tbuckley/cabot-search huggingface dataset:
Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial
Authors: Sudeep Gupta, Amita Maheshwari, Pallavi Parab, Umesh Mahantshetty, Rohini Hawaldar, Supriya Sastri (Chopra), Rajendra Kerkar, Reena Engineer, Hemant Tongaonkar, Jaya Ghosh, Seema Gulia, Neha Kumar, T. Surappa Shylasree, Renuka Gawade, Yogesh Kembhavi, Madhuri Gaikar, Santosh Menon, Meenakshi Thakur, Shyam Shrivastava, Rajendra Badwe
Journal: Journal of Clinical Oncology (2018)

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.
An injectable conductive hydrogel encapsulating plasmid DNA-eNOs and ADSCs for treating myocardial infarction
Authors: Wei Wang, Baoyu Tan, Jingrui Chen, Rui Bao, Xuran Zhang, Shuang Liang, Yingying Shang, Wei Liang, Yuanlu Cui, Guanwei Fan, Huizhen Jia, Wenguang Liu
Journal: Biomaterials (2018)
Circulating Tumor DNA in HER2-Amplified Breast Cancer: A Translational Research Substudy of the NeoALTTO Phase III Trial
Authors: Françoise Rothé, Maria Joao Silva, David Venet, Christine Campbell, Ian Bradburry, Ghizlane Rouas, Evandro de Azambuja, Marion Maetens, Debora Fumagalli, Vanessa Rodrik-Outmezguine, Serena Di Cosimo, Daniela Rosa, Stephen Chia, Andrew Wardley, Takayuki Ueno, Wolfgang Janni, Jens Huober, Jose Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou, Sarah-Jane Dawson, Michail Ignatiadis
Journal: Clinical Cancer Research (2019)

In the neoadjuvant treatment (NAT) setting, dual HER2-targeted therapy is associated with increased pathologic complete response (pCR) rates compared with each therapy alone. Biomarkers allowing to predict treatment response during NAT are needed. We aim to evaluate whether circulating tumor DNA (ctDNA) is associated with response to anti-HER2-targeted therapy.Plasma DNA collected before NAT, at week 2, and before surgery from patients enrolled in the NeoALTTO trial was assessed using digital PCR for PIK3CA and TP53 mutation detection.A total of 69 of 455 (15.2%) patients had a PIK3CA and/or TP53 mutation detected in the baseline tumor sample and evaluable ctDNA results from baseline samples. CtDNA was detected in 41%, 20%, and 5% patients before NAT, at week 2, and before surgery, respectively. ctDNA detection before NAT was significantly associated with older age and ER-negative status. ctDNA detection before NAT was associated with decreased odds of achieving pCR (OR = 0.15; 95% CI, 0.034-0.7; P = 0.0089), but not with event-free survival (EFS). Analyses for EFS were underpowered. Interestingly, the patients with HER2-enriched subtype tumors and undetectable ctDNA at baseline had the highest pCR rates. In contrast, patients with persistent ctDNA detection at baseline and week 2 had the lowest rate of pCR.ctDNA detection before neoadjuvant anti-HER2 therapies is associated with decreased pCR rates. Interestingly, patients with HER2-enriched tumors and undetectable ctDNA at baseline had the highest pCR rates, therefore appearing as the best candidates for treatment deescalation strategies.
Familial PFAPA syndrome in childhood with evolution to febrile urticaria/angioedema after puberty
Authors: Cosby A. Stone, Kalpana Manthiram, Yong H. Park, Ashley L. Blaske, Susan Kroop, Andrew S. Nickels, Hirsh D. Komarow, Amanda Ombrello, JaeJin Chae, David Kastner, Amy K. Robertson, John Newman, John A. Phillips, Rizwan Hamid
Journal: Journal of Allergy and Clinical Immunology (2018)
Phase II, Multicenter Trial, Exploring "Chemo-Sparing" Strategy Associating Obinutuzumab+Ibrutinib Followed By a MRD Driven Strategy, in Previously Untreated Symptomatic Medically Fit Chronic Lymphocytic Leukemia Patients (CLL): Preliminary Results of the Induction Phase of the Icll-07 Filo Study
Authors: Anne-Sophie Michallet, Marie-Sarah Dilhuydy, Fabien Subtil, Valérie Rouille, Beatrice Mahe, Kamel Laribi, Bruno Villemagne, Gilles Andre Salles, Olivier Tournilhac, Alain Jacques Delmer, Christelle Portois, Brigitte Pegourie, Veronique Leblond, Cecile Tomowiak, Sophie de Guibert, Frederique Orsini, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc Mathieu Fornecker, Loic Ysebaert, Caroline Dartigeas, Margot Truchan, Thérèse Aurran, Florence Cymbalista, Stéphane Leprêtre, Vincent Levy, Florence Nguyen Khac, Magali Le Garff-Tavernier, Carmen Aanaei, Michel Ticchioni, Remi Letestu, Pierre Feugier
Journal: Blood (2017)
Facial flushing in response to alcohol and the risk of esophageal cancer: A case-control study based on Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC)
Authors: Akio Hiraki, Keitaro Matsuo, Takeshi Suzuki, Takakazu Kawase, Shunzo Hatooka, Masayuki Shinoda, Hideo Tanaka
Journal: Cancer Research (2008)

