tbuckley/cabot-search huggingface dataset:
NEUROTROPHINS AND CILIARY NEUROTROPHIC FACTOR - THEIR BIOLOGY AND PATHOLOGY
Authors: H Sariola, K Sainio, U Arumae, M Saarma
Journal: Annals of Internal Medicine (1994)

Neurotrophins (NTFs) and ciliary neurotrophic factor (CNTF) induce the differentiation of neuronal cells, rescue them from naturally occurring death, and trigger neuronal regeneration. The NTFs bind to two classes of cell surface receptors, whereas CNTF receptor is composed of three subunits. The functions of these polypeptide survival factors with trophic action on nerve cells have recently been approached by the targeted disruption of the CNTF, NTF and their receptor genes by the homologous recombination technique. The embryonic growth and morphogenesis of these gene 'knock-out' mice is normal, but they develop with defects in various subsets of the peripheral nervous system, and the homozygous mutant mice often die during the early postnatal period. Disturbances in the biology of NTFs and CNTF have recently been implicated in the pathogenesis of certain common neurodegenerative disorders, such as Parkinson's disease, motor neurone diseases, and Alzheimer's disease. Intensive research on their pharmaceutical perspective has, therefore, been provoked. All neurotrophins and CNTF can now be synthesized on a large scale as biologically active recombinant proteins, and several alternatives for their local applications to the target tissue have been presented. Their therapeutic potential is discussed.
Trends in Alcoholic Fatty Liver Disease
Authors: Jinxiang Zhang, Yong Lin, Lanjing Zhang
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
Arterial infusion of recombinant human adenoviral p53 gene in treatment of advanced pancreatic cancer.
Authors: Jinggang Mo, Bing He, Kai Tan, Xiaopin Yang, Xusheng Zhuang, Libin Ruan
Journal: Journal of Clinical Oncology (2012)

e14523 Background: There are few treatment options for unresectable advanced pancreatic cancer. Here we report beneficial effects of arterial infusion of recombinant human adenoviral p53 gene (rAdp53) in treatment of the late-stage pancreatic cancer. Methods: Sixteen patients having an average age of 56.8 years old, 11 males and 5 females, with unresectable advanced pancreatic cancer were treated using arterial infusion of rAdp53 at dose of 2-4×10 12 viral particles (VP) per 3 days for 4 times. The rAdp53diluted into 10 ml ofsaline solution were slowly injected into arterial branches supplying the tumor. Results: Among 16 patients, 56.3% (9/16) achieved a partial response. Overall one year survival rate was 62.5%. Jaundice of 7 in 10 patients was reduced. The ascites of 8 in11 cases was absorbed. General symptoms associated with the late-stage pancreatic cancer were relieved in 81.3% (13/16) of cases. There were no significant side effects or complications observed except for transient fever. Conclusions: The treatment of arterial infusion of rAdp53 showed the beneficiary effects of both safety and efficacy and is a treatment option for unresectable advanced pancreatic cancer.
Age and Birth Cohort–Adjusted Rates of Suicide Mortality Among US Male and Female Youths Aged 10 to 19 Years From 1999 to 2017
Authors: Bin Yu, Xinguang Chen
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Strategic planning to curb increasing suicide rate among US youths requires unbiased measures of suicide mortality, as the unadjusted suicide mortality rates conventionally used in describing time trends and sex patterns are confounded by the differences in chronological age and year of birth. <h3>Objective</h3> To measure time trends and sex differences in suicide mortality among US youths using age and birth cohort (age-cohort)–adjusted rates. <h3>Design, Setting, and Participants</h3> This population-based multiyear cross-sectional study of US youths aged 10 to 19 years was a secondary analysis of the suicide data for January 1, 1999, to December 31, 2017, derived from the Wide-Ranging Online Data for Epidemiologic Research, a database prepared by the US Centers for Disease Control and Prevention to promote research. Data analysis was conducted from May 24 to May 27, 2019. <h3>Main Outcomes and Measures</h3> Age-cohort–adjusted suicide mortality rates by year and sex were used as the main outcomes. These adjusted rates were calculated based on the period effect estimated with the age-period-cohort (APC) modeling method. Participants' age, year of birth, and the year when suicide occurred were used as time-related risk factors. <h3>Results</h3> Age-cohort–adjusted suicide mortality rates were estimated successfully by year and by sex. The adjusted rates were obtained after controlling for a V-shaped cohort effect and a curved age effect that also differed by sex. The unadjusted suicide mortality rate for male youths increased from 7.4 per 100 000 in 1999 to 10.7 per 100 000 in 2017, while the adjusted rate increased from 4.9 per 100 000 in 1999 to 8.7 per 100 000 in 2017. The unadjusted suicide mortality rates for female youths were 1.6 per 100 000 in 1999 and 3.5 per 100 000 in 2017, while the adjusted rates were 1.7 per 100 000 in 1999 and 4.2 per 100 000 in 2017. <h3>Conclusions and Relevance</h3> Findings of this study indicate a more rapid increase and smaller male-female difference in suicide rates among US youths since 1999 than those shown by the unadjusted suicide mortality rates. The adjusted rates provide unbiased data that are needed for evidence-based decision-making and strategies to curb the increasing suicide rates among US youths.
Predictive rules for optical diagnosis of &lt; 10-mm colorectal polyps based on a dedicated software
Authors: Cesare Hassan, Raf Bisschops, Pradeep Bhandari, Emmanuel Coron, Helmut Neumann, Oliver Pech, Loredana Correale, Alessandro Repici
Journal: Endoscopy (2019)

