tbuckley/cabot-search huggingface dataset:
Clinical application of comprehensive next-generation sequencing-based genomic profiling for identification of actionable genomic alterations in pediatric solid tumors and hematolymphoid malignancies: The Foundation Medicine pediatric experience.
Authors: Matthew J. Hawryluk, Kai Wang, Juliann Chmielecki, Siraj M. Ali, Gary A. Palmer, Sean Downing, John Curran, Lazaro Garcia, Emily White, Doron Lipson, Roman Yelensky, Philip J. Stephens, Vincent A. Miller, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2014)

10035 Background: Oncology is undergoing a paradigm shift with the advent and increasingly successful utilization of targeted therapies. Unfortunately, many pediatric tumors lack approved targeted therapies, and routine genomic profiling of pediatric tumors has yet to be broadly applied. Comprehensive testing platforms are required to determine the landscape of genomic alterations in pediatric solid tumors and thereby broaden therapeutic options. We have developed a next-generation sequencing-based test, optimized for routine clinical FFPE specimens, and report here on over 340 pediatric patients’ tumors analyzed to date in our CLIA-certified, CAP-accredited laboratory. Methods: Hybridization capture of 3,320 exons from 182 cancer-related genes and 37 introns of 14 genes commonly rearranged in cancer (previous version of the test) or 3,769 exons from 236 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer (current version of the test) was applied to ≥ 50ng of DNA extracted from over 340 pediatric tumors. Genomic alterations were identified and reported for these patient samples. Results: Successful profiles were generated from 343 pediatric patient specimens from individuals ≤21 years old at the time of sample procurement. The pediatric clinical experience consists of: adrenal and soft tissue neuroblastomas (n=83), sarcomas (n=53), brain (n=42), bone sarcomas (n=26), leukemias (n=30), rhabdomyosarcomas (n=17), liver (n=16), kidney (n=14), lung (n=13), lymphomas (n=7), and other tumors (n=42). Conclusions: Comprehensive NGS-based genomic profiling identified alterations in a majority of 343 unselected pediatric cancer clinical cases and more than half of these patients were found to have at least one alteration targeted by a therapeutic on the market or in clinical trials. Widespread deployment of this approach may provide treatment options for pediatric cancer patients requiring systemic approaches.
Do neurocognitive scat3 test scores differ between non-concussed national footballers living with and without disability? a cross-sectional study
Authors: Richard Weiler, Willem Van Mechelen, Colin Fuller, Osman Ahmed, Evert Verhagen
Journal: British Journal of Sports Medicine (2017)

Objective To determine if cross-sectional differences exist using SCAT3 scores for non-concussed England footballers with and without disability. Design Cross-sectional between group comparison of first-time collected SCAT3 scores. Setting All England team doctors and physiotherapists commenced between 1st August 2013 and 31st July 2014 standardised annual SCAT3 testing on England footballers following the Zurich 2012 concussion guidelines. Participants A convenience sample of England national football team players (total: 249; male: 174, female: 75), of whom 185 were athletes without disability (male: 119; female: 66) and 64 athletes with disability (male learning disability: 17; male cerebral palsy: 28; male blind: 10; female deaf: 9). Assessment and outcome measures Comparison between groups of median SCAT3 section scores was made with the non-parametric Mann-Whitney-Wilcoxon ranked-sum test. Main results Compared to male footballers without disability, male footballers with disability scored significantly higher for total number of symptoms and symptom severity. However, male footballers with learning disability demonstrated no difference with total number of symptoms and scored significantly lower on immediate memory and delayed recall . Male blind footballers scored significantly higher for total concentration and delayed recall. Male footballers with cerebral palsy scored significantly higher on balance testing and significantly lower on immediate memory. Conclusions The results of this study suggest that significant cross-sectional between-group variability exists in SCAT3 section scores when non-concussed footballers with disability are compared to footballers without disability. Future concussion consensus guidelines should recognise these between group differences and generate separate SCAT3 guidelines for the growing number of elite athletes living with disability. Competing interests None.
French comment on article Detection of lesions in dysplastic Barrett’s esophagus by community and expert endoscopists1 Détection de lésions dysplasiques sur EBO par endoscopistes expert et communautaires
Journal: Endoscopy (2017)

