tbuckley/cabot-search huggingface dataset:
Abstract A18: Gut microbiota changes in response to treatment with ursodeoxycholic acid (UDCA)
Authors: Talima Pearson, J Gregory Caporaso, Monica Yellowhair, Jessica A. Martinez, Betsy Wertheim, Denise Roe, Patricia Thompson-Canino, Peter Lance
Journal: Cancer Research (2017)

Abstract Compelling evidence suggests that gut flora influences colorectal cancer risk through direct effects on colonic bile acid composition. Bile acids are widely implicated in the etiology of colorectal cancer with the strongest evidence involving a detrimental role for the secondary BA, deoxycholic acid (DCA) and a protective effect of ursodeoxycholic acid (UDCA). In a study of patients with prior colorectal adenomas who were randomized to UDCA (n=188 males, 64 females), a bile acid based intervention aimed at modulating bile acid composition, or placebo (n=162 males, 89 females), we determined effects of the intervention on the gut microbiome through 16S rRNA sequencing and bile acid composition at baseline using mass spectrometry. We observe a consistent shift in microbial composition for males (t=5.83, p=3.6e-8) and females (t=3.14, p=0.003) treated with UDCA. No effect was observed in the placebo group for either males (t=-0.08, p=0.93) or females (t=-0.09, p=0.92). There were significant correlations between the gut microbiome and BA composition (r=0.31, p&amp;lt;0.001). This suggests that UDCA treatment had an effect on the gut microbial communities relative to the placebo group. Interestingly, the magnitude of the change in the microbiome over time is similar in the two groups, but UDCA treatment seems to drive specific microbiome changes. These results are consistent with our previously reported observation that UDCA appears to have a greater effect in men for the prevention of colorectal adenomatous polyps, while increasing risk for women. Citation Format: Talima Pearson, J Gregory Caporaso, Monica Yellowhair, Jessica A. Martinez, Betsy Wertheim, Denise Roe, Patricia Thompson-Canino, Peter Lance. Gut microbiota changes in response to treatment with ursodeoxycholic acid (UDCA). [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A18.
Final Results of Phase 1 MMRC Trial of Selinexor, Carfilzomib, and Dexamethasone in Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Andrzej Jakubowiak, Jagoda Jasielec, Cara A. Rosenbaum, Craig E. Cole, Ajai Chari, Jennifer Nam, Erica Severson, Leonor A Stephens, Kathryn McDonnell, Shaun Rosebeck, Todd Zimmerman, Theodore Karrison, Jeffrey Zonder
Journal: Blood (2016)
Ruxolitinib Provides Reductions in Splenomegaly Across Subgroups: An Analysis of Spleen Response in the COMFORT-II Study
Authors: Claire N. Harrison, Jean-Jacques Kiladjian, Heinz Gisslinger, Dietger Niederwieser, Francesco Passamonti, Roger J. Waltzman, Norbert Hollaender, Deborah S. Hunter, Richard S. Levy, Laurent Knoops, Francisco Cervantes, Alessandro M. Vannucchi, Tiziano Barbui, Giovanni Barosi
Journal: Blood (2011)
Schizophrenia and the dynamic genome
Authors: Patrick F. Sullivan
Journal: Genome Medicine (2017)

Copy number variation (CNV) is a widely replicated risk factor for psychiatric disorders such as schizophrenia, although the mechanisms by which CNVs confer risk are currently unclear.Recent studies have provided robust evidence of CNVs associated with schizophrenia and have highlighted a potential role for schizophrenia risk-associated CNVs in impairing inhibitory learning; these studies highlight how insights can be gained into the associations of CNVs with schizophrenia.
Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction
Authors: Thomas Engstrøm, Henning Kelbæk, Steffen Helqvist, Dan Eik Høfsten, Lene Kløvgaard, Peter Clemmensen, Lene Holmvang, Erik Jørgensen, Frants Pedersen, Kari Saunamaki, Jan Ravkilde, Hans-Henrik Tilsted, Anton Villadsen, Jens Aarøe, Svend Eggert Jensen, Bent Raungaard, Hans E. Bøtker, Christian J. Terkelsen, Michael Maeng, Anne Kaltoft, Lars R. Krusell, Lisette O. Jensen, Karsten T. Veien, Klaus Fuglsang Kofoed, Christian Torp-Pedersen, Kasper Kyhl, Lars Nepper-Christensen, Marek Treiman, Niels Vejlstrup, Kiril Ahtarovski, Jacob Lønborg, Lars Køber
Journal: JAMA Cardiology (2017)

Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage.To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat.Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation.A combination of all-cause death and hospitalization for heart failure.During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure.Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival.clinicaltrials.gov Identifier: NCT01435408.
Post Transplant Lymphoproliferative Disorders: Prognostic Features and Rituximab Impact In a 120 Case Single Institution Series
Authors: Francesca Montanari, Govind Bhagat, Venkatraman Seshan, Sean Clark-Garvey, Jasmine M. Zain, Catherine S. Diefenbach, Erin McCormick, Meaghan Conroy, Meghan Crook, Bachir Alobeid, Owen A. O'Connor
Journal: Blood (2010)
Abstract B04: From modeling to in vivo tracking: a new platform for the design of delivery vectors that exploit tumor microfluidics
Authors: Sara Nizzero, Sergey Litvinov, Dmitry Alexeev, Athena Economides, Enrica De Rosa, Joy Wolfram, Petros Koumoutsakos, Mauro Ferrari
Journal: Cancer Research (2017)

Abstract Within the field of oncology, a new perspective has recently emerged, where cancer treatment is viewed as a transport problem that can be addressed with nanomedicine. In fact, because of the unique local conditions of transport and microfluidics in the tumor environment, microparticles and nanoparticles that exhibit specific geometries have proven advantageous to enhance preferential delivery of drugs to tumor tissue. However, the theoretical and modeling backbone required to describe, understand, and manipulate such flow-specific design advantages is currently limited to semi-analytical methods. These methods have proven successful in explaining the power and efficacy of geometrical targeting. Nevertheless, since such approaches have limited predictive power, they are not ideal tools for the systematic development of a new class of efficient and customizable delivery vectors. In this work, we propose an innovative and rational approach for understanding the delivery of micro- and nanotherapeutics to cancer tissue by modeling transport in tumor microvessels. Specifically, we focus on the differences between healthy and tumor vasculature that affect fluid mechanics. We tackle this problem with a combined experimental and modeling approach. Our model is based on a Navier-Stokes solver for complex fluids based on dissipative particle dynamics (DPD) simulations, where blood constituents (i.e. red blood cells, neutrophils, platelets) and microparticles/nanoparticles interact through forces or collisions of different nature. The model is calibrated and validated with real-time flow chamber experiments. With this modeling approach, complex geometrical structures and interactions can be implemented with high computational efficiency. We use our innovative platform to analyze the differences in margination of micro- and nanostructures in tumor versus healthy microvasculature. We address the fundamental structural differences between tumor vessels and healthy vessels by systematically reconstructing the characteristic patterns of endothelial fenestrations, radius variability, and blood flow. Our parametric analysis is then compared with in vivo tracking studies in animal models. Our approach and results open the way to the understanding and rational design of a new class of nanoparticle and microparticle-based delivery strategies that exploit tumor-specific microfluidics. Citation Format: Sara Nizzero, Sergey Litvinov, Dmitry Alexeev, Athena Economides, Enrica De Rosa, Joy Wolfram, Petros Koumoutsakos, Mauro Ferrari. From modeling to in vivo tracking: a new platform for the design of delivery vectors that exploit tumor microfluidics. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B04.
PP81. A CASE OF EXTRACRANIAL GLIOBLASTOMA WITH METASTASIS IN PLEURA &amp; LIVER
Authors: Dr Lalith Seneviratne, Dr Aurora Sanz-Torres, Dr Zin Oo
Journal: Neuro-Oncology (2017)

BACKGROUND: Extraneural and extracranial metastases of Glioblastoma (GB) are rarely reported in literature and accounted to be around 0.2% all GB patients CASE PRESENTATION: We are presenting a 66 year old Caucasian male who presented with acute confusion, dizziness and dysphagia in May 2014 at which time the imaging revealed a 5cm * 4cm mass lesion with surrounding oedema in the left temporal lobe. Had maximum surgical debulking followed by concurrent chemo-radiotherapy 60Gy in 30 fractions over 6 weeks with daily oral Temozolomide 75mg/m2 although could not manage to continue with Temozolamide during last few days of treatment on account of the acute kidney injury. Showed significant response to the concurrent chemo-radiation following which proceeded to adjuvant Temozolomide chemotherapy and patient declined treatment after completion of 3 cycles for no apparent significant reason apart from generalized pruritus of skin and constipation which resolved with symptomatic management. Thereafter he was followed up in the clinic with repeat MRI scans the first of which in 4 months showed stable disease but the follow up MRI scan in 8 months showed debatable early disease progression which was confirmed 2 months later to be definite early disease progression at the primary site, extending to the adjacent corpus callosum. Whilst being suggested to re-challenge with Temozolomide, a month later presented with shortness of breath due to malignant pleural effusion and coincidentally noted liver metastasis. Pleural effusion was drained and was re-commenced on adjuvant Temozolomide but re-admitted with recurrent pleural effusion and died following acute clinical deterioration. His overall survival was 20 months, progression free survival was 17 months and ended up with metastatic disease at 18 months and died of the complications of metastatic disease 2 months later before he could start chemotherapy. CONCLUSION: Although rare in incidence, extra-neural metastasis from primary glioblastoma can be very aggressive and life threatening. Since the incidence seems to increase with time, maintaining a central registry and involvement in clinical trials would help to formulate ideal management protocol. KEYWORDS: Glioblastoma, Extra-neural metastasis, Extracranial metastasis, Case report
Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy
Authors: Brian M. Casey, Elizabeth A. Thom, Alan M. Peaceman, Michael W. Varner, Yoram Sorokin, Deborah G. Hirtz, Uma M. Reddy, Ronald J. Wapner, John M. Thorp, George Saade, Alan T.N. Tita, Dwight J. Rouse, Baha Sibai, Jay D. Iams, Brian M. Mercer, Jorge Tolosa, Steve N. Caritis, J. Peter VanDorsten
Journal: New England Journal of Medicine (2017)

Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).
A randomized phase III study of a cisplatin (CDDP) and docetaxel (DOC) with or without irinotecan (CPT) in pts with advanced NSCLC: Okayama Lung Cancer Study Group OLCSG 0403 trial.
Authors: Toshiaki Okada, Masahiro Tabata, Yoshihiko Segawa, Haruhito Kamei, Takuo Shibayama, Kenichi Gemba, Nagio Takigawa, Keitaro Matsuo, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2012)

7560 Background: CDDP-based doublet chemotherapy provides a significant but modest survival prolongation in untreated advanced NSCLC with MST of around 12 months. Based on the favorable efficacy profile in our previous phase II trial of triplet chemotherapy with CDDP, DOC, and CPT (response rate: 57.1%, MST: 17 months) (JTO 2007), we conducted a phase III study to compare this regimen with CDDP and DOC doublet therapy in the first-line setting. Methods: Pts were randomly allocated to the triplet therapy (A arm; CDDP 60 mg/m 2 , day 1; DOC 60 mg/m 2 , day 1; and CPT 60 mg/m 2 , day 2; q3 wks, determined based on our phase I study result) or a standard doublet chemotherapy (B arm; CDDP 80 mg/m 2 , and DOC 60 mg/m 2 , day 1; q3 wks). The primary endpoint was OS whilst secondary endpoints included response rates, PFS, and toxicity. Results: Between 2004 and 2009, 120 pts were enrolled (A/B: 60 pts each). Objective response was comparable between the arms (18 pts [30%] each, p = 0.571). As for toxicity, grade 3-4 neutropenia, principal toxicity, was observed in 93% vs. 58% (p &lt; 0.001). Although grade 3 febrile neutropenia was observed in 53% and 18% of the pts (p &lt; 0.001), none of whom further developed toxic deaths. At a median follow-up time of 64.2 months, median PFS time and 1-year PFS rate were 5.3 vs. 4.3 months and 13.3% vs. 11.7%, respectively (stratified logrank test; p = 0.872). There was also no difference in OS (MST, 16.8 vs. 12.2 months; 1-year OS rate, 68.0% vs. 53.0%; stratified logrank test; p = 0.846). Subgroup analysis for OS showed that never smokers (HR = 0.366; 95% CI = 0.072-1.866) tended to benefit from the triplet chemotherapy compared with ever-smokers (HR = 1.380; 95% CI = 0.771-2.473) despite no statistical significance (p for interaction = 0.150). Similar trend in interaction between treatment effect and smoking status was also observed in PFS. Conclusions: This triplet chemotherapy failed to produce a significant antitumor activity as compared with the standard doublet therapy.
Geographical disparities in HIV prevalence and care among men who have sex with men in Malawi: results from a multisite cross-sectional survey
Authors: Andrea L Wirtz, Gift Trapence, Dunker Kamba, Victor Gama, Rodney Chalera, Vincent Jumbe, Rosemary Kumwenda, Marriam Mangochi, Stephane Helleringer, Chris Beyrer, Stefan Baral
Journal: The Lancet HIV (2017)
A New Fusion Gene NUP98-IQCG Identified in an Acute T/Myeloid Leukemia with t(3;11)(q29q13;p15) Translocation.
Authors: Qin Pan, Yong-Jin Zhu, Bai-Wei Gu, Xun Cai, Xue-Tao Bai, Hai-Yang Yuan, Jiang Zhu, Zhu Chen, Yong-Quan Xue, Sai-Juan Chen
Journal: Blood (2007)
Decreased Expression of Stem Cell-Specific Genes in Aplastic Anemia; Possible Regulation of HOXB4 Gene by GATA-2.
Authors: Hisayuki Yokoyama, Hideo Harigae, Shinichiro Takahashi, Yoko Okitsu, Johji Yamamoto, Yasuo Tohmiya, Minami Fujiwara, Kenichi Ishizawa, Junichi Kameoka, Naoko Minegishi, Mitsuo Kaku, Takeshi Sasaki
Journal: Blood (2004)
Cover Image: Aquagenic wrinkling of the palms: a clue to underlying cystic fibrosis heterozygosity
Authors: E.C. Dupuis, A.J. Sperou, L. Fiorillo
Journal: British Journal of Dermatology (2017)

