tbuckley/cabot-search huggingface dataset:
An Uncommon Electrocardiogram Demonstrating a Common Cardiac Problem
Authors: Gregg G. Gerasimon
Journal: JAMA Internal Medicine (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 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
The Agency for Healthcare Research and Quality and the Development of a Learning Health Care System
Authors: Andrew B. Bindman
Journal: JAMA Internal Medicine (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 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
Epigenomic and functional analyses reveal roles of epialleles in the loss of photoperiod sensitivity during domestication of allotetraploid cottons
Authors: Qingxin Song, Tianzhen Zhang, David M. Stelly, Z. Jeffrey Chen
Journal: Genome biology (2017)

Polyploidy is a pervasive evolutionary feature of all flowering plants and some animals, leading to genetic and epigenetic changes that affect gene expression and morphology. DNA methylation changes can produce meiotically stable epialleles, which are transmissible through selection and breeding. However, the relationship between DNA methylation and polyploid plant domestication remains elusive. We report comprehensive epigenomic and functional analyses, including ~12 million differentially methylated cytosines in domesticated allotetraploid cottons and their tetraploid and diploid relatives. Methylated genes evolve faster than unmethylated genes; DNA methylation changes between homoeologous loci are associated with homoeolog-expression bias in the allotetraploids. Significantly, methylation changes induced in the interspecific hybrids are largely maintained in the allotetraploids. Among 519 differentially methylated genes identified between wild and cultivated cottons, some contribute to domestication traits, including flowering time and seed dormancy. CONSTANS (CO) and CO-LIKE (COL) genes regulate photoperiodicity in Arabidopsis. COL2 is an epiallele in allotetraploid cottons. COL2A is hypermethylated and silenced, while COL2D is repressed in wild cottons but highly expressed due to methylation loss in all domesticated cottons tested. Inhibiting DNA methylation activates COL2 expression, and repressing COL2 in cultivated cotton delays flowering. We uncover epigenomic signatures of domestication traits during cotton evolution. Demethylation of COL2 increases its expression, inducing photoperiodic flowering, which could have contributed to the suitability of cotton for cultivation worldwide. These resources should facilitate epigenetic engineering, breeding, and improvement of polyploid crops.
Utilisation of brain network activation in the concussed athlete a case series
Authors: Ilan J Danan, Vernon B Williams, Bert R Mandelbaum
Journal: British Journal of Sports Medicine (2017)

Objective While the approach to concussion and post-concussion syndrome management remains largely clinical, significant advancements have been made in identifying potential biomarkers to aid in the diagnosis and management of head injures. One such potential biomarker is Brain Network Activation (BNA) analysis. BNA is a multi-channel, EEG-ERP based platform that involves algorithmic analysis to provide a network map of cortical activity and quantitative data during specific tasks. Design Case Series. Setting Outpatient, clinic-based. Participants Three (3) athletes. Outcome measures Analysis of the subject’s BNA performance yieldsa BNA score,which reflects the degree of similarity between the performance of the subject and the normative data. BNA scores are further placed into one of three subcategories: Working Memory and Attention (Target Stimuli), Automatic Attention Orienting (Novel Stimuli), and Sensory (Frequent Stimuli). Each subject underwent a BNA analysis while symptomatic, followed by repeat analyses once subjects were identified as clinically asymptomatic. Main results In each of the three studies, there were improvements in BNA scores identified in one, or several, subcategories. More importantly, improvements in BNA scores directly correlated with clinical improvement in the post-concussive setting. Conclusions Approach to concussion management, in both the short-term and long-term setting, remains largely clinical. Current research seeks a more objective means of assessing not only potential structural abnormalities following a concussion, but also an improved means of assessing a patient’s neurocognitive status. BNA has proven to be an effective, supportive tool in allowing clinicians and patients to objectify one’s progress following a concussive injury. Competing interests None.
