tbuckley/cabot-search huggingface dataset:
Forkhead box A2 regulates biliary heterogeneity and senescence during cholestatic liver injury in mice‡
Authors: Kelly McDaniel, Fanyin Meng, Nan Wu, Keisaku Sato, Julie Venter, Francesca Bernuzzi, Pietro Invernizzi, Tianhao Zhou, Konstantina Kyritsi, Ying Wan, Qiaobing Huang, Paolo Onori, Heather Francis, Eugenio Gaudio, Shannon Glaser, Gianfranco Alpini
Journal: Hepatology (2016)

Biliary‐committed progenitor cells (small mouse cholangiocytes; SMCCs) from small bile ducts are more resistant to hepatobiliary injury than large mouse cholangiocytes (LGCCs) from large bile ducts. The definitive endoderm marker, forkhead box A2 (FoxA2), is the key transcriptional factor that regulates cell differentiation and tissue regeneration. Our aim was to characterize the translational role of FoxA2 during cholestatic liver injury. Messenger RNA expression in SMCCs and LGCCs was assessed by polymerase chain reaction (PCR) array analysis. Liver tissues and hepatic stellate cells (HSCs) from primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) patients were tested by real‐time PCR for methylation, senescence, and fibrosis markers. Bile duct ligation (BDL) and multidrug resistance protein 2 (MDR2) knockout mice (MDR2 –/– ) were used as animal models of cholestatic liver injury with or without healthy transplanted large or small cholangiocytes. We demonstrated that FoxA2 was notably enhanced in murine liver progenitor cells and SMCCs and was silenced in human PSC and PBC liver tissues relative to respective controls that are correlated with the epigenetic methylation enzymes, DNA methyltransferase (DNMT) 1 and DNMT3B. Serum alanine aminotransferase and aspartate aminotransferase levels in nonobese diabetic/severe combined immunodeficiency mice engrafted with SMCCs post‐BDL showed significant changes compared to vehicle‐treated mice, along with improved liver fibrosis. Enhanced expression of FoxA2 was observed in BDL mouse liver after SMCC cell therapy. Furthermore, activation of fibrosis signaling pathways were observed in BDL/MDR2 –/– mouse liver as well as in isolated HSCs by laser capture microdissection, and these signals were recovered along with reduced hepatic senescence and enhanced hepatic stellate cellular senescence after SMCC engraft. Conclusion: The definitive endoderm marker and the positive regulator of biliary development, FoxA2, mediates the therapeutic effect of biliary‐committed progenitor cells during cholestatic liver injury. (H epatology 2017;65:544‐559).
Coexpression of BTLA and PD-1 Identifies a Novel CD4 T-Cell Exhaustion Phenotype in Human Hepatocellular Carcinoma
Authors: Q. Zhao, Z.-L. Huang, L. Peng, P. Wang, C. Lin, D.-M. Kuang, L. Zheng, Z. Gao
Journal: Journal of Hepatology (2016)
MIR-155: A Double Faced Microrna with Respect to its Impact on Tumorigenesis in both Natural Killer Cells and their Target Hepatocytes
Authors: M.A. Rahmoon, R.A. Youness, A.I. Gomaa, I. Waked, H.M. El Tayebi, A.I. Abdelaziz
Journal: Journal of Hepatology (2016)
How could we identify the ‘old’ patient in gastric cancer surgery? A single centre cohort study
Authors: Leonardo Solaini, Silvia Ministrini, Arianna Coniglio, Sara Cavallari, Beatrice Molteni, Gian Luca Baiocchi, Nazario Portolani, Guido Alberto Massimo Tiberio
Journal: International Journal of Surgery (2016)
Hepatitis C virus double‐stranded RNA is the predominant form in human liver and in interferon‐treated cells
Authors: Arielle Klepper, Francis J. Eng, Erin H. Doyle, Ahmed El‐Shamy, Adeeb H. Rahman, M. Isabel Fiel, Gonzalo Carrasco Avino, Moonju Lee, Fei Ye, Sasan Roayaie, Meena B. Bansal, Margaret R. MacDonald, Thomas D. Schiano, Andrea D. Branch
Journal: Hepatology (2016)

