tbuckley/cabot-search huggingface dataset:
The association between heatwaves and risk of hospitalization in Brazil: A nationwide time series study between 2000 and 2015
Authors: Qi Zhao, Shanshan Li, Micheline S. Z. S. Coelho, Paulo H. N. Saldiva, Kejia Hu, Rachel R. Huxley, Michael J. Abramson, Yuming Guo
Journal: PLoS Medicine (2019)

To our knowledge, no study has assessed the association between heatwaves and risk of hospitalization and how it may change over time in Brazil. We quantified the heatwave-hospitalization association in Brazil during 2000-2015.Daily data on hospitalization and temperature were collected from 1,814 cities (>78% of the national population) in the hottest five consecutive months during 2000-2015. Twelve types of heatwaves were defined with daily mean temperatures of ≥90th, 92.5th, 95th, or 97.5th percentiles of year-round temperature and durations of ≥2, 3, or 4 consecutive days. The city-specific association was estimated using a quasi-Poisson regression with constrained distributed lag model and then pooled at the national level using random-effect meta-analysis. Stratified analyses were performed by five regions, sex, 10 age groups, and nine cause categories. The temporal change in the heatwave-hospitalization association was assessed using a time-varying constrained distributed lag model. Of the 58,400,682 hospitalizations (59% women), 24%, 34%, 21%, and 19% of cases were aged <20, 20-39, 40-59, and ≥60 years, respectively. The city-specific year-round daily mean temperatures were 23.5 ± 2.8 °C on average, varying from 26.8 ± 1.8 °C for the 90th percentile to 28.0 ± 1.6 °C for the 97.5th percentile. We observed that the risk of hospitalization was most pronounced for heatwaves characterized by high daily temperatures and long durations across Brazil, except for the minimal association in the north (the hottest region). After controlling for temperature, the association remained for severe heatwaves in the south and southeast (cold regions). Children 0-9 years, the elderly ≥70 years, and admissions for perinatal conditions were most strongly associated with heatwaves. Over the study period, the strength of the heatwave-hospitalization association declined substantially in the south, while an apparent increase was observed in the southeast. The main limitations of this study included the lack of data on individual temperature exposure and measured air pollution.There are geographic, demographic, cause-specific, and temporal variations in the heatwave-hospitalization associations across the Brazilian population. Considering the projected increase in frequency, duration, and intensity of heatwaves, future strategies should be developed, such as building early warning systems, to reduce the health risk associated with heatwaves in Brazil.
Desynchronization of the Germinal Center Dynamics and Remodeling of the Tumor Microenvironment Characterize KMT2D-Driven Lymphomagenesis
Authors: Gabriel Brisou, Manon Zala, Laurine Gil, Giulia Pagano, Agnès Bru, Inaki Cervera-Marzal, Delphine Potier, Sebastien Nin, Lionel Chasson, Caroline Laprie, Sarah Huet, Gilles Salles, Pierre Milpied, Bertrand Nadel, Sandrine Roulland
Journal: Blood (2018)
Head and Neck Cancers, Version 2.2013
Authors: David G. Pfister, Kie-Kian Ang, David M. Brizel, Barbara A. Burtness, Paul M. Busse, Jimmy J. Caudell, Anthony J. Cmelak, A. Dimitrios Colevas, Frank Dunphy, David W. Eisele, Jill Gilbert, Maura L. Gillison, Robert I. Haddad, Bruce H. Haughey, Wesley L. Hicks, Ying J. Hitchcock, Merrill S. Kies, William M. Lydiatt, Ellie Maghami, Renato Martins, Thomas McCaffrey, Bharat B. Mittal, Harlan A. Pinto, John A. Ridge, Sandeep Samant, David E. Schuller, Jatin P. Shah, Sharon Spencer, Randal S. Weber, Gregory T. Wolf, Frank Worden, Sue S. Yom, Nicole R. McMillian, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2013)

