tbuckley/cabot-search huggingface dataset:
Identification of a RAI1-associated disease network through integration of exome sequencing, transcriptomics, and 3D genomics
Authors: Maria Nicla Loviglio, Christine R. Beck, Janson J. White, Marion Leleu, Tamar Harel, Nicolas Guex, Anne Niknejad, Weimin Bi, Edward S. Chen, Isaac Crespo, Jiong Yan, Wu-Lin Charng, Shen Gu, Ping Fang, Zeynep Coban-Akdemir, Chad A. Shaw, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, Jacques Rougemont, Ioannis Xenarios, James R. Lupski, Alexandre Reymond
Journal: Genome Medicine (2016)

Smith-Magenis syndrome (SMS) is a developmental disability/multiple congenital anomaly disorder resulting from haploinsufficiency of RAI1. It is characterized by distinctive facial features, brachydactyly, sleep disturbances, and stereotypic behaviors. We investigated a cohort of 15 individuals with a clinical suspicion of SMS who showed neither deletion in the SMS critical region nor damaging variants in RAI1 using whole exome sequencing. A combination of network analysis (co-expression and biomedical text mining), transcriptomics, and circularized chromatin conformation capture (4C-seq) was applied to verify whether modified genes are part of the same disease network as known SMS-causing genes. Potentially deleterious variants were identified in nine of these individuals using whole-exome sequencing. Eight of these changes affect KMT2D, ZEB2, MAP2K2, GLDC, CASK, MECP2, KDM5C, and POGZ, known to be associated with Kabuki syndrome 1, Mowat-Wilson syndrome, cardiofaciocutaneous syndrome, glycine encephalopathy, mental retardation and microcephaly with pontine and cerebellar hypoplasia, X-linked mental retardation 13, X-linked mental retardation Claes-Jensen type, and White-Sutton syndrome, respectively. The ninth individual carries a de novo variant in JAKMIP1, a regulator of neuronal translation that was recently found deleted in a patient with autism spectrum disorder. Analyses of co-expression and biomedical text mining suggest that these pathologies and SMS are part of the same disease network. Further support for this hypothesis was obtained from transcriptome profiling that showed that the expression levels of both Zeb2 and Map2k2 are perturbed in Rai1 –/– mice. As an orthogonal approach to potentially contributory disease gene variants, we used chromatin conformation capture to reveal chromatin contacts between RAI1 and the loci flanking ZEB2 and GLDC, as well as between RAI1 and human orthologs of the genes that show perturbed expression in our Rai1 –/– mouse model. These holistic studies of RAI1 and its interactions allow insights into SMS and other disorders associated with intellectual disability and behavioral abnormalities. Our findings support a pan-genomic approach to the molecular diagnosis of a distinctive disorder.
Baseline Serum Cytokines Profiles in Mantle Cell Lymphoma Correlates with Outcome
Authors: Anthony R Mato, James Greenberg, Mary E Putt, K. Stephen Suh, Yvonne Remache, Tania Zielonka, Kathryn Waksmundzki, Ewelina A Protomastro, Susan Stives, Tatyana Feldman, Pritish K. Bhattacharyya, Xiao Yang, Kar Fai Chow, Alex Campaiola, Andrew L Pecora, Andre Goy
Journal: Blood (2012)
N6 -Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection
Authors: Nandan S. Gokhale, Alexa B.R. McIntyre, Michael J. McFadden, Allison E. Roder, Edward M. Kennedy, Jorge A. Gandara, Sharon E. Hopcraft, Kendra M. Quicke, Christine Vazquez, Jason Willer, Olga R. Ilkayeva, Brittany A. Law, Christopher L. Holley, Mariano A. Garcia-Blanco, Matthew J. Evans, Mehul S. Suthar, Shelton S. Bradrick, Christopher E. Mason, Stacy M. Horner
Journal: Cell Host & Microbe (2016)
GW26-e2369 Nicotine Exposure Causes GATA4 and Tbx5 Gene Repression by DNA Hypermethylation during Cardiac Myogenesis
Authors: Xueyan Jiang, Xiaohong Li, Juan Feng, Qinxiong Lin, Ming Yang, Yangxin Li, Yong-Jian Geng, Mengzhen Zhang, Liping Mai, Xiyong Yu
Journal: Journal of the American College of Cardiology (2015)
Autocrine IGF-1/IGF-1R Signaling Is Responsible for PI3K/Akt Constitutive Activation in Acute Myeloid Leukemia.