3913  Epidemiologic studies have consistently shown a strong relation between the risk of esophageal cancer and alcohol drinking. After drinking alcohol, facial flushing as a result of acetaldehydemia is exhibited especially in persons with inactive aldehyde dehydrogenase 2 (ALDH2). We previously found that facial flushing is related with ALDH2 and alcohol dehydrogenase 2 (ADH2) genotypes; however, also found that not all facial flushing is completely explained by these polymorphisms. Therefore, we hypothesized that facial flushing may have impact on risk of esophageal cancer independent of ALDH2/ADH2 genotypes. To clarify the significance of self-reported facial flushing in response to alcohol on the risk of esophagus cancer, we conducted a case-control study based on Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) with 225 esophagus cancer subjects and 675 age and sex-matched non-cancer controls. Incident esophagus cancer cases newly diagnosed form 2000 to 2005 were deemed eligible and new out-patients without cancer in the same period of time were eligible for controls. Flushing was entered under the three categories of never, sometimes, and always. Genotyping of ADH2 and ALDH2 were based on TaqMan Assays. We assessed the effect of flushing in terms of the odds ratios (ORs) and their 95% confidence interval (CIs) calculated with logistic regression models. The risk of esophageal cancer was increased in those who sometimes (OR = 2.10; 95% CIs: 1.17-3.78) or never (OR = 2.61; 95% CIs: 1.56-4.38) exhibit facial flushing compared with those who always exhibit it after adjusting potential confounders including age, sex, drinking and smoking habit, and ADH2 and ALDH2 genotypes. When stratified by the amount of alcohol drinking, the risk of esophageal cancer was increased in those who sometimes (OR = 2.04; 95% CIs: 0.94-4.47) or never (OR = 2.70; 95% CIs: 1.88-7.27) exhibit facial flushing compared with those who always exhibit it in heavy drinker, however, this trend was not observed in never or moderate drinker. Furthermore, when stratified by the amount of ADH2 or ALDH2 genotype, this trend was consistently observed in all genotypes. In conclusion, these results suggest that self-reported facial flushing in response to alcohol has a significant impact on the risk of esophageal cancer irrespective of ADH2 and ALDH2 genotypes.
Prognostic Role of Gene Mutations in Chronic Myelomonocytic Leukemia (CMML) Patients Treated with Hypomethylating Agents. a Report on 183 Patients
Authors: Matthieu Duchmann, Fevzi Yalniz, Alessandro Sanna, David A Sallman, Catherine C. Coombs, Aline Renneville, Olivier Kosmider, Thorsten Braun, Uwe Platzbecker, Lise Willems, Lionel Ades, Michaela Fontenay, Raajit K. Rampal, Eric Padron, Nathalie Droin, Claude Preudhomme, Valeria Santini, Mrinal M. Patnaik, Pierre Fenaux, Éric Solary, Raphael Itzykson
Journal: Blood (2017)
miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance
Authors: Xiaojie Deng, Zhen Liu, Xiong Liu, Qiaofen Fu, Tongyuan Deng, Juan Lu, Yiyi Liu, Zixi Liang, Qingping Jiang, Chao Cheng, Weiyi Fang
Journal: Molecular Therapy (2018)
Cancer risk associated with chronic diseases and disease markers: prospective cohort study
Authors: Huakang Tu, Chi Pang Wen, Shan Pou Tsai, Wong-Ho Chow, Christopher Wen, Yuanqing Ye, Hua Zhao, Min Kuang Tsai, Maosheng Huang, Colin P Dinney, Chwen Keng Tsao, Xifeng Wu
Journal: BMJ (2018)