These NCCN Guidelines Insights focus on nutrition and supportive care for patients with head and neck cancers. This topic was a recent addition to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers. The NCCN Guidelines Insights focus on major updates to the NCCN Guidelines and discuss the new updates in greater detail. The complete version of the NCCN Guidelines for Head and Neck Cancers is available on the NCCN Web site (NCCN.org).
The Biocompatibility Challenges in the Total Artificial Heart Evolution
Authors: Eleonora Dal Sasso, Andrea Bagno, Silvia T.G. Scuri, Gino Gerosa, Laura Iop
Journal: Annual Review of Biomedical Engineering (2019)

There are limited therapeutic options for final treatment of end-stage heart failure. Among them, implantation of a total artificial heart (TAH) is an acceptable strategy when suitable donors are not available. TAH development began in the 1930s, followed by a dramatic evolution of the actuation mechanisms operating the mechanical pumps. Nevertheless, the performance of TAHs has not yet been optimized, mainly because of the low biocompatibility of the blood-contacting surfaces. Low hemocompatibility, calcification, and sensitivity to infections seriously affect the success of TAHs. These unsolved issues have led to the withdrawal of many prototypes during preclinical phases of testing. This review offers a comprehensive analysis of the pathophysiological events that may occur in the materials that compose TAHs developed to date. In addition, this review illustrates bioengineering strategies to prevent these events and describes the most significant steps toward the achievement of a fully biocompatible TAH.
ECG Challenge: April 12, 2016
Authors: Philip Podrid
Journal: Circulation (2016)

ECG Challenge 1516A 58-year-old man with a history of hypertension being treated with amlodipine and hydrochlorthiazide and coronary artery disease being treated with a β-blocker and Imdur presents to his cardiologist for a routine physical examination.His pulse is noted to be irregular, and a 12-lead ECG is obtained.
ECG Challenge: April 26, 2016
Authors: Philip Podrid
Journal: Circulation (2016)

ECG Challenge 1708A 34-year-old man with a history of atrioventricular nodal reentrant tachycardia being treated with a β-blocker and verapamil presents to the emergency department with complaints of fatigue and a slow heartrate.A 12-lead ECG is obtained.What is the diagnosis?
Case 6-2019: A 29-Year-Old Woman with Nausea, Vomiting, and Diarrhea
Authors: Alexander Y. Walley, Sarah E. Wakeman, George Eng
Journal: New England Journal of Medicine (2019)

A Woman with Nausea, Vomiting, and Diarrhea A 29-year-old woman was evaluated at a primary care clinic affiliated with this hospital because of nausea, vomiting, and diarrhea. She reported a history of nonprescribed oxycodone use and requested injectable naltrexone. A diagnosis and management decisions were made.
Breast MRI and X-ray mammography registration using gradient values
Authors: Eloy García, Yago Diez, Oliver Diaz, Xavier Lladó, Albert Gubern-Mérida, Robert Martí, Joan Martí, Arnau Oliver
Journal: Medical Image Analysis (2019)

Breast magnetic resonance imaging (MRI) and X-ray mammography are two image modalities widely used for early detection and diagnosis of breast diseases in women. The combination of these modalities, traditionally done using intensity-based registration algorithms, leads to a more accurate diagnosis and treatment, due to the capability of co-localizing lesions and susceptibles areas between the two image modalities. In this work, we present the first attempt to register breast MRI and X-ray mammographic images using intensity gradients as the similarity measure. Specifically, a patient-specific biomechanical model of the breast, extracted from the MRI image, is used to mimic the mammographic acquisition. The intensity gradients of the glandular tissue are directly projected from the 3D MRI volume to the 2D mammographic space, and two different gradient-based metrics are tested to lead the registration, the normalized cross-correlation of the scalar gradient values and the gradient correlation of the vectoral gradients. We compare these two approaches to an intensity-based algorithm, where the MRI volume is transformed to a synthetic computed tomography (pseudo-CT) image using the partial volume effect obtained by the glandular tissue segmentation performed by means of an Expectation-Maximization algorithm. This allows us to obtain the digitally reconstructed radiographies by a direct intensity projection. The best results are obtained using the scalar gradient approach along with a transversal isotropic material model, obtaining a target registration error (TRE), in millimeters, of 5.65 ± 2.76 for CC- and of 7.83 ± 3.04 for MLO-mammograms, while the TRE is 7.33 ± 3.62 in the 3D MRI. We also evaluate the effect of the glandularity of the breast as well as the landmark position on the TRE, obtaining moderated correlation values (0.65 and 0.77 respectively), concluding that these aspects need to be considered to increase the accuracy in further approaches.
Abstract 110: Adiponectin Inhibits TNF-a-Induced Vascular Inflammatory Response via Caveolin-Mediated Ceramidase Recruitment and Activation
Authors: Yajing Wang, Wayne Lau, Erhe Gao, Walter Koch, Xin Ma
Journal: Circulation Research (2013)

