tbuckley/cabot-search huggingface dataset:
Cardiac Troponin T and Troponin I in the General Population
Authors: Paul Welsh, David Preiss, Caroline Hayward, Anoop S.V. Shah, David McAllister, Andrew Briggs, Charles Boachie, Alex McConnachie, Sandosh Padmanabhan, Claire Welsh, Mark Woodward, Archie Campbell, David Porteous, Nicholas L. Mills, Naveed Sattar
Journal: Circulation (2019)

There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We aimed to compare and contrast (1) the association of cTnT and cTnI with CVD and non-CVD outcomes, and (2) their determinants in a genome-wide association study.High-sensitivity cTnT and cTnI were measured in serum from 19 501 individuals in Generation Scotland Scottish Family Health Study. Median follow-up was 7.8 years (quartile 1 to quartile 3, 7.1-9.2). Associations of each troponin with a composite CVD outcome (1177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined by using Cox models. A genome-wide association study was conducted using a standard approach developed for the cohort.Both cTnI and cTnT were strongly associated with CVD risk in unadjusted models. After adjusting for classical risk factors, the hazard ratio for a 1 SD increase in log transformed troponin was 1.24 (95% CI, 1.17-1.32) and 1.11 (1.04-1.19) for cTnI and cTnT, respectively; ratio of hazard ratios 1.12 (1.04-1.21). cTnI, but not cTnT, was associated with myocardial infarction and coronary heart disease. Both cTnI and cTnT had strong associations with CVD death and heart failure. By contrast, cTnT, but not cTnI, was associated with non-CVD death; ratio of hazard ratios 0.77 (0.67-0.88). We identified 5 loci (53 individual single-nucleotide polymorphisms) that had genome-wide significant associations with cTnI, and a different set of 4 loci (4 single-nucleotide polymorphisms) for cTnT.The upstream genetic causes of low-grade elevations in cTnI and cTnT appear distinct, and their associations with outcomes also differ. Elevations in cTnI are more strongly associated with some CVD outcomes, whereas cTnT is more strongly associated with the risk of non-CVD death. These findings help inform the selection of an optimal troponin assay for future clinical care and research in this setting.
Agricultural Risk Factors Influence Microbial Ecology in Honghu Lake
Authors: Maozhen Han, Melissa Dsouza, Chunyu Zhou, Hongjun Li, Junqian Zhang, Chaoyun Chen, Qi Yao, Chaofang Zhong, Hao Zhou, Jack A Gilbert, Zhi Wang, Kang Ning
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Agricultural activities, including stock-farming, planting industry, and fish aquaculture, can affect the physicochemical and biological characters of freshwater lakes. However, the effects of pollution producing by agricultural activities on microbial ecosystem of lakes remain unclear. Hence, in this work, we selected Honghu Lake as a typical lake that is influenced by agriculture activities. We collected water and sediment samples from 18 sites, which span a wide range of areas from impacted and less-impacted areas. We performed a geospatial analysis on the composition of microbial communities associated with physicochemical properties and antibiotic pollution of samples. The co-occurrence networks of water and sediment were also built and analyzed. Our results showed that the microbial communities of impacted and less-impacted samples of water were largely driven by the concentrations of TN, TP, NO3−-N, and NO2−-N, while those of sediment were affected by the concentrations of Sed-OM and Sed-TN. Antibiotics have also played important roles in shaping these microbial communities: the concentrations of oxytetracycline and tetracycline clearly reflected the variance in taxonomic diversity and predicted functional diversity between impacted and less-impacted sites in water and sediment samples, respectively. Furthermore, for samples from both water and sediment, large differences of network topology structures between impacted and less-impacted were also observed. Our results provide compelling evidence that the microbial community can be used as a sentinel of eutrophication and antibiotics pollution risk associated with agricultural activity; and that proper monitoring of this environment is vital to maintain a sustainable environment in Honghu Lake.
C-KIT mutation may be a novel prognostic factor in t(8;21)-acute myeloid leukemia in children
Authors: Akira Shimada, Tomohiko Taki, Ichiro Tsukimoto, Ken Tabuchi, Ryoji Hanada, Akio Tawa, Masahiro Tsuchida, Keizo Horibe, Souichi Adachi, Yasuhide Hayashi
Journal: Cancer Research (2005)

