tbuckley/cabot-search huggingface dataset:
Response to Sung, Rosenberg, and Yang
Authors: Ching-hung Lin, Yoon sim Yap, Kyung-hun Lee, Winnie Yeo, Takayuki Ueno, Huiping Li, Shu-min Huang, Yen-shen Lu
Journal: JNCI Journal of the National Cancer Institute (2019)

We reply to the comments by Sung et al. about absolute risk vs proportion of breast cancer subtypes and the effect of screening and obesity in breast cancer.First, although the absolute risk of estrogen receptor (ER)-positive cancers was similar for young women in Asian or Pacific Islanders (APIs) and white Americans, this analysis could be influenced by the incidence of breast cancer.For low-incidence areas such as East Asia, the finding of a higher proportion of ER-positive breast cancers among young women cannot be demonstrated by such an analysis.If a Westernization of lifestyles is the only reason for the rapid increase of breast cancer among young women in East Asia, the proportions of pathological features should be similar between the East Asian and US populations.Therefore, genetic factors likely play a critical role.Additionally, APIs-which include individuals who are Indian, Pakistani, Chinese, Filipino, Guamanian, Native Hawaiian, Japanese, Kampuchean, Korean, Laotian, Samoan, Tongan, and Vietnamese-are populations with heterogeneous genetic backgrounds.We analyzed the Surveillance, Epidemiology, and End Results (SEER) database ( 1) and revealed the trends of ER positivity and triple-negative breast cancer among Chinese, Japanese, and Korean (C-J-K) populations, among selected API groups (defined by APIs except C-J-K), and among white Americans.The trends in age-specific ER positivity and triple-negative breast cancer incidence differed between the C-J-K and selected API groups (Figure 1).Studies for age-specific incidence rates of breast cancer have consistently demonstrated that the individuals from these places cannot be considered a single homogeneous group (2,3).Second, the increase in mammography screening in East Asian countries may not be the cause of the increase in the Figure 1.Observed age-specific proportions of estrogen receptor-positive (ERþ) and triple-negative breast cancer (TNBC) female breast cancer in Surveillance, Epidemiology, and End Results Chinese, Japanese, and Korean (C-J-K), selected Asian or Pacific Islanders (APIs), and white Americans for the years 2010-2013.
Abstract #820: Combination studies of tyrosine kinase inhibitors (TKIs): Assessment of potential cytotoxic synergy of ARQ 197 with sorafenib or sunitinib
Authors: Chang-Rung Chen, Jeff Szwaya, Atipat Rojnuckarin, Uma Uppalapati, Li Huang, Enkeleda Nakuci, Susan Cornell-Kennon, Jennifer Brown, Denise McSweeney, Charles Bruseo, Thomas Chan
Journal: Cancer Research (2009)

ARQ 197 is a novel, clinically well-tolerated orally available anti-cancer drug candidate shown to inhibit c-Met driven tumors in vitro and in vivo. To complement Phase I data showing clinical response as a single agent, we sought to explore the potential synergy of ARQ 197 with two marketed TKIs, sorafenib and sunitinib. A panel of 87 human cancer cell lines encompassing a spectrum of genotypes and tissue origins were surveyed in 72 h MTS cytotoxicity assays across a wide range of compound concentrations. Isobologram analyses categorized drug combinations as synergistic, additive, or antagonistic. The combination of ARQ 197 and sorafenib revealed synergistic cytotoxicity in NCI-H522 (NSCLC), MDA-MB-231 (breast), A375 (melanoma), NCI-H526 (SCLC), and in HeLa cervical carcinoma cell lines. Additivity was seen with the ARQ 197/sorafenib combination in the HCC1395 breast cancer line, the Colo205 and SW480 colon cancer lines, the Caki-1 (RCC) line, the squamous cell carcinoma A431 line, the NCI-H358 (NSCLC) cell line, and 3 hepatocellular carcinomas (JHH-4, PLC/PRF/5, SK-Hep-1). The remainder of the cell lines showed resistance (19 cell lines) to either ARQ 197, sorafenib or both agents, antagonism (14 cell lines) to the combination of ARQ 197 and sorafenib, or yielded equivocal data. In contrast to sorafenib, the combination of ARQ 197 and sunitinib showed no clear synergy with any of the 87 cell lines tested. Quite striking was the number of cell lines (46 in total) in which antagonism of ARQ 197 and sunitinib was evident. In summary, the combination of ARQ 197 and sorafenib revealed a number of tumor types in which the compounds were synergistic with respect to cytotoxicity. This data may be informative in the design of combination therapy regimens for ARQ 197.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 820.
Infographic. The many shades of adiposity
Authors: Bruno Paula Caraça Smirmaul, Deepika Laddu, Ross Arena
Journal: British Journal of Sports Medicine (2019)

