tbuckley/cabot-search huggingface dataset:
De Subitaneis Mortibus
Authors: THOMAS N. JAMES, PAUL PUECH
Journal: Circulation (1974)

A twenty-two-year-old woman with type A Wolff-Parkinson-White syndrome had a long history of paroxysmal tachycardia and died of a stroke. Until the last two years of life the tachycardias responded to medical treatment, but thereafter they could only be terminated with electrical shock. During one such shock her sinus rhythm disappeared and for over a year she had only atrioventricular (A-V) junctional rhythm although paroxysms of tachycardia persisted. Special studies of the heart after death included serial sections of the entire A-V ring. Nonspecific degenerative disease of both atria included the internodal pathways. Both the sinus node artery and the A-V node artery were narrowed by mural thickening. The sinus node was generally intact but virtually all atrionodal connections were degenerated. The A-V node was similarly detached from its atrial connections but was in direct continuity with the His bundle. The right bundle branch was interrupted at its origin. Within the central fibrous body there were numerous lacunae and one long cleft extending from atrial to ventricular septum parallel to the A-V node. Although the cleft contained cells, there was no direct A-V connection. At the right lateral A-V junction a long thin cylinder of Purkinje cells lay parallel to the tricuspid valve ring and connected to the atrium but not the ventricle. Beneath the left atrial appendage there was a fault in the mitral annulus through which there was a direct A-V connection. Most of this connection was composed of P cells and thus resembled the patient's own sinus node. The atrial connection was to Bachmann's bundle, which was extensively degenerated. The ventricular connection was to ordinary working myocardium midway between epicardium and endocardium. Some functional implications of these anatomical findings are discussed.
Abstract 13907: Transplantation of Brown Adipose Tissue Inhibits Atherosclerosis in Apoe Deficient Mice via Activation of Fgf-21/adiponectin Axis
Authors: Masakazu Kikai, Kensuke Terada, Keita Yamamoto, Shinichiro Motoyama, Naotoshi Wada, Noriyuki Wakana, Hiroyuki Yamada
Journal: Circulation (2015)

[Background] Brown adipose tissue (BAT), a key nonshivering thermogenic tissue, has been recently identified as an endocrine organ to regulate metabolic homeostasis. Experimental BAT transplantation has been reported to improve glucose tolerance and insulin sensitivity; however, the beneficial effect of BAT transplantation on atherogenesis remains undefined. [Method and Result] Interscapular BAT was harvested from 12-week-old mice (C57BL/6) and transplanted into the visceral cavity in 12-week-old recipient apoE-/- mice. After 3 months of high-cholesterol diet, atherosclerosis development was evaluated. BAT transplanted mice showed a modest, but significant, decrease in body weight and increase in mean blood pressure compared with sham control mice (4.7%, 12%, respectively, P&lt;0.05). Food intake and lipid profile except for triglyceride level did not differ between the 2 groups. Oil-red-O staining of entire aorta showed a significant decrease in atherosclerotic lesion area in BAT transplanted mice by 19.7 % compared with sham control mice (P&lt;0.05). Histomorphological analysis of transplanted BAT graft showed a similar appearance as white adipose tissue rather than brown adipose tissue. Consistently, mRNA expression levels of brown adipose tissue-related genes such as UCP-1 and PGC-1α were markedly decreased compared with those in endogenous BAT. Interestingly, transplanted BAT graft showed a significantly increased mRNA expression level of fibroblast growth factor-21 (FGF-21), while its expression level in liver was comparable between the 2 groups. The serum concentration of FGF-21 was also increased in BAT transplanted mice (49%, P&lt;0.05), accompanied by the higher concentration of circulating adiponectin (36%, P&lt;0.05). Serum concentration of adiponectin was negatively correlated with the percentage of plaque area (r=-0.44, P&lt;0.05), suggesting that transplanted BAT graft exerts atheroprotective effect via activation of FGF-21/adiponectin axis. [Conclusion] Our findings demonstrated for the first time that BAT transplantation reduces atherosclerosis development, and phenotypic modulation of BAT graft could be a potential therapeutic strategy for preventing atherosclerotic diseases.
Secretory RAB GTPase 3C modulates IL6-STAT3 pathway to promote colon cancer metastasis and is associated with poor prognosis
Authors: Yu-Chan Chang, Chia-Yi Su, Ming-Huang Chen, Wei-Shone Chen, Chi-Long Chen, Michael Hsiao
Journal: Molecular Cancer (2017)

