Miracle-dz/UniFAR-FTUs huggingface dataset:
The microbiome modulating activity of bile acids

ABSTRACT Bile acids are potent antibacterial compounds and play an important role in shaping the microbial ecology of the gut. Here, we combined flow cytometry, growth rate measurements (OD600), and NMR- and mass spectrometry-based metabolomics to systematically profile the impact of bile acids on the microbiome using in vitro and in vivo models. This study confirmed that (1) unconjugated bile acids possess more potent antibacterial activity than conjugated bile acids; (2) Gram-positive bacteria are more sensitive to bile acids than Gram-negative bacteria; (3) some probiotic bacteria such as Lactobacillus and Bifidobacterium and 7α-dehydroxylating bacteria such as Clostridium scindens show bile acid resistance that is associated with activation of glycolysis. Moreover, we demonstrated that (4) as one of most hydrophobic bile acids, lithocholic acid (LCA) shows reduced toxicity to bacteria in the cecal microbiome in both in vivo and in vitro models; (5) bile acids directly and rapidly affect bacterial global metabolism including membrane damage, disrupted amino acid, nucleotide, and carbohydrate metabolism; and (6) in vivo, short-term exposure to bile acids significantly affected host metabolism via alterations of the bacterial community structure. This study systematically profiled interactions between bile acids and gut bacteria providing validation of previous observation and new insights into the interaction of bile acids with the microbiome and mechanisms related to bile acid tolerance.
Mechanisms of negative membrane curvature sensing and generation by ESCRT III subunit Snf7

Certain proteins have the propensity to bind to negatively curved membranes and generate negative membrane curvature. The mechanism of action of these proteins is much less studied and understood than those that sense and generate positive curvature. In this work, we use implicit membrane modeling to explore the mechanism of an important negative curvature sensing and generating protein: the main ESCRT III subunit Snf7. We find that Snf7 monomers alone can sense negative curvature and that curvature sensitivity increases for dimers and trimers. We have observed spontaneous bending of Snf7 oligomers into circular structures with preferred radius of ~20 nm. The preferred curvature of Snf7 filaments is further confirmed by the simulations of preformed spirals on a cylindrical membrane surface. Snf7 filaments cannot bind with the same interface to flat and curved membranes. We find that even when a filament has the preferred radius, it is always less stable on the flat membrane surface than on the interior cylindrical membrane surface. This provides an additional energy for membrane bending which has not been considered in the spiral spring model. Furthermore, the rings on the cylindrical spirals are bridged together by helix 4 and hence are extra stabilized compared to the spirals on the flat membrane surface.
Statin use is associated with improved survival in multiple myeloma: A Swedish population‐based study of 4315 patients

Statin use has been associated with reduced cancer‐specific mortality among patients with several cancer types, including multiple myeloma (MM). We aimed to further elucidate the association of statin use and dose intensity with MM survival. Using Swedish population‐based national health registers, we identified all incident MM diagnoses occurring January 1, 2007 to December 31, 2013 and their drug dispensations and comorbidities. We assessed statin exposure in 6‐month periods pre‐ and post‐diagnosis, treated diagnosis as baseline for calculating survival time, and calculated hazard ratios (HR) and 95% confidence intervals (CI) of exposure‐related MM‐specific and all‐cause mortality using Cox regression. We assessed statin exposure during the entire follow‐up and risk of MM‐specific mortality in a nested case‐control analysis. We classified dose intensity according to American College of Cardiology/American Heart Association recommendations. We ascertained 4315 MM cases during follow‐up. Statin use was associated with reduced MM‐specific mortality (pre‐diagnosis use multivariate‐adjusted HR, 95% CI: 0.83, 0.71‐0.96; 6 months post‐diagnosis: 0.73, 0.60‐0.89; entire follow‐up: 0.65, 0.52‐0.80) and (more weakly) with all‐cause mortality. Intensity analyses suggested a dose‐response; MM‐specific mortality decreased with increasing statin intensity in all time windows (eg, 6 months post‐diagnosis: low [0.76 (0.56‐1.03)], medium [0.73 (0.58‐0.92)], high [0.33 (0.08‐1.32)] intensity). However, relatively few patients received high intensity treatment, and the trend was statistically significant only for unadjusted pre‐diagnosis use.
Eukaryotic Cell Permeabilisation to Identify New Putative Chlamydial Type III Secretion System Effectors Secreted within Host Cell Cytoplasm

