tbuckley/cabot-search huggingface dataset:
Posterior fossa syndrome and long-term neuropsychological outcomes among children treated for medulloblastoma on a multi-institutional, prospective study
Authors: Jane E Schreiber, Shawna L Palmer, Heather M Conklin, Donald J Mabbott, Michelle A Swain, Melanie J Bonner, Mary L Chapieski, Lu Huang, Hui Zhang, Amar Gajjar
Journal: Neuro-Oncology (2017)

Patients treated for medulloblastoma who experience posterior fossa syndrome (PFS) demonstrate increased risk for neurocognitive impairment at one year post diagnosis. The aim of the study was to examine longitudinal trajectories of neuropsychological outcomes in patients who experienced PFS compared with patients who did not.Participants were 36 patients (22 males) who experienced PFS and 36 comparison patients (21 males) who were matched on age at diagnosis and treatment exposure but did not experience PFS. All patients underwent serial evaluation of neurocognitive functioning spanning 1 to 5 years post diagnosis.The PFS group demonstrated lower estimated mean scores at 1, 3, and 5 years post diagnosis on measures of general intellectual ability, processing speed, broad attention, working memory, and spatial relations compared with the non-PFS group. The PFS group exhibited estimated mean scores that were at least one standard deviation below the mean for intellectual ability, processing speed, and broad attention across all time points and for working memory by 5 years post diagnosis. Processing speed was stable over time. Attention and working memory declined over time. Despite some change over time, caregiver ratings of executive function and behavior problem symptoms remained within the average range.Compared with patients who do not experience PFS, patients who experience PFS exhibit greater neurocognitive impairment, show little recovery over time, and decline further in some domains. Findings highlight the particularly high risk for long-term neurocognitive problems in patients who experience PFS and the need for close follow-up and intervention.
Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and Non-L265P Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
Authors: Sydney Dubois, Pierre-Julien Viailly, Elodie Bohers, Philippe Bertrand, Philippe Ruminy, Vinciane Marchand, Catherine Maingonnat, Sylvain Mareschal, Jean-Michel Picquenot, Dominique Penther, Jean-Philippe Jais, Bruno Tesson, Pauline Peyrouze, Martin Figeac, Fabienne Desmots, Thierry Fest, Corinne Haioun, Thierry Lamy, Christiane Copie-Bergman, Bettina Fabiani, Richard Delarue, Frédéric Peyrade, Marc Andre, Nicolas Ketterer, Karen Leroy, Gilles A. Salles, Thierry Jo Molina, Hervé Tilly, Fabrice Jardin
Journal: Blood (2016)
Safety and results of anti-PD1 combined with radiosurgery for the treatment of melanoma brain metastases.
Authors: Caroline Gaudy Marqueste, Romain Carron, Florent Amatore, Nausicaa Malissen, Xavier Muracciole, Anderson Loundou, Laura Troin, Sandrine Monestier, Stéphanie Mallet, Marie-Aleth Richard, Jean Regis, Jean Jacques Grob
Journal: Journal of Clinical Oncology (2017)

