tbuckley/cabot-search huggingface dataset:
Benefit of direct-acting antiviral therapy in hepatitis C virus (HCV) monoinfected and HIV-HCV coinfected patients with mixed cryoglobulinemia
Authors: M. Diakite, K. Hartig-Lavie, P. Miailhes, P. Pradat, A.-C. Uhrés, F. Zoulim, M.-N. Sarda
Journal: Journal of Hepatology (2017)
IMPDH exerts a tumor-suppressing role in hepatocellular carcinoma
Authors: K. Chen, B. Ma, K. Sideras, W. Cao, L.J.W.V.D. Laan, D. Sprengers, R. Smits, H.J. Metselaa, J. Kwekkeboom, M.P. Peppelenbosch, Q. Pan
Journal: Journal of Hepatology (2017)
PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitude of ensuing antibody and CD8+ T cell responses
Authors: Toshiki Sekiya, Junya Yamagishi, John Henry V. Gray, Paul G. Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C. Jackson, Brendon Y. Chua
Journal: Biomaterials (2017)
The association of Geriatric Assessment (GA) identified deficits and 30-day re-admission in hospitalized older cancer patients.
Authors: Trevor Augustus Jolly, Caroline Joy Mariano, Allison Mary Deal, Grant Richard Williams, Shani Malia Alston, Ashley Leak Bryant, Mackenzi Pergolotti, Hyman B. Muss
Journal: Journal of Clinical Oncology (2015)

e20537 Background: Hospital readmission is a major healthcare concern. We aimed to investigate whether GA-identified deficits are associated with subsequent readmission in non-electively admitted older cancer patients. Methods: During an unplanned hospitalization, English speaking cancer patients ≥ 70 years were invited to complete a brief, primarily self-administered GA (Hurria et al. Cancer 2005) incorporating measures of comorbidity, polypharmacy, cognitive, functional, psychosocial, and nutritional status. Fisher's exact test was used to compare those with and without readmission. Results: Ninety patients; mean age 77 (range 70-96), 56% female, 78% white, 22% black, 73% greater than high school education, 31% living alone, 24% gynecologic tumors, 59% metastatic and 33% non-metastatic disease, 46% evaluated during treatment. Infection (20%) was the most frequent reason for hospitalization. The GA identified physical function (PF) deficits (53%), instrumental activity of daily living (IADL) dependencies (63%), cognitive impairment (12%), ≥ 10% body weight loss (31%), polypharmacy ( ≥ 10 concurrent medication) (53%), falls ( ≥ 1 in 6 months) (35%), and mental health (MH) dysfunction (14%). In our sample, readmission was not associated with living alone, PF deficit, dependent IADL, cognitive impairment, weight loss, polypharmacy, falls, MH dysfunction, length of stay (0-3 vs ≥ 4 days) or receipt of referral to allied professionals for interventions (48%). Overall, the 30-day readmission rate was 29% (Institutional rate 17.6%, Medicare beneficiaries 17-23%). Patients < 80 years (p = 0.04) and those with metastatic disease (p = 0.04) were more likely to be readmitted. Conclusions: Our findings suggest high 30-day readmission rates, nearly double the institutional and Medicare beneficiaries’ rate, among non-electively admitted older cancer patients. The GA measures used in this pilot study were generally not associated with re-admission. As multiple factors influence readmission beyond age and disease stage, expansion of this cohort and prospective randomized controlled trials are warranted to fully assess the utility of GA in this setting and patient population.
Cognitive Behavior Therapy May Sustain Antidepressant Effects of Intravenous Ketamine in Treatment-Resistant Depression
Authors: Samuel T. Wilkinson, DaShaun Wright, Madonna K. Fasula, Lisa Fenton, Matthew Griepp, Robert B. Ostroff, Gerard Sanacora
Journal: Psychotherapy and Psychosomatics (2017)

