tbuckley/cabot-search huggingface dataset:
Reply
Authors: Aijaz Ahmed, Rachel Beckerman, Zobair M. Younossi
Journal: Hepatology (2017)

Potential conflict of interest: Dr. Beckerman consults for Gilead. Dr. Ahmed consults and received grants from Gilead. He consults for AbbVie. Reply: We agree with Liu and colleagues that the populations most significantly affected by hepatitis C virus (HCV) infection, in particular the African American population within the United States, are underrepresented in clinical trials for chronic HCV infection. However, overall sustained virological response rates for all‐oral direct‐acting antivirals (DAA) such as ledipasvir/sofosbuvir are comparable across racial groups in real‐world settings, retrospective pooled analyses of clinical trial data, and studies from the US Department of Veterans Affairs health database.1 Therefore, inclusion of ASTRAL‐4 data is unlikely to bias the results of our analysis significantly. We agree that inequity in access to DAAs remains a major issue in the United States, particularly in the incarcerated population. Rationing by insurance companies has resulted in limited access to treatment: Medicaid patients can be denied access to DAAs if ongoing use of injectable drugs or alcohol is noted.2 Inequity in access is thus a major barrier to achieving the complete eradication of HCV infection and may be contributing to increasing the disease burden. A societal perspective supports an informed public discussion, and, as all‐oral DAAs have been associated with significant benefits on patient reported outcomes,3 framing our analysis from this perspective would only increase the cost‐effectiveness of pretransplant all‐oral DAA treatment. Indeed, others have taken a societal perspective to demonstrate the cost‐effectiveness of all‐oral DAAs in the prison setting.4 With the high burden that HCV infection imposes on the US health care system, individuals, and society, the importance of efforts to eradicate HCV cannot be understated: we believe it is critical to establish a national policy to eradicate HCV. This will require significant up‐front financial investment, resources, and public and political will. Considering the long‐term benefits of HCV cure (including reduction of complications of HCV‐related diseases, improvement of patient reported outcomes, and associated costs), after an initial investment, this strategy will benefit all stakeholders. Therefore, in the current political environment, collaborative advocacy is more important than ever with pursuit of nondiscriminatory access policy to DAA agents. Taking into account the demonstrated clinical and economic outcomes associated with pretransplant all‐oral DAA use, we join Liu et al. in urging payers, health organizations, and policymakers to endorse global eradication of HCV infection as the unified goal of HCV antiviral therapy.
HIV Care Outcomes Among Men Who Have Sex With Men With Diagnosed HIV Infection — United States, 2015
Authors: Sonia Singh, Andrew Mitsch, Baohua Wu
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

National Gay Men's HIV/AIDS Awareness Day is observed each year on September 27 to direct attention to the ongoing and disproportionate impact of human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS) on gay, bisexual, and other men who have sex with men (MSM) (https://www.cdc.gov/hiv/risk/gender/msm) in the United States.MSM represent approximately 2% of the U.S. population (1); however, in 2015, MSM accounted for 69.8% of all new diagnoses including 3.0% who were also persons who inject drugs (2).In 2014, among all persons living with HIV infection, an estimated 615,400 were MSM (3).Of these MSM, an estimated 17% had undiagnosed HIV infection.Among 358,151 MSM living with diagnosed HIV in 38 jurisdictions with complete reporting of CD4 and viral load data at year-end 2014, 58% were retained in continuous care, and 61% were virally suppressed (<200 copies of HIV RNA/mL detected at the most recent viral load test) (3).CDC supports a range of measures to reduce HIV infection among MSM (https://www.cdc.gov/hiv/group/msm/index.html).Information about National Gay Men's HIV/ AIDS Awareness Day is available at https://www.cdc.gov/features/ngmhaad.
Clinical outcomes of temporary mechanical circulatory support as a direct bridge to heart transplantation: a nationwide Spanish registry
Authors: Eduardo Barge‐Caballero, Luis Almenar‐Bonet, Francisco Gonzalez‐Vilchez, José L. Lambert‐Rodríguez, José González‐Costello, Javier Segovia‐Cubero, María A. Castel‐Lavilla, Juan Delgado‐Jiménez, Iris P. Garrido‐Bravo, Diego Rangel‐Sousa, Manuel Martínez‐Sellés, Luis De la Fuente‐Galan, Gregorio Rábago‐Juan‐Aracil, Marisa Sanz‐Julve, Daniela Hervás‐Sotomayor, Sonia Mirabet‐Pérez, Javier Muñiz, Maria G. Crespo‐Leiro
Journal: European Journal of Heart Failure (2017)
Glutamic Acid from Normal and Cancerous Tissue
Authors: J. M. Johnson
Journal: JNCI Journal of the National Cancer Institute (1940)

