tbuckley/cabot-search huggingface dataset:
PTH-094 Indirect treatment comparison of ustekinumab versus other biologics in moderate to severe crohn’s disease: a 1-year treatment sequence analysis
Authors: M Pacou, L Mesana, A Gauthier, D Naessens, S Sloan, S Danese, S Bonovas, K Abrams
Journal: Gut (2017)

Introduction  Indirect evidence is needed to better inform decision-makers on the clinical efficacy of ustekinumab in Crohn’s disease (CD). Network meta-analyses in CD are challenged by withdrawal trial designs limiting placebo arm transitivity. A treatment sequence analysis was conducted to compare one year efficacy of biologics in CD.  Method  A systematic literature review identified randomised controlled trials for induction and maintenance of clinical efficacy evaluating infliximab, adalimumab, or vedolizumab. Separate analyses were conducted for clinical response (Crohn’s Disease Activity Index (CDAI) reduction of 100 points) and remission (CDAI under 150) in patients having either failed conventional or anti-TNF therapy. The relative probability of achieving response at the end of induction was multiplied by the conditional probability of maintaining response or remission after one year. End of maintenance placebo-to-placebo rates (only available from ustekinumab trials) were externally imputed using patient data, adjusted for the proportion of responders and remitters at the end of induction in each trial. Analyses were performed in a Bayesian framework to generate posterior distribution probabilities for ustekinumab to perform better than its comparators.  Results  In patients who failed conventional therapy, Bayesian probabilities for better remission or response at 1 year with ustekinumab compared to adalimumab or vedolizumab ranged from 51%(OR[CrI]:1.01 [0.40;2.40]) to 97%(OR[CrI]:1.91 [0.96;3.78]). When comparing ustekinumab to infliximab, probabilities ranged from 16%(OR[CrI]:0.41 [0.05;2.13]) to 34%(OR[CrI]:0.69 [0.08;3.73]). In patients who failed anti-TNF therapy, probabilities for better response or remission at 1 year with ustekinumab compared to adalimumab or vedolizumab ranged from 44%(OR[CrI]:0.94 [0.45;1.97]) to 97%(OR[CrI]:1.89 [0.97;3.67]).  Conclusion  This novel approach deals with issues of similarity and transitivity and seems most appropriate to compare one year efficacy of biologics in CD. Looking at the entire treatment sequence suggests a higher likelihood of response or remission at year 1 with ustekinumab compared to vedolizumab or adalimumab, with the lower probabilities for remission and versus adalimumab weekly dosing.  Disclosure of Interest  M. Pacou: None Declared, L Mesana: None Declared, A Gauthier: None Declared, D Naessens Conflict with: Janssen Pharmaceutica NV, S Sloan Conflict with: Janssen Global Services LLC, S Danese: None Declared, S Bonovas: None Declared, K Abrams: None Declared
Role of metformin, aspirin and statin in cancer prevention: A population- based study
Authors: P. Phetchoo, T. Reungwetwattana, S. Oranratnachai, N. Thongmung, S. Aiempradir, S. Rattanasiri, P. Vathesatogkit, A. Thakkinstian, P. Sritara
Journal: Annals of Oncology (2017)
P2.03b-073 High Concordance of Somatic SNVs between Tumor-Only and Tumor-Normal Testing: Implications for Clinical Practice
Authors: Xia Ran, Wei Dong, Yang Guo, Xuehong Meng, Lingchen Xiao, Xiaomin Li, Longgang Wei, Zhi Jiang, Dongmei Lin
Journal: Journal of Thoracic Oncology (2017)
Transthoracic Echocardiographic Findings of Mitral Regurgitation Caused by Commissural Prolapse
Authors: Kyung-Jin Kim, Hyung-Kwan Kim, Jun-Bean Park, Ho-Young Hwang, Yeonyee E. Yoon, Yong-Jin Kim, Goo-Young Cho, Kyung-Hwan Kim, Dae-Won Sohn, Hyuk Ahn
Journal: JACC. Cardiovascular imaging (2017)
Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances Chemotherapy in Pancreatic Cancer
Authors: Kathleen F. Ludwig, Wenting Du, Noah B. Sorrelle, Katarzyna Wnuk-Lipinska, Mary Topalovski, Jason E. Toombs, Victoria H. Cruz, Shinichi Yabuuchi, N.V. Rajeshkumar, Anirban Maitra, James B. Lorens, Rolf A. Brekken
Journal: Cancer Research (2017)

