tbuckley/cabot-search huggingface dataset:
Medical leaders have their say on NHS’s greatest achievements
Authors: Eliza Slawther
Journal: BMJ (2018)

As the NHS approaches its 70th birthday, The BMJ has invited its readers to say what they think is the NHS’s most important achievement. From medical breakthroughs to the care and reassurance it provides patients, hundreds of NHS success stories spring to mind.

This week The BMJ asked medical leaders from a range of specialties to put forward their suggestions.

Simon Wessely, professor of psychological medicine at King’s College London, highlights the dramatic reduction in the number of mental health patients who are treated as inpatients as a standout achievement. “When the NHS was founded 97% of people with mental illness were treated in hospitals. Now it’s 3%,” he said.

Helen Stokes-Lampard, chair of the Royal College of General Practitioners, said …
Lymphoedema management to prevent acute dermatolymphangioadenitis in podoconiosis in northern Ethiopia (GoLBeT): a pragmatic randomised controlled trial
Authors: Henok Negussie, Meseret Molla, Moses Ngari, James A Berkley, Esther Kivaya, Patricia Njuguna, Greg Fegan, Abreham Tamiru, Abebe Kelemework, Trudie Lang, Melanie J Newport, Andy McKay, Fikre Enquoselassie, Gail Davey
Journal: The Lancet Global Health (2018)

Podoconiosis (also known as endemic, non-filarial elephantiasis) affects about 4 million subsistence farmers in tropical Africa. Poor awareness of the condition and inadequate evidence for the efficacy of treatment mean that no government in an endemic country yet offers lymphoedema management for patients with podoconiosis. Among patients with filarial lymphoedema, trials suggest that limb care is effective in reducing the most disabling sequelae: episodes of acute dermatolymphangioadenitis. We aimed to test the hypothesis that a simple, inexpensive lymphoedema management package would reduce the incidence of acute dermatolymphangioadenitis in adult patients with podoconiosis in northern Ethiopia.
TCTAP C-092 Non-ST Elevation Myocardial Infarction with Double Chronic Total Occlusions
Authors: Tien-Chi Huang, Chun-Yuan Chu, Wen-Hsien Lee, Po-Chao Hsu, Cheng-An Chiu, Ho-Ming Su, Tsung-Hsien Lin, Chee-Siong Lee, Heueh-Wei Yen, Wen-Chol Voon, Wen-Ter Lai, Sheng-Hsiung Sheu
Journal: Journal of the American College of Cardiology (2018)
A Novel Low Affinity CD19CAR Results in Durable Disease Remissions and Prolonged CAR T Cell Persistence without Severe CRS or Neurotoxicity in Patients with Paediatric ALL
Authors: Sara Ghorashian, Anne Marijn Kramer, Sarah Jayne Albon, Gary Wright, Fernanda Castro, Bilyana Popova, Joan Casanovas Company, Catherine Irving, Winston Vetharoy, Rachel Richardson, Danielle Pinner, Jan Chu, Giovanna Lucchini, Juliana Silva, Oana Ciocarlie, Sarah Inglott, Kim Champion, Allan Hackshaw, Farzin Farzaneh, Robert Chiesa, Kanchan Rao, Anupama Gopala Rao, Philip Ancliffe, Sujith Samarasinghe, Ajay Vora, Paul Veys, Rachael Hough, Robert Wynn, Martin Pule, Persis J Amrolia
Journal: Blood (2017)
Abstract 18338: Genomics-metabolomics Integrative Approach Reveals Novel Biomarkers In DPYS Associated With Higher Glucose Change After Treatment With Atenolol
Authors: Felipe A de Oliveira, Mohamed H Shahin, Yan Gong, Catrin W McDonough, Amber L Beitelshees, John G Gums, Arlene B Chapman, Eric Boerwinkle, Stephen T Turner, Reginald F Frye, Oliver Fiehn, Rima Kaddurah-Daouk, Julie A Johnson, Rhonda M Cooper-DeHoff
Journal: Circulation (2015)

