tbuckley/cabot-search huggingface dataset:
A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos
Authors: Kristin M. Burkart, Tamar Sofer, Stephanie J. London, Ani Manichaikul, Fernando P. Hartwig, Qi Yan, María Soler Artigas, Lydiana Avila, Wei Chen, Sonia Davis Thomas, Alejandro A. Diaz, Ian P. Hall, Bernardo L. Horta, Robert C. Kaplan, Cathy C. Laurie, Ana M. Menezes, Jean V. Morrison, Elizabeth C. Oelsner, Deepa Rastogi, Stephen S. Rich, Manuel Soto-Quiros, Adrienne M. Stilp, Martin D. Tobin, Louise V. Wain, Juan C. Celedón, R. Graham Barr
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.Objectives: Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.Methods: GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.Measurements and Main Results: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEV1 in ZSWIM7 (rs4791658; P = 4.99 × 10−9) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 × 10−9) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; P = 1.92 × 10−8) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10−8) regionally replicated. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos at the genome-wide significance level.Conclusions: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.
Results from the Phase 3 DUOTM Trial: A Randomized Comparison of Duvelisib Vs Ofatumumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Authors: Ian W. Flinn, Peter Hillmen, Marco Montillo, Zsolt Nagy, Árpád Illés, Gabriel Etienne, Julio Delgado, Bryone Jean Kuss, Constantine S. Tam, Zoltán Gasztonyi, Fritz Offner, Scott D Lunin, Francesco Bosch, Matthew S. Davids, Nicole Lamanna, Ulrich Jaeger, Paolo Ghia, Florence Cymbalista, Craig A. Portell, Alan P Skarbnik, Amanda Cashen, Virginia Kelly, Barry Turnbull, Stephan Stilgenbauer
Journal: Blood (2017)
PTH-111 Clinical and psychosocial predictors of abdominal pain frequency in patients with inflammatory bowel disease
Authors: L Sweeney, M Artom, H Proudfoot, C Norton, W Czuber-Dochan
Journal: Gut (2017)

Introduction  Pain is a commonly experienced and burdensome symptom in patients with Inflammatory Bowel Disease (IBD). A substantial number of patients continue to experience pain while the disease is in remission. Research exploring factors in IBD-pain is sparse. This study aimed to explore sociodemographic, clinical and psychosocial factors associated with pain frequency in patients with IBD.  Method  Patients recruited from outpatient IBD services completed the United Kingdom Inflammatory Bowel Disease Questionnaire (UK IBDQ) and a number of sociodemographic, clinical and psychosocial measures. In the secondary analysis of these data, item 13 from the UK IBDQ measuring pain frequency,  “On how many days over the last two weeks have you felt pain in your abdomen?”,  was utilised as the primary outcome. Sociodemographic, disease-related and laboratory data were retrieved from patients’ hospital electronic medical records. Patients completed a number of self-report measures including: IBD-Fatigue Scale (IBD-F) and Multidimensional Fatigue Inventory (MFI), Hospital Anxiety and Depression Scale (HADS), IBD-Distress Scale (IBD-DS), Cohen Perceived Stress Scale (PSS), Brief Illness Perceptions Questionnaire (BIPQ) and Cognitive and Behavioural Responses to Symptoms Questionnaire (CBSQ). Univariate and multivariate analyses were conducted to test the relationship between pain frequency and sociodemographic, clinical and psychosocial variables.  Results  182 patients with IBD took part in the study (57% female, 64% Crohn’s Disease, mean age 37.0 years). In univariate analyses, greater pain frequency was significantly associated with disease activity and fatigue. Female patients, those with active disease and taking steroids reported significantly more pain frequency. All emotional, cognitive and behavioural factors in psychosocial measures had significant positive correlations with pain frequency. In multivariate analyses, disease activity (p=0.01) and fatigue measured by the MFI (p=0.04), were significant predictors of pain frequency and explained 26% of the variance. Emotional, cognitive and behavioural factors were not found to predict pain frequency.  Conclusion  Fatigue and disease activity were independent predictors of pain frequency in patients with IBD. Utilising a single pain item from the IBDQ, none of the psychosocial factors were found to predict pain frequency. Further research, using more comprehensive pain measures, capturing pain severity and frequency is required to explore the relationship between pain and psychosocial factors in IBD. This knowledge may help in the development of pain management interventions.  Disclosure of Interest  None Declared
Brentuximab vedotin plus AVD for non-bulky limited stage Hodgkin lymphoma: A phase II trial.
Authors: Jeremy S. Abramson, Jon E. Arnason, Ann S. LaCasce, Robert Redd, Jeffrey A. Barnes, Lubomir Sokol, Robin Joyce, David Avigan, Donna S. Neuberg, Tak Takvorian, Ephraim P. Hochberg, Celeste M. Bello
Journal: Journal of Clinical Oncology (2015)