Hepatitis C virus (HCV) is unique among RNA viruses in its ability to establish chronic infection in the majority of exposed adults. HCV persists in the liver despite interferon (IFN)‐stimulated gene (ISG) induction; robust induction actually predicts treatment failure and viral persistence. It is unclear which forms of HCV RNA are associated with ISG induction and IFN resistance during natural infections. To thoroughly delineate HCV RNA populations, we developed conditions that fully separate the strands of long double‐stranded RNA (dsRNA) and allow the released RNAs to be quantified in reverse transcription/polymerase chain reaction assays. These methods revealed that dsRNA, a pathogen‐associated molecular pattern (PAMP), comprised 52% (standard deviation, 28%) of the HCV RNA in the livers of patients with chronic infection. HCV dsRNA was proportionally higher in patients with the unfavorable IL28B TT (rs12979860) genotype. Higher ratios of HCV double‐stranded to single‐stranded RNA (ssRNA) correlated positively with ISG induction. In Huh‐7.5 cells, IFN treatment increased the total amount of HCV dsRNA through a process that required de novo viral RNA synthesis and shifted the ratio of viral dsRNA/ssRNA in favor of dsRNA. This shift was blocked by ribavirin (RBV), an antiviral drug that reduces relapse in HCV patients. Northern blotting established that HCV dsRNA contained genome‐length minus strands. Conclusion : HCV dsRNA is the predominant form in the HCV‐infected liver and has features of both a PAMP and a genomic reservoir. Interferon treatment increased rather than decreased HCV dsRNA. This unexpected finding suggests that HCV produces dsRNA in response to IFN, potentially to antagonize antiviral defenses. (H epatology 2017;66:357–370).
Les infections entériques à Salmonella à Guipúzcoa, en Espagne, de 1983 à 2000
Authors: J. M Marimon, E Pérez-Trallero, M. Gomariz, C. Rodríguez-Andres, C. López-Lopategui
Journal: Eurosurveillance (2003)

L'incidence des infections enteriques a Salmonella a Guipuzcoa, en Espagne, a ete evaluee par l'etude d'une population stable de 1983 a 2000. Seuls les cas confirmes par coproculture ont ete inclus. L'incidence annuelle moyenne chez les enfants de moins de deux ans etait de 1121 pour 100 000 (IC 95% ; 1 060-1 181). Ce groupe d'âge presentait le risque relatif (RR) le plus eleve, 16,2 fois superieur a celui des plus de 14 ans. Salmonella Enteritidis etait le serotype predominant (80,4% des cas), suivi de Salmonella Typhimurium (11,7%).
Spectrum of NAFLD Severity in a Large Population using Software-Combined Tests of Steatosis, Necroinflammatory Activity, and Fibrosis (Fibromax) in Comparison with Patients with Chronic Hepatitis C
Authors: T. Poynard, O. Deckmyn, M. Munteanu, Y. Ngo, F. Drane, J.M. Castille, C. Housset, V. Ratziu and Fibrofrance
Journal: Journal of Hepatology (2016)
UK performs fifth in the world on sustainable development goals
Authors: Ingrid Torjeson
Journal: BMJ (2016)

The UK is ranked fifth in the world on its performance against the sustainable development goals for health, the first global analysis has shown.

The analysis, unveiled at a special event at the UN General Assembly in New York on 21 September and published in the Lancet , showed that Iceland was ranked first of 188 countries, followed by Singapore, Sweden, and Andorra.1 The poorest performers were in Africa—Central African Republic followed by Somalia, South Sudan, Niger, and Chad.