9552 Background: Anti-PD1 are now pivotal in the treatment of metastatic melanoma (MM). Some concerns have emerged regarding the risk/benefit ratio of their combination with stereotactic radiosurgery. Methods: Retrospective assessment of the interaction between Gamma-Knife radiosurgery (GKRS) and anti-PD1 in terms of toxicity and OS in mm patients (pts) with BM. Patients were included if they were under anti-PD1 (PRE) at time of GKRS, or if they had started anti-PD1 concomitantly with GKRS (CO), or had received anti-PD1 within 3 months after GKRS (POST). Results: Among 47 pts who received GKRS and anti-PD1 during their disease course, 35 fulfilled PRE or CO or POST criteria (anti PD1 1 st line therapy in 10 pts and 2 d or more in 25 pts). One pt died before radiological evaluation. GKRS targeted a single BM in 10 pts and multiple BMs in 24 (max 19 BMs). Out of the 128 BMs treated, 6 cases of increase of preexisting edema (4.7%) and 8 hemorrhages (6.25%) occurred in 12 pts, but only 5 events (5%) were regarded as Adverse Radiation effects (ARE), being symptomatic in 3 pts (8% of pts). One BM had to be resected because of the occurrence of a symptomatic hemorrhage with hemiparesis 9 month after treatment. Median follow- up from GKRS was 13.7 mths. Median overall survival (OS) from GKRS and 1 st BM were 14.8 and 26.5 mths respectively, with 6 and 12 mths 0S rates from GKRS of 65.7% and 57%, respectively. Local failure was observed in 5 pt. Median time to new BM was 12.6 mths. There was no significant difference in outcomes in pts, depending on PRE, CO and POST conditions. Conclusions: In this series, the largest to date of pts with BMs treated by GKRS and anti-PD1,ARE were within the expected range and survival rates appear promising. Given the natural propensity of MM-BMs for bleeding and edema our data do not support an increased risk with the combination of GKRS and anti-PD1. Regarding the timing between anti-PD1 administration and GKRS our data do not support a higher efficacy or higher toxicity among the 3 following potential mechanisms: immuno- sensitization to radiation (PRE), immuno-radio direct synergy (CO) or radiosensitization to immunotherapy (POST).
Ibrutinib Disrupts the Metabolic Program of CLL Cells in-Vivo
Authors: Uri Rozovski, David M. Harris, Ping LI, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan A. Burger, Susan M. O'Brien, Prithviraj Bose, Philip A. Thompson, Nitin Jain, William G. Wierda, Michael Keating, Zeev Estrov
Journal: Blood (2016)
Supraclavicular block versus interscalene brachial plexus block for shoulder surgery: A meta-analysis of clinical control trials
Authors: C.W. Guo, J.X. Ma, X.L. Ma, B. Lu, Y. Wang, A.X. Tian, L. Sun, Y. Wang, B.C. Dong, Y.B. Teng
Journal: International Journal of Surgery (2017)
Genomic Landscape of Atypical Adenomatous Hyperplasia and Their Progression to Lung Adenocarcinomas
Authors: S. Sivakumar, F.A. San Lucas, T.L. McDowell, W. Lang, L. Xu, J. Fujimoto, J. Zhang, I.I. Wistuba, F.A. Futreal, J. Fukuoka, Y. Yatabe, S. Dubinett, A. Spira, J. Fowler, E. Hawk, P. Scheet, H. Kadara
Journal: Journal of Thoracic Oncology (2017)
Significant Hepatic Fibrosis Among Treatment-Naive Chronic Hepatitis B Virus With Increased Hepatitis B Virus DNA and Normal Alanine Aminotransferase
Authors: Robert J. Wong, Angelica Le, My T. Nguyen, Huy N. Trinh, Andrew Huynh, My Tops Ly, Huy A. Nguyen, Khanh K. Nguyen, Jenny Yang, Ruel T. Garcia, Brian Levitt, Eduardo da Silveira, Robert G. Gish
Journal: Clinical Gastroenterology and Hepatology (2017)
Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer–Predisposing Mutations in Pheochromocytomas and Paragangliomas
Authors: Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, María Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascón
Journal: Clinical Cancer Research (2017)

Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes.Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases.Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2, c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio.Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR.
Zika virus infection and microcephaly in Vietnam
Authors: Meng Ling Moi, Thi Thu Thuy Nguyen, Co Thach Nguyen, Thi Bich Hau Vu, Mya Myat Ngwe Tun, Tho Duoc Pham, Ngoc Thanh Pham, Thuan Tran, Kouichi Morita, Thi Quynh Mai Le, Duc Anh Dang, Futoshi Hasebe
Journal: The Lancet Infectious Diseases (2017)
Modulation of RhoA associated signaling by lovastatin and celecoxib in human colon cancer cells.
Authors: Suresh Guruswamy, Vernon Steele, Levy Kopelovich, Chinthalapally Rao
Journal: Cancer Research (2008)

