tbuckley/cabot-search huggingface dataset:
Adult social care: specific new tax is needed or NHS funding will suffer, say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2018)

People and employers should have to pay a specific contribution in the form of a tax that will be used to fund adult social care, MPs on two influential committees have concluded.

The need for a “social care premium” is growing, says a joint report1 published on 27 June by the parliamentary committees on health and social care and on housing, communities and local government.

The report on long term funding of adult social care says that the current system is “under very great and unsustainable strain” and that, without significant change, recently announced extra resources for the NHS2 …
Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study
Authors: Miriam Nickel, Alessandro Simonati, David Jacoby, Susanne Lezius, Dirk Kilian, Benjamin Van de Graaf, Odelya E Pagovich, Barry Kosofsky, Kaleb Yohay, Matthew Downs, Peter Slasor, Temitayo Ajayi, Ronald G Crystal, Alfried Kohlschütter, Dolan Sondhi, Angela Schulz
Journal: The Lancet Child & Adolescent Health (2018)
Recurrent Glioblastoma Treated with Recombinant Poliovirus
Authors: Annick Desjardins, Matthias Gromeier, James E. Herndon, Nike Beaubier, Dani P. Bolognesi, Allan H. Friedman, Henry S. Friedman, Frances McSherry, Andrea M. Muscat, Smita Nair, Katherine B. Peters, Dina Randazzo, John H. Sampson, Gordana Vlahovic, William T. Harrison, Roger E. McLendon, David Ashley, Darell D. Bigner
Journal: New England Journal of Medicine (2018)

The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma, confirmed on histopathological testing, with measurable disease (contrast-enhancing tumor of ≥1 cm and ≤5.5 cm in the greatest dimension). The study evaluated seven doses, ranging between 107 and 1010 50% tissue-culture infectious doses (TCID50), first in a dose-escalation phase and then in a dose-expansion phase.From May 2012 through May 2017, a total of 61 patients were enrolled and received a dose of PVSRIPO. Dose level -1 (5.0×107 TCID50) was identified as the phase 2 dose. One dose-limiting toxic effect was observed; a patient in whom dose level 5 (1010 TCID50) was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed. To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use, dose level 5 was deescalated to reach the phase 2 dose. In the dose-expansion phase, 19% of the patients had a PVSRIPO-related adverse event of grade 3 or higher. Overall survival among the patients who received PVSRIPO reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months.Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential. The survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. (Funded by the Brain Tumor Research Charity and others; ClinicalTrials.gov number, NCT01491893 .).
The transcription factor Rfx7 limits metabolism of NK cells and promotes their maintenance and immunity
Authors: Wilson Castro, Sonia T. Chelbi, Charlène Niogret, Cristina Ramon-Barros, Suzanne P. M. Welten, Kevin Osterheld, Haiping Wang, Giorgia Rota, Leonor Morgado, Eric Vivier, Miro E. Raeber, Onur Boyman, Mauro Delorenzi, David Barras, Ping-Chih Ho, Annette Oxenius, Greta Guarda
Journal: Nature Immunology (2018)
Dorsal tegmental dopamine neurons gate associative learning of fear
Authors: Florian Groessl, Thomas Munsch, Susanne Meis, Johannes Griessner, Joanna Kaczanowska, Pinelopi Pliota, Dominic Kargl, Sylvia Badurek, Klaus Kraitsy, Arash Rassoulpour, Johannes Zuber, Volkmar Lessmann, Wulf Haubensak
Journal: Nature Neuroscience (2018)
Multi‐ethnic comparisons of diabetes in heart failure with reduced ejection fraction: insights from the HF‐ACTION trial and the ASIAN‐HF registry
Authors: Lauren B. Cooper, Jonathan Yap, Wan Ting Tay, Tiew‐Hwa K. Teng, Michael MacDonald, Inder S. Anand, Abhinav Sharma, Christopher M. O'Connor, William E. Kraus, Robert J. Mentz, Carolyn S. Lam
Journal: European Journal of Heart Failure (2018)
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
Authors: Panos Zanos, Ruin Moaddel, Patrick J. Morris, Lace M. Riggs, Jaclyn N. Highland, Polymnia Georgiou, Edna F. R. Pereira, Edson X. Albuquerque, Craig J. Thomas, Carlos A. Zarate, Todd D. Gould
Journal: Pharmacological Reviews (2018)

