tbuckley/cabot-search huggingface dataset:
Abstract 18023: In vivo Validation of Area Change Ratio to Estimate Myofiber Strain in the Heart
Authors: Hiroshi Ashikaga, Jeffrey H Omens
Journal: Circulation (2011)

Background: Area change ratio (AC) using the 3-D speckle tracking echocardiography is emerging as a mechanical index that approximates myofiber shortening by incorporating both circumferential and longitudinal shortening. However, AC has not been validated against myofiber strain in the heart in vivo , and its physiological significance remains unclear. Methods and Results: We studied the time course of AC in the anterior mid-left ventricular wall of normal canine heart in vivo (n=14) during atrial pacing over the entire cardiac cycle using transmurally implanted markers and biplane cineradiography (8 msec/frame). AC was calculated as the myocardial area change relative to the elemental material area on the circumferential- longitudinal plane at the reference configuration (= end diastole). AC was compared with myofiber strain that was determined from transmural fiber orientations directly measured in the heart tissue. The time course of both AC and myofiber strain was determined in the subepicardial, midwall, and subendocardial layers. The time course of AC and myofiber strain was significantly different (P&lt;0.05), and the difference was more pronounced towards the endocardium (Figure). AC consistently overestimated myofiber shortening. The timing of the peak AC was significantly delayed compared to that of the peak myofiber shortening (P&lt;0.05). Conclusions: AC is significantly different from myofiber strain both in magnitude and timing in vivo. AC overestimates myofiber shortening, and the overestimation is worse towards the endocardial layers, likely resulting from crossfiber deformation that is inherently included in AC. The significant delay in estimating the peak myofiber shortening may hinder accurate optimization and/or responder identification for cardiac resynchronization therapy.
Self-management of Chronic Disease
Authors: Donnell D. Etzwiler
Journal: JAMA (2003)

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Classification and diagnostic criteria in Sjögren’s syndrome: a long-standing and still open controversy
Authors: Claudio Vitali, Nicoletta Del Papa
Journal: Annals of the Rheumatic Diseases (2017)

Most rheumatic diseases are multisystem disorders that are heterogeneous in their presentation, course and outcome. These conditions still lack a single clinical, laboratory, pathological or radiological feature that could serve as a ‘gold standard’ in support of diagnosis and/or classification. Thus, the development of criteria for use in clinical care and research studies has been an important challenge in these disorders.1

From the theoretical and methodological point of view, classification and diagnostic criteria are quite different. Classification criteria are standardised tools that are aimed at selecting well-defined and homogenous groups of patients for research and at guaranteeing comparability across studies. They are not designed to be used for the clinical diagnosis in individual patients and may be defective in capturing some cases with a less common clinical presentation or course.2

Diagnostic criteria are generally less stringent and usually include a wider variety of disease features. Their aim is to accurately identify as many people with that condition as possible.1 Given the complexity of systemic rheumatic disorders, the development of diagnostic criteria in these diseases is certainly difficult. Therefore, optimal diagnostic criteria have not been defined for most of the rheumatic diseases and the diagnosis, given the suspicion of one of these disorders, is commonly based on a decision-making process by physicians who have to evaluate a complex combination of symptoms, signs, diagnostic tests and rule out other confounding or similar diseases.

As a consequence of these theoretical assumptions, the diagnostic criteria are commonly characterised by high sensitivity and negative predictive value, whereas the classification criteria classically possess high specificity and positive predictive value to minimise the risk of classifying false positive patients as having the …
Trisomy 10 in adult pre-B-cell leukemia
Authors: Atsuo Okamura, Akinori Yamaguchi, Shinichi Shimizu, Seizo Kadowaki, Kazuo Chihara, Toshimitsu Matsui, Takao Fujimoto, Kaori Kanki, Kazuyoshi Fujio
Journal: American Journal of Hematology (1999)
HTLVIseronegative, genomepositive adult Tcell leukemia: Report of a case
Authors: Tetsuya Kubota, Takayuki Ikezoe, Eiji Hakoda, Takashi Sawada, Hirokuni Taguchi, Isao Miyoshi
Journal: American Journal of Hematology (1996)