Ketamine has shown rapid though short-lived antidepressant effects. The possibility of concerning neurobiological changes following repeated exposure to the drug motivates the development of strategies that obviate or minimize the need for longer-term treatment with ketamine. In this open-label trial, we investigated whether cognitive behavioral therapy (CBT) can sustain or extend ketamine's antidepressant effects.Patients who were pursuing ketamine infusion therapy for treatment-resistant depression were invited to participate in the study. If enrolled, the subjects initiated a 12-session, 10-week course of CBT concurrently with a short 4-treatment, 2-week course of intravenous ketamine (0.5 mg/kg infused over 40 min) provided under a standardized clinical protocol.Sixteen participants initiated the protocol, with 8 (50%) attaining a response to the ketamine and 7 (43.8%) achieving remission during the first 2 weeks of protocol. Among ketamine responders, the relapse rate at the end of the CBT course (8 weeks following the last ketamine exposure) was 25% (2/8). On longer-term follow-up, 5 of 8 subjects eventually relapsed, the median time to relapse being 12 weeks following ketamine exposure. Among ketamine remitters, 3 of 7 retained remission until at least 4 weeks following the last ketamine exposure, with 2 retaining remission through 8 weeks following ketamine exposure. Ketamine nonresponders did not appear to benefit from CBT.CBT may sustain the antidepressant effects of ketamine in treatment-resistant depression. Well-powered randomized controlled trials are warranted to further investigate this treatment combination as a way to sustain ketamine's antidepressant effects.
Impact of Acute-on-Chronic Liver Failure on response to treatment with terlipressin and albumin in patients with type 1 hepatorenal syndrome
Authors: S. Piano, H.H. Schmidt, X. Ariza, A. Amoros, A. Romano, E. Solà, A.L. Gerbes, M. Bernardi, C. Alessandria, J. Trebicka, F. Nevens, T. Gustot, V. Arroyo, P. Gines, P. Angeli
Journal: Journal of Hepatology (2017)
Direct activation of Nlrp3 inflammasome in hepatic stellate cells leads to upregulation of fibrotic markers
Authors: M.E. Inzaugarat, M.D. McGeough, T.M. Holtmann, M. Frissen, C.D. Johnson, H.H. Hoffman, A.E. Feldstein, C. Trautwein, A. Wree
Journal: Journal of Hepatology (2017)
Binding of a monoclonal antibody that targets anionic phospholipids on tumor vasculature is dependent upon interaction with plasma protein beta2-glycoprotein I
Authors: Eun Jung Han, Eun Kyu Park, Dong Hyuck Seo, Woo Kyu Kang, Eun Jung Kang, Min-Young Kim, Jung Joon Lee, Soo Jin Lee, Hyun Ah Kang, Jeong-Yoon Kim
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

2179 

A promising target for tumor vasculature is phosphatidylserine (PS), an anionic phospholipid that resides exclusively on the inner leaflet of the plasma membrane under normal conditions. We have previously shown that PS becomes exposed on the surface of viable endothelial cells (EC) in solid tumors, likely in response to oxidative stresses that exist in the tumor microenvironment. To target PS on tumor vasculature, a murine monoclonal antibody (3G4) was developed. 3G4 specifically localizes to the vasculature of solid tumors. Treatment of mice with 3G4 inhibits growth of murine and human tumors and enhances the anti-tumor effects of standard radio- and chemo-therapeutic strategies. Therefore, 3G4 is a promising new therapeutic agent for treatment of solid tumor malignancies. We demonstrate here that the interaction between 3G4 and PS is dependent on antibody binding to the plasma glycoprotein beta2-glycoprotein I (β2GPI). When purified from a hybridoma converted to grow under serum-free conditions, 3G4 does not bind PS-coated ELISA plates unless serum is added to the binding reaction A similar phenomenon was described in the early 1990s, when “anti-cardiolipin antibodies” from patients with Anti-Phospholipid Syndrome (APS) were shown to require various plasma proteins (such as β2GPI or prothrombin) for binding to cardiolipin. Screening a panel of serum proteins for reactivity with 3G4 by ELISA and western blot identified β2GPI as the primary antigen for 3G4. β2GPI is a 50 kDa glycoprotein composed of five domains, including the positively charged domain V that binds anionic phospholipids. However, the interaction with anionic phospholipids is rather weak under physiological conditions. We demonstrate that 3G4 binds domain II of β2GPI and enhances the binding of β2GPI to EC induced to expose PS (PS-positive) 40- to 50-fold. We also show that binding of 3G4 to PS-positive EC is dependent on the lipid binding domain of β2GPI (domain V), since enzymatic cleavage of the lipid binding site abrogates both binding to PS and to EC. Finally, we demonstrate that the 3G4/β2GPI/PS binding interaction requires multivalent binding of 3G4 to β2GPI, since 3G4 Fab’ fragments do not bind PS-positive ECs. Together, the data suggest that 3G4 targets tumor vessels by increasing the binding affinity of β2GPI to PS exposed on tumor EC.
Alectinib versus crizotinib in patients with ALK -positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial
Authors: Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Miyako Satouchi, Toshiyuki Kozuki, Takehito Shukuya, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Takashi Asakawa, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura
Journal: The Lancet (2017)
Treatment with neoadjuvant BRAF Inhibition Yields Responses in Patients (pts) with High Risk Borderline Resectable Stage III Melanoma.
Authors: Rodabe Navroze Amaria, Jennifer Ann Wargo, Zachary A Cooper, Michael T. Tetzlaff, Alexandre Reuben, Michael A. Davies, Jeffrey E. Gershenwald, Hong Jiang, Jacob Austin-Breneman, Jeffrey Edwin Lee, Patrick Hwu, Wen-Jen Hwu, Janice N. Cormier, Richard Eldon Royal, Anthony Lucci, Sapna Pradyuman Patel, Adi Diab, Isabella Claudia Glitza, Elizabeth M Burton, Merrick I. Ross
Journal: Journal of Clinical Oncology (2015)

