tbuckley/cabot-search huggingface dataset:
CEA clearance pattern as a predictor for pathologic complete response after neoadjuvant chemoradiation for rectal cancer: Results of the FOWARC trial.
Authors: Huabin Hu, Jianwei Zhang, Yue Cai, Ping Lan, Lei Wang, Meijin Huang, Liang Kang, Jianping Wang, Yanhong Deng
Journal: Journal of Clinical Oncology (2016)

e15112 Background: Approximately 10% to 30% locally advanced rectal cancer patients receiving neoadjuvant chemoradiation (CRT) will have a pathologic complete response (pCR). Predicting pCR can have a significant effect on patients in terms of helping confer prognosis, possibly enabling organ preservation, and potentially avoiding unnecessary surgery. The aim of this study was to investigate the predictive value of carcinoembryonic antigen (CEA) clearance pattern for the tumor response to preoperative CRT in rectal cancer patients with elevated CEA levels. Methods: A total of 71 patients with elevated CEA levels ( > 5ng/ml) were randomly assigned to receive neoadjuvant 5-FU-based chemotherapy with pelvic radiation in FOWARC trial. Serum CEA were measured at six different time points, including base line, and the 2, 4, 6, 8 and 14 weeks during CRT. An exponential trend line was drawn using the six CEA values. Patients were categorized into two groups based on R2 values calculated through trend line, which indicates the correlation coefficient between exponential graph and measured CEA values: exponential decrease group (0.9 < R2≦1.0), and non-exponential decrease group (R2≦0.9). Results: 31 patients were classified as CEA exponential decrease group, and 40 patients were in non-exponential decrease group. 11 (15%) of 71 patients were achieved pCR. CEA decrease with exponential pattern was a significant independent predictor for TRG (0-1) (OR: 3.04, CI 1.10-8.43), good down-staging (ypTNM stage 0-I) (OR 7.26, CI 1.79-29.37) and pCR (OR 10.15, CI 1.50-68.62) in multivariate analysis, and the AUC for pCR was 0.726, which was the strongest factor among clinicopathologic indexes (clinical T stage,tumor differentiation, tumor length, circumferential extent, and normalization of post-CRT CEA level). Conclusions: The pattern of CEA clearance, a simple clinical parameter, normally available in everyday practice, was a independent predictor of pCR for rectal cancer patients. These results would be beneficial to guide individualized treatment strategies for this patients with elevated CEA levels. Clinical trial information: NCT01211210.
Abstract 224: Crosstalk Between Mitochondrial and ER Death Pathways in the Heart
Authors: Agnieszka Biala, Yan Wang, Rimpy Dhingra, Hongying Gang, Lorrie Kirshenbaum
Journal: Circulation Research (2012)

Alternative gene splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Previously we determined the hypoxia-inducible protein Bnip3 is integral component of the mitochondrial death pathway that can signal apoptosis and autophagy but the precise mechanisms that differentially regulates these divergent processes remains cryptic. Herein, we provide novel evidence that inclusion or skipping of exon3 of Bnip3 mRNA by alternative splicing generates proteins with distinct and opposing actions on autophagy and cell survival. Metabolic stress imposed by hypoxia or nutrient deprivation resulted in the synthesis of two Bnip3 mRNA isoforms in post-natal ventricular myocytes in vitro and in vivo. Notably, one Bnip3 mRNA comprised of exons 1 through exon 6 encoded a protein of 26kDa, while a second mRNA generated by the fusion of exon2 and exon4 encoded a truncated Bnip3 protein of 8.2kDa. Sequence analysis revealed the truncated isoform encodes a conserved C-terminus domain that exclusively targets Bnip3 to the endoplasmic reticulum and not mitochondrion. While the 26kDa Bnip3 induced mitochondrial perturbations and autophagy, the spliced variant suppressed Bnip3- induced mitochondrial defects and autophagy. Furthermore, genetic knock-down or mutations within the C-terminus of the spliced variant defective for ER targeting sensitized cardiac myocytes to mitochondrial ROS production and death. To our knowledge our data provide the first direct evidence for a novel survival mechanism whereby the metabolic status of the cell programs autophagy or apoptosis by preferentially targeting Bnip3 isoforms to mitochondria or ER during metabolic stress.
Frequency of genetic homologous recombination (HR) alterations in metastatic cutaneous melanoma.
Authors: Kevin Kim, Stanley P. L. Leong, Mark I. Singer, Brian M Parrett, John Moretto, David R. Minor, Elham Vosoughi, Sherri Z. Millis, Jeffrey S. Ross, Mohammed Kashani-Sabet
Journal: Journal of Clinical Oncology (2017)

