tbuckley/cabot-search huggingface dataset:
Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy
Authors: Zinal S. Chheda, Gary Kohanbash, Kaori Okada, Naznin Jahan, John Sidney, Matteo Pecoraro, Xinbo Yang, Diego A. Carrera, Kira M. Downey, Shruti Shrivastav, Shuming Liu, Yi Lin, Chetana Lagisetti, Pavlina Chuntova, Payal B. Watchmaker, Sabine Mueller, Ian F. Pollack, Raja Rajalingam, Angel M. Carcaboso, Matthias Mann, Alessandro Sette, K. Christopher Garcia, Yafei Hou, Hideho Okada
Journal: The Journal of Experimental Medicine (2017)

The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector. TCR-transduced HLA-A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly suppressed the progression of glioma xenografts in mice. Alanine-scanning assays suggested the absence of known human proteins sharing the key amino acid residues required for recognition by the TCR, suggesting that the TCR could be safely used in patients. These data provide us with a strong basis for developing T cell–based therapy targeting this shared neoepitope.
Rapid Differential Diagnosis of Breast Microcalcification Using Targeted Near‐Infrared Fluorophores
Authors: Min Ho Park, Wonbong Lim, Danbi Jo, Jin Seok Jung, Subin Kim, Jangho Kim, Hyo Soon Lim, Ji Shin Lee, Jung‐Joon Min, Hoon Hyun
Journal: Advanced Healthcare Materials (2017)

Abstract Early detection and differential diagnosis of breast microcalcifications are of significant importance in effective treatment of early breast cancer, because mineral composition of breast calcification is directly associated with different pathological states. However, applying image‐based modalities for component identification in breast calcification remains challenging, because no calcification‐specific contrast agent is available to distinguish between benign and malignant (type I and type II, respectively) calcifications of breast lesions. In this study, real‐time near‐infrared (NIR) fluorescence imaging of breast microcalcifications using targeted NIR fluorophores in combination with dual‐channel NIR fluorescence imaging system is reported. This strategy can be used to solve major problem in mammography and ultrasonography methods for the differentiation of benign and malignant microcalcifications. Thus, this novel technology shows significant potential for breast cancer diagnosis and image‐guided surgery performed with increased precision and efficiency by providing differential diagnosis of breast microcalcifications.
Abstract 13929: Cardiopulmonary Fitness Index a Novel Index That Improves Prognostic Assessment of Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Yi Tang, Qin Luo, Zhihui Zhao, Liu Gao, Qi Jin, Changming Xiong, Zhihong Liu
Journal: Circulation (2016)

Background: Peak oxygen consumption or ventilator efficiency, which can better provide prognostic information in patients with idiopathic pulmonary arterial hypertension (IPAH) remains controversial, and studies showed circulatory power and ventilatory power were both variables predictive of prognosis in patients with left heart failure. This study was aimed to assess whether circulatory power and ventilatory power were also variables predictive of prognosis in patients with IPAH, and whether a new variable that was defined as peak oxygen consumption (peak VO 2 ) divided by minute ventilation/carbon dioxide production at anaerobic threshold (VE/VCO 2 @AT), which we labeled cardiopulmonary fitness index, can better predict prognosis in patients with IPAH. Methods: Patients with newly diagnosed IPAH underwent symptom-limited cardiopulmonary exercise testing from 1 January 2011 to 1 January 2014 in Fuwai hospital and were followed for up to 66 months for major cardiac events (mortality and lung transplantation). Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. Results: One hundred forty-two patients with IPAH (105 female, mean age, 33±11years) were studied. During follow-up (mean: 43±14 months), 25 patients died and 1 patient underwent lung transplantation. In a univariate analysis, peak VO 2 , VO 2 @AT , VE/VCO 2 @AT, cardiopulmonary fitness index , circulatory power, ventilatory power, peak heart rate , NT-ProBNP, pulmonary vascular resistance (PVR), cardiac index (CI ) , WHO functional class were all predictive of cardiac events (all P&lt; 0.05). Multivariate analysis demonstrated that only NT-ProBNP and cardiopulmonary fitness index were the indicators of prognosis (chi-square=7.51, P =0.006; chi-square=7.26, P =0.007, respectively).The mortality rates of 1- , 2- and 3-year for patients with cardiopulmonary fitness index≤0.29 mL·kg –1 ·min –1 were 8.3%, 16.6% and 23.3% respectively. Conclusions: Cardiopulmonary fitness index, rather than circulatory power or ventilatory power provides prognostic information in patients with IPAH. ClinicalTrials.gov: NCT02061787.
Chromosomal Abnormalities in Offspring of Young Cancer Survivors: A Population-Based Cohort Study in Denmark
Authors: Betina Frydenlund Nielsen, Anne Aarslev Schmidt, John J Mulvihill, Kirsten Frederiksen, E Janet Tawn, Marilyn Stovall, Christoffer Johansen, John D Boice, Jeanette Falck Winther
Journal: JNCI Journal of the National Cancer Institute (2017)

