tbuckley/cabot-search huggingface dataset:
Concordance and Reproducibility of Melanoma Staging According to the 7th vs 8th Edition of the <i>AJCC Cancer Staging Manual</i>
Authors: Joann G. Elmore, David E. Elder, Raymond L. Barnhill, Stevan R. Knezevich, Gary M. Longton, Linda J. Titus, Martin A. Weinstock, Margaret S. Pepe, Heidi D. Nelson, Lisa M. Reisch, Andrea C. Radick, Michael W. Piepkorn
Journal: JAMA Network Open (2018)

<h3>Importance</h3> The recently updated American Joint Committee on Cancer (AJCC) classification of cancer staging, the<i>AJCC Cancer Staging Manual</i>, 8th edition (<i>AJCC 8</i>), includes revisions to definitions of T1a vs T1b or greater. The Melanoma Pathology Study database affords a comparison of pathologists' concordance and reproducibility in the microstaging of melanoma according to both the existing 7th edition<i>(AJCC 7</i>) and the new<i>AJCC 8</i>. <h3>Objective</h3> To compare<i>AJCC 7</i>and<i>AJCC 8</i>to examine whether changes to the definitions of T1a and T1b or greater are associated with changes in concordance and reproducibility. <h3>Design, Setting, and Participants</h3> In this diagnostic study conducted as part of the national Melanoma Pathology Study across US states, 187 pathologists interpreting melanocytic skin lesions in practice completed 4342 independent case interpretations of 116 invasive melanoma cases. A consensus reference diagnosis and participating pathologists' interpretations were classified into the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis class IV (T1a) or class V (≥T1b) using both the<i>AJCC 7 </i>and<i>AJCC 8</i>criteria. <h3>Main Outcomes and Measures</h3> Concordance with consensus reference diagnosis, interobserver reproducibility, and intraobserver reproducibility. <h3>Results</h3> For T1a diagnoses, participating pathologists' concordance with the consensus reference diagnosis increased from 44% (95% CI, 41%-48%) to 54% (95% CI, 51%-57%) using<i>AJCC 7</i>and<i>AJCC 8</i>criteria, respectively. The concordance for cases of T1b or greater increased from 72% (95% CI, 69%-75%) to 78% (95% CI, 75%-80%). Intraobserver reproducibility of diagnoses also improved, increasing from 59% (95% CI, 56%-63%) to 64% (95% CI, 62%-67%) for T1a invasive melanoma, and from 74% (95% CI, 71%-76%) to 77% (95% CI, 74%-79%) for T1b or greater invasive melanoma cases. <h3>Conclusions and Relevance</h3> Melanoma staging in<i>AJCC 8</i>shows greater reproducibility and higher concordance with a reference standard. Improved classification of invasive melanoma can be expected after implementation of<i>AJCC 8</i>, suggesting a positive impact on patients. However, despite improvement, concordance and reproducibility remain low.
Immune Factors in Deep Vein Thrombosis Initiation
Authors: Ivan Budnik, Alexander Brill
Journal: Trends in Immunology (2018)

Deep vein thrombosis (DVT) is a major origin of morbidity and mortality. While DVT has long been considered as blood coagulation disorder, several recent lines of evidence demonstrate that immune cells and inflammatory processes are involved in DVT initiation. Here, we discuss these mechanisms, in particular, the role of immune cells in endothelial activation, and the immune cascades leading to expression of adhesion receptors on endothelial cells. We analyze the specific recruitment and functional roles of different immune cells, such as mast cells and leukocytes, in DVT. Importantly, we also speculate how immune modulation could be used for DVT prevention with a lower risk of bleeding complications than conventional therapeutic approaches.
Synergistic antileukemic therapies in NOTCH1-induced T-ALL
Authors: Marta Sanchez-Martin, Alberto Ambesi-Impiombato, Yue Qin, Daniel Herranz, Mukesh Bansal, Tiziana Girardi, Elisabeth Paietta, Martin S Tallman, Jacob M Rowe, Kim De Keersmaecker, Andrea Califano, Adolfo Ferrando
Journal: Clinical Cancer Research (2017)