Overweight and obesity, defined as ‘ abnormal or excessive fat accumulation that may impair health’ ,1 has nearly tripled since 1975. With ~1.9 billion and 650 million adults overweight and obese, respectively, these conditions have reached epidemic levels,1 with devastating health consequences.2 Traditionally, in clinical practice, diagnosis is made with the use of anthropometric measures (height and weight, waist and hip circumferences), while weight loss is the treatment goal for all interventions. Despite this, the scientific understanding of the pathophysiology of obesity has evolved, revealing ‘the many shades of adiposity’ (figure 1) that underlie this …
Tumor microenvironment responsive drug delivery systems
Authors: Qunye He, Jun Chen, Jianhua Yan, Shundong Cai, Hongjie Xiong, Yanfei Liu, Dongming Peng, Miao Mo, Zhenbao Liu
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisfied systemic circulation, low targeting efficiency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more efficient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic efficiency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inflammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed.
TCT-13 Alirocumab Improve Coronary Plaque Vulnerability: First Randomized Control Trial to Assess the Effect of Alirocumab for Plaque Vulnerability Using Optical Coherence Tomography
Authors: Yoichiro Sugizaki, Hiromasa Otake, Hiroyuki Kawamori, Takayoshi Toba, Akira Nagasawa, Hiroyuki Onishi, Ryo Takeshige, Shinsuke Nakano, Yoichiro Matsuoka, Kosuke Tanimura, Yu Takahashi, Yusuke Fukuyama
Journal: Journal of the American College of Cardiology (2019)
TCT-154 In-Hospital Outcome of Endovascular Intervention Versus Surgical Revascularization Among Patients With Atrial Fibrillation
Authors: Homam Moussa Pacha, Yasser Al-khadra, Fahed Darmoch, Mohamad Soud, Anwar Zaitoun, Chun Shing Kwok, Mamas Mamas, Amir Kaki, Santiago Garcia, Subhash Banerjee, Salman Arain, George Vetrovec, James Glazier, Rajiv Tayal, Babar Basir, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2019)
European Respiratory Society guideline on long-term management of children with bronchopulmonary dysplasia
Authors: Liesbeth Duijts, Evelien R. van Meel, Laura Moschino, Eugenio Baraldi, Magda Barnhoorn, Wichor M. Bramer, Charlotte E. Bolton, Jeanette Boyd, Frederik Buchvald, Maria Jesus del Cerro, Andrew A. Colin, Refika Ersu, Anne Greenough, Christiaan Gremmen, Thomas Halvorsen, Juliette Kamphuis, Sailesh Kotecha, Kathleen Rooney-Otero, Sven Schulzke, Andrew Wilson, David Rigau, Rebecca L. Morgan, Thomy Tonia, Charles C. Roehr, Marielle W. Pijnenburg
Journal: European Respiratory Journal (2019)