Authors: Nicolas Chapuis, Jerome Tamburini, Pascale Cornillet-Lefebvre, Lucile Gillot, Valérie Bardet, Lise Willems, Sophie Park, Alexa Samantha Green, Norbert Ifrah, Francois Dreyfus, Patrick Mayeux, Catherine Lacombe, Didier Bouscary
Journal: Blood (2008)
Prognostic Value of FDG Uptake of Portal Vein Tumor Thrombosis in Patients With Locally Advanced Hepatocellular Carcinoma
Authors: Jeong Won Lee, Sang Hyun Hwang, Do Young Kim, Kwang-Hyub Han, Mijin Yun
Journal: Clinical Nuclear Medicine (2016)

This study aimed to evaluate the prognostic value of F-FDG uptake of portal vein tumor thrombosis (PVTT) for predicting progression-free survival (PFS) and overall survival (OS) in patients with locally advanced hepatocellular carcinoma (HCC).The study retrospectively included 166 HCC patients with PVTT and no extrahepatic metastases who underwent staging FDG PET/CT. Tumor-to-liver uptake ratio (TLR) and PVTT-to-liver uptake ratio (PLR) were measured for each patient, and the prognostic values of clinical factors, TLR, and PLR were assessed. Furthermore, patients were classified into 2 subgroups according to TLR, and the prognostic value of PLR was evaluated in each subgroup.Median PFS and OS were 6.2 and 10.1 months, respectively. On multivariate analysis, tumor size (P = 0.006) and PLR (P = 0.03) were independent prognostic factors for PFS, whereas Child-Pugh class (P = 0.02) and PLR (P = 0.02) were independent prognostic factors for OS. Tumor-to-liver uptake ratio was a significant prognostic factor for PFS and OS on univariate analysis but failed to show significance on multivariate analysis. In both patient subgroups with low and high TLR, PLR remained a significant prognostic factor for predicting OS (P = 0.04 for all).FDG uptake of PVTT, but not FDG uptake of HCC, is an independent prognostic factor for PFS and OS in HCC patients with PVTT and no extrahepatic metastasis. Given the prognostic significance, it is strongly encouraged to use FDG uptake of PVTT in further risk stratification for HCC patients with PVTT.
Intervertebral administration of 153Samarium with kyphoplasty for vertebral metastases
Authors: H. Ashamalla, E. Cardoso, L. Weng, S. Rafla, M. Macedon, N. Panigrahi
Journal: Journal of Clinical Oncology (2006)

13136 Background: Kyphoplasty is an effective procedure to alleviate pain in metastatic vertebrae. 153 Samarium-EDTMP ( 153 Sm) is used for palliative treatment of multiple bone metastases. The hematological toxicity is the main limiting factor. Objectives: Study the feasibility of intervertebral administration of 153 SM with Kyphoplasty. Assess procedure related morbidities specifically haematological since a direct vertebral route is planned though to a much smaller dose. Methods: IRB approval for an off label use of 153Sm-EDTMP was obtained. Six patients with documented vertebral bone metastasis and pathological compression fractures were studied (Thoracic in 2 and lumbar in 4). Primary cancer was lung in 2, prostate (1), maxillary sinus (1), myeloma (1) and colon (1). Serial dilution of 153 SM was performed to obtain 2 mci/1ml. Kyphoplasty procedure was carried out using the known protocol. 2 mCi of 153 Sm was admixed with the bone cement and administered under tight radiation safety measures. Serial nuclear body scans were obtained. Pain assessment was evaluated using analog pain score at 1, 7 and 30 days. Serial blood counts are followed. Results: All patients tolerated procedure well. No immediate procedure(s) related morbidities were noted. One case was not technically satisfactory and no significant uptake was detected in the injected vertebra. Nuclear scan done on 0 revealed excellent radiotracer uptake in the other 5 vertebrae injected. The absorbed radiotracer was seen to target other skeletal metastatic lesions in 2 patients. There was no significant change in WBC, HCT or Platelets seen in blood counts obtained over one month post-procedure. Except for the first patient, no appreciable radiation leakage was encountered. Pain score was reduced from a mean of 8.5 to 3.2 during the first week and was maintained below score of 4 at one month assessment. Conclusions: The combination of intervertebral administration of 153 SM and Kyphoplasty seems to be well tolerated. No haematological side effects were encountered; probably due to the use of only 2 mci compared to over 70 mci in intravenous administration. Pain control seems to be satisfactory at areas treated. Analysis of procedure related radiological changes is underway. No significant financial relationships to disclose.