e21033 Background: In various cancer types, cells with “BRCA-like” or HR mutations/alterations have been shown to be sensitive to PARP inhibitors in preclinical studies. In ovarian cancer, PARP inhibitors have shown improved response rate and progression-free survival in clinical studies. We investigated the frequency of HR mutations/alterations in melanoma. Methods: Comprehensive genomic profiling, (next-generation sequencing [NGS]) that included the entire coding sequence of 315 cancer-related genes was performed on formalin-fixed, paraffin-embedded tumor samples. The patient and tumor characteristics were obtained from electronic health records. Results: At our institution (CPMC), 59 patients underwent NGS analysis of melanoma specimens. Eighteen (30.5%) harbored a mutation in at least 1 of the HR genes in their tumor. The patient characteristics are: median age 69, male (83%), primary head and neck melanoma (61%), absence of ulceration at the primary site (86%) and mitotic rate &gt;1 mm/m2 (86%). Tumor mutation burden was high in 12 (67%) patients and low in 1 (6%) patient. The most commonly altered gene was ARID2 (11.9%), followed by ARID1A, FANCA, ATM, BRCA1 (3.4% each). Three patients had multiple HR alterations: one with mutations in ARID1A, BRCA1 and MRE11A, one with mutations in ARID2 and ATM, and one with mutations in ARID2 and CHEK2. Among the 18 patients with HR mutation(s), concurrent NF1, NRAS, BRAF (V600), and KIT mutations were found in 7 (39%), 6 (33%), 5 (28%) and 1 (6%) patients, respectively. A larger dataset analyzed by Foundation Medicine (FM) (n=1,986) showed a similar pattern: The most common mutations/alterations were ARID2, followed by ARID1A, ATM, ATRX, BRCA2, ATR, BRCA1, BRIP1 and FANCA (Table). Conclusions: HR mutations / alterations are frequently observed in metastatic melanoma. Melanomas with these alterations may represent a unique subset of patients who could potentially benefit from PARP inhibitors. [Table: see text]
Pathologic Outcomes of Laparoscopic vs Open Mesorectal Excision for Rectal Cancer
Authors: Thomas W. A. Koedam, H. Jaap Bonjer, Antonio M. Lacy
Journal: JAMA Surgery (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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
P2.04: Characteristics and Long Term Outcomes of Advanced Pleural Mesothelioma in Latin America (MeSO-CLICaP)
Authors: Oscar Arrieta, Andrés F. Cardona, Luis Corrales-Rodriguez, George Oblitas, Leonardo Rojas, Ludwing Bacon, Claudio Martin, Mauricio Cuello, Luis Mass, Beatriz Wills, Carlos Vargas, Hernán Carranza, Jorge Otero, María Angelina Pérez, Lisde González, Luis Chirinos, Rafael Rosell
Journal: Journal of Thoracic Oncology (2016)
Report of the Secretary of Agriculture 1940
Journal: JAMA (1941)

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
Abstract P210: Human Atrial Nonmyocytes Secrete Prohypertrophic, High-Molecular-Weight FGF-2, Which Is Upregulated by Angiotensin II via AT-1 and AT-2 Receptors, as Well as ERK and MMP Activation
Authors: Jon-Jon R Santiago, Leslie J McNaughton, Barbara E Nickel, Robert R Fandrich, Rakesh C Arora, Elissavet Kardami
Journal: Circulation Research (2011)

Background: Very little is known about the expression and role of fibroblast growth factor-2 (FGF-2) isoforms in the human heart. Using the rat model we have documented that high molecular weight Hi-FGF-2 rather than the commonly studied 18 kDa low molecular weight isoform Lo-FGF-2 is a potent inducer of cardiac hypertrophy in vitro and in vivo ; and that Hi-FGF-2 is expressed and secreted predominantly by cardiac non-myocytes (fibroblasts). We have now examined (i) the expression of Hi-FGF-2 in adult human heart (atria) and heart-derived non-myocytes (HDNM), and; (ii) signals regulating Hi-FGF-2 expression in HDNM. Methods/Results: Atrial tissue, obtained from patients undergoing cardiac surgery, (blinded study), was used to obtain extracts, and to isolate migratory cells (fibroblastic, HDNM). All tissue extracts (n=30) contained Hi- as well as Lo-FGF-2, assessed by Western blotting. Amounts of total FGF-2 varied from 1.5 - 25.5 pg per µg of extracted protein. Immunohistochemistry of paraffin-embedded atrial tissue sections and immunofluorescence of HDNM illustrated that human Hi-FGF-2 is localized mainly in the nucleus but is also present in cytoplasm. As was the case with rat- (ventricle and/or atria) derived fibroblasts, HDNM expressed predominantly Hi-FGF-2 (90% of total). The expression/secretion of Hi-FGF-2 by HDNM, as well as by human embryonic heart-derived fibroblasts, was significantly up-regulated by angiotensin II (Ang II). Simultaneous inhibition of both AT-1 as well as AT-2 receptors (by losartan and PD123319, respectively) was required to fully prevent Ang II-induced Hi-FGF-2 up-regulation. In addition, both inhibition of ERK activation (by U0126), or MMP activity (by MMP-2 Inhibitor I) fully prevented Ang II-induced up-regulation of human Hi-FGF-2. Conclusions: We have shown for the first time that human heart-derived fibroblastic cells express and secrete pro-hypertrophic Hi-FGF-2 in culture; and thus are likely to do so in vivo . Our data also suggest that the beneficial effects of drugs targeting Ang II signal transduction may be due, in part to their effects on Hi-FGF-2 accumulation.
Home-to-Home Time — Measuring What Matters to Patients and Payers
Authors: Michael L. Barnett, David C. Grabowski, Ateev Mehrotra
Journal: New England Journal of Medicine (2017)