Introduction: β-blockers, including atenolol, are among the most widely prescribed antihypertensive drug classes. However, their use has been associated with hyperglycemia and incident diabetes, which poses concern for prescribers and patients. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study is a multicenter clinical trial with one of its objectives to identify genetic influences on adverse metabolic events in patients treated with atenolol. Here we report a genomics-metabolomics integrative approach to identify biomarkers associated with atenolol-induced glucose change. Methods: PEAR participants were genotyped using the Illumina Omni 1M-Quad Chip. Metabolite profiles were acquired through GC-TOF-MS. Association between baseline levels of metabolites and glucose change was conducted using a multivariate linear regression model adjusted for age, gender and baseline fasting glucose. Genomics-metabolomics integration included selecting SNPs within genes involved in the synthesis and degradation of top metabolites and testing their effect on glucose change in 234 atenolol-treated Caucasians in PEAR, adjusting for age, gender, baseline glucose and principal components 1 and 2. A false discovery rate (FDR) of .05 was used to adjust for multiple comparisons. Replication of significant SNPs was conducted in an additional 228 participants treated with atenolol in PEAR. Results: Metabolomics analysis revealed 3 metabolites associated with glucose change that passed FDR adjustment. The top metabolite signal was beta-alanine. Increasing levels of baseline beta-alanine was significantly correlated with greater glucose increases after atenolol treatment (p=.0003). A total of 79 SNPs in 12 genes in the beta-alanine pathway were explored. SNP rs2669429 in DPYS was significantly associated with glucose change, after FDR adjustment. We found that G allele carriers had significantly greater glucose change compared with non-carriers (p=.0006; β=+2.76 mg/dL). This finding was successfully replicated in the other 228 patients who received atenolol (p=.04; β=+1.86 mg/dL). Conclusions: These results suggest that beta alanine and DPYS rs2669429 SNP might be an important predictor of atenolol-induced dysglycemia.
Physical Inactivity and Mental Health in Late Adolescence
Authors: Mark R. Beauchamp, Eli Puterman, David R. Lubans
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Short-term evaluation of hepatocellular carcinoma after locoregional treatment: Usefulness of contrast-enhanced ultrasonography
Authors: G. Gibiino, M.E. Ainora, M. Pompili, M. Garcovich, L. Riccardi, E.D. Stasio, F. Ponziani, A.M.D. Gaetano, G. Ludovico Rapaccini, A. Gasbarrini, M. Assunta Zocco
Journal: Journal of Hepatology (2018)
A phase III trial of <i>nab</i>-paclitaxel versus dacarbazine in chemotherapy-naive patients with metastatic melanoma: A subanalysis based on <i>BRAF</i> status.
Authors: Evan Hersh, Michele Del Vecchio, Michael Paul Brown, Richard Kefford, Carmen Loquai, Alessandro Testori, Caroline Robert, Mingyu Li, Ileana Elias, Markus F. Renschler, Axel Hauschild
Journal: Journal of Clinical Oncology (2013)

