tbuckley/cabot-search huggingface dataset:
Dose intensity of nab-paclitaxel and gemcitabine chemotherapy in metastatic pancreatic cancer.
Authors: Alexander Lim, Dae Won Kim, Kunhwa Kim, Richard D. Kim, Salvatore Michael Bottiglieri
Journal: Journal of Clinical Oncology (2019)

251 Background: Combination chemotherapy with nab-paclitaxel/gemcitabine is a standard of care option in metastatic pancreatic cancer management with increasing use due to an improvement in median overall survival of 1.8 months compared to gemcitabine alone. It is also used in practice in the second and third-line settings for patients that have progressed on fluorouracil based regimens. As the utility of this combination chemotherapy has grown, dose intensity (DI) in relation to survival outcome is an important measure for real world application. Methods: Fifty-six patients that were 18 years or older with metastatic pancreatic cancer treated with nab-paclitaxel/gemcitabine as first-line therapy from January 1, 2013 to December 31, 2014 at Moffitt Cancer Center were identified through medical records. The subjects were retrospectively reviewed, and demographic, treatment outcomes (survival and progression), and DI were collected. Overall survival was calculated with Kaplan Meier survival curves. Multi-Cox regression models estimated multivariable-adjusted hazard ratio with 95% confidence intervals. Results: There was no significant relationship between receiving a DI &gt; 85% regimen in relation to independent variables of age &gt; 65, sex, primary site, and known distant metastasis; however DI &gt; 85% was significant for patients that received additional chemotherapy following nab-paclitaxel/gemcitabine (p = 0.044). The DI &gt; 85% group compared to the &lt; 85% group had a hazard ratio (HR) for all-cause mortality of 0.285 (0.106-0.764, p = 0.013). Six and 12-month survival were higher in the DI &gt; 85% group (p = 0.009, p = 0.02 respectively). Conclusions: DI &gt; 85% for nab-paclitaxel/gemcitabine compared to DI &lt; 85% may have a lower all-cause mortality and higher 6 and 12-month survival.
Association Between Screen Time and Children’s Performance on a Developmental Screening Test
Authors: Sheri Madigan, Dillon Browne, Nicole Racine, Camille Mori, Suzanne Tough
Journal: JAMA Pediatrics (2019)

Excessive screen time is associated with delays in development; however, it is unclear if greater screen time predicts lower performance scores on developmental screening tests or if children with poor developmental performance receive added screen time as a way to modulate challenging behavior.To assess the directional association between screen time and child development in a population of mothers and children.This longitudinal cohort study used a 3-wave, cross-lagged panel model in 2441 mothers and children in Calgary, Alberta, Canada, drawn from the All Our Families study. Data were available when children were aged 24, 36, and 60 months. Data were collected between October 20, 2011, and October 6, 2016. Statistical analyses were conducted from July 31 to November 15, 2018.Media.At age 24, 36, and 60 months, children's screen-time behavior (total hours per week) and developmental outcomes (Ages and Stages Questionnaire, Third Edition) were assessed via maternal report.Of the 2441 children included in the analysis, 1227 (50.2%) were boys. A random-intercepts, cross-lagged panel model revealed that higher levels of screen time at 24 and 36 months were significantly associated with poorer performance on developmental screening tests at 36 months (β, -0.06; 95% CI, -0.10 to -0.01) and 60 months (β, -0.08; 95% CI, -0.13 to -0.02), respectively. These within-person (time-varying) associations statistically controlled for between-person (stable) differences.The results of this study support the directional association between screen time and child development. Recommendations include encouraging family media plans, as well as managing screen time, to offset the potential consequences of excess use.
Drug Hypersensitivity Reactions: Are There Differences Between Children And Adults?
Authors: Larissa S. Brandão, Fabiana A. Nunes, Patricia Guerzet Ayres Bastos, Patrícia Guerzet, Alex E. Lacerda, Cristina F.S.T. Piza, Fernanda Marcelino, Mara Felix, Gladys Queiroz, Daniela Raeder, Luiz Alexandre Rocha, Dirceu Sole, Inês Cristina Camelo-Nunes, Luis Felipe Ensina
Journal: Journal of Allergy and Clinical Immunology (2019)
Vigilance state fluctuations and performance using brain–computer interface for communication
Authors: Barry Oken, Tab Memmott, Brandon Eddy, Jack Wiedrick, Melanie Fried-Oken
Journal: Brain-Computer Interfaces (2018)