Le risque annuel de dégénérescence d’un endobrachyoesophage (EBO) est très faible, estimé à environ 0,3 %. Cependant, lorsqu’il existe des lésions de dysplasie de bas grade (sous réserve qu’elles soient confirmées par un anatomopathologiste expert), ce risque croit pour atteindre 4,7 à 13,4 % par an selon les études. De plus, des études suggèrent qu’une surveillance endoscopique adéquate est corrélée à une détection de cancer à un stade précoce et à une meilleure survie. En outre, l’ablation par radiofréquence des lésions planes, ou la résection des lésions en relief permettent un traitement rapide en cas de découverte de lésions dysplasiques. L’ensemble de ces éléments plaide en faveur de la surveillance des patients ayant un EBO, mais pose le problème de la capacité des endoscopistes à identifier les lésions dysplasiques au cours de la surveillance, et du type de centre devant réaliser la prise en charge thérapeutique des EBO.
Re: Umberto Leone Roberti Maggiore, Simone Ferrero, Massimo Candiani, et al. Bladder Endometriosis: A Systematic Review of Pathogenesis, Diagnosis, Treatment, Impact on Fertility, and Risk of Malignant Transformation. Eur Urol 2017;71:790–807
Authors: Rodolfo Montironi, Silvia Gasparrini, Antonio Lopez-Beltran, Liang Cheng, Francesco Massari, Francesco Montorsi, Marina Scarpelli
Journal: European Urology (2017)
Omega-3 fatty acids for aromatase inhibitor–induced musculoskeletal symptoms in women with early-stage breast cancer (SWOG S0927).
Authors: Dawn L. Hershman, Joseph M. Unger, Katherine D. Crew, Shaker R. Dakhil, Danielle Awad, Heather Greenlee, Lori M. Minasian, Lisa Hansen, Danika Lew, Julie Gralow, James Lloyd Wade, Frank L. Meyskens, Carol Moinpour
Journal: Journal of Clinical Oncology (2014)

9532 Background: Musculoskeletal symptoms are the most common side effect of aromatase inhibitors (AIs) and can result in decreased quality of life and discontinuation of therapy. Omega-3-fatty acids (O3-FAs) have anti-inflammatory effects and can be effective in decreasing arthralgias from rheumatologic conditions. Omega-3 fatty acids are used by 25% of breast cancer survivors. Methods: Women with early-stage breast cancer, taking an AI for ≥90 days and who had a worst pain/stiffness score of ≥5 of 10 using the Brief Pain Inventory (BPI-WP) were randomized to receive either 3.3 grams of O3-FAs or placebo (soybean/corn oil) daily for 12 weeks. Subjects completed quality of life (FACT-ES) and pain assessment (WOMAC, M-SACRAH) at baseline, weeks 6, 12 and 24. Multiple linear regression was used to examine the difference in BPI-WP (primary outcome) between the two groups. Clinically significant change was defined as ≥2-point drop from baseline. Results: Among 262 patients registered, 249 were considered evaluable with 122 women in the O3-FA arm and 127 in the placebo arm. No notable imbalances by arm were observed. Baseline BPI-WP was 6.98 and 7.09 in the O3-FA and placebo groups respectively. The mean observed BPI-WP score decreased by 1.74 points at 12 weeks compared to baseline with omega-3, decreased by1.50 points with placebo and decreased further by 24 weeks (2.22 & 1.81 points, respectively) despite discontinuation at 12 weeks. In a linear regression adjusting for the baseline score, osteoarthritis and taxane use, adjusted 12-week BPI-WP scores were similar in both arms (p=0.58). The proportion of patients with a ≥ 2-point drop in 12 week BPI -WP was 61% on Omega-3 and 57% on Placebo, p=.44. O3-FAs resulted in increased grade ≥1 diarrhea (15 vs 6 patients). Serial fasting blood is being analyzed for cholesterol and inflammatory markers. Conclusions: We found a substantial (60%) and sustained improvement of AI arthralgias with both the omega-3 and placebo, but found no meaningful difference between the groups. These results suggest either the placebo (soybean/corn oil) had beneficial effects or that a large placebo effect should be expected when conducting trials for AI arthralgias. Clinical trial information: NCT01385137.
Pertuzumab in combination with trastuzumab plus an aromatase inhibitor in patients with hormone receptor-positive, HER2-positive metastatic breast cancer: A randomized phase II study (PERTAIN).
Authors: Mothaffar F. Rimawi, Christopher John Poole, Jean-Marc Ferrero, Juan R. De la Haba Rodriguez, Lada Mitchell, Christina H. Pelizon, Grazia Arpino
Journal: Journal of Clinical Oncology (2012)

