tbuckley/cabot-search huggingface dataset:
Macrotrabecular‐massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance
Authors: Marianne Ziol, Nicolas Poté, Giuliana Amaddeo, Alexis Laurent, Jean‐Charles Nault, Frédéric Oberti, Charlotte Costentin, Sophie Michalak, Mohamed Bouattour, Claire Francoz, Georges Philippe Pageaux, Jeanne Ramos, Thomas Decaens, Alain Luciani, Boris Guiu, Valérie Vilgrain, Christophe Aubé, Jonathan Derman, Cécile Charpy, Jessica Zucman‐Rossi, Nathalie Barget, Olivier Seror, Nathalie Ganne‐Carrié, Valérie Paradis, Julien Calderaro
Journal: Hepatology (2017)

We recently identified a histological subtype of hepatocellular carcinoma (HCC), designated as "macrotrabecular-massive" (MTM-HCC) and associated with specific molecular features. In order to assess the clinical relevance of this variant, we investigated its prognostic value in two large series of patients with HCC treated by either surgical resection or radiofrequency ablation (RFA). We retrospectively included 237 HCC surgical samples and 284 HCC liver biopsies from patients treated by surgical resection and RFA, respectively. Histological slides were reviewed by pathologists specialized in liver disease, and the MTM-HCC subtype was defined by the presence of a predominant (>50%) macrotrabecular architecture (more than six cells thick). The main clinical and biological features were recorded at baseline. Clinical endpoints were early and overall recurrence. The MTM-HCC subtype was identified in 12% of the whole cohort (16% of surgically resected samples, 8.5% of liver biopsy samples). It was associated at baseline with known poor prognostic factors (tumor size, alpha-fetoprotein level, satellite nodules, and vascular invasion). Multivariate analysis showed that MTM-HCC subtype was an independent predictor of early and overall recurrence (surgical series: hazard ratio, 3.03; 95% confidence interval, 1.38-6.65; P = 0.006; and 2.76; 1.63-4.67; P < 0.001; RFA series: 2.37; 1.36-4.13; P = 0.002; and 2.19; 1.35-3.54; P = 0.001, respectively). Its prognostic value was retained even after patient stratification according to common clinical, biological, and pathological features of aggressiveness. No other baseline parameter was independently associated with recurrence in the RFA series.The MTM-HCC subtype, reliably observed in 12% of patients eligible for curative treatment, represents an aggressive form of HCC that may require more specific therapeutic strategies. (Hepatology 2018;68:103-112).
Basic understanding and therapeutic approaches to target toll‐like receptors in cancerous microenvironment and metastasis
Authors: Mojtaba Khajeh Alizadeh Attar, Muhammad Ayaz Anwar, Mahsa Eskian, Mahsa Keshavarz‐Fathi, Sangdun Choi, Nima Rezaei
Journal: Medicinal Research Reviews (2017)