Length of hospital stay is no longer an accurate reflection of the patient's experience of an episode of inpatient care. Time spent in a post-acute care facility must be added to time spent in the hospital to capture the true span of a hospitalization episode.
Abstract 132: The First Mouse Mutants of a Novel Epigenetic Modifier, Rearranged L-Myc Fusion, Display Defects in Heart Development
Authors: Lauren M Bourke, Sarah Harten, Vandhana Bharti, Harry Oey, Nadia Whitelaw, Emma Whitelaw
Journal: Circulation Research (2015)

Rearranged L-Myc Fusion, Rlf, was recently identified as a novel epigenetic modifier from a mouse N-ethyl-N-nitrosourea mutagenesis screen. The mice used in this study carry a multi-copy green fluorescent protein (GFP) transgene linked to an erythroid specific α-globin promoter that is sensitive to epigenetic silencing. Three independent mouse lines with mutations in Rlf were each found to have a decrease in GFP expression, suggesting Rlf acts an epigenetic modifier. Our study is the first to reveal a role for Rlf in epigenetics. Preliminary phenotyping has found loss of Rlf results in perinatal lethality. Late gestation homozygous null Rlf mutants were found to weigh significantly less than their heterozygous or wild type littermates. Histological analysis of mid gestation embryos has identified a potential heart defect in homozygous mutants. Rlf mutants display a thin compact layer, an overabundance of trabeculae and a fenestrated interventricular septum. The Rlf mutant phenotype is reminiscent of ventricular noncompaction defects observed in humans, such as left ventricular noncompaction cardiomyopathy. RNA-seq analysis of mid gestation Rlf wild type and null hearts, prior to the observation of a cardiac defect, was undertaken to determine which pathways may be regulated by Rlf in the heart. More genes were observed to be significantly down-regulated in Rlf mutant hearts compared to wild types. Pathway analysis of differentially expressed genes showed genes involved in cell-cell adhesion, cell signalling, glycosylation and the Notch pathway were dysregulated. These findings indicate that Rlf may play a critical role in cardiac development. Whole genome bisulphite sequencing of different embryonic tissue/stages has shown loss of Rlf results in an increase in methylation at a large number of distinct loci across the genome. Many of which were found to overlap sites reported to be putative regulatory elements, and histone marks associated with active or poised regulatory elements in the heart. Our data suggest Rlf plays a key role in regulating gene expression pathways during heart development. These are the first mouse mutants available to study how Rlf functions as an epigenetic modifier and the phenotypic consequences of Rlf inactivation.
Adjuvant capesitabine in combination with docetaxel (T), epirubicin (E), and cyclophosphamide (C) in the treatment of early breast cancer (BC): 10-year survival results from the randomized FinXX trial.
Authors: Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Riikka Huovinen, Arja Jukkola-Vuorinen, Minna Tanner, Riitta Kokko, Päivi Auvinen, Outi Lahdenperä, Kenneth Villman, Paul Nyandoto, Greger Nilsson, Marja Murashev, Paula Poikonen-Saksela, Petri Bono, Vesa Kataja, Henrik Lindman
Journal: Journal of Clinical Oncology (2016)

