tbuckley/cabot-search huggingface dataset:
Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer During Follow-Up and Prognosis
Authors: Elisabeth Trapp, Wolfgang Janni, Christian Schindlbeck, Julia Jückstock, Ulrich Andergassen, Amelie de Gregorio, Marianna Alunni-Fabbroni, Marie Tzschaschel, Arkadius Polasik, Julian G Koch, Thomas W P Friedl, Peter A Fasching, Lothar Haeberle, Tanja Fehm, Andreas Schneeweiss, Matthias W Beckmann, Klaus Pantel, Volkmar Mueller, Brigitte Rack, Christoph Scholz
Journal: JNCI Journal of the National Cancer Institute (2018)

The prognostic relevance of circulating tumor cells (CTCs) at the time of primary diagnosis has been well established. However, little information is available regarding their prognostic relevance to follow-up care.The multicenter, open-label, phase III SUCCESS A trial compared two adjuvant chemotherapy regimens followed by 2 vs 5 years of zoledronate for early-stage, high-risk breast cancer patients. The presence of CTCs was assessed before and 2 years after chemotherapy using the FDA-approved CellSearch System. Overall survival (OS) and disease-free survival (DFS) were analyzed using univariate log-rank tests and multivariable Cox regressions. OS and DFS were measured starting from an assessment of CTCs 2 years after the completion of chemotherapy. All statistical tests were two-sided.The sample included 1087 patients who participated in the translational research program of the SUCCESS A trial and for whom sufficient translational data were available regarding CTC status at baseline and at the 2-year follow-up visit. Two years after chemotherapy, 198 (18.2%) patients were CTC-positive. The median follow-up after this timepoint was 37 months. Cox regressions that included CTC status at baseline revealed that CTC status 2 years after chemotherapy had statistically significant and independent prognostic relevance for OS (hazard ratio [HR] = 3.91, 95% confidence interval [CI] = 2.04 to 7.52, P < .001) and DFS (HR = 2.31, 95% CI = 1.50 to 3.55, P < .001).The presence of CTCs 2 years after chemotherapy was associated with decreased OS and DFS. Based on these results, active individualized surveillance strategies for breast cancer survivors based on biomarkers should be reconsidered.
Epigenetic regulation of RCAN1 expression in kidney disease and its role in podocyte injury
Authors: Huilin Li, Weijia Zhang, Fang Zhong, Gokul C. Das, Yifan Xie, Zhengzhe Li, Weijing Cai, Gengru Jiang, Jae Choi, Mohamad Sidani, Deborah P. Hyink, Kyung Lee, Paul E. Klotman, John Cijiang He
Journal: Kidney International (2018)
Endometrioid Intraepithelial Neoplasia
Authors: Yu-Li Chiu, Jyh-Seng Wang, Nan-Jing Peng
Journal: Clinical Nuclear Medicine (2018)

The report describes a 55-year-old woman with postmenopausal abnormal vaginal spotting. PET/CT revealed focal hot F-FDG uptake in the fundus portion of the uterine cavity, and pathology of hysteroscopic dilation and curettage showed endometrioid intraepithelial neoplasia of uterine endometrium, an endometrial precancer. This case points to the significance of F-FDG PET/CT in determining the dilation and curettage site for the postmenopausal women with abnormal vaginal spotting. Increased F-FDG activity in the region of the uterus must be investigated to determine the possibilities of primary malignancies, metastases, and benign diseases.
Abstract 18364: Cumulative Psychosocial Stress & Ideal Cardiovascular Health in Women: Data According to Race/Ethnicity
Authors: Rachel Alice Siliki Mbassa, Alan M Zaslavsky, David R Williams, Slopen B Natalie, Julie Buring, Michelle A Albert
Journal: Circulation (2016)

Introduction: Research implicates acute and chronic stressors in racial/ethnic health disparities, but the joint impact of multiple stressors and their effect on racial/ethnic disparities in cardio...
The intimate relationship between gut microbiota and cancer immunotherapy
Authors: Arielle Elkrief, Lisa Derosa, Laurence Zitvogel, Guido Kroemer, Bertrand Routy
Journal: Gut Microbes (2018)

Immunotherapy is widely used to treat a large variety of malignancies and has revolutionized the therapeutic approach to cancer. Major efforts are ongoing to identify biomarkers that predict response to immunotherapy as well as new strategies to improve ICI efficacy and clinical outcomes. Studies have shown that the gut microbiome determines the extent to which ICIs may invigorate the anticancer immune response. Here, the authors review recent studies that have described the effects of the gut microbiota on the efficacy of CTLA-4 and PD-1 inhibitors and outline potential future clinical directions of these findings.
Expanding the Evidence Base in Geriatric Oncology: Action Items From an FDA-ASCO Workshop
Authors: Laura A Levit, Harpreet Singh, Heidi D Klepin, Arti Hurria
Journal: JNCI Journal of the National Cancer Institute (2018)

