tbuckley/cabot-search huggingface dataset:
Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients
Authors: J. R. Bedarf, F. Hildebrand, L. P. Coelho, S. Sunagawa, M. Bahram, F. Goeser, P. Bork, U. Wüllner
Journal: Genome Medicine (2017)

Parkinson's disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker. We performed metagenomic shotgun analyses and compared the fecal microbiomes of 31 early stage, L-DOPA-naïve PD patients to 28 age-matched controls. We found increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) were markedly lowered in PD samples. The observed differences could reliably separate PD from control with a ROC-AUC of 0.84. Functional analyses of the metagenomes revealed differences in microbiota metabolism in PD involving the ẞ-glucuronate and tryptophan metabolism. While the abundances of prophages and plasmids did not differ between PD and controls, total virus abundance was decreased in PD participants. Based on our analyses, the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in summary relates to 90% of PD patients) had no overall influence on taxa abundance or microbial functions. Our data revealed differences of colonic microbiota and of microbiota metabolism between PD patients and controls at an unprecedented detail not achievable through 16S sequencing. The findings point to a yet unappreciated aspect of PD, possibly involving the intestinal barrier function and immune function in PD patients. The influence of the parkinsonian medication should be further investigated in the future in larger cohorts.
Abstract P266: Molecular Markers of Endothelial Sensitivity to TNFα
Authors: Eugenia Mata-Greenwood
Journal: Circulation Research (2011)

TNF alpha mediated inflammation has been correlated with cardiovascular diseases. Significant interindividual variability to anti-TNF biologicals has been demonstrated in clinical trials. The objective of this study is to unravel the molecular markers of sensitivity to TNF which could be used as predictors of therapeutic efficacy or disease progression. We have isolated and tested a set of 20 HUVECs for their sensitivity to TNF as determined by up-regulation of pro-inflammatory genes such as the Intracellular Adhesion Molecule 1 (ICAM1) and the NADPH oxidase subunit 4 (NOX4). We found that 75% of HUVECs (15/20) responded strongly to TNF compared to the remaining 25% (5/20, p&lt;0.01). Further studies on the TNF signaling pathway indicated that there was a positive correlation between strong response to TNF and higher basal mRNA and protein levels of the mitogen activated protein 3 kinase 1 (MAP3K1 or MEKK1). No further correlations where observed with other signaling components (i.e., TNF receptors, TRAFs, and other MAP3Ks, MAP2Ks or MAPKs). Strong responders also showed 1) increased upregulation of TNFR1 and TRAF5 protein and mRNA levels, 2) higher phosphorylation of JNK and p38 MAPKs and 3) stronger AP1-driven transcription as shown by luciferase assays. Weak responders showed increased TNF-dependent down-regulation of the TNF receptor 1 and of the MAP3K5 (aka Apoptosis-Signaling Kinase 1, ASK1) and TNF-mediated upregulation of the TNF receptor 2 compared to strong responders. Promoter and mRNA stability studies revealed that differences between strong and weak responders in MAP3K1 and MAP3K5 regulation occurs at the transcriptional level. Studies of promoter polymorphisms are undergoing. We conclude that MAP3K1 and MAP3K5 are novel molecular markers of endothelial sensitivity to TNF and future studies on these genes could reveal novel genetic markers for translational research.
The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale
Authors: Ruben J Echemendia, Willem Meeuwisse, Paul McCrory, Gavin A Davis, Margot Putukian, John Leddy, Michael Makdissi, S John Sullivan, Steven P Broglio, Martin Raftery, Kathryn Schneider, James Kissick, Michael McCrea, Jiří Dvořák, Allen K Sills, Mark Aubry, Lars Engebretsen, Mike Loosemore, Gordon Fuller, Jeffrey Kutcher, Richard Ellenbogen, Kevin Guskiewicz, Jon Patricios, Stanley Herring
Journal: British Journal of Sports Medicine (2017)

The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument.
P12.08 Proteome and phosphoproteome analysis identifies STAT1 as a novel target in different grade meningiomas
Authors: S. Ferluga, D. Baiz, J. Dunn, D. A. Hilton, K. Bassiri, V. Sharma, C. Adams, E. Lasonder, C. Hanemann
Journal: Neuro-Oncology (2017)