An HTLV-I-seronegative case of adult T-cell leukemia (ATL) carrying the HTLV-I genome is reported. Screening serological tests were negative and Western blot analysis revealed only a faint band for HTLV-I p24. Polymerase chain reaction (PCR) disclosed the presence of HTLV-I gag, pol, env, pX, and LTR sequences in the lymph node and peripheral blood. Southern blot analysis revealed a monoclonal integration of HTLV-I in the lymph node and peripheral blood. The tumor cells expressed viral antigens after short-term culture. The clinical course was consistent with ATL in that the patient exhibited hypercalcemia and abnormal lymphocytosis as well as hepatosplenomegaly and lymphadenopathy. We recommend that PCR analysis for HTLV-I be performed even in seronegative cases when ATL is clinically suspected. © 1996 Wiley-Liss, Inc.
Referral to a cancer center (CC), medical oncologist (MO), and use of systemic treatment (ST) in stage IV non-small cell lung cancer (NSCLC) patients: Comparison of years 2003-2006 and 2010 cohorts in a single Canadian institution.
Authors: Jenny J. Ko, Mingfu Liu, Shannon Otsuka, William Boland, Kate Skolnik, James Macklow, Donald Morris, D. Gwyn Bebb
Journal: Journal of Clinical Oncology (2014)

e19056 Background: Despite evidence for survival improvement, only about 25% of stage IV NSCLC patients receive ST. Factors affecting referral to CC, MO, and use of ST are largely unknown. Methods: Stage IV NSCLC patients in Southern Alberta were identified from the provincial cancer registry. Baseline characteristics, referral to CC and MO, and reasons for referral/treatment decisions, were collected from electronic charts. Multivariate analyses were performed to compare median overall survival (mOS), referral and treatment patterns in two cohorts. Results: 925 patients from 2003-2006 and 261 from 2010 were included (n=1186): median age 68.2 yrs (range 32-96). In 2003-2006, more patients were referred to CC (94.3 vs. 82.8%, p<0.0001), but less received traditional chemotherapy (TC) than in 2010 (22.2 vs. 43.1%, p<0.0001). Referral to CC/MO and use of TC correlated with survival (p<0.0001): mOS 16.0 months in those receiving TC vs. 3.7 months in those not referred to CC. Patients who received TC were younger than those who were not referred to CC (p<0.0001). Reasons for no referral to MO, including rapid decline (30.5%), patient wish (16.4%), poor ECOG (12.5%), and a decision to manage symptoms only (10.6%), were similar to those for foregoing TC. EGFR status correlated significantly with referral and TC only in 2010 cohort. Metastasis pattern (M1a or M1b) and pulmonary embolism correlated significantly with referral and TC only in 2003-2006 cohort. Distance to CC did not impact referral or TC (p=0.56). Among patients referred to MO, 88 (17.2%) and 26 (23.2%) patients received biologics in the 2003-2006 and 2010 cohorts, respectively, with mOS of 22.5 months in 2003-2006 and 15.2 months in 2010 (Log-rank p=0.13). Conclusions: Our experience confirms that ST improves mOS yet has low uptake in stage IV NSCLC. Most factors limiting ST uptake appear non-modifiable. While a more rapid referral process may provide patients access to ST before deterioration, greater availability of well tolerated drugs for all NSCLC patients will likely be the most important factor in increasing ST uptake in this population.
Metformin Suppresses the GRP78-Dependent Delivery of Aggresomes to Autophagosomes to Enhance the Anti-Myeloma Benefit of Proteasome Inhibition
Authors: Sajjeev Jagannathan, Nikhil Vad, Mohamed A.Y. Abdel Malek, Ehsan Malek, James J. Driscoll
Journal: Blood (2014)
Intestinal fungi contribute to development of alcoholic liver disease
Authors: An-Ming Yang, Tatsuo Inamine, Katrin Hochrath, Peng Chen, Lirui Wang, Cristina Llorente, Sena Bluemel, Phillipp Hartmann, Jun Xu, Yukinori Koyama, Tatiana Kisseleva, Manolito G. Torralba, Kelvin Moncera, Karen Beeri, Chien-Sheng Chen, Kim Freese, Claus Hellerbrand, Serene M.L. Lee, Hal M. Hoffman, Wajahat Z. Mehal, Guadalupe Garcia-Tsao, Ece A. Mutlu, Ali Keshavarzian, Gordon D. Brown, Samuel B. Ho, Ramon Bataller, Peter Stärkel, Derrick E. Fouts, Bernd Schnabl
Journal: Journal of Clinical Investigation (2017)

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.
Patterns of Relapse in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Who Achieve Complete Molecular Response with Chemotherapy Plus a Tyrosine Kinase Inhibitor
Authors: Nicholas J. Short, Farhad Ravandi, Jorge E. Cortes, Rebecca Garris, Susan M. O'Brien, Keyur P. Patel, Jeffrey L. Jorgensen, Joseph D Khoury, Guillermo Garcia-Manero, Deborah A Thomas, Hagop M. Kantarjian, Elias J. Jabbour
Journal: Blood (2016)
Identification of a Poor-Prognosis BRAF-Mutant Like Populationof Patients With Colon Cancer. Journal of Clinical Oncology,30(12):12BB-1295, 2012
Authors: Vlad Popovici, Eva Budinská, Sabine Tejpar, Scott Weinrich, Heather Estrella, Graeme Hodgson, Eric Van Cutsem, Tao Xie, Fred Bosman, Arnaud Roth, Mauro Delorenzi
Journal: Journal of Clinical Oncology (2012)
More than just climate: Income inequality and sex ratio are better predictors of cross-cultural variations in aggression
Authors: Jaimie Arona Krems, Michael E. W. Varnum
Journal: Behavioral and Brain Sciences (2017)

