tbuckley/cabot-search huggingface dataset:
Brief Physician Advice for Problem Drinkers
Authors: Michael Guarnieri
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The article by Dr Fleming and colleagues<sup>1</sup>demonstrates that advice protocols partially modified drinking behavior and improved health outcomes for at-risk problem drinkers in a primary care setting. However, numerous studies have revealed no effect or only weak positive effects of advice on lifestyle changes.<sup>2</sup>The encouraging results in the study on problem drinking by Fleming et al may have been because of an intervention effect. The study did not include a control group that was given nonrelevant medical advice. Members of the no-advice control group had a 20% reduction in alcohol use, perhaps because they were questioned about alcohol use 4 times during a 12-month period. A multinational study conducted by the World Health Organization found similar results.<sup>3</sup> As Dr Parish indicates in his Editorial,<sup>4</sup>those who argue that counseling by physicians affects a range of problem behaviors and that strong evidence supports counseling recognize
Bendamustine for anaplastic gliomas.
Authors: Marc C. Chamberlain, Howard Colman, Jeffrey J. Raizer
Journal: Journal of Clinical Oncology (2016)

2051 Background: There is no standard therapy for recurrent anaplastic glioma (AG). Salvage therapies include alkylator-based chemotherapy (temozolomide [TMZ] or lomustine [CCNU]), re-resection with or without carmustine implants, re-irradiation and bevacizumab. Bendamustine is a novel bifunctional alkylator with CNS penetration but never evaluated in AG. Objective: Assess response and toxicity of bendamustine in bevacizumab naïve recurrent AG following prior radiotherapy (RT) and TMZ in a prospective Phase II trial. Methods: 26 adults (16 males; 10 females: median age 40 years {range 30-65}) with RT and TMZ refractory recurrent AG (14 anaplastic astrocytoma, 7 anaplastic oligodendroglioma, 5 anaplastic oligoastrocytoma) were treated with bendamustine. 12 patients were treated at 1st and 14 at 2nd recurrence. Prior salvage therapy included re-resection in 14 (12 with 2nd and 2 with 3rd resection), chemotherapy in 11 and re-RT in 2. A cycle of bendamustine was defined as 2 consecutive days of treatment (100mg/m2/day) administered once every 4 weeks (maximum number of cycles 6). Success of treatment was defined as progression free survival (PFS) at 6 months > 40%. Results: Grade 3 treatment-related toxicities included lymphopenia (11 patients), myalgia, pneumonia, diarrhea, leukopenia, allergic reaction and thrombocytopenia in 1 patient each. Three patients had grade 4 lymphopenia. No grade 5 toxicities were seen. One patient discontinued therapy due to toxicity (allergic reaction). Bendamustine dose was delayed in 3 patients (total of 5 events). There were no dose reductions. The median number of cycles of therapy was 3 (range 1-8). Best radiographic response was progressive disease in 12 (46%), stable disease in 13 (50%) and partial response in 1 (4%). Response did not differ by histology. Median PFS was 2.7 months (range 1-52 months), 6-month PFS was 27% and 12-month PFS was 8%. Conclusions: In this small prospective series of patients with recurrent AG refractory to TMZ and bevacizumab naive, bendamustine appears to have modest single agent activity though not meeting pre-specified criteria (40% 6-month PFS) and manageable toxicity. The study was supported in part through research funds provided by TEVA Pharmaceuticals and the National Comprehensive Cancer Network. Clinical trial information: NCT00823797.
<i>TP53</i> mutations emerge in circulating cell-free DNA obtained from patients undergoing treatment with the HDM2 antagonist SAR405838.
Authors: James Wilson Watters, Mark Andrew Dickson, Gary K. Schwartz, Axel Le Cesne, Rastislav Bahleda, Andrew J. Wagner, Edwin Choy, Maja J. De Jonge, Madelyn Light, Joonil Jung, Joon Sang Lee, Sandrine Mace
Journal: Journal of Clinical Oncology (2015)