4725  C-KIT and FLT3 is a type III receptor tyrosine kinase (RTK) and the c-KIT gene mutation is associated with adult acute myeloid leukemia (AML) patients with t(8;21) or inv(16). The incidence of c-KIT mutation and prognostic significance in pediatric t(8;21)-AML remains uncertain. There were 46 patients (29.1%) with t(8;21)-AML confirmed by cytogenetics and/or RT-PCR (AML1-MTG8 chimeric mRNA) in 158 AML patients treated on Japan pediatric AML cooperative treatment protocol, AML 99. We performed the mutational analyses in TK2 domain (exon 17) of c-KIT, internal tandem duplication (ITD) of FLT3 and TK2 domain (exon 21) of FLT3 using RT-PCR followed by direct sequencing. Eight of 46 patients (17.4%) showed TK2 domain mutation of c-KIT (N822K 3 patients,N822T,D816H,D816V,V825A,A814S 1 patient each). Among them, 5 patients showed 1st relapse within 14 months after diagnosis and received allogenic stem cell transplantation (allo-SCT) in 2nd CR. One of five patients died of 2nd relapse. Two patients who received allo-SCT in 1st CR (at 6 and 8 months after diagnosis) have not relapsed. Two of 38 (5.3%) patients without c-KIT mutation have relapsed. In total, 7 of 46 patients (15.2%) have relapsed in this study. The significant difference between patients with or without c-KIT mutation was observed in 3-year event free survival and relapse rate (p
Ectopic and visceral fat deposition in lean and obese type 2 diabetes patients
Authors: E Levelt, M Pavlides, R Banerjee, M Mahmod, C Kelly, J Sellwood, R Ariga, S Thomas, J Francis, C T Rodgers, W Clarke, N Sabharwal, C Antoniades, J Schneider, M Robson, K Clarke, T Karamitsos, O Rider, S Neubauer
Journal: Journal of the American College of Cardiology (2016)
GENE-17. TUMOR-DERIVED CELL-FREE DNA MAY BE FREQUENTLY DETECTED BY CLINICAL TARGETED SEQUENCING OF CEREBROSPINAL FLUID IN CHILDREN WITH BRAIN TUMORS
Authors: Kristine Karvonen, Christina Lockwood, Bonnie Cole, Shannon Stasi, Jeff Stevens, Jason Hauptman, Amy Lee, Sarah Leary
Journal: Neuro-Oncology (2019)

INTRODUCTION: Targeted sequencing of somatic DNA obtained from pediatric brain tumor tissue is of clinical utility in forming an integrated molecular and histologic diagnosis as well as evaluating therapeutic targets. The evaluation of cell-free DNA (cfDNA) from blood or cerebrospinal fluid (CSF) has not yet been clinically validated in pediatric brain tumors. METHODS: Using a clinically validated targeted 262 next-generation gene sequencing platform, we evaluated cfDNA in 15 subjects with CSF and plasma samples paired with pediatric brain tumor tissue including medulloblastoma (n=7), atypical teratoid-rhabdoid tumor (n=2), diffuse midline glioma (n=4), pilocytic astrocytoma and pleomorphic xanthoastrocytoma (n=1 each). Informed consent was obtained from all subjects and this study was approved by the institutional review board. CSF was obtained at the time of surgery or from ventriculostomy in 3 cases each, and from diagnostic lumbar puncture in the remainder. RESULTS: cfDNA from CSF was successfully isolated from 8/15 (53%) subjects, and was sufficient for sequencing in 6/8 samples. Somatic mutations and copy-number changes found in cfDNA from CSF corresponded to changes found by tumor sequencing in all cases. Tumor-derived cfDNA was detected in as little as 200 microliters of CSF, and in the absence of cytological evidence of tumor. Tumor-derived cfDNA was not detected in plasma samples. CONCLUSION: The evaluation of cfDNA from CSF shows promise for clinical applications in pediatric brain tumor diagnosis and disease monitoring. A longitudinal prospective study of cfDNA detection in CSF for disease monitoring is planned.
Altered proteasome function in right ventricular hypertrophy
Authors: Tanja Heitmeier, Akylbek Sydykov, Christina Lukas, Christina Vroom, Martina Korfei, Aleksandar Petrovic, Karin Klingel, Andreas Günther, Oliver Eickelberg, Norbert Weissmann, Hossein Ardeschir Ghofrani, Werner Seeger, Friedrich Grimminger, Ralph Theo Schermuly, Silke Meiners, Djuro Kosanovic
Journal: Cardiovascular Research (2019)

