tbuckley/cabot-search huggingface dataset:
Development and Validation of a Sudden Cardiac Death Prediction Model for the General Population
Authors: Rajat Deo, Faye L. Norby, Ronit Katz, Nona Sotoodehnia, Selcuk Adabag, Christopher R. DeFilippi, Bryan Kestenbaum, Lin Y. Chen, Susan R. Heckbert, Aaron R. Folsom, Richard A. Kronmal, Suma Konety, Kristen K. Patton, David Siscovick, Michael G. Shlipak, Alvaro Alonso
Journal: Circulation (2016)

Most sudden cardiac death (SCD) events occur in the general population among persons who do not have any prior history of clinical heart disease. We sought to develop a predictive model of SCD among US adults.
Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk Factors, and Effects on Quality of Life
Authors: Michael D. Crowell, Sarah B. Umar, W. Leroy Griffing, John K. DiBaise, Brian E. Lacy, Marcelo F. Vela
Journal: Clinical Gastroenterology and Hepatology (2016)
Breast Cancer Among Radiologic Technologists
Authors: M. Swift, M. B. Daly, L. Bernstein, S. M. Love
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The contribution of low doses of ionizing radiation to breast cancer incidence remains uncertain because definitive studies have not been done. In their report, Dr Boice and colleagues<sup>1</sup>claim the following: "Employment as a radiologic technologist... was not found to increase the risk of breast cancer. The contribution of prolonged exposure to relatively low doses of ionizing radiation to breast cancer risk was too small to be detectable at this time." If correct, this study would be strong evidence for the safety of low-dose exposure to ionizing radiation. Unfortunately, this study is so flawed that it provides no evidence about breast cancer induction after low-dose ionizing radiation. Boice and colleagues matched 5 control radiologic technologists to each breast cancer case for sex, date of birth, calendar year of certification, and length of time between certification and breast cancer diagnosis for cases or index date for controls.
Antibiotic prescribing and expenditures in outpatient adults in Greece, 2010 to 2013: evidence from real-world practice
Authors: Georgia Kourlaba, Effrossyni Gkrania-Klotsas, Eleni Kourkouni, Georgios Mavrogeorgos, Theoklis E Zaoutis
Journal: Eurosurveillance (2016)

We provide a representative analysis of antibiotic prescribing, identify factors associated with broad-spectrum antibiotic prescribing and assess the costs associated with antibiotic use in adult outpatients in Greece. Outpatient antibiotic prescriptions for patients older than 19 years between 2010 and 2013 in Greece were extracted from the IMS Health Xponent database. Prescribing rate and total cost for prescribed antibiotics were calculated. Multivariate logistic regression was used to identify factors related to broad-spectrum antibiotic prescribing. More than 20 million antibiotics were prescribed during the study period, an annual rate of 768 prescribed antibiotics per 1,000 adults. Overall, 33.5% of antibiotics were prescribed for acute respiratory tract infections (ARTIs) for which antibiotics are often not indicated. Macrolides (29.9%), cephalosporins (26.9%) and fluoroquinolones (21.0%) were the most commonly prescribed antibiotic classes. The majority (89.0%) of antibiotics were broad-spectrum. Antibiotic expenditures were approximately EUR 185 million during the study period. Factors associated with broad-spectrum prescribing included older patient age, specialty pulmonologists or otorhinolaryngologists, training in eastern Europe, diagnosis of ARTI, acute diagnosis, and first episode of disease. Broad-spectrum antibiotic prescribing for ARTIs is common in adult Greek outpatients and frequently inappropriate. These data indicate the need for initiatives aiming to control antibiotic prescribing.
uPA receptor and its interaction partners: Impact as potential therapeutic targets in triple-negative breast cancer.
Authors: Michaela Aubele, Michaela Christina Huber, Natalie Falkenberg, Eva Gross, Herbert Braselmann, Axel Karl Walch, Manfred Schmitt
Journal: Journal of Clinical Oncology (2015)