Toll-like receptors (TLRs) are transmembrane components that sense danger signals, like damage- and pathogen-associated molecular pattern molecules, as receptors, and maintain homeostasis in tissues. They are mainly involved in immune system activation through a variety of mediators, which either carry out (1) elimination of pathogenic threats and redressing homeostatic imbalances or (2) contribution to the initiation and worsening of pathological conditions, including cancers. Under physiological conditions, TLRs coordinate the innate and adaptive immunity, and inhibit autoimmune disorders. In pathological conditions, such as cancer, they can present both tumor and receptor-specific roles. Although the roles of individual TLRs in various cancers have been described, the effects of targeting TLRs to treat cancer and prevent metastasis are still controversial. A growing body of literature has suggested contribution of both activators and inhibitors of TLR signaling pathway for cancer treatment, dependent on several context-specific factors. In short, TLRs can play dual roles with contradictory outcomes in neoplastic conditions. This hampers the development of TLR-based therapeutic interventions. A better understanding of the interwoven TLR pathways in cancerous microenvironment is necessary to design TLR-based therapies. In this review, we consider the molecular mechanisms of TLRs signaling and their involvement in tumor progression. Therapeutic modalities targeting TLRs for cancer treatment are discussed as well.
Circulating triacylglycerols but not pancreatic fat associate with insulin secretion in healthy humans
Authors: Bettina Nowotny, Sabine Kahl, Birgit Klüppelholz, Barbara Hoffmann, Guido Giani, Roshan Livingstone, Peter J. Nowotny, Valerie Stamm, Christian Herder, Andrea Tura, Giovanni Pacini, Jong-Hee Hwang, Michael Roden
Journal: Metabolism (2017)
Prognostic value of methylator phenotype in stage III colon cancer treated with oxaliplatin-based adjuvant chemotherapy
Authors: C. Gallois, J. Taieb, D. Le Corre, K. Le Malicot, J. Tabernero, C. Mulot, J.-F. Seitz, T. Aparicio, G. Folprecht, C. Lepage, E. Mini, J.-L. Van Laethem, J.F. Emile, P. Laurent-Puig
Journal: Annals of Oncology (2017)
First combined intravenous and intracerebral application of an oncolytic virus, parvovirus h-1, in a phase I/IIa clinical trial in patients with recurrent glioblastoma multiforme (ParvOryx01).
Authors: Karsten Geletneky, Johannes Huesing, Michael Dahm, Ottheinz Krebs, Bernard Huber, David Capper, Jean Rommelaere, Jacek Hajda, Andreas Unterberg
Journal: Journal of Clinical Oncology (2014)

TPS2111 Background: The management of glioblastoma multiforme (GBM) is an unsolved problem and medium survival has remained at dismal 15 months. Among alternative treatments is the use of oncolytic viruses which preferentially kill tumor cells. Preclinical work using rat glioma models showed that the oncolytic rodent parvovirus H-1PV was able to cure gliomas after single intratumoral or multiple intravenous injections (K. Geletneky et al. Neuro-Oncology 2010), forming the basis for a clinical trial with H-1PV. Methods: ParvOryx01 (NCT01301430) is a dose-escalation phase I/IIa clinical trial treating patients with recurrent GBM with H-1PV. The trial has two arms of 9 patients each, subdivided in 3 dose groups of 1E6, 5E7 and 1E9 pfu H-1PV. In arm A patients first receive an intratumoral injection of H-1PV followed by tumor resection and virus injection in the tumor-surrounding infiltration zone 10 days after the first treatment. In arm B patients receive for the first time in a clinical trial a combined intravenous/intracerebral virus injection. At days 1 to 5 half of the designated dose is injected intravenously followed by tumor resection and virus injection in the peritumoral brain as in arm A. Main inclusion criteria are a single and completely resectable recurrent GBM, 18+ years of age, confirmed diagnosis of GBM (WHO IV), failed previous radio- and/or chemotherapy, Karnofsky Performance Score ≥60, commitment to omit exposure to infants < 18 months of age. Patients have to be isolated during treatment (K. Geletneky et al. BMC Cancer 2012). Arm A has been completed without DLT. As intratumoral injection in arm A led to asymptomatic systemic exposure to H-1PV, arm B can be conducted at the two higher dose levels only. Due to the lack of DLT the trial was amended with 3 additional patients in arm A receiving a high dose of 5E9 pfu. At the moment patients are recruited for Arm B and high-dose arm A. The trial design allows for the in depth analysis of infected tumor tissue and H-1PV penetration into the tumor after systemic injection. Clinical trial information: NCT01301430.
Точність методів візуалізації в діагностиці гострого холециститу
Authors: I.Yu. Skyrda, V.М. Gladun, О.V. Zakrevska
Journal: GASTROENTEROLOGY (2020)