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and who have been discharged from the hospital, or who were &gt;36 weeks of postmenstrual age. The guideline was based on predefined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the task force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence. We suggest monitoring with lung imaging using ionising radiation in a subgroup only, for example severe BPD or recurrent hospitalisations, and monitoring with lung function in all children. We suggest to give individual advice to parents regarding daycare attendance. With regards to treatment, we suggest the use of bronchodilators in a subgroup only, for example asthma-like symptoms, or reversibility in lung function; no treatment with inhaled or systemic corticosteroids; natural weaning of diuretics by the relative decrease in dose with increasing weight gain if diuretics are started in the neonatal period; and treatment with supplemental oxygen with a saturation target range of 90–95%. A multidisciplinary approach for children with established severe BPD after the neonatal period into adulthood is preferable. These recommendations should be considered until new and urgently needed evidence becomes available.
TCT-309 Incidence and Clinical Impact of Major Infections Following PCI or CABG for Left Main Disease: Insights From the EXCEL Trial
Authors: Rodrigo Modolo, Gregg Stone, David Kandzari, David Taggart, Marie-Claude Morice, Dimitri Karmpaliotis, William Brown, Ply Chichareon, Norihiro Kogame, Ovidiu Dressler, Yoshinobu Onuma, A. Pieter Kappetein, Joseph Sabik, Patrick Serruys
Journal: Journal of the American College of Cardiology (2019)
Endoscopic treatment of walled-off pancreatic necrosis by simultaneous transgastric and retroperitoneal approaches
Authors: Enrique Pérez-Cuadrado-Robles, Arthur Berger, Guillaume Perrod, Emilia Ragot, Charles André Cuenod, Gabriel Rahmi, Christophe Cellier
Journal: Endoscopy (2019)

Infected walled-off pancreatic necrosis (WOPN) is a severe complication of acute pancreatitis. In cases of extensive WOPN developing away from the stomach wall, endoscopic treatment may not be effective [1]. A complementary treatment by percutaneous drainage can be performed, allowing retroperitoneal access [2] [3]. We report the case of a large and complicated infected WOPN, successfully treated by an innovative double endoscopic necrosectomy approach, associating simultaneous transgastric and retroperitoneal endoscopic necrosectomy.
The Phenotypes of Proliferating Glioblastoma Cells Reside on a Single Axis of Variation
Authors: Lin Wang, Husam Babikir, Sören Müller, Garima Yagnik, Karin Shamardani, Francisca Catalan, Gary Kohanbash, Beatriz Alvarado, Elizabeth Di Lullo, Arnold Kriegstein, Sumedh Shah, Harsh Wadhwa, Susan M. Chang, Joanna J. Phillips, Manish K. Aghi, Aaron A. Diaz
Journal: Cancer Discovery (2019)

