or laparoscopic myotomy is known by all surgeons interested in the field for over 20 years! In fact, a high percentage of pathologic GER (47.6%) was found by the authors 6 months later. What will this percentage be after 10 years? In the 1980s we performed 2 experimental studies in which it was demonstrated that transabdominal myotomy is responsible for development of pathologic GER and esophagitis in all cases. Simple myotomy, without antireflux procedure, supported by Ellis must be performed by transthoracic or thoracoscopic approach and this procedure should be compared with transabdominal or laparoscopic myotomy with fundoplication. In fact, transthoracic approach preserves hiatal attachments that, on the contrary, are cut during esophageal transabdominal mobilization: this mobilization causes thoracic dislocation of the Lower Esophageal Sphincter (LES), that, with myotomy, is responsible for GER development. Dor’s procedure, added to myotomy, has an antireflux effect when the gastric fundus is sutured to the crural pillars as well as to the myotomy edges: in this way the lower esophagus, kept in the abdomen and undergone to the abdominal pressure, acts as a new “high pressure zone. ” I have been performing this technique of “anchorage” since the 1980s. Besides, the authors report a LES mean pressure of 13.7 and 13.9 mm Hg in both groups of patients. In patients submitted to simple myotomy this pressure is too high in my opinion and it means that muscular fibers were not completely cut. Using intraoperative esophageal manometry (I EM) we got a LES pressure close to zero after myotomy and this pressure increases after fundoplication. Finally, I believe that 6 months is too short-term to evaluate the results of this kind of surgery. In conclusion, I think that today, on the basis of the literature and the international surgical experience, abdominal surgeons must associate fundoplication to myotomy in the management of achalasia. On the contrary, thoracic surgeons, on the basis of Ellis experience, can perform a simple myotomy by transthoracic or thoracoscopic approach. A comparison between these 2 techniques will tell us which the best one is.
ESA-RANDOMIZED CONTROLLED TRIAL Impact of Surgical Technique on Long-term Complication Rate After Laparoscopic Adjustable Gastric Banding (LAGB)

Benjamin Le Coq, MD, Vincent Frering, MD,y Mohammed Ghunaim, MD, Pierre Campan, MD,z André Dabrowski, MD,§ Emmanuel Mulliez, MD, jj Eric Loridan, MD, Frédéric Combemale, MD,yy Franck Denimal, MD,zz Fanelly Torres, MD, Gregory Baud, MD, Camille Thibault, Guelareh Dezfoulian, MD,§§ Laurent Arnalsteen, MD, Alain Duhamel, MD, PhD,jjjj François Pattou, MD, and Robert Caiazzo, MD, PhD , on Behalf of the OSEAN Study Group
Coping for missing content and missing links in document network embedding: student research abstract

Searching through networks of documents is an important task. A promising path to improve the performance of information retrieval systems in this context is to leverage dense node and content representations learned with embedding techniques. However, these techniques cannot learn representations for documents that are either isolated or whose content is missing. To tackle this issue, assuming that the topology of the network and the content of the documents correlate, we propose to estimate the missing node representations from the available content representations, and conversely. Inspired by recent advances in machine translation, we detail in this paper how to learn a linear transformation from a set of aligned content and node representations. The projection matrix is efficiently calculated in terms of the singular value decomposition. The usefulness of the proposed method is highlighted by the improved ability to predict the neighborhood of nodes whose links are unobserved based on the projected content representations, and to retrieve similar documents when content is missing, based on the projected node representations.
Molecular characterization of k-casein allelic variants in Bulgarian buffalo breed

This study aimed to analyze the genetic polymorphism at the k-CN (CSN3) locus in the Murrah Bulgarian buffalo breed. A 221 bp fragment of exon IV of CSN3 gene was amplified and sequenced to detect polymorphisms in 215 animals. Genotyping, by means of sequence alignments, revealed the presence of one polymorphism at codon 135 that occurs with a substitution of a Thr (ACC) of the A genetic variant for an Ile (ATC) of the B genetic variant, while codon 148 resulted monomorphic for the presence of an Ala residue (GCT). Additionally a silent mutation Thr-Thr (ACC/ACT) occurs at 136 codon position. Genotypes frequencies at codon 135 were 0.56 (AA), 0.40 (AB) and 0.04 (BB) being the gene frequencies 0.76 and 0.24 for the A and B allele respectively. No significant deviation from Hardy-Weinberg Equilibrium was observed.
Influence of 3D Printed Topological Structure on Lightweight Mullite Load Bearing Board in Thermal Environment