The effect of fatigue and drowsiness on brain-computer interface (BCI) performance was evaluated. 20 healthy participants performed a standardized 11-minute calibration of a Rapid Serial Visual Presentation BCI system five times over two hours. For each calibration, BCI performance was evaluated using area under the receiver operating characteristic curve (AUC). Self-rated measures were obtained following each calibration including the Karolinska Sleepiness Scale and a standardized boredom scale. Physiological measures were obtained during each calibration including P300 amplitude, theta power, alpha power, median power frequency and eye-blink rate. There was a significant decrease in AUC over the five sessions. This was paralleled by increases in self-rated sleepiness and boredom and decreases in P300 amplitude. Alpha power, median power frequency, and eye-blink rate also increased but more modestly. AUC changes were only partly explained by changes in P300 amplitude. There was a decrease in BCI performance over time that related to increases in sleepiness and boredom. This worsened performance was only partly explained by decreases in P300 amplitude. Thus, drowsiness and boredom have a negative impact on BCI performance. Increased BCI performance may be possible by developing physiological measures to provide feedback to the user or to adapt the classifier to state.
The Electronic Asthma Management System (eAMS) improves primary care asthma management
Authors: Samir Gupta, Courtney Price, Gina Agarwal, David Chan, Sanjeev Goel, Louis-Philippe Boulet, Alan G. Kaplan, Gerald Lebovic, Muhammad Mamdani, Sharon E. Straus
Journal: European Respiratory Journal (2019)

A high prevalence of suboptimal asthma control is attributable to known evidence–practice gaps. We developed a computerised clinical decision support system (the Electronic Asthma Management System (eAMS)) to address major care gaps and sought to measure its impact on care in adults with asthma. This was a 2-year interrupted time-series study of usual care (year 1) versus eAMS (year 2) at three Canadian primary care sites. We included asthma patients aged ≥16 years receiving an asthma medication within the last 12 months. The eAMS consisted of a touch tablet patient questionnaire completed in the waiting room, with real-time data processing producing electronic medical record-integrated clinician decision support. Action plan delivery (primary outcome) improved from zero out of 412 (0%) to 79 out of 443 (17.8%) eligible patients (absolute increase 0.18 (95% CI 0.14–0.22)). Time-series analysis indicated a 30.5% increase in physician visits with action plan delivery with the intervention (p&lt;0.0001). Assessment of asthma control level increased from 173 out of 3497 (4.9%) to 849 out of 3062 (27.7%) eligible visits (adjusted OR 8.62 (95% CI 5.14–12.45)). Clinicians escalated controller therapy in 108 out of 3422 (3.2%) baseline visits versus 126 out of 3240 (3.9%) intervention visits (p=0.12). At baseline, a short-acting β-agonist alone was added in 62 visits and a controller added in 54 visits; with the intervention, this occurred in 33 and 229 visits, respectively (p&lt;0.001). The eAMS improved asthma quality of care in real-world primary care settings. Strategies to further increase clinician uptake and a randomised controlled trial to assess impact on patient outcomes are now required.
Case of Solitary Peritoneal Metastasis From Atypical Bronchopulmonary Carcinoid on 18F-FDG PET/CT
Authors: Sachin Gawde, Ashok Singhal, Amrita Kasat, Siddharth Parekh, Veena Ramaswamy
Journal: Clinical Nuclear Medicine (2019)

Atypical lung carcinoids frequently metastasize to mediastinal nodes, liver, bone, lungs, and brain and rarely to ovaries, pancreas, subcutaneous, and skin. Solitary peritoneal metastasis is extremely rare and unreported previously. We present a case of a 36-year-old woman with cough, hemoptysis, dyspnea with detection of lung mass, and incidental detection of pelvic mass. Fine needle aspiration cytology failed to reveal the true nature of both the lesions. FDG PET/CT showed intensely avid mediastinal nodes, left lung, and rectouterine masses. Core biopsy from lung mass revealed atypical carcinoid without appreciable uptake on Ga-DOTANOC scan. Subsequent postchemotherapy CT scan shows significant regression in lung and peritoneal masses.
Fibrinography: A Multiwavelength Light‐Scattering Assay of Fibrin Structure
Authors: Carhel Dassi, Landry Seyve, Xabel García, Emmanuelle Bigo, Raphaël Marlu, François Caton, Benoît Polack
Journal: HemaSphere (2019)

