tbuckley/cabot-search huggingface dataset:
Deep Uncertainties in the Criteria for Physician Aid-in-Dying for Psychiatric Patients
Authors: Tomasz Żuradzki, Piotr Grzegorz Nowak
Journal: The American Journal of Bioethics (2019)

In their insightful article, Brent Kious and Margaret Battin (2019) correctly identify an inconsistency between an involuntary psychiatric commitment for suicide prevention and physician aid-in-dying (PAD).They declare that it may be possible to resolve the problem by articulating "objective standards for evaluating the severity of others' suffering," but ultimately they admit that this task is beyond the scope of their article since the solution depends on "a deep and difficult" question about comparing the worseness of two possible scenarios: letting someone die (who could have been helped) with not letting someone die (whose suffering could only be alleviated by death).In our commentary, we argue that creating such standards is more difficult than the authors assume because of the many types of deep uncertainties we have to deal with: (1) diagnostic, (2) motivational, and (3) existential (cf. Żuradzki 2017).A "diagnostic" uncertainty was overlooked by Kious and Battin since they did not fully recognize the unique nature of the diagnosis of mental illnesses.They rightly point out that terminality in physician aid-in-dying requests is not important per se and should be treated rather as an instrument to determine that a further life for a given patient would be most likely "worse than death."However, this may only be grasped in some cases of somatic illnesses, where it is at least sometimes possible to make an unquestionable diagnosis and prognosis based on the understanding of pathophysiological mechanisms.For example, if a doctor supposes that a patient has prostate cancer, she can easily verify her hypothesis by referring the patient for a prostate biopsy.In the case of mental illnesses, there is usually no such a laboratory method of diagnosis confirmation, even if one considers mental illness as
Accurate quantification of astrocyte and neurotransmitter fluorescence dynamics for single-cell and population-level physiology
Authors: Yizhi Wang, Nicole V. DelRosso, Trisha V. Vaidyanathan, Michelle K. Cahill, Michael E. Reitman, Silvia Pittolo, Xuelong Mi, Guoqiang Yu, Kira E. Poskanzer
Journal: Nature Neuroscience (2019)
TCT-162 Impact of Thrombocytopenia on Subsequent 1-Year Major Adverse Cardiovascular Event (MACE) in Non–ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS)
Authors: Jonathan Fang, Anthony Wong, Kwong Yue Eric Chan, Arthur Yung, Catherine Shea, Michael Sze, Timothy Un, Hung-Fat Tse, Ki-Wan Kelvin Chan, Cheung Chi Simon Lam, Chor Cheung Tam, Yui-Ming LAM
Journal: Journal of the American College of Cardiology (2019)
TCT-444 Left Ventricular Thinning and Distension to Mimic Heart Failure and Functional Mitral Regurgitation in Swine Hearts: A Platform to Test New Transcatheter Mitral and Heart Failure Devices
Authors: Elorm Agra, Kirthana Suresh, Daisuke Onohara, Muralidhar Padala
Journal: Journal of the American College of Cardiology (2019)
SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder
Authors: Valentina Del Dotto, Farid Ullah, Ivano Di Meo, Pamela Magini, Mirjana Gusic, Alessandra Maresca, Leonardo Caporali, Flavia Palombo, Francesca Tagliavini, Evan Harris Baugh, Bertil Macao, Zsolt Szilagyi, Camille Peron, Margaret A. Gustafson, Kamal Khan, Chiara La Morgia, Piero Barboni, Michele Carbonelli, Maria Lucia Valentino, Rocco Liguori, Vandana Shashi, Jennifer Sullivan, Shashi Nagaraj, Mays El-Dairi, Alessandro Iannaccone, Ioana Cutcutache, Enrico Bertini, Rosalba Carrozzo, Francesco Emma, Francesca Diomedi-Camassei, Claudia Zanna, Martin Armstrong, Matthew Page, Nicholas Stong, Sylvia Boesch, Robert Kopajtich, Saskia Wortmann, Wolfgang Sperl, Erica E. Davis, William C. Copeland, Marco Seri, Maria Falkenberg, Holger Prokisch, Nicholas Katsanis, Valeria Tiranti, Tommaso Pippucci, Valerio Carelli
Journal: Journal of Clinical Investigation (2019)

Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the mitochondrial single-strand binding protein (SSBP1) in 4 families with dominant and 1 with recessive inheritance. We show that SSBP1 mutations in patient-derived fibroblasts variably affect the amount of SSBP1 protein and alter multimer formation, but not the binding to ssDNA. SSBP1 mutations impaired mtDNA, nucleoids, and 7S-DNA amounts as well as mtDNA replication, affecting replisome machinery. The variable mtDNA depletion in cells was reflected in severity of mitochondrial dysfunction, including respiratory efficiency, OXPHOS subunits, and complex amount and assembly. mtDNA depletion and cytochrome c oxidase-negative cells were found ex vivo in biopsies of affected tissues, such as kidney and skeletal muscle. Reduced efficiency of mtDNA replication was also reproduced in vitro, confirming the pathogenic mechanism. Furthermore, ssbp1 suppression in zebrafish induced signs of nephropathy and reduced optic nerve size, the latter phenotype complemented by WT mRNA but not by SSBP1 mutant transcripts. This previously unrecognized disease of mtDNA maintenance implicates SSBP1 mutations as a cause of human pathology.
Association of Optimism With Cardiovascular Events and All-Cause Mortality
Authors: Alan Rozanski, Chirag Bavishi, Laura D. Kubzansky, Randy Cohen
Journal: JAMA Network Open (2019)

Optimism and pessimism can be easily measured and are potentially modifiable mindsets that may be associated with cardiovascular risk and all-cause mortality.To conduct a meta-analysis and systematic review of the association between optimism and risk for future cardiovascular events and all-cause mortality.PubMed, Scopus, and PsycINFO electronic databases were systematically searched from inception through July 2, 2019, to identify all cohort studies investigating the association between optimism and pessimism and cardiovascular events and/or all-cause mortality by using the following Medical Subject Heading terms: optimism, optimistic explanatory style, pessimism, outcomes, endpoint, mortality, death, cardiovascular events, stroke, coronary artery disease, coronary heart disease, ischemic heart disease, and cardiovascular disease.Data were screened and extracted independently by 2 investigators (A.R. and C.B.). Adjusted effect estimates were used, and pooled analysis was performed using the Hartung-Knapp-Sidik-Jonkman random-effects model. Sensitivity and subgroup analyses were performed to assess the robustness of the findings. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed.Cardiovascular events included a composite of fatal cardiovascular mortality, nonfatal myocardial infarction, stroke, and/or new-onset angina. All-cause mortality was assessed as a separate outcome.The search yielded 15 studies comprising 229 391 participants of which 10 studies reported data on cardiovascular events and 9 studies reported data on all-cause mortality. The mean follow-up period was 13.8 years (range, 2-40 years). On pooled analysis, optimism was significantly associated with a decreased risk of cardiovascular events (relative risk, 0.65; 95% CI, 0.51-0.78; P < .001), with high heterogeneity in the analysis (I2 = 87.4%). Similarly, optimism was significantly associated with a lower risk of all-cause mortality (relative risk, 0.86; 95% CI, 0.80-0.92; P < .001), with moderate heterogeneity (I2 = 73.2%). Subgroup analyses by methods for assessment, follow-up duration, sex, and adjustment for depression and other potential confounders yielded similar results.The findings suggest that optimism is associated with a lower risk of cardiovascular events and all-cause mortality. Future studies should seek to better define the biobehavioral mechanisms underlying this association and evaluate the potential benefit of interventions designed to promote optimism or reduce pessimism.
Analysis of Leukemogenic Effects of RUNX1 and CSF3R Mutations Using Congenital Neutropenia (CN)/AML Patient-Derived Induced Pluripotent Stem Cells (iPSCs)
Authors: Benjamin Dannenmann, Maksim Klimiankou, Christian Lindner, Azadeh Zahabi, Regine Bernhard, Tatsuya Morishima, Cornelia Zeidler, Lothar Kanz, Karl Welte, Julia Skokowa
Journal: Blood (2016)
Authors’ reply to Henderson
Authors: Lee Hooper, Tracey Brown, Julii Brainard, Asmaa Abdelhamid, Xia Wang, Fujian Song
Journal: BMJ (2019)