To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers.Prospective cohort study.Standard medical screening program in Taiwan.405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years.Cancer incidence and cancer mortality.A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk associated with chronic diseases and markers was attenuated by 48% for cancer incidence and 27% for cancer mortality.Chronic disease is an overlooked risk factor for cancer, as important as five major lifestyle factors combined. In this study, chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death. Physical activity is associated with a nearly 40% reduction in the cancer risk associated with chronic diseases.
Abstract 16472: Advanced vs. Basic Life Support in the Treatment of Out-of-Hospital Cardiopulmonary Arrest in the Resuscitation Outcomes Consortium
Authors: Michael C Kurz, Robert Schmicker, Brian Leroux, Graham Nichol, Thomas Aufderheide, Sheldon Cheskes, Randal Gray, Jamie Jasti, Paul Kudenchuk, Gary Vilke, Jason Buick, Lynn Wittwer, Ritu Shani, Ashley Brienza, Ronald Straight, Henry E Wang
Journal: Circulation (2016)

Objective: Prior studies using hospital-based insurance claims data suggest higher survival after out-of-hospital cardiac arrest (OHCA) with basic (BLS) than advanced life support (ALS) prehospital...
Seven-day access to NHS primary care: how does England compare with Europe?
Authors: Sarah Rosenberg-Wohl, Geva Greenfield, Azeem Majeed, Benedict Hayhoe
Journal: Journal of the Royal Society of Medicine (2018)

Healthcare systems globally are facing an increasing demand for care under stable or decreasing resources. It is often assumed that providing easier access to community-based general practice during evenings and weekends can reduce demand for emergency and other unscheduled care services, promoting more appropriate care and reducing the costs associated with expensive hospital-based treatment. However, evidence for this is mixed.1–3 In England’s NHS there is political pressure to expand general practice surgeries’ opening hours to progress towards a ‘seven-day NHS’.4

When considering extension of primary care opening hours in England, it is useful to compare primary care access across other countries in the European Union. Despite differences in healthcare commissioning and funding, European countries face comparable challenges such as ageing populations and increases in chronic conditions and mental health problems, all of particular relevance to primary care.5 This paper examines England’s current in-hours general practice services relative to those of European countries in order to better contextualise the debate on extending general practice opening hours.
Abstract #847: A fully human antibody that inhibits the integrin avb6 reduces tumor growth and modulates key biomarkers
Authors: Simon Barry, Ian Foltz, Avril Alfred, Zhu Cao, Neil Smith, Viv Jacobs, Cath Eberlein, Jaspal Kang, Steve Powell, Karen McDaid, Jane Kendrew
Journal: Cancer Research (2009)