Response to Imatinib in e13a2 Versus e14a2 BCR-ABL Fusion Transcripts in Chronic Myeloid Leukemia Saudi Patients
Authors: Wafa M. Elbjeirami, Amal S. Alabdulwahab, Hussein G. ELSayed, Nermeen Adel Abdelghaffer, Noha Elnagdi, Hanadi Al-Jedani, Nahla Abd Allatif, Abdulaziz Al Shaikh, Faisal Al-Allaf
Journal: Blood (2016)
MEDU-09. SUBGROUP-DIRECTED STRATIFICATION OF DISEASE RISK IN INFANT MEDULLOBLASTOMA
Authors: D. Hicks, G. Rafiee, E.C. Schwalbe, C.I. Howell, J.C. Lindsey, R.M. Hill, A. Smith, S. Crosier, A. Joshi, K. Robson, S. Wharton, T. Jacques, D. Williamson, S. Bailey, S.C. Clifford
Journal: Neuro-Oncology (2017)

Systematic characterisation of the molecular pathology of infant medulloblastoma (iMB), particularly in relation to the consensus molecular subgroups and outcomes, is urgently required to inform contemporary treatments, risk-stratification and clinical trials. Comprehensive central clinical and pathological review, subgroup assignation, copy number profiling and mutational features were assembled for 208 iMBs (0-5yrs). iMB represented a three-subgroup disease with MBSHH and MBGrp3 predominant (41% each; MBGrp4, 17%). MBGrp3 was strongly associated with LCA (23%, 14/62) and MYC amplification (19%, 12/62). Presence of either feature defined a very high-risk group (27% (18/62); 10yr OS, 23%), with common rapid progression on current therapies. Remaining MBGrp3 tumours were standard risk (73% (45/62; 10yr OS, 74%) but could be further stratified by chromosome 11 status into standard (with Chr11 loss, 33% (19/62); 10yr OS, 84%) and high (without Chr11 loss, 40% (25/62); 10yr OS, 65%) risk groups. MBSHH and DN/MBEN pathology showed a strong association (72% (50/69); p=6.8x10-19), but classic (CLA; n=15) and LCA (n=4) tumours (28%; 19/69) were also observed, independent of patient age. Sub-total resection (STR; HR 6.3, p=3.1x10-5) and DN/MBEN (HR 0.1, p=0.004) were identified as independent prognostic factors in multivariate analysis, unlike metastatic (M+) disease and other biological features tested, which were not associated with survival. A novel cross-validated MBSHH survival model defined CLA/LCA and/or STR tumours as very high-risk (44% (27/61); 10yr OS, 24%), with 18.8-fold relative-risk compared to favourable-risk totally-resected DN/MBEN disease (56% (34/61); 10yr OS, 93%). Only MBSHH DN/MBEN tumours showed potential of rescue at relapse following initial therapy (56% survival post-relapse); other relapses were almost universally fatal. Combined diagnostic assessment of iMB subgroup, pathology and molecular biomarkers will be essential to direct improved risk-stratified therapies, and novel approaches for very high-risk patients.
IMMU-22. PHASE IB IMMUNOTHERAPY CLINICAL TRIAL WITH THE USE OF AUTOLOGOUS DENDRITIC CELLS PULSED WITH AN ALLOGENIC TUMORAL CELL LINES LYSATE IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Andres Morales La Madrid, Jaume Mora, Ofelia Cruz, Vicente Santa-Maria Lopez, Sara Perez-Jaume, Antonio Guillen, Sonia Paco, Angel M Carcaboso, Patricia Puerta, Noelia Salvador, Manuel Juan, Daniel Benitez-Ribas, Raquel Cabezon, Georgina Flórez-Grau, Mari Carmen Molero
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is a lethal condition, and therefore novel approaches are needed. Monocyte-derived dendritic cells (mDCs) pulsed with tumor antigens, as professional antigen-presenting cells, are a promising strategy for immunotherapy of invasive brain tumors. METHODS Our Ib pilot study explored the use of immunotherapy with mDCs for the treatment of newly diagnosed DIPG. Patient′s mDCs were extracted after irradiation and were primed with an allogenic tumor lysate from five patients with K27M-mutated DIPGs. The principal goal of this study was to establish the feasibility and safety of the intradermic administration of these mDC vaccines in patients with DIPG. In the absence of progression, patients received maintenance boosts of tumor lysate. Additionally, we evaluated the non-specific and antitumoral immune response generated in peripheral blood mononuclear cells (PBMC) and in cerebrospinal fluid (CSF) cells. RESULTS Nine patients were included in the study (2016–2018). Vaccines fabrication was feasible and administered in all cases without grade 3 or 4 toxicities. KLH (9/9 patients) and antitumor (8/9 patients) specific responses were identified in PBMC. Immunological responses were also confirmed in T-lymphocytes from the CSF of two patients. Twenty-four month overall survival and progression free survival was 33.3% (95 % CI 13.2% to 84.0 %) and zero, respectively. DISCUSSION These results demonstrate that mDC vaccination is feasible, safe, and generates a DIPG-specific immune response detected in PBMC and CSF. There was a trend in improved OS when compared to historic controls. This strategy shows a promising immunotherapy backbone for future combination schemas.