Anti-inflammatory and vascular protective actions of adiponectin (APN) are well-recognized. However, many fundamental questions remain unanswered. The current study attempted to identify the APN receptor subtype responsible for APN’s vascular protective action, and investigate the role of ceramidase activation in APN anti-inflammatory signaling. Wild type (WT) or gene manipulated HUVEC were treated with TNFα in the presence and absence of APN. The effect of APN on TNFα-induced inflammatory and oxidative/nitrative stress was determined. In WT HUVEC, APN significantly reduced TNFα-induced ICAM-1 expression and attenuated TNFα-induced superoxide and peroxynitrite formation (P&lt;0.01). These anti-inflammatory actions were virtually abolished by AdipoR1-, but not AdipoR2-, knockdown (KD). Treatment with APN significantly increased neutral ceramidase (nCDase) activity (3.7-fold, P&lt;0.01). AdipoR1-KD markedly (P0.05), reduced APN-induced nCDase activation. More importantly, siRNA mediated nCDase-KD markedly blocked the effect of APN upon TNFα-induced ICAM-1 expression (P0.05), and modestly inhibited APN anti-inflammatory effect (P87% of APN-induced nCDase activation was lost. Whereas APN treatment failed to inhibit TNFα-induced ICAM-1 expression, treatment with S1P or SEW (S1P receptor agonist) remained effective in Cav1-KD cells in reducing TNFα-induced ICAM-1 expression (P&lt;0.01). AdipoR1 and Cav1 co-localized and co-precipitated in HUVECs. APN treatment did not affect this interaction. Moreover, re-expression of WT Cav1 in Cav1-KD cells restored nCDase activation in response to APN (P&lt;0.01 vs. vehicle), whereas re-expression of a mutated Cav1 blocking AdipoR1/Cav1 interaction failed to restore APN-mediated nCDase activation. Finally, there is weak basal Cav1/nCDase interaction, which significantly increased following APN treatment. These results demonstrate for the first time that APN inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1- dependent fashion.
Blocking Triggering Receptor Expressed on Myeloid Cells‐1‐Positive Tumor‐Associated Macrophages Induced by Hypoxia Reverses Immunosuppression and Anti‐Programmed Cell Death Ligand 1 Resistance in Liver Cancer
Authors: Qinchuan Wu, Wuhua Zhou, Shengyong Yin, Yuan Zhou, Tianchi Chen, Junjie Qian, Rong Su, Liangjie Hong, Haohao Lu, Feng Zhang, Haiyang Xie, Lin Zhou, Shusen Zheng
Journal: Hepatology (2019)