TPS654^ Background: Resistance to endocrine therapy in patients (pts) with breast cancer remains a major clinical concern. Preclinical studies suggest that complete blockade of the hormone receptor (HR) combined with the inhibition of HER family members may be necessary to overcome resistance and improve clinical outcome in HR-positive and HER2-positive breast cancer (BC). The combination of pertuzumab (P) and trastuzumab (H) with docetaxel significantly improves patient outcome by blocking, more efficiently and completely, the HER signalling pathway. This benefit, however, may be smaller in HR-positive patients. PERTAIN is the first clinical trial to study whether a more potent blockade of the HER pathway with P and H in combination with endocrine therapy may restore or enhance endocrine sensitivity of HER2-positive BC and provide an effective treatment option in pts with HER2-positive and HR-positive MBC. Methods: PERTAIN is a multicenter, open-label, Phase II trial for post-menopausal women with HER2- and HR-positive BC, studying the efficacy of the combination of P plus H with an aromatase inhibitor (AI) as first-line therapy for MBC. Pts will be randomized 1:1 to Arm 1 (P: 840 mg loading dose, 420 mg q3w IV; H: 8 mg/kg loading dose, 6 mg/kg q3w IV; AI [anastrozole 1 mg or letrozole 2.5 mg qd po]) or Arm 2 (H + AI at same dose as Arm 1). Pts in either arm may also receive induction chemotherapy (docetaxel or paclitaxel) for up to 18 weeks at the investigator’s discretion. Study medication will be administered until disease progression or unacceptable toxicity. Pts must not have previously been treated with anti-HER2 agents except H and/or lapatinib in the (neo)adjuvant setting, and must have no CNS involvement or clinically significant cardiovascular disease. The primary endpoint is PFS, and secondary endpoints include overall survival, overall response rate, clinical benefit rate, duration of response, time to response, safety and tolerability, and quality of life. The study opened in January 2012 and will recruit 250 pts. Analysis of the primary endpoint will be performed after 165 PFS events using the Kaplan-Meier approach.
Mathematical fixation: Search viewed through a cognitive lens
Authors: Steven Phillips, Yuji Takeda
Journal: Behavioral and Brain Sciences (2017)

Abstract We provide a mathematical category theory account of the size and location of the authors' Functional View Field (FVF). Category theory explains systematic cognitive ability via universal construction, that is, a necessary and sufficient condition for composition of cognitive processes. Similarly, FVF size and location is derived from a (universal) construction called a fibre (pullback) bundle.
An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever
Authors: Nga Tran Vu Thieu, Tan Trinh Van, Anh Tran Tuan, Elizabeth J. Klemm, Chau Nguyen Ngoc Minh, Phat Voong Vinh, Duy Pham Thanh, Thanh Ho Ngoc Dan, Trung Pham Duc, Pinky Langat, Laura B. Martin, Jorge Galan, Li Liang, Philip L. Felgner, D. Huw Davies, Hanna K. de Jong, Rapeephan R. Maude, Masako Fukushima, Lalith Wijedoru, Aniruddha Ghose, Rasheda Samad, Arjen M. Dondorp, Abul Faiz, Thomas C. Darton, Andrew J. Pollard, Guy E. Thwaites, Gordon Dougan, Christopher M. Parry, Stephen Baker
Journal: Journal of Infection (2017)

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients.IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease.IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid.We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations.
Emoticons in text may function like gestures in spoken or signed communication
Authors: Laurie Beth Feldman, Cecilia R. Aragon, Nan-Chen Chen, Judith F. Kroll
Journal: Behavioral and Brain Sciences (2017)

Abstract We draw parallels between emoticons in textual communication and gesture in signed language with respect to the interdependence of codes by describing two contexts under which the behavior of emoticons in textual communication resembles that of gesture in speech. Generalizing from those findings, we propose that gesture is likely characterized by a nuanced interdependence with language whether signed, spoken or texted.
Thrombopoietin-Receptor Agonist in Systemic Lupus Erythematosus Associated Immune Thrombocytopenia: Results of the 16 Patients from the French Cohort
Authors: Louis Terriou, Zelie Guitton, Miguel Hie, Zahir Amoura, James B. Bussel, Mohamed Hamidou, Eric Rosenthal, jean-Christophe Lega, Raphaele nove-Josserand, Bertrand Lioger, Axel Chaminade, Nadine magy-Bertrand, Sylvain Audia, Matthieu Mahevas, Bertrand Godeau
Journal: Blood (2016)
Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use
Authors: Aaron L. Baggish, Rory B. Weiner, Gen Kanayama, James I. Hudson, Michael T. Lu, Udo Hoffmann, Harrison G. Pope
Journal: Circulation (2017)