Chlamydia trachomatis and Waddlia chondrophila are strict intracellular bacteria belonging to the Chlamydiales order. C. trachomatis is the most frequent bacterial cause of genital and ocular infections whereas W. chondrophila is an opportunistic pathogen associated with adverse pregnancy outcomes and respiratory infections. Being strictly intracellular, these bacteria are engaged in a complex interplay with their hosts to modulate their environment and create optimal conditions for completing their life cycle. For this purpose, they possess several secretion pathways and, in particular, a Type III Secretion System (T3SS) devoted to the delivery of effector proteins in the host cell cytosol. Identifying these effectors is a crucial step in understanding the molecular basis of bacterial pathogenesis. Following incubation of infected cells with perfringolysin O, a pore-forming toxin that binds cholesterol present in plasma membranes, we analysed by mass spectrometry the protein content of the host cell cytoplasm. We identified 13 putative effectors secreted by C. trachomatis and 19 secreted by W. chondrophila. Using Y. enterocolitica as a heterologous expression and secretion system, we confirmed that four of these identified proteins are secreted by the T3SS. Two W. chondrophila T3SS effectors (hypothetical proteins Wcw_0499 and Wcw_1706) were further characterised and demonstrated to be early/mid-cycle effectors. In addition, Wcw_1706 is associated with a tetratricopeptide domain-containing protein homologous to C. trachomatis class II chaperone. Furthermore, we identified a novel C. trachomatis effector, CT460 that localises in the eukaryotic nucleus when ectopically expressed in 293 T cells.
Complement C1q mediates the expansion of periportal hepatic progenitor cells in senescence-associated inflammatory liver

Significance This study has identified C1q in the chronic hepatitis liver as an unorthodox signal for activating the essential β-catenin pathway in hepatic progenitor cells (HPCs) and liver tumors, which is critical for their proliferation and dedifferentiation. Inhibition of C1q not only effectively suppressed the expansion, but also facilitated the differentiation of HPCs and liver tumors. However, it spared the orthodox β-catenin function in pericentral normal hepatocytes. C1q thus becomes a potential therapeutic target for liver tumors derived from HPCs in patients with chronic hepatitis. Most hepatocellular carcinomas (HCCs) develop in patients with chronic hepatitis, which creates a microenvironment for the growth of hepatic progenitor cells (HPCs) at the periportal area and subsequent development of HCCs. We investigated the signal from the inflammatory liver for this pathogenic process in the hepatic conditional β-catenin knockout mouse model. Senescent β-catenin–depleted hepatocytes in aged mice create an inflammatory microenvironment that stimulates periportal HPC expansion but arrests differentiation, which predisposes mice to the development of liver tumors. The release of complement C1q from macrophages in the inflammatory niche was identified as the unorthodox signal that activated the β-catenin pathway in periportal HPCs and was responsible for their expansion and de-differentiation. C1q inhibitors blocked the β-catenin pathway in both the expanding HPCs and the liver tumors but spared its orthodox pathway in pericentral normal hepatocytes. This mechanism has been validated in human liver specimens from patients with chronic hepatitis. Taken together, these results demonstrate that C1q- mediated activation of β-catenin pathway in periportal HPCs is a previously unrecognized mechanism for replenishing hepatocytes in the inflammatory liver and, if unchecked, for promoting hepatocarcinogenesis. C1q may become a new target for blocking carcinogenesis in patients with chronic hepatitis.
Health-related quality of life (HRQoL) and symptom burden in patients (Pts) with myelofibrosis (MF) in the COMFORT-II study.