8505 Background: ABVD plus radiation is standard therapy for limited HL, but carries risks of bleomycin-lung injury and radiation toxicity. Brentuximab vedotin is highly active in relapsed HL. We evaluated brentuximab plus AVD (A-AVD) for non-bulky stage I-II HL. Methods: This is a multicenter phase 2 study. Patients received a lead in cycle of brentuximab monotherapy 1.2mg/kg on days 1 and 15, followed by a PET scan. Patients then received 4-6 cycles of A-AVD, based on interim PETCT. The primary endpoint is complete response rate (CRR). A sample size of 34 was required to detect a CRR of 93% with 91% power and alpha error of 0.10. Results: 34 patients were enrolled. Median age is 36 (20–75). Risk was early favorable in 62%, unfavorable in 38%. The best CRR was 100%. After the monotherapy lead in, 18/34 subjects (53%) were in CR. After 2 cycles of A-AVD, 33 were in CR (97%), and 1 was removed for toxicity. At end of treatment (EOT), 30 (88%) were in CR, 2 were interpreted as progressive disease (PD), and 2 were removed for toxicity. At EOT, 8 subjects had PET scans interpreted as positive on central review, 6 of which were felt to be reactive by investigators. All 6 subjects were in confirmed CR on brief follow-up scan with no intervening therapy, confirming false positive scans. Two cases were considered PD at EOT, 1 of whom received 2 further cycles of AVD alone and was back in CR, suggesting that scan may also have been a false positive. At a median follow-up of 14 months, the PFS and OS are 90% and 97%. The most common adverse events were peripheral neuropathy (74%), fatigue (71%), nausea (24%), neutropenia (68%), anemia (56%), constipation (56%), diarrhea (35%), abdominal pain (32%), ALT elevation (29%) and febrile neutropenia (29%). Grade 3-4 toxicity occurred in 26/34 patients: neutropenia (56%), febrile neutropenia (29%) and peripheral neuropathy (24%). One elderly patient died of neutropenic sepsis in the first A-AVD cycle. One patient was removed for grade 2 hypersensitivity despite premedication. Brentuximab reductions were required in 38%, most for peripheral neuropathy. Conclusions: A-AVD x 4 produced a high CRR but with more toxicity than expected from AVD alone. False positive PET scans were common on EOT imaging and warrants further attention. Clinical trial information: NCT01534078.
Five-Year Survival Results: Frontline Brentuximab Vedotin in Combination with CHP in Patients with CD30-Expressing Peripheral T-Cell Lymphomas
Authors: Michelle A. Fanale, Steven M. Horwitz, Andres Forero-Torres, Nancy L. Bartlett, Ranjana H. Advani, Barbara Pro, Robert W. Chen, Andrew Davies, Tim M. Illidge, Mayur Uttarwar, Dirk Huebner, Hong Ren, Andrei R. Shustov
Journal: Blood (2017)
Genomic Biomarkers to Predict Response to Hypomethylating Agents in Patients with Myelodysplastic Syndromes (MDS)
Authors: Aziz Nazha, Mikkael A. Sekeres, Rafael Bejar, Rami S. Komrokji, John Barnard, Karam Al-Issa, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, David P. Steensma, Amy E. DeZern, Gail J. Roboz, Guillermo Garcia-Manero, Benjamin L. Ebert, Jaroslaw P. Maciejewski
Journal: Blood (2017)
Long-Term Follow-up on Adult Patients with Philadelphia-Chromosome Positive Acute Myeloid Leukemia Who Were Treated with Interim Imatinib Followed By Allogeneic Hematopoietic Cell Transplantation
Authors: Heeje Kim, Gi June Min, Jae-Ho Yoon, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Sung Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
Journal: Blood (2017)
Culture's Influence on Stressors, Parental Socialization, and Developmental Processes in the Mental Health of Children of Immigrants
Authors: Su Yeong Kim, Seth J. Schwartz, Krista M. Perreira, Linda P. Juang
Journal: Annual Review of Clinical Psychology (2018)