Abstract Background The BASIC classification for predicting in vivo colorectal polyp histology incorporates both surface and pit/vessel descriptor domains. This study aimed to define new BASIC classes for adenomatous and hyperplastic polyps. Methods A video library (102 still images/videos of &lt; 10-mm polyps using white-light [WLI] and blue-light imaging [BLI]) was reviewed by seven expert endoscopists. Polyps were rated according to the individual descriptors of the three BASIC domains (surface/pit/vessel). A model to predict polyp histology (adenomatous or hyperplastic) was developed using multivariable logistic regression and subsequent “leave-one-out” cross-validation. New BASIC rules were then defined by Delphi agreement. The overall accuracy of these rules when used by experts was evaluated according to the level of confidence and light type. Results The strength of prediction for adenomatous histology from 2175 observations assessed by area under the curve (AUC; 95 % confidence interval) was poor-to-fair for the surface descriptors (0.50 [0.33 – 0.69] for mucus; 0.68 [0.57 – 0.79] for irregular surface), but stronger for pits (0.87 [0.80 – 0.96] for featureless/round/not round) and vessels (0.80 [0.65 – 0.87] for not present/lacy/pericryptal). By combining the domains, a good-to-excellent prediction was shown (AUC 0.89 [0.81 – 0.96]). After the definition of new BASIC rules for adenomatous and hyperplastic polyps, accuracy for high confidence BLI predictions was 90.3 % (86.3 % – 93.2 %), which was superior to high confidence WLI (83.7 % [77.3 % – 87.7 %]) and low confidence BLI predictions (77.7 % [61.1 % – 88.6 %]). Conclusions Based on the strength of prediction, the new BASIC classes for adenomatous and hyperplastic histology show favorable results for accuracy and confidence levels.
Implementation of an Electronic Medical Record Tool for Early Detection of Deep Vein Thrombosis in the Ambulatory Oncology Setting: The Cleveland Clinic Experience
Authors: Girish Kunapareddy, Benjamin Switzer, Madison Conces, Pramod Pinnamaneni, Bhumika J. Patel, Sagar S. Patel, Alicia Redden, Dana E. Angelini, Keith McCrae, Brad Pohlman, Alok A. Khorana
Journal: Blood (2017)
Lipid-Dependent Regulation of Ion Channels and G Protein–Coupled Receptors: Insights from Structures and Simulations
Authors: Anna L. Duncan, Wanling Song, Mark S.P. Sansom
Journal: The Annual Review of Pharmacology and Toxicology (2019)

Ion channels and G protein–coupled receptors (GPCRs) are regulated by lipids in their membrane environment. Structural studies combined with biophysical and molecular simulation investigations reveal interaction sites for specific lipids on membrane protein structures. For K channels, PIP 2 plays a key role in regulating Kv and Kir channels. Likewise, several recent cryo-EM structures of TRP channels have revealed bound lipids, including PIP 2 and cholesterol. Among the pentameric ligand-gated ion channel family, structural and biophysical studies suggest the M4 TM helix may act as a lipid sensor, e.g., forming part of the binding sites for neurosteroids on the GABA A receptor. Structures of GPCRs have revealed multiple cholesterol sites, which may modulate both receptor dynamics and receptor oligomerization. PIP 2 also interacts with GPCRs and may modulate their interactions with G proteins. Overall, it is evident that multiple lipid binding sites exist on channels and receptors that modulate their function allosterically and are potential druggable sites.
GATA3-Controlled Nucleosome Eviction Drives <i>MYC</i> Enhancer Activity in T-cell Development and Leukemia
Authors: Laura Belver, Alexander Y. Yang, Robert Albero, Daniel Herranz, Francesco G. Brundu, S. Aidan Quinn, Pablo Pérez-Durán, Silvia Álvarez, Francesca Gianni, Marissa Rashkovan, Devya Gurung, Pedro P. Rocha, Ramya Raviram, Clara Reglero, Jose R. Cortés, Anisha J. Cooke, Agnieszka A. Wendorff, Valentina Cordó, Jules P. Meijerink, Raúl Rabadan, Adolfo A. Ferrando
Journal: Cancer Discovery (2019)

Long-range enhancers govern the temporal and spatial control of gene expression; however, the mechanisms that regulate enhancer activity during normal and malignant development remain poorly understood. Here, we demonstrate a role for aberrant chromatin accessibility in the regulation of MYC expression in T-cell lymphoblastic leukemia (T-ALL). Central to this process, the NOTCH1-MYC enhancer (N-Me), a long-range T cell-specific MYC enhancer, shows dynamic changes in chromatin accessibility during T-cell specification and maturation and an aberrant high degree of chromatin accessibility in mouse and human T-ALL cells. Mechanistically, we demonstrate that GATA3-driven nucleosome eviction dynamically modulates N-Me enhancer activity and is strictly required for NOTCH1-induced T-ALL initiation and maintenance. These results directly implicate aberrant regulation of chromatin accessibility at oncogenic enhancers as a mechanism of leukemic transformation. SIGNIFICANCE: MYC is a major effector of NOTCH1 oncogenic programs in T-ALL. Here, we show a major role for GATA3-mediated enhancer nucleosome eviction as a driver of MYC expression and leukemic transformation. These results support the role of aberrant chromatin accessibility and consequent oncogenic MYC enhancer activation in NOTCH1-induced T-ALL.This article is highlighted in the In This Issue feature, p. 1631.
The Membership Committee of the ESC
Authors: Cecilia Linde, Cecilia Linde, Michael Glikson, Julia Mascherbauer, Zuzana Motovska, Stephan Gielen, Claire Bouleti, Jelena Celutkiene, Avital Porter, Jeremy Pearson, Alida Caforio, Bernard Cosyns, Kristina Haugaa, Jean-Claude Deharo, Mihaela Grecu, Paul Dendale, Silvia Castelletti, Sofie Gevaert, Sambola Antonia, Michael Haude, Martine Gilard, Mitja Lainscak, Ewa Anita Jankowska, Elena Marques-Sule, Lis Neubeck, Ozge Ozden Tok, Edit Gara, Stavros Konstantinides, Stavros Konstantinides, Christian Wolpert, Pekka Raatikainen, Nikola Pavlovic
Journal: Cardiovascular Research (2019)
Abstract MP25: Adiposity-related DNA Methylation as a Predictor of Coronary Heart Disease in Adult African Americans: The Atherosclerosis Risk in Communities Study
Authors: Steve Nguyen, Weihua Guan, Megan L Grove, Jan Bressler, Yun Li, Myriam Fornage, Eric Boerwinkle, Kari E North, James S Pankow, Ellen W Demerath
Journal: Circulation (2016)