We have previously developed a fibrin structural assay dedicated to purified fibrinogen-thrombin system. Here, we extend the pertinence of this test, called Fibrinography, to tissue factor-triggered plasma coagulation. We show that Fibrinography determines quantitatively the structure of fibrin fibers in plasma with an excellent reproducibility. We compare this assay with the commonly used single wavelength turbidity method, showing that the latter is not a proper structural assay, but determines essentially the fibrinogen content in plasma. In addition, we also show, in model plasmas, that Fibrinography is able to discriminate normal and hypocoagulant plasmas, and even between hypercoagulant plasmas. Therefore, Fibrinography, by measuring the final step of the coagulation cascade, may be used to evaluate patients' plasma in hypo- or hypercoagulant diseases.
Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for <i>PIK3CA</i>-altered head and neck cancer
Authors: Matthew L. Hedberg, Noah D. Peyser, Julie E. Bauman, William E. Gooding, Hua Li, Neil E. Bhola, Tian Ran Zhu, Yan Zeng, Toni M. Brand, Mi-Ok Kim, Richard C.K. Jordan, Scott VandenBerg, Victor Olivas, Trever G. Bivona, Simion I. Chiosea, Lin Wang, Gordon B. Mills, Jonas T. Johnson, Umamaheswar Duvvuri, Robert L. Ferris, Patrick Ha, Daniel E. Johnson, Jennifer R. Grandis
Journal: The Journal of Experimental Medicine (2019)

PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09–0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14–0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.
Imaging metabotropic glutamate receptor system: Application of positron emission tomography technology in drug development
Authors: Youwen Xu, Zizhong Li
Journal: Medicinal Research Reviews (2019)

The diversity seen in the mode of pharmacology and the numerous glutamate receptor subtypes have previously complicated drug development efforts. Nonetheless, recent clinical trials of drug candidates that accommodate the glutamatergic intricate pharmacology have yielded encouraging results. Target engagement is an important requirement for the advancement of central nervous system drug candidates into clinical trial. Positron emission tomography (PET) tracer technology has the unique ability to give the direct insight into the relationship between the level of receptor occupancy and the administered dose, thus establishing a direct link between the level of target exposure and the drug efficacy in human. This review is focused on the advancement of mGlu5 , mGlu 1 , and mGlu 2 receptor-related PET tracer technology: PET tracer development strategies, PET tracer selection in receptor occupancy studies, the scopes and limitations to use PET to measure receptor occupancy for the drug candidates with different pharmacology, and how to use the measurements of receptor occupancy as a translational biomarker for decision-making in an innovative drug development program.
A Simple, Rapid, and Inexpensive Color-Based Hemoglobin Assay As a Robust Screening Test for Severe Anemia in Limited Resource Settings
Authors: Marina Perez-Plazola, Erika Tyburski, Luke R. Smart, Thad A. Howard, Sophie Perier, Russell E. Ware, Wilbur A Lam, Patrick T. McGann
Journal: Blood (2018)
Placental Growth Factor as an Indicator of Maternal Cardiovascular Risk After Pregnancy
Authors: Laura Benschop, Sarah Schalekamp-Timmermans, Zoe A. Broere-Brown, Jeanine E. Roeters van Lennep, Vincent W.V. Jaddoe, Jolien W. Roos-Hesselink, M. Kamran Ikram, Eric A.P. Steegers, James M. Roberts, Robin E. Gandley
Journal: Circulation (2019)