To examine whether cancer survivors diagnosed before age 35 years are more likely to have offspring with chromosomal abnormalities than their siblings, chromosomal abnormalities were determined in a population-based cohort of 14 611 offspring (14 580 live-born children and 31 fetuses) of 8945 Danish cancer survivors and 40 859 offspring (40 794 live-born children and 65 fetuses) of 19 536 siblings. Chromosomal abnormalities include numeric and structural abnormalities. Odds ratios were estimated by multiple logistic regression models comparing the risk of chromosomal abnormalities among survivors' offspring with that in siblings' offspring. In a subgroup of survivors with gonadal radiation doses (mean = 0.95 Gy for males and 0.91 Gy for females), no indication of a dose response was found. Overall, no increased risk of chromosomal abnormalities among survivors' offspring was observed compared with their siblings' offspring (odds ratio = 0.99, 95% confidence interval = 0.67 to 1.44, two-sided P = .94), with similar risk between male and female survivors. Cancer survivors were not more likely than their siblings to have children with a chromosomal abnormality.
Des cas humains d'orthopoxvirose simienne au Kasaï oriental, Zaïre (1996-1997)
Authors: P. T. Mwanbal, K F Tshioko, A Moudi, V Mukinda, G. N. Mwema, D Messinger, L Okito, D Barakymfyte, P Malfait, R G Pebody, M Szczeniowski, K Esteves, D Heymann, Y Hutin, R J Williams, A. S. Khan, J J Esposito
Journal: Eurosurveillance (1997)

L'orthopoxvirus simien, appele aussi virus du monkeypox ou virus de la variole du singe, circule de maniere enzootique dans les forets ombrophiles d'Afrique centrale et occidentale ; il peut se transmettre a l'homme, causant un syndrome dont les manifestations cliniques sont analogues a celles de la variole (eruption pustuleuse, fievre, symptomes respiratoires avec une issue fatale dans certains cas). De fevrier a aout 1996, un total de 71 cas cliniques d'orthopoxvirose simienne, dont 6 mortels, se sont declares dans 13 villages de la zone sanitaire de Katako-Kombe (population en 1996 : 15 698 habitants), sous-region de Sankuru, region du Kasai oriental (Zaire)
Abstract 18131: Prior Chemotherapy Does Not Provide Additional Predictive Value to Other Stage A Heart Failure Risk Factors for Left Ventricular Systolic Function
Authors: Mark T Nolan, Hilda Yang, Faraz Pathan, Makoto Saito, Kazuaki Negishi, Thomas H Marwick
Journal: Circulation (2016)

Introduction: Prior chemotherapy (PC) is diagnostic of stage A Heart Failure (SAHF), but its association with LV systolic dysfunction in the community has not been compared with other SAHF risk fac...
Medicaid Coverage for Family Planning — Can the Courts Stop the States from Excluding Planned Parenthood?
Authors: Sara Rosenbaum
Journal: New England Journal of Medicine (2017)