Abstract Although tumor-propagating cells can be derived from glioblastomas (GBM) of the proneural and mesenchymal subtypes, a glioma stem-like cell (GSC) of the classic subtype has not been identified. It is unclear whether mesenchymal GSCs (mGSC) and/or proneural GSCs (pGSC) alone are sufficient to generate the heterogeneity observed in GBM. We performed single-cell/single-nucleus RNA sequencing of 28 gliomas, and single-cell ATAC sequencing for 8 cases. We found that GBM GSCs reside on a single axis of variation, ranging from proneural to mesenchymal. In silico lineage tracing using both transcriptomics and genetics supports mGSCs as the progenitors of pGSCs. Dual inhibition of pGSC-enriched and mGSC-enriched growth and survival pathways provides a more complete treatment than combinations targeting one GSC phenotype alone. This study sheds light on a long-standing debate regarding lineage relationships among GSCs and presents a paradigm by which personalized combination therapies can be derived from single-cell RNA signatures, to overcome intratumor heterogeneity. Significance: Tumor-propagating cells can be derived from mesenchymal and proneural glioblastomas. However, a stem cell of the classic subtype has yet to be demonstrated. We show that classic-subtype gliomas are comprised of proneural and mesenchymal cells. This study sheds light on a long-standing debate regarding lineage relationships between glioma cell types. See related commentary by Fine, p. 1650. This article is highlighted in the In This Issue feature, p. 1631
TCT-336 Use of a Percutaneous Temporary Mechanical Circulatory Support as a Bridge to Decision in Advanced Heart Failure Patients Listed for Heart Transplantation
Authors: Alexis Okoh, Mohammad Thawabi, Nawar Al Obaidi, Setri Fugar, Swaiman Singh, Justin Gold, Sergio Waxman, Rajiv Tayal, Najam Wasty
Journal: Journal of the American College of Cardiology (2019)
A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial
Authors: Philip J Mease, Josef S Smolen, Frank Behrens, Peter Nash, Soyi Liu Leage, Lingnan Li, Hasan Tahir, Melinda Gooderham, Eswar Krishnan, Hong Liu-Seifert, Paul Emery, Sreekumar G Pillai, Philip S Helliwell
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To compare efficacy and safety of ixekizumab (IXE) to adalimumab (ADA) in biological disease-modifying antirheumatic drug-naïve patients with both active psoriatic arthritis (PsA) and skin disease and inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARDs). Methods Patients with active PsA were randomised (1:1) to approved dosing of IXE or ADA in an open-label, head-to-head, blinded assessor clinical trial. The primary objective was to evaluate whether IXE was superior to ADA at week 24 for simultaneous achievement of a ≥50% improvement from baseline in the American College of Rheumatology criteria (ACR50) and a 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI100). Major secondary objectives, also at week 24, were to evaluate whether IXE was: (1) non-inferior to ADA for achievement of ACR50 and (2) superior to ADA for PASI100 response. Additional PsA, skin, treat-to-target and quality-of-life outcome measures were assessed at week 24. Results The primary efficacy endpoint was met (IXE: 36%, ADA: 28%; p=0.036). IXE was non-inferior for ACR50 response (IXE: 51%, ADA: 47%; treatment difference: 3.9%) and superior for PASI100 response (IXE: 60%, ADA: 47%; p=0.001). IXE had greater response versus ADA in additional PsA, skin, nail, treat-to-target and quality-of-life outcomes. Serious adverse events were reported in 8.5% (ADA) and 3.5% (IXE) of patients. Conclusions IXE was superior to ADA in achievement of simultaneous improvement of joint and skin disease (ACR50 and PASI100) in patients with PsA and inadequate response to csDMARDs. Safety and tolerability for both biologicals were aligned with established safety profiles.
TCT-819 Safety and Efficacy of Mechanical Circulatory Support With Impella or Intra-Aortic Balloon Pump for High-Risk Percutaneous Coronary Intervention and/or Cardiogenic Shock: Insights From a Network Meta-Analysis
Authors: Toshiki Kuno, Hisato Takagi, Tomo Ando, Satoshi Miyashita, Masaki Kodaira, Yohei Numasawa, John Fox, Sripal Bangalore
Journal: Journal of the American College of Cardiology (2019)
Trends in epidemiology of melanoma <i>in situ</i> in Greece: data from a melanoma reference centre during the period 2000–2018
Authors: M. Kostaki, M. Plaka, A. Stergiopoulou, K. Kypreou, V. Chardalia, V. Chasapi, D. Polydorou, A. Stratigos
Journal: British Journal of Dermatology (2019)
TCT-247 The Relationship Between Balloon Pressure and Midterm Restenosis in Second-Generation DES Implantation for Non–Left Main Trunk Bifurcation Lesions by Culotte Stenting
Authors: Koya Okabe, Masanobu Ohya, Kohei Osakada, Takenobu Shimada, Ryosuke Murai, Katsuya Miura, Hidewo Amano, Shunsuke Kubo, Takeshi Tada, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazushige Kadota
Journal: Journal of the American College of Cardiology (2019)
Harnessing Ion-Binding Sites for GPCR Pharmacology
Authors: Barbara Zarzycka, Saheem A. Zaidi, Bryan L. Roth, Vsevolod Katritch
Journal: Pharmacological Reviews (2019)

