tbuckley/cabot-search huggingface dataset:
DDIS-27. TARGETING ATP DOCKING AND P35/P25 BINDING OF CDK5 IN GLIOMA STEM CELLS USING SYNTHETIC INHIBITORS
Authors: Subhas Mukherjee, Gary Schiltz, Matt Clutter, Rama Mishra, Cheryl Olson, Bilge Dunder, Nitya Sharma, Steven Markwell, Daniel Brat
Journal: Neuro-Oncology (2019)

Abstract The survival advantage of glioma stem cells (GSCs) represents a critical mechanism for growth, therapy resistance and recurrence in glioblastoma. So far, targeting GSCs has not been highly specific, since these cells co-opt the normal developmental signaling pathways. We have demonstrated that the activated CDK5-CREB1 signaling axis regulates GSC self-renewal and also promotes radiation-resistance. Thus targeting CDK5 signaling is highly rational, yet there are challenges. Most of the available CDK5 inhibitors also target other CDKs non-specifically. In collaboration with The Center for Molecular Evolution and Drug Discovery, we are developing novel CDK5 inhibitors that are highly potent and specific. METHODOLOGY: The CKD5-p25 crystal structure (pdb code 1UNL) was used to conduct a virtual high throughput screen (vHTS). A library of 10 million commercially available compounds which had been filtered to ensure they possessed good drug-like properties was screened against the crystal structure. The top 33 compounds based on their predicted target binding, synthetic feasibility and availability were tested in an in vitro kinase assay to measure CDK5 inhibition. RESULTS: Of the 33 potential hit, 11 compounds showed a CDK5 inhibition of &lt; 50 µM. These 11 hits represent 4 distinct chemical scaffolds. Two of them have IC50 &lt; 1 µM, with one compound having an IC50 &lt; 0.4 µM. The vHTS and subsequent in vitro testing have therefore confirmed the identification of several new series of potent CDK5 hit compounds. We are now characterizing the kinase selectivity of our different hit series and evaluating their activity in cell-based assays. This will help focus efforts on the most promising 1–2 scaffolds for further medicinal chemistry optimization to improve the compounds’ potency, selectivity and brain penetration. Ultimately, our optimized compounds will be tested in GBM models to demonstrate their effectiveness in inhibiting CDK5 as a new approach for treating GBM.
Splenic Marginal Zone B Lymphocytes Regulate Cardiac Remodeling After Acute Myocardial Infarction in Mice
Authors: Yanyi Sun, Cristina Pinto, Stéphane Camus, Vincent Duval, Paul Alayrac, Ivana Zlatanova, Xavier Loyer, Jose Vilar, Mathilde Lemitre, Angélique Levoye, Meritxell Nus, Hafid Ait-Oufella, Ziad Mallat, Jean-Sébastien Silvestre
Journal: Journal of the American College of Cardiology (2022)
Febrile seizures.
Authors: D P Addy
Journal: BMJ (1980)

hyperthyroid patients and observed no change in serum T3 concentrations.2We realise that these 3-adrenergic blocking drugs are less activethanpropranolol as membrane-stabilising agents, both as a local anaesthetic and in their action on intracellular cardiac potentials,3 but we would have expected to see a fall in serum T3 levels if the mechanism proposed by Dr Heyma and others is correct.
Nebulizer therapy. Guidelines. British Thoracic Society Nebulizer Project Group
Journal: Thorax (1997)

Asthma Campaign (on behalf of asthma patients), The Cystic Fibrosis Trust (on behalf The consensus meeting was supported by an educational of patients with cystic fibrosis), Breathe Easy grant from Medic-Aid Ltd.The project group is grateful for the secretarial support of Mrs Elaine Power.
Post-GWAS functional analysis identifies CUX1 as a regulator of p16INK4a and cellular senescence
Authors: Danli Jiang, Wei Sun, Ting Wu, Meijuan Zou, Sathish Babu Vasamsetti, Xiaoyu Zhang, Yihan Zhao, Julie A. Phillippi, Amr H. Sawalha, Sina Tavakoli, Partha Dutta, Jonathan Florentin, Stephen Y. Chan, Tammy S. Tollison, None Di Wu, Jing Cui, Ian Huntress, Xinxia Peng, Toren Finkel, Gang Li
Journal: Nature Aging (2022)