Abstract Van Lange et al. argue that variations in climate explain cross-societal variations in violence. We suggest that any approach seeking to understand cross-cultural variation in human behavior via an ecological framework must consider a wider array of ecological variables, and we find that income inequality and sex ratio are better predictors than climate of cross-societal variations in violence.
Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer
Authors: Hengyu Lu, Nicole Villafane, Turgut Dogruluk, Caitlin L. Grzeskowiak, Kathleen Kong, Yiu Huen Tsang, Oksana Zagorodna, Angeliki Pantazi, Lixing Yang, Nicholas J. Neill, Young Won Kim, Chad J. Creighton, Roel G. Verhaak, Gordon B. Mills, Peter J. Park, Raju Kucherlapati, Kenneth L. Scott
Journal: Cancer Research (2017)

Abstract Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in The Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2, and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors. Our fusion construction strategy also enabled domain-function studies of BRAF fusion genes. Our results confirmed other reports that the transforming activity of BRAF fusions results from truncation-mediated loss of inhibitory domains within the N-terminus of the BRAF protein. BRAF mutations residing within this inhibitory region may provide a means for BRAF activation in cancer, therefore we leveraged the modular design of our fusion gene construction methodology to screen N-terminal domain mutations discovered in tumors that are wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic mutation, F247L, whose expression robustly activated the MAPK pathway and sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools will facilitate rapid fusion gene construction for subsequent functional characterization and translation into personalized treatment strategies. Cancer Res; 77(13); 3502–12. ©2017 AACR.
Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren’s syndrome
Authors: Shinya Tasaki, Katsuya Suzuki, Ayumi Nishikawa, Yoshiaki Kassai, Maiko Takiguchi, Rina Kurisu, Yuumi Okuzono, Takahiro Miyazaki, Masaru Takeshita, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Kazuhiro Ikeura, Kazuyuki Tsunoda, Rimpei Morita, Akihiko Yoshimura, Hiroyoshi Toyoshiba, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2017)

Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology.We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation.Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 -T cells- were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS.Our multiomics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Diabetic Ketoacidosis in Infants, Children, and Adolescents
Authors: Joseph Wolfsdorf, Nicole Glaser, Mark A. Sperling
Journal: Diabetes Care (2006)

The adage “A child is not a miniature adult” is most appropriate when considering diabetic ketoacidosis (DKA). The fundamental pathophysiology of this potentially life-threatening complication is the same as in adults. However, the child differs from the adult in a number of characteristics.

1 ) The younger the child, the more difficult it is to obtain the classical history of polyuria, polydipsia, and weight loss. Infants and toddlers in DKA may be misdiagnosed as having pneumonia, reactive airways disease (asthma), or bronchiolitis and therefore treated with glucocorticoids and/or sympathomimetic agents that only compound and exacerbate the metabolic derangements. Because the diagnosis of diabetes is not suspected as it evolves, the duration of symptoms may be longer, leading to more severe dehydration and acidosis and ultimately to obtundation and coma. Even in developed countries, some 15–70% of all newly diagnosed infants and children with diabetes present with DKA (1–8). Generally, the rates of DKA are inversely proportional to rates of diabetes in that community, but throughout the U.S., the overall rates of DKA at diagnosis have remained fairly constant at ∼25% (6). DKA, defined by blood bicarbonate  14 years but did not differ significantly by sex or ethnicity (6).

2 ) The higher basal metabolic rate and large surface area relative to total body mass in children requires greater precision in delivering fluids and electrolytes. The degree of dehydration is expressed as a function of body weight, i.e., 10% dehydration implies 10% loss of total body weight as water. However, the calculation of basal requirements, although a constant per unit …
Abstract 26: Fibroblast Growth Factor 21 Prevents Diabetic Cardiomyopathy by Attenuating Cardiac Lipotoxicity via Erk1/2-dependent Signaling Pathway in Mice
Authors: Yi Tan, Chi Zhang, Xiaoqing Yan, Zhifeng Huang, Junlian Gu, Shanshan Zhou, Minglong Shao, Wenke Feng, Xiaokun Li
Journal: Circulation Research (2015)