Activation of the receptor tyrosine kinase Axl is associated with poor outcomes in pancreatic cancer (PDAC), where it coordinately mediates immune evasion and drug resistance. Here, we demonstrate that the selective Axl kinase inhibitor BGB324 targets the tumor-immune interface to blunt the aggressive traits of PDAC cells in vitro and enhance gemcitibine efficacy in vivo Axl signaling stimulates the TBK1-NFκB pathway and innate immune suppression in the tumor microenvironment. In tumor cells, BGB324 treatment drove epithelial differentiation, expression of nucleoside transporters affecting gemcitabine response, and an immune stimulatory microenvironment. Our results establish a preclinical mechanistic rationale for the clinical development of Axl inhibitors to improve the treatment of PDAC patients.Significance: These results establish a preclinical mechanistic rationale for the clinical development of AXL inhibitors to improve the treatment of PDAC patients. Cancer Res; 78(1); 246-55. ©2017 AACR.
Claudin 1, 3, 4, and 7 expression in triple-negative breast cancer.
Authors: Beom Seok Ko, Hee Jeong Kim, Jong Han Yu, jong Won Lee, Byung Ho Sohn, Sung-Bae Kim, Gyungyub Gong, Sei-Hyun Ahn
Journal: Journal of Clinical Oncology (2013)

1070 Background: Triple negative breast cancer (TNBC) often grows rapidly and has poor prognosis, with a high recurrence rate. Because conventional endocrine treatment and HER2 targeted therapy for TNBC is invalid, chemotherapy is the only systemic treatment for TNBC. It is known that several subtypes within the TNBC show different responses to chemotherapy, depending on the subtypes. Recently, a claudin (CLDN) low breast cancer has been identified, exhibiting low expressions of CLDNs 1, 3, 4 and 7. CLDNs are transmembrane proteins that seal tight junctions and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Methods: Surgically removed, formalin-fixed, paraffin-embedded breast cancers from 341 TNBC patients were analyzed to identify CLDN expression.They underwent wide local excision or mastectomy between March, 2004 and December, 2007 at the breast surgery unit of Asan Medical Central Hospital. Results: In our tumor series, we found 45.0% (153/339) of high expressing cases for CLDN1, 57.0% (192/337) for CLDN3, 57.6% (194/337) for CLDN4 and 44.0% (149/339) for CLDN7. Overall, we found 20.5% (70/341) of cases were within the low CLDN expression group and 79.5% (271/341) of tumors were within the high expression group of CLDN1, 3, 4 ,7. Although the high CLDN expression group was significantly associated with positive lymph node status and higher stage, there were no significant differences between CLDN low and high groups in disease free survival (p=0.477) or overall survival (p=0.253). Conclusions: CLDN high tumors are associated with poor prognosis features, but they are not an independent prognostic factor in TNBC patients. However, the mechanisms underlying the different roles of CLDNs in tumorigenesis are largely unclear. Studying the associations of these CLDNs with the TNBC subgroup of breast cancers might provide us with potential diagnostic biomarkers or therapeutic targets for cancer cells.
Abstract 20932: Dynamic Regulation of Myocardial Long Noncoding RNAs in Human Heart Failure and Reverse Remodeling With Left Ventricular Assist Device Support
Authors: Xianghai Liao, Rong Lu, Autumn Clemons, Raia Blum, Lauren Truby, Arthur R Garan, Melana Yuzefpolskaya, Paolo Colombo, Gordana Vunjak-Novakovic, Veli K Topkara
Journal: Circulation (2017)