In patients with pulmonary hypertension, right ventricular hypertrophy (RVH) is a detrimental condition that ultimately results in right heart failure and death. The ubiquitin proteasome system has been identified as a major protein degradation system to regulate cardiac remodelling in the left heart. Its role in right heart hypertrophy, however, is still ambiguous.RVH was induced in mice by pulmonary artery banding (PAB). Both, expression and activity of the proteasome was found to be up-regulated in the hypertrophied right ventricle (RV) compared to healthy controls. Catalytic inhibition of the proteasome by the two proteasome inhibitors Bortezomib (BTZ) and ONX-0912 partially improved RVH both in preventive and therapeutic applications. Native gel analysis revealed that specifically the 26S proteasome complexes were activated in experimental RVH. Increased assembly of 26S proteasomes was accompanied by elevated expression of Rpn6, a rate-limiting subunit of 26S proteasome assembly, in hypertrophied cardiomyocytes of the right heart. Intriguingly, patients with RVH also showed increased expression of Rpn6 in hypertrophied cardiomyocytes of the RV as identified by immunohistochemical staining.Our data demonstrate that alterations in expression and activity of proteasomal subunits play a critical role in the development of RVH. Moreover, this study provides an improved understanding on the selective activation of the 26S proteasome in RVH that might be driven by the rate-limiting subunit Rpn6. In RVH, Rpn6 therefore represents a more specific target to interfere with proteasome function than the commonly used catalytic proteasome inhibitors.
EPEN-01. CHARACTERIZATION AND DRUG TESTING IN PRECLINICAL EPENDYMOMA MODELS
Authors: Ashleigh Lester, Sylvia Chung, Shane Whittaker, Robert Rapkins, Kerrie McDonald
Journal: Neuro-Oncology (2019)

INTRODUCTION: Currently there are no effective chemotherapeutic treatments for ependymomas, with maximal surgical excision and radiotherapy the mainstays of treatment. The identification of at least 9 molecularly distinct subgroups, suggests effective treatments are likely to be subgroup specific and subgroup focused preclinical investigations are urgently needed. However, such investigations have been hampered by the lack of appropriate in vitro and in vivo models in which to test potential treatments. This study aims to establish such models for the purpose of testing novel subgroup specific drug treatments. METHODS/RESULTS: Ependymoma samples from two patients have been successfully cultured in neurobasal media, with the cells growing both as adherent cultures and neurospheres. Whole genome DNA methylation screening and IHC, categorized the samples as falling within the ST-RELA and PFA subgroups respectively. Drug testing on ST-RELA neurospheres has shown treatment with Bortezomib, in combination with either Vorinostat or Panobinostat, results in significant synergistic benefits, with neurosphere viability reduced to almost zero, using doses that are half the IC50 of each drug. Preliminary analysis suggests the drugs are leading to an increase in apoptosis. Brain slice co-culture models have been successfully established, for the purpose of further drug testing and investigating the effects of the drugs upon normal brain tissue. Cells dissociated from the ST-RELA patient sample and low passage cultures, injected intracranially into NSG mice, resulted in tumour formation in 6 of the 19 mice, with plans underway to test the drug combinations in PDX mouse models. CONCLUSION: In the absence of known driver mutations for 8 of the 9 ependymoma subgroups, the establishment of patient derived preclinical models provides a mechanism for testing novel subgroup specific treatments. The current results suggest that Bortezomib in combination with histone deacetylase inhibitors may be an effective treatment in patients with ST-RELA ependymomas.
Abstract 16377: Sudden Cardiac Arrest Related to Coronary Vasospasm: Frequency, Characteristics and Outcomes
Authors: Victor Waldmann, Wulfran Bougouin, Nicole Karam, Ardalan Sharifzadehgan, Kumar Narayanan, Olivier Varenne, Christian Spaulding, Alain Cariou, Xavier Jouven, Eloi Marijon
Journal: Circulation (2017)