Дослідження проведено для оцінки діагностичної точності при гострому холециститі, гострому холангіті та отримання зведених даних. Інформаційний пошук результатів клінічних досліджень, систематичних оглядів, метааналізів, клінічних настанов стосовно чутливості та специфічності гепатобіліарної сцинтиграфії, ультразвукового дослідження, магнітно-резонансної томографії, комп’ютерної томографії при гострому холециститі проводився в базі Cochrane library, Medline/PubMed та в інших пошукових системах за ключовими словами: gallstone disease, acute cholecystitis, US, cholescintigraphy, CT, MR, sensitivity, specificity з січня 2000 р. до лютого 2014 р. Критерії включення: а) чіткі критерії для визначення позитивного результату візуалізації; б) операції і/або клінічні спостереження були використані як еталон; в) достатньо наведено даних, щоб оцінити число істинно позитивних, негативних результатів, хибнопозитивних і хибнонегативних результатів.У дослідженнях з оцінкою гепатобіліарної сцинтиграфії чутливість (88,5 % (95% ДІ: 81–97 %)) і специфічність (91,8 % (95% ДІ: 86–93 %)) були порівнянні з даними 2012 року, але чутливість трохи нижча в нашому дослідженні. Для досліджень з оцінкою УЗД чутливість становила 84,4 % (95% ДІ: 76–93 %) при специфічності 85,1 % (95% ДІ: 78–91 %), що трохи вище порівняно з даними, отриманими в систематичному огляді 2012 року. Ми показали, що магнітно-резонансна томографія і ультразвукове дослідження не виявили статистично значимих відмінностей у діагностиці потовщення стінки жовчного міхура, наявності каменів у ньому, наявності перихолецистичної рідини або гострого холециститу (р &gt; 0,05). Чутливість для гострого холециститу становила 89,4 % (95% ДІ: 85–91 %) і специфічність — 87,2 % (95% ДІ: 83–99 %) для магнітно-резонансної томографії. Цей метод еквівалентний ультразвуковому дослідженню в діагностиці жовчнокам’яної хвороби, потовщення стінки жовчного міхура, визначенні наявності перихолецистичного набряку й гострого холециститу в пацієнтів із симптомами гострого болю в правому верхньому квадранті живота. Особливо в сонографічно складних пацієнтів магнітно-резонансна томографія може застосовуватися як більш швидкий і простий метод діагностики.
Performance of the BacT/Alert Virtuo Microbial Detection System for the culture of sterile body fluids: prospective multicentre study
Authors: R.C. She, M.G. Romney, W. Jang, T. Walker, J.K. Karichu, S.S. Richter
Journal: Clinical Microbiology and Infection (2017)

<h2>Abstract</h2><h3>Objectives</h3> Continuous monitoring blood culture systems are commonly used for sterile body fluid cultures. In this multicentre study, we evaluated the performance of the new-generation BacT/Alert Virtuo system compared to the BacT/Alert 3D and conventional culture for the recovery of microorganisms from sterile body fluids. <h3>Methods</h3> Peritoneal, cerebrospinal, pericardial, pleural and synovial fluids from adult patients submitted for culture were collected from three different centres. Specimens were inoculated into two bottles of the same bottle type (SA, SN, FA Plus or FN Plus) in equal volumes for simultaneous incubation in the Virtuo and 3D instruments. Each specimen was also Gram stained and seeded to solid media. <h3>Results</h3> A total of 811 specimens were inoculated to 1257 bottle pairs. The Virtuo and 3D showed equivalent recovery of clinically significant microorganisms (127/155, 81.9%, vs. 126/155, 81.3%, respectively). Solid media cultures recovered fewer pathogens than either continuous monitoring system (95/155, 61.3%, p <0.001), including significantly fewer <i>Enterobacteriaceae</i> and enterococci. The Virtuo was significantly faster than the 3D in median time to detection of isolates from the same specimen (12.5 (range, 2.8–101.5) hours vs. 15.5 (range, 4.3–78.5) hours, p <0.001). Direct specimen Gram stain detected the eventual pathogen in 30 (26.1%) of 115 significant positive specimens. <h3>Conclusions</h3> The BacT/Alert Virtuo system was equivalent to the 3D system in organism recovery from sterile body fluid culture but showed faster detection of growth as a result of design enhancements.
Risk Factors Associated with Peanut Allergy in a High Risk Infant Cohort (CoFAR)
Authors: Scott H. Sicherer, Robert A. Wood, Tamara T. Perry, Stacie M. Jones, Donald Y.M. Leung, Alice Henning, Peter Dawson, A. Wesley Burks, Robert W. Lindblad, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2018)
Using Network Oriented Research Assistant (NORA) Technology to Compare Digital Photographic With In-Person Assessment of Acne Vulgaris
Authors: Hannah M. Singer, Timothy Almazan, Noah Craft, Consuelo V. David, Samantha Eells, Crisel Erfe, Cynthia Lazzaro, Kathy Nguyen, Katy Preciado, Belinda Tan, Vishal A. Patel
Journal: JAMA Dermatology (2017)