9030 Background: Activating mutations of BRAF V600 can be found in 40%-50% of melanomas and are related to poor prognosis. In a phase 3 trial for the treatment of metastatic melanoma (MM) in chemotherapy-naive patients, nab-paclitaxel (nab-P) vs dacarbazine (DTIC) demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), assessed by independent radiological review (IRR), and a trend toward prolonged overall survival (OS) at the interim survival analysis. The study also explored the effect of BRAF status on the efficacy parameters. Methods: Chemotherapy-naive patients with stage IV melanoma (M1c stage 65%; elevated LDH 28%) and ECOG performance status 0-1 were randomized to nab-P 150 mg/m 2 on days 1, 8, and 15 of a 28-day cycle (n = 264) or DTIC 1000 mg/m 2 on day 1 of each 21-day cycle (n = 265) independent of BRAF status. Prespecified subgroup analyses of final PFS and interim OS in subgroups by BRAF status (V600E mutant, wild-type, or unknown) were performed. Results: BRAF mutation status was balanced between the treatment arms, with 36% and 38% of patients with known BRAF mutation status in the nab-P and DTIC arms, respectively. Patient characteristics were also balanced within BRAF subgroups. As shown in the Table, advantage in the nab-P arm vs DTIC arm was observed for both PFS and interim OS regardless of BRAFmutation status. Poststudy BRAF inhibitor treatment was also balanced. Conclusions: In this phase III trial, treatment effect was independent of BRAF mutation status, benefiting all patients who received nab-P vs DTIC. Therefore nab-P should be considered in the armamentarium for all chemotherapy-naive patients with MM. Clinical trial information: NCT00864253. [Table: see text]
Inhibition of IL6 trans-signaling leads to NAFLD, mature-onset obesity and metabolic syndrome
Authors: T. Lanton, O. Levkovitch, S. Perles, J. Tam, S. Udi, J. Rachmilewitz, R. Abramovitch, S. Rose-John, E. Galun, J. Axelrod
Journal: Journal of Hepatology (2018)
Harry Potter, Magic, and Medicine
Authors: Arjun Gupta
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
Radiosensitivity of Lung Metastases by Primary Histology and Implications for Stereotactic Body Radiation Therapy Using the Genomically Adjusted Radiation Dose
Authors: Kamran A. Ahmed, Jacob G. Scott, John A. Arrington, Arash O. Naghavi, G. Daniel Grass, Bradford A. Perez, Jimmy J. Caudell, Anders E. Berglund, Eric A. Welsh, Steven A. Eschrich, Thomas J. Dilling, Javier F. Torres-Roca
Journal: Journal of Thoracic Oncology (2018)
Comparison of effectiveness and cost-effectiveness of an intensive community supported discharge service versus treatment as usual for adolescents with psychiatric emergencies: a randomised controlled trial
Authors: Dennis Ougrin, Richard Corrigall, Jason Poole, Toby Zundel, Mandy Sarhane, Victoria Slater, Daniel Stahl, Paula Reavey, Sarah Byford, Margaret Heslin, John Ivens, Maarten Crommelin, Zahra Abdulla, Daniel Hayes, Kerry Middleton, Benita Nnadi, Eric Taylor
Journal: The Lancet Psychiatry (2018)

Intensive community treatment to reduce dependency on adolescent psychiatric inpatient care is recommended in guidelines but has not been assessed in a randomised controlled trial in the UK. We designed a supported discharge service (SDS) provided by an intensive community treatment team and compared outcomes with usual care.
Enhancer Remodeling and MicroRNA Alterations Are Associated with Acquired Resistance to ALK Inhibitors
Authors: Mi Ran Yun, Sun Min Lim, Seon-Kyu Kim, Hun Mi Choi, Kyoung-Ho Pyo, Seong Keun Kim, Ji Min Lee, You Won Lee, Jae Woo Choi, Hye Ryun Kim, Min Hee Hong, Keeok Haam, Nanhyung Huh, Jong-Hwan Kim, Yong Sung Kim, Hyo Sup Shim, Ross Andrew Soo, Jin-Yuan Shih, James Chih-Hsin Yang, Mirang Kim, Byoung Chul Cho
Journal: Cancer Research (2018)

