tbuckley/cabot-search huggingface dataset:
Abstract 87: Nuclear localization of p70 S6 kinase in ovarian cancer
Authors: Jing ZHOU, Sally K. TO, Alice S. WONG
Journal: Cancer Research (2018)

Abstract Ovarian cancer is highly metastatic with a poor prognosis. The p70 S6 kinase (p70S6K) is a downstream effector of the phosphatidylinositol-3 kinase/Akt pathway that is frequently activated in ovarian cancer. Constitutive activation of p70S6K is significantly more often in malignant ovarian tumors than in normal or benign tissues, suggesting a role for p70S6K in tumor development and progression. In addition to its well-established role in cell growth and survival, we showed for the first time that p70S6K plays a pivotal role in other aspects of tumor progression such as metastasis. Here, we further showed that this was associated with the nuclear localization of p70S6K. Treatment of cells with the CRM1 inhibitor, leptomycin B, retained p70S6K in the nucleus. Growth factor stimuli led to p70S6K phosphorylation and triggered nuclear translocation of p70S6K. The phosphorylation was sensitive to p70S6K inhibitors. We further identified a potential region that was important in its nuclear localization. Expression of nuclear localization signal-p70S6K enhanced tumor cell migration and invasion when compared to non-targeted p70S6K. Our findings identify a region responsible for the nuclear entry of p70S6K and demonstrate a functional significance of nuclear p70S6K in tumor progression (This work is supported by RGC grant 17103417). Citation Format: Jing ZHOU, Sally K. TO, Alice S. WONG. Nuclear localization of p70 S6 kinase in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 87.
Abstract 14769: The Relationship Between Regular Physical Exercise and Nocturnal Blood Pressure in Korean Ambulatory Blood Pressure Monitoring Study
Authors: Bae Keun Kim, Lee Yonggu, Lim Young-Hyo, Jinho Shin
Journal: Circulation (2014)

Introduction: There have been many reports showing that regular physical exercise can reduce the blood pressure (BP). Thus physical exercise is one of the important components of lifestyle modification of hypertension. It is known that nocturnal BP is an independent factor for the cardiovascular event but there are few studies for the relationship between physical exercise and nocturnal BP. Hypothesis: Hypothesized regular physical exercise reduced nocturnal BP, therefore, we aimed to analyze the relationship between regular physical exercise assessed by a questionnaire (7-day physical activity recall) and nocturnal BP in the general population. Methods: Among 4145 subjects whose data for both clinical data and ambulatory blood pressure monitoring (ABPM) data file from the 5308 Korean ABPM (KorABP) study subjects, 3689 subjects were analyzed. The exclusion criteria was age less than 20 years (n=84), missing data for the questionnaire for physical exercise (n=372). Physical exercise was defined as regular structured exercise which intensity was heavier than the fast walking for 30 minutes. The count was recorded as the number per week. Results: Age was 55.5 ± 14.1 years and female was 45.9 %. Prevalence of hypertension, antihypertensive medication (AHM), diabetes and cardiovascular diseases were 58.9%, 32.5%, 13.0%, and 21.1%, respectively. Daytime and nighttime systolic BP was 138.5 ± 17.2 mmHg and 126.3 ± 18.8 mmHg. When adjusted for age, sex, BMI, and AHM, exercise frequency was independently decreased daytime systolic BP (β = -0.52 mmHg per ex-ercise, p = 0.02). For the nighttime systolic BP further adjusted by daytime systolic BP and sleep quality, ex-ercise frequency was an independent factor (β = -0.26 mmHg per exercise, p = 0.002). The statistical significances were observed even for only for 1 times per week. When further adjusted by smoking, exercise frequency was in-dependent for nocturnal dipping (β = 0.18% per exercise, p = 0.015). Conclusions: Regular physical exercise is independently associated with lower nocturnal BP also lower daytime BP and with increased nocturnal dipping, which was independent of AHM status.
Carcinogenicity of isobutyl nitrite, β-picoline, and some acrylates
Authors: Hans Kromhout, Melissa Friesen, M Mathilde Marques, Consolato Maria Sergi, Mohamed Abdallah, Geza Benke, Mark Cesta, Dori Germolec, Keith Houck, Gaku Ichihara, Charles William Jameson, Jun Kanno, Igor Pogribny, Camilla Svendsen, Lamia Benbrahim-Tallaa, Kathryn Z Guyton, Yann Grosse, Fatiha El Ghissassi, Véronique Bouvard, Amy Hall, Corentin Jaillet, Heidi Mattock, Kurt Straif, Hans Kromhout, Melissa Friesen, M. Matilde Marques, Consolato Maria Sergi, Mohamed Abdallah, Geza Benke, Mark F. Cesta, Dori Germolec, Keith Houck, Gaku Ichihara, Charles William Jameson, Jun Kanno, Igor Pogribny, Camilla Svendsen, Lamia Benbrahim-Tallaa, Kathryn Guyton, Yann Grosse, Fatiha El Ghissassi, Véronique Bouvard, Amy Hall, Corentin Jaillet, Heidi Mattock, Kurt Straif
Journal: The Lancet Oncology (2018)
Abstract 438: High-quality CNV segments from low-coverage whole genome sequencing from FFPE cancer biopsies based on an evaluation of multiple CNV tools
Authors: HoJoon Lee, Li Charlie Xia, Stephanie Greer, John Bell, Sue M. Grimes, Christina Wood Bouwens, Giwon Shin, Billy TC Lau, Lucas Johnson, Noemi Andor, Kenneth Day, Mickey Miller, Helaman Escobar, Lincoln Nadauld, Hanlee P. Ji, Paul Van Hummelen
Journal: Cancer Research (2018)