Abstract Accumulation of senescent cells with age is an important driver of aging and age-related diseases. However, the mechanisms and signaling pathways that regulate senescence remain elusive. In this report, we performed post-genome-wide association studies (GWAS) functional studies on the CDKN2A/B locus, a locus known to be associated with multiple age-related diseases and overall human lifespan. We demonstrate that transcription factor CUX1 (Cut-Like Homeobox 1) specifically binds to an atherosclerosis-associated functional single-nucleotide polymorphism (fSNP) (rs1537371) within the locus and regulates the CDKN2A/B- encoded proteins p14 ARF , p15 INK4b and p16 INK4a and the antisense noncoding RNA in the CDK4 (INK4) locus (ANRIL) in endothelial cells (ECs). Endothelial CUX1 expression correlates with telomeric length and is induced by both DNA-damaging agents and oxidative stress. Moreover, induction of CUX1 expression triggers both replicative and stress-induced senescence via activation of p16 INK4a expression. Thus, our studies identify CUX1 as a regulator of p16 INK4a -dependent endothelial senescence and a potential therapeutic target for atherosclerosis and other age-related diseases.
Clinical Lectures Delivered at Charing Cross Hospital
Authors: H. Salter
Journal: BMJ (1863)

<h3>ABSTRACT</h3> The human liver is an essential multifunctional organ, and liver diseases are rising with limited treatment options. However, the cellular complexity and heterogeneity of the liver remain poorly understood. Here, we performed single-cell RNA-sequencing of ~5,000 cells from normal liver tissue of 6 human donors to construct the first human liver cell atlas. Our analysis revealed previously unknown sub-types among endothelial cells, Kupffer cells, and hepatocytes with transcriptome-wide zonation of these populations. We show that the EPCAM<sup>+</sup> population is highly heterogeneous and consists of hepatocyte progenitors, cholangiocytes and a <i>MUC6</i><sup>+</sup> stem cell population with a specific potential to form liver organoids. As proof-of-principle, we applied our atlas to unravel phenotypic changes in cells from hepatocellular carcinoma tissue and to investigate cellular phenotypes of human hepatocytes and liver endothelial cells engrafted into a humanized <i>FAH</i><sup>-/-</sup> mouse liver. Our human liver cell atlas provides a powerful and innovative resource enabling the discovery of previously unknown cell types in the normal and diseased liver.
Abstract 17241: National Trends in Systolic and Diastolic Heart Failure From 2004 to 2014
Authors: Aasim Afzal, Tariq Nisar, Aaron Kluger, Aayla Jamil, Joost Felius, Shelley A Hall, Parag Kale
Journal: Circulation (2018)

Introduction: Heart Failure (HF) affects 6 million people in the US and costs $30.7B/year. Prior studies have shown declines in hospitalization rates, length of stay (LOS), and mortality for HF patients, but it is unclear if these trends hold true for both systolic HF (SHF) and diastolic HF (DHF). To better assess the epidemiological and economic burden of HF, we assessed the trends in LOS, mortality, and cost for both SHF and DHF. Methods: We identified hospitalizations for SHF (primary diagnosis ICD-9 codes 428.1, 428.2x, 428.4x or 428.9) and DHF (code 428.3x) from 2004 to 2014 in the National Inpatient Sample (NIS). National estimates were calculated using the NIS sampling weights. LOS, in-patient mortality, charges, demographics, and co-morbidities were abstracted. Results: We found an overall decreasing trend in LOS for HF, with LOS declining more sharply for DHF than for SHF hospitalizations (Cuzick test; Table 1 and Fig. 1). In 2014, LOS for DHF was on average 4.1 hours shorter than for SHF (95% confidence interval [CI] 3.5 - 4.6h). Inpatient mortality decreased despite an increase in number of co-morbidities for both groups, but in 2014 the odds of a patient dying with SHF were higher than for DHF (odds ratio 1.16, CI (1.14, 1.17). Total charges increased for SHF but remained relatively unchanged for DHF. In 2014, a hospitalization for SHF cost on average $10,349 more than for DHF (p&lt;0.001). Conclusion: While DHF costs have remained relatively unchanged, SHF costs have risen between 2004 and 2014 despite an overall decrease in LOS and concurrent decline in inpatient mortality. This cost increase may have resulted, in part, from increased use of advanced support devices in these patients. Further studies will be needed to identify the reasons for increased cost of care such as use of percutaneous mechanical circulatory support devices.
Cardiopulmonary Critical Care
Authors: Richard W. Carlson
Journal: JAMA (1991)