150 Background: Triple-negative breast cancers (TNBC), which lack expression of estrogen (ER), progesterone (PR), and HER2 receptors are characterized by tumor tissue expression of the urokinase-type plasminogen activator receptor (uPAR) system. Methods: We evaluated uPAR and its interaction partners (uPAR-interactome) by immunohistochemistry (IHC) in tissue microarrays (TMA) prepared from ~300 TNBC tumor tissue specimens and in the TNBC model cell lines BT549 and MDA-MB231. Protein expression of 25 different factors constituting the uPAR-interactome was evaluated by IHC; several of the uPAR-protein complexes were identified employing the proximity ligation assay (PLA). Results were correlated with histomorphological parameters and survival of the patients. RNA interference was employed in the TNBC cell lines for several of the parameters assessed. To analyze effects of uPAR and/or uPA depletion on malignant cell behavior, proliferation, migration, and invasion assays as well as Western blot, PLA, immunoprecipitation, mass spectrometry, and immunohistochemistry were conducted. Results: After downregulation of uPAR and uPA in TNBC cell lines, significantly reduced cell proliferation, invasion, and migration were observed. Furthermore, interaction between uPAR and IGF1R (insulin-like growth factor1 receptor) was shown, and several novel interaction proteins of uPAR could be identified, such as Cyr61 (cysteine-rich angiogenic inducer61). In TNBC tumor specimens, association between uPAR expression and histological grade plus expression of cathepsin B, IGF1R, IR (insulin receptor), and plasminogen was shown. Expression of KLK4 (stromal) and Ki67 was correlated with disease-free survival of the patients. Presence of uPAR/IGF1R protein complexes was associated with histological grade, with the expression of PAI-1, Ki-67, p27, and cathepsin B. Conclusions: Our findings demonstrate that uPAR and its interacting partners, expressed in TNBC tumor tissues, may be considered as potential novel therapeutic targets for this fatal disease.
The angiogenic make up of human hepatocellular carcinoma does not favour VEGF/angiopoietin driven sprouting neovascularization
Authors: Wenjiao Zeng, Annette S. Gouw, Marius van den Heuvel, Sibrand Poppema, Nong Zhang, Inge Plateel, Koert P. De Jong, Grietje Molema
Journal: Hepatology (2007)
Abstract 2085: Increased Regional Coronary Vascular Resistance During Hyperemia in Hypertrophic Cardiomyopathy Is Associated with Reduced Myocardial Blood Volume
Authors: Hiroshi Komatsu, Satoshi Yamada, Masanao Naya, Hisao Onozuka, Taisei Mikami, Nagara Tamaki, Hiroyuki Tsutsui
Journal: Circulation (2007)