1001 Background: The role of capecitabine (X) in the adjuvant treatment of BC is not established, and few long-term survival data are available. In an analysis of the Finland Capecitabine Trial (FinXX), based on a median FU of 59 months (JCO 2012;30:11-8), patients (pts) treated with X-containing adjuvant chemotherapy did not have significantly longer recurrence-free survival (RFS) as compared with the control group (HR 0.79, 95% CI 0.60-1.04, P= .087), but in an exploratory analysis a significant benefit emerged in the subset with triple negative BC (TNBC; ER-, PgR-, and HER2-; HR 0.48, 95% CI 0.26-0.88). Methods: Eligible pts had either axillary node-positive or high-risk node-negative BC (tumor >20 mm and PgR-). Pts were randomly assigned centrally either to 3 3-wkly cycles of docetaxel (T, 80 mg/m2) followed by 3 3-wkly cycles of C600 E75 F600 (T-CEF) or to 3 3-wkly cycles of TX (T60 , X1800 for dd. 1-15) followed by 3 3-wkly cycles of C600 E75 X1800 (TX-CEX). A total of 1,500 patients were entered to FinXX from 20 sites in Finland or Sweden between Jan 27, 2004, and May 29, 2007 (T-CEF, 747; TX-CEX, 753). Five pts withdrew consent. The data collection cut-off date for this preplanned analysis was Dec 31, 2015. Results: During a median FU of 10.3 yrs 142 RFS events occurred in the TX-CEX group and 161 in the T-CEF group (HR 0.85, 95% CI 0.68-1.07; P= .168), and 120 and 141 pts died, respectively (HR 0.83, 95% CI 0.65-1.06, P= .132; 92 vs. 113 pts died from BC). Pts with TNBC (n=202) had more favorable RFS (HR 0.43, 0.24-0.79: P= .007) and survival (HR 0.55, 0.31-0.96, P= .037) when treated with TX-CEX compared to T-CEF; no significant benefit was found in other ER/PgR/HER2-defined subgroups. The numbers of contralateral BCs (T-CEF, 24; TX-CEX, 28) and other second cancers (T-CEF, 41; TX-CEX, 35) were similar. AML was diagnosed in 4 pts. Conclusions: Integration of X to the taxane-anthracycline backbone did not prolong RFS or survival. The survival benefit in favor of TX-CEX had persisted in the TNBC subgroup, but this finding should be viewed with caution due to the small subgroup size and the exploratory nature of the analysis. Clinical trial information: NCT00114816.
Foley catheterisation versus oral misoprostol for induction of labour in hypertensive women in India (INFORM): a multicentre, open-label, randomised controlled trial
Authors: Shuchita Mundle, Hillary Bracken, Vaishali Khedikar, Jayashree Mulik, Brian Faragher, Thomas Easterling, Simon Leigh, Paul Granby, Alan Haycox, Mark A Turner, Zarko Alfirevic, Beverly Winikoff, Andrew D Weeks
Journal: The Lancet (2017)
Challenges affecting training in occupational medicine
Authors: Ian Aston
Journal: BMJ (2017)

In response to Nicholson,1 2 I provide details of the challenges affecting occupational medicine training.

Specialist training is expensive; the majority takes place in the NHS, with a small proportion occurring outside. Occupational medicine training currently takes place in commercial organisations, Defence Medical Services, and the NHS. All training positions produce specialists with the same core set of skills and knowledge needed to be an …
A First for Giant Cell Arteritis
Authors: Rebecca Voelker
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Medical leaders celebrate the ascent of woman
Authors: Anne Gulland
Journal: BMJ (2017)

Richard H Smith

The BMJ ’s editor in chief, Fiona Godlee, gathered together an unprecedented number of female medical leaders earlier this week in celebration of the fact that eight medical royal colleges are now led by women.

The senior women are (left to right) Sue Bailey, chair of the Academy of Medical Royal Colleges; Kate Lovett, dean of the Royal College of Psychiatrists; Carrie MacEwen, chair elect of the Academy of Medical Royal Colleges and former president of the Royal College of Ophthalmologists; Nicola Strickland, president of the Royal College of Radiologists; Jane Dacre, president of the Royal College of Physicians; …
Assessment of Head Collision Events During the 2014 FIFA World Cup Tournament
Authors: Michael D. Cusimano, Julia Casey, Ruiwei Jing, Anamika Mishra, Michael Solarski, Kristina Techar, Shudong Zhang
Journal: JAMA (2017)

The consensus statement from the 2012 and 2016 International Conference on Concussion in Sport, adopted by Federation Internationale de Football Association (FIFA), indicates that players showing any feature of concussion should be immediately withdrawn from play and assessed by sideline health care personnel. 1Such recommendations and their enforcement may influence officiating, coaching, and play of millions of young players.The incidence, characteristics, and assessment of head collision events incurred during the 2014 FIFA World Cup were studied to evaluate compliance with the consensus statement.Methods | Four trained reviewers identified head collisions through observation of video footage of all 64 matches of the 2014 FIFA World Cup with complete agreement.Video analysis has been shown to be reliable and valid for evaluating head injury in sport. 2,3Any event involving head contact in which a player did not continue playing immediately afterward was defined as a head collision event.Details regarding whether and by whom the players were assessed and the outcome of the assessment were collected on standardized forms.Observable effects of the collision on the player (slow to get up, disoriented, obvious disequilibrium, unconsciousness, seizure-like movements, head clutching) were documented as potential signs of concussion. 4 Although no accepted cutoff for the number of signs that might indicate a concussion exists, we analyzed players with 2 or more signs.