The prevalence of concussion within the military academies: findings from the concussion assessment, research, and education (care) consortium
Authors: Kathryn L O’Connor, C Dain Allred, Kenneth L Cameron, Darren E Campbell, Megan N Houston, Brian R Johnson, Chris D’Lauro, Gerald McGinty, Patrick G O’Donnell, Karen Y Peck, Steven J Svoboda, Michael McCrea, Thomas McAllister, Steven P Broglio
Journal: British Journal of Sports Medicine (2017)

Objective Describe prevalence and risk factors for concussion among USA Service Academy cadets. Design Prospective. Setting Three USA Service Academies. Participants NCAA and non-NCAA athlete cadets (n=7636, 22% female) enrolled in the CARE Consortium (2014–2015). Assessment of risk factors NCAA status, contact-sport, gender, and brief sensation seeking scale (BSSS) were examined as risk factors for previous concussion. Outcome measures Number of previous concussions. Main results 21% of cadets reported a previous concussion with median time from injury being 2.5 years (IQR 0.99–4.57). At least one previous concussion occurred in 18% of freshman prior to Service Academy enrollment and 12% of sophomore through senior cadets sustained a concussion during their time at the academy. Cadets who are NCAA athletes had a 1.57 (95% CI: 1.12–2.19) greater odds of sustaining a concussion at the academy than non-NCAA cadets. Poisson regression modelling the number of previous concussions revealed significant main effects for contact-sport and BSSS. Controlling for BSSS, contact-sport cadets had 1.82 (95% CI: 1.69–1.95) times the prevalence rate of previous concussion compared to non-contact sport athletes. Additionally, controlling for contact-sport, higher BSSS scores increased prevalence of previous concussions by 1.17 (95% CI: 1.10–1.24) times. Conclusions Overall concussion prevalence among all service academy cadets is similar to prevalence of concussion previously reported for NCAA athletes. Within the academies, cadets who are also NCAA athletes have greater odds of concussion, likely due to increased risk exposure. Contact-sport status and increased sensation seeking is associated with increased number of previous concussions. Competing Interests/ Acknowledgements This project was supported, in part, with support from the Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium, funded, in part by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DOD). The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Ford Detrick MD 21702–5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program under Award NO W81XWH-14-2-0151. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense (DHP funds.)
Метаболічна терапія в комплексному лікуванні пацієнтів із коморбідністю хронічного панкреатиту та стабільної ішемічної хвороби серця
Authors: L.S. Babinets, N.A. Melnyk
Journal: GASTROENTEROLOGY (2017)

Метаболічна терапія — це один із небагатьох способів відновлення нормальної роботи всіх життєво важливих органів і систем. Метою роботи було дослідити ефективність курсового лікування метаболічним препаратом Вазонат (мельдонію дигідрат) щодо корекції прооксидантно-антиоксидантних та трофологічних порушень у хворих із коморбідним перебігом хронічного панкреатиту (ХП) та стабільної ішемічної хвороби серця (СІХС). У дослідження було включено 90 пацієнтів із ХП у поєднанні із СІХС, яких було поділено на дві групи (залежно від програм лікування): І група (45 хворих) отримувала загальноприй­няте лікування; ІІ група (45 хворих) окрім загальноприйнятого лікування додатково отримувала препарат Вазонат за такою схемою: по 5 мл в/в струминно 1 раз на день протягом 10 днів з подальшим прийомом по 1 капсулі (250 мг) 2 рази на день протягом одного місяця. Було доведено, що додавання до комплексної терапії хворих із коморбідністю ХП та СІХС препарату Вазонат більшою мірою сприяє покращенню показників трофологічного та прооксидантно-антиоксидантного статусу, ніж стандартна базисна терапія.