Meningiomas are slow growing tumours of the meninges that affect brain and spinal cord. They account for a quarter of all primary brain tumours of the central nervous system. Accordingly to the WHO classification system, meningiomas are classified as grade I, atypical grade II and malignant grade III. Symptoms include headaches, focal neurological signs depending on localisation and seizures. The standard of treatment for these tumours is (radio)surgery. Nevertheless, it is estimated that one third of meningiomas cannot be operated or can be only partially resected, often leaving patients with significant morbidity. Current chemotherapies are not effective therefore it is a great medical need to find novel therapeutic options. We aimed to identify novel targets/biomarkers by analysing proteome and phosphoproteome of different grade meningiomas. Frozen tumour specimens as well as meningioma-derived primary tumour cells were analysed by mass spectrometry to decipher proteome and phosphoproteome. ­Phosphoproteins were isolated by an additional purification step. Overall we analysed 22 meningiomas (8 grade I, 8 grade II and 6 grade III) for the proteome and 14 for the phosphoproteome (5 grade I, 5 grade II and 4 grade III). Comparative studies were performed to identify aberrantly overexpressed proteins and dysregulated pathways compared to healthy human meninges (N=3). Among the proteins found significantly upregulated in meningioma vs. normal controls we identified STAT1, a member of the Jak/STAT signalling pathway. Validation studies performed on primary meningioma cells confirmed that the total amount of the protein was overexpressed about four times compared to normal human meningeal cells. Additionally, both phosphorylation sites (Y701 and S727) on STAT1 were aberrantly activated in meningioma cells but not in meningeal cells. Immunohistochemical analysis confirmed an upregulation of phosphorylated STAT1(Y701) especially on grade III meningiomas, in agreement with expression studies, although with high variability across samples. When the Jak/STAT signaling pathway gets activated in response to cytokines and growth factors, STAT1 is phosphorylated by activated JAKs and translocate into the nucleus to regulate gene expression. In primary meningioma cells we found that the amount of cytoplasmic pSTAT1(Y701) was markedly increased in vitro, without interferon stimulation and also in serum-free conditions, suggesting a cytokine-independent mechanism for pSTAT1 activation. Finally, STAT1 knocked down resulted in a significant reduction of cellular proliferation showed as a decrease in Ki67-positive cells and a decrease expression of Cyclin D1. These data altogether suggest STAT1 as a novel potential target in meningiomas.
P16.14 Treatment of thalamic glial lesions: surgery versus biopsy
Authors: M. P. Schiariti, E. Monti, G. Bertolini, F. Restelli, B. Pollo, M. Broggi, F. Acerbi, E. La Corte, P. Ferroli
Journal: Neuro-Oncology (2017)