e20097 Background: Significant advances have been made in the treatment of stage IV melanoma through the use of targeted therapies in patients (pts) with BRAF V600 mutations. However, there is a critical unmet need to develop more effective strategies for patients with earlier stages of disease, particularly high-risk stage III. We report here our initial experience with neoadjuvant targeted therapy in pts with high risk, borderline resectable regional metastases. Methods: Pts with high risk, borderline resectable stage III melanoma harboring a BRAF V600 E or K mutation were treated with eight weeks of neoadjuvant BRAF inhibitor (BRAFi) therapy, either alone or combined with a MEK inhibitor (MEKi), followed by radiographic imaging and surgical resection. Preoperative therapy was administered up until the day prior to surgery. Results: 1 pt was treated with neoadjuvant BRAFi and 4 pts with BRAFi/MEKi. Neoadjuvant therapy was well tolerated in all pts. All pts had radiographic responses to therapy including 3 partial responses and 2 stable disease by response evaluation criteria in solid tumors version 1.1. There were no significant post-operative wound healing complications. Pathologic evaluation of surgical specimens demonstrated extensive fibrosis with little to no viable tumor cells in 2 pts, and significant necrosis with remaining viable tumor in the other 3 pts. Genomic and immune profiling studies on these and other patients treated with this approach are ongoing. Conclusions: The current standard of care for pts with clinical stage III melanoma is surgery with or without adjuvant interferon-based therapy. Neoadjuvant therapy has not been feasible historically due to the limited efficacy of systemic therapies. Our initial experience supports that neoadjuvant targeted therapy (BRAFi +/- MEKi) for 8 weeks in pts with a BRAF V600 mutation is well tolerated, safe, and results in a high rate of clinical and pathological responses. Randomized clinical trials are indicated, and are now ongoing, to definitively determine the safety and clinical benefit of neoadjuvant therapy in clinical stage III melanoma.
Exploring the patient perceived impact of non-alcoholic steatohepatitis
Authors: L.C. Doward, M.-M. Balp, K.E. Stewart, D. Cryer, A. Langford, J. Twiss, N. Agashivala, C.A. Brass, Q.M. Anstee, A. Sanyal
Journal: Journal of Hepatology (2017)
Delay in diagnosis and treatment of soft tissue sarcomas (STS): Causes of late intervention and their role in prognosis—A prospective, multidisciplinary group study.
Authors: Alessandro Comandone, Elisa Berno, Antonella Boglione, Cristiano Oliva, Manuela Ingui', Alessandra Linari, Elena Giubellino, Giancarlo Gino, Elena Maria Brach del Prever, Carlo Faletti, Raimondo Piana, Marco Turbiglio, Gabriella Monasterolo, Paolo Pochettino, Orietta Dal Canton, Simona Chiado' Cutin, Paola Bergnolo
Journal: Journal of Clinical Oncology (2012)