The role of FGF21 plays in the development and progression of diabetic cardiomyopathy (DCM) has not been addressed. Here we demonstrated that type 1 diabetes decreased FGF21 levels in the blood, but up-regulated cardiac fgf21 expression about 40 fold at 2 months and 3-1.5 fold at 4 and 6 months after diabetes, which indicated a cardiac specific FGF21 adaptive up-regulation. To define the critical role of FGF21 in DCM, type 1 diabetes was induced in FGF21 knock out (FGF21KO) mice. At 1, 2 and 4 months after diabetes onset, no significant differences between FGF21KO and wild type (WT) diabetic mice in blood glucose and triglyceride levels were observed. But FGF21KO diabetic mice showed earlier and more severe cardiac dysfunction, remodeling and oxidative stress, as well as greater increase in cardiac lipid accumulation than WT diabetic mice. Mechanistically, FGF21 reduced palmitate-induced cardiac cell death, which was accompanied by up-regulation of cardiac Erk1/2, p38 MAPK and AMPK phosphorylation. Inhibition of each kinase with its inhibitor and/ or siRNA revealed that FGF21 prevents palmitate-induced cardiac cell death via up-regulating the Erk1/2-dependent p38 MAPK/AMPK signaling pathway. In vivo administration of FGF21, but not FGF21 plus ERK1/2 inhibitor, to diabetic mice significantly prevented cardiac cell death and reduced inactivation of Erk1/2, p38 MAPK and AMPK, and prevented cardiac remodeling and dysfunction at late-stage. Our results demonstrate that cardiac FGF21 decompensation may contribute to the development of DCM and FGF21 may be a therapeutic target for the treatment of diabetic cardiac damage via activation of Erk1/2-P38 MAPK-AMPK signaling.
Selinexor in Combination with Bortezomib and Dexamethasone (SdB) Demonstrates Significant Activity in Patients with Refractory Multiple Myeloma (MM) Including Proteasome-Inhibitor Refractory Patients: Results of the Phase I Stomp Trial
Authors: Nizar J. Bahlis, Rami Kotb, Michael Sebag, Heather J. Sutherland, Richard LeBlanc, Darrell White, Christopher P. Venner, Tom Kouroukis, Debra Bergstrom, Arleigh McCurdy, Marc Lalancette, William Bensinger, Suzanne Lentzsch, Aldo Del Col, Michael Kauffman, Sharon Shacham, Jacqueline Jeha, Carla Picklesimer, Jean-Richard Saint-Martin, Cassandra Choe-Juliak, Christine Chen
Journal: Blood (2016)
Pharmacological management—inhaled treatment
Authors: Graeme P Currie, Brian J Lipworth
Journal: BMJ (2006)

Chronic obstructive airways disease (COPD) is a heterogeneous condition, and all patients should be viewed as individuals—not only in terms of presentation, history, symptoms, and disability, but also in response to treatment. Acceptability to the patient, possible adverse effects, and efficacy of treatment are important factors to consider when prescribing inhaled drugs. The titration of drug treatment in COPD is usually based on the degree of airflow obstruction, severity of symptoms, exercise tolerance, and frequency of exacerbations.

For all patients with established COPD, prescribe a short acting inhaled bronchodilator (β2 agonist or anticholinergic, or both in combination).



Patients with COPD have pulmonary hyperinflation, with increased functional residual capacity (red) and decreased inspiratory capacity (white). This increases the volume at which tidal breathing (oscillating line) occurs and places the respiratory muscles at mechanical disadvantage. Hyperinflation worsens with exercise and reduces exercise tolerance (dynamic hyperinflation). Inhaled bronchodilators improve dynamic hyperinflation and hyperinflation at rest, reducing the work of breathing and increasing exercise tolerance



Short acting β2 agonists such as salbutamol reduce breathlessness and improve lung function, and are effective when used “as required.” They act directly on bronchial smooth muscle and cause the airways to dilate for up to six hours.

Short acting anticholinergics such as ipratropium reduce breathlessness, improve lung function, improve health related quality of life, and reduce the need for rescue medication. They offset high resting bronchomotor tone and improve airway calibre for up to six hours.

Both drugs in combination (salbutamol plus ipratropium delivered via a metered dose inhaler) have been shown to confer greater improvement in lung function than either drug given alone.

For patients with persistent symptoms and exacerbations, prescribe a long acting bronchodilator. Current guidelines recommend …
Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma
Authors: Robert J.S. Coelen, Marcia P. Gaspersz, Tim A. Labeur, Jeroen L.A. van Vugt, Susan van Dieren, François E.J.A. Willemssen, Chung Y. Nio, Jan N.M. IJzermans, Heinz-Josef Klümpen, Bas Groot Koerkamp, Thomas M. van Gulik
Journal: Clinical Gastroenterology and Hepatology (2017)