Bone Marrow-Derived Mesenchymal Stem Cell Homing to Breast Cancer but Not Colon and Renal Cancer and VEGF-C and VEGF-R3 Play the Key Role in Tumor Homing Effect in the Syngeneic Mice (Balb/c) Model,
Authors: Su-Peng Yeh, Wen-Jyi Lo, Chang-Fang Chiu
Journal: Blood (2011)
Effect of complementary alternative medical (CAM) therapy on tumor response, control and recurrence in prostate cancer patients (PCpts) treated with radiation therapy (RT)
Authors: L. R. Cain, J. Flynn, D. Kelly, B. Eden, M. Sumner, K. Anderson, S. Birdsall, J. Martin, L. Dounaevskaia, L. Alschuler
Journal: Journal of Clinical Oncology (2007)

15585 Background. CAM therapy in pts receiving RT has been questioned due to possible interference with oxidative mechanisms aimed at killing tumor cells. We addressed this controversy by analyzing tumor response, control and recurrence in PCpts treated with RT + CAM. Methods. The population consisted of 125 RT-treated PCpts with localized tumors: CAM cohort (n=69; median age=62.5 yrs; range=46–81); nonCAM cohort (n=56; median age=61.0 yrs; range=48–80). For the CAM cohort, 41%, 42%, 9% and 7% had T1c, T2a, T2b and T2c tumors respectively with 1 T3b tumor; for the nonCAM cohort, 39%, 38%, 14% and 7% had T1c, T2a, T2b and T2c tumors respectively with 1 T3a tumor. RT consisted of external beam therapy (4500–5000 cGy) in conjunction with high dose rate brachytherapy (600- 650 cGy/fraction x 2–3 fractions) administered over 6–8 weeks; this occurred for 65/69 CAM and 52/56 nonCAM pts. The remaining pts received either HDR monotherapy, tomotherapy, or IMRT + tomotherapy. In addition, 5/69 CAM and 2/56 nonCAM pts received hormonal therapy. CAM regimens included at least one antioxidant (range=1–7) including Green Tea Extract; Melatonin; and high-potency multivitamins. All pts were monitored ≥ 24 months post radiation therapy. Results. In the CAM cohort, median pretreatment PSA was 5.95ng; nadir PSA was 0.08ng; and last PSA was 0.18ng with median followup of 28.96 (range=24–46) months; 3 biochemical failures were seen at 6, 10 and 12 months. In the nonCAM cohort, median pretreatment PSA was 6.4ng; nadir PSA was 0.06ng; and last PSA was 0.166ng with median followup of 28.26 (range=24–43) months; 2 biochemical failures at 13 and 28 months with 1 death at 37 months were seen. Conclusion. Concomitant CAM treatment does not effect RT-mediated tumor response, control or recurrence rates in PCpts with localized disease. Neither the magnitude of the response or its durability for at least 2 years are negatively affected by CAM-based antioxidant supplements designed to improve patient tolerance and quality of life. Investigations in well-defined populations receiving consistent CAM regimens offer the opportunity to elucidate positive benefits for patient management. No significant financial relationships to disclose.
