tbuckley/cabot-search huggingface dataset:
Correlation of IDH mutation, 1p/19q co-deletion and <sup>18</sup>FET-PET derived time-to-peak analysis as prognostic markers in glioma
Authors: Bogdana Suchorska, Theo Kraus, Annamaria Biczok, Michael Weller, Marcus Unterrainer, Ulrich Schueller, Christine Schmid-Tannwald, Peter Bartenstein, Armin Giese, Joerg Tonn, Nathalie Lisa Albert
Journal: Journal of Clinical Oncology (2016)

2058 Background: Stratification of glial tumors according to IDH mutation and 1p/19q co-deletion status will gain further importance for tumor classification and treatment in the near future. In analogy, factors derived from 18FET-PET uptake dynamics such as time-to-peak (TTP) analysis allow discrimination between different prognostic groups. The present study aims at correlating molecular tumor characteristics and TTP analysis and to analyze associations with clinical outcome. Methods: 300 patients with de novo WHO grade II-IV gliomas with 18FET-PET imaging at diagnosis were grouped according to IDH mutation and 1p/19q co-deletion status into 3 subgroups (IDH wildtype, IDH mut/non co-del 1p/19q and IDH mut/co-del 1p/19q). Clinical and imaging factors such as age, Karnofsky performance status, treatment and 18FET-PET derived TTP analysis were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. Results: PFS and OS was longest in the IDH mut/co-del 1p/19q subgroup followed by IDH mut/non co-del 1p/19q and IDH wt patients (p < 0.0001). Furthermore, outcome stratified by mean TTP of 17.5 minutes revealed significantly longer PFS and OS in patients with TTP > 17.5 minutes (p < 0.0001 for PFS and OS). Outcome analysis according to the mean TTP of 17.5 minutes within the three subgroups showed TTP to be correlated with PFS/OS within the IDH mut/ non co-del 1p/19q subgroup (p = 0.03 for OS/PFS), but not within the IDH mut/ co-del 1p/19q (p = 0.32 for PFS/p = 0.26 for OS) or the IDH wt (p = 0.63 for PFS and p = 0.05 for OS) subgroup. Conclusions: 18FET-PET derived dynamic analysis delivers additional prognostic information in the sub-group of IDH mut/ no co-del 1p/19q glioma concerning both progression free and overall survival.
Comparisons of Safety-Net and Non–Safety-Net Hospitals
Authors: Jeffrey L. Williams
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Vitamin Supplementation in Elderly Persons
Authors: François Girodon, Marie Christine Boutron-Ruault, Pilar Galan, Serge Hercberg
Journal: JAMA (2003)

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
Evaluation Of Large Granular Lymphocytes and Endothelial-Cell-Related Biomarkers In Patients With Chronic Myeloblastic Leukemia: Comparison Among 3 TKIs
Authors: Tomoki Ito, Nobuhiko Uoshima, Yasuhiro Maeda, Masaaki Hotta, Hideaki Yoshomura, Shinya Fujita, Atsushi Satake, Kazuyoshi Ishii, Fumiaki Urase, Kunio Hayashi, Shosaku Nomura
Journal: Blood (2013)
Factors Affecting the Development of Atrial Fibrillation and Atrial Flutter (AF) Following Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT).
Authors: Mary Lee H. Villanueva, Fausto R. Loberiza, James O. Armitage, Robert G. Bociek, Apar Kishor Ganti, James C. Lynch, Farhan Majeed, Stefano R. Tarantolo, Jo Torrey, Julie M. Vose, Philip J. Bierman
Journal: Blood (2005)
Targeted tumor sequencing using matched normal DNA to assess mutational load.
Authors: Gargi D. Basu, Tracey White, Subha Krishnan, Laura Gonzalez, Janine R LoBello, Kevin R Lau, Michael Syring, Nathan Garinger, Sherri Z. Millis, Thomas Royce, Ahmet Kurdoglu, John D. Carpten, Michael J Demeure
Journal: Journal of Clinical Oncology (2016)