RAB GTPases are important in the regulation of membrane trafficking and cell movement. Recently, exocytic RABs have received increasing attention in cancer research. However, the functional roles of exocytic RABs in colorectal carcinogenesis remain to be elucidated. Immunohistochemistry analysis of a microarray containing 215 colorectal adenocarcinoma tissues was used to identify the association between exocytic RABs and patient prognosis. Complementary functional RAB3C overexpression and knockdown experiments were performed. The molecular mechanism of RAB3C in inducing colon cancer cell metastasis was determined. High RAB3C expression in patients was found to be significantly associated with advanced pathological stage, distant metastasis and poor prognosis. Multivariate analyses showed that high RAB3C expression was an independent prognostic marker in overall (P = 0.001) and disease-free survival (P < 0.001). Furthermore, our experimental results showed an increase in the migration and invasion ability of RAB3C-overexpressing colon cancer cells and increased metastatic nodules in a mouse metastasis model. The effect of RAB3C-overexpressing cell-conditioned medium was found to significantly promote the migration ability of parental colon cancer cells, thus suggesting that the promotion of migration is exocytosis dependent. Upregulation of other exocytic RABs was also seen in RAB3C-overexpressing cells. Through microarray and proteomics analyses, increased production of multiple cytokines was observed in RAB3C-overexpressing cell lines, and the IL-6 pathway was the top pathway whose members exhibited gene expression changes after RAB3C overexpression, according to Ingenuity Pathway Analysis. Blocking IL-6 with IL-6 antibody treatment or IL-6 knockdown significantly inhibited the migration potential of RAB3C-overexpressing colon cancer cells. In addition, IL-6 was found to induce STAT3 phosphorylation in RAB3C-overexpressing colon cancer cells, thus promoting migration. Ruxolitinib, a JAK2 inhibitor, was found to significantly inhibit RAB3C-induced colon cancer cell migration. Our study revealed that RAB3C overexpression promotes tumor metastasis and is associated with poor prognosis in colorectal cancer, through modulating the ability of cancer cells to release IL-6 through exocytosis and activate the JAK2-STAT3 signaling pathway. These results further suggest that inhibition of STAT3 phosphorylation in the RAB3C-IL-6-STAT3 axis by using Ruxolitinib may be a new therapeutic strategy to combat metastatic colon cancers.
18F-FDG PET/CT of Brown Adipose Tissue Hyperactivation Associated With Pregnancy and Paraganglioma
Authors: Anna Margherita Maffione, Lucia Rampin, Sotirios Chondrogiannis, Maria Cristina Marzola, Patrick M. Colletti, Domenico Rubello
Journal: Clinical Nuclear Medicine (2017)