6626^ Background: Ruxolitinib has demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms and QoL in 2 phase 3 studies (COMFORT-I and -II) in pts with primary MF (PMF), post-polycythemia vera-MF (PPV-MF), or post-essential thrombocythemia-MF (PET-MF). The prevalence of individual symptoms among these pts has not been defined. We evaluated the baseline HRQoL and symptoms among pts enrolled in COMFORT-II. Methods: COMFORT-II is a randomized, open-label, multicenter, phase 3 study comparing ruxolitinib with best available therapy. HRQoL and symptoms were assessed at baseline using the European Organisation for the Research and Treatment of Cancer QoL Questionnaire–Core 30 (EORTC QLQ‑C30) and Functional Assessment of Cancer Therapy–Lymphoma (FACT‑Lym); this analysis summarizes these scores for all pts, regardless of assigned treatment. Results: In COMFORT-II (N = 219), 52% of pts were aged > 65 years and 57% were male. By IPSS criteria (Cervantes et al. 2009), 40% had i.
Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is frequently characterized by glucocorticoid (GC) resistance, which is associated with inferior outcomes, thus highlighting the need for novel therapeutic approaches for GC-resistant T-ALL. The pre-T-cell receptor (pTCR)/TCR signaling pathways play a critical role in cell fate decisions during physiological thymocyte development, with an interplay between TCR and glucocorticoid receptor (GR) signaling determining the T-lymphocyte selection process. We performed an shRNA screen in vitro and in vivo in T-ALL cell lines and patient-derived xenograft (PDX) samples to identify vulnerabilities in the pTCR/TCR pathway and identified a critical role for the lymphocyte cell-specific kinase (LCK) in cell proliferation. LCK knockdown or inhibition with dasatinib (DAS) caused cell cycle arrest. Combination of DAS with dexamethasone (DEX) resulted in significant drug synergy leading to cell death. The efficacy of this drug combination was underscored in a randomized phase II-like murine trial, recapitulating an early phase human clinical trial. T-ALL expansion in immunocompromised mice was significantly impaired using this drug combination, compared to mice receiving control vehicle or single drug treatment, highlighting the immediate clinical relevance of this drug combination for high-risk T-ALL patients. Our results thus provide a strategy to improve the efficacy of current chemotherapy platforms and circumvent GC resistance.
DYSPHAGIA AND VOCAL FOLD PARALYSIS IN CHILDREN AND ADOLESCENTS WITH BRAIN TUMORS

1Department of Speech-Language Pathology from Institute of Pediatric Oncology of Federal University of São Paulo (IOP-GRAACC/UNIFESP), São Paulo, Brazil 2Pediatric Oncologist of Institute of Pediatric Oncology of Federal University of São Paulo (IOPGRAACC/UNIFESP), São Paulo, Brazil 3Otorhinolaryngologist of Institute of Pediatric Oncology (IOP-GRAACC/UNIFESP), São Paulo, Brazil 4Pediatric Neurosurgeon of Institute of Pediatric Oncology (IOP-GRAACC/UNIFESP), São Paulo, Brazil
Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer

Epacadostat is a potent and highly selective inhibitor of indoleamine 2,3‐dioxygenase 1 (IDO1). Here we report results from the open‐label, dose‐escalation, Phase 1b ECHO‐110 study evaluating epacadostat plus atezolizumab in patients with previously treated Stage IIIB/IV nonsmall cell lung cancer (NSCLC). Eligible patients had received ≥1 prior line of platinum‐based chemotherapy (≥2 cycles) and no prior checkpoint/IDO inhibitors treatment. Oral epacadostat (25, 50, 75, 100, 200 or 300 mg) was administered twice daily (BID) with intravenous atezolizumab 1,200 mg every 3 weeks (Q3W). Primary endpoints were safety, tolerability and dose‐limiting toxicities (DLTs). Twenty‐nine patients received ≥1 dose of treatment. The maximum tolerated dose of epacadostat was not reached. Two patients had DLTs: one patient with Grade 3 dehydration and hypotension (epacadostat 200 mg BID); one patient with Grade 3 hyponatremia and Grade 4 autoimmune encephalitis (epacadostat 300 mg BID). Twenty‐three patients (79%) had treatment‐related adverse events (AEs); seven patients (24%) experienced Grade 3/4 events; five patients (17%) discontinued treatment due to treatment‐related AEs. No fatal treatment‐related AEs occurred. One patient achieved a partial response (objective response rate, 3%), which was maintained for 8.3 months; eight patients had stable disease. Baseline tumoral programmed cell death ligand 1 (PD‐L1) and IDO expression were low among patients with evaluable samples (1 of 23 expressed PD‐L1; 5 of 17 expressed IDO). Epacadostat pharmacokinetics was comparable to historical controls. Epacadostat, at doses up to 300 mg BID, combined with atezolizumab 1,200 mg Q3W was well tolerated in patients with previously treated NSCLC, although clinical activity was limited.
Comparative Study of Carrying Angle between Dominant and Non Dominanat Limb in Kashmiri Population

