tbuckley/cabot-search huggingface dataset:
Deficits in dynamic balance during tandem gait after concussion may be exacerbated by dual-tasks
Authors: RC Lynall, JT Blackburn, KM Guskiewicz, SW Marshall, P Plummer, JP Mihalik
Journal: British Journal of Sports Medicine (2017)

Objective Expert consensus recommends tandem gait (heel-to-toe walking) to assess concussion. Failure rate when only assessing time-to-task completion is unacceptably high among healthy participants. Our purpose was to assess tandem gait centre of pressure and dual-task cost with and without cognitive distraction in recently concussed individuals. Design Cross-sectional. Setting University. Subjects Thirty college-aged recreational athletes in two 15-person groups: 1) recent concussion (median time post-concussion=126 days, range 28-432d), and 2) healthy sex-, age- (±1 yr), mass- (±10%), and height- (±5%) matched controls. Intervention Participants completed 3 trials each of 4 tandem gait conditions: 1) tandem gait (eyes open, no cognitive distraction), 2) tandem gait (eyes closed, no cognitive distraction), 3) tandem gait (eyes open, Brooks Visuospatial Task cognitive distraction), and 4) tandem gait (eyes closed, Brooks Visuospatial Task cognitive distraction). Outcome measures Centre of pressure velocity, speed, path length, and dual-task cost. Results The recent concussion group (25.15 cm/s) demonstrated slower tandem gait velocity compared to the control group (29.20 cm/s; p=0.049; 95% CI:0.02-8.06 cm/s). After controlling for group velocity differences, the recent concussion group (23.5%) had higher centre of pressure speed dual-task cost during the eyes closed dual-task condition than did the control group (16.3%; p=0.032; 95% CI:2.70-11.48%). Conclusions We observed subtle centre of pressure group differences more than one month after post-concussion return to activity. It remains unclear if these differences impact clinical outcomes post-concussion. Longitudinal investigations should study acute post-concussion movement deficits, and discern the recovery of these deficits in comparison to recovery using traditional concussion assessment tools. Competing interests None.
Polymorphonuclears Display a New Type of Abnormal Cytologic Granules (Chediak Higashi-Like) in a Very Rare Syndrome Linked to a Biallelic Defect of WDR81
Authors: Marion Eveillard, Myriam Chevalier, Thomas Besnard, Benjamin Cogne, Alice Kuster, Stephane Bezieau, Marie C Bene, Claire Beneteau
Journal: Blood (2016)
Inhibition of breast cancer progression by a medicinal herb Ocimum sanctum
Authors: Pratima Nangia-Makker, Larry Tait, Victor Hogan, Fred Miller, Avraham Raz
Journal: Cancer Research (2006)

2170    Ocimum sanctum  (OS) also known as holy basil or tulsi, belonging to mint family (Labiateae) has been one of the most popular herbs used in European and Asian countries for the treatment of various ailments since ancient times. We reported earlier that aqueous extracts collected from the leaves of this herb inhibited chemotaxis of breast cancer cell lines MDA-MB-435, MDA-MB-231 and endothelial cell line HUVEC towards specific chemo attractants, capillary tube formation in 3 dimensional cultures of HUVEC on Matrigel, TPA induced increase of COX-2 in MDA-MB-231 cells, and MDA-MB-231 cells induced angiogenesis in Matrigel plug assay in nude mice. To explore if OS extracts have an inhibitory effect on breast cancer, we used two human breast cancer cell lines for tumorigenic studies; namely MDA-MB-435 and MCF10A DCIS.com (DCIS.com) cells. MDA-MB-435 cells form undifferentiated adenocarcinomas in nude mice. Injection of DCIS.com cells into nude mice results in lesions that are predominantly DCIS subtype. In 3 weeks, the lesions show a DCIS like pathology consisting of ducts surrounded by complete basement membrane and extensive angiogenesis in the stroma. The ducts develop into a complete comedo phenotype by 6 weeks. When OS extracts were fed to nude mice injected with MDA-MB-435 or DCIS.com cells, there was a significant reduction in the rate of tumor growth in the treated mice. The tumors in OS fed mice grew at similar rates as the water fed controls initially, though their overall size was smaller than the controls. After reaching a tumor volume of approximately 150mm 3  in DCIS.com or 200 mm 3  in MDA-MB-435 the growth rate started to slow down. The inhibition in tumor growth was due to reduced cell proliferation and angiogenesis as indicated by immunohistochemical analysis utilizing anti CD34 (neo angiogenesis) and anti proliferating cell nuclear antigen (PCNA) antibodies. Furthermore, there was also a reduced expression of COX-2, MMP-9 and redistribution of VEGF from stromal epithelial compartments to epithelial compartment in the OS treated xenografts. A comparative analysis of the temporal development between normal and OS treated DCIS.com xenografts indicates a delay towards progression to DCIS-like phenotype by oral administration of OS. Based on our data we conclude that OS extract inhibit tumor growth and progression by affecting cell proliferation and angiogenesis and it could be developed into a breast cancer preventive and therapeutic agent.
HGG-20. NEURONAL ACTIVITY PROMOTES PEDIATRIC GLIOMA INVASION
Authors: Tessa Johung, Kathryn Taylor, Humsa Venkatesh, Anna Geraghty, Michelle Monje
Journal: Neuro-Oncology (2017)