Introduction: Thalamic tumors are a heterogeneous subset of deep lesions linked by topographical and behavioral features that recently re-gained interest in neurosurgical community. Glioma represents the most frequent neoplastic lesion in this site, and the treatment is still debated. With the present study we aimed to retrospectively analyze clinical, radiological and pathological data of patients affected by thalamic gliomas treated at our institution over the last 10 years, to better define indications for surgical treatment or tumor biopsy. Material and Methods: Pathology and surgical databases IRB-approved from our Neurosurgical Department were retrospectively reviewed to identify patients with histological diagnosis of thalamic gliomas. Clinical pre-operative and post-operative data along with demographic, histological, follow-up information and surgical treatment modalities were collected. Correlations between different variables (tumor grade, extent of resection, pediatric or adult age, post-operative Karnofsky Performance Status (KPS)) were evaluated using univariate analysis according to the Kaplan-Meier method. A p-value ≤ 0.05 was considered significant. Results: There were 55 patients (22 m, 33 f, mean age 37y), with a mean pre-operative volume of 52 cm3 in the surgery group (SG) and 32 cm3 in the biopsy group (BG). 31 patients underwent surgical resection while 24 underwent stereotactic or frameless biopsy. Early (within 72 hrs) post-operative mortality was 3% in the SG, and null in BG. After 3 months we observed a decrease in KPS greater than 10 points in 5 patients in SG and in 8 patients in BG. 2 patients in each group died within 3 months due to tumor progression. In the early post-operative period the mean KPS decreased in the SG while it was stable in the BG; this trend progressively turned around in the following months, due to medical and rehab therapy in the SG and disease progression in BG. In SG, the 25 patients who recovered the pre-operative clinical status within 3 months presented a significant increase in overall survival (OS) compared to BG (p = 0,01). OS was significantly longer in the SG compared to the BG (27mo. vs 11mo. respectively; p = 0,02). A gross total or subtotal resection was positively associated with an increase in OS (p = 0,01). Moreover, a pre-operative tumor volume exceeding 32 cm3 was significantly associated (p = 0,03) with a decrease in the OS. Although there were no statistical differences (p = 0,16) in terms of OS between adult and pediatric patients (<18 years), there was anyway a trend towards a longer OS period in the last group (16mo. vs 34mo. in the entire population, and 13mo. vs 22mo. in the SG). Conclusion: Surgery is showed to be a safe alternative to biopsy in thalamic gliomas. This option may improve prognosis as depicted by our data. When surgery is performed, the extent of resection represents the most important prognostic factor in terms of OS.
Establishment and characterization of arsenic trioxide resistant KB/ATO cells
Authors: Yun-Kai Zhang, Chunling Dai, Chun-gang Yuan, Hsiang-Chun Wu, Zhijie Xiao, Zi-Ning Lei, Dong-Hua Yang, X. Chris Le, Liwu Fu, Zhe-Sheng Chen
Journal: Acta Pharmaceutica Sinica B (2017)

Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.
Increase paediatric trainee numbers to meet workforce shortfall, says Royal College
Authors: Abi Rimmer
Journal: BMJ (2017)

The Royal College of Paediatrics and Child Health (RCPCH) has called for an increase in training numbers to meet a shortfall in the paediatric workforce.

On 27 April the college published its report The State of Child Health: The Paediatric Workforce. It called on the government to fund 465 more paediatrics training places in each year for the next five years to expand the consultant workforce by 752 doctors.

“Numbers have failed to keep pace with patient numbers, leading to dangerous pressure …
Urban-Rural Differences in Diabetes-Associated Mortality in China—Reply
Authors: Fiona Bragg, Liming Li, Zhengming Chen
Journal: JAMA (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 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
P17.06 Comparison of intensity modulated radiation therapy (IMRT) and conventional three dimensional conformal radiotherapy(3DCRT) in supratentorial astrocytic series WHO grade III- IV primary malignant brain tumors
Authors: I. A. Khaleel, H. Govardhan
Journal: Neuro-Oncology (2017)

Objectives: To determine whether Intensity Modulated Radiotherapy (IMRT) improves target coverage, target homogeneity, target conformity, critical tissue sparing without increasing the total integral dose to the non target brain tissue to the three dimensional conformal radiotherapy in Supratentorial Astrocytic series WHO grade III-IV primary malignant brain tumor. Methods and Materials: 50 patients of malignant glioma treated with 3DCRT were selected for a comparative dosimetric evaluation with IMRT. Target volumes, organ at risk (OAR), dose volume constrains were used for planning. Cumulative dose volume histogram of target volumes and organ at risk (OAR), normal brain tissue integral dose, target coverage, target homogeneity, target conformity, and normal tissue sparing with 3DCRT and IMRT planning were compared. Relevant Statistical test was performed to determine the differences and significance. Results:In all 50 patients examined, there was no significant difference in target coverage between IMRT and 3DCRT plans with slightly superiority in 3DCRT plan in the range of 95-100% of prescribed. IMRT improved target conformity, dose reduction to normal tissues including brain stem (Dmean by 17%, Dmax by 12%), optic chiasm(Dmean by 33%, Dmax by 22%), ipsilateral optic nerve(Dmean by 54 %, Dmax by 46%), contralateral optic nerve (Dmean by 42%, Dmax by 38%), Rt eye (Dmean by 37%, Dmax by 29%), Lt eye (Dmean by 33 %, Dmax by 35%), Hippocampus-combined (Dmean by 42%, Dmax 30%), p< 0.001. The 3DCRT reduced the overall integral dose to brain tissue by approximately 8%, p < 0.001 with IMRT. The Sub ventricular zone radiation dose was better covered by 3DCRT when compared to IMRT (ipsilateral SVZ mean dose- 54Gy Vs 42Gy, contralateral 44Gy Vs 35Gy, P<0.005). Conclusion:These results indicate that IMRT treatment for high grade glioma allows for improved target conformity, better critical tissue sparing without increasing the integral dose to normal brain tissue. But on dose to sub ventricular zone is low by IMRT compared to 3DCRT.
P03.02 Histological Spectrum Of Oligodendroglial Tumours: IDH1/2, ATRX And 1p19q
Authors: A. D. Wadile
Journal: Neuro-Oncology (2017)