Abstract This 32-year-old woman presented with pregnancy-related arterial hypertension unresponsive to antihypertensive therapy. During cesarean delivery, a lobulated retroperitoneal mass was discovered. 18 F-FDG PET/CT performed 18 days postpartum demonstrated the hyperactive retroperitoneal mass and extensive hyperactivated brown adipose tissue. The mass was surgically removed, revealing a para-aortic multicentric paraganglioma. After surgery, blood pressure normalized, and serum chromogranin A and urinary metanephrines normalized. Brown adipose tissue hypermetabolism disappeared on follow-up FDG PET. Her initial FDG PET demonstrated brown adipose tissue hyperactivation, which may have been caused by the combination of hormonal changes in pregnancy and the paraganglioma.
Case 70-1963
Authors: Gerald S. Foster, Edgar B. Taft
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A forty-six-year-old woman entered the hospital because of hematemesis.The patient had consumed alcohol excessively for many years. Two years previously anorexia, jaundice and abdominal swelling developed, and the presence of liver disease and diabetes mellitus was established; insulin therapy was begun. Four months before admission hematemesis occurred, and five transfusions of blood were given. On the evening before entry she again vomited blood. There was no past history of hepatitis or of industrial exposure to toxic chemicals.Physical examination revealed an apprehensive, jaundiced woman who was vomiting large quantities of blood. Numerous spider . . .
Abstract 66: Discovery of a Novel Pharmaceutical Class as Potential Heart Failure Treatment
Authors: Tromondae K Feaster, Jonathan E Hempel, Charles H Williams, Audrey Y Frist, Hyun S Hwang, Bjorn C Knollmann, Charles C Hong
Journal: Circulation Research (2015)

Utilizing an unbiased in vivo phenotypic chemical screening platform in zebrafish embryos, our laboratory has identified a number of novel compounds with high selectivity for a wide range of cellular targets, including kinases (CK2a, DRAK2, DYRK2 and bone morphogenetic protein receptors), GPCRs (lysophosphatidic acid receptor 1, and extracellular proton sensor), p300 histone acetyltransferase, and phosphodiesterase-4 (PDE4). While the compounds we discovered have therapeutic implications for a wide range of diseases, our translational work has focused on addressing the cardiovascular diseases. Heart failure (HF) is a leading cause of disability and mortality in US, affecting about 6 million Americans, and the incidence of heart failure is anticipated to increase substantially in the coming decades. Yet, current HF pharmaceuticals are palliative, and the outlook for HF drug pipeline is uncertain. Within this backdrop, we recently discovered eggmanone, an extraordinarily selective PDE4 inhibitor which has no known off-target. An usual feature of eggmanone is that it increases cAMP levels specifically in distinct cellular microdomains, without raising the total cellular cAMP content. In isolated mouse cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), eggmanone increases cardiac contractility by targeting a discrete myocyte microdomain without causing significant changes in myocyte calcium cycling. Importantly, eggmanone enhances systolic function in mice with failing hearts without increasing the heart rate. These results raise the exciting possibility that a microdomain-specific PDE4 inhibitor like eggmanone may be useful as an inotropic therapy for HF which avoids the pitfalls of traditional PDE inhibitors, whose utility has been limited by proarrhythmia, tachyphylaxis and cardiotoxicity.
がん:幹細胞性に関連するZEB1‐MSRB3軸は細胞の適応性と乳がんゲノムの安定性を支配する
Authors: Morel Anne‐Pierre, Pommier Roxane M, Ruiz Emmanuelle, Devouassoux‐Shisheboran Mojgan, Chassot Christelle, Pinatel Christiane, Fauvet Frederique, Saintigny Pierre, Moyret‐Lalle Caroline, Lachuer Joeel, Wierinckx Anne, Cox David G, Ansieau Stephane, Caramel Julie, Vigneron Arnaud M, Tissier Agnes, Puisieux Alain, Ginestier Christophe, Cabaud Olivier, Wicinski Julien, Finetti Pascal, Bertucci Francois, Birnbaum Daniel, Charafe‐Jauffret Emmanuelle, Combaret Valerie, Wang Qing, Thomas Emilie, Despras Emmanuelle, Jauffret Jean‐Luc, Guitton Jerome, Radosevic‐Robin Nina, Penault‐Llorca Frederique, Hollande Frederic
Journal: Nature Medicine (2017)
Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690
Authors: Mohammed Kashani-Sabet, Mehdi Nosrati, James R. Miller, Richard W. Sagebiel, Stanley P.L. Leong, Andrew Lesniak, Schuyler Tong, Sandra J. Lee, John M. Kirkwood
Journal: Clinical Cancer Research (2017)