Anaplastic lymphoma kinase (ALK) inhibitors are highly effective in patients with ALK fusion-positive lung cancer, but acquired resistance invariably emerges. Identification of secondary mutations has received considerable attention, but most cases cannot be explained by genetic causes alone, raising the possibility of epigenetic mechanisms in acquired drug resistance. Here, we investigated the dynamic changes in the transcriptome and enhancer landscape during development of acquired resistance to ALK inhibitors. Histone H3 lysine 27 acetylation (H3K27ac) was profoundly altered during acquisition of resistance, and enhancer remodeling induced expression changes in both miRNAs and mRNAs. Decreased H3K27ac levels and reduced miR-34a expression associated with the activation of target genes such as AXL. Panobinostat, a pan-histone deacetylase inhibitor, altered the H3K27ac profile and activated tumor-suppressor miRNAs such as miR-449, another member of the miR-34 family, and synergistically induced antiproliferative effects with ALK inhibitors on resistant cells, xenografts, and EML4-ALK transgenic mice. Paired analysis of patient samples before and after treatment with ALK inhibitors revealed that repression of miR-34a or miR-449a and activation of AXL were mutually exclusive of secondary mutations in ALK. Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy.Significance: Epigenetic deregulation drives acquired resistance to ALK inhibitors in ALK-positive lung cancer. Cancer Res; 78(12); 3350-62. ©2018 AACR.
Spleen stiffness decrease as mirror of portal hypertension changes after successful interferon-free therapy in chronic-HCV patients
Authors: F. Ravaioli, E. Dajti, A. Colecchia, V. Alemanni, G. Marasco, M. Tamé, F. Azzaroli, S. Brillanti, G. Mazzella, D. Festi
Journal: Journal of Hepatology (2018)
Enhanced Levels and Enhanced Clonogenic Capacity of Blood Progenitor Cells Following Administration of Stem Cell Factor Plus Granulocyte Colony-Stimulating Factor to Humans
Authors: C.G. Begley, R. Basser, R. Mansfield, B. Thomson, W.R.L. Parker, J. Layton, B. To, J. Cebon, W.P. Sheridan, R.M. Fox, M.D. Green
Journal: Blood (1997)
P483The potential pathological role of cardiac autoantibodies in the development of heart failure
Authors: P Van Den Hoogen, MMH Huibers, R A Weger, A H Schoneveld, J D Laman, P A Doevendans, JPG Sluijter
Journal: Cardiovascular Research (2018)

The idea of regulatory impact of purinergic signaling in the functioning of different type of cells and in this way in the pathogenesis of many diseases is now very popular and finds confirmations in different investigations.The aim of the study was to compare subsets of peripheral T-lymphocytes and the expression on their surface ectonucleotidases CD39 and CD73 in patients with severe and mild aortic stenosis and to assume the involvement of T-cell immunity in valve calcification process.We examined 33 patients with severe calcified aortic stenosis (AS) undergoing surgical heart valve replacement (Median of flow gradient was 48.3 (44.0;54.9))(1 group), 47 patients with moderate AS (Median of flow gradient was 20.5 (14.0;28.0))(2 group) and 42 healthy volunteers (3 group).Median age in the first group was 62.5 (57.0;66.0), in the second -58.0 (45.0;66.0), in the third -48.5 (43.0;53.0)years.The relative number of peripheral naı ¨ve (N, CD45RAþCD62Lþ), central memory (CM, CD45RA-CD62Lþ), effector memory (EM, CD45RA-CD62L-) and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RAþCD62L-) CD45þCD3þCD4þ (Th), CD45þCD3þCD8þ (Tcyt) and CD45þCD3þCD4þCD25bright (Treg) cells as well as the percentages of CD39-and CD73-positive cell within above-mentioned T cell subsets were measured using multicolor flow cytometry.The levels of Tcyt (p¼0.04) and TEMRA Tcyt (p¼0.007) were increased in patients with severe stenosis comparing with mild stenosis.Meanwhile level of Naı ¨ve Treg (p¼0.01) and TEMRA Treg (p<0.001) were decreased.Analyzing the total expression level of ectonucleotidases on T-cells we found that level of CD73þCD39-was decreased in patients with mild stenosis comparing with severe (p<0.001) and with healthy donors (p<0.001).Changes in peripheral T-cells subpopulations in patients with severe aortic stenosis were more pronounced than in healthy donors and patients with moderate stenosis.Taking all the data together we propose that patients with severe stenosis have overexpressed proinflammatory status than the patients with moderate stenosis.Meanwhile decreased number of CD73þCD39-(anti-inflammatory) T-cells in the case of mild stenosis proves this statement and indicates the participation of purinergic signaling in regulation of T-cells inflammation.
Antigen Presentation Keeps Trending in Immunotherapy Resistance
Authors: Anusha Kalbasi, Antoni Ribas
Journal: Clinical Cancer Research (2018)