The sustainable development goals are 17 universal goals, 169 targets, and 230 indicators set by the United Nations in 2015 to prompt action on …
Rheumatological Patients are at Risk of Chronic HEV Infection: A Multicentric European Study
Authors: S. Pischke, J. Von Felden, J.M. Peron, L. Alric, H. Wedemeyer, U. Spengler, P. Schnitzler, D. Bettinger, S. Schlabe, J. Cornelissen, C.H. zu Siederdissen, M.T. Giordani, G. Par, R. Thimme, A.W. Lohse, C. Aitken, R.A. de Man, V. Mallet
Journal: Journal of Hepatology (2016)
Pediatric Death from Meningococcal Disease in a Family of Romani Travelers — Sarasota, Florida, 2015
Authors: Eboni Crawford, Michael Drennon, Tiffany Winston
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On January 31, 2015, the Sarasota County Office of the Medical Examiner notified the on-call epidemiologist at the Florida Department of Health, Bureau of Epidemiology of a possible death from meningococcal disease in a male child aged 17 months. The child was part of a large non-English-speaking Romani family (whose members self-identified as Gypsies), who arrived in Florida after traveling in Texas and Europe during the previous 2 months. The child had no history of prior meningococcal immunization. The family reported that the child had been sick for at least 7 days with an ear infection; however, this diagnosis was not confirmed by a physician. Because of increasing fever and onset of vomiting, emergency medical service (EMS) staff members were contacted and the child was transported to a local emergency department on January 29, 2015. Although he was reportedly interactive and alert during registration, he developed a rash while in the emergency department, his condition rapidly deteriorated, and he died within four hours. An autopsy was performed on January 30, and on January 31, the medical examiner reported Gram-negative diplococci in the cerebrospinal fluid (CSF). The on-call epidemiologist notified the Sarasota County epidemiologist to initiate investigation of the case and identify contacts at risk and needing chemoprophylaxis.
Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions: A Systematic Review
Authors: Su Golder, Yoon K. Loke, Kath Wright, Gill Norman
Journal: PLoS Medicine (2016)

We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events.Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published.There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events.
Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia
Authors: C. Rueda, M. Puig-Asensio, J. Guinea, B. Almirante, M. Cuenca-Estrella, O. Zaragoza, B. Padilla, P. Muñoz, J. Guinea, J.R. Paño Pardo, J. García-Rodríguez, C. García Cerrada, J. Fortún, P. Martín, E. Gómez, P. Ryan, C. Campelo, I. de los Santos Gil, V. Buendía, B.P. Gorricho, M. Alonso, F.S. Sanz, J.M. Aguado, P. Merino, F. González Romo, M. Gorgolas, I. Gadea, J.E. Losa, A. Delgado-Iribarren, A. Ramos, Y. Romero, I. Sánchez Romero, O. Zaragoza, M. Cuenca-Estrella, J. Rodriguez-Baño, A. Isabel Suarez, A. Loza, A.I. Aller García, E. Martín-Mazuelos, M.R. Pérez de Pipaón, J. Garnacho, C. Ortiz, M. Chávez, F.L. Maroto, M. Salavert, J. Pemán, J. Blanquer, D. Navarro, J.J. Camarena, R. Zaragoza, V. Abril, C. Gimeno, S. Hernáez, G. Ezpeleta, E. Bereciartua, J.L. Hernández Almaraz, M. Montejo, R.A. Rivas, R. Ayarza, A.M. Planes, I.R. Camps, B. Almirante, J. Mensa, M. Almela, M. Gurgui, F. Sánchez-Reus, J. Martinez-Montauti, M. Sierra, J.P. Horcajada, L. Sorli, J. Gómez, A. Gené, M. Urrea, M. Valerio, A. Díaz-Martín, F. Puchades, A. Mularoni
Journal: Clinical Microbiology and Infection (2016)

ObjectiveParadoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG.MethodsWe analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results with clinical outcome of the patients.ResultsAround 70% (484/690) of the isolates exhibited TE to azoles. Candida tropicalis showed the highest presence of TE (39/53 isolates exhibited residual growth >25% of control). No TE was seen in most of the isolates from the psilosis complex. PG was mainly associated with echinocandins. In patients treated with fluconazole within the first 48 hours after blood sampling (n = 221), the presence of TE to azoles tended to be associated with lower 30-day mortality (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25–1.00) but not with clinical failure (OR 0.85, 95% CI 0.45–1.54). In the subgroup of 117 patients treated with echinocandins, the presence of PG was not associated with patient's response to antifungal treatment (OR for 30-day mortality 1.63, 95% CI 0.76–4.03; OR for clinical failure 1.17, 95% CI 0.53–2.70).ConclusionsTE or PG are widely expressed among Candida spp., although they do not seem to influence clinical outcome.
Tc-99m labeled small-molecule inhibitors of prostate-specific membrane antigen (PSMA): New molecular imaging probes to detect metastatic prostate adenocarcinoma (PC).
Authors: Joseph Osborne, Naveed Hassan Akhtar, Shankar Vallabhajosula, Anastasia Nikolopoulou, Kevin P. Maresca, Shawn M. Hillier, John L. Joyal, Robert Crummet, Thomas Armor, Scott T. Tagawa, David M. Nanus, Stanley J. Goldsmith, John W. Babich
Journal: Journal of Clinical Oncology (2012)