Tumor‐associated macrophages (TAMs) are recognized as antitumor suppressors, but how TAMs behave in the hypoxic environment of hepatocellular carcinoma (HCC) remains unclear. Here, we demonstrated that hypoxia inducible factor 1α induced increased expression of triggering receptor expressed on myeloid cells‐1 (TREM‐1) in TAMs, resulting in immunosuppression. Specifically, TREM‐1‐positive (TREM‐1 + ) TAMs abundant at advanced stages of HCC progression indirectly impaired the cytotoxic functions of CD8 + T cells and induced CD8 + T‐cells apoptosis. Biological and functional assays showed that TREM‐1 + TAMs had higher expression of programmed cell death ligand 1 (PD‐L1) under hypoxic environment. However, TREM‐1 + TAMs could abrogate spontaneous and PD‐L1‐blockade‐mediated antitumor effects in vivo , suggesting that TREM‐1 + TAM‐induced immunosuppression was dependent on a pathway separate from PD‐L1/programmed cell death 1 axis. Moreover, TREM‐1 + TAM‐associated regulatory T cells (Tregs) were crucial for HCC resistance to anti‐PD‐L1 therapy. Mechanistically, TREM‐1 + TAMs elevated chemokine (C‐C motif) ligand 20 expression through the extracellular signal‐regulated kinase/NF‐κβ pathway in response to hypoxia and tumor metabolites leading to CCR6 + Foxp3 + Treg accumulation. Blocking the TREM‐1 pathway could significantly inhibit tumor progression, reduce CCR6 + Foxp3 + Treg recruitment, and improve the therapeutic efficacy of PD‐L1 blockade. Thus, these data demonstrated that CCR6 + Foxp3 + Treg recruitment was crucial for TREM‐1 + TAM‐mediated anti‐PD‐L1 resistance and immunosuppression in hypoxic tumor environment. Conclusion : This study highlighted that the hypoxic environment initiated the onset of tumor immunosuppression through TREM‐1 + TAMs attracting CCR6 + Foxp3 + Tregs, and TREM‐1 + TAMs endowed HCC with anti‐PD‐L1 therapy resistance.
A Pooled Analysis of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients Treated with the Dual PI3K and HDAC Inhibitor Fimepinostat (CUDC-907), Including Patients with MYC-Altered Disease
Authors: Daniel J. Landsburg, Radhakrishnan Ramchandren, Petronella J Lugtenburg, Kevin R. Kelly, Anas Younes, Robert Gharavi, David P. Tuck, Stefan Klaus Barta
Journal: Blood (2018)
Addressing Medicine’s Bias Against Patients Who Are Overweight
Authors: Rita Rubin
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Combined Venetoclax and Ibrutinib for Patients with Previously Untreated High-Risk CLL, and Relapsed/Refractory CLL: A Phase II Trial
Authors: Nitin Jain, Philip A Thompson, Alessandra Ferrajoli, Jan A. Burger, Gautam Borthakur, Koichi Takahashi, Prithviraj Bose, Zeev Estrov, Elias J. Jabbour, Marina Konopleva, Yesid Alvarado, Tapan Kadia, Musa Yilmaz, Courtney D. DiNardo, Maro Ohanian, Jorge E. Cortes, Rashmi Kanagal-Shamanna, Keyur Patel, Naveen Garg, Xuemei Wang, Nina Fru, Nichole Cruz, Varsha Gandhi, William Plunkett, Hagop M. Kantarjian, Michael J. Keating, William G Wierda
Journal: Blood (2017)
Reply
Authors: Fabio Caputo, Marco Domenicali, Mauro Bernardi
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. We thank Dr. Braillon and Dr. Naudet for their interest in our review article.1 Based on their comments, several aspects need to be clarified and pointed out. First, we addressed a specific patient population presenting alcohol use disorder (AUD) and alcohol‐induced chronic liver disease (ALD) in an advanced stage. The cited Cochrane review 2 appeared after the acceptance of our review and, most important, dealt with the use of baclofen in AUD, with and without liver disease. It is relevant to outline that all randomized and open studies assessing the efficacy of baclofen in patients with AUD and ALD clearly showed that this favors the maintaining of abstinence from alcohol even at a low dose (30 mg/day), a result fully confirmed by a recent randomized trial.3 Second, when discussing about the approach to patients with an advanced (end‐stage) liver disease, which was the matter dealt with in our review, it cannot be under‐rated that the approved medications are contraindicated in this context, because of the risk of either liver toxicity (naltrexone and disulfiram) or hepatic encephalopathy (acamprosate). Thus, topiramate and baclofen only remain even though they have to be used off‐label. Third, there is no doubt that abstinence is the sole goal to be achieved in patients with end‐stage liver disease. Indeed, the perspective of the “harm reduction” was not even mentioned in our review. Fourth, baclofen adverse events and poisoning have been reported with much higher doses than those indicated in ALD. In this context, baclofen safety is also endorsed by the European Association for the Study of the Liver, clearly stating that topiramate and baclofen represent the safest anticraving drugs.4 Finally, we would like to recall that the French ANSM (Agence nationale de sécurité du medicament) has recently approved the use of baclofen for the treatment of AUD with the warning not to exceed 80 mg/day.5 All considered, in a context where the interruption of abstinence could be rapidly fatal, once nonpharmacological attempts have failed and approved medications are risky, we think that available evidence fully justifies the use of baclofen.
Reactive oxygen species and vascular endothelial growth factor (VEGF) in ovarian cancer patients
Authors: O.G. Trifanescu, F. Topliceanu, B.-A. Gusoiu, L.N. Gales, R. Anghel
Journal: Annals of Oncology (2019)