Long-term Mortality and End-Stage Renal Disease in a Type 1 Diabetes Population Diagnosed at Age 15–29 Years in Norway
Authors: Vibeke Gagnum, Lars C. Stene, Torbjørn Leivestad, Geir Joner, Torild Skrivarhaug
Journal: Diabetes Care (2016)

To study long-term mortality, causes of death, and end-stage renal disease (ESRD) in people diagnosed with type 1 diabetes at age 15-29 years.This nationwide, population-based cohort with type 1 diabetes diagnosed during 1978-1982 (n = 719) was followed from diagnosis until death, emigration, or September 2013. Linkages to the Norwegian Cause of Death Registry and the Norwegian Renal Registry provided information on causes of death and whether ESRD was present. A clinical committee reviewed the causes of death. We calculated standardized mortality ratios (SMRs) for comparison with the background population.During 30 years' follow-up, 4.6% of participants developed ESRD and 20.6% (n = 148; 106 men and 42 women) died. Cumulative mortality by years since diagnosis was 6.0% (95% CI 4.5-8.0) at 10 years, 12.2% (10.0-14.8) at 20 years, and 18.4% (15.8-21.5) at 30 years. The SMR was 4.4 (95% CI 3.7-5.1). Mean time from diagnosis of diabetes to ESRD was 23.6 years (range 14.2-33.5). Death was caused by chronic complications (32.2%), acute complications (20.5%), violent death (19.9%), or any other cause (27.4%). Death was related to alcohol in 15% of cases. SMR for alcohol-related death was 6.8 (95% CI 4.5-10.3), for cardiovascular death was 7.3 (5.4-10.0), and for violent death was 3.6 (2.3-5.3).The cumulative incidence of ESRD was low in this cohort with type 1 diabetes followed for 30 years. Mortality was 4.4 times that of the general population, and more than 50% of all deaths were caused by acute or chronic complications. A relatively high proportion of deaths were related to alcohol.
The Epidemiology of First-Episode Psychosis in Early Intervention in Psychosis Services: Findings From the Social Epidemiology of Psychoses in East Anglia [SEPEA] Study
Authors: James B. Kirkbride, Yasir Hameed, Gayatri Ankireddypalli, Konstantinos Ioannidis, Carolyn M. Crane, Mukhtar Nasir, Nikolett Kabacs, Antonio Metastasio, Oliver Jenkins, Ashkan Espandian, Styliani Spyridi, Danica Ralevic, Suneetha Siddabattuni, Ben Walden, Adewale Adeoye, Jesus Perez, Peter B. Jones
Journal: American Journal of Psychiatry (2016)

Few studies have characterized the epidemiology of first-episode psychoses in rural or urban settings since the introduction of early intervention psychosis services. To address this, the authors conducted a naturalistic cohort study in England, where such services are well established.All new first-episode psychosis cases, 16-35 years old, presenting to early intervention psychosis services in the East of England were identified during 2 million person-years follow-up. Presence of ICD-10 F10-33 psychotic disorder was confirmed using OPCRIT [operational criteria for psychotic illness]. Incidence rate ratios were estimated following multivariable Poisson regression, adjusting for age, sex, ethnicity, socioeconomic status, neighborhood-level deprivation, and population density.Of 1,005 referrals, 687 participants (68.4%) fulfilled epidemiological and diagnostic criteria for first-episode psychosis (34.0 new cases per 100,000 person-years; 95% CI=31.5-36.6). Median age at referral was similar for men (22.5 years; interquartile range: 19.5-26.7) and women (23.4 years; interquartile range: 19.5-29.1); incidence rates were highest for men and women before 20 years of age. Rates increased for ethnic minority groups (incidence rate ratio: 1.4; 95% CI=1.1-1.6), as well as with lower socioeconomic status (incidence rate ratio: 1.3; 95% CI=1.2-1.4) and in more urban (incidence rate ratio: 1.4;95%CI=1.0-1.8) and deprived (incidence rate ratio: 2.1; 95% CI=1.3-3.3) neighborhoods, after adjustment for confounders.Pronounced variation in psychosis incidence, peaking before 20 years old, exists in populations served by early intervention psychosis services. Excess rates were restricted to urban and deprived communities, suggesting that a threshold of socioenvironmental adversity may be necessary to increase incidence. This robust epidemiology can inform service development in various settings about likely population-level need.