173 Background: Sensitive and specific imaging remains a clinically-relevant problem for men with PC. PSMA is a well established target for imaging of PC with therapeutic implications. We have recently developed novel 99m Tc-labeled small molecule inhibitors of the enzymatic domain of PSMA based on glutamate-urea-glutamate and glutamate-urea-lysine pharmacophores, and contain a bis-imidazole chelator to complex Tc-99m. Preclinical studies with PSMA positive LNCaP cells and xenografts demonstrate that 99m Tc-MIP-1404 and 99m Tc-MIP-1405 bind to PSMA with high affinity and localize in tumors rapidly. This study reports the first human data in men with metastatic PC and in healthy male subjects. Methods: Under an exploratory IND, using a cross-over design, the pharmacokinetics, biodistribution, and tumor uptake of 99m Tc-MIP-1404 and 99m Tc-MIP-1405 were compared in 6 healthy men and 6 men with radiographic evidence of metastatic PC. Whole body images were obtained at 10 min, 1, 2, 4 and 24 hr. Single photon emission computed tomography (SPECT) was performed between 3–4 hours post injection. Results: Both agents cleared the blood rapidly with MIP-1404 demonstrating significantly lower urinary activity (7%) compared to MIP-1405 (26%). Both agents showed persistent uptake in the salivary, lacrimal and parotid glands. Uptake in liver and kidney was acceptable for imaging at 1-2 hr post injection (PI). In men with PCa, both agents rapidly localized in bone and lymph node lesions as early as 1 hr PI. SPECT demonstrated excellent lesion contrast. Good correlation was seen with bone and CT scans, In majority of patients, more lesions including sub-cm lymph nodes were seen with 99m Tc-MIP-1404 and 99m Tc-MIP-1405. The high contrast images exhibited signal:noise ratios from 3:1 to 28:1 at 4 and 24 hr. Conclusions: 99m Tc-MIP-1404 and 99m Tc-MIP-1405 identified a greater number of lesions than bone scans and rapidly detected soft tissue PC lesions including sub-cm lymph nodes. Since 99m Tc-MIP-1404 has minimal activity in the bladder, further work is planned to correlate imaging findings with histopathology in patients with high risk clinically-localized PC.
A decade of globalization: Trends in participation of investigators from lower-resource economies in phase III lung cancer trials.
Authors: Z. Lwin, S. Amin, K. Fernandes, J. Wong, M.K. Krzyzanowska
Journal: Journal of Clinical Oncology (2010)