Abstract Changes in DNA copy number, i.e., somatic CNVs, are common genetic aberrations in cancers. The effects of CNV include alteration in gene dosage across large segments of the cancer genome affecting the expression of cancer driver genes by amplifications, or cancer suppressor genes by deletions. In addition, CNVs are markers of underlying rearrangements within or between chromosomes and there is increasing evidence supporting a greater role for CNVs in developing and maintaining neoplastic cell population diversity. Copy number aberrations can be estimated from next generation sequencing data, with high sensitivity and genomic resolution by sequencing the whole genome (WGS). For this study, we demonstrated that high quality CNV calls can be extracted in a fast and cost-effective way from low-coverage whole genome sequencing. Novaseq S2 flowcells (Illumina Inc) enables to obtain an average coverage of 3-4x per sample after pooling up to 96 samples per flowcell. We examined three different copy number detection tools (CNVkit, BicSeq, and seqCBS) from paired tumor and normal WGS using microarray data as a reference. Pearson correlations were computed between the reference and CNVs from the WGS in two fashion; i) segment based and ii) gene based. The segment based comparison used sliding window of 100 K bp while gene based comparison used segments at the gene level. We found high correlations between microarray and WGS segments. The highest correlations were obtained by CNVkit, ranging from 0.964 to 0.985 (SD: 0.973 - 0.007) and BicSeq, ranging from 0.963 to 0.986 (SD: 0.975 - 0.008). These results open the prospect of assessing large cancer cohorts of hundreds of samples at a reasonable cost. We are planning to apply this method to a large cohort of Stage III colon cancer patients and determine the clinical relevance of CNVs for survival. Citation Format: HoJoon Lee, Li Charlie Xia, Stephanie Greer, John Bell, Sue M. Grimes, Christina Wood Bouwens, Giwon Shin, Billy TC Lau, Lucas Johnson, Noemi Andor, Kenneth Day, Mickey Miller, Helaman Escobar, Lincoln Nadauld, Hanlee P. Ji, Paul Van Hummelen. High-quality CNV segments from low-coverage whole genome sequencing from FFPE cancer biopsies based on an evaluation of multiple CNV tools [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 438.
Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences
Authors: Stefano Aringhieri, Marco Carli, Shivakumar Kolachalam, Valeria Verdesca, Enrico Cini, Mario Rossi, Peter J. McCormick, Giovanni U. Corsini, Roberto Maggio, Marco Scarselli
Journal: Pharmacology & Therapeutics (2018)
Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis
Authors: Massimo Federico, María Dolores Caballero Barrigón, Luigi Marcheselli, Vittoria Tarantino, Martina Manni, Clementine Sarkozy, Sara Alonso-Álvarez, Marielle Wondergem, Guillaume Cartron, Armando Lopez-Guillermo, Djamila Issa, Franck Morschhauser, Miguel Alcoceba, Eva Kimby, Chiara Rusconi, Martine Chamuleau, Harald Holte, Sandra Lockmer, Silvia Montoto, Maria Gomes da Silva, Igor Aurer, Emanuele Zucca, Ewa Paszkiewicz-Kozik, Carla Minoia, Tetiana Skrypets, Yngvild Nuvin Blaker, Gilles Salles, Bertrand Coiffier
Journal: The Lancet Haematology (2018)
Abstract 19539: Associations of Soluble CD14, Interleukin-6, C-Reactive Protein and Leukocyte Count With Insulin Resistance and Incident Diabetes in Older Adults
Authors: Sanyog G Shitole, Mary L Biggs, Alexander P Reiner, Kenneth J Mukamal, Luc Djoussé, Joachim H Ix, Russell P Tracy, David Siscovick, Jorge R Kizer
Journal: Circulation (2016)

Background:  The roles of fat mass expansion and inflammation in insulin resistance and diabetes are well recognized. Experiments show that sCD14, an acute phase protein released by the liver or secreted by macrophages, modulates inflammatory activity and insulin resistance. Whether sCD14 is a risk factor for clinical dysglycemia, and how this association compares to other markers of inflammation, has not been studied.   Methods:  We investigated associations of sCD14, IL-6, CRP and total WBC with insulin resistance (QUICKI, HOMA2-IR) and incident diabetes in the Cardiovascular Health Study, a population-based cohort of adults ≥65 years. Since the mostly white original cohort (1989) and black supplemental cohort (1992) had different extents of f/u glucose ascertainment, analyses were race-stratified. Linear and Cox regression models adjusted for age, sex, BMI, SBP, HTN medication, smoking, alcohol, physical activity, eGFR, estrogen, CVD and CHF.   Results:  There were 5380 subjects not on baseline anti-glycemic therapy (age 73±6, 58% women, 14% black). After adjustment, sCD14 showed associations with both insulin resistance measures in whites but not blacks (Table). IL-6, CRP and WBC were associated with one or both measures in both race groups, but were strongest for WBC. These associations persisted after joint inclusion for all markers except sCD14 (not shown). After f/u through 2011, 376 (whites) and 84 (blacks) diabetes cases occurred. sCD14 was not associated with diabetes in whites or blacks (Table). IL-6, CRP and WBC were associated with diabetes in whites but not blacks, again strongest for WBC. After joint inclusion, these persisted for CRP and WBC but not IL-6.   Conclusions:  In older adults, sCD14 was associated with insulin resistance, but not incident diabetes, in whites, whereas IL-6, CRP and WBC were associated with both outcomes in whites, but only insulin resistance in the smaller black subgroup. WBC emerged as the strongest determinant of dysglycemic risk.
Firearm-Related Injury and Death
Authors: Sheila Leavitt
Journal: Annals of Internal Medicine (2018)

Letters3 July 2018Firearm-Related Injury and DeathSheila Leavitt, MDSheila Leavitt, MDNewton, Massachusetts (S.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0166 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Taichman and colleagues' (1) editorial about the health toll of gun violence with interest. Physician advocacy and patient education are of course the responsibility of clinicians. However, given the intransigence of the U.S. Congress in passing needed gun safety legislation, I believe that physicians should also use our considerable economic clout to reward states with sane gun laws (for example, those with a score of C or higher from the Giffords Law Center to Prevent Gun Violence) and withhold our personal and professional dollars (by choice of conference location, investments, and the like) from rogue ...References1. Taichman DB, Bauchner H, Drazen JM, Laine C, Peiperl L. Firearm-related injury and death: a U.S. health care crisis in need of health care professionals. Ann Intern Med. 2017;167:824-5. [PMID: 29052714]. doi:10.7326/M17-2657 LinkGoogle Scholar2. Phillips A. How LGBT activists win in states like Georgia: emphasize economics, not just equality. The Washington Post. 28 March 2016. Accessed at www.washingtonpost.com/news/the-fix/wp/2016/03/28/how-lgbt-activists-beat-back-unfriendly-laws-emphasize-economics-not-just-equality/?utm_term=.84c7c128fa57 on 24 May 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: Newton, Massachusetts (S.L.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0166. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFirearm-Related Injury and Death: A U.S. Health Care Crisis in Need of Health Care Professionals Darren B. Taichman , Howard Bauchner , Jeffrey M. Drazen , Christine Laine , and Larry Peiperl Metrics 3 July 2018Volume 169, Issue 1Page: 64KeywordsBisexualsConflicts of interestDisclosureFirearm injuriesLegislationPatient advocacySafetySportsViolent crime ePublished: 3 July 2018 Issue Published: 3 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
New Genetic Links to Depression May Pave the Way for Novel Treatment Strategies
Authors: Tracy Hampton
Journal: JAMA (2018)

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Reliability and accuracy of a novel classification system using peroral cholangioscopy for the diagnosis of bile duct lesions
Authors: Carlos Robles-Medranda, Manuel Valero, Miguel Soria-Alcivar, Miguel Puga-Tejada, Roberto Oleas, Jesenia Ospina-Arboleda, Haydee Alvarado-Escobar, Jorge Baquerizo-Burgos, Carlos Robles-Jara, Hannah Pitanga-Lukashok
Journal: Endoscopy (2018)

Abstract Background The aim of this study was to propose a novel, comprehensive, macroscopic classification for bile duct lesions. Methods A two-stage protocol was designed. In Stage I, a retrospective study (September 2013 to September 2015) of patients with bile duct lesions detected by peroral cholangioscopy (POCS) was performed. A total of 315 images with at least 6 months of follow-up were recorded, analyzed, and correlated to histology, and were classified as non-neoplastic (one of three types, 1 – 3) or neoplastic (one of four types, 1 – 4) based on morphological and vascular patterns. In Stage II, a prospective, nonrandomized, double-blind study was performed from December 2015 to December 2016 to validate the proposed classification. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and positive and negative likelihood ratios (LR + and LR – , respectively) were calculated (gold standard: 6-month follow-up). Inter- and intraobserver agreement (kappa value, κ) among experts and non-experts were calculated. Results 171 patients were included (65 retrospective; 106 prospective). In Stage I, 28/65 cases were neoplastic and 37 /65 were non-neoplastic, according to the final diagnosis. In Stage II, 56/106 were neoplastic with a sensitivity, specificity, PPV, NPV, LR + , and LR – for neoplastic diagnosis of 96.3 %, 92.3 %, 92.9 %, 96 %, 12.52, and 0.04, respectively. The proposed classification presented high reproducibility among observers, for both neoplastic and subtypes categories. However, it was better for experts (κ &gt; 80 %) than non-experts (κ 64.7 % – 81.9 %). Conclusion The novel classification system could help physicians to distinguish non-neoplastic from neoplastic bile duct lesions.
Abstract 1003: Improving the functional taxonomy of breast cancer-associated fibroblasts by single-cell RNA sequencing reveals clinically relevant cellular subsets
Authors: Michael Bartoschek, Kristian Pietras
Journal: Cancer Research (2018)

Abstract Aim: The traditional tumor cell-centric view of cancer has been replaced in the past years with the appreciation of the importance of the tumor microenvironment for the malignant phenotype. Cancer-associated fibroblasts (CAFs) are the main constituent of the breast tumor microenvironment, although the exact origin and role of CAF subpopulations in disease initiation, progression and response to treatment remain unclear. Therefore, cancer therapies targeting CAFs are not available. Methods: Here, we delineate the heterogeneity of CAFs through single-cell RNA sequencing of 768 EPCAM-CD31-CD45-NG2- cells from the MMTV-PyMT mouse model of breast cancer. Results and discussion: Unbiased transcriptional clustering and differential gene expression analysis revealed four populations, with functionally distinct transcriptional profiles. The existence of these cell populations was further validated by immunostaining in experimental and human tumors revealing a preferential localization of each CAF subtype within the tumor microenvironment. Gene profiles specific to each CAF subpopulation held prognostic capability in clinical cohorts and correlated to known functional gene profiles. Our high-resolution comparison of single-cell transcriptomes in CAFs reveals previously unappreciated functional diversity within the tumor microenvironment. Conclusions: Ultimately, our delineation of an improved taxonomy of breast CAFs reveals a previously unappreciated functional diversity within the tumor microenvironment and opens the possibility for biomarker-driven development of new drugs for precision medicine. Citation Format: Michael Bartoschek, Kristian Pietras. Improving the functional taxonomy of breast cancer-associated fibroblasts by single-cell RNA sequencing reveals clinically relevant cellular subsets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1003.
A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer
Authors: Ashish Kulkarni, Vineethkrishna Chandrasekar, Siva Kumar Natarajan, Anujan Ramesh, Prithvi Pandey, Jayashree Nirgud, Harshangda Bhatnagar, Driti Ashok, Amrendra Kumar Ajay, Shiladitya Sengupta
Journal: Nature Biomedical Engineering (2018)
Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome
Authors: Tomoko Horinouchi, Kandai Nozu, Tomohiko Yamamura, Shogo Minamikawa, Takashi Omori, Keita Nakanishi, Junya Fujimura, Akira Ashida, Mineaki Kitamura, Mitsuhiro Kawano, Wataru Shimabukuro, Chizuko Kitabayashi, Aya Imafuku, Keiichi Tamagaki, Koichi Kamei, Kenjirou Okamoto, Shuichiro Fujinaga, Masafumi Oka, Toru Igarashi, Akinori Miyazono, Emi Sawanobori, Rika Fujimaru, Koichi Nakanishi, Yuko Shima, Masafumi Matsuo, Ming Juan Ye, Yoshimi Nozu, Naoya Morisada, Hiroshi Kaito, Kazumoto Iijima
Journal: Journal of the American Society of Nephrology (2018)

Background X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS. Methods We examined transcript expression for all patients with suspected splicing abnormalities who were treated at one hospital between January of 2006 and July of 2017. Additionally, we recruited 46 males from 29 families with splicing abnormalities to examine genotype-phenotype correlation in patients with truncating ( n =21, from 14 families) and nontruncating ( n =25, from 15 families) mutations at the transcript level. Results We detected 41 XLAS families with abnormal splicing patterns and described novel XLAS atypical splicing patterns ( n =14) other than exon skipping caused by point mutations in the splice consensus sequence. The median age for developing ESRD was 20 years (95% confidence interval, 14 to 23 years) among patients with truncating mutations and 29 years (95% confidence interval, 25 to 40 years) among patients with nontruncating mutations ( P =0.001). Conclusions We report unpredictable atypical splicing in the COL4A5 gene in male patients with XLAS and reveal that renal prognosis differs significantly for patients with truncating versus nontruncating splicing abnormalities. Our results suggest that splicing modulation should be explored as a therapy for XLAS with truncating mutations.
Quality and Safety in Health Care, Part XLII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

Implantable cardioverter defibrillators for both primary and secondary prevention have been successful in decreasing sudden cardiac death. The Implantable Cardioverter Defibrillator Registry was established partly for reimbursement for primary prevention. However, the registry also has been helpful in better understanding the risks and appropriate selection of patients to receive these devices, serving as an impetus for quality improvement by giving outcome information to the contributing institutions regarding their performance relative to the national results, and increasing research. It is also expected to be helpful to compare results from different devices and provide information to the public.
Professional Football Participation and Mortality—Reply
Authors: Atheendar S. Venkataramani, Maheer B. Gandhavadi, Anupam B. Jena
Journal: JAMA (2018)

In Reply We agree with Drs Smith and Siddiqi that the estimated mortality hazard may be clinically meaningful, but because it is based on a small number of deaths, further follow-up is necessary. We would encourage this interpretation even if the P value had fallen below .05.
Caroli’s disease associated with biliary papillomatosis and cholangiolithiasis
Authors: Chi Yuan, Jianrong Liu, Xianghong Zhou, Chuncheng Wu
Journal: Endoscopy (2018)

A 52-year-old man presented with constant right upper quadrant pain and repeated episodes of fever for 6 months, accompanied with cutaneous and scleral icterus. Laboratory tests suggested a rise in bilirubin. A computed tomography (CT) scan showed obvious dilatation of the intra- and extrahepatic bile ducts, and patchy high density shadows in the intrahepatic bile ducts that were thought to be stones ([Fig. 1]).