GW26-e3872 Association between elevated Serum Alanine Aminotransferase and Cardiometabolic Risk Factors in Rural Chinese Population: A Cross-Sectional Study
Authors: Shuang Chen, Xiaofan Guo, Xingang Zhang, Shasha Yu, Hongmei Yang, Mohan Jiang, Guozhe Sun, Zhao Li, Yingxian Sun
Journal: Journal of the American College of Cardiology (2015)
Treatment With The Potent PI3K-δ,γ Inhibitor IPI-145 Is Associated With Rapid Decreases In Specific Cytokines, Chemokines and Matrix Metalloproteinases In The Serum Of Patients With Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma
Authors: Mark Douglas, Ken Allison, Synder Ted, Kerstin Allen, Brad S. Kahl, Steven M. Horwitz, Ian W. Flinn, Patrick Kelly, Howard M. Stern
Journal: Blood (2013)
Racial and ethnic disparities in the survival of adolescents and young adults (AYA) with acute myeloid leukemia (AML).
Authors: Urshila Durani, Adam C Bartley, Ronald S. Go
Journal: Journal of Clinical Oncology (2016)

297 Background: Unlike acute lymphoblastic leukemia, no studies have examined the effect of race on survival among AML in AYA using national data. Methods: We studied patients in the US National Cancer Data Base aged 15-39 diagnosed with AML from 2001-2011 (excluding acute promyelocytic leukemia). AMLs harboring inv(16) or t(8;21) were defined as good-risk. We examined overall survival (OS) according to race/ethnicity and survival trends over three time-periods: 2001-2004, 2005-2008, and 2009-2011. Results: We identified 8,986 patients, with a mean follow-up of 37 months. The median OS according to race/ethnicity was 56, 49, 41, and 22 months for Asians/Pacific Islanders (A/PI), Hispanics, Whites, and Blacks respectively (P &lt; 0.001). OS improved over time among Whites only, with respective median OS of 31, 43, and 49 months (P &lt; 0.001). Multivariate analysis adjusting for socio-demographics, travel distance, and AML type, showed that, compared to Whites, Blacks had a significantly worse and Hispanics a significantly better OS (Table). Conclusions: We found significant disparities in OS among racial/ethnic subgroups in AYA with AML despite adjustment for socio-demographic factors. Blacks had the worse and Hispanics the best outcome. In the past decade, OS improved only among the Whites. Further studies should examine provider and patient care delivery factors that may contribute to these disparities. [Table: see text]
Peripherally Inserted Central Catheters (PICCs) Implantation in the Clinical Management of Oncohematologic Patients: Results of a Large Multicenter, Retrospective Study of the REL Group (Rete Ematologica Lombarda - Lombardy Hematologic Network, Italy)
Authors: Nicola Stefano Fracchiolla, Elisabetta Todisco, Andrea Bilancia, Sara Gandolfi, Valentina Mancini, Laura Marbello, Massimo Bernardi, Andrea Assanelli, Nicola Orofino, Ramona Cassin, Mariarita Sciumè, Francesca Guidotti, Roberto Cairoli, Fabio Ciceri, Armando Santoro, Agostino Cortelezzi, Giuseppe Rossi
Journal: Blood (2015)
A stromal-associated gene expression signature predicting for survival in a series of patients with advanced high-grade serous ovarian cancer
Authors: T. Bonome, G. Samimi, M. Randonovich, J. Brady, S. Ghosh, S. Ng, S. C. Mok, M. J. Birrer
Journal: Journal of Clinical Oncology (2007)

5552 Background: Prognostic gene expression signatures have been derived for undissected serous ovarian epithelial tumors, yet the specific contribution of stromal cells to patient survival has not been addressed. The aim of this study is to identify stromal genes impacting patient survival in the context of serous ovarian cancer. Methods: Expression profiling utilizing Affymetrix U133 Plus 2.0 oligonucleotide arrays was completed for 50 microdissected stromal samples derived from high-grade, late-stage serous tumors displaying a broad spectrum of survival endpoints. A semi-supervised dimension reduction method employing multivariate Cox regression and principal components analysis was applied to the expression data to identify genes associated with patient survival and establish a predictive model. qRT-PCR was employed to validate the microarray expression data. Results: Cox regression analysis identified 267 significant genes. The first 6 principal components of these genes, representing &gt;65% of total variance, entered a multivariate Cox model through which the relative hazard of future patients can be predicted. To confirm our finding, the microarray data underwent leave-one-out validation. The patients were equally divided into low- and high-risk groups and non-parametric Kaplan-Meier analysis and log rank test demonstrated the two groups were significantly different in survival (p = 0.0115). Genes associated with cell survival and migration were identified in the prognostic signature. For validation, qRT-PCR data for all 50 specimens was correlated with microarray expression values for a series of select prognostic genes. Conculsions: In this study, we characterized and validated a stromal dervied prognostic signature associated with poor patient survival. Contained in this novel predictor may be stromal targets suitable for the design of new therapeutic interventions, or use as independent diagnostic markers. No significant financial relationships to disclose.