Children of immigrants represent one in four children in the United States and will represent one in three children by 2050. Children of Asian and Latino immigrants together represent the majority of children of immigrants in the United States. Children of immigrants may be immigrants themselves, or they may have been born in the United States to foreign-born parents; their status may be legal or undocumented. We review transcultural and culture-specific factors that influence the various ways in which stressors are experienced; we also discuss the ways in which parental socialization and developmental processes function as risk factors or protective factors in their influence on the mental health of children of immigrants. Children of immigrants with elevated risk for mental health problems are more likely to be undocumented immigrants, refugees, or unaccompanied minors. We describe interventions and policies that show promise for reducing mental health problems among children of immigrants in the United States.
Abstract 16089: Effect of Non-targeted Community CPR Education on Bystander CPR Performance
Authors: Amy Uber, Rick C Sadler, Todd Chassee, Joshua C Reynolds
Journal: Circulation (2016)

Introduction: Only 37% of OHCA cases receive bystander CPR (bCPR) in Kent County, MI. In May, 2014, prehospital providers offered one-time point-of-care compression-only CPR training (CPR-INT) to p...
Abstract 20874: Left Ventricular Unloading With Percutaneous Ventricular Assist Device is Comparable to Direct Left Ventricular Vent During Extracorporeal Life Support
Authors: Sarah Tepper, Moises Baltazar Garcia, Molly Pisani, Gregory Ewald, Jasvindar Singh, Muhammad Faraz Masood, Keki Balsara, Akinobu Itoh
Journal: Circulation (2016)

Introduction: Patients supported with extracorporeal life support (ECLS) can experience severe complications from increased left ventricular afterload. The Impella percutaneous ventricular assist d...
COP1/DET1/ETS axis regulates ERK transcriptome and sensitivity to MAPK inhibitors
Authors: Yuanyuan Xie, Zhen Cao, Elissa W.P. Wong, Youxin Guan, Wenfu Ma, Jenny Q. Zhang, Edward G. Walczak, Devan Murphy, Leili Ran, Inna Sirota, Shangqian Wang, Shipra Shukla, Dong Gao, Simon R.V. Knott, Kenneth Chang, Justin Leu, John Wongvipat, Cristina R. Antonescu, Gregory Hannon, Ping Chi, Yu Chen
Journal: Journal of Clinical Investigation (2018)

Aberrant activation of MAPK signaling leads to the activation of oncogenic transcriptomes. How MAPK signaling is coupled with the transcriptional response in cancer is not fully understood. In 2 MAPK-activated tumor types, gastrointestinal stromal tumor and melanoma, we found that ETV1 and other Pea3-ETS transcription factors are critical nuclear effectors of MAPK signaling that are regulated through protein stability. Expression of stabilized Pea3-ETS factors can partially rescue the MAPK transcriptome and cell viability after MAPK inhibition. To identify the players involved in this process, we performed a pooled genome-wide RNAi screen using a fluorescence-based ETV1 protein stability sensor and identified COP1, DET1, DDB1, UBE3C, PSMD4, and COP9 signalosome members. COP1 or DET1 loss led to decoupling between MAPK signaling and the downstream transcriptional response, where MAPK inhibition failed to destabilize Pea3 factors and fully inhibit the MAPK transcriptome, thus resulting in decreased sensitivity to MAPK pathway inhibitors. We identified multiple COP1 and DET1 mutations in human tumors that were defective in the degradation of Pea3-ETS factors. Two melanoma patients had de novo DET1 mutations arising after vemurafenib treatment. These observations indicate that MAPK signaling–dependent regulation of Pea3-ETS protein stability is a key signaling node in oncogenesis and therapeutic resistance to MAPK pathway inhibition.
Carboxydichlorofluorescein (CDCF): A fluorescent drug surrogate for multidrug resistance protein-5 (MRP5) mediated transport
Authors: Susan Pratt, Donald C. Paul, Xiaoling Xia, Sheng-Bin Peng, Anne H. Dantzig
Journal: Cancer Research (2004)