Interview with Prof. Sara Rosenbaum on the implications of an appeals court’s decision not to stop Arkansas from excluding Planned Parenthood from its Medicaid program. (08:08)Download A federal appeals court has decided a case involving Arkansas’ efforts to exclude Planned Parenthood from its Medicaid program, ruling that courts cannot intervene to halt injuries to beneficiaries before they occur. If the decision stands, other states may follow suit.
Putting Psychosis Into Sociocultural Context
Authors: Ezra Susser, Gonzalo Martínez-Alés
Journal: JAMA Psychiatry (2017)

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
Adaptive servo‐ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE‐HF
Authors: Martin R. Cowie, Holger Woehrle, Karl Wegscheider, Eik Vettorazzi, Susanne Lezius, Wolfgang Koenig, Frank Weidemann, Gillian Smith, Christiane Angermann, Marie‐Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K. Simonds, Virend K. Somers, Faiez Zannad, Helmut Teschler
Journal: European Journal of Heart Failure (2017)
The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future
Authors: Benjamin A. Plog, Maiken Nedergaard
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.
Discovery of IDO1 Inhibitors: From Bench to Bedside
Authors: George C. Prendergast, William P. Malachowski, James B. DuHadaway, Alexander J. Muller
Journal: Cancer Research (2017)

Small-molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here, pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds, indoximod, epacadostat, and navoximod, that were first to be evaluated as IDO inhibitors in clinical trials. As immunometabolic adjuvants to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic. Cancer Res; 77(24); 6795-811. ©2017 AACR.
National Patterns of Carotid Revascularization Before and After the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST)
Authors: Fadar Oliver Otite, Priyank Khandelwal, Amer M. Malik, Seemant Chaturvedi
Journal: JAMA Neurology (2017)

The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) showed greater safety of carotid artery stenting (CAS) in patients younger than 70 years and carotid endarterectomy (CEA) in those older than 70 years. It is unknown how the result of CREST has influenced carotid revascularization choices in the United States.To evaluate national patterns in CAS performance in patients older than 70 years in the post-CREST (2011-2014) compared with the pre-CREST (2007-2010) era.All adults older than 70 years undergoing carotid revascularization in the United States from 2007 to 2014 were retrospectively identified from the 2007-2014 National Inpatient Sample using International Classification of Disease, Ninth Revision procedural codes. From 61 324 882 unweighted hospitalizations contained in the 2007-2014 National Inpatient Sample, 494 733 weighted carotid revascularization admissions in adults older than 70 years were identified using International Classification of Disease, Ninth Revision procedural codes.The proportion of CAS performed in all age groups over time was estimated and multivariable-adjusted models were used to compare the odds of receiving CAS in the pre-CREST with those in the post-CREST era in adults older than 70 years.A total of 41.8% of all patients were women, and mean (SE) age at presentation was 78.1 (0.03) years. A total of 16.3% of CAS and 10.1% of CEA procedures were performed in patients with symptomatic stenosis. The proportion of patients older than 70 years receiving CAS increased from 11.9% in the pre-CREST to 13.8% in the post-CREST era (P = .005). In multivariable models, the odds of receiving CAS increased by 13% in all patients older than 70 years in the post-CREST compared with the pre-CREST period (odds ratio [OR], 1.13, 95% CI, 1.00-1.28, P = .04), including symptomatic women (OR, 1.31, 1.05-1.65, P = .02). Symptomatic stenosis (OR 1.39; 95% CI, 1.27-1.52; P < .001), congestive heart failure (OR, 1.48; 95% CI, 1.35-1.63; P < .001), and peripheral vascular disease (OR, 1.35; 95% CI, 1.27-1.43; P < .001) were associated with higher odds of CAS; comorbid hypertension (OR, 0.70; 95% CI, 0.66-0.74; P < .001), smoking (OR, 0.84; 95% CI, 0.78-0.91; P < .001), and weekend admission (OR, 0.77; 95% CI, 0.68-0.88; P < .001) were negatively associated with the odds of CAS.Despite concerns for higher periprocedural complications with CAS in elderly patients, the odds of CAS increased in the post-CREST compared with pre-CREST era in patients older than 70 years, including symptomatic women.
Abstract 14384: Scar Homogeneization Ablation in Patients With Ischemic Cardiomyopathy: Comparison Between Remote Magnetic Navigation and Manual Ablation
Authors: Luigi Di Biase, Roderick Tung, J. David Burkhardt, Jorge Romero, Chintan Trivedi, Sanghamitra Mohanty, Carola Gianni, Pasquale Santangeli, Rong Bai, Rodney Horton, Javier Sanchez, G. Joseph Gallinghouse, Patrick Hranitzky, Amin Al-Ahmad, Dhanujaya Lakkireddy, Dhanujaya Lakkireddy, Madhu Reddy, Salwa Beheiry, Richard Hongo, Kalyanam Shivkumar, Andrea Natale
Journal: Circulation (2015)