As part of the ongoing efforts to address the lack of clinical research on older adults with cancer, the American Society of Clinical Oncology (ASCO) and the US Food and Drug Administration cosponsored a public workshop on geriatric oncology in November 2017. The goals were to review progress, build collaborations across stakeholders, and generate new action items for increasing the evidence base for treating older adults with cancer. It built on previous work of the Institute of Medicine, ASCO, and the U13 Conferences convened by the Cancer and Aging Research Group, the National Cancer Institute, and the National Institute of Aging between 2010 and 2015. The workshop drew a diverse group of presenters, panelists, and attendees, including academic and clinical oncologists, regulators, other government officials, representatives from industry, and patient advocacy groups. Attendees at the workshop were tasked with proposing next steps to address the lack of evidence on treating older adults with cancer. Based on the workshop discussions, four new action items to move the field forward were developed: 1) increase enrollment of older adults in clinical trials, 2) collect more information on older adults enrolled on clinical trials, 3) expand the use of real-world data in research on older adults, and 4) strengthen collaboration between stakeholders to develop advocacy and policy solutions. These action items, alongside the previous ASCO, Institute of Medicine, and U13 recommendations, provide a strategy for improving the evidence base for treating older adults with cancer and ensuring all patients with cancer receive high-quality, evidence-based care.
Abstract 11571: Relatively Preserved Brain Volume is Associated With More Distensible Common Carotid Arteries
Authors: Dhananjay Vaidya, Paul A Nyquist, Lisa R Yanek, Brian G Kral, Taryn F Moy, Lewis C Becker, Diane M Becker
Journal: Circulation (2013)

Background: Cerebral atrophy, defined as smaller whole brain volume (WBV) as a percentage of intracranial volume (ICV), is associated with decreased cognitive function. Atrophy is strongly associat...
Bone Morphogenetic Protein 9 Is a Mechanistic Biomarker of Portopulmonary Hypertension
Authors: Ivana Nikolic, Lai-Ming Yung, Peiran Yang, Rajeev Malhotra, Samuel D. Paskin-Flerlage, Teresa Dinter, Geoffrey A. Bocobo, Kathleen E. Tumelty, Anthony J. Faugno, Luca Troncone, Megan E. McNeil, Xiuli Huang, Kathryn R. Coser, Carol S. C. Lai, Paul D. Upton, Marie Jose Goumans, Roham T. Zamanian, C. Gregory Elliott, Arthur Lee, Wei Zheng, Stephen P. Berasi, Christine Huard, Nicholas W. Morrell, Raymond T. Chung, Richard W. Channick, Kari E. Roberts, Paul B. Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: BMP9 (bone morphogenetic protein 9) is a circulating endothelial quiescence factor with protective effects in pulmonary arterial hypertension (PAH). Loss-of-function mutations in BMP9, its receptors, and downstream effectors have been reported in heritable PAH.Objectives: To determine how an acquired deficiency of BMP9 signaling might contribute to PAH.Methods: Plasma levels of BMP9 and antagonist soluble endoglin were measured in group 1 PAH, group 2 and 3 pulmonary hypertension (PH), and in patients with severe liver disease without PAH.Measurements and Main Results: BMP9 levels were markedly lower in portopulmonary hypertension (PoPH) versus healthy control subjects, or other etiologies of PAH or PH; distinguished PoPH from patients with liver disease without PAH; and were an independent predictor of transplant-free survival. BMP9 levels were decreased in mice with PH associated with CCl4-induced portal hypertension and liver cirrhosis, but were normal in other rodent models of PH. Administration of ALK1-Fc, a BMP9 ligand trap consisting of the activin receptor-like kinase-1 extracellular domain, exacerbated PH and pulmonary vascular remodeling in mice treated with hypoxia versus hypoxia alone.Conclusions: BMP9 is a sensitive and specific biomarker of PoPH, predicting transplant-free survival and the presence of PAH in liver disease. In rodent models, acquired deficiency of BMP9 signaling can predispose to or exacerbate PH, providing a possible mechanistic link between PoPH and heritable PAH. These findings describe a novel experimental model of severe PH that provides insight into the synergy between pulmonary vascular injury and diminished BMP9 signaling in the pathogenesis of PAH.
Abstract 19610: Safety of Percutaneous Left Atrial Appendage Suture Ligation: Results From the Largest Us Registry
Authors: Dhanunjaya Lakkireddy, Sampath Gunda, Muhammad R Afzal, Madhu Reddy, Randall J Lee, Jayant Nath, Hosakote Nagaraj, Christopher Ellis, Eric Altman, Brian Lee, David Wilber, Saibal Kar, Ryan Ferrell, Sudharani Bommana, Donita Atkins, Nitish Bhadwar, Mauricio Sanchez, Varuna Gadiyaram, David Tschopp, Rudolph Evonich, Abdi Rasekh, Jie Cheng, Douglas Gibson, Earnest Matthew
Journal: Circulation (2015)