Journal Article Glutamic Acid from Normal and Cancerous Tissue Get access J. M. Johnson J. M. Johnson senior chemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 1, 1940-1941, Pages 113–117, https://doi.org/10.1093/jnci/1.1.113 Published: 01 August 1940
Case 30-2017
Authors: Roby P. Bhattacharyya, Efren J. Flores, Marwan M. Azar
Journal: New England Journal of Medicine (2017)

A 65-year-old woman with autoimmune hepatitis presented for an evaluation for liver transplantation. Fever, hypotension, and worsening liver and renal failure developed. A blood culture revealed corkscrew-shaped gram-negative rods. A diagnosis was made.
Acquired hemophilia A resolution in a hepatitis C virus/human immunodeficiency virus–coinfected patient with cure of hepatitis C by direct‐acting antiviral agents
Authors: Laetitia Mauge, Juliette Pavie, Dominique Batisse, Luc Darnige
Journal: Hepatology (2017)

1Assistance Publique-Hôpitaux de Paris, Hôpital européen Georges Pompidou, Service d'Hématologie biologiqueParisFrance 2INSERM UMR-S970Centre de Recherche Cardiovasculaire de ParisParisFrance 3Sorbonne Paris Cité, Université Paris DescartesParisFrance 4Assistance Publique-Hôpitaux de Paris, Hôpital européen Georges Pompidou, Service d'Immunologie cliniqueParisFrance *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Laetitia Mauge, M.D.Hématologie Biologique, Hôpital Européen Georges Pompidou20 rue Leblanc75015 Paris, FranceE‐mail: [email protected]Tel: +33‐156093905
Vav3 oncogene, a quanine nucleotide exchange factor for Rac/Rho GTPases, is a coactivator for nuclear receptors and involved in human breast cancer.
Authors: Kiwon Lee, Yin Liu, Amy Wang, Jun Qin Mo, Jinsong Zhang, Zhongyun Dong, Shan Lu
Journal: Cancer Research (2007)

2518  Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor (AR), and stimulates growth in prostate cancer cells. The current study is to determine the role of Vav3 in human breast cancer. We found that Vav3 activates estrogen receptor-alpha (ER-alpha), stimulates growth of breast cancer cells, and potentiates EGF activity for cell growth and ER-alpha activation. Vav3, as a signal molecule, also activates ER-alpha partially via PI3K-Akt signaling. Consistent with its function for AR, the DH domain of Vav3 is responsible for ER-alpha activation. Further analysis revealed that Vav3 upregulates the activities of both steroid hormone receptors ER-alpha, progesterone receptor (PR), and glucocorticoid receptor (GR), and non-steroid hormone receptors, such as retinoic acid receptor-alpha (RAR-alpha). Vav3 also showed an additive effect with other coactivators, including SRC1, TIF2, RAC3/SRC3, and E6-AP. Furthermore, we found that Vav3 interacts with both AR and ER-alpha via the DH domain, suggesting that Vav3 functions as a coactivator for nuclear receptors. More importantly, we found that Vav3 is overexpressed in 82% of human breast cancer. Our data suggest that Vav3 oncogene is a protein with multiple functions, including a novel coactivator activity for nuclear receptors in addition to the quanine nucleotide exchange factor (GEF) activity for Rho family GTPases. Vav3 oncogene may play a critical role in breast cancer.
Efficacy and safety of third-line treatment with anlotinib in patients with refractory advanced non-small-cell lung cancer (ALTER-0303): a randomised, double-blind, placebo-controlled phase 3 study
Authors: Baohui Han, Kai Li, Qiming Wang, Yizhuo Zhao, Li Zhang, Jianhua Shi, Zhehai Wang, Yin Cheng, Jianxing He, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin, Baolan Li, Yinlan Chen, Jianying Zhou, Donglin Wang
Journal: The Lancet Oncology (2017)
Sex- and Dose-Specific Effects of Maternal Bisphenol A Exposure on Pancreatic Islets of First- and Second-Generation Adult Mice Offspring
Authors: Amita Bansal, Cetewayo Rashid, Frances Xin, Changhong Li, Erzsebet Polyak, Anna Duemler, Tom van der Meer, Martha Stefaniak, Sana Wajid, Nicolai Doliba, Marisa S. Bartolomei, Rebecca A. Simmons
Journal: Environmental Health Perspectives (2017)

