tbuckley/cabot-search huggingface dataset:
Molecular characteristics and prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX.
Authors: Dae-Won Lee, Sae Won Han, Hyun Jung Lee, Ye-Young Rhee, Jeong Mo Bae, Nam-Yun Cho, Kyung-Hun Lee, Tae Yong Kim, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Seung-Yong Jeong, Kyu Joo Park, Jae-Gahb Park, Gyeong Hoon Kang, Tae-You Kim
Journal: Journal of Clinical Oncology (2013)

3550 Background: There have been controversies in prognostic impact of mucinous histology in colorectal cancer (CRC) and its implication in pts treated with adjuvant FOLFOX is unclear. This study aimed at elucidating the molecular characteristics and prognostic implication of mucinous histology in pts treated with adjuvant FOLFOX. Methods: Stage II and III CRC pts who received adjuvant FOLFOX were analyzed. Pts were grouped according to the mucinous content: &gt; 50%, mucinous adenocarcinoma (MAC); &lt; 50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, nonmucinous adenocarcinoma (NMA). Clinicopathologic features, MSI status (N = 518), CpG island methylator phenotype (CIMP) (N = 322) BRAF mutation (N = 269) and disease-free survival (DFS) were compared. Results: Among a total of 521 pts, 27 (5.2%) had MAC, 41 (7.9%) AIM, and 453 (86.9%) NMA. MAC and AIM had higher frequency of proximal location and lower angiolymphatic invasion. MAC had higher proportion of T4 tumors. AIM had higher frequency of age ≥65 years and female. In terms of molecular characteristics, MAC and AIM showed similarly higher proportion of MSI-high and CIMP-high compared to NMA. BRAF mutation also showed similar trend. In contrast to the similarities between MAC and AIM, DFS was significantly different. MAC showed significantly worse DFS compared with AIM and NMA, whereas AIM and NMA showed similar DFS. Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted HR 7.96, 95% CI 3.76-16.8). Conclusions: AIM and MAC has distinct clinico-pathologic features and molecular characteristics compared with NMA. Only MAC but not AIM has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX compared with NMA. [Table: see text]
Review: Transcriptional Regulation of CD4+ T Cell Differentiation in Experimentally Induced Arthritis and Rheumatoid Arthritis
Authors: Yuya Kondo, Masahiro Yokosawa, Shunta Kaneko, Kotona Furuyama, Seiji Segawa, Hiroto Tsuboi, Isao Matsumoto, Takayuki Sumida
Journal: Arthritis & Rheumatology (2017)

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the joint synovium and infiltration by activated inflammatory cells. CD4+ T cells form a large proportion of the inflammatory cells invading the synovial tissue, and are involved in the RA pathologic process. In general, CD4+ T cells differentiate into various T helper cell subsets and acquire the functional properties to respond to specific pathogens, and also mediate some autoimmune disorders such as RA. Because the differentiation of T helper cell subsets is determined by the expression of specific transcription factors in response to the cytokine environment, these transcription factors are considered to have a role in the pathology of RA. Treg cells control an excess of T cell-mediated immune response, and the transcription factor FoxP3 is critical for the differentiation and function of Treg cells. Treg cell dysfunction can result in the development of systemic autoimmunity. In this review, we summarize how the expression of transcription factors modulates T helper cell immune responses and the development of autoimmune diseases, especially in RA. Understanding the role of transcription factors in the pathogenesis of autoimmunity may lead to novel therapeutic strategies to control the differentiation and function of both T helper cells and Treg cells.
The M5 Cell: A Color-Opponent Intrinsically Photosensitive Retinal Ganglion Cell
Authors: Maureen E. Stabio, Shai Sabbah, Lauren E. Quattrochi, Marissa C. Ilardi, P. Michelle Fogerson, Megan L. Leyrer, Min Tae Kim, Inkyu Kim, Matthew Schiel, Jordan M. Renna, Kevin L. Briggman, David M. Berson
Journal: Neuron (2017)
Resolvins suppress tumor growth and enhance cancer therapy
Authors: Megan L. Sulciner, Charles N. Serhan, Molly M. Gilligan, Dayna K. Mudge, Jaimie Chang, Allison Gartung, Kristen A. Lehner, Diane R. Bielenberg, Birgitta Schmidt, Jesmond Dalli, Emily R. Greene, Yael Gus-Brautbar, Julia Piwowarski, Tadanori Mammoto, David Zurakowski, Mauro Perretti, Vikas P. Sukhatme, Arja Kaipainen, Mark W. Kieran, Sui Huang, Dipak Panigrahy
Journal: The Journal of Experimental Medicine (2017)