In the preface to the first edition of this book, Dr Dantzker indicated that the goal was to provide insights into the pathophysiology of disease processes that affect the heart and lung, with application of this knowledge to develop therapeutic approaches to the critically ill. The second edition has been substantially expanded and updated so that it comes closer to this goal. Several of the original chapters have been enlarged and revised, and a number of new chapters and topics have been added. Although the book continues to emphasize the heart and lungs, other topics, including renal and fluid and electrolyte balance, are treated more fully. These changes should make the volume even more appealing to the intensivist. The editor has assembled an impressive group of contributors who are experts in their respective fields. The first of three sections deals with pathophysiology and includes ten chapters on a variety of
Racial differences in survival outcomes for early-stage (T1 tumor) penile cancer: Analysis from the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Nellowe Candelario, Elizabeth Molina, Maria Teresa Bourlon, Simon P. Kim, Elizabeth R Kessler, Philippe E. Spiess, Thomas W. Flaig
Journal: Journal of Clinical Oncology (2022)

5 Background: Penile cancer is a rare malignancy that accounts for less than 1% of male cancers in the United States. Localized disease, particularly T1 tumors (no invasion the corpora spongiosum, corpora cavernosa or adjacent structures using the AJCC 7th edition staging system) are potentially curable with local surgery. We present the racial differences in survival outcomes for T1, penile cancer from the SEER database. Methods: From 2004 to 2016, we identified all patients with T1 (coded as T1, T1a, T1b),N0,M0 penile cancer in the SEER-18 database were included. Univariate Kaplan-Meier analysis and multivariable (adjusting for age, year of diagnosis, race, socioeconomic status, primary tumor site and type of surgery) Cox-Regression analysis were conducted to investigate prognostic variables for cancer specific survival (CCS). Results: A total of 4,406 patients were identified with penile cancer; 1,941 patients had T1 disease and were further evaluated (Table). On multivariable analysis, Black (HR: 1.72, CI 1.01- 2.94; p=0.046) and Hispanic individuals (HR: 2.15, CI 1.36- 3.40; p= 0.001) had worse CSS compared to the White men with T1 disease. Logistic regression analysis shows no difference in the application of primary surgical resection by race (p=0.065). In the univariate analysis, patients who underwent primary site surgery had better 5-year CSS (HR: 0.36, CI 0.22-0.60; p &lt;0.001). Among those undergoing primary surgery, the 5-year CSS was superior with excisional biopsy (HR: 0.22, CI 0.12-0.40; p &lt; 0.001) compared to simple/partial removal of the primary tumor. Conclusions: Significant racial disparities in CSS exist in early-stage penile cancer patients. CSS is worse in Black and Hispanic T1 penile cancer patients compared to White patients. CSS is also decreased in those without any primary surgery and in those treated with simple/partial surgical removal compared to excisional biopsy. Further research on the cause of racial disparity outcomes in penile cancer is needed.[Table: see text]
Evaluation of Antimicrobial Drug Use and Concurrent Infections During Hospitalization of Patients With COVID-19 in Japan
Authors: Junpei Komagamine, Taku Yabuki, Kohei Matsumoto, Nao Tanaka
Journal: JAMA Network Open (2022)

A recent meta-analysis 1,2 and a prospective study 3 reported that bacterial coinfection and secondary infection among patients with COVID-19 infection are uncommon.However, in these studies, antimicrobial drugs were prescribed for approximately 70% of patients with the disease. 2 Therefore, data are needed on patients with COVID-19 infection who do not routinely receive an antimicrobial drug prescription, to identify the true rate of concurrent infection in this patient population.At the
MOTOR NOTES FOR MEDICAL MEN
Authors: H. M. Buist
Journal: BMJ (1921)

FOR the first time since thle outbreak of war it may be written that a motor show for medical men is being hield in London.The exhibition opened yesterday at Olympia, Kensington, and the White City, Shepherd's Bush, by the Society of Motor Manufacturers and Traders under the patronage of the King, reveals complete reversion of policy on the part of the world's motor car manufacturers.
Association Between High-Deductible Health Plans and Hernia Acuity
Authors: Kirbi Yelorda, Liam Rose, M. Kate Bundorf, Huda A. Muhammad, Arden M. Morris
Journal: JAMA Surgery (2022)