Henderson mentions mechanisms which would be expected to lead to increased polyunsaturated fat intake being harmful to diabetic control.1 Excessive free fatty acid flux from adipose tissue followed by upregulation of oxidation of polyunsaturated fats and increased generation of free radicals both suggest that higher intakes of polyunsaturated fats would lead to higher levels of oxidation products, exacerbating insulin resistance, damaging …
Serum B-Cell Maturation Antigen As a Biomarker for Chronic Lymphocytic Leukemia Treated with Ibrutinib
Authors: Clare Sun, Camilia Soof, Alankrita Taneja, Sarah E. M. Herman, Erika Cook, Kyle Udd, Haiming Chen, Eric Sanchez, Xin Tian, Inhye E. Ahn, James R Berenson, Adrian Wiestner
Journal: Blood (2017)
TCT-386 Long-Term Outcomes After Left Main PCI: An Individual Patient-Data Pooled Analysis of 21 Randomized Controlled Trials
Authors: Mayank Yadav, Pieter Smits, Clemens von Birgelen, Patrick Serruys, Roxana Mehran, Ajay Jayant Kirtane, Gary Mintz, Mahesh Madhavan, Bjorn Redfors, Aaron Crowley, Mengdan Liu, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
Advancing antimicrobial strategies for managing oral biofilm infections
Authors: Yang Jiao, Franklin R. Tay, Li-na Niu, Ji-hua Chen
Journal: International Journal of Oral Science (2019)

Abstract Effective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells. The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years. Antimicrobial dental materials based on antimicrobial agent release, contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface. Among the therapeutic approaches for managing biofilms in clinical practice, antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms, and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches. Nevertheless, more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data. The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.
Early Enrichment of ESR1 Mutations and the Impact on Gene Expression in Presurgical Primary Breast Cancer Treated with Aromatase Inhibitors
Authors: Mariana Ferreira Leal, Ben P. Haynes, Eugene Schuster, Belinda Yeo, Maria Afentakis, Lila Zabaglo, Vera Martins, Richard Buus, Andrew Dodson, Maggie C.U. Cheang, Ian E. Smith, Lesley-Ann Martin, Mitch Dowsett
Journal: Clinical Cancer Research (2019)

Abstract Purpose: To investigate the presence of ESR1 mutations in primary estrogen-receptor–positive (ER+) breast cancer treated with extended (&amp;gt;4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression. Experimental Design: We evaluated ER, progesterone receptor, and Ki67 by immunostaining, ESR1 mutations by droplet-digital PCR and expression of over 800 key breast cancer genes in paired pre- and post-NAI tumor samples from 87 ER+ breast cancer patients. Results: Cell proliferation and estrogen-regulated genes (ERG) remained suppressed in most tumors indicative of persistent response to NAI. Enrichment of ESR1 mutations was found in five tumors and predominantly in patients receiving therapy for &amp;gt;6 months. ESR1-mutant tumors showed increased expression of ESR1 transcript and limited suppression of ERGs and proliferation-associated genes in response to NAI. ESR1 wild-type tumors with high residual proliferation (Ki67r ≥10%; 15/87 tumors) showed lower ESR1/ER expression pre- and post-therapy and lower ERGs. Tumors with ESR1 mutations or Ki67r ≥10% showed less inhibition of estrogen response, cell cycle, and E2F-target genes. Conclusions: Ligand-independent ER signaling, as a result of ESR1 mutation or reduced ER dependence, identified after extended NAI therapy, can guide early selection of patients who would benefit from combination therapy.
Risk and predictors of psoriasis in breast cancer patients : A Swedish population based cohort study
Authors: Haomin Yang, Judith S. Brand, Jingmei Li, Jonas F. Ludvigsson, Emilio Ugalde-Morales, Flaminia Chiesa, Per Hall, Kamila Czene
Journal: Cancer Research (2018)