Cancer therapy reduces tumor burden by killing tumor cells, yet it simultaneously creates tumor cell debris that may stimulate inflammation and tumor growth. Thus, conventional cancer therapy is inherently a double-edged sword. In this study, we show that tumor cells killed by chemotherapy or targeted therapy (“tumor cell debris”) stimulate primary tumor growth when coinjected with a subthreshold (nontumorigenic) inoculum of tumor cells by triggering macrophage proinflammatory cytokine release after phosphatidylserine exposure. Debris-stimulated tumors were inhibited by antiinflammatory and proresolving lipid autacoids, namely resolvin D1 (RvD1), RvD2, or RvE1. These mediators specifically inhibit debris-stimulated cancer progression by enhancing clearance of debris via macrophage phagocytosis in multiple tumor types. Resolvins counterregulate the release of cytokines/chemokines, including TNFα, IL-6, IL-8, CCL4, and CCL5, by human macrophages stimulated with cell debris. These results demonstrate that enhancing endogenous clearance of tumor cell debris is a new therapeutic target that may complement cytotoxic cancer therapies.
Being “fat but fit” does not increase longevity
Authors: Nigel Hawkes
Journal: BMJ (2017)

The widely publicised claim that life lasts longer for those who are modestly overweight is a myth, a new study has shown.

The idea that being “fat but fit” confers advantages comes from many observational studies suggesting that on average those whose body mass index (BMI) is slightly higher than ideal live longer. But, say Bristol University researchers, people are often thin because they are already ill with the diseases that will ultimately kill them. They don’t die early because they’re thin; they are thin because they are already ill or dying.

David Carslake and George Davey-Smith, together with other colleagues from Bristol and Norway, set out to test the relationship by comparing when people died not …
Abstract P172: Birth Weight, Maternal Pre-pregnancy Body Mass Index and Adulthood Vitamin D Levels: The Jerusalem Perinatal Study
Authors: Amy Moore, Hagit Hochner, Colleen Sitlani, Michelle A Williams, David S Siscovick, Yechiel Friedlander, Daniel A Enquobahrie
Journal: Circulation (2012)