Endogenous ions play important roles in the function and pharmacology of G-protein coupled receptors (GPCRs). Historically the evidence for ionic modulation of GPCR function dates to 1973 with studies of opioid receptors, where it was demonstrated that physiologic concentrations of sodium allosterically attenuated agonist binding. This Na<sup>+</sup>-selective effect was distinct from effects of other monovalent and divalent cations, with the latter usually counteracting sodium's negative allosteric modulation of binding. Since then, numerous studies documenting the effects of mono- and divalent ions on GPCR function have been published. While ions can act selectively and nonselectively at many sites in different receptors, the discovery of the conserved sodium ion site in class A GPCR structures in 2012 revealed the unique nature of Na<sup>+</sup> site, which has emerged as a near-universal site for allosteric modulation of class A GPCR structure and function. In this review, we synthesize and highlight recent advances in the functional, biophysical, and structural characterization of ions bound to GPCRs. Taken together, these findings provide a molecular understanding of the unique roles of Na<sup>+</sup> and other ions as GPCR allosteric modulators. We will also discuss how this knowledge can be applied to the redesign of receptors and ligand probes for desired functional and pharmacological profiles. <h3>SIGNIFICANCE STATEMENT</h3> The function and pharmacology of GPCRs strongly depend on the presence of mono and divalent ions in experimental assays and in living organisms. Recent insights into the molecular mechanism of this ion-dependent allosterism from structural, biophysical, biochemical, and computational studies provide quantitative understandings of the pharmacological effects of drugs in vitro and in vivo and open new avenues for the rational design of chemical probes and drug candidates with improved properties.
TCT-768 Suture-Mediated Patent Foramen Ovale Closure With NobleStitch: Efficacy at 3 Months Transesophageal Follow-Up
Authors: Marco Ancona, Francesco Moroni, Alessandro Beneduce, Abdallah Abba Aji, Barbara Bellini, Luca Ferri, Cristina Capogrosso, Francesco Ancona, Alaide Chieffo, Eustachio Agricola, Matteo Montorfano
Journal: Journal of the American College of Cardiology (2019)
A Topographical Atlas of the Spinal Cord.
Journal: JAMA (1902)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Authors: S. Filetti, C. Durante, D. Hartl, S. Leboulleux, L.D. Locati, K. Newbold, M.G. Papotti, A. Berruti
Journal: Annals of Oncology (2019)

Key MessageThis ESMO Clinical Practice Guideline provides updated state-of-the-art recommendations on management of thyroid cancer (diagnosis, treatment and follow-up), compiled by a multidisciplinary author panel and accompanied by level of evidence and grade of recommendation, depending on the strength of supporting data and magnitude of benefit from particular interventions. This ESMO Clinical Practice Guideline provides updated state-of-the-art recommendations on management of thyroid cancer (diagnosis, treatment and follow-up), compiled by a multidisciplinary author panel and accompanied by level of evidence and grade of recommendation, depending on the strength of supporting data and magnitude of benefit from particular interventions.
Germline microsatellite genotypes differentiate children with medulloblastoma
Authors: Samuel Rivero-Hinojosa, Nicholas Kinney, Harold R Garner, Brian R Rood
Journal: Neuro-Oncology (2019)

The germline genetic events underpinning medulloblastoma (MB) initiation, and therefore the ability to determine who is at risk, are still unknown for the majority of cases. Microsatellites are short repeated sequences that make up ~3% of the genome. Repeat lengths vary among individuals and are often nonrandomly associated with disease, including several cancers such as breast, glioma, lung, and ovarian. Due to their effects on gene function, they have been called the "tuning knobs of the genome."
Discovery of Novel Sequences in 1,000 Swedish Genomes
Authors: Jesper Eisfeldt, Gustaf Mårtensson, Adam Ameur, Daniel Nilsson, Anna Lindstrand
Journal: Molecular Biology and Evolution (2019)

Novel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin.