tbuckley/cabot-search huggingface dataset:
Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts
Authors: Ary Serpa Neto, Rodrigo Octavio Deliberato, Alistair E. W. Johnson, Lieuwe D. Bos, Pedro Amorim, Silvio Moreto Pereira, Denise Carnieli Cazati, Ricardo L. Cordioli, Thiago Domingos Correa, Tom J. Pollard, Guilherme P. P. Schettino, Karina T. Timenetsky, Leo A. Celi, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz
Journal: Intensive Care Medicine (2018)
Reappraisal of Ischemic Heart Disease
Authors: Juan-Carlos Kaski, Filippo Crea, Bernard J. Gersh, Paolo G. Camici
Journal: Circulation (2018)

In recent years, it has become apparent that coronary microvascular dysfunction plays a pivotal pathogenic role in angina pectoris. Functional and structural mechanisms can affect the physiological function of the coronary microvasculature and lead to myocardial ischemia in people without coronary atheromatous disease and also in individuals with obstructive coronary artery disease. Abnormal dilatory responses of the coronary microvessels, coronary microvascular spasm, and extravascular compressive forces have been identified as pathogenic mechanisms in both chronic and acute forms of ischemic heart disease. The condition characterized by anginal symptoms and evidence of myocardial ischemia triggered by coronary microvascular dysfunction, in the absence of obstructive coronary disease, is known as microvascular angina. The concept of microvascular angina, however, may extend further to include patients with obstructive coronary artery disease and individuals with angina after coronary revascularization or heart transplantation because coronary microvascular dysfunction contributes to myocardial ischemia in many such patients. Patients with microvascular angina constitute a sizeable proportion of all cases of stable angina undergoing diagnostic coronary angiography and of those with persisting angina after successful coronary revascularization. Coronary microvascular dysfunction is also often responsible for angina in individuals with cardiomyopathy and heart valve disease as well as acute coronary syndrome cases such as Takotsubo syndrome and myocardial infarction with no obstructive coronary artery disease. Patients with stable microvascular angina present typically with effort or rest chest pain and a reduced coronary flow reserve or microvascular spasm. This condition, which affects women and men, can markedly impair quality of life and prognosis and represents a substantial cost burden to healthcare systems and individuals alike. In recent years, progress in the diagnosis of myocardial ischemia and the use of tests to investigate functional and structural causes for a reduced coronary flow reserve and microvascular spasm have allowed the identification of an increased number of cases of microvascular angina in everyday clinical practice. Although some of the available anti-anginal drugs may be helpful, treatment of coronary microvascular dysfunction remains a major challenge. The present article discusses the fundamental role that coronary microvascular dysfunction plays in the pathogenesis of ischemic heart disease, the clinical characteristics of patients presenting with microvascular angina, and possible diagnostic and therapeutic strategies.
Caring for Critically Ill Patients in Humanitarian Settings
Authors: James S. Lee, Simon W. P. Roberts, Kanya Götsch, Ulrike Moeller, Laura Hawryluck
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Critical care medicine is far from the first medical field to come to mind when humanitarian action is mentioned, yet both critical care and humanitarian action share a fundamental purpose to save the lives and ease the suffering of people caught in acute crises. Critically ill children and adults will be present regardless of resource limitations and irrespective of geography, regional or cultural contexts, insecurity, or socioeconomic status, and they may be even more prevalent in a humanitarian crisis. Critical care is not limited to the walls of a hospital, and all hospitals will have critically ill patients regardless of designating a specific ward an ICU. Regular and consistent consideration of critical care principles in humanitarian settings provides crucial guidance to intensivists and nonintensivists alike. A multidisciplinary, systematic approach to patient care that encourages critical thinking, checklists that encourage communication among team members, and context-specific critical care rapid response teams are examples of critical care constructs that can provide high-quality critical care in all environments. Promoting critical care principles conveys the message that critical care is an integral part of health care and should be accessible to all, no matter the setting. These principles can be effectively adopted in humanitarian settings by normalizing them to everyday clinical practice. Equally, core humanitarian principles-dignity, accountability, impartiality, neutrality-can be applied to critical care. Applying principles of critical care in a context-specific manner and applying humanitarian principles to critical care can improve the quality of patient care and transcend barriers to resource limitations.
Platelet count and bevacizumab response in high-grade glioma patients.
Authors: Patricia Alves de Oliveira Ferreira, Viviane Teodoro Oliveira Fernandes, Fábio Nasser Santos, Alexandre Andre Balieiro Anastacio da Costa
Journal: Journal of Clinical Oncology (2014)