3069   Combinational regimens offer promise for chemoprevention because they allow the use of low doses for blocking multiple signaling pathways. The identification of molecular targets responsible for synergistic tumor inhibitory effects is extremely important. We have shown that a combination of celecoxib (COX-2 inhibitor) and lovastatin (HMG-R inhibitor) provides synergistic tumor inhibitory effects in preclinical models (Swamy MV et al, Cancer Res. 2006, 66:7370-7; Reddy BS et al, Cancer Res. 2006 66: 4542-6). An analysis of tissues from azoxymethane (AOM) induced rat colon tumors show a ten-fold increase in RhoA compared to normal colonic mucosa. The Rho/ROCK pathway plays an important role in cancer progression by modulating the expression of several proteins like E-cadherin, PKCδ and cell cycle regulatory proteins. We tested the hypothesis that the reduced tumor incidence and size observed in pre-clinical models treated with lovastatin and/or celecoxib may be associated with a decrease in RhoA associated signaling. Therefore, in the current study, we analyzed the molecular mechanism involved in the synergistic action of lovastatin and celecoxib on RhoA/ROCK signaling. HCT116 cells were treated for 24 hours with 25 μM lovastatin and 50 μM celecoxib either alone or in combination and western blots was performed to analyze the expression of Rho/ROCK signaling pathway proteins. Because RhoA/ROCK signaling is involved in cytoskeleton organization and cell motility, we studied the effect of lovastatin and/or celecoxib on actin cytoskeleton and cell motility using immunofluroscence and 3-D migration experiments. Both lovastatin and celecoxib treatment led to a decrease in RhoA, ROCK and PKCδ with lovastatin showing a greater effect than celecoxib. However, celecoxib showed a greater decrease in cyclin A, cyclin D1, pRb and E2F1 expression when compared to lovastatin. Interestingly, the combination treatment showed a significant decrease in Rho/ROCK signaling pathway proteins indicative of a synergistic effect. In contrast, celecoxib, lovastatin and the combination increased E-cadherin expression by 2, 3 and 5 fold respectively. Immunofluroscence results showed that lovastatin, celecoxib and their combination treatment decreased actin cytoskeleton formation by ~65, 50 and 93% respectively. 3-D cell culture migration experiments showed that lovastatin, celecoxib and the combination led to ~78, 65 and 95% decrease in cell motility/migration. The results from the current study suggest that a combination of lovastatin and celecoxib exerts a synergistic effect by down-regulation of RhoA/ROCK pathway. RhoA may therefore be useful as a target for colon cancer prevention and treatment. (Support by the NCI R01-94962 and NCI-CN-53300)
Abstract P222: T-Type Calcium Channels Regulate NFAT Signaling in Cardiomyocytes and Are Expressed in Chronic Hypoxic Right Ventricle
Authors: Leanne L Cribbs, Florentina Pluteanu
Journal: Circulation Research (2011)