Ketamine, a racemic mixture consisting of (<i>S</i>)- and (<i>R</i>)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these effects. Dissociative, psychotomimetic, cognitive, and peripheral side effects associated with short-term or prolonged exposure, as well as recreational ketamine use, are also discussed. We further describe ketamine's pharmacokinetics, including its rapid and extensive metabolism to norketamine, dehydronorketamine, hydroxyketamine, and hydroxynorketamine (HNK) metabolites. Whereas the anesthetic and analgesic properties of ketamine are generally attributed to direct ketamine-induced inhibition of <i>N</i>-methyl-D-aspartate receptors, other putative lower-affinity pharmacological targets of ketamine include, but are not limited to, γ-amynobutyric acid (GABA), dopamine, serotonin, sigma, opioid, and cholinergic receptors, as well as voltage-gated sodium and hyperpolarization-activated cyclic nucleotide-gated channels. We examine the evidence supporting the relevance of these targets of ketamine and its metabolites to the clinical effects of the drug. Ketamine metabolites may have broader clinical relevance than was previously considered, given that HNK metabolites have antidepressant efficacy in preclinical studies. Overall, pharmacological target deconvolution of ketamine and its metabolites will provide insight critical to the development of new pharmacotherapies that possess the desirable clinical effects of ketamine, but limit undesirable side effects.
Marijuana Use, Respiratory Symptoms, and Pulmonary Function
Authors: Mehrnaz Ghasemiesfe, Divya Ravi, Marzieh Vali, Deborah Korenstein, Mehrdad Arjomandi, James Frank, Peter C. Austin, Salomeh Keyhani
Journal: Annals of Internal Medicine (2018)

The health effects of smoking marijuana are not well-understood.To examine the association between marijuana use and respiratory symptoms, pulmonary function, and obstructive lung disease among adolescents and adults.PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library from 1 January 1973 to 30 April 2018.Observational and interventional studies published in English that reported pulmonary outcomes of adolescents and adults who used marijuana.Four reviewers independently extracted study characteristics and assessed risk of bias. Three reviewers assessed strength of evidence. Studies of similar design with low or moderate risk of bias and sufficient data were pooled.Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio [RR], 2.04 [95% CI, 1.02 to 4.06]) and sputum production (RR, 3.84 [CI, 1.62 to 9.07]). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 [CI, 1.71 to 11.19]), sputum production (RR, 3.40 [CI, 1.99 to 5.79]), wheezing (RR, 2.83 [CI, 1.89 to 4.23]), and dyspnea (RR, 1.56 [CI, 1.33 to 1.83]). Data on pulmonary function and obstructive lung disease were insufficient.Few studies were at low risk of bias, marijuana exposure was limited in the population studied, cohorts were young overall, assessment of marijuana exposure was not uniform, and study designs varied.Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient.None. (PROSPERO: CRD42017059224).
Trade challenges at the World Trade Organization to national noncommunicable disease prevention policies: A thematic document analysis of trade and health policy space
Authors: Pepita Barlow, Ronald Labonte, Martin McKee, David Stuckler
Journal: PLoS Medicine (2018)

Background It has long been contested that trade rules and agreements are used to dispute regulations aimed at preventing noncommunicable diseases (NCDs). Yet most analyses of trade rules and agreements focus on trade disputes, potentially overlooking how a challenge to a regulation's consistency with trade rules may lead to 'policy or regulatory chill' effects whereby countries delay, alter, or repeal regulations in order to avoid the costs of a dispute. Systematic empirical analysis of this pathway to impact was previously prevented by a dearth of systematically coded data. Methods and findings Here, we analyse a newly created dataset of trade challenges about food, beverage, and tobacco regulations among 122 World Trade Organization (WTO) members from January 1, 1995 to December 31, 2016. We thematically describe the scope and frequency of trade challenges, analyse economic asymmetries between countries raising and defending them, and summarise 4 cases of their possible influence. Between 1995 and 2016, 93 food, beverage, and tobacco regulations were challenged at the WTO. 'Unnecessary' trade costs were the focus of 16.4% of the challenges. Only one (1.1%) challenge remained unresolved and escalated to a trade dispute. Thirty-nine (41.9%) challenges focussed on labelling regulations, and 18 (19.4%) focussed on quality standards and restrictions on certain products like processed meats and cigarette flavourings. High-income countries raised 77.4% (n = 72) of all challenges raised against low- and lower-middle–income countries. We further identified 4 cases in Indonesia, Chile, Colombia, and Saudi Arabia in which challenges were associated with changes to food and beverage regulations. Data limitations precluded a comprehensive evaluation of policy impact and challenge validity. Conclusions Policy makers appear to face significant pressure to design food, beverage, and tobacco regulations that other countries will deem consistent with trade rules. Trade-related influence on public health policy is likely to be understated by analyses limited to formal trade disputes.
Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer
Authors: Howard I. Scher, Ryon P. Graf, Nicole A. Schreiber, Anuradha Jayaram, Eric Winquist, Brigit McLaughlin, David Lu, Martin Fleisher, Sarah Orr, Lori Lowes, Amanda Anderson, Yipeng Wang, Ryan Dittamore, Alison L. Allan, Gerhardt Attard, Glenn Heller
Journal: JAMA Oncology (2018)