The diffusely infiltrating nature of pediatric high-grade glioma (pHGG) is a characteristic hallmark of this disease and represents a major contributor to the dire prognosis seen for pHGG of all neuroanatomical locations, most notably in H3K27M-mutant diffuse midline gliomas such as DIPG. Despite the fact that widespread infiltration is a defining aspect of this group of diseases, the molecular and cellular determinants of pHGG migration and invasion are not well understood. We have previously shown that neuronal activity regulates pHGG growth. Here, we investigated the role of neuronal activity on glioma invasion using conditioned media (CM) generated from optogenetically stimulated, spontaneously active or TTX-silenced acute cortical slices. RNA-seq data revealed gene expression changes in cortical pHGG cells exposed to active CM, with an increased expression of several known glioma migratory/invasive factors including AQP4, TTYH1 and CHI3L1. We observed a marked increase in the invasive capacity of pHGG and DIPG patient-derived cultures upon the addition of active CM in both transwell and three-dimensional (3D) in vitro invasion assays. Analysis of several candidate proteins identified via proteomic screens highlighted two secreted factors, GRP78 and CRTAC1, which alone were sufficient to increase pHGG invasion. Abrogation of this pro-infiltrative effect was seen upon immunodepletion of GRP78 from the CM. Conversely CRISPR knockout of the Nogo receptor (NgR), on which CRTAC1 acts as an exogenous antagonist, markedly increased in vitro DIPG cell invasion. Both CRTAC1 and GRP78 have been shown to modulate RhoA activity in putatively complimentary ways, and we observed a significant reduction in RhoA activation upon exposure to active CM. As Rho-ROCK signalling modulates actin reorganisation and cell motility, this highlights a novel means by which the neural microenvironment drives glioma progression and potentially identifies a new set of therapeutic targets to limit glioma spread.
Upregulation of BRCA1: an independent prognostic variable in completely resected chemonaive non-small-cell lung cancer (NSCLC) patients (p)
Authors: Marcin Skrzypski, Pedro Mendez, Imane Chaib, Laia Perez Roca, Maria Perez Cano, Monica Botia, Miquel Taron, Ewa Jassem, Jacek Jassem, Rafael Rosell
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2702 