Purpose: To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or low-dose IFNα-2b versus observation.Experimental Design: Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides. The prognostic impact of each marker was first assessed by recording its expression value relative to the median. A multimarker index was then developed to combine marker expression levels by counting for each patient the number of markers with high expression. The impact of the multimarker index on relapse-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier analysis, and both univariate and multivariate Cox regression analyses.Results: By Kaplan-Meier analysis, high multimarker expression scores were significantly predictive of RFS (P < 0.001) and OS (P < 0.001). Stepwise multivariate Cox regression analysis with backward elimination that included routine clinical and histologic prognostic factors revealed high multimarker expression scores and tumor thickness as the only factors significantly and independently predicting RFS and OS. Stepwise multivariate Cox regression analyses that also included treatment type and number of positive lymph nodes generated identical results for both RFS and OS. In the molecularly defined low-risk subgroup, patients treated with high-dose IFN had a significantly improved RFS compared with patients in the other two subgroups (P < 0.05).Conclusions: These results validate the independent impact of combined expression levels of SPP1, RGS1, and NCOA3 on survival of melanoma in a prospectively collected cohort. Clin Cancer Res; 23(22); 6888-92. ©2017 AACR.
Comparing Public Safety Outcomes for Traditional Probation vs Specialty Mental Health Probation
Authors: Jennifer L. Skeem, Sarah Manchak, Lina Montoya
Journal: JAMA Psychiatry (2017)

<h3>Importance</h3> Probation is a cornerstone of efforts to reduce mass incarceration. Although it is understudied, specialty probation could improve outcomes for the overrepresented group of people with mental illness. <h3>Objective</h3> To test whether specialty probation yields better public safety outcomes than traditional probation. <h3>Design, Setting, and Participants</h3> A longitudinal observational study with group matching on age, sex, race/ethnicity, probation time, and offense at 2 urban agencies that exemplify specialty and traditional probation. Enrollment began October 19, 2005; follow-up data were complete January 26, 2013. Participants were 359 diverse probationers with serious mental health problems and functional impairment. Probationers and officers were assessed 3 times (for probationers, 6-month retention, 315 of 359 [88%]; 12-month retention 304 of 359 [85%]) and follow-up records were obtained. Machine learning algorithms were combined with a targeted maximum likelihood estimation, a double robust estimator that accounts for associations between confounders and both treatment assignment and outcomes. Statistical analysis was conducted from January 1, 2016 to May 5, 2017. <h3>Interventions</h3> Specialty probationers were assigned to small, homogeneous caseloads supervised by experts. Prior data indicate that specialty officers had better relationships with probationers, participated more in probationers' treatment, and relied more on positive compliance strategies than traditional officers. <h3>Main Outcomes and Measures</h3> Violence during 1 year, determined by probationer report, officer report, and records, and rearrest during a period of 2 to 5 years, according to Federal Bureau of Investigation records. <h3>Results</h3> Participants were 183 specialty (73.8% of 248 eligible) and 176 traditional (56.6% of 311 eligible) probationers (205 men and 154 women; mean [SD] age, 36.9 [10.6]). Although specialty probation had no significant effect on violence (odds ratio, 0.97; 95% CI, 0.69-1.36), the odds of rearrest were 2.68 times higher for traditional probationers than for specialty probationers (95% CI, 1.86-3.84;<i>P</i> &lt; .001). At 2 years, estimated probabilities of rearrest were 28.6% for specialty probationers and 51.8% for traditional probationers. Survival analyses indicate that arrest effects endured up to 5 years. <h3>Conclusions and Relevance</h3> Although it did not specifically reduce violence, well-implemented specialty probation appears to be effective in reducing general recidivism. Reform efforts for people with mental illness could leverage probation—a ubiquitous and revitalized node of the justice system.
Aspirin and Gastrointestinal Bleeding
Journal: JAMA (1969)

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SKI AND SNOWBOARD SCHOOL PROGRAMS: INCIDENCE OF GRADE-SPECIFIC INJURY
Authors: Maya Djerboua, R Sran, T Mitra, K Russell, K White, C Goulet, CA Emery, BE Hagel
Journal: British Journal of Sports Medicine (2017)