<h3>Importance</h3> A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need. <h3>Objective</h3> To determine whether a validated assay for the nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells can determine differential overall survival among patients with mCRPC treated with taxanes vs ARS inhibitors. <h3>Design, Setting, and Participants</h3> This blinded correlative study conducted from December 31, 2012, to September 1, 2016, included 142 patients with histologically confirmed mCRPC and who were treated at Memorial Sloan Kettering Cancer Center, The Royal Marsden, or the London Health Sciences Centre. Blood samples were obtained prior to administration of ARS inhibitors or taxanes as a second-line or greater systemic therapy for progressing mCRPC. <h3>Main Outcomes and Measures</h3> Overall survival after treatment with an ARS inhibitor or taxane in relation to pretherapy AR-V7 status. <h3>Results</h3> Among the 142 patients in the study (mean [SD] age, 69.5 [9.6] years), 70 were designated as high risk by conventional prognostic factors. In this high-risk group, patients positive for AR-V7 who were treated with taxanes had superior overall survival relative to those treated with ARS inhibitors (median overall survival, 14.3 vs 7.3 months; hazard ratio, 0.62; 95% CI, 0.28-1.39;<i>P</i> = .25). Patients negative for AR-V7 who were treated with ARS inhibitors had superior overall survival relative to those treated with taxanes (median overall survival, 19.8 vs 12.8 months; hazard ratio, 1.67; 95% CI, 1.00-2.81;<i>P</i> = .05). <h3>Conclusions and Relevance</h3> This study suggests that nuclear-localized AR-V7 protein in circulating tumor cells can identify patients who may live longer with taxane chemotherapy vs ARS inhibitor treatment.
Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification
Authors: Masahiro Uni, Yosuke Masamoto, Tomohiko Sato, Yasuhiko Kamikubo, Shunya Arai, Eiji Hara, Mineo Kurokawa
Journal: Leukemia (2018)
Virtual Care as a Specialty
Authors: Lee H. Schwamm
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 1732: Gp96-Ig/costimulator combination platform improves T cell priming and enhances immunity, memory, and tumor elimination
Authors: Louise Giffin, Louis Gonzalez, Jason Rose, Jeff Hutchins
Journal: Cancer Research (2018)

Abstract In this study, we report that addition of checkpoint inhibition and T cell costimulators into the Heat Biologics gp96-Ig-based vaccine platform elicits stronger antigen-specific CD8+ T cell activation and expansion, stimulates memory precursor cell activation, and enhances rejection of murine tumors. Despite the dramatic successes of checkpoint inhibitors in limited populations of cancer patients, 60-90% of patients are still failing to respond to these therapies. It is widely believed that approaches such as ours that target multiple facets of the immune system, including combinations with checkpoint inhibition and costimulator agonism, will be required to improve patient outcomes. Heat Biologics' first-generation ImPACT vaccine is a cell-based therapy that utilizes representative tumor cell lines expressing the antigen chaperone, gp96-Ig, to efficiently prime antigen-specific CD8+ T cells. Heat recently developed a next generation vaccine called ComPACT (COMbination Pan-Antigen Cytotoxic Therapy) that incorporates expression of a T cell costimulator (OX40L-Ig) and gp96-Ig within a single vaccine cell line. In multiple murine tumor and tumor-naive models, ComPACT elicits more potent activation of antigen-specific T cells as well as expansion of CD127+KLRG1- memory precursor cells, leading to a detectable memory response. Furthermore, ComPACT lacks the toxic systemic inflammatory cytokine production and proliferation of non-specific CD4+ T cells and Tregs observed with systemic administration of OX40 agonist antibodies. ComPACT also leads to high frequencies of IFNγ+, TNFα+, granzyme B+ and IL-2+ antigen-specific CD8+ T cells in mice at both priming and boosting, which increases rejection of established murine melanoma (B16.F10) and colon cancer (CT26) tumors and increased overall survival. Here, we have further assessed ImPACT and ComPACT-OX40L in combination with the anti-PD1 checkpoint inhibitor and with expression of an additional cell-secreted T cell costimulator, TL1A-Ig. In various murine models we show that these treatments synergize effectively to amplify antigen-specific T cells, program a functional memory response, and eliminate tumors. The combination of ComPACT-OX40L/TL1A with αPD1 or αPD-L1 may therefore translate into an efficacious approach to treat human cancers. Citation Format: Louise Giffin, Louis Gonzalez, Jason Rose, Jeff Hutchins. Gp96-Ig/costimulator combination platform improves T cell priming and enhances immunity, memory, and tumor elimination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1732.
Correlates and Outcomes of Physician Burnout
Authors: Eric Y. Chang, Nicolas Bakinde, Anam Umar
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Screening for Osteoporosis
Authors: Jane A. Cauley
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Web-Based Platform vs Genetic Counselors in Educating Patients About Carrier Results From Exome Sequencing—Reply
Authors: Barbara B. Biesecker, Katie L. Lewis, Leslie G. Biesecker
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Oligonucleotide Drugs for Transthyretin Amyloidosis
Authors: Joel N. Buxbaum
Journal: New England Journal of Medicine (2018)

In this issue of the Journal, Adams et al.1 and Benson et al.2 report the results of two randomized, double-blind, controlled trials testing the therapeutic efficacy of two different chemically modified oligonucleotides to treat transthyretin amyloidosis, which is an autosomal dominant hereditary polyneuropathy related to the organ deposition of mutant forms of the transthyretin protein (encoded by mutated TTR) over time. The circulating protein is synthesized predominantly in the liver, but there is also important local production in the eye by retinal pigment epithelial cells and by the choroid plexus epithelium. Transthyretin proteins form a homotetramer; tetramers containing at least . . .