Background: The intrauterine experience and pre-pregnancy maternal characteristics have demonstrated importance in the development of life course risk for chronic diseases. Vitamin D has been associated with several chronic diseases including cardiometabolic diseases. Whether offspring birth weight and maternal pre-pregnancy body mass index (BMI) are associated with adulthood vitamin D levels is unknown. Further, the role of adulthood BMI in these relationships is not clear. Methods: We examined associations of offspring birth weight and maternal pre-pregnancy BMI with offspring adulthood vitamin D levels among a subset of the Jerusalem Perinatal Study (JPS) population, a birth cohort of Jerusalem residents born between 1974 and 1976. Offspring aged 30-35 years, sampled based on maternal pre-pregnancy body mass index (BMI) and offspring birth weight, and their mothers were recruited as part of the JPS-1 study. Data were collected using interviews and field physical examinations. Fasting blood specimens were obtained for vitamin D measurements. We used liquid chromatography-tandem mass spectroscopy to measure total vitamin D (25-[OH] D). Sample-weighted multiple regression models, adjusted for potential confounders, were used to examine associations, and determine coefficients and 95% confidence intervals. Results: Mean total vitamin D levels was 23.48ng/ml among study participants. Birth weight was not related to vitamin D levels in adulthood. Pre-pregnancy BMI was inversely associated with offspring adulthood vitamin D levels, both before (β=-0.24, p-value=0.005) and after adjustment for birth weight (β=-0.24, p-value=0.015). However, the association was attenuated by including current offspring BMI in the models (β=-0.17, p-value=0.061) or both current BMI and birth weight (β=-0.16, p-value=0.120). In addition, the association between maternal pre-pregnancy BMI with current offspring BMI was not altered by adulthood vitamin D level. Conclusion: Maternal pre-pregnancy is potentially associated with adulthood vitamin D levels. This association may be mediated at least in part by offspring current BMI. Future studies are warranted to investigate whether the observed associations are due to genetic factors or other characteristics of the intrauterine environment.
Association of Quantitative Metastatic Lymph Node Burden With Survival in Hypopharyngeal and Laryngeal Cancer
Authors: Allen S. Ho, Sungjin Kim, Mourad Tighiouart, Cynthia Gudino, Alain Mita, Kevin S. Scher, Anna Laury, Ravi Prasad, Stephen L. Shiao, Nabilah Ali, Chrysanta Patio, Jon Mallen-St. Clair, Jennifer E. Van Eyk, Zachary S. Zumsteg
Journal: JAMA Oncology (2017)

Nodal staging for laryngohypopharyngeal cancers is based primarily on size and laterality, with less value placed on absolute number of metastatic lymph nodes (LNs). We are aware of no studies to date that have specifically addressed the prognostic effect of quantitative nodal burden in larynx or hypopharynx malignancies.To assess the independent impact of quantitative metastatic LN burden on mortality risk.Univariate and multivariable models were constructed to evaluate the association between patients' number of metastatic LNs and their survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Participants were patients with squamous cell carcinoma of the larynx or hypopharynx undergoing upfront surgical resection for curative intent at a US hospital between 2004 and 2013, as identified in the National Cancer Database. A neck dissection of a minimum of 10 LNs was required.Overall survival.Overall, 8351 cases were included (mean [SD] age, 61 [10.1] years; 6499 men [77.8%]; 4710 patients with metastatic LNs and 3641 with no metastatic LNs). Mortality risk escalated continuously without plateau as number of metastatic nodes increased, with the hazard per node (hazard ratio [HR], 1.19; 95% CI, 1.16-1.23; P < .001) most pronounced up to 5 positive LNs. Extranodal extension was also associated with increased mortality (HR, 1.34; 95% CI, 1.13-1.59; P < .001). Increasing number of nodes examined was associated with improved survival, albeit to a lesser degree (per 10 LNs: HR, 0.97; 95% CI, 0.96-0.98; P < .001) and without a detectable change point. Other nodal factors, including nodal size, contralateral LN involvement (TNM stage N2c), and lower LN involvement (levels 4-5), were not associated with mortality in multivariable models when accounting for number of positive LNs. A novel, parsimonious nodal staging system derived by recursive partitioning analysis exhibited greater concordance with survival than the TNM staging system outlined in the American Joint Committee on Cancer's AJCC Staging Manual, 8th edition.The number of metastatic nodes is a predominant independent factor associated with mortality in hypopharyngeal and laryngeal cancers. Moreover, standard nodal staging factors like LN size and contralaterality have no independent prognostic value when accounting for positive LN number. Deeper integration of quantitative metastatic nodal disease may simplify staging and better triage the need for adjuvant therapy.
Multi-Omics of Adult T Cell Acute Lymphoblastic Leukemia
Authors: Martin Neumann, Michael P Schroeder, Lorenz Bastian, Jutta Ortiz Tanchez, Cornelia Schlee, Konstandina Isaakidis, Alva Rani James, Lars R. Fransecky, Sebastian Vosberg, Stefan Krebs, Helmut Blum, Stefan Schwartz, Thomas Burmeister, Dieter Hoelzer, Philipp A. Greif, Monika Brüggemann, Nicola Goekbuget, Claudia D. Baldus
Journal: Blood (2017)
Short-term outcomes following endoscopic submucosal dissection of large protruding colorectal neoplasms
Authors: Taku Sakamoto, Yutaka Saito, Fumihiko Nakamura, Seiichiro Abe, Hiroyuki Takamaru, Masau Sekiguchi, Masayoshi Yamada, Takeshi Nakajima, Takahisa Matsuda, Hidetsugu Yamagishi, Hiroyuki Kato
Journal: Endoscopy (2017)