Introduction: In patients with hypertrophic cardiomyopathy ( HCM ), myocardial blood flow ( MBF ) is decreased during hyperemia because of high coronary vascular resistance. Recently myocardial blood volume ( MBV ) can be estimated in vivo using myocardial contrast echocardiography ( MCE ) with the compensation for acoustic field inhomogeneity. The relationship between MBV and coronary resistance, however, has not been investigated. We thus assessed the hypothesis that increased regional coronary vascular resistance during hyperemia in HCM is associated with reduced MBV. Methods: In 13 patients with HCM ( H , 53±16 years) with asymmetric septal hypertrophy and 9 normal volunteers ( N , 54±11 years), MCE was performed under infusion of Levovist at rest and during hyperemia induced by ATP. Apical 4-chamber views of intermittent harmonic power Doppler imaging were acquired at end-diastole of every sixth beat. MBV was calculated as 10 X/10 ×100%, where X was myocardial contrast intensity minus contrast intensity of the adjacent intracavity blood pool in dB. 15 O-water PET was performed to measure regional MBF. These parameters were measured in the interventricular septum ( IVS ) and LV posterolateral ( PL ) wall. Regional coronary vascular resistance was calculated as (mean blood pressure)/MBF. Results: Wall thickness was significantly greater in H than in N (IVS: 19±4 vs 10±1 mm, p&lt;0.0001; PL: 10±1 vs 9±1 mm, p&lt;0.05). MBV of IVS was lower in H than in N (rest: 2.1±0.7 vs 3.5±1.1%, p&lt;0.01; hyperemia: 2.1±1.3 vs 4.3±1.7%, p&lt;0.01), whereas MBV of PL wall did not differ between groups. Coronary resistance at rest did not differ between groups, but the resistance during hyperemia was significantly greater in H than in N (IVS: 59±16 vs 31±14 mmHg·min·g·ml −1 , p&lt;0.001; PL: 40±10 vs 30±11 mmHg·min·g·ml −1 , p&lt;0.05). Coronary resistance at rest did not correlate with MBV, whereas that during hyperemia inversely correlated with MBV during hyperemia (r=−0.77, p&lt;0.0001) as well as MBV at rest (r=−0.65, p&lt;0.0001). Conclusions: Increased coronary vascular resistance during hyperemia in HCM was significantly associated with reduced MBV. MCE is useful for assessing the dynamic function of coronary circulation in the clinical setting.
Using eye-tracking to quantify the impact of prostate cancer treatments on male libido: A pilot study.
Authors: Charlenn Skead, Vivian Tsang, Jaime L Palmer-Hague, Richard J Wassersug, Eleni Nasiopoulos, Alan Kingstone
Journal: Journal of Clinical Oncology (2016)

231 Background: Eye-tracking research has demonstrated that heterosexual men with normal testosterone levels attend visually to features of women associated with fertility, notably their breast size and waist to hip ratio. As such, eye-tracking data can serve as an implicit measure of a man’s libido. Many treatments for prostate cancer (PCa)—in particular androgen deprivation therapy (ADT)—depress sexual interest in men, but there is no objective measure of the intensity of this effect. Here we explore whether eye-tracking can be used to quantify the impact of PCa treatments on men’s libido. Methods: We used an IRB-approved deception protocol to explore the validity of eye-tracking technology for assessing the level of sexual interest of PCa patients and normal controls. Three age-matched groups of heterosexual men aged 50 years and older were recruited. They were: PCa patients using ADT, PCa patients not using ADT, and healthy controls. Unaware that their eye movements were being tracked, all were exposed to photographs of female models, either fully clothed (neutral) or minimally clothed (sexy). Number and duration of eye fixations on target areas of the female models’ bodies were recorded. Results: Trends observed in our preliminary data suggest that men on ADT exhibit differential patterns of visual attention to sexual stimuli compared to men in the other two groups. Although confirmation with a larger sample size is required, such shifts in attention may provide an objective measure of the influence of cancer treatments on the libido of PCa patients. Conclusions: Eye-tracking technology may provide a reliable and objective technique for measuring the libido of cancer patients. Such data could help patients be better informed about psychological side effects when making treatment decisions. They could also lead to ways to both study and reduce the impact of PCa treatments on men’s sexual interest.
Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma.
Authors: Enrique M. Ocio, María-Victoria Mateos, Felipe Prosper, Jesus Martin, Albert Oriol Rocafiguera, Isidro Jarque, Rebeca Iglesias, Cristina Motlloo, Maria Sole, Paula Rodriguez-Otero, Sara Martinez, Eva Fernandez-Garcia, Jean-Marie Michot, Arturo Soto-Matos, Jose Rodriguez Diaz -Pavon, Vincent Ribrag, Jesus San Miguel
Journal: Journal of Clinical Oncology (2016)