Risk and predictors of psoriasis in breast cancer patients : A Swedish population based cohort study
Hodgkin's Disease
Authors: Henry Jackson, Frederic Parker
Journal: New England Journal of Medicine (1946)

THIS concluding paper of the series on various aspects of Hodgkin's disease concerns treatment and prognosis.Treatment Hodgkin's Paragranuloma It is difficult to give advice on the treatment of Hodgkin's paragranuloma. In view of the apparently localized nature of the disease in many cases and the excellent results of surgery in 2 of our cases, it seems reasonable to advocate radical dissection, followed by irradiation whenever the condition seems to be sharply confined to a readily accessible region. It must be pointed out, nevertheless, that there have been recurrences in 3 of 5 cases in which surgical excision was practiced, . . .
Medicare to Cover CAR T-Cell Therapies
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
Severe Silicosis in Engineered Stone Fabrication Workers — California, Colorado, Texas, and Washington, 2017–2019
Authors: Cecile Rose, Amy Heinzerling, Ketki Patel, Coralynn Sack, Jenna Wolff, Lauren Zell-Baran, David Weissman, Emily Hall, Robbie Sooriash, Ronda B. McCarthy, Heidi Bojes, Brian Korotzer, Jennifer Flattery, Justine Lew Weinberg, Joshua Potocko, Kirk D. Jones, Carolyn K. Reeb-Whitaker, Nicholas K. Reul, Claire R. LaSee, Barbara L. Materna, Ganesh Raghu, Robert Harrison
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Silicosis is an incurable occupational lung disease caused by inhaling particles of respirable crystalline silica. These particles trigger inflammation and fibrosis in the lungs, leading to progressive, irreversible, and potentially disabling disease. Silica exposure is also associated with increased risk for lung infection (notably, tuberculosis), lung cancer, emphysema, autoimmune diseases, and kidney disease (1). Because quartz, a type of crystalline silica, is commonly found in stone, workers who cut, polish, or grind stone materials can be exposed to silica dust. Recently, silicosis outbreaks have been reported in several countries among workers who cut and finish stone slabs for countertops, a process known as stone fabrication (2-5). Most worked with engineered stone, a manufactured, quartz-based composite material that can contain >90% crystalline silica (6). This report describes 18 cases of silicosis, including the first two fatalities reported in the United States, among workers in the stone fabrication industry in California, Colorado, Texas, and Washington. Several patients had severe progressive disease, and some had associated autoimmune diseases and latent tuberculosis infection. Cases were identified through independent investigations in each state and confirmed based on computed tomography (CT) scan of the chest or lung biopsy findings. Silica dust exposure reduction and effective regulatory enforcement, along with enhanced workplace medical and public health surveillance, are urgently needed to address the emerging public health threat of silicosis in the stone fabrication industry.
Challenges and Opportunities for Childhood Cancer Drug Development
Authors: Peter J. Houghton, Raushan T. Kurmasheva, Michael M. Gottesman
Journal: Pharmacological Reviews (2019)

Cancer in children is rare with approximately 15,700 new cases diagnosed in the United States annually. Through use of multimodality therapy (surgery, radiation therapy, and aggressive chemotherapy), 70% of patients will be "cured" of their disease, and 5-year event-free survival exceeds 80%. However, for patients surviving their malignancy, therapy-related long-term adverse effects are severe, with an estimated 50% having chronic life-threatening toxicities related to therapy in their fourth or fifth decade of life. While overall intensive therapy with cytotoxic agents continues to reduce cancer-related mortality, new understanding of the molecular etiology of many childhood cancers offers an opportunity to redirect efforts to develop effective, less genotoxic therapeutic options, including agents that target oncogenic drivers directly, and the potential for use of agents that target the tumor microenvironment and immune-directed therapies. However, for many high-risk cancers, significant challenges remain.
TCT-835 Impact of Early Intervention With Alogliptin on Coronary Plaque Regression in Patients with Acute Coronary Syndromes: A Prospective, Single-Center, Randomized Trial
Authors: Shinnosuke Kikuchi, Kozo Okada, Kiyoshi Hibi, Naoki Nakayama, Eiichi Akiyama, Yasushi Matsuzawa, Nobuhiko Maejima, Noriaki Iwahashi, Masami Kosuge, Toshiaki Ebina, Kouichi Tamura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2019)
Underwater endoscopic submucosal dissection of an obstructing giant colonic lipoma
Authors: Angelo Caruso, Costantino Sgamato, Helga Bertani, Flavia Pigò, Santi Mangiafico, Giuseppe Grande, Rita Luisa Conigliaro
Journal: Endoscopy (2019)