e13013 Background: Increased platelet count (PC) has been related to worse outcomes in solid tumors such as ovarian cancer. In high grade glioma (HGG) patients its role has not been elucidated. Although the exactly relationship between platelets and tumor cells is not clear, they may contribute to tumor growth and angiogenesis through growth factors and angiogenesis factors release such as VEGF. The aim of this work is to evaluate the associaton of PC with survival and response to bevacizumab in HGG patients. Methods: It is a retrospective review of eletronic medical charts from 45 patients with HGG treated with bevacizumab in second or later treatment lines. We evaluated the impact of high PC higher than median in overal survival (OS) and progression freee survival (PFS) by the log rank test and cox regression and overall response rate (ORR) assessed by MRI using chi-square test and logistic regression. Results: With a median follow-up time of 12.5 months the median OS (mOS) after bevacizumab was 14.6 months, PFS was 7.1 months and the ORR was 68.4% as assessed by MRI. Three patients received bevacizumab alone, 2 with temozolamide and 40 with irinotecan. Median PC was 222,000. Although not statisticaly significatn, patients with PC > median had worse outcomes with a mOS of 6.4 versus 17.5 months (p=0.53) and mPFS was 3.6 versus 7.1 in favor of lower PC (p=0.88). Patients with higher PC had a significatly worse ORR, with complete or partial response in 16.7% versus 76.7% (p=0.01). Corticosteroid dose was associated to worse OS and PFS but no ORR. There was no association between corticosteroid dose and higher PC (p=0.58). Conclusions: These results suggest that increased platelet count is associated with worse response to bevacizumab based therapy in HGG patients and should be evaluated in a larger population.
Visualization of perforin/gasdermin/complement-formed pores in real cell membranes using atomic force microscopy
Authors: Yuying Liu, Tianzhen Zhang, Yabo Zhou, Jiping Li, Xiaoyu Liang, Nannan Zhou, Jiadi Lv, Jing Xie, Feiran Cheng, Yiliang Fang, Yunfeng Gao, Ning Wang, Bo Huang
Journal: Cellular and Molecular Immunology (2018)

Different types of pores ubiquitously form in cell membranes, leading to various types of cell death that profoundly influence the fate of inflammation and the disease status. However, these pores have never truly been visualized to date. Atomic force microscopy (AFM), which is emerging as a powerful tool to analyze the mechanical properties of biomolecules and cells, is actually an excellent imaging platform that allows biological samples to be visualized by probing surface roughness at the level of atomic resolution. Here, membrane pore structures were clearly visualized using AFM. This visualization not only describes the aperture and depth of the pore complexes but also highlights differences among the pores formed by perforin and gasdermins in tumor cell membranes and by complement in immune cell membranes. Additionally, this type of visualization also reveals the dynamic process of pore formation, fusion, and repair.
Response by Schiavon et al to Letters Regarding Article, “Effects of Bariatric Surgery in Obese Patients With Hypertension: The GATEWAY Randomized Trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension)”
Authors: Carlos A. Schiavon, Dimas Ikeoka, Eliana V. Santucci, Renato N. Santos, Lucas P. Damiani, Alexandre B. Cavalcanti, Luciano F. Drager
Journal: Circulation (2018)
Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy
Authors: Thomas Bertero, William M. Oldham, Eloise M. Grasset, Isabelle Bourget, Etienne Boulter, Sabrina Pisano, Paul Hofman, Floriant Bellvert, Guerrino Meneguzzi, Dmitry V. Bulavin, Soline Estrach, Chloe C. Feral, Stephen Y. Chan, Alexandre Bozec, Cedric Gaggioli
Journal: Cell Metabolism (2018)
Lactic Acidosis, Metformin Use, and Dose-Response Association—Reply
Authors: Benjamin Lazarus, Jung-Im Shin, Morgan E. Grams
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops
Authors: Yu Guo, Andrew A. Perez, Dennis J. Hazelett, Gerhard A. Coetzee, Suhn Kyong Rhie, Peggy J. Farnham
Journal: Genome biology (2018)