Background Participating in school sanctioned skiing and snowboarding programs is a great way to encourage physical activity in youth. However, there is little evidence on the rates of ski and snowboard injuries in school programs. This information is important to inform guidelines on appropriate activities for school physical education programs. Objective To evaluate incidence of grade group-specific ski and snowboard-related injuries. Design Historical cohort study. Setting Ski and snowboard school programs hosted at a ski area in Southern Alberta, Canada. Participants Students partaking in skiing/snowboarding during the 2013–2014 season at a ski area in Southern Alberta (N=16260 visits). Assessment of Risk Factors Risk factors observed include grade (1–3, 4–6, 7–12), ability (self-rated skill level), sex, activity and socioeconomic status (SES). Main Outcome Measurements Injury rates and injury severity. Injury information was extracted from Accident Report Forms completed by the ski patrol. Severe injuries were defined as patient final destination listed as hospital. Rate denominator data were obtained from school enrolment forms. Results Forty of 107 (24%) injuries reported to the ski patrol were severe. Adolescents (grade 7–12) were found to have a higher crude rate of injury (91/10,000 visits) than children (grades 1–3: 25/10,000 visits; grades 4–6: 25/10,000 visits). When adjusted for other observed risk factors (sex, activity, ability and SES) no significant differences were found for rate of injury between the three grade groups (1–3, 4–6 and 7–12). No severe injuries were observed in the grade 1–3 group. Conclusions Results indicate that participants in the grade 1–3 group had the lowest crude and adjusted rate of injury and did not sustain any severe injuries. Respectively, the grade 7–12 group had the highest rate of crude injury, both overall and severe. These results will help inform ski and snowboard programs and safety guidelines for physical activity programs in schools.
HAMSTRING INJURIES IN MAJOR AND MINOR LEAGUE BASEBALL: ARE THEY PREVENTABLE?
Authors: Holly Silvers-Granelli, James Zachazewski, Bernard Li, Stephanie Insler, Bert Mandelbaum, Christopher Ahmad, Lynn Snyder-Mackler
Journal: British Journal of Sports Medicine (2017)

Background Hamstring injuries are the leading cause of time loss injury in professional baseball, accounting for 6% of all injuries. Objective To test the efficacy of a hamstring injury prevention program (HIP) designed to address the incidence of acute and chronic hamstring injuries and re-injuries that occur in professional baseball. Design Prospective cluster cohort study. Setting Major (MAJ) and Minor (MIN) League Professional Baseball (USA). Patients (Participants) One Major and Minor League organization served as the intervention (INT) team; which encompassed Rookie, Fall Ball, Class A, AA, AAA and MAJ rosters (6 total teams). A total of 213 athletes were consented: MIN: N=173 and MAJ: N=40 . Intervention Athletes completed a questionnaire detailing their HSI history. The HIP was disseminated to the medical staff, which was instructed on program implementation. Main Outcome Measurements The data was analysed for program compliance and hamstring injury (HSI) rates compared to the control group (CON). Results There were 2 HSI's in the INT vs. 79 in the CON in the MAJ (IR: 0.025 INT vs 0.068 CON, p&lt;0.05); constituting a 25% reduction in HSI. There were 7 HSI's in the INT vs. 297 in the CON (IR: 0.039 INT vs. 0.065 CON, p&lt;0.05), constituting a 40% reduction in MIN HSI. There was a significant reduction in time loss due to injury. There were 9 INT vs. 25.9 CON days lost, resulting in a 65.3% reduction in time loss in the MAJ (p&lt;0.05). The Minor League reported 11.63 INT vs. 21.3 CON days lost, resulting in a 45.3% reduction in time loss (p&lt;0.05). Conclusions The reduction in HSI is consistent with existing literature with respect to the efficacy of an HIP to reduce HSI in athletes. This study is continuing for an additional competitive season (three year prospective).