Gastrointestinal (GI) lipomas are rare (0.2 % – 4.4 % of benign GI subepithelial tumors) and usually asymptomatic. Giant colonic lipomas (> 4 cm) may cause symptoms such as bleeding or intestinal occlusion and surgical resection is considered the treatment of choice [1] [2]. With the development of endoscopic submucosal dissection (ESD), we have been able to resect larger tumors. We report a case of a large colonic lipoma treated by ESD.
TCT-743 Comparison of Patient and Clinical Factors Within Echocardiogram Reports to Predict Disparity in Care of Patients With Severe Aortic Stenosis
Authors: Hemal Gada, Amit Vora, Daniel O’Hair, Cara Brigman, Loren Wagner, Chris Rogers, Logan Brigman, Navjot Kohli
Journal: Journal of the American College of Cardiology (2019)
Treatment of Seizure Disorders (Epilepsy)
Authors: Mary Louise Scholl
Journal: New England Journal of Medicine (1963)

Petit-Mal SeizuresThis classification includes only patients who have simple staring spells accompanied by unconsciousness usually lasting for less than thirty seconds and whose electroencephalograms display the typical spike-and-wave activity of 2 1/2 to 3 per second. These spells can generally be precipitated if the patient is made to hyperventilate. This type of seizure is seen between the ages of four and twelve years and rarely after puberty. The spells may be infrequent or may recur as often as several hundred times a day. Organic brain disease is very rare in patients who exhibit only petit-mal attacks. Therefore, the prognosis . . .
Benefit:Risk Profile of Budesonide in Obstructive Airways Disease
Authors: Donald P. Tashkin, Brian Lipworth, Ralph Brattsand
Journal: Drugs (2019)

Airway inflammation is a major contributing factor in both asthma and chronic obstructive pulmonary disease (COPD) and represents an important target for treatment. Inhaled corticosteroids (ICS) as monotherapy or in combination therapy with long-acting β2-agonists or long-acting muscarinic antagonists are used extensively in the treatment of asthma and COPD. The development of ICS for their anti-inflammatory properties progressed through efforts to increase topical potency and minimise systemic potency and through advances in inhaled delivery technology. Budesonide is a potent, non-halogenated ICS that was developed in the early 1970s and is now one of the most widely used lung medicines worldwide. Inhaled budesonide's physiochemical and pharmacokinetic/pharmacodynamic properties allow it to reach a rapid and high airway efficacy due to its more balanced relationship between water solubility and lipophilicity. When absorbed from the airways and lung tissue, its moderate lipophilicity shortens systemic exposure, and its unique property of intracellular esterification acts like a sustained release mechanism within airway tissues, contributing to its airway selectivity and a low risk of adverse events. There is a large volume of clinical evidence supporting the efficacy and safety of budesonide, both alone and in combination with the fast- and long-acting β2-agonist formoterol, as maintenance therapy in patients with asthma and with COPD. The combination of budesonide/formoterol can also be used as an as-needed reliever with anti-inflammatory properties, with or without regular maintenance for asthma, a novel approach that is already approved by some country-specific regulatory authorities and currently recommended in the Global Initiative for Asthma (GINA) guidelines. Budesonide remains one of the most well-established and versatile of the inhaled anti-inflammatory drugs. This narrative review provides a clinical reappraisal of the benefit:risk profile of budesonide in the management of asthma and COPD.