Following surgical resection in operable NSCLC, 5-year survival is 60% in stage I (T1-2N0M0), 39% in stage IIB (T2N1M0) and 23% in stage IIIA (T1-3N2M0), with relapse commonly in the form of distant metastases. The average benefit of adjuvant chemotherapy is 5%, ranging from nil in stage I to 15% in stage II-IIIA. Caretaker genes involved in keeping genetic alterations to a minimum include the nucleotide excision repair genes ERCC1 and myeloid zinc finger 1 (MZF1), which mediates ERCC1 expression, and other stability genes, such as BRCA1, which control processes involving large portions of chromosomes. Thioredoxin-1 (TRX1) is a redox protein overexpressed in NSCLC that is correlated with poor prognosis, and TWIST contributes to metastasis by promoting epithelial-mesenchymal transition. In order to identify p with a high risk of relapse, we investigated the expression of these 5 transcripts in frozen resected tumors from 126 resected NSCLC p by real-time quantitative PCR. Gene expression was normalized using β-actin and 18SrRNA expression as internal references. Adenocarcinoma (adeno), 33 p; squamous cell carcinoma (SCC), 93 p. Stage: IA, 18 p; IB, 53 p; IIB, 33 p; IIIA, 22 p. Tumoral transcript expression with β-actin: ERCC1, 1.23; MZF1, 0.53; BRCA1, 3.65; TRX1, 1.82; TWIST, 7.75. A strong correlation was observed between the expression of ERCC1, MZF1 and BRCA1 (P<0.001). Expression of each of the 5 transcripts was higher in SCC than in adeno (P<0.001). Median survival (MS): low ERCC1 (<1.5) = not reached (NR), high ERCC1 = 33 months (m) (P=0.21); low MZF1 (<0.5) = NR, high MZF1 = 33 m (P=0.04); low BRCA1 (<5) = NR, high BRCA1 = 22 months (m) (P=0.01); low TRX1 (<0.8) = NR, high TRX1 = 39.5 m (P=0.02); no differences in MS according to levels of TWIST. In a multivariate Cox model for survival, BRCA1 and stage emerged as independent prognostic variables; hazard ratios: 2 for high BRCA1 (P=0.02); 8 for stage IIIA (P=0.001). Increased BRCA1 is associated with shorter survival, and BRCA1 assessment could be useful for customizing adjuvant chemotherapy.
MEDU-03. MEDULLOBLASTOMA GENOMIC SUBGROUP-SPECIFIC OUTCOMES IN IRRADIATED CHILDREN ABOVE 3 YEARS TREATED AT KING FAHAD MEDICAL CITY (KFMC)
Authors: Musa Al-Harbi, Nahla Mobarak, Othman Mosleh, Malak Abedalthagafi
Journal: Neuro-Oncology (2017)

Medulloblastoma (MB) is the most common malignant brain tumor in children. WHO 2016 classify MB into four distinct molecular subgroups. The aim of this study is to characterize the molecular MB subgroups and correlate it with defined clinical outcomes in Middle Eastern children. A retrospective study of newly diagnosed MB in 55 children (>3 year and < 16 year) was collected. All treated at KFMC between 2009–2016. Molecular analysis was done using next generation targeted sequencing (NGS) for 560 cancer-relevant genes. 38(69.1%) are male and 17 (30.9%) are females, median age at diagnosis 83 months. Classic MB 39(70.9%), Desmoplastic/nodular MB 10 (18.2%), MB- extensive nodularity 2(3.6%) and LC/Anaplastic MB 4(7.3%), 21 patients (71%) had metastatic disease M2/3. 28 (50.4%) patients treated as average-risk and 27 (48.6%) treated as high-risk. Molecular analysis was done for 31 patients: 3 WNT group (9.7%), 5 SHH (16, 1%), 3 group 3 (9.7%), and 12 group 4 (38.7%), 8(25.8%) non-WNT/non-SHH. A median follow-up of 36 months: PFS for the entire study patients was 81.8% and 3-year OS was 83.6. 3-year PFS across the 5 subgroups was statistically significant difference in a pooled analysis. Three-year PFS for the WNT subgroup was 100%, for the SHH subgroup 80% for Group Three 33.3%, for Group Four 83.3% and for the Non WNT/Non SHH group 75% (p<0.001 across all 5 subgroups). This is the first study in Middle East which highlights the prognostic implications of MB genomic subgroups. Our result was excellent compared to international studies although most of our patients had unfavorable molecular subgrouping. Our group 4 patients had better survival than previously reported. NGS classification has potential for future reduction of standard therapy for children with favorable molecular subgroup and real implication for precision medicine in our oncology practice.
ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA
Authors: John B. Nelson
Journal: The Journal of Experimental Medicine (1953)

The hepatitis of Princeton weanlings was not prevented by the prior injection of terramycin nor was the virus inactivated by exposure to room temperature. Eperythrozoon coccoides was not demonstrable in blood films from Swiss and Princeton mice infected with the corresponding type of hepatitis virus. Combined infection with this virus and eperythrozoa, originally obtained by Dr. R. B. McGhee from mice in association with Plasmodium berghei, was attended by the appearance of numerous organisms in the blood. The development of eperythrozoa in dually infected Princeton mice had no effect on the outcome of the hepatitis. In Swiss mice, animals with high natural resistance to hepatitis virus, the pathogenicity of this agent was markedly enhanced by combined infection with eperythrozoa. Eperythrozoa were maintained throughout 18 successive passages in normal Princeton and Swiss weanlings with intact spleens. The combined infection of Princeton mice with eperythrozoa and the virus component of Gledhill, Dick, and Andrewes, which is nearly inactive when injected alone, resulted in acute hepatitis with fatal outcome.
La lithotripsie extracorporelle est une technique sure et efficace dans la population de patients pédiatrique atteints de pancréatite chronique
Journal: Endoscopy (2017)