Conflicts of interest: none declared. Dear Editor, Within 2 min of water immersion, this patient developed characteristic changes of aquagenic wrinkling of the palms (AWP). A rare dermatosis, AWP is distinguished by the transient appearance of white oedematous papules and plaques amid excessive wrinkling of volar skin within minutes of water exposure. It is common in cystic fibrosis (CF),1 and is reported in 9–25% of CF carriers.2 Despite having an unremarkable family history, our patient carried the often associated delta F508 mutation in CFTR. Although not validated, the timing to symptom onset may distinguish carrier status. Given the associations, CF screening and genetic testing should be considered for all patients with AWP.
Abstract P5-09-04: Assessment of breast cancer risk among atomic-bomb survivors based on <i>ATM</i> polymorphisms, radiation dose, and age at exposure
Authors: T Hayashi, K Yoshida, W Ohishi, S Kyoizumi, Y Kusunoki, K Nakachi
Journal: Cancer Research (2017)

Abstract RERF's epidemiological study on atomic bomb survivors has found increased incidence of several types of cancers with increased radiation dose. A great deal of inter-individual variation in susceptibility to radiation-associated breast cancer could not be explained solely by radiation dose, suggesting the possibility of partial involvement of DNA repair capacity. Of 11 known single nucleotide polymorphisms (SNPs) of the DNA repair gene ATM, we selected a particular SNP (located in the 5' untranslated region and therefore thought to be associated with ATM gene expression) and examined the association with radiation-associated breast cancer in the context of an RERF A-bomb survivor cohort study. A follow-up survey of 3,040 female members of the RERF Immunogenome Study Cohort during 1981-2009 identified a total of 108 breast cancer cases. ATM genotypes (ATM-G/G, -G/A, and -A/A) were determined by the TaqMan assay method for all cohort members. Relative risks (RRs) of breast cancer were estimated for radiation dose, the ATM genotypes, and the combined categories of dose levels and genotypes. As a result, RR of breast cancer significantly increased with increased radiation dose (RR = 1.46/Gy, 95% CI: 1.19-1.80). A-bomb survivors with ATM-G/G homozygote revealed a significantly-increased RR of breast cancer (RR = 1.74, 95%CI: 1.18-2.56), using as a reference the risk of those with ATM-A/A homozygotes combined with ATM-G/A heterozygotes. When dividing the subjects into two groups by age at exposure (under 20 years of age and over 20), RR of breast cancer significantly increased with radiation dose in the group aged less than 20 years at exposure (RR = 1.65/Gy, 95% CI: 1.29-2.11), but no significant increase in RR by genotype was observed. In the group aged over 20 years at exposure, there was no significant increase in RR of breast cancer by dose, but RR of breast cancer significantly increased among ATM-G/G homozygotes, using as a reference the risk of ATM-A/A homozygotes combined with ATM-G/A heterozygotes (RR = 2.28, 95%CI: 1.28-4.06). In all analyses, no interaction between RR of breast cancer and combinations of radiation dose and genotype was detected. These findings suggested that the ATM genotypes and radiation dose might affect the risk of breast cancer among A-bomb survivors and that the significance of such impact might differ by age at exposure. Citation Format: Hayashi T, Yoshida K, Ohishi W, Kyoizumi S, Kusunoki Y, Nakachi K. Assessment of breast cancer risk among atomic-bomb survivors based on ATM polymorphisms, radiation dose, and age at exposure [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-04.
Gene Expression Profiling (GEP) of Whole Bone Marrow Biopsies in Complete Remission (BMB-CR) of Multiple Myeloma (MM) Patients Treated On Total Therapy Protocols – Normalization of GEP Signature in Comparison with Normal Donor BMB (BMB-NL) and Consequences for Progression-Free Survival (PFS)
Authors: Christoph Heuck, Pingping Qu, Sarah Waheed, Saad Z Usmani, Frits van Rhee, Madhav V. Dhodapkar, Joshua Epstein, Qing Zhang, Donald Johann, Bart Barlogie
Journal: Blood (2012)