Introduction: Coronary vasospasm (CVS) is a well-established cause of sudden cardiac arrest (SCA), and emerging evidence indicates a significant risk of recurrent arrhythmic events in this conditio...
Modulating inflammation for cancer therapy
Authors: Birgit Ritter, Florian R. Greten
Journal: The Journal of Experimental Medicine (2019)

A link between chronic inflammation and development of tumors is well established. Moreover, it has become evident that tumorigenesis is not a cell autonomous disease, and an inflammatory microenvironment is a prerequisite of basically all tumors, including those that emerge in the absence of overt inflammation. This knowledge has led to the development of anti-inflammatory concepts to treat and prevent cancer. In contrast, immunotherapies, in particular checkpoint inhibitors, representing the most significant progress in the therapy of several malignancies depend on the presence of a pro-inflammatory “hot” environment. Here, we discuss pro- and anti-inflammatory concepts for the treatment of cancer.
BAD guidelines for the management of HS (acne inversa) 2018
Authors: J.R. Ingram, F. Collier, D. Brown, T. Burton, J. Burton, M.F. Chin, N. Desai, T.E.E. Goodacre, V. Piguet, A.E. Pink, L.S. Exton, M.F. Mohd Mustapa
Journal: British Journal of Dermatology (2019)

Hidradenitis suppurativa (HS) is a long‐term skin condition causing multiple boils in skin creases such as the arm pits and groins. The boils are painful and produce pus, and permanent scarring occurs as the disease progresses. As a result, it has a large impact on quality of life. HS affects about 1 in 100 of the UK population and it tends to start in early adulthood. The British Association of Dermatologists commissioned a HS guideline development group composed of information specialists, a HS patient and carer, and UK clinicians including dermatologists, a dermatology nurse, plastic surgeon and general practitioner (GP). The group, based in the UK, were asked to produce treatment recommendations based on a systematic review of the evidence. The evidence was converted to recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Nearly 3000 evidence records were identified through database searches. Initial recommendations for HS management by GPs and hospital clinics include to provide a patient information leaflet, record baseline disease severity, measure pain and treat if needed, measure quality of life, record a count of skin lesions, and provide wound dressings if required. Patients should be screened for cardiovascular disease risk factors as well as for depression and anxiety. Patients should also be offered smoking cessation and weight management referral if relevant. A treatment ladder of medical therapy is recommended, starting with oral tetracyclines, then the combination of clindamycin and rifampicin, acitretin in men and non‐fertile women, dapsone and progressing to adalimumab injections if required. Surgical treatment with wide removal and a range of closure methods is placed towards the end of the medical treatment pathway, reflecting current UK practice and a relative lack of evidence. Future research recommendations and audit criteria are included.
Using Genetics to Plan Future Randomized Trials of Lipoprotein(a) Lowering—How Much Reduction, for How Long, and in Whom?
Authors: George Thanassoulis
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Evaluation of Ivermectin vs Permethrin for Treating Scabies—Summary of a Cochrane Review
Authors: Stefanie Rosumeck, Alexander Nast, Corinna Dressler
Journal: JAMA Dermatology (2019)

Is the use of ivermectin in patients infested with scabies associated with improved clinical and safety outcomes compared with permethrin?Both ivermectin and permethrin treatment were associated with high clearance rates. There is low-certainty evidence that ivermectin was associated with slightly lower rates of complete clearance after 1 week compared with permethrin, 5%, cream (relative risk [RR], 0.65; 95% CI, 0.54-0.78). After 2 weeks, there was no difference in efficacy (RR, 0.91; 95% CI, 0.76-1.08; low-certainty evidence), or in the number of participants with adverse events (week 4: RR, 1.30; 95% CI, 0.35-4.83; low-certainty evidence).
GERM-01. CLINICAL COURSE OF INTRACRANIAL GERM CELL TUMOR IN ONE INSTITUTE IN DEVELOPING COUNTRY
Authors: Patcharee Komvilaisak, Piyathida Wongmas, Amnat Kitkhundee, Nipaporn Tewattanarat, Narudom Supakalin
Journal: Neuro-Oncology (2019)