Abstract Background Although submucosal dissection is useful for treating laterally spreading colorectal tumors, there is little information regarding the endoscopic treatment of large protruding colorectal neoplasms. Here, we aimed to evaluate the clinical outcomes of endoscopic submucosal dissection for protruding colorectal neoplasms ≥ 20 mm in diameter. Methods In total, 112 consecutive patients undergoing treatment between January 2005 and June 2017 were enrolled retrospectively. The study period was divided into six periods to evaluate any changes in outcomes over time. We reviewed all short-term clinical outcomes, including lesion characteristics, procedure time, and percentages of en bloc resection, curative resection, adverse events, and treatment discontinuation. Results The percentages of en bloc, en bloc R0, and en bloc curative resections were 88 %, 82 %, and 59 %, respectively. Perforation occurred in 11 patients (10 %), and the endoscopic procedure was discontinued in five patients (4 %) because of technical difficulty. For lesions ≥ 40 mm in diameter, the procedure time showed a statistically significant decreasing trend in the latter half of the study period. However, the rate of cure did not improve along with enhancements to the procedure’s technological aspects. Conclusions Although endoscopic submucosal dissection for large protruding lesions has advanced in terms of its technical aspects, its ability to cure large protruding neoplasms has not shown gratifying results.
Significance and mechanism of androgen receptor overexpression and androgen receptor/mechanistic target of rapamycin cross‐talk in hepatocellular carcinoma
Authors: Hong Zhang, Xiao‐Xing Li, Yang Yang, Yanjie Zhang, Hui‐Yun Wang, X.F. Steven Zheng
Journal: Hepatology (2017)

Hepatocellular carcinoma (HCC) is a male‐dominant cancer, and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous antiandrogen and anti‐AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% of HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR‐dependent transcriptome, stimulates oncogenic growth, and determines therapeutic response to enzalutamide, a second generation of AR antagonist. However, AR inhibition evokes feedback activation of AKT‐mTOR (mechanistic target of rapamycin) signaling, a central regulator for cell growth and survival. On the other hand, mTOR promotes nuclear AR protein expression by restraining ubiquitin‐dependent AR degradation and enhancing AR nuclear localization, providing a mechanistic explanation for nuclear AR overexpression in HCC. Finally, cotargeting AR and mTOR shows significant synergistic anti‐HCC activity and decreases tumor burden by inducing apoptosis in vivo . Conclusion: Nuclear AR overexpression is associated with the progression and prognosis of HCC. However, enzalutamide alone has limited therapeutic utility attributed to feedback activation of the AKT‐mTOR pathway. Moreover, mTOR drives nuclear AR overexpression. Cotargeting AR and mTOR is a promising therapeutic strategy for HCC. (H epatology 2018;67:2271‐2286).
Moral Choices for Today’s Physician
Authors: Donald M. Berwick
Journal: JAMA (2017)

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
Early Dynamic Changes in 'Salvaged Area at Risk' Assessed by Serial MRI at 3t in Patients With Acute Coronary Syndrome
Authors: E Dall'Armellina, A C Lindsay, Robson, T Karamitsos, J M Francis, K M Channon, A P Banning, R Kharbanda, S Neubauer, R P Choudhury
Journal: Circulation (2009)
Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis Mimicking Lymphoma on FDG PET/CT
Authors: Qingqing Pan, Yaping Luo, Huanwen Wu, Yanru Ma, Fang Li
Journal: Clinical Nuclear Medicine (2017)