Alterations in intracellular calcium (Ca 2+ ) have a significant impact on Ca 2+ signaling, an integral part of the cardiac response to pathological conditions. The calcineurin/NFAT signaling pathway is a well established Ca 2+ -dependent mechanism for transcriptional regulation of ventricular remodeling target genes. Although low voltage-activated T-type Ca 2+ channels are not normally present in the adult myocardium, they reappear in conditions of hypertrophy and heart failure, where their functions remain poorly understood. To further investigate T-type Ca 2+ channels, we have employed cultured neonatal rat ventricular myocytes (NRVM) and rat models of pulmonary hypertension that lead to right ventricular (RV) hypertrophy and heart failure. To assay for NFAT activation in cardiomyocytes, NRVM were infected with NFATc1-GFP and nuclear localization of GFP was measured. NFAT activation was markedly stimulated by over expressing the human Ca v 3.2 T-type Ca 2+ channel cDNA in NRVM, and this activation was inhibited by cyclosporin A (a calcineurin inhibitor), by T-type selective concentrations of mibefradil and NiCl 2 , and in the absence of extracellular Ca 2+ . To investigate the up regulation of cardiac T-type Ca 2+ channels in vivo , rats were maintained in chronic hypoxia, where they developed significantly elevated RV systolic pressure, RV hypertrophy and reduced cardiac output. Electrophysiological measurements revealed elevated membrane capacitance in RV myocytes indicative of RV hypertrophy, and T-type current density was also increased. Myocytes isolated from the RV of pulmonary hypertensive rats that displayed elevated T-type currents and RV dysfunction, also showed impaired contractility with decreased sensitivity to Ca 2+ . The results in NRVM suggest that T-type channels contribute to hypertrophic signaling via their interaction with calcineurin/NFAT signaling intermediaries. Furthermore, T-type channels are expressed in the RV during pulmonary hypertension where they influence RV myocyte contractility. Thus, when expressed in pathological conditions, T-type Ca 2+ channels may play a dual role as a signaling intermediary, as well as a modifier of ventricular contractile function.
MiR-155/miR-150 network regulates progression through the disease phases of chronic lymphocytic leukemia
Authors: K Vargova, M Pesta, P Obrtlikova, N Dusilkova, L Minarik, J Vargova, A Berkova, Z Zemanova, K Michalova, M Spacek, M Trneny, T Stopka
Journal: Blood Cancer Journal (2017)

Chronic lymphocytic leukemia (CLL) is a slowly developing progression-prone disease.MicroRNAs miR-155 and miR-150 are small inhibitors of gene expression in B-cells that were previously connected to the pathogenesis of CLL.We herein evaluated relationship of miR-155/miR-150 network with clinical and routine laboratory parameters of the CLL patient cohort utilizing multivariate analyses and found its association with overall survival and progression of CLL.Aggressive course in CLL affects ~20-40% patients as indicated by the clonal-evolution data. 1 One of the strongest aggressive course associates is 17p13 deletion occurring in 5-10% of CLL patients. 24][5] Recently, miR-155 has been connected with CLL aggressiveness 6 and progression of the monoclonal B-cell lymphocytosis (MBL). 7Our group suggested that it is the transcriptional upregulation of the miR-155 host gene (MIR155HG) via the Myeloblastoma proto-oncogene (MYB) that lead to the increased level of the mature miR-155 in CLL, which may represent the molecular pathway of CLL aggressiveness. 8
Defenders against overdiagnosis
Authors: Richard Hurley
Journal: BMJ (2017)

There’s money to be made in diagnosis. Consider the buzz around immunosignature tests for antibodies to diagnose cancers or infections. Many other fledgling diagnostic technologies (breath testing for lung cancer, patches for vital sign monitoring, biomarkers for Alzheimer’s disease) have also shown enough clinical promise to seduce the capital investors.

Indeed, global revenues in the mobile health monitoring market are expected to grow 10-fold between 2012 and 2018, to £17bn (€19.4bn; $22.2bn), and the annual global biomarker market …
Abstract 19520: Hybrid PET/CT Imaging Five Days After Myocardial Infarction Provides Accurate Assessment of the Ischemic Area at Risk But Overestimates Myocardial Infarct Size in Swine
Authors: Brian R Weil, George Techiryan, Saurabh Malhotra, James A Fallavollita, John M Canty
Journal: Circulation (2016)

Introduction: Recent clinical studies suggest that fasting 18F-fluorodeoxyglucose (FDG) PET imaging may enable retrospective assessment of the ischemic area at risk (AAR) within the first week afte...
EASIX in patients with acute graft-versus-host disease: a retrospective cohort analysis
Authors: Thomas Luft, Axel Benner, Sonata Jodele, Christopher E Dandoy, Rainer Storb, Ted Gooley, Brenda M Sandmaier, Natalia Becker, Aleksandar Radujkovic, Peter Dreger, Olaf Penack
Journal: The Lancet Haematology (2017)
Sham surgery versus labral repair or biceps tenodesis for type II SLAP lesions of the shoulder: a three-armed randomised clinical trial
Authors: Chih-Kai Hong, Wei-Ren Su
Journal: British Journal of Sports Medicine (2017)