Exposure to the environmental endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with the increased risk of diabetes and obesity. However, the underlying mechanisms remain unknown. We recently demonstrated that perinatal BPA exposure is associated with higher body fat, impaired glucose tolerance, and reduced insulin secretion in first- (F1) and second-generation (F2) C57BL/6J male mice offspring.We sought to determine the multigenerational effects of maternal bisphenol A exposure on mouse pancreatic islets.Cellular and molecular mechanisms underlying these persistent changes were determined in F1 and F2 adult offspring of F0 mothers exposed to two relevant human exposure levels of BPA (10μg/kg/d-LowerB and 10mg/kg/d-UpperB).Both doses of BPA significantly impaired insulin secretion in male but not female F1 and F2 offspring. Surprisingly, LowerB and UpperB induced islet inflammation in male F1 offspring that persisted into the next generation. We also observed dose-specific effects of BPA on islets in males. UpperB exposure impaired mitochondrial function, whereas LowerB exposure significantly reduced β-cell mass and increased β-cell death that persisted in the F2 generation. Transcriptome analyses supported these physiologic findings and there were significant dose-specific changes in the expression of genes regulating inflammation and mitochondrial function. Previously we observed increased expression of the critically important β-cell gene, Igf2 in whole F1 embryos. Surprisingly, increased Igf2 expression persisted in the islets of male F1 and F2 offspring and was associated with altered DNA methylation.These findings demonstrate that maternal BPA exposure has dose- and sex-specific effects on pancreatic islets of adult F1 and F2 mice offspring. The transmission of these changes across multiple generations may involve either mitochondrial dysfunction and/or epigenetic modifications. https://doi.org/10.1289/EHP1674.
<i>Cic</i> Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation
Authors: Rui Yang, Lee H. Chen, Landon J. Hansen, Austin B. Carpenter, Casey J. Moure, Heng Liu, Christopher J. Pirozzi, Bill H. Diplas, Matthew S. Waitkus, Paula K. Greer, Huishan Zhu, Roger E. McLendon, Darell D. Bigner, Yiping He, Hai Yan
Journal: Cancer Research (2017)

Inactivating mutations in the transcriptional repression factor Capicua (CIC) occur in approximately 50% of human oligodendrogliomas, but mechanistic links to pathogenesis are unclear. To address this question, we generated Cic-deficient mice and human oligodendroglioma cell models. Genetic deficiency in mice resulted in a partially penetrant embryonic or perinatal lethal phenotype, with the production of an aberrant proliferative neural population in surviving animals. In vitro cultured neural stem cells derived from Cic conditional knockout mice bypassed an EGF requirement for proliferation and displayed a defect in their potential for oligodendrocyte differentiation. Cic is known to participate in gene suppression that can be relieved by EGFR signal, but we found that cic also activated expression of a broad range of EGFR-independent genes. In an orthotopic mouse model of glioma, we found that Cic loss potentiated the formation and reduced the latency in tumor development. Collectively, our results define an important role for Cic in regulating neural cell proliferation and lineage specification, and suggest mechanistic explanations for how CIC mutations may impact the pathogenesis and therapeutic targeting of oligodendroglioma. Cancer Res; 77(22); 6097-108. ©2017 AACR.
Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability
Authors: Panagiotis Galanos, George Pappas, Alexander Polyzos, Athanassios Kotsinas, Ioanna Svolaki, Nickolaos N. Giakoumakis, Christina Glytsou, Ioannis S. Pateras, Umakanta Swain, Vassilis L. Souliotis, Alexandros G. Georgakilas, Nicholas Geacintov, Luca Scorrano, Claudia Lukas, Jiri Lukas, Zvi Livneh, Zoi Lygerou, Dipanjan Chowdhury, Claus Storgaard Sørensen, Jiri Bartek, Vassilis G. Gorgoulis
Journal: Genome biology (2018)