Prevalence of Intracranial germ cell tumor is more common in southeast Asian. 31 children less than 18-year-old were included during 5-year period from 2012 until now. There were 25 male, 6 female with mean age of 12.5 yrs. Clinical presentations were blurred vision (19), headache (18), vomiting (9), alternation of consciousness (8), polyuria (7), seizure (3) and endocrine dysfunction (2). The most common location of intracranial germ cell tumor is pineal (22) followed by suprasellar(14), thalamus (1), 5 cases had multiple location and 3 cases had spinal metastasis. Among of 31 cases, 17 were diagnosed with germinoma, 5 germinoma with elevated –HCG, 7 non-germinoma, 2 immature teratoma. Surgical treatment includes tumor biopsy in 21, tumor removal in 5, ventriculoperitoneal shunt in 13. All patients received chemotherapy then radiotherapy. Complications related to disease and treatment were hypothyroid (17), adrenal insufficiency (17), diabetes insipidus (17), visual loss (5), optic nerve atrophy (4), obesity (2). There were 31 cases in complete remission. Intracranial germ cell tumor in this study is predominate in male 4:1 ratio compared to female. Increased intracranial pressure and diplopia are common presenting symptoms followed by polyuria. This tumor is successful outcome of treatment. Panhypopituitarism and diabetes insipidus are complicated to the disease and treatment, requiring life-long medication replacement. HIGH GRADE GLIOMA
Balancing the Risks and Benefits of Surgical Prophylaxis
Authors: Mary T. Hawn, Lisa Marie Knowlton
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
ATRT-07. TARGETING PRIMARY CILIOGENESIS IN ATYPICAL TERATOID/RHABDOID TUMORS
Authors: Lena Blümel, Kornelius Kerl, Nan Qin, Johannes Berlandi, Katharina Thiel, Isabel Tegeder, Astrid Jeibmann, Eunice Paisana, Carlos Custódia, Daniel Picard, Maike Langini, Kai Stühler, Frauke-Dorothee Meyer, Bastian Malzkorn, Max C Liebau, Pascal D Johann, Serap Erkek, Marcel Kool, Stefan M Pfister, Michael C Frühwald, Cláudia C Faria, Arndt Borkhardt, Guido Reifenberger, Martin Hasselblatt, Marc Remke
Journal: Neuro-Oncology (2019)

Atypical teratoid/rhabdoid tumors (AT/RT) are among the most common malignant brain tumors in infants. Comprehensive genomic studies revealed three distinct molecular subgroups (AT/RT-TYR, -MYC and -SHH). As primary cilia (PC) have already been shown to play a pivotal role in other tumor entities, we aimed to characterize the distribution of PC across AT/RT subgroups and to target primary ciliogenesis in these tumors with dismal prognosis. We performed immunofluorescence to detect PC in AT/RT primary tumor sections and cell lines. The functional role of PC was investigated in vitro by knockdown of KIF3A. The relevance of primary ciliogenesis in AT/RT biology was further elucidated in vivo using a fly model of SMARCB1 deficiency and an orthotopic mouse model. We detected PC in all AT/RT primary tumor sections and cell lines investigated in this study. Notably, we observed a significant subgroup-specific difference in the proportion of PC-positive cells. Specifically, AT/RT-TYR demonstrated the highest percentage of ciliated cells. Knockdown of KIF3A significantly reduced cell proliferation and stem cell properties. Additionally, apoptosis was significantly increased via upregulation of JAK1/STAT1 signaling. In a fly model of SMARCB1 deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with >20% of flies reaching adulthood. Finally, we demonstrated a significantly prolonged survival in an orthotopic xenograft model upon knockdown of KIF3A. In conclusion, our results implicate PC as a key feature of AT/RT biology and suggest primary ciliogenesis as a potential therapeutic target, especially in AT/RT-TYR.