Teledermatology has undergone exponential growth in the past 2 decades. Many technological innovations are becoming available without necessarily undergoing validation studies for specific dermatologic applications.To determine whether patient-taken photographs of acne using Network Oriented Research Assistant (NORA) result in similar lesion counts and Investigator's Global Assessment (IGA) findings compared with in-person examination findings.This pilot reliability study enrolled consecutive patients with acne vulgaris from a single general dermatology practice in Los Angeles, California, who were able to use NORA on an iPhone 6 to take self-photographs. Patients were enrolled from January 1 through March 31, 2016. Each individual underwent in-person and digital evaluation of his or her acne by the same dermatologist. A period of at least 1 week separated the in-person and digital assessments of acne.All participants were trained on how to use NORA on the iPhone 6 and take photographs of their face with the rear-facing camera.Reliability of patient-taken photographs with NORA for acne evaluation compared with in-person examination findings. Acne assessment measures included lesion count (total, inflammatory, noninflammatory, and cystic) and IGA for acne severity.A total of 69 patients (37 male [54%] and 32 female [46%]; mean [SD] age, 22.7 [7.7] years) enrolled in the study. The intraclass correlation coefficients of in-person and photograph-based acne evaluations indicated strong agreement. The intraclass correlation coefficient for total lesion count was 0.81; for the IGA, 0.75. Inflammatory lesion count, noninflammatory lesion count, and cyst count had intraclass correlation coefficients of 0.72, 0.72, and 0.82, respectively.This study found agreement between acne evaluations performed in person and from self-photographs with NORA. As a reliable telehealth technology for acne, NORA can be used as a teledermatology platform for dermatology research and can increase access to dermatologic care.
Yellowish lesions in the oesophagus
Authors: Kenta Hamada, Yasushi Yamasaki, Jun-ichi Kubota, Hiroyuki Okada
Journal: Gut (2017)

Clinical presentation A 51-year-old man, who had no previous disease, underwent a screening oesophagogastroduodenoscopy, which revealed multiple yellowish lesions in the middle thoracic oesophagus. All lesions were ≤3 mm in size and slightly elevated. Each lesion showed one or two white protrusions on the surface (figure 1). We observed that one lesion looked obviously different from the others and showed yellowish granular spots (figure 2). A biopsy was performed on a representative lesion among the slightly elevated yellowish lesions with white protrusions (figure 3). A biopsy was repeated on a lesion showing yellowish granular spots (figure 4). Blood tests which were examined on the same day, including triglyceride and cholesterol, were within normal limits. Figure 1 Slightly elevated yellowish lesions with white protrusions in the middle thoracic oesophagus. Figure 2 A lesion showing yellowish granular spots in the middle thoracic oesophagus. Question What is the diagnosis?
Abstract 16067: Phosphorylation of Lamin-A/C Modulates Peak Sodium Current in a Patient With Cardiac Conduction Disease
Authors: Michael Olaopa, Katherine Spoonamore, Peng-Sheng Chen, Tomohiko Ai, Matteo Vatta
Journal: Circulation (2015)