Introduction: Carrying angle (CA) is the angle subtended by median axis of the arm with fully extended and supinated forearm. There is scarcity of evidence in the literature regarding differences between the CA in both sexes depending upon the ossification of arm and forearm bones and comparison of CA between dominant and non dominant limb. Study aimed at comparison of data obtained by measuring CA by manual method between dominant and non dominant limb in age group 18 – 30 years. Material and Methods: CA was measured in 200 individuals of both sexes by clinical method with a manual goniometer. Results: Present study shows the significant gender difference and significant difference between dominant and non dominant limb. Conclusion: Unnecessary x ray exposure to children, young adults and pregnant women can be avoided, by measuring CA by clinical methods.
SEROPREVALENCE STUDY OF RUBELLA VIRUS INFECTION AMONG BAD OBSTETRIC HISTORY AND PRIMIGRAVIDA PREGNANT WOMEN IN IRAQ

This study was designed to investigate Rubella infection among pregnant women in relation with age and trimester of pregnancy. Venous blood was collected from 170 aborted women from different private laboratories during the period between December 2014 to march 2015. The randomly selected serum samples was tested for specific anti Rubella antibodies (IgM & IgG) using a commercial ELISA kit (Human Germany), the Series of 170 patients that had bad obstetric history and 80 pregnant women had primigravida that aborted in different times(1st, 2nd, and 3rd trimester of pregnancy). The results showed that the anti Rubella IgM among group I, was (48.9%) 44 out of 90 was higher than group II which was (36.25%) 29 out of 80 women and anti Rubella IgG in group II 57 out of 80 which was (71%) higher than in group I, which was 63 out of 90 (70%). So, anti Rubella antibodies IgM, IgG were 33 out of 90 (57.9%) in group I and (42.11%) 24 out of 80 in group II. The total of 170 women patients with mean age 27-7 years ranged between (16-42) years consisted of 61% aged between 16-30 years, 38.9% aged between 31-42 years for group I, and 62.5% within 16-30, 37.5% between 31-42 years. The gestational periods for group I were 55.56%, 3556%, 8.9% in the first, second and third trimester, 48-75%, 25%, 13.75% for group II in the first, second and third trimester of pregnancy. It could be concluded from this study that seroprevalence of Rubella infection among pregnant women and the high percentage of infection among those patients who extremely high level of ignorance about the disease so, every pregnant women should be tested for Rubella serological status. World Journal of Pharmaceutical Research SJIF Impact Factor 5.990 Volume 4, Issue 8, 378-384. Research Article ISSN 2277– 7105
Division, result and score margin alter the physical and technical performance of elite wheelchair tennis players

ABSTRACT This study determined the physical and technical demands of elite wheelchair tennis (WT) match-play, how the demands differed between divisions (Men, Women, Quad) and the effect that set result and score margin had on these demands. Seventeen WT players were monitored during a singles competition. Physical measures of performance were analysed using an indoor tracking system and inertial measurement units. Technical measures of performance were examined using video analysis. Physical measures of performance differed by division (Men > Women > Quad) for most parameters. Rallies were longer during Men’s (P = 0.027) and Women’s (P = 0.004) matches compared to Quad’s and fewer shots were hit off 2 bounces in Men’s matches compared to Women’s and Quad’s (P ≤ 0.026). High-speed activity (HSA) increased during losing sets (P = 0.043). Most physical measures of performance increased by moderate to large effects during sets with a small score margin (≤3 games differential). Mean speed and HSA were similar during losing sets, regardless of margin, but decreased (large effects) when winning by a large margin. This study demonstrated the physical and technical demands that elite WT players need to be prepared for and how situational factors can influence these demands.
Bartın Üniversitesi Sağlık Hizmetleri Meslek Yüksekokulu Öğrencilerinde Beslenme Alışkanlıkları ve Obezite Prevalansı