Introduction: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression and have been implicated in various biological processes. Modulating lncRNA levels could be a plausible strategy for the treatment of heart failure (HF), however the specific lncRNAs responsible for cardiac reverse remodeling remain largely unknown. Hypothesis: Myocardial lncRNAs mediate reverse remodeling through cis -regulation of the neighboring mRNAs Methods: RNA sequencing was performed using total RNA isolated from failing human myocardium before (n=21) and after (n=12) left ventricular assist device (LVAD) implantation as well as from non-failing controls (n=5). Mapped reads for all GENCODE v26 lncRNAs were calculated. Differentially regulated mRNAs and lncRNAs were identified using a fold-change cut-off of 2 and a false discovery rate of 5%. Pearson correlation coefficient was used to determine the relationship between lncRNA and neighboring mRNAs. Results: 81 incident HF and 47 reverse remodeling lncRNAs were identified (Figure 1A). 46 HF lncRNAs (56.8%) were normalized following LVAD support and showed reciprocal regulation in the pre- vs. post-LVAD myocardium (Figure 1B). Recovery lncRNAs included recently described Myheart (originating in the MYH7 locus) as well as novel lncRNAs (NPPA-AS1, RORB-AS1, lnc-TECRL). Majority of the antisense, intergenic, and intronic myocardial lncRNAs demonstrated a positive correlation with neighboring genes suggesting cis -regulation by lncRNAs during cardiac reverse remodeling (Figure 1C). Conclusions: Myocardial lncRNAs are dynamically regulated during myocardial remodeling (HF) and reverse remodeling with LVAD support. Mechanical unloading is accompanied by partial normalization of the pathological lncRNA signature. Further studies will determine mechanisms by which neighboring protein coding genes are regulated by lncRNAs in the failing human heart.
Association of Dermatologist Density With the Volume and Costs of Dermatology Procedures Among Medicare Beneficiaries
Authors: Sally Y. Tan, Daphne Tsoucas, Arash Mostaghimi
Journal: JAMA Dermatology (2017)

The persistent shortage of dermatologists in the United States affects access to care and patient outcomes.To characterize the effect of geographic variations in dermatologist density on the provision of dermatology procedures within Medicare.This was a cross-sectional study using the 2013 Medicare Provider Utilization and Payment Database. Dermatology-related procedures were defined by the top 50 billing codes accounting for more than 95% of procedures billed by dermatologists. Billing codes corresponding to evaluation and monitoring visits and dermatopathology were excluded. Total costs were estimated from the Centers for Medicare & Medicaid Services physician fee schedule, based on the nonfacility national payment amount with no modifiers. Nationally representative administrative database that includes 100% of charges billed by noninstitutional clinicians covered under Medicare Part B. A total of 10 391 dermatologists practicing within the 50 states and Washington, DC, were included. The Medicare-eligible population was defined as all persons 65 years or older.Density of dermatologists, categorized into first (5.3 per 100 000 persons ≥65 years) through fifth (54.8 per 100 000 persons ≥65 years) quintiles.Utilization of dermatology procedures (mean volume per 100 000 persons ≥65 years) and total cost (mean amount billed per person ≥65 years) by clinician type across quintiles of dermatologist density.In 2013, dermatologists billed Medicare for 28 million procedures costing $2.21 billion. Mean billed amount by dermatologists per person 65 years or older was $15.87 in the lowest-density quintile vs $92.02 in the highest-density quintile. This trend suggests that each interval increase of 10 dermatologists per 100 000 persons 65 years or older is correlated with a $14.81 increase in Medicare spending on dermatology procedures (95% CI, 8.28-21.34; P = .005). Utilization of these procedures differed among clinician types, with dermatologists largely performing destruction of premalignant lesions and PCPs primarily doing injections.There is evidence of supply-sensitive variation in the provision of dermatology procedures for the Medicare-eligible population; higher dermatologist density is correlated with increased utilization of dermatology procedures and subsequent billed charges to Medicare. Further research is needed to determine the effect of such variations on outcomes and whether incentives can better align dermatologists with areas of clinical need.
Mother is awarded £9m for “wrongful birth” after GP error
Authors: Clare Dyer
Journal: BMJ (2017)

A mother has been awarded £9m (€10m; $12m) in compensation after a GP’s negligence resulted in her giving birth to a severely disabled child.1 Omodelle Meadows was awarded the sum for the wrongful birth of her son, Adejuwon, who has severe haemophilia and autism.