Background: Epigenetic modifications such DNA methylation variation comprise a potentially useful new class of biomarkers that may improve coronary heart disease (CHD) risk stratification, or better capture early pathophysiological processes. However, replicated associations of DNA methylation and CHD are few, and existing studies are primarily cross-sectional and restricted to European ancestry populations. Given the strong association of excess adiposity with CHD risk, we tested 41 DNA methylation variants (CpG sites) that were previously reported to be associated with BMI in African Americans (AA), and tested their association with incident CHD in AA adults. Methods: Genome-wide DNA methylation variation was assayed at a single time point in stored frozen leukocyte samples using the Illumina HM450K chip in a subset of 1,797 AA participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study of cardiovascular disease risk conducted in four U.S. communities. Methylation beta values and other continuous covariates were winsorized prior to analysis to reduce outlier influence. Incident CHD cases were identified through annual telephone interviews and medical records review. Proportional hazards regression (frailty) models examined the relationship between DNA methylation beta values and incident CHD with separate models for each of the 41 CpGs, with a random effect specified for chip. Fully adjusted models included age, BMI, sex, center, education, household income, leisure time activity, alcohol and tobacco use, white blood cell count and imputed cell type differentials. To explore the relationship between DNA methylation and CHD risk accounting for major CHD risk factors, mediator models additionally contained prevalent hypertension status, blood glucose, and total and HDL cholesterol. A Bonferroni-corrected p value of 0.00122 was set as the threshold for statistical significance. Results: There were 224 cases of incident CHD out of 1,797 individuals at risk. One CpG, cg09664445 near CLUH was significantly associated with incident CHD in the full (HR=1.47, 95%CI=1.26, 1.72) and mediator model (HR=1.46, 95% CI=1.24, 1.71) while cg06500161 near ABCG1 was significant in the full model only (HR=1.34, 95% CI=1.15, 1.56). Conclusion: Two obesity-related DNA methylation variants were associated with incident CHD independent of known risk factors and potential confounders. In the literature, CLUH is involved in mitochondrial biogenesis while promoter hypermethylation of ABCG1 was previously found to increase CHD risk and atherosclerosis. Replication in additional cohorts is required to further investigate the predictive value of DNA methylation variants over established risk factors and biomarkers for CHD.
Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells
Authors: Marie Pouzolles, Alice Machado, Mickaël Guilbaud, Magali Irla, Sarah Gailhac, Pierre Barennes, Daniela Cesana, Andrea Calabria, Fabrizio Benedicenti, Arnauld Sergé, Indu Raman, Quan-Zhen Li, Eugenio Montini, David Klatzmann, Oumeya Adjali, Naomi Taylor, Valérie S. Zimmermann
Journal: Journal of Allergy and Clinical Immunology (2019)
Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome
Authors: Damien J. Cabral, Swathi Penumutchu, Elizabeth M. Reinhart, Cheng Zhang, Benjamin J. Korry, Jenna I. Wurster, Rachael Nilson, August Guang, William H. Sano, Aislinn D. Rowan-Nash, Hu Li, Peter Belenky
Journal: Cell Metabolism (2019)
CUT&amp;RUNTools: a flexible pipeline for CUT&amp;RUN processing and footprint analysis
Authors: Qian Zhu, Nan Liu, Stuart H. Orkin, Guo-Cheng Yuan
Journal: Genome biology (2019)