MEDU-05. THE ROLE OF GABA METABOLISM IN MEDULLOBLASTOMA
Authors: Vahan Martirosian, Krutika Deshpande, Gregory Shackelford, Alex Julian, Michelle Lin, Anat Erdreich-Epstein, Thomas Chen, Josh Neman
Journal: Neuro-Oncology (2017)

BACKGROUND: Brain tumors are the most common cause of childhood oncological death, and medulloblastoma (originating in the cerebellum) is the most common malignant pediatric brain tumor. In the microenvironment of the brain, especially the cerebellum, variables related to GABA, the major inhibitory neurotransmitter in the nervous system, are particularly prominent. Abnormal GABAergic Receptor activation has been described in in aggressive MYC-driven Group 3 medulloblastoma. However these studies did not look at the metabolic contribution of GABA for the development of medulloblastomas. In addition to its role in neurotransmission through GABA receptor, GABA can act as a trophic factor during nervous system development to influence cellular events including proliferation, migration, differentiation, synapse maturation, and cell death. Under conditions that inhibit the tricarboxylic acid cycle (TCA), impair respiration, and enhance the accumulation of reactive oxygen intermediates, GABA can be used as an NADH energy source for growth through the GABA-shunt pathway regulators (ABAT, SSADH, GAT-1, GAT-3). Therefore, we hypothesize that blocking GABA-metabolic-shunt will lead to growth suppression and invasiveness of medulloblastoma in the cerebellar GABA-rich microenvironment. RESULTS: Our results show RNA microarray from patient medulloblastoma tissue have high expression of GABA-shunt regulators with ~3-fold increase in the expression of ABAT in MYC amplified versus non-amplified MYC tumors. When medulloblastomas were supplemented with GABA, there was a significant fold change in expression of GABA-shunt mediators and induction of large and stable tumor spheres with Epithelial-Mesenchymal Transition gene expression signature. We next investigated whether a novel perrilyl alcohol-based small molecule NEO216 targeted the GABA-shunt metabolic pathway. NEO216 administration significantly reduced GABA-mediated NADH levels, reversed EMT-profiling, leading to loss of sphere formation. CONCLUSION: Thus, the expression of GABA-metabolic shunt in medulloblastoma could be a malignant microenvironmental adaptation for growth and metastasis that could potentially be exploited through targeted therapy for patients benefit.
Tumor dose response to 5,6-dimethylxanthenone-4-acetic acid (DMXAA) assessed by in vivo magnetic resonance spectroscopy
Authors: Lesley D. McPhail, Yuen-Li Chung, Basetti Madhu, Simon Clark, John R. Griffiths, Lloyd R. Kelland, Simon P. Robinson
Journal: Cancer Research (2004)

50   The selective targeting of the blood supply of tumors offers a novel and promising approach to cancer chemotherapy. The killing of relatively few vascular endothelial cells in tumors should lead to the death of large areas of tumor and moreover, resistance may be less likely to occur when targeting endothelial cells that are genetically stable. One of the lead vascular targeting agents is DMXAA, an agent that has been shown to cause a rapid, selective and prolonged shutdown in tumor blood flow both in preclinical mouse models and in patients. DMXAA induces both direct effects on tumor endothelial cells (leading to rapid apoptosis) and indirect effects (platelet aggregation, induction of serotonin and tumor necrosis factor within the tumor). DMXAA has completed two Phase I trials wherein blood flow reduction intumors was seen across a wide-range of doses from 500 to 4900mg/m 2 . A third small dose-determining trial is ongoing. The aims of this study were to determine the effect of dose on blood flow reduction and to identify relevant pharmacodynamic endpoints of response to DMXAA using preclinical tumor models in either mice (HT29 human colon cancer xenografts) or rats (GH3 prolactinoma) for possible application in future clinical studies. Interestingly, the maximum tolerated single dose of DMXAA in mice was approximately only 25mg/kg, while in rats it was around 400mg/kg (while in patients in the Phase I trial, doses of 4.9g/m 2  were reached).  