Background: 1p19q co-deletion is requisite for diagnosis of oligodendroglial tumours. Design: FFPE tissues of histological spectrum of oligodendroglial tumours were evaluated for 1p19q deletion by FISH, IDH1/2 mutation and ATRX. Results: 260 oligodendroglial tumours [ODG: 29, ODG-A:129, OA:22, OA-A:68, GBM-O:12] with age range of 19–77 years. 99.2% (n: 258) cases were of cerebral hemispheric [53.5% frontal (n: 138), 14.7% mixed frontal (n: 38), 31.8% non-frontal (n: 82)]. 2 (0.08%) were thalamic. 119 of 158 (75.3%) pure oligodendrogliomas [ODG: 27 and ODG-A: 92], 21 of 90 (23.3%) mixed oligoastrocytic tumours [OA: 6 and OA-A: 15] and 1of 12 (8.3%) GBM-O were 1p19q co-deleted. 9 showed isolated 1p deletion (3.8%) and 15 showed isolated 19q deletion (5.8%). 144 (65.5%) pure oligodendrogliomas (ODG: 26 and ODG-A: 118), 71 (32.3%) oligoastrocytomas (OA: 19 and OA-A: 52) and 5 (2.5%) GBM-O were IDH1/2 mutated [IDH1R132H:201 (91.4%); IDH1R132S: 6 (3.1%), IDH1R132C: 2 (1%), IDH1R132L:1 (0.5%) and IDH1R132G: 1(0.5%), IDH2R172K: 7 (3.2%), one each (0.5%) showed IDH2R172M and IDH2R172W mutations]. 6.3% (9/142) of pure oligodendroglial cases showed loss of ATRX protein; while 58% (45/78) and 22.2% (2/22) of oligoastrocytic and GBM-O cases showed loss of ATRX protein respectively. The cases were subgrouped into 5 distinct molecular subsets: A (mIDH1/2, 1p19q co-deleted and ATRX retained) - 118 [56.4%; pure ODG:101(63%), OAs:17 (18.7%) and GBM-O:0], B (mIDH1/2, 1p19q non-deleted and ATRX loss) - 36 [17.2%; pure ODG:4(2.5%), OAs:31(34.1%) and GBM-O:1); C (mIDH1/2, 1p19q non-deleted and ATRX retained) - 27 [12.9%; pure ODG:18 (11.2%), OAs:7 (7.7%) and GBM-O:2]; D (wIDH1/2, 1p19q non-deleted and ATRX retained) - 14 [6.6%; pure ODG:4, OAs:6 and GBM-O:4]; E (wIDH1/2,1p19q non-deleted and ATRX loss) - 12 [5.7%; pure ODG:2, OAs:9 and GBM-O:1] Conclusions: Histologically pure oligodendrogliomas can rarely show ATRX protein loss and not all histologically pure oligodendroglial tumours with mIDH1/2 and retained ATRX protein were 1p19q co-deleted by FISH. This prudently raises a question of sensitiveness of FISH as technique to detect 1p19q co-deletion or is there any 1p19q independent alteration existing for oligodendrogliomas.
pKDR/KDR ratio predicts response in a phase I/II pharmacodynamic study of erlotinib and bevacizumab for recurrent or metastatic head and neck cancer (HNC)
Authors: T. Y. Seiwert, D. W. Davis, D. Yan, A. M. Mauer, T. Karrison, M. Kozloff, A. Dekker, S. J. Wong, E. E. Vokes, E. E. Cohen
Journal: Journal of Clinical Oncology (2007)