2515 Background: SAR405838 is an oral antagonist of HDM2 that results in p53 induction. In an ongoing Phase I study, p53 activation was demonstrated at doses that have an acceptable safety profile. We sought to develop a method for sequencing circulating cell-free DNA (ccfDNA) for the non-invasive monitoring of genetic changes in the tumor that may impact the activity of SAR405838 Methods: Baseline tumor and serially collected plasma samples were obtained from de-differentiated liposarcoma (DDLPS) patients undergoing treatment with SAR405838 at the maximum tolerated dose (300 mg QD). Tumor biopsies were sequenced using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies). A custom next-generation sequencing targeted gene panel was developed for ccfDNA. Sequencing libraries were prepared using custom xGen Lockdown probes (IDT). Sequencing was performed using the Illumina HiSeq 2500. Mutations were determined using a custom pipeline combining calls from MuTec and Lofreq. Mutation confirmation was performed using RainDance droplet digital PCR. Results: Tumor and plasma samples were available from 18 patients. All tumors were determined to be TP53 wild-type at baseline. From ccfDNA, greater than 10,000X coverage of target sequence was achieved. No TP53 mutations were identified at variant allele frequency (VAF) > 1% in the baseline ccfDNA samples. 27 non-synonymous mutations in TP53 were identified at VAF > 1% in ccfDNA from patients undergoing treatment. All TP53 mutations were previously reported in COSMIC, and all are located in the DNA-binding domain of p53. Mutation VAF increased during treatment, and multiple TP53 mutations arose within individual patients. All patients undergoing 5 or more cycles of treatment showed evidence of TP53 mutations in ccfDNA. A subset of mutations was selected for validation and all were confirmed using digital PCR. Conclusions: TP53 mutations appear in the ccfDNA of patients during treatment with SAR405838. This may represent the selection of TP53 mutant clones that are resistant to HDM2 inhibition. This finding suggests that HDM2 antagonists should be combined with other mechanisms including agents active in p53 mutant tumors.
Marked fall in ovarian cancer deaths is attributed to oral contraceptive use
Authors: Michael McCarthy
Journal: BMJ (2016)

Death rates from ovarian cancer fell markedly in the European Union, Oceania, and the United States from 2002 to 2012 with larger declines among younger women than among middle aged and older women, a study has found. More modest declines were seen in Latin America and Japan.

The researchers considered the main reason for the decrease to be the use of oral contraceptives, which have been shown to have a long term protective effect against ovarian cancer risk. Oral contraceptives were introduced earlier in the EU and the US than elsewhere, which may explain why these regions have seen the greatest reductions in ovarian cancer, the researchers said.

The study, reported in …
Double-blind, randomized, parallel group, phase III study to demonstrate equivalent efficacy and comparable safety of CT-P6 and trastuzumab, both in combination with paclitaxel, in patients with metastatic breast cancer (MBC) as first-line treatment.
Authors: Young-Hyuck Im, Petro Odarchenko, Daniela Grecea, Dmitry Komov, Chernobay Valentynovych Anatoliy, Sudeep Gupta, Yaroslav V. Shparyk, Priscilla B. Caguioa, Anatoly Makhson, Dmitriy Krasnozhon, Rubi Khaw Li, Dzmitry Noryk, Yurii Oleksiiovych Vinnyk, Gia Nemsadze, Ho Ung Kim, Sang-Joon Lee
Journal: Journal of Clinical Oncology (2013)

629 Background: CT-P6(C) is an anti-HER2 MoAb, a biosimilar to trastuzumab (T). This trial is a global phase III study to compare C with T, both in combination with paclitaxel (P) as first-line treatment in women with HER2+ MBC. Methods: 475 patients with centrally confirmed HER2+ MBC were randomized to receive either C+P (n=244) or T+P (n=231). Patients had to have a baseline LVEF ≥50% and no history of serious cardiac disease. Study medication was as follows: C or T 8 mg/kg i.v. (day 1), followed by 3-weekly C or T 6 mg/kg. P (175 mg/m 2 3-weekly) was co-administered. The primary endpoint was overall response rate (ORR) as determined by independent review. Pooled analysis with data from phase I/IIb (NCT01084863) and III studies (NCT01084876) was predefined and endorsed by the EMA. Patient safety was monitored throughout the study by an independent data monitoring committee. Treatment was continued until disease progression, death or patient’s withdrawal. Results: In the pooled ITT population, ORR was 57% for C+P and 62% for T+P (difference: 5%; 95% CI: -0.14, 0.04) during the first 8 cycles of treatment. The limits of the 95% CIs for the difference in the proportions of responders were contained within the pre-defined range [-0.15, 0.15] required for equivalence. Median time to progression and median time to response were 11.07 vs. 12.52 months (P =0.10), and 1.38 vs. 1.38 months (P =0.37) for C+P and T+P, respectively. Frequency of treatment-related AEs is shown in the Table. Conclusions: Equivalence of C and T was observed for ORR in patients with HER2+ MBC in combination with P as first-line therapy. Secondary efficacy endpoints also supported the comparability between C and T. C was well tolerated with a safety profile comparable to that of T. Clinical trial information: NCT01084876. [Table: see text]
P0959 : Dietary intervention completely reverses non-alcoholic steatohepatitis in obese and insulin resistant mice
Authors: J. Verbeek, I. Vanhorebeek, P. Spincemaille, G. Van den Berghe, I. Vander Elst, P. Windmolders, J. van Pelt, P. Bedossa, F. Nevens, B. Cammue, K. Thevissen, D. Cassiman
Journal: Journal of Hepatology (2015)
Heterogeneity in Suspected Non–Alzheimer Disease Pathophysiology Among Clinically Normal Older Individuals
Authors: Elizabeth C. Mormino, Kathryn V. Papp, Dorene M. Rentz, Aaron P. Schultz, Molly LaPoint, Rebecca Amariglio, Bernard Hanseeuw, Gad A. Marshall, Trey Hedden, Keith A. Johnson, Reisa A. Sperling
Journal: JAMA Neurology (2016)