Background: Epicardial ligation of left atrial appendage (LAA) is an attractive alternative to oral anticoagulation for patients with atrial fibrillation and high risk of bleeding. Objectives: To delineate the safety of epicardial ligation of the LAA for stroke prevention in atrial fibrillation Methods: This is a retrospective, multicenter registry of consecutive patients undergoing LAA ligation with the LARIAT device at 14 U.S. sites. The primary endpoint was procedural success, defined as device success (suture deployment and &lt;5 mm leak by post-procedure transesophageal echocardiography), and no major complication at discharge (death, myocardial infarction, stroke, major bleeding requiring transfusion, or cardiac perforation requiring cardiac surgery). Results: A total of 610 patients underwent LARIAT exclusion of LAA. The mean age of the participants was 71 (SD: ± 10) years. The mean CHADs2VASc and HASBLED score was 2.74(±1.33) and 3.87 (±1.8) respectively. Epicardial access was obtained using micro-puncture needle in 60 percent of the cases. The acute closure was achieved in 554 (91 %) patients. Cardiac perforation needing continued drainage and transfusion occurred in 12 patients (1.96 %). Perforation of epigastric artery occurred in 2 patients (0.3 %). Eight patients (1.3 %) required open heart surgery. Five patients required &gt; 2 weeks of treatment for pericarditis. No myocardial infarction or stroke happened in the peri-procedural period. One patient died as complication of the procedure. A follow up transesophageal echocardiogram (TEE) was performed in 76 % of the patients that showed a leak of &lt; 5 mm and thrombus in 49 (8 %) and 12 (1.96 %) patients respectively. Conclusions: In this largest multicenter experience of LAA ligation with the LARIAT device, the rate of acute closure was high with significantly fewer complications compared to limited contemporary data. The use of micro-puncture is probably safer approach to avoid cardiac injury during epicardial access. A prospective randomized trial is required to adequately define clinical efficacy, optimal post-procedure medical therapy, and the effect of operator experience on procedural safety.
Hepatitis A outbreak linked to imported frozen strawberries by sequencing, Sweden and Austria, June to September 2018
Authors: Theresa Enkirch, Ronnie Eriksson, Sofia Persson, Daniela Schmid, Stephan W. Aberle, Emma Löf, Bengt Wittesjö, Birgitta Holmgren, Charlotte Johnzon, Eva X. Gustafsson, Lena M. Svensson, Lisa Labbé Sandelin, Lukas Richter, Mats Lindblad, Mia Brytting, Sabine Maritschnik, Tatjana Tallo, Therese Malm, Lena Sundqvist, Josefine Lundberg Ederth
Journal: Eurosurveillance (2018)

Between June-September 2018, 20 hepatitis A cases were notified in six counties in Sweden. Combined epidemiological and microbiological investigations identified imported frozen strawberries produced in Poland as the source of the outbreak. Sequence analysis confirmed the outbreak strain IB in the strawberries with 100 % identity and the respective batch was withdrawn. Sharing the sequence information internationally led to the identification of 14 additional cases in Austria, linked to strawberries from the same producer.
Mediastinal Duplication Cyst on 99mTc Pertechnetate Scan
Authors: Vanshika Gupta, Ritu Verma, Ethel Belho, Nikhil Seniaray
Journal: Clinical Nuclear Medicine (2018)