10055 Background: STS are 1% of malignant tumors in adults. Rarity, heterogeneity in presentation, low expertise in primary care physicians (PCP) or in general hospitals, organisation problems in specialized centers may cause a delay in both diagnosis and treatment. Aim of this study is to acknowledge the barriers to optimal care and the consequences of the delay on prognosis. Methods: Patients with STS of the extremities, trunk, retroperitoneum treated and followed from 1999 to 2011 by the same multidisciplinary group were included. Time and pattern of symptoms onset, anatomic site, tumor volume, patients’ age, gender and home, interval between diagnosis and surgical treatment or neoadjuvant chemotherapy; time to start adjuvant RT or CT were considered in a univariate - multivariate analysis. Results: 449 adult patient (53% F, 47% M, median age 55 years) were followed for a median time of 116.38 months. 65.7% of STS were at the extremities, 17.6% retroperitoneal, 16.7% at the trunk wall. Median volume at diagnosis was 8 cm for trunk and extremities; 15 cm for retroperitoneum. Commonest histologies: liposarcoma. 18.2%; leiomyo 16.8%; mixofibro 13.6%. Increasing mass, pain, and abdominal disconfort were the main revealing signs of diseases. Median time of delay were: from onset of symptom to first medical visit 68 days for trunk and extremities, 82 for retroperitoneum; 104 days from symptoms to histological diagnosis; 129 days from symptoms to start of therapy. Time to surgery after definitive diagnosis was 12 days in extremities and 21 in abdomen. Adjuvant CT started 22 days after surgery for extremities, 25 in trunk, 35 in retroperitoneum. RT initiated after 78 days. Longer delay in treatment lead to worse prognosis: MS 89.95 months if delay was &gt; 3 months; 190.40 months if wait was &lt; 3 months (p 0.007). Conclusions: Low self consciousness of the patient; misdiagnosis or inadequate approach in general hospitals; late referral to specialized centres are 75% of the cause of wasted time. Organization problems at the referral Centre concur for 25% of delay. Guidelines implementation and educational programme among general population and PCP are necessary.
Common variation near glial-derived neurotrophic factor is associated with progression of hepatic collagen content in a genome-wide association study of liver fibrosis phenotypes in patients with primary sclerosing cholangitis
Authors: P. Shea, G. Hirschfield, M. Shiffman, B. McColgan, Z. Goodman, R. Myers, M. Subramanian, B. Eksteen, H. Janssen, C. Bowlus, A. Muir, A. Montano-Loza, J. McHutchison, M. Manns, R. Chapman, S. Kleinstein, C. Levy, D. Goldstein
Journal: Journal of Hepatology (2017)
Dementia Care, Women's Health, and Gender Equity
Authors: Nicholas T. Bott, Clifford C. Sheckter, Arnold S. Milstein
Journal: JAMA Neurology (2017)

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The effect of ribavirin dosage on the kinetics of viral load decline and drug exposures in plasma and liver with OBV/PTV/r + DSV treatment in patients with chronic hepatitis C virus genotype 1a infection
Authors: A.H. Talal, E.O. Dumas, B. Bauer, R.M. Rejman, A. Ocque, G.D. Morse, D. Lucic, G.A. Cloherty, J. King, H. Zhang, D.E. Cohen, N. Shulman, J.-M. Pawlotsky, C. Hézode
Journal: Journal of Hepatology (2017)
Development of novel epigenetic inhibitors for the treatment of hepatocellular carcinoma
Authors: M. Bárcena-Varela, J. Oyarzabal, J.M. Banales, J. Prieto, L. Alvarez-Asiain, F. Prosper, C. Berasain, M.A. Avila, M.G. Fernandez-Barrena
Journal: Journal of Hepatology (2017)
The impact of primary melanoma histotype on overall survival and response to immunotherapy.
Authors: Eric M. Robinson, Christine Salvaggio, Sung Won Han, Sarah Ann Weiss, Melissa Wilson, Inês E. D. Pires Silva, Russell S. Berman, David Polsky, Richard L. Shapiro, Anna C. Pavlick, Judy Zhong, Iman Osman
Journal: Journal of Clinical Oncology (2015)