About half of people younger than 65 years with private insurance are enrolled in a high-deductible health plan (HDHP). While these plans entail substantially higher out-of-pocket costs for patients with chronic medical conditions who require ongoing care, their effect on patients undergoing surgery who require acute care is poorly understood. It is plausible that higher out-of-pocket costs may lead to delays in care and more complex surgical conditions.
Molecular characterization of renal cell carcinoma with venous tumor thrombus: Genomic aberrations with renal vein wall invasion.
Authors: Xiaoxi Dong, Cheng Liu, Shidong Jia, Jianjun Yu, Lulin Ma
Journal: Journal of Clinical Oncology (2022)

385 Background: Renal cell carcinoma (RCC) patients with tumor thrombus (TT) have been observed distinct phenotypes of TT: deeply invading into the wall of renal vein/inferior vena cava (IVC) (DITT) or minimal/non-invasion (NITT), with different surgical strategy and post-thrombectomy outcome. However, the molecular characters of DITT/NITT have not been investigated, due to operational challenges and limited patient access. Methods: In this study, primary tumor and TT samples from 68 patients having IVC thrombectomy were prospectively collected for DNA mutation profiling and RNA expression profiling, using Predicine panel-based next generation sequencing and transcriptome RNA-SEQ, respectively. Next-generation sequencing and bioinformatics data analysis was conducted in Colleges of American Pathologist (CAP)-accredited laboratory in Shanghai, China (Huidu Shanghai Medical Sciences Ltd.). Kaplan–Meier survival analysis was performed to analyze the correlation between DITT/NITT and clinical outcome, and p-values were calculated using log-rank test. Results: When metastasis was detected, patients with DITT showed significantly shorter overall survival comparing to patients with NITT (P &lt; 0.05, log-rank test). However, this difference was not observed in non-metastatic group. Successful sequencing has been achieved in 100% (68/68) patients. NITT tumor bulks more frequently carried mutations in PTEN, TP53 and epigenetic regulators such as SETD2, PBRM1 and KDM5C and had higher expression of cell cycle related pathway genes. In contrast, DITT had lower expression of genes encoding cell adhesion and extracellular matrix molecules such as ADAM33, NCAM1 and FLRT2, which could contribute to higher invasiveness. Conclusions: To our knowledge, this is the first large study to systematically interrogate genomic landscape and molecular features of different TT phenotypes in RCC patients. The differential genomic mutation and gene expression landscapes across the two groups may reflect biologic differences and clinical implications such as tumor invasiveness and aggressiveness.
Abstract 106: Emergency Medical Response for Non-Hospitalized Patient Events in a Children’s Hospital
Authors: Olivia L Hoffman, Jane Romano, Monica E Kleinman
Journal: Circulation (2018)

Introduction: Hospital-based Code Blue (CB) teams are designed for hospitalized patients (HP) with unanticipated medical emergencies outside of an intensive care unit (ICU). At our pediatric institution, the same team responds to CB calls involving non-hospitalized patients (NHP) such as outpatients, visitors, and staff. The appropriate team composition for responses to NHP emergencies in a children’s hospital has not yet been studied. Hypothesis: There are significant differences between the characteristics of NHP and HP who require emergency medical response, and the majority of responses for NHP do not require advanced emergency or critical care. Methods: We analyzed a retrospective cohort of CB responses at a large, urban, academic children’s medical center over a one-year period (January 1 - December 31, 2017). Rapid response team (different from CB team) activations were excluded. We evaluated the demographic and clinical characteristics of NHP-related CB responses and compared them to HP-related CB responses. Results: The Code Blue team was activated 168 times, of which 135 (80.4%) were NHP-related and 33 (19.6%) were HP-related. Ninety-one (67.4%) of the NHP responses involved adults (age &gt;18 years) compared to 6 (18.2%) of the HP. The CB team transferred 107 (79.3%) of the NHP to an emergency department, and 19 (75.6%) of the HP to an ICU for further care. The primary type of condition and most common critical interventions performed by the CB team are listed in the table below. Conclusions: Code blue activations in our children’s hospital more often involve NHP than HP. NHP responses are more likely to involve adults and infrequently require critical interventions. Use of a pediatric CB team for initial response to NHP events may be an unnecessary use of pediatric critical care resources. Future studies are warranted to evaluate the most effective CB team structure, training, and certification for NHP emergency responses.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009–2013
Authors: Quinn T. Ostrom, Haley Gittleman, Jordan Xu, Courtney Kromer, Yingli Wolinsky, Carol Kruchko, Jill S. Barnholtz-Sloan
Journal: Neuro-Oncology (2016)
Code of practice for the clinical assessment of licensed medicinal products in general practice.
Journal: BMJ (1983)