In order to achieve the purpose of resource and energy saving in the process of producing ceramics products, the hollow lightweight load bearing board in thermal environment with topological structures was made by 3D printing. In this study, the load bearing board manufactured with different topological structures such as vertical grid, oblique square grid, and honeycomb grid was printed by direct ink writing technology using the same raw material of kaolin clay and α-Al2O3 powder. The three kinds of samples were sintered at 1450°C × 3 h. The effect of printed structures on mechanical property of load bearing board samples was investigated. Moreover, the finite element simulation was used to study the stress distribution of the load bearing board. Comparing with results obtained by three kinds of samples, honeycomb grid supported samples proved to be the most appropriate structure in various directions comprehensively.
Comparing the Single-item Visual Analog Scale with Multi-item Hospital Anxiety and Depression Scale, and Patient Health Questionnaire-9 to Diagnose Depression in Patients with Idiopathic Parkinson’s Disease

Background: Depression is one of the common non-motor symptoms in patients with Parkinson disease (PD), which can have a negative effect on the quality of life of the patients. Therefore, it is necessary to have suitable, accurate, cheap, and simple diagnostic tools to identify depression in patients with PD and apply a proper treatment. The current study aimed at comparing the single-item visual analog scale (VAS) with the multi-item hospital anxiety and depression scale (HADS) and patient health questionnaire-9 (PHQ-9) in respect to their sensitivity and specificity to diagnose depression in patients with idiopathic PD. Methods: The current cross sectional, comparative study employed the simple non-probability method and selected 79 patients with idiopathic PD, with the mean (SD) age of 59.10 (10.84) years and the average (SD) of disease progression level of 3.24 (1.13), based on Hoehn and Yahr scale. The single-item scale VAS and multi-item tests HADS and PHQ-9 were used as an index tests, and Beck depression inventory (BDI) was employed as the reference test to evaluate depression in 3 levels of lack of (or mild) depression, moderate depression, and severe depression using 90% sensitivity and 90% specificity. To determine the sensitivity, specificity, and the ability of each index test in order to diagnose depression, agreement percent of index tests with reference test and receiver operating characteristic (ROC) analysis were used. Results: The results of ROC analysis showed that VAS (AUC = 0.84) and HADS (AUC = 0.87) and PHQ-9 (AUC = 0.85) possessed similar abilities to discriminate depression in patients with PD. The sensitivity of VAS, HADS, and PHQ-9 tests in moderate or greater threshold were 92%, 96%, and 89%, respectively, and in severe threshold were 64%, 79%, and 49%, respectively. Specificity of these tests in moderate or greater threshold were 42%, 50%, and 62%, respectively, and in severe threshold were 88%, 77%, and 88%, respectively. The highest agreement level with BDI in mild/moderate and severe levels of depression were found in VAS and PHQ-9, respectively. Conclusions: The single-item scale VAS, similar to multi-item tests HADS and PHQ-9, had a low to high sensitivity and specificity to diagnose depression in moderate or greater and severe thresholds in patients with PD.
The impact of the Neonatal Intensive Care Unit on sensory and developmental outcomes in infants born preterm: A scoping review

Introduction Preterm infants admitted to the Neonatal Intensive Care Unit are at higher risk of poor neurodevelopmental and sensory outcomes. There is interest in establishing whether elements of the Neonatal Intensive Care Unit sensory environment may influence the sensory and overall development of these infants. Method The purpose of this scoping review was to provide a comprehensive overview of relevant research regarding the sensory elements of the Neonatal Intensive Care Unit, and their short- and long-term influence on preterm infants. This scoping review is underpinned by the six-stage framework by Arksey and O’Malley. Results There are few studies that have directly examined the influence of the Neonatal Intensive Care Unit environment upon the sensory and developmental outcomes of infants born preterm, in infancy. The findings of the studies included in this review suggest that the Neonatal Intensive Care Unit sensory environment may alter developmental trajectories of preterm infants. However, low-quality evidence exists in this field, with much of the literature being preliminary. Conclusion Further experimental studies are required that combine multiple methods of assessment to more rigorously understand the sensory characteristics of the Neonatal Intensive Care Unit, and their relationship with developmental outcomes across early childhood.
Determinant of Sesame Export Performance in Ethiopia: A Panel Gravity Model Application