Abstract We introduce CUT&amp;RUNTools as a flexible, general pipeline for facilitating the identification of chromatin-associated protein binding and genomic footprinting analysis from antibody-targeted CUT&amp;RUN primary cleavage data. CUT&amp;RUNTools extracts endonuclease cut site information from sequences of short-read fragments and produces single-locus binding estimates, aggregate motif footprints, and informative visualizations to support the high-resolution mapping capability of CUT&amp;RUN. CUT&amp;RUNTools is available at https://bitbucket.org/qzhudfci/cutruntools/ .
<i>Notes from the Field:</i> Fatal <i>Naegleria fowleri</i> Meningoencephalitis After Swimming in Hot Spring Water — California, 2018
Authors: Duc J. Vugia, James Richardson, Thomas Tarro, Chairut Vareechon, Pia S. Pannaraj, Elizabeth Traub, Jennifer R. Cope, Sharon Balter
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
Declining US Fertility
Authors: Bridget Kuehn
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
Insights From a Patient With Lung Cancer—Party Therapy Is Way Better Than Chemotherapy
Authors: David B. Sykes
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Survival with splenectomy in splenic marginal zone lymphoma: Analysis of the Surveillance, Epidemiology and End Results (SEER) database.
Authors: Adam J. Olszewski
Journal: Journal of Clinical Oncology (2012)

8044 Background: The role of splenectomy as the primary therapy for splenic marginal zone lymphoma has been questioned. We studied relative survival in SMZL and the impact of splenectomy on lymphoma-specific survival (LSS). Methods: SMZL cases (diagnosed in 1993-2008) were derived from the SEER database. Age, sex and race-matched actuarial survival data were summarized. Factors predictive of splenectomy were studied using logistic regression with a subsequent propensity score (PS)-weighted survival analysis. Results: 1071 patients were identified with a median age of 69 years (range, 25-96) and a median follow up of 33 months. 53% were women and 92% were white. 70% of the lymphomas were stage III/IV with B symptoms recorded in 22.3%. 54% of patients underwent splenectomy. The significant factors predictive of surgery included younger age (p&lt;10 -14 ), stage I/II (p&lt;10 -15 ), B-symptoms (p=0.003), no prior malignancy (p=0.002), with significantly lower rates in black patients (OR 0.41, 95%CI 0.21-0.80, p=0.008), on the Pacific Coast (OR 0.62, 95%CI 0.47-0.81, p=0.0004) and with decreasing rates over time (p=0.0002). The actuarial 5-year relative survival was 82.8% (95%CI 77.9-86.7%) with no difference by sex (p=0.79), race or stage. 54% of deaths were related to SMZL with the estimated LSS of 80.8% (95%CI 78-84%). Splenectomy was not associated with improved LSS in propensity score-stratified log-rank test (p=0.60) or in the PS-weighted Cox model (HR=0.93, 95%CI 0.62-1.38, p=0.70). Advancing age (HR 1.05, 95%CI 1.03-1.07, p&lt;10 -8 ) and presence of B-symptoms (HR=1.98, 95%CI 1.30-3.01, p=0.002) were significantly predictive of death from SMZL, with no evidence of improvement in LSS over the years (HR=0.97, 95%CI=0.91-1.03, p=0.34). There was also no detectable impact of splenectomy on survival in patients who ultimately died of SMZL (p=0.83). Conclusions: In this cohort, the largest studied to date, splenectomy did not demonstrate a survival benefit in SMZL. Patients continue to have decreased survival despite advances in other indolent B-cell lymphomas. The role of splenectomy versus chemoimmunotherapy remains to be determined.
Tackle prescription drug dependency with improved clinician training, says review
Authors: Elisabeth Mahase
Journal: BMJ (2019)

A landmark report into prescription drugs that have a risk of dependency has concluded that more high quality research is needed on withdrawal effects—especially of antidepressants—as well as on the harms of dependence and withdrawal and how to avoid them.

Public Health England’s major review of prescribed drugs1 is the first of its kind. Commissioned by the government in 2017, it looked at dependence on benzodiazepines, z drugs, gabapentinoids, opioids for chronic non-cancer pain, and antidepressants.

It found that one in four adults in England—11.5 million people—were prescribed at least one of these classes of drugs in primary care in the year ending March 2018. Of those receiving a prescription in March 2018, between 22% and 32% (depending on the medicine class) had been taking the drugs for at least the previous three years.

Altogether 930 000 people in England were continuously prescribed antidepressants from April 2015 to March 2018 while 540 000 were continuously prescribed an opioid. …