A 3-year-old boy presented with intermittent abdominal pain, melena, and anemia since 2 months. Upper gastrointestinal endoscopy did not reveal any significant abnormality. The child was then referred for Tc-pertechnetate scan to rule out the presence of ectopic functioning gastric mucosa. Tc-pertechnetate scan revealed abnormal tracer accumulation in the thoracic region, which persisted in the delayed images, suspicious for being ectopic gastric mucosa. Subsequently, ultrasound and contrast-enhanced CT (CECT) scans of the chest revealed a large multiseptate cystic lesion in the retrocardiac region, corresponding to the site of increased tracer uptake on Tc-pertechnetate scan.
P3.CR-23 Multilobar Adenocarcinoma: A Case Report and Review of the Literature of Papillary Eccrine Adenocarcinoma Presenting with Respiratory Failure
Authors: J. Turner, W. Hanna, T. Dudney, S. Baveja, G. Sneed, H. Huang, W. Hohenforst-Schmidt, P. Zarogoulidis
Journal: Journal of Thoracic Oncology (2018)
American Academy of Allergy, Asthma and Immunology response to the <scp>EAACI</scp>/<scp>GA</scp><sup>2</sup><scp>LEN</scp>/<scp>EDF</scp>/<scp>WAO</scp> guideline for the definition, classification, diagnosis, and management of Urticaria 2017 revision
Authors: Robert A. Wood, David A. Khan, David M. Lang, Mary Beth Fasano, David B. Peden, Paula J. Busse, Melody C. Carter, Jeffrey G. Demain, Chitra Dinakar, Mitchell H. Grayson, Sharon B. Markovics, Scott H. Sicherer, Kelly D. Stone, Kathleen E. Sullivan, Paul V. Williams, Thomas A. Fleisher, Thomas B. Casale
Journal: Allergy (2018)
Partially Open HIV-1 Envelope Structures Exhibit Conformational Changes Relevant for Coreceptor Binding and Fusion
Authors: Haoqing Wang, Christopher O. Barnes, Zhi Yang, Michel C. Nussenzweig, Pamela J. Bjorkman
Journal: Cell Host & Microbe (2018)

HIV-1 Env, a trimer of gp120-gp41 heterodimers, mediates membrane fusion after binding host receptor CD4. Receptor binding displaces V1V2 loops from Env's apex, allowing coreceptor binding and opening Env to enable gp41-mediated fusion. We present 3.54 Å and 4.06 Å cryoelectron microscopy structures of partially open soluble native-like Env trimers (SOSIPs) bound to CD4. One structure, a complex with a coreceptor-mimicking antibody that binds both CD4 and gp120, stabilizes the displaced V1V2 and reveals its structure. Comparing partially and fully open Envs with closed Envs shows that gp41 rearrangements are independent of the CD4-induced rearrangements that result in V1V2 displacement and formation of a 4-stranded bridging sheet. These findings suggest ordered conformational changes before coreceptor binding: (1) gp120 opening inducing side-chain rearrangements and a compact gp41 central helix conformation, and (2) 4-stranded bridging-sheet formation and V1V2 displacement. These analyses illuminate potential receptor-induced Env changes and inform design of therapeutics disrupting viral entry.
PD-L2 expression as a predictive biomarker for the response to anti-PD-1 drugs in non-small cell lung cancer patients
Authors: Shinkichi Takamori, Kazuki Takada, Gouji Toyokawa, Koichi Azuma, Tomoko Jogo, Akihiko Kawahara, Fumihiko Hirai, Tetsuzo Tagawa, Jun Akiba, Tomoaki Hoshino, Yoshihiko Maehara
Journal: Annals of Oncology (2018)
Abstract MP75: Assessment of the Genetic Role of Potential Metabolic Therapeutic Targets Along Insulin Signaling and Adipogenesis Pathways
Authors: Kei Hang K Chan, Haiyan Xu, Xi Rossi Luo, Simin Liu
Journal: Circulation (2016)