Abstract Background Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design of appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property of p21 WAF1/Cip1 , showing that its chronic expression in a p53-deficient environment causes genomic instability by deregulation of the replication licensing machinery. Results We now demonstrate that p21 WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low- and high-fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we find that the DSBs are repaired by Rad52-dependent break-induced replication (BIR) and single-strand annealing (SSA) repair pathways. Conversely, the error-free synthesis-dependent strand annealing (SDSA) repair route is deficient. Surprisingly, Rad52 is activated transcriptionally in an E2F1-dependent manner, rather than post-translationally as is common for DNA repair factor activation. Conclusions Our results signify the importance of mutational signatures as guides to disclose the repair history leading to genomic instability. We unveil how chronic p21 WAF1/Cip1 expression rewires the repair process and identifies Rad52 as a source of genomic instability and a candidate therapeutic target.
HIPEC in treatment of gastric cancer with high risk of carcinomatosis: Russians Regional Centre experience.
Authors: Alexey Privalov, Andrey Vazenin, Andrey Antonov
Journal: Journal of Clinical Oncology (2017)

e15501 Background: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a treatment method in patients with gastric cancer having a high risk of development of peritoneal carcinomatosis which can improve treatment results. Methods: HIPEC in a "prophylactic" setting in gastric patients having a high risk of peritoneal carcinomatosis development has been applied in our centre since 2015. This method was used in cases of diffuse type poor-differentiated tumor histology , massive tumor invasion of the stomach serosa and relatively young age of the patient. A “closed” HIPEC technique, with 3 inflow and 3 outflow catheters, RAND HT performer and 7 liters of saline solution with 200 mg cisplatinum was performed. Up to this moment we have treated 8 patients with gastric surgery added by HIPEC. There were 4 men and 4 women. Median age was 48 years. In 2 cases distal subtotal gastric resection was performed, in other 6 cases - total gastrectomy with a D2 lymph nodes dissection. In 2 cases was also performed an edge resection of the pancreas. 2 procedures were performed in cases with ovarian metastases and local diaphragm canceromatosis, with complete cytoreduction. Median surgery time was 4 hours. Results: There was no mortality in early postoperative period, with 25% morbidity. In one case a severe postoperative pancreonecrosis occured which required several re-operations. In one case there has been an acute renal failure, after 3 dialyse sessions the renal function was recovered. Median post-operative hospital stay was 20 days. Two patients are alive without progression on 14 and 23 months respectively. One patient developed a local anastomotic recurrence, no other progression was found, and anastomosis extirpation was performed. Patients having ovarian metastases and local canceromatosis progressed in 6 months, in other cases progression was found in 6 to 12 months. Conclusions: The use of HIPEC doesn't result in elevation of complications or mortality rate. It shows a trend to improve the results of treatment gastric cancer. In cases of already existing canceromatosis the effectiveness of HIPEC is doubtful.
Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients
Authors: Maria Patrizia Carrieri, Camelia Protopopescu, Fabienne Marcellin, Silvia Rosellini, Linda Wittkop, Laure Esterle, David Zucman, François Raffi, Eric Rosenthal, Isabelle Poizot-Martin, Dominique Salmon-Ceron, François Dabis, Bruno Spire
Journal: Journal of Hepatology (2017)
Discussion of Methotrexate Dosage
Authors: Sinead A Maguire, Claire Marie Sheehy
Journal: Annals of the Rheumatic Diseases (2017)