Background: Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of midpregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later-life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in midpregnancy, identify not only a subset of women at risk for pregnancy complications but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome. Methods: In a population-based prospective cohort study of 5475 women, we computed gestational age–adjusted multiples of the medians of early pregnancy and midpregnancy PlGF concentrations. Information on pregnancy complications (preeclampsia, small for gestational age, and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy, we measured maternal systolic and diastolic blood pressures, cardiac structure (aortic root diameter, left atrial diameter, left ventricular mass, and fractional shortening), carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibers. Blood pressure was also measured 9 years after pregnancy. Results: Women were on average 29.8 (SD, 5.2) years of age in pregnancy, were mostly European (55.2%), and 14.8% developed a pregnancy complication. Quartile analysis showed that especially women with midpregnancy PlGF in the lowest quartile (the low-PlGF subset) had a larger aortic root diameter (0.40 mm [95% CI, 0.08–0.73]), left atrial diameter (0.34 mm [95% CI, −0.09 to 0.78]), left ventricular mass (4.6 g [95% CI, 1.1–8.1]), and systolic blood pressure (2.3 mm Hg [95% CI, 0.93–3.6]) 6 years after pregnancy than women with the highest PlGF. Linear regression analysis showed that higher midpregnancy PlGF concentrations were associated with a smaller aortic root diameter (−0.24 mm [95% CI, −0.39 to −0.10]), smaller left atrial diameter (−0.75 mm [95% CI, −0.95 to −0.56]), lower left ventricular mass (−3.9 g [95% CI, −5.5 to −2.3]), and lower systolic blood pressure (−1.1 mm Hg [95% CI, −1.7 to −0.46]). These differences persisted after the exclusion of women with complicated pregnancies. Conclusions: Women with low PlGF in midpregnancy have a greater aortic root diameter, left atrial diameter, and left ventricular mass and higher systolic blood pressure 6 and 9 years after pregnancy compared to women with higher PlGF, including women with uncomplicated pregnancies. The pathophysiological implications of lower PlGF concentrations in midpregnancy might provide insight into the identification of pathways contributing to greater cardiovascular risk factor burden.
Abstract 12143: A Validation Study of Phenotype-guided Genetic Testing Using the Mayo HCM Genotype Predictor Score for Japanese Patients With Hypertrophic Cardiomyopathy
Authors: Toshihiro Moriki, Toru Kubo, Yuri Ochi, Asa Takahashi, Takayoshi Hirota, Naohito Yamasaki, Hiroaki Kitaoka
Journal: Circulation (2017)

Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal-dominant disorder mainly caused by mutations in sarcomere genes. Clinical course of HCM patients wit...
Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: Relevance of non-characterized nodules
Authors: Zoe Mariño, Anna Darnell, Sabela Lens, Victor Sapena, Alba Díaz, Ernest Belmonte, Christie Perelló, Jose Luis Calleja, Maria Varela, Manuel Rodriguez, Carlos Rodriguez de Lope, Susana Llerena, Xavier Torras, Adolfo Gallego, Margarita Sala, Rosa María Morillas, Beatriz Minguez, Jordi Llaneras, Susana Coll, José Antonio Carrion, Mercedes Iñarrairaegui, Bruno Sangro, Ramón Vilana, Manel Sole, Carmen Ayuso, José Ríos, Xavier Forns, Jordi Bruix, María Reig
Journal: Journal of Hepatology (2019)
Abstract P2-08-27: Not presented
Authors: JM Rayen, GH Poole, C Rhodes
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Rayen JM, Poole GH, Rhodes C. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-27.
Comprehensive profiling of immune landscape in gastrointestinal (GI) and head and neck (HN) cancers via computational deconvolution.
Authors: Christopher Szeto, Saihitha Veerapaneni, Kevin Kazmierczak, Stephen Charles Benz, Sandeep K. Reddy, Dongyao Yan
Journal: Journal of Clinical Oncology (2019)

579 Background: Immune contexture shapes oncogenesis, tumor progression and response to therapy. Traditional techniques for studying the microenvironment, such as flow cytometry, are limited by low throughput. Recently, computational methods using transcriptomic data have enabled deconvolution of tumor immune landscape, particularly in colorectal cancer (CRC). However, the immune profiles of other GI and HN cancers remain unclear. We proposed that elucidating the immune compositions in those cancers would reveal biological insights and potentially therapeutic targets. Methods: 464 GI tumors with RNA-Seq data (∼200x10 6 reads per tumor) from a commercial database were available for analysis. Tumors were categorized into CRC, gastroesophageal (GE), HN, and biliary cancer. A curated panel of 122 genes that discriminate between 28 immune subsets was identified. For each of these immune signatures, a database containing 1880 unselected tumors was used to define a distribution of expression. The study samples were then scored for their deviances within such distributions.In addition to immune deconvolution, each of the 464 tumors were assigned to one of the colorectal Consensus Molecular subtypes (CMS). Significant enrichment for immune subsets between locations and CMS was analyzed. Results: Unsupervised clustering revealed 2 clusters with distinct immune profiles, which largely separated CRC from HN/GE tumors (silhouette coefficient = 0.14). Eosinophils are more abundant in GI cancers than others. HN/GE tumors were characterized by abundant NK and Tregs (adj. p &lt; 0.001), and were predominantly classified as the immune-active CMS1 (adj. p &lt; 0.001). CRC was significantly associated with high eosinophils and fibroblasts (adj. p &lt; 0.0001). Biliary tumors spanned both immune-type clusters, and were frequently classified as the stromal-rich CMS4 (adj. p &lt; 0.0001). Immature dendritic cells were sparse in GI tumors, especially GE. Conclusions: Upper and lower GI tumors have distinct immune contextures, which may differentially impact the efficacy of immunotherapy. Comprehensive immune profiling may facilitate the identification of targetable immune subsets.
Multicenter phase Ib/II study of biweekly trifluridine/tipiracil with bevacizumab combination for patients with metastatic colorectal cancer refractory to standard therapies (BiTS study).
Authors: Masahito Kotaka, Hironaga Satake, Koji Oba, Yoshinori Kagawa, Hisateru Yasui, Masato Nakamura, Takanori Watanabe, Toshihiko Matsumoto, Takayuki Kii, Tetsuji Terazawa, Akitaka Makiyama, Nao Takano, Mitsuru Yokota, Yoshihiro Okita, Koreatsu Matoba, Hiroko Hasegawa, Akihito Tsuji, Naoki Nagata, Junichi Sakamoto, Takeshi Kato
Journal: Journal of Clinical Oncology (2019)