Recent genome-wide association studies (GWAS) have identified more than 100 loci associated with increased risk of prostate cancer, most of which are in non-coding regions of the genome. Understanding the function of these non-coding risk loci is critical to elucidate the genetic susceptibility to prostate cancer.We generate genome-wide regulatory element maps and performed genome-wide chromosome confirmation capture assays (in situ Hi-C) in normal and tumorigenic prostate cells. Using this information, we annotate the regulatory potential of 2,181 fine-mapped prostate cancer risk-associated SNPs and predict a set of target genes that are regulated by prostate cancer risk-related H3K27Ac-mediated loops. We next identify prostate cancer risk-associated CTCF sites involved in long-range chromatin loops. We use CRISPR-mediated deletion to remove prostate cancer risk-associated CTCF anchor regions and the CTCF anchor regions looped to the prostate cancer risk-associated CTCF sites, and we observe up to 100-fold increases in expression of genes within the loops when the prostate cancer risk-associated CTCF anchor regions are deleted.We identify GWAS risk loci involved in long-range loops that function to repress gene expression within chromatin loops. Our studies provide new insights into the genetic susceptibility to prostate cancer.
Dkk1 blocks Wnt-induced osteoprotegerin production in osteoblast progenitors in multiple myeloma
Authors: Ya-Wei Qiang, Yu Chen, Nathan Brown, Jeffrey Rubin, Stuart Rudikoff, Bart Barlogie, John Shaughnessy
Journal: Cancer Research (2007)

2050   Multiple myeloma (MM), a fatal malignancy of plasma cells growing systemically in bone, causes osteolytic bone lesions. Bone turnover is regulated by the coupled activity of osteoblasts (OB) and osteoclasts (OC). OC differentiation is positively modulated by the receptor activator of nuclear factor kappa B ligand (RANKL) and negatively regulated by the decoy receptor, osteoprotegerin (OPG). Although the RANKL/OPG axis appears to be deregulated in MM, little is known about how MM cells might promote this process. Wnt signaling promotes bone formation and OB differentiation and overexpression of an active form beta-catenin in OB leads to upregulation of OPG, indicating that Wnt signaling in OB regulates osteoclastogenesis. We have demonstrated that MM cells express Dkk1, a soluble antagonist of canonical Wnt signaling, and that increased levels of Dkk1 in serum from MM is linked to bone lesions and MM serum can inhibit OB differentiation in a Dkk1-specific manner. To better understand the molecular mechanisms of the osteolytic process in MM, we investigated the role of canonical Wnt signaling in regulating the RANKL/OPG axis in OB progenitors. By real time quantitative PCR (qPCR) and ELISA analysis, we demonstrate that Wnt3a significantly induced OPG in C2C12 cells, a pluripotential mesenchymal progenitor. This Wnt3a-induced increase in OPG was significantly inhibited by pretreatment of the cells with recombinant Dkk1 or conditioned medium from an MM cell line constitutively expressing Dkk1. Inhibition of canonical Wnt signaling by transfection with siRNA to Wnt co-receptors LRP5/6 and or a dominant negative beta-catenin abrogated both endogenous and Wnt3a-induced OPG relative to controls. Interestingly, Dkk2, which has been shown to promote OB differentiation, significantly blocked Wnt3a-induced increase in OPG. Finally, treatment of the cells with plasma from bone marrow of MM pateints with high concentrations (> 100 ng/ml) of Dkk1 inhibited both OPG mRNA and protein in C2C12 cells. While Wnt3a stimulated OPG, it had a negative effect on RANKL mRNA as accessed by qPCR. Constitutive expression of Dkk1 lead to increased production of RANKL. Our results suggest that canonical Wnt signaling plays an important role in regulating the RANKL/OPG axis and that Dkk1 secretion by MM cells directly inhibits osteoblast differentiation while indirectly promoting osteoclastogenesis. Restoring proper Wnt signaling in MM may prevent bone lesions and possibly disease progression.
Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review
Authors: Anthony Matthews, Susannah Stanway, Ruth E Farmer, Helen Strongman, Sara Thomas, Alexander R Lyon, Liam Smeeth, Krishnan Bhaskaran
Journal: BMJ (2018)