Background: Hypoxia plays an important role in ovarian cancer and understanding the role of reactive oxygen species and VEGF may identify patients who benefit the most from targeted therapies. The aims of the study were to determine the intensity of oxidative stress in ovarian cancer patients and to establish a connection between the presence of the reactive oxygen species (ROS) and VEGF. Methods: Forty-one patients diagnosed with epithelial ovarian carcinoma stage II-IV between 2010 and 2017, who underwent multimodality treatment (surgery and chemotherapy) were included in the study. ROS measured in dynamic (four determinations between every cycle) were malondialdehyde to evaluate the lipid peroxidation, ceruloplasmin, SH- albumin thiols groups and total antioxidants. Results: There was an increase in the value of ROS: malondialdehyde mean value was 8.5 μmol/100 ml (normal value 4 μmol/100 ml); ceruloplasmin mean value was 147.8U.I. (normal value 120U.I), both showing an active oxidative process in patients with ovarian cancer. A small decrease of the value of thiols (397 vs. 450 μmol/l) and a small increase of total antioxidants was noticed (1.45 vs. 1.4 μmol). All four compounds decreased between the first determination and the fourth one. There was a strong correlation between lipid peroxides levels and ceruloplasmin (Pearson correlation 0.315 p = 0.005) and between lipid peroxides and thiols groups (Pearson correlation 0.23 p = 0.039). There was a correlation between thiols and antioxidants (Pearson correlation 0.33 p = 0.003). Lipid peroxidation and ceruloplasmin were significantly higher in patients with residual disease (p = 0.039, p = 0.046) emphasizing that the tumor is a generator of oxidative stress. Mean VEGF levels were elevated 983.42 pg/ml, and VEGF levels statistically significant corelates with malondialdehyde (Pearson correlation 0.439, p = 0.036). Conclusions: Tumours produce ROS in excess in patients with advanced ovarian adenocarcinoma. Those ROS are corelated between each other and with VEGF and act as signalling molecules. Legal entity responsible for the study: National Institute of Oncology Al. Treistioreanu. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Efficacy of an Extended Half-Life GlycoPEGylated rFVIII (N8-GP): Pooled Analysis of ABR (Results from Two Clinical Trials)
Authors: Pratima Chowdary, Lone Hvitfeldt Poulsen, Miguel A Escobar, Susan Kearney, Meera B. Chitlur, Robert Klamroth, Mudi Misgav, Claude Negrier, Wan Hui Ong Clausen, Frank Driessler, Andrea Landorph, Elena Santagostino
Journal: Blood (2018)
Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles
Authors: C. William Hanke, Kenneth R. Beer, Eggert Stockfleth, Jason Wu, Theodore Rosen, Sharon Levy
Journal: Journal of the American Academy of Dermatology (2010)
STING palmitoylation as a therapeutic target
Authors: Anne Louise Hansen, Kojiro Mukai, Francisco J. Schopfer, Tomohiko Taguchi, Christian K. Holm
Journal: Cellular and Molecular Immunology (2019)

Gain-of-function mutations in the STING-encoding gene TMEM173 are central to the pathology of the autoinflammatory disorder STING-associated vasculopathy with onset in infancy (SAVI). Furthermore, excessive activity of the STING signaling pathway is associated with autoinflammatory diseases, including systemic lupus erythematosus and Aicardi–Goutières syndrome (AGS). Two independent studies recently identified pharmacological inhibitors of STING. Strikingly, both types of compounds are reactive nitro-containing electrophiles that target STING palmitoylation, a posttranslational modification necessary for STING signaling. As a consequence, the activation of downstream signaling molecules and the induction of type I interferons were inhibited. The compounds were effective at ameliorating inflammation in a mouse model of AGS and in blocking the production of type I interferons in primary fibroblasts from SAVI patients. This mini-review focuses on the roles of palmitoylation in STING activation and signaling and as a pharmaceutical target for drug development.