11599 Background: Immune checkpoint inhibitors have therapeutic benefit in the treatment of various cancers; however, an elucidation of the molecular determinants of response to such therapy is needed. A high nonsynonymous mutation burden in tumors is associated with improved response to checkpoint blockade. In this study we determined the relationship of several altered genes/pathways in solid tumor samples that appeared to be significantly mutated (SM). Methods: Comprehensive genomic profiling was performed on 374 advanced solid tumor samples. Targeted sequencing was performed on 562 cancer associated genes, and analysis of matched tumor-normal DNA was performed to filter out germline variants and identify true somatic mutations. Samples with greater than 17 mutations were considered SM based on extrapolation from other reports and considering the number of genes interrogated by our panel. Results: Our analysis revealed that 13% (48/374) of tumors were significantly mutated, exhibiting 17 or greater nonsynonymous mutations occurring in a wide variety of solid tumors including but not limited to lung, CRC and melanoma. Over 90% of mutations were either frameshift, missense or splice site alterations, which may result in tumor-specific neoantigens and increased amounts of tumor-infiltrating lymphocytes (TILs). Loss of function mutations in MMR genes indicative of MMR deficiency which has been associated with increased response to immune checkpoint blockade were present in 21% (10/48) of SM cases. Mutations in polymerase e (POLE), indicative of high neoantigen load, were identified in 17% (8/48) of SM cases. Genes in SWI/SNF pathway were mutated in 65% (31/48) of SM cases, which included loss of function mutations in ARID1A. Mutations in DNA repair genes, including homologous recombination, base excision and nucleotide excision repair pathway, were noted in over half of the cases with the hypermutant phenotype. Conclusions: Our findings suggest that 13% of solid tumors have high nonsynonymous mutation burden which may be associated with benefit from checkpoint inhibitor therapy. Targeted gene panel sequencing may identify significantly mutated cases that are potential candidates for clinical trials with immune-therapeutics.
Depression Severity and Effect of Antidepressant Medications
Authors: Takefumi Suzuki
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method
Authors: Carole D. Mitnick, Richard A. White, Chunling Lu, Carly A. Rodriguez, Jaime Bayona, Mercedes C. Becerra, Marcos Burgos, Rosella Centis, Theodore Cohen, Helen Cox, Lia D'Ambrosio, Manfred Danilovitz, Dennis Falzon, Irina Y. Gelmanova, Maria T. Gler, Jennifer A. Grinsdale, Timothy H. Holtz, Salmaan Keshavjee, Vaira Leimane, Dick Menzies, Giovanni Battista Migliori, Meredith B. Milstein, Sergey P. Mishustin, Marcello Pagano, Maria I. Quelapio, Karen Shean, Sonya S. Shin, Arielle W. Tolman, Martha L. van der Walt, Armand Van Deun, Piret Viiklepp
Journal: European Respiratory Journal (2016)

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
Mesenchymal Stem Cell As a Salvage Treatment For Refractory Acute Graft-Versus-Host Disease: a Matched Pair Analysis
Authors: Ke Zhao, Rui Lou, Fen Huang, Yanwen Peng, Zujun Jiang, Ke Huang, Yu Zhang, Zhiping Fan, Hongsheng Zhou, Can Liu, Yang Xiao, Jing Sun, Peng Xiang, Qifa Liu
Journal: Blood (2013)
Challenges and Opportunities in Protease-Activated Receptor Drug Development
Authors: Justin R. Hamilton, JoAnn Trejo
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Protease-activated receptors (PARs) are a unique class of G protein-coupled receptors (GPCRs) that transduce cellular responses to extracellular proteases. PARs have important functions in the vasculature, inflammation, and cancer and are important drug targets. A unique feature of PARs is their irreversible proteolytic mechanism of activation that results in the generation of a tethered ligand that cannot diffuse away. Despite the fact that GPCRs have proved to be the most successful class of druggable targets, the development of agents that target PARs specifically has been challenging. As a consequence, researchers have taken a remarkable diversity of approaches to develop pharmacological entities that modulate PAR function. Here, we present an overview of the diversity of therapeutic agents that have been developed against PARs. We further discuss PAR biased signaling and the influence of receptor compartmentalization, posttranslational modifications, and dimerization, which are important considerations for drug development.
Mortality Risk Stratification by Combining <i>BRAF </i>V600E and <i>TERT</i> Promoter Mutations in Papillary Thyroid Cancer
Authors: Rengyun Liu, Justin Bishop, Guangwu Zhu, Tao Zhang, Paul W. Ladenson, Mingzhao Xing
Journal: JAMA Oncology (2016)