A substantial proportion of clinically normal (CN) older individuals are classified as having suspected non-Alzheimer disease pathophysiology (SNAP), defined as biomarker negative for β-amyloid (Aβ-) but positive for neurodegeneration (ND+). The etiology of SNAP in this population remains unclear.
Flamsa Reduced-Intensity Conditioning Regimen in AML Patients – Role of Re-Induction and Disease State Prior to Transplant
Authors: Udo Holtick, Alexander Shimabukuro-Vornhagen, Geothy Chakupurakal, Sebastian Theurich, Silke Leitzke, Dominik Wolf, Michael Hallek, Michael S. von Bergwelt-Baildon, Christof Scheid, Jens Chemnitz
Journal: Blood (2014)
Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma
Authors: William J Sheehan, David T Mauger, Ian M Paul, James N Moy, Susan J Boehmer, Stanley J Szefler, Anne M Fitzpatrick, Daniel J Jackson, Leonard B Bacharier, Michael D Cabana, Ronina Covar, Fernando Holguin, Robert F Lemanske, Fernando D Martinez, Jacqueline A Pongracic, Avraham Beigelman, Sachin N Baxi, Mindy Benson, Kathryn Blake, James F Chmiel, Cori L Daines, Michael O Daines, Jonathan M Gaffin, Deborah A Gentile, W Adam Gower, Elliot Israel, Harsha V Kumar, Jason E Lang, Stephen C Lazarus, John J Lima, Ngoc Ly, Jyothi Marbin, Wayne J Morgan, Ross E Myers, J Tod Olin, Stephen P Peters, Hengameh H Raissy, Rachel G Robison, Kristie Ross, Christine A Sorkness, Shannon M Thyne, Michael E Wechsler, Wanda Phipatanakul
Journal: New England Journal of Medicine (2016)

Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial.Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events.Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).
Chemosensitization and Mobilization Of AML/ALL/MDS With Plerixafor (AMD 3100), a CXCR4 Antagonist: A Phase I Study Of Plerixafor + Cytarabine and Etoposide In Pediatric Patients With Acute Leukemia and MDS
Authors: Todd Michael Cooper, Sharyn D. Baker, Jennifer Direnzo, Tanya M. Trippett, Lia Gore, Aru Narendran, Keith J. August, Michael J. Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Edward Allan R. Sison, Patrick Brown
Journal: Blood (2013)
Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma
Authors: A. Keith Stewart, Meletios A. Dimopoulos, Tamás Masszi, Ivan Špička, Albert Oriol, Roman Hájek, Laura Rosiñol, David S. Siegel, Ruben Niesvizky, Andrzej J. Jakubowiak, Jesus F. San-Miguel, Heinz Ludwig, Jacqui Buchanan, Kim Cocks, Xinqun Yang, Biao Xing, Naseem Zojwalla, Margaret Tonda, Philippe Moreau, Antonio Palumbo
Journal: Journal of Clinical Oncology (2016)

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.
<i>Pitx2</i> modulates a <i>Tbx5</i> -dependent gene regulatory network to maintain atrial rhythm
Authors: Rangarajan D. Nadadur, Michael T. Broman, Bastiaan Boukens, Stefan R. Mazurek, Xinan Yang, Malou van den Boogaard, Jenna Bekeny, Margaret Gadek, Tarsha Ward, Min Zhang, Yun Qiao, James F. Martin, Christine E. Seidman, Jon Seidman, Vincent Christoffels, Igor R. Efimov, Elizabeth M. McNally, Christopher R. Weber, Ivan P. Moskowitz
Journal: Science Translational Medicine (2016)