Introduction: Deleterious variants in the LMNA gene, which encodes for Lamin-A/C, have been shown to be associated with cardiac conduction diseases (CCDs) and cardiomyopathy. We previously reported that two LMNA variants found in patients presenting with CCDs can prevent the LMNA -mediated activation of peak sodium current (I Na ). In addition, western blot analyses showed phosphorylation of Lamin at serine 22 (S22) was reduced in HEK293 cells expressing either variant. Thus, we sought to investigate what potential role S22 plays on modulating Nav1.5 function. In this study, we focused our analyses on one of the two variants, which is c.1634G&gt;A (p.R545H) in LMNA . We tested the hypothesis that S22 affects peak I Na . Methods and Results: We generated two plasmids that mimic unphosphorylated wild type LMNA ( p.S22A ) and constitutively phosphorylated mutant LMNA ( p.S22D-p.R545H ). We measured and compared peak I Na using patch clamp techniques in HEK293 cells transfected with each LMNA and SCN5A plasmids. Our study showed that p.S22A significantly prevented the LMNA -mediated activation of peak I Na by 63% compared to wild type ( p.S22A : -121 ±11 pA/pF, N =10 vs. wild type LMNA : -340 ±45 pA/pF, N=10, Mann-Whitney U =2, p&lt;0.0005 one-tailed). On the contrary, p.S22D-p.R545H partially restored the reduced peak I Na by 44% ( p.S22D-p.R545H : -137 ±43 pA/pF, N=7 vs. p.R545H : -95 ±15 pA/pF, N=10, Mann-Whitney U =27, p&lt;0.1 one-tailed). Conclusions: Our data indicate the loss of phosphorylation at S22 significantly reduces the LMNA -mediated activation of peak I Na . In the disease state, constitutive phosphorylation partially restores, yet fails to normalize peak I Na . Our observation suggests that S22 could represent a potential therapeutic target in patients with LMNA -mediated CCD. To our knowledge, this is the first study to functionally link phosphorylation of Lamin-A/C at S22 to peak I Na levels and Nav1.5 function.
Abstract 16824: Transmural Myocardial Scar Assessed by Cardiac Computed Tomography Predicts Response to Cardiac Resynchronization Therapy
Authors: Daniel B Fyenbo, Anders Sommer, Jørgen T Kühl, Klaus F Kofoed, Bjarne L Nørgaard, Mads B Kronborg, Kirsten Bouchelouche, Jens C Nielsen
Journal: Circulation (2016)

Introduction: Myocardial scar located near the left ventricular (LV) lead and scar burden negatively influence the response to cardiac resynchronization therapy (CRT). Cardiac computed tomography (...
Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma
Authors: A.F. Herrera, J. Palmer, P. Martin, S. Armenian, N.-C. Tsai, N. Kennedy, F. Sahebi, T. Cao, L.E. Budde, M. Mei, T. Siddiqi, L. Popplewell, S.T. Rosen, L.W. Kwak, A. Nademanee, S.J. Forman, R. Chen
Journal: Annals of Oncology (2017)
Abstract 19914: Female Sex Hormones Do not Protect Against Cardiomyocyte Dysfunction in Aortic-Banded Miniature-Swine
Authors: Jessica A Hiemstra, T D Olver, Jenna C Edwards, Michelle D Lambert, Jan R Ivey, Pam K Thorne, Kerry S McDonald, Timothy L Domeier, Craig A Emter
Journal: Circulation (2016)