Meadows has a nephew with haemophilia who was born in 2006 and she wanted to avoid having a child with the condition. In August 2006 she consulted a GP who arranged blood tests. But the tests she was given could establish only whether a patient had haemophilia and not whether she was a carrier of the gene. To obtain that information, she would have had to be referred to a haematologist for …
The syntax of priming
Authors: William O'Grady
Journal: Behavioral and Brain Sciences (2017)

Abstract Priming reflects the reactivation of processing routines that map strings of words onto semantic representations (and vice versa) without the mediation of syntactic structure, including the “flat structure” that Branigan &amp; Pickering (B&amp;P) propose. Key evidence for this claim comes from the possibility of priming relations involving subject-verb sequences, which are not syntactic constituents.
“2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS).” Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, …
Authors: Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa Mcdonagh, Luc Pierard, Pedro Trindade, Maurizio Zompatori
Journal: European Respiratory Journal (2015)
Manipulating human dendritic cell phenotype and function with targeted porous silicon nanoparticles
Authors: Sebastian O. Stead, Steven J.P. McInnes, Svjetlana Kireta, Peter D. Rose, Shilpanjali Jesudason, Darling Rojas-Canales, David Warther, Frédérique Cunin, Jean-Olivier Durand, Christopher J. Drogemuller, Robert P. Carroll, P. Toby Coates, Nicolas H. Voelcker
Journal: Biomaterials (2017)
Ingredients of intelligence: From classic debates to an engineering roadmap
Authors: Brenden M. Lake, Tomer D. Ullman, Joshua B. Tenenbaum, Samuel J. Gershman
Journal: Behavioral and Brain Sciences (2017)

Abstract We were encouraged by the broad enthusiasm for building machines that learn and think in more human-like ways. Many commentators saw our set of key ingredients as helpful, but there was disagreement regarding the origin and structure of those ingredients. Our response covers three main dimensions of this disagreement: nature versus nurture, coherent theories versus theory fragments, and symbolic versus sub-symbolic representations. These dimensions align with classic debates in artificial intelligence and cognitive science, although, rather than embracing these debates, we emphasize ways of moving beyond them. Several commentators saw our set of key ingredients as incomplete and offered a wide range of additions. We agree that these additional ingredients are important in the long run and discuss prospects for incorporating them. Finally, we consider some of the ethical questions raised regarding the research program as a whole.
P3.02b-104 Rebiopsy for Patients with Non-Small-Cell Lung Cancer after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Failure
Authors: Xuefei Li, Chunxia Su, Shengxiang Ren, Chao Zhao, Tao Jiang, Caicun Zhou
Journal: Journal of Thoracic Oncology (2017)
Utility of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and mean platelet volume (MPV) predictive and prognostic biomarkers in patients with hepatocellular carcinoma, prostate carcinoma, stomach carcinoma, aplastic anemia
Authors: V.S. Srikanth, M.G. Pillai, T. Tushar, J. Ashwin, K. Cinzia
Journal: Annals of Oncology (2017)
Older adults may not consider life expectancy an important factor in cancer screening
Authors: Clement Chung
Journal: CA A Cancer Journal for Clinicians (2017)

Key Points Although many elderly individuals considered their age and health status to be relevant in making decisions regarding cancer screening, they often did not understand the role of life expectancy. It is important for providers to incorporate patient preference into communication strategies regarding cancer screening. In the context of good physician‐patient relationships, discussions regarding discontinuing cancer screening generally do not negatively affect older adults' views of their physicians.
Association of anxiety and depression concerns with overall levels of patient reported distress during radiotherapy.
Authors: Robin Landy, Dale Alan Whitaker, Niveditha Jagadesh, Gerald Strong, Nicolette Chimato, Michael Heckman, Tasneem Kaleem, Steven J. Buskirk, Laura Vallow, Katherine S. Tzou, Stephen Ko, Jennifer Layton Peterson, Atiya Day, Kimberly Nelson, Jacob Habboush, Byron C. May, Robert Clell Miller
Journal: Journal of Clinical Oncology (2017)