e16506 Background: Globalization of clinical trials has facilitated access to the latest medical interventions for patients and investigators from low- and middle-income countries (LMCs) but raises some ethical concerns. We explored the trends in participation of investigators from LMCs in phase III lung cancer trials during the past decade and trial characteristics when LMC investigators were involved. Methods: A MEDLINE search was conducted to identify all phase III lung cancer trials published in English from 1999-2008. Data on trial design, type of intervention, funding, representation of investigators from different economies, use of local ethics boards and the local relevance of the trial was abstracted from each article using a standardized form. Summary statistics were used to describe results while Fisher's exact test and logistic regression were used to identify trial characteristics associated with involvement of investigators from LMCs. Results: Among 173 lung cancer trials published between 1999-2008, 32 (19%) trials had at least one author from a LMC and an additional 3 (2%) trials had investigator participation from LMCs without authorship. Most investigators were from middle- rather than low-income countries and were usually middle authors. Of the trials published between 2004-2008, 23% included at least one author from a LMC versus 14% of those published between 1999-2003. Majority of the studies (82%) documented approval by country specific ethics board but no studies indicated whether the consent form was translated when appropriate. In univariate analysis, the use of placebo (p = 0.0005), use of monoclonal antibodies (p = 0.003) and industry funding (p < 0.001) were more common in studies that included at least one investigator from a LMC. In multivariable analysis, only type of funding was associated with LMC investigator participation with 59% of such studies explicitly reporting industry funding whereas only 19% of studies not involving LMC investigators reporting industry funding (p = 0.0003). Conclusions: Few phase III lung cancer trials include LMC investigators, rarely in leadership roles, but those that do more frequently report industry sponsorship. No significant financial relationships to disclose.
Treatment with Glucocorticoids Interferes with Bile Acid Homeostasis by Affecting Fxr/Fgf19-Mediated Ileum-Liver Crosstalk
Authors: M.R. Romero, F. Al-Aqil, M.J. Monte, E. Herraez, R. Rosales, M.A. Serrano, F. Jimenez, L. Sanz-Ortega, R. Gonzalez, C. Pizarro, J.C. Aranda, B. Ocon, I. Uriarte, O. Martinez-Augustin, F.S. de Medina, M.A. Avila, J.J. Marin
Journal: Journal of Hepatology (2016)
Sofosbuvir and Ledipasvir versus Sofosbuvir and Simeprevir Combination Therapy in the Management of Acute Hepatitis C: A Randomized Open Label Prospective Clinical Pilot Study. Slam C Study
Authors: P.P. Basu, N.J. Shah, M.M. Aloysius, L. Kavali, E. Shehi, R.S. Brown
Journal: Journal of Hepatology (2016)
Monitoring the Effect of Large Volume Paracenthesis on Systemic Hemodynamics Parameters Using the Non-Invasive Cardiac System a Pilot Study
Authors: T. Berdichevski, E. Weizman, M. Arad, Y. Sharabi, R. Hemi, O. Cohen-Ezra, P. Weizz, K. Tzaref, A. Jonuzi, S. Lev, Z. Ben-Ari
Journal: Journal of Hepatology (2016)
Interferon-Free, Direct-Acting Antiviral Agents Regimens in Hepatitis C are more Effective, Better Tolerated, and Decrease Fatigue during Treatment in Real-Life Conditions
Authors: A. Pariente, A.-J. Rémy, J.-P. Arpurt, C. Renou, F. Heluwaert, H. Lison, R. Arotcarena, I. Rosa-Hézode, A. Pauwels, F. Bourhis, G. Macaigne, X. Causse, G. Barjonet, S. de Montigny-Lenhardt, V. Jouannaud, H. Salloum, C. Pilette, S. Hommel, M. Schnee, E. Geagea, E. Maringe, Y. Le Bricquir, H. Labadie, J. Henrion, B. Lesgourgues
Journal: Journal of Hepatology (2016)
Susceptibility to Spontaneous Apoptosis of Peripheral Blood Granulocytes from Patients with Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia.
Authors: Laura Aguilera, David Dominguez, Encarna Perez-Vila, Beatriz Bellosillo, Francesc Sole, Joan Buch, Carles Besses, Sergi Serrano, Lourdes Florensa, Mar Bellido
Journal: Blood (2004)
Dupuytren disease is highly prevalent in male field hockey players aged over 60 years
Authors: Dieuwke C Broekstra, Edwin R van den Heuvel, Rosanne Lanting, Tom Harder, Inge Smits, Paul M N Werker
Journal: British Journal of Sports Medicine (2016)

Dupuytren disease is a fibroproliferative hand condition. The role of exposure to vibration as a risk factor has been studied with contradictory results. Since field hockey is expected to be a strong source of hand-arm vibration, we hypothesised that long-term exposure to field hockey is associated with Dupuytren disease.In this cross-sectional cohort study, the hands of 169 male field hockey players (IQR: 65-71 years) and 156 male controls (IQR: 59-71 years) were examined for signs of Dupuytren disease. Details about their age, lifestyle factors, medical history, employment history and leisure activities were gathered. Prior to the analyses, the groups were balanced in risk factors using propensity score matching. The association between field hockey and Dupuytren disease was determined using a subject-specific generalised linear mixed model with a binomial distribution and logit link function (matched pairs analysis).Dupuytren disease was observed in 51.7% of the field hockey players, and in 13.8% of the controls. After propensity score matching, field hockey playing as dichotomous variable, was associated with Dupuytren disease (OR=9.42, 95% CI 3.01 to 29.53). A linear dose-response effect of field hockey (hours/week x years) within the field hockey players could not be demonstrated (OR=1.03, 95% CI 0.68 to 1.56).We found that field hockey playing has a strong association with the presence of Dupuytren disease. Clinicians in sports medicine should be alert to this less common diagnosis in this sport.
Posaconazole as Prophylaxis in Immunocompromised Patients: A Single Center Experience
Authors: Sameh Ayari, Thomas Gastinne, Thierry Guillaume, Patrice Chevallier, Steven le Gouill, Nicolas Blin, Xiao Ma, Eolia Brissot, jean Luc Harousseau, Philippe Moreau, Philippe Moreau, Mohamad Mohty, Jacques Delaunay
Journal: Blood (2008)