Through a gain-of-function kinome screen, MEX3B was identified as a mediator of resistance to T-cell immunotherapy not previously identified using CRISPR-based screens. MEX3B is a posttranscriptional regulator of HLA-A, validating the critical role of tumor-intrinsic antigen presentation in T-cell immunotherapy and indicating a new putative molecular target. Clin Cancer Res; 24(14); 3239-41. ©2018 AACRSee related article by Huang et al., p. 3366.
The efficacy and clinical outcome of transjugular intrahepatic portosystemic shunts in the management of ectopic variceal bleeding: a multicenter retrospective study
Authors: R. Oey, K. de Wit, A. Moelker, T. Atalik, O. van Delden, G. Maleux, N. Erler, B. Takkenberg, R. De Man, F. Nevens, H. Van Buuren
Journal: Journal of Hepatology (2018)
Added Value of SPECT/CT in the Evaluation of Sacral Fracture in Patients With Lung Cancer
Authors: Zhen Zhao, Ke Zhou, Bin Liu
Journal: Clinical Nuclear Medicine (2018)

We describe the sacral fractures from 2 lung cancer patients that were confirmed by SPECT/CT. The utilization of SPECT/CT in lung cancer patients can help characterizing the nature of sacral lesions on planar bone scintigraphy.
Humidity-regulated CLCA2 protects the epidermis from hyperosmotic stress
Authors: Kristin Seltmann, Michael Meyer, Jitka Sulcova, Tobias Kockmann, Ulrike Wehkamp, Stephan Weidinger, Ulrich auf dem Keller, Sabine Werner
Journal: Science Translational Medicine (2018)

High environmental humidity rescues atopic dermatitis-like signs in mice, and CLCA2 protects the epidermis from hyperosmotic stress.
Assessing the predictability of <i>IDH</i> mutation and <i>MGMT</i> methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T
Authors: Daniel Paech, Johannes Windschuh, Johanna Oberhollenzer, Constantin Dreher, Felix Sahm, Jan-Eric Meissner, Steffen Goerke, Patrick Schuenke, Moritz Zaiss, Sebastian Regnery, Sebastian Bickelhaupt, Philipp Bäumer, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Peter Bachert, Mark Edward Ladd, Heinz-Peter Schlemmer, Alexander Radbruch
Journal: Neuro-Oncology (2018)

Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla.Thirty-one patients with newly diagnosed glioma were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser effect (NOE) and isolated amide proton transfer (APT; downfield NOE-suppressed APT = dns-APT) CEST signals (mean value and 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T.dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05).Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.
BMS-986036, a PEGylated fibroblast growth factor 21 analogue for the treatment of non-alcoholic steatohepatitis: A population pharmacokinetics and exposure-response analysis
Authors: G. Tirucherai, M. Magnusson, C. Acharya, E. Charles, D. Shevell, R. Christian, Y. Luo
Journal: Journal of Hepatology (2018)
Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates
Authors: Karen J. Parker, Joseph P. Garner, Ozge Oztan, Erna R. Tarara, Jiang Li, Valentina Sclafani, Laura A. Del Rosso, Katie Chun, Sean W. Berquist, Michael G. Chez, Sonia Partap, Antonio Y. Hardan, Elliott H. Sherr, John P. Capitanio
Journal: Science Translational Medicine (2018)

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. These monkeys showed differences in specific neuropeptide and kinase signaling pathways compared to socially competent male monkeys. Using a discovery and replication design, we identified arginine vasopressin (AVP) in cerebrospinal fluid (CSF) as a key marker of group differences in monkey sociality; we replicated these findings in an independent monkey cohort. We also confirmed in an additional monkey cohort that AVP concentration in CSF is a stable trait-like measure. Next, we showed in a small pediatric cohort that CSF AVP concentrations were lower in male children with ASD compared to age-matched male children without ASD (but with other medical conditions). We demonstrated that CSF AVP concentration was sufficient to accurately distinguish ASD cases from medical controls. These data suggest that AVP and its signaling pathway warrant consideration in future research studies investigating new targets for diagnostics and drug development in ASD.