A code of practice for the clinical assessment of licensed drugs by physicians in general practice has been developed jointly by the British Medical Association, the Royal Society of General Practitioners, and the Association of the British Pharmaceutical Industry. The new code, reproduced in full here, outlines the reasons drug assessments outside hospitals are needed; defines the roles of pharmaceutical firms, ethics committees, and investigators; lists items that must be included in research protocols; and offers guidelines on confidentiality, publication of results, and remuneration.
Abstracts
Journal: Annals of the Rheumatic Diseases (1957)

ACTH, Cortisone, and other Steroids; Other General Subjects.At the end of each section is a list of titles ofarticles noted but not abstracted.Not all sections may be represented in any one issue.The section "ACTH, Cortisone, and other Steroids" includes abstracts and titles of articles dealing with research into the scope and modus operandi of
Association of Deepwater Horizon Oil Spill Response and Cleanup Work With Risk of Developing Hypertension
Authors: Richard K. Kwok, W. Braxton Jackson, Matthew D. Curry, Patricia A. Stewart, John A. McGrath, Mark Stenzel, Tran B. Huynh, Caroline P. Groth, Gurumurthy Ramachandran, Sudipto Banerjee, Gregory C. Pratt, Aubrey K. Miller, Xian Zhang, Lawrence S. Engel, Dale P. Sandler
Journal: JAMA Network Open (2022)

Exposure to hydrocarbons, fine particulate matter (PM2.5), and other chemicals from the April 20, 2010, Deepwater Horizon disaster may be associated with increased blood pressure and newly detected hypertension among oil spill response and cleanup workers.
Strengthening a Study of Diabetes Progression After Statin Use—Reply
Authors: Ishak A. Mansi, Ildiko Lingvay, Carlos A. Alvarez
Journal: JAMA Internal Medicine (2022)

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 Journals 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
Which pill?
Authors: J Drife
Journal: BMJ (1983)

Which pill?The publicity surrounding the two recent Lancet papers' 2 on cancer and oral contraceptives has-as predicted3-caused public concern, and has put general practitioners in a difficult position.Women have been advised to go to their doctors for advice, but doctors have been given little time to discuss the reliability and implications of the reports-which contain a complex mixture of epidemiology and endocrinology.The patients who are asking for advice fall into three groups.Women taking the pill want to know whether to stop it or change to another brand; those who have taken the pill in the past want to know if they fall into a high risk category requiring special screening; and women who have not yet taken the pill may ask when-if ever-it will be safe to start.Before these questions can be answered the two Lancet papers must first be put into perspective.The Oxford Family Planning Association study' looked at the incidence of all forms of cervical neoplasia among 3154 parous women using the intrauterine contraceptive device and 6838 parous pill users (many of whom had been taking formulations with 50 ug or more of oestrogen).The women on the pill had a 750 greater incidence of cervical neoplasia and the risk was related to duration of pill use.Vessey and his coauthors therefore suggested that the pill may directly affect the cervix, but confirmatory evidence for this is scanty and, as the authors point out, the effect they observed may have been due to other factors such as sexual activity.Age at first intercourse4 and number of partners5 are important risk factors for cervical cancer but were not documented in this study- though the finding that pill users were slightly younger at mar- riage and at first term pregnancy may suggest that they began intercourse earlier than women using intrauterine contraceptive devices.This trend may have been strong enough to override the opposing trend in other risk factors.Other similar studies have produced conflicting results.'Further investigation is needed to confirm or refute Vessey's suggestion that the pill may have a direct effect on the cervix in addition to its in- direct effect via sexual activity.,Recent publicity may have given women an exaggerated impression of the risks: in Vessey's study the background risk of all types of cervical neoplasia (including dysplasia) was 1 in 1000 woman years and this was doubled by prolonged use of the pill.Preliminary data from the Royal College of General Practitioners' study suggest that the excess risk of invasive cervical carcinoma among pill users is less than 1 in 14 000.6All cancers in Vessey's study were detected at a curable stage, and regular