Increased expression of the integrin avb6 occurs in a number of human cancers including lung, colorectal, breast, head and neck, and prostate cancer. In normal tissues avb6 plays a key role in modulating the activation of latent TGFb, by binding the TGF-b latency associated peptide LAP through the high affinity binding site RGDLxxL. In addition avb6 also binds the extracellular matrix component fibronectin. By binding both latent TGF-b and fibronectin avb6 has the potential to influence tumour growth by activating both TGF-b or classical integrin mediated signalling pathways. Using XenomaxTM technology we have isolated high affinity antibodies to avb6. One of these antibodies, 264RAD, potently inhibits binding to TGF-b LAP with an Ic50 of less than 70ng/ml in HT29 and Detroit562 cells. This antibody also binds the related integrin avb8, giving partial inhibition of binding to TGF-b LAP, but is selective over all other integrins tested. The impact of 264RAD on the growth of Detroit 562 tumours and a range of biomarkers was assessed. 264RAD delivered marked inhibition of tumour growth, but moreover had a profound impact on various biomarkers. On chronic dosing 264RAD reduced pERK, Ki67, and modified pPaxillin and pFAK within the tumour. Interestingly although neutralising TGF-b is known to reduce the growth of Detroit562 tumours, no change in pSMAD1/5 was detected. These data suggest that avb6 impacts Detroit562 tumour growth through modulating key integrin mediated pathways distinct from classic TGF-b mediated signalling.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 847.
Abstract 20664: Is Aspirin Needed as an Antiplatelet Therapy in Patients With Atrial Fibrillation Undergoing Coronary Intervention?
Authors: Serdar Farhan, Usman Baber, Birgit Vogel, Jaya Chandrasekhar, Pooja Vijay, Srushti Shah, Sabato Sorrentino, Samantha Sartori, Jason Kovacic, Madhav Sharma, Pedro Moreno, Zhen Ge, Gennaro Giustino, George Dangas, Roxana Mehran, Samin Sharma
Journal: Circulation (2017)

Introduction: Prescription pattern of antiplatelet therapy in patients with atrial fibrillation (AF) requiring percutaneous coronary intervention (PCI) vary between hospitals and countries. In 2012...
Abstract 13206: Culprit and Non-Culprit Recurrent Ischemic Events in Post-Myocardial Infarction Patients: Data From SWEDEHEART
Authors: Christoph Varenhorst, Saga Johansson, Pål Hasvold, Magnus Janzon, Per Albertsson, Margret Leosdottir, Kristina Hambraeus, Stefan James, Tomas Jernberg, Bodil Svennblad, Bo Lagerqvist
Journal: Circulation (2016)

Introduction: Long-term disease progression post myocardial infarction (MI) is inadequately understood and recurrences appear at the stented lesion or in untreated progressive lesions. Hypothesis: We studied the pattern and angiographic properties (culprit/non-culprit) of recurrent-MI (re-MI) in a large real-world patient population. Methods: We performed a prospective cohort study in 99,546 first-occurrence MI patients enrolled in Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) between 1 Jan 2006 and 31 Dec 2014. Results: A culprit lesion could be identified in 41,006 patients who underwent coronary angiography. Of those, 2,361 patients suffered a re-MI where the angiography could detect the infarct origin: 587 originated from the culprit lesion- and 1,774 from the non-culprit lesion. The cumulative event probability for re-MI within 8 years (estimated by Kaplan-Meier) related to the culprit lesion was 0.027 (0.023-0.030) as compared with 0.080 (0.075-0.085) for a non-culprit lesion (Figure). At the index infarction, patients with subsequent culprit vs. non-culprit re-MIs were overall similar according to baseline characteristics: gender (men: 69% vs. 72%), age (66 vs. 65 years), infarction type (STEMI: 54% vs. 52%), diabetic status (22% vs. 21%), current smoking (32 % vs. 30 %), hyperlipidemia (statin treatment: 20 vs. 23 %) and hypertension (44.1% vs. 47.5%). Patients with culprit re-MIs were somewhat less likely to have 3-vessel disease at index (12% vs 17%) but procedural characteristics such as number of stents, total stent length and mean stent diameter were similar between groups. Conclusions: In a large cohort of first-occurrence MI patients undergoing PCI, the risk of reinfarction not originating from a previously stented lesion was three times higher than the risk of lesions originating from a previously stented lesion.
Abstract 368: Biomechanical Properties of Scar ECM: from the Acute to Chronic Stages of Myocardial Infarction
Authors: Bryn Brazile, J. R Butler, Sourav Patnaik, Yanyi Xu, Andrew Claude, Raj Prabhu, Lakiesha Williams, Jianjun Guan, Jun Liao
Journal: Circulation Research (2015)