BRAF V600E and TERT promoter mutations can coexist in papillary thyroid cancer (PTC). This genetic duet was indicated to be involved in the aggressiveness of PTC, but its prognostic value in PTC-related mortality remains to be specifically established.To establish the prognostic power of this genetic duet in PTC-specific mortality.This genetic-clinical correlation study examined BRAF V600E and TERT promoter mutations (chr5:1,295,228C>T and chr5:1,295,250C>T) and PTC-specific mortality in 1051 patients (764 women and 287 men) with a median (interquartile range [IQR]) age of 46 (36-57) years, with a median (IQR) follow-up time of 89 (48-142) months (7.4 years).BRAF V600E and TERT promoter mutation patterns and associated patient deaths caused by PTC.Papillary thyroid cancer-specific mortality occurred in 4 of 629 patients (0.6%) with neither mutation; 7 of 292 (2.4%) with BRAF V600E alone; 4 of 64 (6.3%) with TERT promoter mutation alone; and 15 of 66 (22.7%) with the genetic duet; and deaths per 1000-person years in patients harboring neither mutation, BRAF V600E alone, TERT mutation alone, or both mutations were 0.80 (95% CI, 0.30-2.13), 3.08 (95% CI, 1.47-6.46), 6.62 (95% CI, 2.48-17.64), and 29.86 (95% CI, 18.00-49.52), respectively. Compared with patients harboring neither mutation, HRs (95% CIs) for PTC-specific mortality were 3.08 (0.87-10.84) for BRAF V600E alone; 8.18 (2.04-32.75) with TERT mutation alone; and 37.77 (12.50-114.09) with both mutations. Papillary thyroid cancer-specific mortality for cases with both mutations remained significant (HR, 9.34; 95% CI, 2.53-34.48) after adjustment for clinicopathological factors, and the genetic duet showed a strong incremental and synergistic impact over either mutation alone. Kaplan-Meier analyses revealed a flat PTC-specific patient survival curve with neither mutation, a modest decline in the curve with either mutation alone, and a sharp decline in the curve with coexisting mutations. Even more robust mortality associations of the genetic duet were seen when only conventional-variant PTC (CPTC) was analyzed (HR, 54.46; 95% CI, 12.26-241.82), which remained strongly significant (HR, 18.56; 95% CI, 2.97-116.18) after adjustment for clinicopathological factors.These results demonstrate a simple 4-genotype classification of PTC, particularly CPTC, with a disease-specific mortality risk order of the genetic duet>>>>BRAF V600E alone = TERT promoter mutation alone > wild-type for both genes, representing a powerful molecular prognostic system that can help pinpoint patients with the highest mortality risk.
Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2 Diabetes: A Follow-up Analysis of a Randomized Clinical Trial
Authors: Stephanie K. Tanamas, Pierre-Jean Saulnier, Gudeta D. Fufaa, Kevin M. Wheelock, E. Jennifer Weil, Robert L. Hanson, William C. Knowler, Peter H. Bennett, Robert G. Nelson
Journal: Diabetes Care (2016)

To determine whether early administration of losartan slows progression of diabetic kidney disease over an extended period.We conducted a 6-year clinical trial in 169 American Indians with type 2 diabetes and urine albumin/creatinine ratio <300 mg/g; 84 participants were randomly assigned to receive losartan and 85 to placebo. Primary outcome was a decline in glomerular filtration rate (GFR; iothalamate) to ≤60 mL/min or to half the baseline value in persons who entered with GFR <120 mL/min. At enrollment, GFR averaged 165 mL/min (interquartile range 49-313 mL/min). During the trial, nine persons reached the primary outcome with a hazard ratio (HR; losartan vs. placebo) of 0.50 (95% CI 0.12-1.99). Participants were then followed posttrial for up to 12 years, with treatment managed outside the study. The effect of losartan on the primary GFR outcome was then reanalyzed for the entire study period, including the clinical trial and posttrial follow-up.After completion of the clinical trial, treatment with renin-angiotensin system inhibitors was equivalent in both groups. During a median of 13.5 years following randomization, 29 participants originally assigned to losartan and 35 to placebo reached the primary GFR outcome with an HR of 0.72 (95% CI 0.44-1.18).Long-term risk of GFR decline was not significantly different between persons randomized to early treatment with losartan and those randomized to placebo. Accordingly, we found no evidence of an extended benefit of early losartan treatment on slowing GFR decline in persons with type 2 diabetes.
Head injuries in youth are often linked to psychiatric disorders and disability, study finds
Authors: Nigel Hawkes
Journal: BMJ (2016)

Head injuries in childhood and adolescence are strongly linked with a range of outcomes including psychiatric disorders, low educational attainment, increased risk of disability, and early death, a study of Swedish health and census data has shown.