182 Background: The purpose of this study was to examine the associations of three different measures of anxiety and depression with patient reported distress (PRD) level and survival after radiotherapy (RT). Methods: 518 patients who underwent RT between 2012 and 2016 were included in this retrospective study. PRD was assessed at the time of RT using the NCCN thermometer and a 30 question survey of distress related items. PRD and clinical and demographic data was retrospectively collected and analyzed. The three measures this study focused on that assessed patient anxiety and depression involved asking patients about their level of concern regarding feeling down, regarding loss of interest, and regarding feeling nervous. Associations between baseline patient characteristics and survival after start of RT were evaluated using single variable Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Associations of level of concern regarding patient anxiety/depression with survival after RT were evaluated using single variable and multivariable Cox proportional hazards regression models. Results: Overall, PRD level and concern regarding anxiety/depression were positively correlated (p &lt; 0.001). Additionally, there was a significant association between level of concern regarding feeling down and palliative patients (p = 0.03). There was also a significant association between level of concern regarding loss of interest and palliative patients (p = 0.03), with level of concern highest for thorax, breast, and head and neck. There was also a significant different between level of concern regarding feeling nervous and gender (p = 0.05). There was not a significant difference between any of the three measures and survival after RT (all p ≥ 0.21). Conclusions: Anxiety and depression in patients receiving palliative and curative RT was associated with overall distress. Baseline screening of PRD may identify patients who would benefit from intervention to address the causes of their underlying anxiety and depression.
A real world treatment study of osimertinib: ASTRIS study Korean subgroup analysis
Authors: B.C. Cho, D-W Kim, K. Park, J-S Lee, S.S. Yoo, J.H. Kang, S.Y. Lee, C.H. Kim, S.H. Jang, Y-C Kim, H-K Yoon, S-W Kim
Journal: Annals of Oncology (2017)
KEYNOTE-412: Phase 3 trial of pembrolizumab plus chemoradiation (CRT) vs CRT alone for locally advanced head and neck squamous cell carcinoma (LA-HNSCC)
Authors: C-J Yen, J-P Machiels, L. Licitra, D. Rischin, J. Waldron, B. Burtness, V. Gregoire, Y. Tao, J. Yorio, S. Aksoy, S. Ikeda, R-L Hong, J.Y. Ge, H. Brown, B. Bidadi, L. Siu
Journal: Annals of Oncology (2017)
P3.02c-054 Prognostic Role of cfDNA in Patients with NSCLC under Treatment with Nivolumab
Authors: Federica Biello, Angela Alama, Maria Giovanna Dal Bello, Simona Coco, Irene Vanni, Erika Rijavec, Carlo Genova, Giulia Barletta, Giovanni Rossi, Claudia Maggioni, Nidia Sofia Diaz Gaitan, Roberta Distefano, Franco Merlo, Francesco Grossi
Journal: Journal of Thoracic Oncology (2017)
Prognostic significance of pre- to postoperative dynamics of prognostic nutritional index in patients with renal cell carcinoma who underwent radical nephrectomy
Authors: M. Kang, H.H. Sung, H.G. Jeon, B.C. Jeong, S.I. Seo, S.S. Jeon, H.Y. Choi, H.M. Lee
Journal: Annals of Oncology (2017)
P2.07-015 Reviving Chemotherapy Sensitivity after Anti-CCR4 mAb (Mogamulizumab) Treatment in Lung Cancer Patients
Authors: K. Kurose, Y. Ohue, M. Isobe, S. Suzuki, H. Wada, R. Ueda, E. Nakayama, M. Oka
Journal: Journal of Thoracic Oncology (2017)
CONSORT-Equity 2017 extension and elaboration for better reporting of health equity in randomised trials
Authors: Vivian A Welch, Ole F Norheim, Janet Jull, Richard Cookson, Halvor Sommerfelt, Peter Tugwell
Journal: BMJ (2017)

We outline CONSORT-Equity 2017 reporting standards, an extension to the CONSORT (Consolidated Standards of Reporting Trials) statement that aims to improve the reporting of intervention effects in randomised trials where health equity is relevant. Health inequities are unfair differences in health that can be avoided by reasonable action. We defined a randomised trial where health equity is relevant as one that assesses effects on health equity by evaluating an intervention focused on people experiencing social disadvantage or by exploring the difference in the effect of the intervention between two groups (or as a gradient across more than two groups) experiencing different levels of social disadvantage, or both. We held a consensus meeting with diverse potential users from high, middle, and low income countries, including knowledge users such as patients and methodologists. We discussed evidence for each proposed extension item from empirical studies, reviews, key informant interviews, and an online survey, aiming to improve clarity of reporting without imposing undue burden on authors. The new guidance contains equity extensions to 16 items from CONSORT 2010 plus one new item on research ethics reporting, with examples of good practice and a brief explanation and elaboration for each. Widespread uptake of this guidance for the reporting of trials where health equity is relevant will make it easier for decision makers to find and use evidence from randomised trials to reduce unfair inequalities in health.