The Notch1 gene is a major oncogenic driver and therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL). However, inhibition of NOTCH signaling with γ-secretase inhibitors (GSIs) has shown limited antileukemic activity in clinical trials. Here we performed an expression-based virtual screening to identify highly active antileukemic drugs that synergize with NOTCH1 inhibition in T-ALL. Among these, withaferin A demonstrated the strongest cytotoxic and GSI-synergistic antileukemic effects in vitro and in vivo. Mechanistically, network perturbation analyses showed eIF2A-phosphorylation–mediated inhibition of protein translation as a critical mediator of the antileukemic effects of withaferin A and its interaction with NOTCH1 inhibition. Overall, these results support a role for anti-NOTCH1 therapies and protein translation inhibitor combinations in the treatment of T-ALL.
Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials
Authors: Reynold A Panettieri, Ulf Sjöbring, AnnaMaria Péterffy, Peter Wessman, Karin Bowen, Edward Piper, Gene Colice, Christopher E Brightling
Journal: The Lancet Respiratory Medicine (2018)
Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy
Authors: Xiao-Mei Qi, Fang Wang, Matthew Mortensen, Ryan Wertz, Guan Chen
Journal: Acta Pharmaceutica Sinica B (2018)

Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention. p38γ is a unique MAPK family member that contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing protein tyrosine phosphatase PTPH1. This PDZ-coupled binding is required for both PTPH1 dephosphorylation and inactivation of p38γ and for p38γ phosphorylation and activation of PTPH1. Moreover, the p38γ/PTPH1 complex can further regulate their substrates phosphorylation and dephosphorylation, which impacts Ras transformation, malignant growth and progression, and therapeutic response. This review will use the p38γ/PTPH1 signaling network as an example to discuss the potential of targeting the kinase/phosphatase signaling complex for development of novel targeted cancer therapy.
BRCA2 Mutation as a Possible Cause of Poor Response to 177Lu-PSMA Therapy
Authors: Hojjat Ahmadzadehfar, Florian Gaertner, Philipp S. Lossin, Bettina Schwarz, Markus Essler
Journal: Clinical Nuclear Medicine (2018)

We present the case of a 66-year-old man with castration-resistant prostate cancer, with an increasing prostate-specific antigen level, and a progressive disease during Lu-PSMA radionuclide therapy. Because the patient had a BRCA2 mutation, poly-ADP ribose polymerase inhibitor therapy was started. The patient showed a dramatic subjective and biological response to this therapy with a progression-free survival of 5 months.
Research on Underrepresented Populations
Authors: Eric Y. Chang, Nicolas Bakinde, Ugochi L. Obih
Journal: JAMA (2018)

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
Rad5, HLTF, and SHPRH: A Fresh View of an Old Story
Authors: Menattallah Elserafy, Arwa A. Abugable, Reham Atteya, Sherif F. El-Khamisy
Journal: Trends in Genetics (2018)