647 Background: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (Bmab) combination therapy has shown a promising activity with manageable safety profile in patients (pts) with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this multicenter, phase Ib/II study was to assess the activity and safety of biweekly FTD/TPI with Bmab combination for pts with mCRC who were refractory or intolerant to standard therapies. Methods: Inclusion criteria were ≥ 20 years; histologically confirmed unresectable mCRC; refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type RAS); ECOG PS 0 or 1; evaluable lesion according to the RECIST version 1.1. Phase Ib part is designed to determine the recommended phase II dose (RP2D), and pts received the RP2D in phase Ib part were included in efficacy and safety populations. The primary endpoint in phase II part was an investigator assessed progression-free survival rate at 16 weeks (16w-PFS) with a hypothesis of 15% considered unacceptable and 38.7% deemed promising. Given a one-sided α of 0.025 and statistical power of 90%, a minimum of 40 pts were required for phase II part. Results: From October 2017 to January 2018, totally 46 pts were enrolled (6 pts in phase Ib and 40 pts in phase II). The RP2D was determined to be 5 mg/kg for Bmab and 30 mg/m 2 for FTD/TPI in phase Ib. Of the 44 eligible pts (median age, 69; male, 55%; PS 0, 57%; right-sided primary, 29.5%), 16w-PFS rate was 40.9 % (95% CI: 26.3 to 56.8 %) and the null hypothesis of 16w-PFS rate ≤ 15% was rejected (p &lt; 0.0001). Response rate and disease control rate were 0 % (95 %CI: 0 to 6.6 %) and 59.1 % (95%CI: 43.3 to 73.7 %), respectively. With a median follow up of 5.86 months (range, 1.53-9.79), median PFS was 4.25 months (95% CI: 2.54 to 5.57). Grade 3 or higher adverse events were hypertension (40.9%), neutropenia (11.4 %), leucopenia (11.4 %), anemia (9.1 %), anorexia (9.1 %), nausea (6.8 %), hyperbilirubinemia (6.8 %) and proteinuria (6.8 %). Conclusions: Bi-weekly FTD/TPI plus Bmab showed promising anti-tumor effect with acceptable toxicities. Clinical trial information: UMIN000029198.
Evaluation of Cough Triggers Among Responders and Non-Responders of Treatment with MK-7264, a P2X3 Receptor Antagonist
Authors: Mandel R. Sher, Surinder Birring, J. Smith, L. McGarvey, Alyn H. Morice, Wen-Chi Wu, Jin Xu, David Muccino
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 16628: Perturbations in IK1 and Calcium Handling Underlie CPVT-like Phenotype in a Cardiac-specific R67Q-KCNJ2 Mutant Mouse
Authors: Louise Reilly, Di Lang, Ravi Vaidyanathan, Sara Abozeid, Cordell Spellman, Hanora Van Ert, Samuel Esch, Jarrett Warden, Jonathan C Makielski, Alexey V Glukhov, L L Eckhardt
Journal: Circulation (2016)

Introduction: KCNJ2 mutations are implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT3). We previously reported KCNJ2 mutation R67Q, associated with adrenergic-induced polymor...