We read with interest the article by Schroder et al 1 on the clinical outcome among labral repair, biceps tenodesis and sham surgery for isolated type II superior labrum anterior posterior (SLAP) lesions in a double-blind randomised clinical trial.2 Patients 18–60 years of age who had shoulder pain for more than 3 months and were unresponsive to the conservative managements were candidates for this trial. Once isolated type II SLAP lesion was confirmed from the arthroscopic examination, each patient was randomly  assigned to either labral repair, biceps tenodesis or sham surgery. The authors concluded that neither labral repair nor biceps tenodesis had any superior benefit over sham surgery.

We appreciated the authors’ great efforts on this randomised control study. However, we have several comments and concerns regarding the study design …
Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology
Authors: Shuta Ishigami, Shinichi Ohtsuki, Takahiro Eitoku, Daiki Ousaka, Maiko Kondo, Yoshihiko Kurita, Kenta Hirai, Yosuke Fukushima, Kenji Baba, Takuya Goto, Naohiro Horio, Junko Kobayashi, Yosuke Kuroko, Yasuhiro Kotani, Sadahiko Arai, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, Hidemasa Oh
Journal: Circulation Research (2017)

Rationale: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. Objective: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. Methods and Results: We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P =0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P &lt;0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P &lt;0.0001) and volumes ( P &lt;0.001), somatic growth ( P &lt;0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status ( P &lt;0.0001) and cardiac fibrosis ( P =0.014) relative to baseline. Conclusions: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and quality of life in patients and reduce parenting stress for their families. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01829750.
Handbook of supply management at first-level health care facilities. 1st version for country adaptation.
Authors: Wardlaw T, Pandey P, Sehgal Ar, Riboud M, Levine D, Goyal M, McCartney Pr, Verma R, Prinja S, Ferreira S, Noce C, Junior As, Goncalves L, Torres S, Kumalo F
Journal: The Lancet (2006)
A systematic review of criteria used to define recovery from sport-related concussion in youth athletes
Authors: Mohammad Nadir Haider, John J Leddy, Sonja Pavlesen, Melissa Kluczynski, John G Baker, Jeffrey C Miecznikowski, Barry S Willer
Journal: British Journal of Sports Medicine (2017)

Objective The Concussion in Sport Group guidelines recommend a multifaceted approach to help clinicians make return to sport decisions. The purpose of this study was to identify the most common multifaceted measures used to define clinical recovery from sport-related concussion in young athletes (high school and/or college level) and to summarise existing knowledge of criteria used to make return to sport decisions. Design Systematic review. Data sources The PubMed (MEDLINE), SPORTDiscus and Embase electronic databases were searched from 1 January 2000 to 1 March 2017 by three independent reviewers. Eligibility criteria Inclusion criteria: elementary, high school and college age groups, and a specific definition of clinical recovery that required two or more measures. Exclusion criteria: review articles, articles using the same sample population, case studies, non-English language and those that used one measure only or did not specify the recovery measures used. Study quality Study quality was assessed using the Downs and Black Criteria. Results Of 2023 publications, 43 met inclusion criteria. Included articles reported the following measures of recovery: somatic symptom resolution or return to baseline (100%), cognitive recovery or return to baseline (86%), no exacerbation of symptoms on physical exertion (49%), normalisation of balance (30%), normal special physical examination (12%), successful return to school (5%), no exacerbation of symptoms with cognitive exertion (2%) and normalisation of cerebral blood flow (2%). Follow-up to validate the return to sport decision was reported in eight (19%) articles. Most studies were case–control or cohort (level of evidence 4) and had significant risk of bias. Conclusion All studies of sport-related concussion use symptom reports to define recovery. A minority of studies used multiple measures of outcome or had clearly defined recovery criteria, the most common being a combination of a self-reported symptom checklist and a computerised neurocognitive test. Future studies ideally should define recovery a priori using objective physiological measures in addition to symptom reports.