Not only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches.
Identification of a sodium pump Na + /K + ATPase α1-targeted peptide for PET imaging of breast cancer
Authors: Qian Wang, Shi-Bing Li, Yi-Ying Zhao, Da-Nian Dai, Hui Du, Yan-Zhu Lin, Jia-Cong Ye, Jing Zhao, Wei Xiao, Yan Mei, Yi-Tai Xiao, Shi-Chu Liu, Yan Li, Yun-Fei Xia, Er-Wei Song, Gang-Hua Tang, Wei-Guang Zhang, Zhi-Jian Li, Xiao-Bin Zheng, De-Hai Cao, Man-Zhi Li, Qian Zhong, Zhong-Ping Chen, Chao-Nan Qian, Wei Fan, Guo-Kai Feng, Mu-Sheng Zeng
Journal: Journal of Controlled Release (2018)
Anticancer efficacy of noble metal nanoparticles relies on reprogramming tumor-associated macrophages through redox pathways and pro-inflammatory cytokine cascades
Authors: Mahuya Sengupta, Ramkrishna Pal, Anupam Nath, Biswajit Chakraborty, Leichombam Mohindro Singh, Biswajit Das, Sujit Kumar Ghosh
Journal: Cellular and Molecular Immunology (2018)
Multicenter Randomized Controlled Crossover Trial Comparing Hemodynamic Optimization Against Echocardiographic Optimization of AV and VV Delay of Cardiac Resynchronization Therapy
Authors: Zachary I. Whinnett, S.M. Afzal Sohaib, Mark Mason, Edward Duncan, Mark Tanner, David Lefroy, Mohamed Al-Obaidi, Sue Ellery, Francisco Leyva-Leon, Tim Betts, Mark Dayer, Paul Foley, Jon Swinburn, Martin Thomas, Raj Khiani, Tom Wong, Zaheer Yousef, Dominic Rogers, Paul R. Kalra, Vignesh Dhileepan, Katherine March, James Howard, Andreas Kyriacou, Jamil Mayet, Prapa Kanagaratnam, Michael Frenneaux, Alun D. Hughes, Darrel P. Francis
Journal: JACC. Cardiovascular imaging (2018)

BRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method.Cardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform.This study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro-B-type natriuretic peptide.A total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro-B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms.Optimization of cardiac resynchronization therapy devices by using noninvasive blood pressure is noninferior to echocardiographic optimization. Therefore, noninvasive hemodynamic optimization is an acceptable alternative that has the potential to be automated and thus more easily implemented. (British Randomized Controlled Trial of AV and VV Optimization [BRAVO]; NCT01258829).
Abstract 18307: T-tubules and Dyad Formation in Engrafted iPSC-Derived Cardiomyocytes With Stable APEX2 Expression
Authors: Takeshi Hatani, Shunsuke Funakoshi, Thomas J Deerinck, Eric A Bushong, Takeshi Kimura, Shinya Yamanaka, Mark H Ellisman, Masahiko Hoshijima, Yoshinori Yoshida
Journal: Circulation (2016)

Background: Although studies have shown the potential of in vivo cardiac transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to treat cardiac diseases in animal...
Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma
Authors: Timothy L. Lochmann, Krista M. Powell, Jungoh Ham, Konstantinos V. Floros, Daniel A. R. Heisey, Richard I. J. Kurupi, Marissa L. Calbert, Maninderjit S. Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J. Souers, C. Patrick Reynolds, Cyril H. Benes, Anthony C. Faber
Journal: Science Translational Medicine (2018)

High-throughput screening identified hypersensitivity of neuroblastomas to H3K27 demethylation inhibition.
Tracing Environmental Exposure from Neurodevelopment to Neurodegeneration
Authors: Amy L. Heffernan, Dominic J. Hare
Journal: Trends in Neurosciences (2018)

Interplay between genetic and environmental factors during critical time windows can have effects that span from neurodevelopment to neurodegeneration. We present the concept of the 'neuroexposome', emphasizing the brain's distinctive response to environmental exposure, and how current 'omics' sciences can inform on both disease pathogenesis and future public health policies.
Challenge anti-migrant policies with evidence, doctors are told
Authors: Richard Hurley
Journal: BMJ (2018)

Doctors should challenge anti-migrant rhetoric that legitimises harmful government policies that deny migrants access to healthcare and leads to social exclusion, a conference on migrant health has heard.

“We must change public narratives when discourse becomes toxic, using facts and evidence,” said Jacqueline Weekers, director of the migration and health division of the United Nations’ International Organization for Migration.

She was speaking at the first World Congress on Migration, Ethnicity, Race, and Health in Edinburgh, held from 16 to 19 May.

Weekers lamented the “appalling lack of political leadership” on migration, and pointed out that “there is no public health without migrant health.”