8006 Background: Despite recent progress, MM remains incurable, hence the need for agents with novel mechanisms of action. Marine-derived plitidepsin targets eEF1A2, a protein overexpressed in MM. Plitidepsin/dexamethasone showed activity in a phase I/II trial conducted in relapsed or refractory MM. Moreover, plitidepsin exhibited synergism with bortezomib and lenalidomide in human MM cell lines and tumor samples. Methods: Relapsed and/or refractory MM patients were included if they had ECOG PS≤2 and CrCL>30 ml/min. Prior hematopoietic stem cell transplantation (HSCT) and previous treatment with bortezomib or other PIs and IMIDs was allowed. Primary objective: identification of the recommended dose (RD) for po dexamethasone (days 1,8,15,22)/s.c. bortezomib (days 1,4,8,11)/i.v. plitidepsin (days 1,15) administered every 4 weeks across 3 dose levels (DLs): DL1: 40 mg/1.0 mg/m2/4.0 mg/m2, DL2: 40mg/1.3mg/m2/4.0mg/m2 and DL3: 40mg/1.3mg/m2/5.0mg/m2. Secondary objectives: evaluation of efficacy and overall safety. Results: Twenty patients were enrolled. Median age was 65, median number of prior regimens was 3.5 (range, 1-10) and 9 patients had undergone HSCT. No dose-limiting toxicities (DLTs) were observed (n=20), therefore the RD was established at DL3. Hematological toxicity was manageable; grade 3-4 events included anemia (25%), neutropenia (25%) and thrombocytopenia (60%). Non-hematological toxicity was mainly mild. Out of 18 patients evaluable for efficacy, 15(83%) had received bortezomib and lenalidomide and 7/15 patients were refractory to lenalidomide. Overall response rate (ORR):56%, including 2 complete responses (11%), 4 very good partial responses (22%), 4 partial responses (22%) (one of them in a patient triple refractory to bortezomib, lenalidomide and pomalidomide) and 3 minimal responses (17%). Clinical benefit: 72%, median PFS: 8.3 months, PFS6months: 58% and DOR 6months: 90% (10 patients are still on-treatment). Conclusions: the RD for dexamethasone/bortezomib/plitidepsin at the tested schedule was established at 40 mg/1.3 mg/m2/5 mg/m2. An ORR of 56% was observed, including ≥ VGPR:33%. The drug combination was well tolerated. Clinical trial information: NCT02100657.
Association between Intraocular Pressure and Rates of Retinal Nerve Fiber Layer Loss Measured by Optical Coherence Tomography
Authors: Alberto Diniz-Filho, Ricardo Y. Abe, Linda M. Zangwill, Carolina P.B. Gracitelli, Robert N. Weinreb, Christopher A. Girkin, Jeffrey M. Liebmann, Felipe A. Medeiros
Journal: Ophthalmology (2016)
Raccoon Roundworm Infection Associated with Central Nervous System Disease and Ocular Disease — Six States, 2013–2015
Authors: Anita D. Sircar, Francisca Abanyie, Dean Blumberg, Peter Chin-Hong, Katrina S. Coulter, Dennis Cunningham, W. Charles Huskins, Charles Langelier, Michael Reid, Brian J. Scott, Debbie-Ann Shirley, Jennifer M. Babik, Aleksandra Belova, Sarah G. H. Sapp, Isabel McAuliffe, Hilda N. Rivera, Michael J. Yabsley, Susan P. Montgomery
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Baylisascaris procyonis, predominantly found in raccoons, is a ubiquitous roundworm found throughout North America. Although raccoons are typically asymptomatic when infected with the parasite, the larval form of Baylisascaris procyonis can result in fatal human disease or severe neurologic outcomes if not treated rapidly. In the United States, Baylisascaris procyonis is more commonly enzootic in raccoons in the midwestern and northeastern regions and along the West Coast (1). However, since 2002, infections have been documented in other states (Florida and Georgia) and regions (2). Baylisascariasis is not a nationally notifiable disease in the United States, and little is known about how commonly it occurs or the range of clinical disease in humans. Case reports of seven human baylisascariasis cases in the United States diagnosed by Baylisascaris procyonis immunoblot testing at CDC are described, including review of clinical history and laboratory data. Although all seven patients survived, approximately half were left with severe neurologic deficits. Prevention through close monitoring of children at play, frequent handwashing, and clearing of raccoon latrines (communal sites where raccoons defecate) are critical interventions in curbing Baylisascaris infections. Early treatment of suspected cases is critical to prevent permanent sequelae.
RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation
Authors: Robert A. Jones, Tyler J. Robinson, Jeff C. Liu, Mariusz Shrestha, Veronique Voisin, YoungJun Ju, Philip E.D. Chung, Giovanna Pellecchia, Victoria L. Fell, SooIn Bae, Lakshmi Muthuswamy, Alessandro Datti, Sean E. Egan, Zhe Jiang, Gustavo Leone, Gary D. Bader, Aaron Schimmer, Eldad Zacksenhaus
Journal: Journal of Clinical Investigation (2016)

Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low–like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration–approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC.
Physical Medicine and Rehabilitation
Authors: J A DeLisa, S S Jain
Journal: JAMA (1991)

Physiatry is an exciting, growing specialty that emphasizes prevention and treatment of disability secondary to injuries. Our treatment goal continues to be to minimize dependence and maximize functional independence to restore individuals to their highest potential and reintegrate them into the community. Physiatrists are involved in the prevention, diagnosis, and rehabilitation of work-related injuries. Cumulative trauma disorders of the upper extremities and cervical spine are a major cause of impairment disability and compensation in manual workers.<sup>1</sup>Despite advances in robotics and automation, industry remains dependent on manual labor and, in some instances, automation has increased the need for certain types of manual workers such as keyboard data operators. Residual functional capacity is being assessed for some occupations and requires a thorough understanding of the occupational demands, particularly in terms of joint motion and muscle activity.<sup>2</sup>Ergonomic assessment of the workplace is considered an essential step in the rehabilitation
Interleukin‐1 and inflammasomes in alcoholic liver disease/acute alcoholic hepatitis and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Authors: Herbert Tilg, Alexander R. Moschen, Gyongyi Szabo
Journal: Hepatology (2016)

Both alcoholic liver disease (ALD) and nonalcoholic fatty liver disease are characterized by massive lipid accumulation in the liver accompanied by inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma in a substantial subgroup of patients. At several stages in these diseases, mediators of the immune system, such as cytokines or inflammasomes, are crucially involved. In ALD, chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides through Toll‐like receptors, e.g., Toll‐like receptor 4. This sensitization enhances the production of various proinflammatory cytokines such as interleukin‐1 (IL‐1) and tumor necrosis factor‐alpha, thereby contributing to hepatocyte dysfunction, necrosis, and apoptosis and the generation of extracellular matrix proteins leading to fibrosis/cirrhosis. Indeed, neutralization of IL‐1 by IL‐1 receptor antagonist has recently been shown to potently prevent liver injury in murine models of ALD. As IL‐1 is clearly linked to key clinical symptoms of acute alcoholic hepatitis such as fever, neutrophilia, and wasting, interfering with the IL‐1 pathway might be an attractive treatment strategy in the future. An important role for IL‐1‐type cytokines and certain inflammasomes has also been demonstrated in murine models of nonalcoholic fatty liver disease. IL‐1‐type cytokines can regulate hepatic steatosis; the NLR family pyrin domain containing 3 inflammasome is critically involved in metabolic dysregulation. Conclusion : IL‐1 cytokine family members and various inflammasomes mediate different aspects of both ALD and nonalcoholic fatty liver disease. (H epatology 2016;64:955‐965)
Prevention of Cervical Cancer in Low-Resource Settings—Reply
Authors: Thomas C. Wright, Louise Kuhn, Lynette Denny
Journal: JAMA (2006)

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K-Ras Mutations and N-Ras Mutations in Childhood Acute Leukemias with and without MLL Rearrangements.
Authors: Der-Cherng Liang, Lee-Yung Shih, Chang-Liang Lai, Tung-Huei Lin, Jen-Fen Fu, Huei-Ying Li, Hsiu-I. Wang, Iou-Jih Hung, Chao-Ping Yang, Tang-Her Jaing, Shu-Huey Chen, Hsi-Che Liu, Lin-Yen Wang
Journal: Blood (2005)