Long-term Survival After Chemoradiotherapy Without Surgery for Rectal Adenocarcinoma
Authors: C. Tyler Ellis, Stacie B. Dusetzina, Hanna Sanoff, Karyn B. Stitzenberg
Journal: JAMA Oncology (2016)

This cohort study examines a hospital-based national cancer registry to assess whether chemoradiotherapy plus proctectomy vs chemoradiotherapy without surgery is associated with worse overall survival in patients with nonmetastatic rectal adenocarcinoma.
Free circulating DNA by RT-PCR as predictor for chemotherapy response in newly diagnosed patients (pts) with advanced non-small cell lung cancer (NSCLC).
Authors: E. S. Santos, T. N. Talebi, L. E. Raez, C. A. Quintero, G. Walker, M. Farias, K. Ramachandran, E. Gordian, J. Gomez, R. Singal
Journal: Journal of Clinical Oncology (2010)

e18107 Background: Tumors shed DNA into the blood stream and the plasma DNA concentrations increase in pathological situations associated with cell death. We propose the measurement of free circulating DNA (FCDNA) as predictor for chemotherapy response (complete: CR, partial: PR, stable: SD or progression: PD) in newly diagnosed patients (pts) with advanced non-small cell lung cancer (NSCLC). Methods: FCDNA was measured (ng/ml) in blood samples from NSCLC patients at baseline and following two cycles of chemotherapy by real time (RT)-PCR for glutathione-s- transefrase P1 (GSTP1) gene. Results: We have enrolled 31 pts; baseline data were available for 26 pts. Characteristics: 19 males. All pts have stage III/IV and 19 were adenocarcinomas. All pts were treated with platinum-based chemotherapy. Responses were documented as: PR: 27%, SD: 58% and PD: 12%. No association was found between baseline level of FCDNA and age (< 68 v ≥ 69, p = 0.200), gender (p = 0.954), ethnicity (p = 0.385), PS (0 v 1/2, p = 0.732), stage (p = 0.978), histology (adenocarcinoma vs. other, p = 0.386), or smoking history (p = 0.648). Measurements obtained after two treatment cycles were available for 13 pts. Nine patients had higher levels of FCDNA after two cycles of chemotherapy as compared with baseline, while four showed a decrease. The difference was marginally significant, p = 0.080, (WSRT). No association was found between baseline FCDNA level and response following two treatment cycles: p = 0.545, Kruskal-Wallis test comparing 7 patients with PR against 15 with SD and 3 with PD. Change in FCDNA was not associated with response status: p = 0.316 comparing 4 PR and 9 SD (8) or PD (1); p = 0.445 with exclusion of the single case of PD. Conclusions: We have seen changes in FCDNA level in pts with NSCLC undergoing palliative chemotherapy; however, these have not achieved statistical significance yet. We have already planed per protocol to increase number of pts and number of samples per pt to see if these results are meaningful. No significant financial relationships to disclose.