Introduction:  Population studies have shown the prevalence of HFpEF sharply increases in women after menopause. Sex differences in cardiomyocyte function may play a role in the development of HFpEF. Thus, the purpose of this study was to determine the impact of ovariectomy (OVX) on cardiomyocyte function in a female mini-swine model of pressure-overload HF induced by aortic-banding (AB). We hypothesized female sex hormones would protect against AB-induced cardiomyocyte calcium handling abnormalities and contractile dysfunction.   Methods:  Female mini-swine were divided into 4 groups; CON (n=6; 47 cells), OVX (n=6; 53 cells), AB (n=6; 51 cells) and AB-OVX (n=7; 51 cells). OVX and AB procedures occurred at 7 and 8 mo. of age, respectively. Six months post-AB, calcium handling and contractile function were measured outside the estrus phase in isolated left ventricular (LV) cardiomyocytes loaded with Fura-2 and stimulated at 0.5Hz. Protein levels (western blot) of the sarco-endoplasmic reticulum calcium-ATPase (SERCA), phospholamban (PLB), and phosphorylated PLB at the threonine-17 (Thr17) site were assessed. Significance was set at P    Results:  Pressure-overload increased LV diastolic wall thickness (ME of AB) without altering internal diastolic dimension (i.e. concentric hypertrophy). Both cardiomyocyte shortening amplitude (ME of AB; CON vs. AB, OVX vs. AB-OVX) and calcium transient amplitude (ME of AB; CON vs. AB) were decreased following pressure-overload. Aortic banding also impaired calcium reuptake (increased Tau - ME of AB; CON vs. AB). SERCA and PLB protein levels were increased in all groups vs. CON (INT). Pressure-overload decreased phosphorylation of PLB at Thr17 (ME of AB; CON vs. AB).   Conclusions:  Contrary to our hypothesis, female sex hormones do not protect against pressure-overload induced cardiomyocyte dysfunction. Impaired cardiomyocyte shortening and calcium transients may be due to decreased sarcoplasmic reticulum calcium sequestration resulting from reduced phosphorylation of PLB at Thr17. Our results show impaired cardiomyocyte function contributes to pressure-overload HF in a translational model with potential relevance to human HFpEF.
Giant symptomatic rectal lipoma resected by endoscopic submucosal dissection
Authors: João Fernandes, Diogo Libânio, Sílvia Giestas, Tarcísio Araújo, David Martinez-Ares, Manuela Certo, Luís Lopes
Journal: Endoscopy (2017)

Gastrointestinal lipomas are benign, slow-growing tumors that are typically diagnosed incidentally during endoscopy [1] [2]. They are more commonly located in the right colon; rectal involvement is uncommon [2] [3] [4] [5]. Lipomas are characteristically asymptomatic but depending on their location and size [1], they can cause symptoms such as bleeding, obstruction, intussusception or prolapse [1] [2] [4]. Only three cases of rectal lipomas presenting with prolapse have been reported in the literature, and they are usually treated surgically.
Abstract 253: Complete Reversal of Xylazine-induced Bradycardia With Intralipid in Female Mice
Authors: Negar Motayagheni, Mansoureh Eghbali
Journal: Circulation Research (2016)

Sudden cardiac arrest accounts for 300 000 to 400 000 deaths annually in united states both in men and women. Cardiac arrest could be due to abnormally slow heart rate known as bradycardia. Bradycardia is a catastrophic event which is associated with significant mortality and morbidity. We have previously shown that Intralipid, an emulsion of soy bean oil, egg yolk phospholipids and glycerol, protects the heart against ischemia/reperfusion injury as well as Bupivacaine induced cardiotoxicity. Here we examined whether intralipid can protects the heart against bradycardia. Wild type female mice C57/Bl6 (2-4 month old) were anesthetized by isoflurane after heparinization. The heart was removed immediately and placed in cold Krebs-Henseleit buffer. The aorta was cannulated and the isolated heart (Langendorff) was perfused with Krebs-Henseleit at 37°C for 15 min for stabilization. Xylazine (100-300 mg) was directly applied to the heart surface for 1-2 min until bradycardia was achieved. The heart was then perfused with either Krebs-Henseleit (KH) solution (control group), or 1% ILP (intralipid group). Hemodynamic parameters and heart rates were recorded with a catheter directly inserted into left ventricle (n=5-8 per group). The heart rates at the baseline before inducing bradycardia was 224±7 beats/min and the left ventricular pressures was 64±4 mmHg. Administration of Xylazine decreased the heart rate significantly to 81±9 beats/min and left ventricular pressure to 5±2 mmHg (p&lt;0.001). Perfusion of the heart with intralipid rapidly restored the heart rate to 209±30 and left ventricular pressure to 59±4 which were not significantly different than their values before inducing bradycardia at the baseline. In the hearts that received Krebs-Henseleit after bradycardia, the heart rate (81±10 beats/min) and left ventricular pressure (20±8 mmHg) were significantly lower than intralipid group. In conclusion Intralipid has the ability to rapidly reverse bradycardia in female mice.