Laurence Gruer, honorary professor of public health at the University of Edinburgh, also speaking at the conference, said: “Fighting discrimination is an endless task. We must commit to engage in this struggle at …
The ontogeny of a 57-Kd cationic antimicrobial protein of human polymorphonuclear leukocytes: localization to a novel granule population
Authors: HA Pereira, JK Spitznagel, EF Winton, WM Shafer, LE Martin, GS Guzman, J Pohl, RW Scott, MN Marra, JM Jr Kinkade
Journal: Blood (1990)
Monitoring of asparagine depletion and anti-l-asparaginase antibodies in adult acute lymphoblastic leukemia treated in the pediatric-inspired GRAALL-2005 trial
Authors: Jérôme Paillassa, Thibaut Leguay, Xavier Thomas, Françoise Huguet, Marie Audrain, Véronique Lheritier, Christine Vianey-Saban, Cécile Acquaviva-Bourdain, Cécile Pagan, Hervé Dombret, Norbert Ifrah, Nicolas Boissel, Mathilde Hunault-Berger
Journal: Blood Cancer Journal (2018)
Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam
Authors: Kathryn E. Holt, Paul McAdam, Phan Vuong Khac Thai, Nguyen Thuy Thuong Thuong, Dang Thi Minh Ha, Nguyen Ngoc Lan, Nguyen Huu Lan, Nguyen Thi Quynh Nhu, Hoang Thanh Hai, Vu Thi Ngoc Ha, Guy Thwaites, David J. Edwards, Artika P. Nath, Kym Pham, David B. Ascher, Jeremy Farrar, Chiea Chuen Khor, Yik Ying Teo, Michael Inouye, Maxine Caws, Sarah J. Dunstan
Journal: Nature Genetics (2018)
Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Followed By HDT-ASCT, Consolidation with Krd and Maintenance with Rd
Authors: Maria-Victoria Mateos, Joaquin Martinez-Lopez, Paula Rodriguez Otero, Veronica Gonzalez-Calle, Marta Sonia Gonzalez, Albert Oriol, Norma C. Gutierrez, Bruno Paiva, Rafael Ríos Tamayo, Laura Rosinol Dachs, Miguel Angel Alvarez, Maria Jose Calasanz, Joan Bargay, Ana Pilar Gonzalez, Adrián Alegre Amor, Fernando Escalante, Belén Iñigo, Noemi Puig, Javier De La Rubia, Ana Isabel Teruel, Maria Teresa Cedena Romero, Felipe De Arriba, Luis Palomera, Miguel T Hernández, Javier Lopez Jimenez, Jesús Martín, Aránzazu García Mateo, Enrique M. Ocio, Joan Bladé, Juan Jose Lahuerta, Jesús San-Miguel
Journal: Blood (2019)
Abstract IA16: The global proteome and phospho-proteome of K-Ras mutant tissues
Authors: Kevin Haigis
Journal: Cancer Research (2018)

Abstract K-Ras is the most commonly mutated oncogene in cancer, and it plays a predominant role in the pathogenesis of cancers of the pancreas, colon, and lung. Mutationally activated K-Ras influences cellular behaviors through broad and complex effects on downstream signal transduction pathways. In an effort to understand the molecular mechanisms underlying the oncogenic properties of mutant forms of K-Ras, we have used multiplexed mass spectroscopy (MS) to quantify proteome-wide changes in protein phosphorylation in primary mouse tissues that are engineered to express mutant K-Ras, either alone or in combination with mutations in other cancer genes. This multidimensional dataset highlights the context dependence of K-Ras signaling because the significant changes in protein abundance and/or phosphorylation due to activation of K-Ras are highly dependent upon both tissue context and cooperating mutations. The dataset also paints a complex picture of signaling downstream of K-Ras within a given tissue, as phosphorylation of many proteins in known Ras effector pathways (i.e., MAPK and PI3K) are unaffected or downregulated by mutationally activated K-Ras. Overall, this study provides an unprecedented view of K-Ras signaling on a global scale and reveals a variety of novel insights into the signal transduction properties of mutant K-Ras alleles. Citation Format: Kevin Haigis. The global proteome and phospho-proteome of K-Ras mutant tissues [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA16.
Tackling the knife violence epidemic requires a radical upgrade in public health investment
Authors: Laura Cattermole, Padmanabhan Badrinath, Abdul Razaq
Journal: BMJ (2018)