We thank Safy et al 1 for their recent article discussing clinical outcomes in early treatment of rheumatoid arthritis with methotrexate and 10 mg daily of prednisolone versus methotrexate alone. This was a post-trial follow-up of the CAMERA II trial, which monitored for radiographic evidence of disease progression, use of biologic disease-modifying antirheumatic drugs (DMARDs) and incidence of glucocorticoid comorbidities. We appreciate the work that …
Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients
Authors: A. Bhimji, A. Bhaskaran, L.G. Singer, D. Kumar, A. Humar, R. Pavan, J. Lipton, J. Kuruvilla, A. Schuh, K. Yee, M.D. Minden, A. Schimmer, C. Rotstein, S. Keshavjee, T. Mazzulli, S. Husain
Journal: Clinical Microbiology and Infection (2017)
Abstract #29: Mitochondrial bioenergetics is an apoptogenic regulator for N-(4-hydroxyphenyl)retinamide in premalignant and malignant prostate epithelial cells
Authors: Numsen Hail, Ping Chen, Jadwiga Kepa
Journal: Cancer Research (2009)

Prostate tumorigenesis is purportedly coupled with an early metabolic switch in transformed prostate epithelial cells that effectively increases their mitochondrial bioenergetic capacity. The synthetic retinoid  N -(4-hydroxyphenyl)retinamide (4HPR) inhibits prostate cancer development  in vivo ,   and triggers prostate cancer cell apoptosis  in vitro . Certain  in vitro  studies suggest that 4HPR-induced apoptosis is associated with reactive oxygen species (ROS) production and mitochondrial disruption, which would advocate a prospective mechanistic basis for 4HPR-mediated prostate cancer chemoprevention. We investigated this tenet by comparing and contrasting the effects of 4HPR on premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. 4HPR promoted a dose- and/or time-dependent apoptosis induction (e.g., cell shrinkage, mitochondrial disruption, the externalization of cell membrane phosphatidylserine, and DNA fragmentation) in PWR-1E and DU-145 cells, which was preceded by and dependent on an increase in mitochondrial ROS production. In this regard, the PWR-1E cells were more sensitive than the DU-145 cells, and they consumed roughly twice as much oxygen as the DU-145 cells suggesting oxidative phosphorylation was higher in the premalignant cells. Interestingly, increasing the [Ca 2+ ] in the culture medium of PWR-1E cells attenuated their proliferation as well as their mitochondrial bioenergetic capacity and the cytotoxic effects of 4HPR. Correspondingly, the respiration-deficient derivatives (i.e., rho0 cells lacking mitochondrial DNA) of DU-145 cells were markedly resistant to 4HPR-induced ROS production and apoptosis. Together, these observations implied that the reduction of mitochondrial bioenergetics protected PWR-1E and DU-145 cells against the cytotoxic effects of 4HPR, and support the concept that oxidative phosphorylation is an essential determinant in 4HPR\#8217;s apoptogenic signaling in transformed human prostate epithelial cells.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 29.
Margaret McCartney: When can I get back to running after my operation?
Authors: Margaret McCartney
Journal: BMJ (2017)

When should I start running after a microdiscectomy? In weeks 1 and 2, walking is challenging enough. Week 3: the last few rays of summery sunshine, and I regard other runners with frank jealousy. I want to go running, but I’m scared of undoing the benefits of surgery. As one protocol says, I have “patient anxiety regarding reherniation risks.”

But where does this anxiety come from? “Sports should be avoided for three months,” says my local leaflet. But sex can be resumed “fairly soon, provided that you avoid any strenuous activity and are lying on your back.” This is unexpected, and I wonder what the evidence is. What will it actually take to undo the surgeon’s good work?

The internet …
Nonhealing Leg Ulcer in a Middle-aged Indian Man
Authors: Keshavamurthy Vinay, Dipankar De, Uma N. Saikia
Journal: JAMA Dermatology (2017)

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