Introduction: Remote magnetic navigation (RMN) and ablation with the magnetic irrigated tip catheter has been reported as a feasible and safe technique for the treatment of ventricular arrhythmias (VA). We compared the procedural benefit and the outcomes of patients with ischemic cardiomyopathy (IC) undergoing VAs ablation with the RMN versus the manual approach. Methods: Consecutive pts with IC undergoing VAs ablation both with RMN and with manual ablation at different Institutions were enrolled. Substrate mapping and ablation technique with scar homogenization were utilized for ablation with the end point of elimination of all abnormal electrograms within and or around the scar area. Procedural data and outcomes were analyzed. Post-ablation pacing maneuvers and isoproterenol were used to verify Vas inducibility. Results: A total of 218 consecutive pts (85.3% male, 69.2±7.7 years, LVEF 30.6±8.2) with IC were included with 80 pts undergoing manual ablation while 138 pts underwent RMN ablation. Patients with a scar size &lt; 60 cm2 at the 3D voltage mapping system were excluded. The mean scar size was 140 ± 61 cm2. VT was inducible in 83% pts with a cycle length of 352.1±70.7 msec. The density of the substrate map was higher in the RMN group when compared to the manual ablation group (553±118 vs 347±97, p&lt;0.001). Acute ablation success was achieved in 217 (99.5%) of pts. The mean procedural duration and fluoroscopy time was 255.8±116.6 min and 34.8±22.9 min respectively. The mean mapping time was lower in the RMN group (80.3 ± 13.8 min) compared to the manual ablation group (96.1 ± 20.3 minutes, p &lt; 0.001), while the radiofrequency time was lower in the manual ablation group(66.1 ± 27.3 min vs. 74.4 ± 20.7 min, p=0.02). At 15.4±6.8 months follow-up the success rate in the RMN group was 81.2% (112) while in the manual ablation group 55 (69%) pts were recurrence free (p=0.037). There was one pericardial tamponade which required pericardiocentesis in the manual ablation group. Conclusion: This study shows that VAs ablation using RMN in pts with IC and a scar size greater than 60 cm2 increases success rate at follow up when compared to manual ablation. The better outcome might be due to the higher amount of time dedicated to RF applications to achieve scar homogenization rather than mapping
EU governments step up efforts against alcohol misuse
Authors: Rory Watson
Journal: BMJ (2017)

European health ministers have warned the drinks industry that it must give the public full information on the ingredients and nutritional values of alcoholic drinks within the next three months. If it does not voluntarily do so by March the EU will begin regulatory procedures that could make the data mandatory.