6021 Background: EGFR activation up-regulates VEGF, which has been correlated with resistance to anti-EGFR agents. We previously reported early results (Vokes, JCO, 2005) of a phase I-II study of the EGFR inhibitor erlotinib (E) with the VEGF antibody bevacizumab (B) in recurrent or metastatic HNC. We now present results from the pharmacodynamic analysis as well as updated outcome data. Methods: Phase I/II trial of fixed dose erlotinib (E) 150 mg orally daily with escalation of bevacizumab (B) to a maximum of 15 mg/kg q 3 weeks and continued at 15 mg/kg in the phase II portion. Pts were randomized to receive the initial bevacizumab dose on either day 1 or 15. Paired biopsies were taken at baseline and after 2 weeks of treatment (after E alone or E+B) and analyzed by immunofluorescence and laser scanning analysis for target inhibition and apoptosis markers (VEGFR2/KDR, EGFR, CD31, and respective activated forms [pKDR, pEGFR]). Results: Paired biopsies were available from 20 patients. At baseline pKDR/KDR (ratio) correlated with clinical outcome and differed significantly between responses (CR&gt;SD: p&lt;0.01; CR&gt;PD: p&lt;0.0005). Interestingly, endothelial cell EGFR levels also appeared to correlate with response (CR+SD&gt;PD: p&lt;0.03). Paired tissue samples showed that E or E +B treatment increased apoptosis in tumor cells (pre: 0.96%, post: 7.02%: p&lt;0.05) and endothelial cells (pre: 0%, post: 12%: p=0.15). Further, E+B treatment reduced expression of endothelial KDR, EGFR and VEGF levels compared to E alone. We previously reported an overall response rate of 14.6% (48 evaluable patients in the phase II cohort). Updated median follow-up was 7.3 months (2.1 years for patients still alive). The updated median overall/ progression free survival was 7.3 months/ 3.9 months with 30.6%/ 8.2% of patients alive at 1/2 years. Conclusions: Compared to E alone the combination of E + B showed increased inhibition of endothelial survival factors. pKDR/KDR appears to predict response to E+B. The promising clinical efficacy of E+B and potential predictive biomarkers warrant further validation in larger cohorts. (Supported by NIH N01 CM-57018–16) No significant financial relationships to disclose.
INJURIES IN 17–19 YEAR-OLD MALE AMATEUR SOCCER PLAYERS
Authors: Stefan Ackermann, Thomas Henke, Wilhelm Bloch
Journal: British Journal of Sports Medicine (2017)

Background There is only a small body of literature regarding injuries in male youth amateur soccer players. Yet such information is fundamental for effective prevention. Objective Analysis of injury patterns among 17–19 year old male amateur soccer players and comparison with adult male amateur and professional players. Design Questionnaire-based retrospective observational cohort study from August 30, 2014 to January 04, 2016. Players were instructed to fill out one general questionnaire and, in case of at least one injury during the relevant period of time, one additional questionnaire per injury. Setting Regional youth amateur soccer level. Participants were recruited from 20 clubs of four regional soccer leagues, representing the fifth and sixth highest level of performance for this age group. Participants 301 players who competed in one of these leagues during the season 2015/16 were included. Main Outcome Measurements Exposure, injured body parts, incidence and time loss. Results 205 players sustained 253 injuries. The incidence was 12.9 injuries per 1,000 h of competition exposure and 1.1 injuries per 1,000 h of practice and friendly games. 82.9% of injuries were located at the lower extremity. Ligaments were injured most frequently (23.3%). 32.0% of all injuries could be graded as severe, 45.1% as moderate, followed by 15.4% mild and 4.7% minimal injuries as defined by Fuller et al . (2006). Physical contact caused injuries most frequently (30.4%), followed by landings (12.9%). Conclusions Injury incidences in male youth amateur soccer were lower, while the portion of severe and moderate injuries was higher than in studies researching professional soccer. The allocation of injuries was almost similar to findings in professional and adult amateur soccer. Although physical contact is cross-study the most important cause of soccer injuries, existing prevention programs almost entirely focus on non-contact injuries. Therefore interventions preventing injuries through physical contact should be developed and validated.