Abstract Objective To investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer. Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources Medline and Embase up until June 2018. Eligibility criteria for selecting studies Studies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer. Appraisal and data extraction Relevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration’s tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies. Results 26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes. Conclusion This review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease outcomes including venous thromboembolism and myocardial infarction, progressing knowledge. Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient’s risk of venous or arterial vascular disease should be an important secondary consideration. Systematic review registration Prospero CRD42017065944.
Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes
Authors: Pedro P.G. Guimaraes, Mingchee Tan, Tuomas Tammela, Katherine Wu, Amanda Chung, Matthias Oberli, Karin Wang, Roman Spektor, Rachel S. Riley, Celso T.R. Viana, Tyler Jacks, Robert Langer, Michael J. Mitchell
Journal: Journal of Controlled Release (2018)
Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry
Authors: Richard Cathomas, Dirk Klingbiel, Brandon Bernard, Anja Lorch, Xavier Garcia del Muro, Franco Morelli, Ugo De Giorgi, Mikhail Fedyanin, Christoph Oing, Hege Sagstuen Haugnes, Marcus Hentrich, Christian Fankhauser, Silke Gillessen, Jörg Beyer
Journal: Journal of Clinical Oncology (2018)

Purpose Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions &lt; 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)–negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking. Patients and Methods We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET. Results Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%. Conclusion FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone.
Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia (vol 47, pg 757, 2015)
Authors: S Kohl, D Zobor, W-C Chiang, N Weisschuh, J Staller, IG Menendez, S Chang, SC Beck, MG Garrido, Sothilingam, MW Seeliger, F Stanzial, F Benedicenti, F Inzana, E Heon, A Vincent, J Beis, TM Strom, G Rudolph, S Roosing, AI den Hollander, Fpm Cremers, I Lopez, H Ren, AT Moore, AR Webster, M Michaelides, RK Koenekoop, E Zrenner, RJ Kaufman, SH Tsang, B Wissinger, JH Lin
Journal: Nature Genetics (2015)
Variation in the Heritability of Child Body Mass Index by Obesogenic Home Environment
Authors: Stephanie Schrempft, Cornelia H. M. van Jaarsveld, Abigail Fisher, Moritz Herle, Andrea D. Smith, Alison Fildes, Clare H. Llewellyn
Journal: JAMA Pediatrics (2018)

IMPORTANCEThe early obesogenic home environment is consistently identified as a key influence on child weight trajectories, but little research has examined the mechanisms of that influence.Such research is essential for the effective prevention and treatment of overweight and obesity.OBJECTIVE To test behavioral susceptibility theory's hypothesis that the heritability of body mass index (BMI) is higher among children who live in more obesogenic home environments. DESIGN, SETTING, AND PARTICIPANTSThis study was a gene-environment interaction twin study that used cross-sectional data from 925 families (1850 twins) in the Gemini cohort (a population-based prospective cohort of twins born in England and Wales between March and December 2007).Data were analyzed from July to October 2013 and in June 2018.EXPOSURES Parents completed the Home Environment Interview, a comprehensive measure of the obesogenic home environment in early childhood.Three standardized composite scores were created to capture food, physical activity, and media-related influences in the home; these were summed to create an overall obesogenic risk score.The 4 composite scores were split on the mean, reflecting higher-risk and lower-risk home environments. MAIN OUTCOMES AND MEASURESQuantitative genetic model fitting was used to estimate heritability of age-adjusted and sex-adjusted BMI (BMI SD score, estimated using British 1990 growth reference data) for children living in lower-risk and higher-risk home environments.RESULTS Among 1850 twins (915 [49.5%] male and 935 [50.5%] female; mean [SD] age, 4.1 [0.4] years), the heritability of BMI SD score was significantly higher among children living in overall higher-risk home environments (86%; 95% CI, 68%-89%) compared with those living in overall lower-risk home environments (39%; 95% CI, 21%-57%).The findings were similar when examining the heritability of BMI in the separate food and physical activity environment domains.CONCLUSIONS AND RELEVANCE These findings support the hypothesis that obesity-related genes are more strongly associated with BMI in more obesogenic home environments.Modifying the early home environment to prevent weight gain may be particularly important for children genetically at risk for obesity.
Systematic Review of Systemic Therapies and Therapeutic Combinations with Local Treatments for High-risk Localized Prostate Cancer
Authors: Lorenzo Tosco, Alberto Briganti, Antony Vincent D’amico, James Eastham, Mario Eisenberger, Martin Gleave, Karin Haustermans, Christopher J. Logothetis, Fred Saad, Christopher Sweeney, Mary-Ellen Taplin, Karim Fizazi
Journal: European Urology (2018)