Recent studies in rat hepatoma cells identified MAP kinase phosphatase 3 (MKP3) as the key player in antagonizing repression of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription by insulin, indicating that MAP kinase phosphatase can crosstalk with metabolic components of the insulin signaling pathways. The family of histone deacetylases (HDACs) is another set of metabolic therapeutic targets of importance as HDAC1 has recently been shown to be involved in regulating preadipocyte differentiation. We therefore investigated the roles of MKP3 (DUSP6 in human), PEPCK (PCK2), HDAC1&amp;2 single nucleotide polymorphisms (SNPs) in relation to obesity and diabetes risk among 7,287 African American (AA), 3,258 Hispanic American (HA), and 3711 Caucasian American (CA) women participating in the national Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) and the Genomics and Randomized Trials Network (GARNET). We found significant association between 43 SNPs in the DUSP6 gene region with risk of obesity (risk variants: range of OR=1.08-1.87; protective variants: 0.72-0.93; all P&lt;0.05) and diabetes (risk variants: range of OR=1.08-1.43; protective variants: 0.84-0.93; all P&lt;0.05). Two PCK2 SNPs were associated with obesity risk (risk variant: OR=1.09, P=0.008; protective variant: OR=0.84, P=0.04). Six HDAC2 SNPs were also found to have association with risk of obesity (range of OR: 0.82-0.90, P&lt;0.05) and diabetes (risk variant: OR=1.16; protective variant: 0.77-0.86; all P&lt;0.05). The rs10506969 (C/T) SNP in the DUSP6 gene identified among AA (reference allele=C, OR=0.86, P=0.02) and HA (OR=0.87, P=0.05) was also confirmed in the CARDIoGRAMplusC4D meta-analysis studies of 63,746 coronary artery disease cases and 130,681 controls (reference allele: T, OR=1.05, P=0.003). Our candidate gene study of American women of three ethnicities identified germline mutations in DUSP6, PCK2, and HDAC2 in relation to obesity and diabetes. These human genetic evidence is comparable to data from animal models that support the notion that MAP kinase phosphatase 3, phosphoenolpyruvate carboxykinase, and histone deacetylase 2 may serve as important metabolic therapeutic targets in lowering risk of obesity and diabetes.
Use of Personal Hearing Protection Devices at Loud Athletic or Entertainment Events Among Adults — United States, 2018
Authors: John Eichwald, Franco Scinicariello, Jana L. Telfer, Yulia I. Carroll
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Tens of millions of U.S. residents have a range of adverse health outcomes caused by noise exposure (1). During 2011-2012, 21 million U.S. adults who reported no exposure to loud or very loud noise at work exhibited hearing damage suggestive of noise-induced hearing loss (2). In addition to the known risk for hearing damage, nonauditory adverse health outcomes and health risks from excessive environmental sound exposure can include effects on the cardiovascular system, metabolism, blood pressure, body weight, cognition, sleep, mental health, quality of life, and overall well-being (1,3,4). CDC analyzed a representative sample of the U.S. adult population (aged ≥18 years) from a 2018 national marketing survey (50 states and the District of Columbia) that included questions about use of hearing protection devices (HPDs) (e.g., ear plugs or ear muffs) during recreational exposure to loud athletic and entertainment events; approximately 8% of respondents reported consistent use of an HPD at these types of events. Among those adults more likely to wear an HPD, 63.8% had at least some college education, and 49.1% had higher income levels. Women and older adults were significantly less likely to use HPDs. These findings suggest a need to strengthen a public health focus on the adverse health effects of excessive noise exposure at home and in recreational settings as well as a need for continued efforts to raise public awareness about the protective value of HPDs.
Abstract 19911: Markers of Survival in Septuagenarians and Octogenarians With Heterozygous or Homozygous Familial Hypercholesterolemia
Authors: Étienne Khoury, Diane Brisson, Gérald Tremblay, Karine Tremblay, Daniel Gaudet
Journal: Circulation (2015)

Objective: Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated low-density lipoprotein-cholesterol (LDL-C) concentrations appearing at birth and is associated with an increased risk of premature atherosclerotic cardiovascular disease (CAD). Some homozygous (Ho) FH subjects survive over 80 years of age and a proportion of heterozygous (He) FH subjects aged over 70 years have never experienced CAD symptoms. The objective of this study consists in identifying genetic, clinical and/or environmental factors associated with survival over 70 years in FH. Methods and Results: The familial analysis of 1,860 French-Canadian FH individuals carrying either the French-canadian Type 1 (15KB deletion) or the French-canadian Type 2, (W66G), which are both FH-causing mutations in the LDLR gene, was performed to identify HoFH and HeFH subjects over 70 years of age. Out of this number, we were able to list a total of 112 subjects (among which 2 HoFH aged 72 and 84 years with baseline cholesterol 18 and 21 mmol/L respectively). Multivariate regression analyses revealed that the gender, high-density lipoprotein-cholesterol (HDL-C) level, the proportion of LDL-C decrease under therapy and the type of mutation in the LDLR gene were significant contributory factors of survival over 80 years or of CAD-free survival over 70 years (p-value under 0.001). In these models, the contribution of HDL-C was independent from that of LDL-C reduction. Notably, HDL-C and gender were shown to be significant covariates of survival among HoFH relatives. Fine phenotyping and exome sequencing analyses are ongoing. Conclusion: Based on a monogenic model of high LDL-C and premature CAD, these results demonstrated that despite the reduction of LDL-C, several other covariates would probably constitute major targets for cardiovascular disease (CVD) risk management.