La lithotripsie extracorporelle pancréatique (LEC) est recommandée en première ligne de traitement des calculs pancréatiques. Cependant les modalités de réalisation chez les patients pédiatriques restent peu établies. L’objectif de ce travail était donc d’évaluer l’innocuité et l’efficacité de la LEC chez les mineurs atteints de pancréatite chronique (PC).
Gefitinib and <i>EGFR</i> Gene Copy Number Aberrations in Esophageal Cancer
Authors: Russell D. Petty, Asa Dahle-Smith, David A.J. Stevenson, Aileen Osborne, Doreen Massie, Caroline Clark, Graeme I. Murray, Susan J. Dutton, Corran Roberts, Irene Y. Chong, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen J. Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Jonathan Wadsley, Ian Chau, David R. Ferry, Zosia Miedzybrodzka
Journal: Journal of Clinical Oncology (2017)

Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status. EGFR CNG was determined by fluorescent in situ hybridization (FISH) using prespecified criteria and EGFR FISH-positive status was defined as high polysomy or amplification. Results Biomarker data were available for 340 patients. In EGFR FISH-positive tumors (20.2%), overall survival was improved with gefitinib compared with placebo (hazard ratio [HR] for death, 0.59; 95% CI, 0.35 to 1.00; P = .05). In EGFR FISH-negative tumors, there was no difference in overall survival with gefitinib compared with placebo (HR for death, 0.90; 95% CI, 0.69 to 1.18; P = .46). Patients with EGFR amplification (7.2%) gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI, 0.07 to 0.64; P = .006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF, and PIK3CA mutations, or for any mutation versus none. Conclusion EGFR CNG assessed by FISH appears to identify a subgroup of patients with esophageal cancer who may benefit from gefitinib as a second-line treatment. Results of this study suggest that anti-EGFR therapies should be investigated in prospective clinical trials in different settings in EGFR FISH-positive and, in particular, EGFR-amplified esophageal cancer.
Brain on Fire: Incentive Salience, Hedonic Hot Spots, Dopamine, Obesity, and Other Hunger Games
Authors: Jameason D. Cameron, Jean-Philippe Chaput, Anders M. Sjödin, Gary S. Goldfield
Journal: Annual Review of Nutrition (2017)

This review examines human feeding behavior in light of psychological motivational theory and highlights the importance of midbrain dopamine (DA). Prospective evidence of both reward surfeit and reward deficit pathways to increased body weight are evaluated, and we argue that it is more complex than an either/or scenario when examining DA's role in reward sensitivity, eating, and obesity. The Taq1A genotype is a common thread that ties the contrasting models of DA reward and obesity; this genotype related to striatal DA is not associated with obesity class per se but may nevertheless confer an increased risk of weight gain. We also critically examine the concept of so-called food addiction, and despite growing evidence, we argue that there is currently insufficient human data to warrant this diagnostic label. The surgical and pharmacological treatments of obesity are discussed, and evidence is presented for the selective use of DA-class drugs in obesity treatment.
Difficulties in Testing the Instrument Strength Independent of Direct Effect Assumption in Mendelian Randomization
Authors: Jack Bowden, Stephen Burgess, George Davey Smith
Journal: JAMA Cardiology (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 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
IGF1R Protein Expression Is Not Associated with Differential Benefit to Concurrent Trastuzumab in Early-Stage HER2+ Breast Cancer from the North Central Cancer Treatment Group (Alliance) Adjuvant Trastuzumab Trial N9831
Authors: Monica M. Reinholz, Beiyun Chen, Amylou C. Dueck, Kathleen Tenner, Karla Ballman, Darren Riehle, Robert B. Jenkins, Xochiquetzal J. Geiger, Ann E. McCullough, Edith A. Perez
Journal: Clinical Cancer Research (2017)

Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism of trastuzumab resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2+ adjuvant N9831 trial.Experimental Design: IGF1R protein expression was determined in tissue microarray sections (three cores per block; N = 1,197) or in whole tissue sections (WS; N = 537) using IHC (rabbit polyclonal antibody against IGF1R β-subunit). A tumor was considered positive (IGF1R+) if any core or WS had ≥1+ membrane staining in >0% invasive cells. Median follow-up was 8.5 years.Results: Of 1,734 patients, 708 (41%) had IGF1R+ breast tumors. IGF1R+ was associated with younger age (median 48 vs. 51, P = 0.007), estrogen receptor/progesterone receptor positivity (78% vs. 35%, P < 0.001), nodal positivity (89% vs. 83%, P < 0.001), well/intermediate grade (34% vs. 24%, P < 0.001), tumors ≥2 cm (72% vs. 67%, P = 0.02) but not associated with race or tumor histology. IGF1R did not affect DFS within arms. Between Arms A and C, patients with IGF1R+ and IGF1R- tumors had DFS HRs of 0.48 (P ≤ 0.001) and 0.68 (P = 0.009), respectively (Pinteraction = 0.17). Between Arms A and B, patients with IGF1R+ and IGF1R- tumors had DFS HRs of 0.83 (P = 0.25) and 0.69 (P = 0.01), respectively (Pinteraction = 0.42).Conclusions: In contrast to preclinical studies that suggest a decrease in trastuzumab sensitivity in IGF1R+ tumors, our adjuvant data show benefit of adding trastuzumab for patients with either IGF1R+ and IGF1R- breast tumors. Clin Cancer Res; 23(15); 4203-11. ©2016 AACR.
Assessment of the automated multiplex-PCR Unyvero i60 ITI® cartridge system to diagnose prosthetic joint infection: a multicentre study
Authors: D. Malandain, P. Bémer, A.G. Leroy, J. Léger, C. Plouzeau, A.S. Valentin, A. Jolivet-Gougeon, D. Tandé, G. Héry-Arnaud, C. Lemarié, M. Kempf, L. Bret, C. Burucoa, S. Corvec, J. Cottin, F. Ducellier, P. Abgueguen, V. Balan, E. Stindel, S. Ansart, A. Greves, G. Aubin, S. Touchais, F. Gouin, D. Boutoille, N. Asseray, L. Happi, J. Guinard, F. Razanabola, C. Mille, A.S. Cognée, L.E. Gayet, G. Le Moal, C. Thomas, J.L. Polard, C. Arvieux, A. Meheut, L. Bernard, P. Rosset, G. Gras, J. Druon, K. Fèvre
Journal: Clinical Microbiology and Infection (2017)
Clinical grade SNaPshot genetic mutation profiling in multiple myeloma.
Authors: Elizabeth O'Donnell, Anuj Kumar Mahindra, Andrew Jenho Yee, Nicole Birrer, Nora Horick, Dianne M. Finkelstein, Darrell R. Borger, A. John Iafrate, Noopur S. Raje
Journal: Journal of Clinical Oncology (2014)

e19571 Background: Whole genome sequencing studies have identified several oncogenic mutations in multiple myeloma (MM). In particular, mutations in BRAF, a potential druggable target, have been identified in 4% of patients. The nature of MM is that it is a chronic, relapsing illness. As MM evolves, there is a role for rapid determination of whether targetable mutations are present to optimize individualized treatment of disease. Methods: Massachusetts General Hospital has developed a CLIA (Clinical Laboratory Improvement Amendments) high-throughput, genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed SNaPshot, uses a highly sensitive multiplexed PCR-based assay to simultaneously identify 70 genetic loci frequently mutated in 15 cancer genes. This assay has been used at our institution for over 4 years for tumor genotyping and to help guide therapeutic decisions for patients with various malignancies. We performed SNaPshot analysis on 67 bone marrow samples from MM patients after isolating genomic DNA from these samples and performing quality assurance tests. Results: Thirty-nine % (26/67) of tumor samples from unique patients harbored candidate mutations. 3/26 were bone marrow (BM) samples from newly diagnosed patients and 23/26 were BM (23/26) and plasmacytoma (3/26) samples from relapsed MM. All samples with mutations had single mutations. Somatic oncogene mutations were found in KRAS (15), NRAS (6), BRAF (2), p53 (2), and HRAS (1). 24/26 patients with mutations versus 26/41 wild type had heavy chain disease (p=.009). Median survival in patients with mutations was 6.6 v 8.7 years in wild type (p=.26). Conclusions: Sequence analysis using SNaPshot on DNA extracted from bone marrow and extramedullary plasmacytomas is feasible and leads to the detection of potentially druggable mutations. Screening MM patients for somatic mutations in oncogenes may provide potential novel targets leading to additional therapies for this patient population.