The more severe the injury, the number of times it is repeated, and the older the person is at the time of injury all increase the risks, researchers reported in PLOS Medicine .1

Amir Sariaslan, of the University of Oxford, UK, and colleagues studied the records of more than 1.1 million Swedish people born from 1973 to 1985, of whom 104 000 (9.1%) had a diagnosis of traumatic brain injury before age 25. This means that they had an injury sufficiently serious to cause some alteration of consciousness and warrant a visit to a hospital emergency department. This would include concussion but also lesser symptoms such as feeling dazed. All of those with a diagnosis of traumatic …
Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury
Authors: Zhentao Man, Xiaoqing Hu, Zhenlong Liu, Hongjie Huang, Qingyang Meng, Xin Zhang, Linghui Dai, Jiying Zhang, Xin Fu, Xiaoning Duan, Chunyan Zhou, Yingfang Ao
Journal: Biomaterials (2016)
Panx3 links body mass index and tumorigenesis in a genetically heterogeneous mouse model of carcinogen-induced cancer
Authors: Kyle D. Halliwill, David A. Quigley, Hio Chung Kang, Reyno Del Rosario, David Ginzinger, Allan Balmain
Journal: Genome Medicine (2016)

Body mass index (BMI) has been implicated as a primary factor influencing cancer development. However, understanding the relationship between these two complex traits has been confounded by both environmental and genetic heterogeneity.In order to gain insight into the genetic factors linking BMI and cancer, we performed chemical carcinogenesis on a genetically heterogeneous cohort of interspecific backcross mice ((Mus Spretus × FVB/N) F1 × FVB/N). Using this cohort, we performed quantitative trait loci (QTL) analysis to identify regions linked to BMI. We then performed an integrated analysis incorporating gene expression, sequence comparison between strains, and gene expression network analysis to identify candidate genes influencing both tumor development and BMI.Analysis of QTL linked to tumorigenesis and BMI identified several loci associated with both phenotypes. Exploring these loci in greater detail revealed a novel relationship between the Pannexin 3 gene (Panx3) and both BMI and tumorigenesis. Panx3 is positively associated with BMI and is strongly tied to a lipid metabolism gene expression network. Pre-treatment Panx3 gene expression levels in normal skin are associated with tumor susceptibility and inhibition of Panx function strongly influences inflammation.These studies have identified several genetic loci that influence both BMI and carcinogenesis and implicate Panx3 as a candidate gene that links these phenotypes through its effects on inflammation and lipid metabolism.
Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial
Authors: Hendrik Nolte, David I. Bernstein, Harold S. Nelson, Jörg Kleine-Tebbe, Gordon L. Sussman, Dorthe Seitzberg, Dorte Rehm, Amarjot Kaur, Ziliang Li, Susan Lu
Journal: Journal of Allergy and Clinical Immunology (2016)
PWE-010 Surveillance procedures in the St Mark's Bowel Cancer Screening Programme
Authors: S Gupta, N Suzuki, C Fraser, M E Vance, B P Saunders, S Thomas-Gibson
Journal: Gut (2010)

<h3>Introduction</h3> The St Mark9s Bowel Cancer Screening Centre (BCSC) rolled out between 2006 and 2007. To date, 1200 colonoscopies have been performed by five accredited screening endoscopists. The programme is now into its third year and therefore second year of surveillance for high-risk patients. <h3>Methods</h3> To review the polyp surveillance procedures performed between Oct 2006 and July 2009. Data regarding the timing, number and size of polyps were collected prospectively. <h3>Result</h3> 1200 colonoscopies were performed between October 2006 and July 2009. 67 were 1-year polyp surveillance procedures (64 for high-risk polyps, two for intermediate risk, one for polyp cancer). There were 6.0 (3.76) polyps found per index procedure and 3.0 (2.4) per surveillance procedure (p&lt;0.0001). In three cases, there were more polyps seen at surveillance than in the index procedure. Polyp size in the index procedure was 18.1 mm (11.8) compared to 5.26 mm (2.99) in the surveillance group (p&lt;0.0001). Three of the 67 surveillance procedures revealed polyps &gt;1 cm (11–16 mm). In two procedures there was an increase in the size of the largest polyp seen (9 mm to 14 mm and 6 mm to 9 mm). In 26 cases, the findings downgraded the risk from high to intermediate and in 30 cases, to low risk. In 11 cases, the risk remained high based on the number and size of polyps. Histologically all were tubular adenomas with low grade dysplasia. <h3>Conclusion</h3> In the majority of cases (62 (92%)) there was a reduction in both the size and number of polyps seen at 1-year surveillance. However, in a small number of cases there were significant polyp findings.