504  CDCF is a cost-effective, simple to use, fluorescent drug surrogate with which to measure multidrug resistance protein –5 (MRP5, ABCC5) mediated transport. As a member of the ATP- binding cassette efflux transporter superfamily, MRP5 confers drug resistance to nucleoside-based drugs such as 6-thioguanine, mercaptopurine, and 5-fluorouracil as well as to antifolate agents such as methotrexate and Alimta. In cellular assays, MRP5 effluxes a fluorescent metabolite of CMFDA (Cell Tracker green), and we have developed a transport assay which measures the uptake of a close fluorescent analog of this metabolite, CDCF, into inside-out membrane vesicles prepared from MRP5 transfected HEK-293 cells. The uptake of CDCF by MRP5 is ATP-dependent and glutathione-independent, and demonstrates typical Michealis-Menten kinetics with a Km of 15 μM and a Vmax of 30 pmol/min/mg prot. These values indicate that MRP5 has a higher affinity for CDCF than for other drug substrates such as methotrexate and Alimta and the metabolite of 5-fluorouracil, 5-fluorodeoxyuridine monophosphate (Km values of 300-1100 μM). MRP5 transport inhibition studies between CDCF and these drug substrates reveal competitive interaction with a common binding site, thereby validating the use of CDCF as a drug surrogate. In addition, the potency of MRP5 inhibitors such as probenecid, MK571, and the phosphodiesterase 5 inhibitors, trequinsin and zaprinast, correlate well between CDCF and these drug substrates, further supporting a common transport binding site. Using membrane vesicles from highly expressing transfected cell lines to evaluate other members of the MRP family revealed that MRP2 (ABCC2) also had a high affinity and high rate of transport of CDCF (Km of 13 μM and a Vmax of 64 pmol/min/mg prot), with or without glutathione. Under these same conditions, MRP1 (ABCC1) and MRP4 (ABCC4) demonstrated very low rates of CDCF transport. This is an interesting observation given that MRP4 has a very similar substrate profile to MRP5 (e.g. antifolates and nucleoside-based compounds), while MRP2 is like MRP5 only in its ability to transport antifolate drugs.
Abnormal mTOR Activation in Autism
Authors: Kellen D. Winden, Darius Ebrahimi-Fakhari, Mustafa Sahin
Journal: Annual Review of Neuroscience (2018)

The mechanistic target of rapamycin (mTOR) is an important signaling hub that integrates environmental information regarding energy availability and stimulates anabolic molecular processes and cell growth. Abnormalities in this pathway have been identified in several syndromes in which autism spectrum disorder (ASD) is highly prevalent. Several studies have investigated mTOR signaling in developmental and neuronal processes that, when dysregulated, could contribute to the development of ASD. Although many potential mechanisms still remain to be fully understood, these associations are of great interest because of the clinical availability of mTOR inhibitors. Clinical trials evaluating the efficacy of mTOR inhibitors to improve neurodevelopmental outcomes have been initiated.
Fractionated Gemtuzumab Ozogamicin in Association with High Dose Chemotherapy: A Bridge to Allogeneic Stem Cell Transplantation in Refractory and Relapsed Acute Myeloid Leukemia?
Authors: Pierre-Edouard Debureaux, Myriam Labopin, Simona Lapusan, Francoise Isnard, Rosa Adaeva, Agnès Bonnin, Pierre Hirsch, Francois Delhommeau, Giorgia Battipaglia, Remy Duléry, Federica Giannotti, Florent Malard, Annalisa Ruggeri, Anne Vekhoff, Ollivier Legrand, Mohamad Mohty, Eolia Brissot
Journal: Blood (2017)
Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon cancer: A cohort study of two cancer centres
Authors: Matthew Grant, Andrew Haydon, Lewis Au, Simon Wilkins, Karen Oliva, Eva Segelov, Yoland Antill, Peter Carne, Pravin Ranchod, Adrian Polglase, Chip Farmer, Martin Chin, Roger Wale, Paul Simpson, Stephen Bell, Stewart Skinner, Paul McMurrick, Jeremy Shapiro
Journal: International Journal of Surgery (2018)
Bortezomib-Thalidomide-Dexamethasone (VTD) As Salvage Treatment in Patients with Multiple Myeloma Candidates for Transplantation in the Real World
Authors: Jule Vasquez, Shirley Quintana, Lourdes Lopez, Cindy Alcarraz, Marco Villena, Silvia Neciosup, Luis Mas, Henry Gomez
Journal: Blood (2017)
State-Specific Prevalence of Tobacco Product Use Among Adults — United States, 2014–2015
Authors: Satomi Odani, Brian S. Armour, Corinne M. Graffunder, Gordon Willis, Anne M. Hartman, Israel T. Agaku
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Despite recent declines in cigarette smoking prevalence, the tobacco product landscape has shifted to include emerging tobacco products* (1,2). Previous research has documented adult use of smokeless tobacco and cigarettes by state (3); however, state-specific data on other tobacco products are limited. To assess tobacco product use in the 50 U.S. states and the District of Columbia (DC), CDC and the National Cancer Institute analyzed self-reported use of six tobacco product types: cigarettes, cigars, regular pipes, water pipes, electronic cigarettes (e-cigarettes), and smokeless tobacco products among adults aged ≥18 years using data from the 2014-2015 Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Prevalence of ever-use of any tobacco product ranged from 27.0% (Utah) to 55.4% (Wyoming). Current (every day or some days) use of any tobacco product ranged from 10.2% (California) to 27.7% (Wyoming). Cigarettes were the most common currently used tobacco product in all states and DC. Among current cigarette smokers, the proportion who currently used one or more other tobacco products ranged from 11.5% (Delaware) to 32.3% (Oregon). Differences in tobacco product use across states underscore the importance of implementing proven population-level strategies to reduce tobacco use and expanding these strategies to cover all forms of tobacco marketed in the United States. Such strategies could include comprehensive smoke-free policies, tobacco product price increases, anti-tobacco mass media campaigns, and barrier-free access to clinical smoking cessation resources (1,4).
High-dose omega-3 fatty acid supplementation to modulate breast tissue biomarkers in premenopausal women at high risk for development of breast cancer.
Authors: Carol J. Fabian, Bruce F. Kimler, Brian K. Petroff, Carola Maria Zalles, Trina Metheny, Jessica A Box, Jennifer L Nydegger, Teresa A. Phillips, Brandon H Hidaka, Susan E Carlson, Linda A deGraffenried, Stephen D Hursting
Journal: Journal of Clinical Oncology (2013)