e20078 Background: Retrospective studies have suggested that primary nodular melanoma (NM) is associated with shorter recurrence-free survival (RFS) compared to superficial spreading melanoma (SSM). This finding has been mainly attributed to NM’s advanced stage due to its greater thickness at time of diagnosis. However, recent studies by our group have demonstrated that NM and SSM may progress through distinct molecular pathways (Salhi A et al., Am J Pathol. 2015). In this study, we tested the hypothesis that primary melanoma histotype (NM vs. SSM) might impact overall survival (OS) independent of AJCC stage. We also explored histotype as a potential biomarker of response to immunotherapy. Methods: We studied a cohort of primary melanoma patients enrolled into a prospective clinicopathological database at NYUMC from 2002-2013 (median follow-up 4.2 years). We compared RFS and OS between primary SSM and NM using the hazard ratio (HR) calculated from the Cox model controlling for thickness, ulceration, mitoses, and lymph node status. In a subset of patients who developed metastases during follow up and were treated with ipilimumab, we determined response rate (RR) using immune-related response criteria and tested the difference in RR and OS between NM and SSM using the HR from the Cox model. Results: 1,325 primary patients were studied (970 SSM, 73%; 355 NM, 27%). NM histotype was a statistically independent negative predictor of RFS (HR = 2.07, p < 0.001) and OS (HR = 1.59, p = 0.017). 84 patients of those who developed metastases were treated with ipilimumab (56 NM, 67%; 28 SSM, 33%). There were no differences in RR and OS in analyses that included all cases; however, in patients without CNS involvement (43 NM, 68%; 20 SSM, 32%), NM patients had shorter OS compared to SSM patients (HR 2.16, p = 0.043). Conclusions: Our data demonstrate that worse outcomes in patients with primary NM cannot be explained only by their advanced stage at diagnosis. Our data also suggest that metastatic melanoma originating from different primary histotypes might retain some biologic differences that can influence clinical outcome after metastasis.
Codon-Optimized RPGR Improves Stability and Efficacy of AAV8 Gene Therapy in Two Mouse Models of X-Linked Retinitis Pigmentosa
Authors: M. Dominik Fischer, Michelle E. McClements, Cristina Martinez-Fernandez de la Camara, Julia-Sophia Bellingrath, Daniyar Dauletbekov, Simon C. Ramsden, Doron G. Hickey, Alun R. Barnard, Robert E. MacLaren
Journal: Molecular Therapy (2017)
Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators
Authors: Ritu Raman, Lauren Grant, Yongbeom Seo, Caroline Cvetkovic, Michael Gapinske, Alexandra Palasz, Howard Dabbous, Hyunjoon Kong, Pablo Perez Pinera, Rashid Bashir
Journal: Advanced Healthcare Materials (2017)

A deeper understanding of biological materials and the design principles that govern them, combined with the enabling technology of 3D printing, has given rise to the idea of "building with biology." Using these materials and tools, bio-hybrid robots or bio-bots, which adaptively sense and respond to their environment, can be manufactured. Skeletal muscle bioactuators are developed to power these bio-bots, and an approach is presented to make them dynamically responsive to changing environmental loads and robustly resilient to induced damage. Specifically, since the predominant cause of skeletal muscle loss of function is mechanical damage, the underlying mechanisms of damage are investigated in vitro, and an in vivo inspired healing strategy is developed to counteract this damage. The protocol that is developed yields complete recovery of healthy tissue functionality within two days of damage, setting the stage for a more robust, resilient, and adaptive bioactuator technology than previously demonstrated. Understanding and exploiting the adaptive response behaviors inherent within biological systems in this manner is a crucial step forward in designing bio-hybrid machines that are broadly applicable to grand engineering challenges.
A glycomic serum marker analysed at one week after liver transplantation is an independent predictor of graft loss during the first year after liver transplantation
Authors: X. Verhelst, A. Geerts, X. Rogiers, A. Vanlander, F. Berrevoet, N. Callewaert, R.I. Troisi, H. Van Vlierberghe
Journal: Journal of Hepatology (2017)