The move to allow the public to make informed choices is part of a wide range of political guidelines EU ministers adopted in Brussels on 8 December to tackle growing alcohol consumption. These aim to contribute …
Woman in labour who was told not to come to hospital wins damages
Authors: Clare Dyer
Journal: BMJ (2017)

The NHS will pay out millions of pounds in damages because a midwife told a mother whose waters had broken not to come to the hospital immediately.

A High Court judge has ruled that negligence by Royal Bolton Hospital NHS Foundation Trust caused Ellen Welsby’s son Thomas to suffer a serious brain injury at his birth in March 2008, leaving him with cerebral palsy.1 Damages have not yet been finalised but typical payouts for cerebral palsy run into millions of pounds. In March 2017 a 10 year old girl received £9.3 million (€10.56m; $12.45m).

In a telephone call to the hospital at 4 am on 26 March, Welsby, expecting her first child, told a midwife that her waters …
The potential effects of pregnancy in a patient with idiopathic pulmonary arterial hypertension responding to calcium channel blockade
Authors: Samuel Bostock, Karen Sheares, John Cannon, Dolores Taboada, Joanna Pepke-Zaba, Mark Toshner
Journal: European Respiratory Journal (2017)

Pulmonary arterial hypertension (PAH) results in increased pulmonary vascular resistance, right ventricular failure and premature death. Around half of patients with PAH are diagnosed with idiopathic pulmonary arterial hypertension (IPAH), where no distinct cause is identified [1, 2]. Patients with IPAH in World Health Organization (WHO) functional classes I–III can be challenged with a vasodilator, such as inhaled nitric oxide, during a right heart catheterisation (RHC) study [3]. "Vasoresponsive" IPAH is universally held to be an excellent prognostic indicator with an entirely different disease course from that in nonresponders [4]. Pregnancy is unequivocally advised against in patients with pulmonary hypertension (PH) as it has been associated with high rates of maternal and fetal death [1, 2]; however, there are limited reports in vasoresponders. Counselling for pregnancy in vasoresponder IPAH needs careful consideration <http://ow.ly/qunk30fXCRH>
Abstract 16049: Diagnostic Yield of Three Years Next Generation Sequencing in Clinical Genetic Diagnostics of Cardiomyopathies
Authors: Paul A van der Zwaag, Renée C Niessen, Ludolf G Boven, Yvonne M Hoedemaekers, Richard J Sinke, Jan D Jongbloed
Journal: Circulation (2016)

Introduction:  The strength of next generation sequencing (NGS) in both research and diagnostics is becoming increasingly evident. NGS is successfully applied to find causal mutations and thus confirm the clinical diagnosis in patients suspected of genetic cardiomyopathies.   Methods:  In 2012 NGS analysis was introduced in the diagnostic clinical genetic laboratory in the University Medical Center Groningen. Since then, we analyzed 1153 patients with several types of cardiomyopathies, as specified by the ordering physicians. We used an enrichment kit targeting 55 genes associated with hereditary cardiomyopathies. Two classification trees were used, taking into account population frequencies, in silico predictions, type and location of mutation, conservation scores, clinical data and information from the literature. Additional haplotype and cosegregation analyses were performed to further support pathogenicity of novel potentially causal mutations that had been identified multiple times.   Results:  Our approach identified a pathogenic mutation in 14% (157/1153) of patients, thereby explaining the clinical phenotype. In 10% (114/1153) one or more likely pathogenic mutations were identified. In 593 patients (51%) a total of 885 variants of unknown clinical significance were found, including the patients who also carried a pathogenic or likely pathogenic mutation. Analysis of the different cardiomyopathy subtypes is ongoing and these results will be presented.   Conclusions:  The results from this large single-center cohort show that NGS provides a conclusive or likely genetic diagnosis in 23% of unselected cardiomyopathy cases. The contribution of the large number of identified variants of unknown significance remains to be elucidated. In the near future, we hope to further characterize these variants by sharing our data with other laboratories both in the Netherlands and abroad and by performing both segregation studies and functional studies.