Obezite; yanlis beslenme, sedanter yasam tarzi, hormonal bozukluklar, genetik faktorler ve psikososyal etmenler nedeniyle sagligi bozacak olcude vucutta asiri yag birikmesi sonucu ortaya cikan kronik bir hastaliktir. Ayrica obezite; kalp-damar hastaliklari, hipertansiyon, solunum yolu hastaliklari, diyabet gibi kronik hastaliklara zemin hazirlayarak psikolojik, sosyal ve ekonomik sorunlara neden olan, yasam kalitesini dusurerek yasam suresini kisaltan, gelismis ve gelismekte olan ulkelerde, her yas grubunda giderek artan oranlarla gorulen, onlenebilir bir halk sagligi sorunudur. Bu calismada saglikli beslenme aliskanliklarinin bozulmasi, hazir gidalarin tuketiminin artmasi ve fiziksel aktivitenin azalmasi gibi riskli, beslenme aliskanliklari ve obezite prevalansi degerlendirilmistir. Bartin Universitesi Saglik Hizmetleri Meslek Yuksekokulu’nda 2014-2015 egitim ogretim yilinda ogrenim goren, rastgele secilen 167 kiz (%58.2), 120 erkek (%41.8) olmak uzere toplam 287 ogrenci arastirmamiza dahil edilmistir. Arastirmada katilimcilarin antropometrik vucut olcumleri yapilmis olup, beslenme aliskanliklarini, fiziksel aktivite durumlarini ve saglikli yasam bicimi davranislarini sorgulamak amaciyla katilimcilara anket uygulanmistir. Arastirmaya katilan erkek ogrencilerin %65’inin kiz ogrencilerin %73.1’inin normal kiloda oldugu, erkek ogrencilerin %21.7’si ve kiz ogrencilerin %16.8’i fazla kilolu oldugu ve erkek ogrencilerin %5.8’i ve kiz ogrencilerin %4.2’sinin obez oldugu gorulmustur. Tum veriler incelendiginde arastirmaya katilan universite ogrencilerinin %69.7’sinin normal kilolu, %18.8’inin fazla kilolu, %6.6’sinin zayif ve %4.9’unun ise obez oldugu tespit edilmistir. Sonuc olarak Ogrencilerin sedanter yasam tarzlari, beslenme aliskanliklari, ana ve ara ogun tuketme ve ogun atlama durumlari gozden gecirilmeli, fiziksel aktiviteyi artirmak icin toplu ulasim araclarini kullanimi yerine mumkun mertebe yurumeleri tesvik edilmelidir. Toplumun her basamagini bilgilendirmek amacli, saglikli yasam tarzi, yeterli ve dengeli beslenme, fiziksel aktivite, obezite ve tedavi yontemleri konularinda, kamu spotu, kitap, dergi ve egitim materyalleri gibi cesitli kaynaklar hazirlanmali ve halka ulastirilmalidir.
Complete Genome Sequences for Two Myoviridae Strains Infecting Cyanobacteria in a Subarctic Lake

We isolated two closely related strains that belong to the Myoviridae family and infect cyanobacteria in a shallow subarctic rock basin lake. Their host was identified as a member of the Synechococcus-Cyanobium complex. Sequenced genomes of the two phages were 244,930 bp and 243,633 bp. We describe their annotation and highlight some noteworthy features. ABSTRACT We isolated two closely related strains that belong to the Myoviridae family and infect cyanobacteria in a shallow subarctic rock basin lake. Their host was identified as a member of the Synechococcus-Cyanobium complex. Sequenced genomes of the two phages were 244,930 bp and 243,633 bp. We describe their annotation and highlight some noteworthy features.
Ensuring the comparability of cross-national survey data on intimate partner violence against women: a cross-sectional, population-based study in the European Union

Objectives To ensure the cross-national comparability of the set of questions addressing physical and sexual intimate partner violence against women (IPVAW) included in the European Union (EU) Agency for Fundamental Rights (FRA) survey. Once the measurement invariance of these measures is established, we aim to make appropriate and valid comparisons of the levels of physical and sexual IPVAW across the EU countries. Design Cross-sectional, population-based study. Participants Data were drawn from the survey conducted by the FRA on violence against women, including the responses of 42 002 adult women from the 28 countries of the EU. Main outcome measures The set of questions addressing lifetime prevalence of physical and sexual IPVAW used in the FRA survey. The psychometric properties (ie, reliability and validity) of these measures were examined, as well as their latent structure and their measurement invariance across the 28 EU countries. Results The physical and sexual IPVAW measures presented adequate internal consistency and validity evidence based on their relations to other variables in all countries. A latent two-factor structure was supported and scalar invariance was established across countries. Our results showed that the average levels of physical and sexual IPVAW were highest in Denmark, Finland, Sweden and UK compared with the rest of the EU countries. In many of the other countries the levels of these types of violence overlapped, especially in the case of sexual IPVAW. Conclusions The findings of this study showed that the set of questions addressing physical and sexual IPVAW included in the FRA survey can be compared across all EU countries, highlighting the importance of testing the measurement equivalence of the instruments used in large sociodemographic surveys in order to make valid cross-national comparisons.