In vivo  MRS ( 31 P or  1 H) was used to assess the bioenergetic status of these tumor models following treatment with increasing DMXAA doses (0, 7.5, 15, 21 and 25mg/kg in mice). In parallel, plasma and tumor pharmacokinetic profiles were determined. DMXAA induced a decrease in tumor energetics (a depletion of high energy nucleoside triphosphates [NTP] and an increase in inorganic phosphate [Pi]) (measured by  31 P MRS) 6 hours after treatment. This was associated with a decrease in choline and an increase in lactate as measured by  1 H MRS. The highest dose of 25mg/kg completely eliminated the high-energy phosphates in comparison to untreated controls; a significant reduction in the ratio of NTP/Pi was also seen at doses of 15 and 21mg/kg DMXAA but not at 7.5mg/kg. There was no apparent correlation of these tumor metabolic changes with the degree of hemorrhagic necrosis 6 hours after treatment, suggesting that  in vivo  MRS is providing early pharmacodynamic markers of response to DMXAA. These MRS findings may be applicable to future clinical studies of DMXAA.
Study of Galfenol direct cytotoxicity and remote microactuation in cells
Authors: Carolina Vargas-Estevez, Andreu Blanquer, Prabesh Dulal, Rafael Pérez del Real, Marta Duch, Elena Ibáñez, Leonardo Barrios, Gonzalo Murillo, Núria Torras, Carme Nogués, Bethanie J.H. Stadler, José A. Plaza, Jaume Esteve
Journal: Biomaterials (2017)
A graded exercise protocol with added cognitive load: a standardised approach for assessing symptom responses following a sports related concussion?
Authors: John Sullivan S, Sridhar Alla, Leigh Hale, Hopin Lee, Paul McCrory
Journal: British Journal of Sports Medicine (2017)

Objective To examine the self-reported concussion symptoms provoked with a controlled sub-maximal exercise protocol, incorporating a cognitive load, in athletes recovering from a sports-related concussion. Design A three group repeated measures study with follow-up. Setting University laboratory. Participants University aged athletes (12 males, 3 females) with a recent (&lt;14 days) sports-related concussion and 30 (24 males and 6 females) matched recreationally active, non-concussed persons. Intervention Three groups: Concussed (Con), Control+exercise+cognitive load (CECL); and Control+exercise (CE) undertook a 19 min standardised sub-maximal progressive exercise protocol. The Con and CECL groups simultaneously completed a package of reaction time tasks (cognitive load).The Con group completed an identical protocol on a subsequent visit. Participants were instructed to “stop” the test any time they wished. Outcome measures The symptom severity score (SSS) obtained from the SCAT2 post-concussion symptom scale was determined prior to, immediately following, and 15 min aftercompleting the exercise protocol. Main results The groups X time interaction (F4,84=31.9, p&lt;001)indicated that the Con group was different from both control groups at all 3 time intervalswith differences between the time points for the Con group, but not for the others.Three members from the Con group did not complete the protocol. A significant visit X time interaction (F1,9=56.04) was seen for the Con group which completed the protocol on 2 occasions. Conclusions The protocoldifferentially provoked symptoms in recently concussed athletes suggesting its potential in standardising assessment procedures to inform return to play decisions. Competing interests Paul McCrory is a co-investigator, collaborator, or consultant on grants relating to mild TBI funded by several governmental organisations. He is Co-Chair of the Australian Centre for Research into Sports Injury and its Prevention (ACRISP), supported by the IOC. He has been reimbursed by the government, professional scientific bodies, and sporting bodies for presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences, and symposiums. He received support since 2001 from CogState Inc for research costs and the development of educational material. He does not hold any individual shares in any company related to concussion or brain injury assessment or technology. None.