Introduction: Myocardial infarction (MI) affects more than 8 million Americans, causing massive heart cell death and heart function decrease. To better understand the scar biomechanics, we characterized the mechanical properties of pure scar ECM, obtained by decellularizing the MI tissues. Materials and Methods: Infarcted rat hearts were generated by a permanent left coronary artery ligation (PLCAL) and harvested at 15 min, 1, 2, and 4 weeks (per acute to chronic stages of MI)(N = 6 each). Scar ECM were obtained by decellularizing the infarcted hearts in 0.1% sodium dodecyl sulfate (SDS) solution for 3 weeks. Scar ECM specimens were trimmed into square shape, and then subjected to biaxial testing with one edge aligned with the circumferential direction and the other edge aligned with the longitudinal direction of the rat heart. After 10 cycle preconditioning, an equibiaxial tension protocol of T circ : T rad = 30:30 N/m was performed to capture the tissue biaxial behavior. Results and Discussion: Scar ECM 15 minutes through 4 weeks post infarction showed a stiffening biaxial behavior along with the time (Fig.1). The decrease of extensibility along longitudinal direction was more noticeable than circumferential direction, which led to a decrease in degree of anisotropy. Conclusions: Scar ECM biomechanics showed a stiffening behavior with a marked reduction in extensibility (longitudinal) with time. This change in biomechanical properties can be correlated to the collagen structure changes with progression of MI. Knowledge of the structural-mechanical relationship of scar ECM will help us understand MI progression and help formulate regenerative therapies.
Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication
Authors: Yuhei Maruzuru, Takeshi Ichinohe, Ryota Sato, Kensuke Miyake, Tokuju Okano, Toshihiko Suzuki, Takumi Koshiba, Naoto Koyanagi, Shumpei Tsuda, Mizuki Watanabe, Jun Arii, Akihisa Kato, Yasushi Kawaguchi
Journal: Cell Host & Microbe (2018)
Secondary Neoplasms of the Female Lower Genital Tract After Hematopoietic Cell Transplantation
Authors: Howard A. Chang, Saro H. Armenian, Thanh H. Dellinger
Journal: Journal of the National Comprehensive Cancer Network (2018)

Hematopoietic cell transplantation (HCT) results in long-term survival (≥10 years) in 85% of patients who survive transplant-related complications within the first 2 years posttransplant. Transplant survivors, however, are at an increased risk of chronic health conditions compared with the general population, including the emergence of secondary malignant neoplasms. In particular, female transplant survivors may face a greater risk of lower genital tract (cervical, vulvar, or vaginal) neoplasms due to chronic immune dysregulation in the peritransplant and posttransplant environment. Persistent immune suppression may facilitate the carcinogenesis of human papillomavirus (HPV), the causative agent of nearly all cervical cancers and most vulvar and vaginal cancers. Nevertheless, the risk of these cancers has not been sufficiently quantified in female transplant survivors. Small clinical studies have shown that the rate of cervical cytological abnormalities increases after allogeneic HCT, but large population-based studies have not consistently demonstrated an increased risk of secondary cervical cancer after transplant compared with the general population; the risk of developing secondary vulvar or vaginal cancer after transplant remains unclear. A better understanding of the natural history of HPV-associated lower genital tract neoplasms and their transplant-related risk factors would help delineate optimal long-term follow-up protocols in this population. In this systematic review, we summarize the current literature on this topic and discuss the implications for cervical cancer screening and vaccination in female transplant recipients.