Torjeson asks whether public health strategies can tackle London’s rise in fatal violence.1 Violence costs the NHS £2.9bn (€3.3bn; $3.9bn) annually. It also affects mental wellbeing and freedom to use outdoor spaces and increases the risks of obesity, cancer, and heart disease.2

A recent BBC news article said that making “a direct link between the number of killings and the number of Bobbies on the beat” …
Nutritional Regulation of Intestinal Stem Cells
Authors: Salvador Alonso, Ömer H. Yilmaz
Journal: Annual Review of Nutrition (2018)

Dietary composition and calorie intake are major determinants of health and disease. Calorie restriction promotes metabolic changes that favor tissue regeneration and is arguably the most successful and best-conserved antiaging intervention. Obesity, in contrast, impairs tissue homeostasis and is a major risk factor for the development of diseases including cancer. Stem cells, the central mediators of tissue regeneration, integrate dietary and energy cues via nutrient-sensing pathways to maintain growth or respond to stress. We discuss emerging data on the effects of diet and nutrient-sensing pathways on intestinal stem cells, as well as their potential application in the development of regenerative and therapeutic interventions.
Abstract IA15: Normal and cancer stem cells in multistage carcinogenesis
Authors: Allan Balmain
Journal: Cancer Research (2018)

Abstract Mouse models of cancer have been instrumental in the development of our understanding of the processes that drive multistage carcinogenesis from the initiation stage to metastasis. In particular, tumors induced in mice by exposure to chemicals that act as mutagens or tumor promoters replicate many of the biologic and genetic features of multistage cancer in human populations. Such models often have a high burden of point mutations and gene copy number changes similar to human tumors of the lung, colon, or skin that are associated with exposure to exogenous environmental agents. These are important features that contribute to tumor heterogeneity—a major cause of drug resistance and poor response to therapy in human cancer patients. The availability of mouse models of tumors with a high mutation burden also offers possibilities for development of immunotherapy approaches that are dependent on expression of novel tumor antigens resulting from carcinogen-induced mutations in tumor DNA. Initiation of chemical carcinogenesis in the mouse is frequently caused by point mutations in genes of the Ras family. The nature of the initiating Ras mutation depends on the carcinogen used, but a similar “mutation signature” is seen throughout the genome of the initiated cell. Tumor cells, however, continually acquire additional new genetic alterations, leading to the emergence of multiple, genetically distinct tumor subclones. By combining the 4-color lineage tracing Confetti mouse with a chemical carcinogenesis model of skin cancer, we have investigated clonal and evolutionary dynamics at every stage of chemical carcinogenesis, from the initiated cell to benign tumors, malignant carcinomas, and ultimately to distant metastases. These studies reveal distinct patterns of clonal evolution at different stages of progression. The growth of subclones within tumors is driven by a stem cell population marked by expression of the Lgr6 gene—a known marker of normal skin stem cells and mediator of Wnt signaling in the epidermis. The use of mouse models for identification of patterns of clonal heterogeneity, and the drivers of clonal growth from cancer stem cells, may offer new possibilities for prevention or treatment of squamous carcinomas. Citation Format: Allan Balmain. Normal and cancer stem cells in multistage carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA15.
Abstract 17195: Improved Surgical Outcomes of Distal Type Cteph
Authors: Keiichi Ishida, Masahisa Masada, Goro Matsumiya
Journal: Circulation (2016)

Introduction: Pulmonary endarterectomy (PEA) is a potentially curative treatment of CTEPH. Nevertheless, nearly a half of patients were deemed inoperable mainly due to inaccessible disease. With in...