Ethiopia’s sesame export earn percentage share in the total export had been rapid declining over the last decades while it was the second commodity in currency grossing of the country. The objective of this study was to examine the determinant factors of Ethiopia’s sesame exports performance, in the aspect of export trade, by the use of a more realistic model approach, a panel gravity model. It used short panel data that cover 11 countries of consistent Ethiopia’s sesame importers for the period of 13 years from 2002 to 2014. The panel unit root test of Levin-Lin-Chu was used for each variable and applied the first difference transformation for the variables that had a unit root. The random effect model results suggested that real gross domestic product of importing countries; Ethiopian real gross domestic product, real exchange rate and weighted distance were found to be the determinant factors of Ethiopia’s sesame exports performance. The estimated results revealed that as real gross domestic product of importing countries increase by 1%, the flows of Ethiopia’s sesame exports performance increase by 1.63%. Based on the finding results, the researcher recommends that the policy maker must adopt the policies that reduce the cost of shipping through improving the infrastructure for shipments sector and contract a free trade agreement with distant countries. The government should encourage the private sector to diversify their products and improving the quality of its products to increase the competitiveness the Ethiopian products in foreign markets.
Life threatening complication of fine needle aspiration of neck mass in a child: a case report

Fine needle aspiration biopsy has become an important first line of investigation in palpable neck masses. It is simple, sensitive, inexpensive and safe investigation. Minor complications include pain, rashes and irritation at the site of aspiration. Life threatening complication occurs rarely. This is a report of child who presented with internal carotid artery injury with a massive hematoma causing respiratory distress following Fine needle aspiration. The child underwent neck exploration with evacuation of hematoma. Though life threatening complications post Fine needle aspiration are rare, this case highlights the precautions to be taken while performing fine needle aspiration in deep seated neck mass.
JULIANA MARTINS AGUIAR_VPS PRONTA

MARTINS, J. A. Genotyping of Giardia duodenalis: detection of mixed infection and genetic recombination in samples of human origin. [Genotipagem de Giardia duodenalis: detecção de infecções mistas e recombinações gênica s em mostras de origem humana]. 2015. 40 f. Tese (Doutorado em Ciências) – Faculdade de M edicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, 2015. Giardia duodenalis is a worldwide distribution enteric protozoan resp onsible for causing infections in a wide variety of mammals, including humans. Even showing little change in their morphology, isolates can be distinguished, ac cording to the analysis of proteins and DNA polymorphisms in at least eight distinct geneti c groups, known assemblages (A H). Only assemblages A and B have been reported in humans and other mam mals. Isolates of assemblage A also can be divided into four s b-assemblages (AI, AII, AIII and AIV). Heterogeneous sequences have been frequently identi fied in studies involving molecular characterization of samples containing multiple cys ts of the parasite. Seeking to study the occurrence of allelic sequence heterozygosity (ASH) and genetic recombination events, the present study aimed to isolate G. duodenalis cysts employing the micromanipulation technique and characterize them molecularly through multilocus analysis involving dh, tpi, orfC4 and bg genes. Ten cysts were individualized and used in t he research. All cysts were equally identified for all genes; nine cysts were c haracterized as assemblage AII and one characterized as assemblage B. The chromatograms derived from the cyst identif ied as assemblage B presented many heterogeneous sites in gdh, bg and orfC4 genes, and in these last two, there were overlaps of alleles AII and B in the sequenced product (heterozygous inter assemblage). PCR products were cloned and the sequences obtained revealed the occurrence of two alleles at this single cyst. The polymorphic sites found in the sequences of the gdh gene indicated intra heterozygosity assemblage B. Although ASH has already been reported in G. duodenalis individualized cysts, these are the first results indicating the presence of two alleles simultaneously in a single individual. These results demonstrate strong evidence that genetic exchange occurs between indiv iduals genetically distinct of G. duodenalis.