Abstract A 15-year-old boy with fever, pancytopenia, and hepatosplenomegaly was diagnosed as hemophagocytic lymphohistiocytosis (HLH). 18 F-FDG PET/CT showed hypermetabolic foci in the liver, spleen, and bone marrow, as well as multiple FDG-avid lymph nodes, which were highly suggestive of lymphoma. Specimens from splenectomy depicted a large number of macrophages/histiocytes with hemophagocytosis of erythrocytes, without evidence of malignancy. Considering increased Epstein-Barr virus (EBV) DNA in peripheral blood and positive staining for EBV-encoded RNA in the spleen, EBV-associated HLH was confirmed. This case indicates that FDG-avid foci in the liver, spleen, and bone marrow may also be seen in EBV-associated HLH.
Surgical revascularization of the celiac artery for persistent intestinal ischemia in short bowel syndrome
Authors: Arnaud Roussel, Alexandre Nuzzo, Quentin Pellenc, Yves Castier, Romain De Blic, Pierre Cerceau, Célia Boulitrop, Mathieu Coblence, Sonia Aguir, Pierre Mordant, Léon Maggiori, Audrey Huguet, Annie Sibert, Francisca Joly, Olivier Corcos
Journal: International Journal of Surgery (2017)
Effect of Losartan on Right Ventricular Dysfunction
Authors: Jouke P. Bokma, Michiel M. Winter, Arie P. van Dijk, Hubert W. Vliegen, Joost P. van Melle, Folkert J. Meijboom, Martijn C. Post, Jacqueline K. Berbee, S. Matthijs Boekholdt, Maarten Groenink, Aeilko H. Zwinderman, Barbara J.M. Mulder, Berto J. Bouma
Journal: Circulation (2017)

Background: The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. Methods: The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] &lt;50%) but without severe valvular dysfunction were eligible. Patients were randomly assigned between losartan (150 mg daily) and placebo with target treatment duration between 18 and 24 months. The primary outcome was RV EF change, determined by cardiovascular MRI in intention-to-treat analysis. Results: Of 95 included patients, 47 patients received 150 mg losartan daily (age, 38.0±12.4 years; 74% male), and 48 patients received placebo (age, 40.6±11.4 years; 63% male). Overall, RV EF did not change in patients allocated to losartan (n=42) (44.4±5.1% to 45.2±5.0%) and placebo (n=46) (43.2±6.3% to 43.6±6.9%). Losartan did not significantly improve RV EF in comparison with placebo (+0.51%; 95% confidence interval, –1.0 to +2.0; P =0.50). No significant treatment effects were found on secondary outcomes: left ventricular EF, peak aerobic exercise capacity, and N-terminal pro–brain natriuretic peptide ( P &gt;0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EF&lt;40%, pulmonary valve replacement, or QRS fragmentation. However, in a post hoc analysis, losartan was associated with improved RV EF in a subgroup (n=30) with nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous pulmonary valve replacement) (+2.7%; 95% confidence interval, +0.1 to +5.4; P =0.045). Conclusions: Losartan had no significant effect on RV dysfunction or secondary outcome parameters in repaired tetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02010905.
Vigilancia de la tuberculosis en Irlanda
Authors: A Smith, D Igoe, D O’Flanagan, T Holohan
Journal: Eurosurveillance (2000)

Los primeros datos no agregados sobre la tuberculosis en Irlanda se recogieron en 1998. Se notifico un total de 424 casos (tasa de 11,7/100.000 habitantes), de los cuales 241 tuvieron cultivo positivo y 122 fueron casos pulmonares con frotis positivo. Hubo solo 35 casos extranjeros y no se identificaron casos resistentes a multiples medicamentos.