1515 Background: We conducted a pilot study of high dose omega-3 fatty acid (FA) supplementation in pre-menopausal women to determine if risk biomarkers for breast cancer in benign breast tissue sampled by random peri-areolar aspiration (RPFNA) could be favorably modulated and to acquire preliminary data on possible mechanism of action. Methods: 36 pre-menopausal women at increased risk for breast cancer were accrued to a trial of 6-month intervention with 4 g daily of omega-3-acid ethyl esters [1.86 g eicosapentaenoic acid (EPA), 1.5 g docosahexaenoic acid (DHA)]. To date, 31 subjects have completed study with RPFNA performed pre- and post-intervention in the follicular phase of the menstrual cycle and specimens evaluated for cytomorphology and proliferation (Ki-67). FA composition was determined in plasma, red blood cells, and RPFNA specimens. Additional specimens were frozen for assessment of hormones, a panel of 11 adipokines and cytokines, and gene expression. Results: The ratio of (EPA+DHA):Arachidonic Acid (AA) levels increased significantly in plasma and erythrocytes by a median of three-fold. There was a significant decrease in blood EPA+DHA between discontinuation at 6 months and 2 weeks later when RPFNA was performed. Despite that, there was favorable modulation for cytologic evidence of atypia (81% at baseline to 42% at off-study; p=0.003), Masood score (medians of 15 to 14; p=0.001), number of epithelial cells recovered (p=0.004) and Ki-67 expression (p=0.025 for 30 women with any Ki-67 at baseline, medians of 1.9% to 0.9%). Serum assays have been completed for 24 subjects. No statistically significant changes were observed for estradiol, testosterone, progesterone, SHBG, IGF-1, IGFBP-3. There was a trend (p=0.056) towards a decrease in resistin. To date, only two subjects have discontinued the study early; grade 2 or greater gastrointestinal side effects have been reported by only two subjects. Conclusions: Favorable modulation of tissue risk biomarkers, cytologic atypia and proliferation along with good tolerability suggests that high dose omega-3 FA esters should be tested further in a placebo controlled trial. Clinical trial information: NCT01252277.
Platelet Response to Lusutrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease and Thrombocytopenia Undergoing Non-Emergency Invasive Procedures: Results from a Phase 3 Randomized, Double-Blind, Placebo-Controlled Study
Authors: Nezam Afdhal, Ajay Duggal, Toshimitsu Ochiai, Tomoko Motomiya, Takeshi Kano, Tsutae Nagata, Markus Peck-Radosavljevic
Journal: Blood (2017)
A Phase II Clinical Trial of the Pan PI3K Inhibitor, Buparlisib, for the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia: Canadian Cancer Trials Group IND.216
Authors: Sarit Assouline, Lilian Amrein, Versha Banerji, Stephen Caplan, Carolyn Jane Owen, Wanda Hasegawa, Sue Robinson, Sudeep Shavikumar, Anca Prica, Anthea Peters, Linda Hagerman, Laura Rodriguez, Tanya Skamene, Lawrence Panasci, Bingshu E. Chen, Annette E Hay
Journal: Blood (2017)