A mouse model reveals how seven atrial fibrillation–related risk genes form a network to control heartbeat.
Photothermal Gene Delivery: Stimuli-Regulated Enzymatically Degradable Smart Graphene-Oxide-Polymer Nanocarrier Facilitating Photothermal Gene Delivery (Adv. Healthcare Mater. 15/2016)
Authors: Hyunwoo Kim, Jinhwan Kim, Minkyung Lee, Hee Cheul Choi, Won Jong Kim
Journal: Advanced Healthcare Materials (2016)

On page 1918, Won Jong Kim and co-workers use disulfide bonding for the rational design of graphene oxide (GO) based nanocarriers. In the lower left side, photothermally triggered gene release is illustrated in cancer cell. Polymer-detached GOis exocytosed, and subsequently gets into the macrophage (middle right). In the macrophage, peroxidase binds to GO, thus degrades it to small fragments which are fluorescent.
Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection
Authors: Haiyin Liu, Reema Jain, Jing Guan, Vivian Vuong, Satoshi Ishido, Nicole L. La Gruta, Daniel H. Gray, Jose A. Villadangos, Justine D. Mintern
Journal: The Journal of Experimental Medicine (2016)

Major histocompatibility complex class II (MHC II) expression is tightly regulated, being subjected to cell type-specific mechanisms that closely control its levels at the cell surface. Ubiquitination by the E3 ubiquitin ligase MARCH 1 regulates MHC II expression in dendritic cells and B cells. In this study, we demonstrate that the related ligase MARCH 8 is responsible for regulating surface MHC II in thymic epithelial cells (TECs). March8(-/-) mice have elevated MHC II at the surface of cortical TECs and autoimmune regulator (AIRE)(-) medullary TECs (mTECs), but not AIRE(+) mTECs. Despite this, thymic and splenic CD4(+) T cell numbers and repertoires remained unaltered in March8(-/-) mice. Notably, the ubiquitination of MHC II by MARCH 8 is controlled by CD83. Mice expressing a mutated form of CD83 (Cd83(anu/anu) mice) have impaired CD4(+) T cell selection, but deleting March8 in Cd83(anu/anu) mice restored CD4(+) T cell selection to normal levels. Therefore, orchestrated regulation of MHC II surface expression in TECs by MARCH 8 and CD83 plays a major role in CD4(+) T cell selection. Our results also highlight the specialized use of ubiquitinating machinery in distinct antigen-presenting cell types, with important functional consequences and implications for therapeutic manipulation.
Transformation Mechanisms of Papillomaviruses
Authors: Schreier, Alan A., Gruber, Jack
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Transformation Mechanisms of Papillomaviruses Get access Alan A. Schreier, Ph.D., Alan A. Schreier, Ph.D. Biological Carcinogenesis Branch Division of Cancer Etiology National Cancer Institute National Institutes of Health Public Health Service U.S. Department of Health and Human ServicesBethesda, Maryland 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar Jack Gruber, Ph.D. Jack Gruber, Ph.D. Biological Carcinogenesis Branch Division of Cancer Etiology National Cancer Institute National Institutes of Health Public Health Service U.S. Department of Health and Human ServicesBethesda, Maryland 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 4, April 1987, Pages 779–784, https://doi.org/10.1093/jnci/78.4.779 Published: 01 April 1987
Clinical Impact of Additional Cytogenetic Aberrations, cKIT- and RAS Mutations and Other Factors in Pediatric t(8;21)-AML
Authors: Kim Klein, Gertjan Kaspers, Christine J. Harrison, Berna Beverloo, Ardine Reedijk, Mathilda Bongers, Jacqueline Cloos, Andrea Pession, Dirk Reinhardt, Martin Zimmermann, Ursula Creutzig, Michael Dworzak, Todd A. Alonzo, Donna Johnston, Michal Zapotocky, Barbara De Moerloose, Alcira Fynn, Vincent Lee, Takashi Taga, Akio Tawa, Anne Auvrignon, Bernward Zeller, Carmen Salgado, Walentyna Balwierz, Alexander Popa, Jeffrey E Rubnitz, Brenda Gibson
Journal: Blood (2014)
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial
Authors: Sebastian Stintzing, Dominik P Modest, Lisa Rossius, Markus M Lerch, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christian Lerchenmüller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Swantje Held, Clemens Giessen-Jung, Markus Moehler, Andreas Jagenburg, Thomas Kirchner, Andreas Jung, Volker Heinemann
Journal: The Lancet Oncology (2016)