Background: Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Methods: Using a cross-sectional cohort design, we recruited 140 experienced male weightlifters 34 to 54 years of age, comprising 86 men reporting ≥2 years of cumulative lifetime AAS use and 54 nonusing men. Using transthoracic echocardiography and coronary computed tomography angiography, we assessed 3 primary outcome measures: left ventricular (LV) systolic function (left ventricular ejection fraction), LV diastolic function (early relaxation velocity), and coronary atherosclerosis (coronary artery plaque volume). Results: Compared with nonusers, AAS users demonstrated relatively reduced LV systolic function (mean±SD left ventricular ejection fraction = 52±11% versus 63±8%; P &lt;0.001) and diastolic function (early relaxation velocity = 9.3±2.4 cm/second versus 11.1±2.0 cm/second; P &lt;0.001). Users currently taking AAS at the time of evaluation (N=58) showed significantly reduced LV systolic (left ventricular ejection fraction = 49±10% versus 58±10%; P &lt;0.001) and diastolic function (early relaxation velocity = 8.9±2.4 cm/second versus 10.1±2.4 cm/second; P =0.035) compared with users currently off-drug (N=28). In addition, AAS users demonstrated higher coronary artery plaque volume than nonusers (median [interquartile range] 3 [0, 174] mL 3 versus 0 [0, 69] mL 3 ; P =0.012). Lifetime AAS dose was strongly associated with coronary atherosclerotic burden (increase [95% confidence interval] in rank of plaque volume for each 10-year increase in cumulative duration of AAS use: 0.60 SD units [0.16–1.03 SD units]; P =0.008). Conclusions: Long-term AAS use appears to be associated with myocardial dysfunction and accelerated coronary atherosclerosis. These forms of AAS-associated adverse cardiovascular phenotypes may represent a previously underrecognized public-health problem.
MEDU-48. MRI TEXTURAL FEATURES CAN DIFFERENTIATE PEDIATRIC POSTERIOR FOSSA TUMORS
Authors: Niha Beig, Ramon Correa, Rajat Thawani, Prateek Prasanna, Chaitra Badve, Deborah Gold, Anant Madabhushi, Peter deBlank, Pallavi Tiwari
Journal: Neuro-Oncology (2017)

BACKGROUND: Medulloblastoma (MB), Ependymomas (EP), & Gliomas are the most common posterior fossa (PF) tumors in children. Reliable, non-invasive biomarker that can distinguish these tumor types would significantly aid clinical management. We recently developed a new computerized descriptor, CoLlAGe, that distinguishes subtly-different pathologies in adult brain tumors. CoLlAGe measures the orientation of local intensity gradients as an estimate of lesion heterogeneity. In this work, we hypothesize that CoLlAGe can identify subtle micro-architectural differences between MB, EP and Glioma on routine MRI scans. METHODS: A retrospective cohort of 59 studies (MB = 22, EP = 12, Glioma = 25) was acquired. After registration, scans were age normalized, skull-stripped, and corrected for intensity inhomogeneities. Every lesion was then expert delineated to obtain a region of interest (ROI). 52 CoLlAGe features were extracted from every ROI for every MRI sequence (T1w, T2w, FLAIR). Wilcoxon rank sum test was used to identify top 10 CoLlAGe features within a training set of 30 patients (MB = 11, EP = 6, G = 13), for differentiating MB from (EP+Glioma), & Glioma from (MB+EP). Using top features, random forest classifiers were built for every sequence, and validated on an independent set of 29 studies (MB = 11, EP = 6, G = 12) by using area under receiver operating characteristic curve (AUROC). RESULTS: On the independent set, we found that sum variance and entropy of CoLlAGe (p< 0.002) on T2w protocol could reliably distinguish MB from (EP+Gliomas) (AUROC = 0.88), and entropy and sum average of CoLlAGe on T2w (p < 0.0003) could differentiate Gliomas from (MB+EP) (AUROC = 0.72). CONCLUSION: Our results suggest that entropy feature of CoLlAGe, a measure of tumor heterogeneity, enabled discrimination of MB from (EP+Glioma). Prospective validation of these features in a larger cohort may improve personalized treatment management for PF tumors.
ENTEROSCOPIA DE MONOBALÓN: ¿ES COMPARABLE A LA ENTEROSCOPIA DE DOBLE BALÓN?
Authors: G Gómez Quiceno, C Romero Mascarell, C Rodriguez-De Miguel, A Gines, G Fernández-Esparrach, O Sendino, A Cárdenas, H Córdova, J Llach, B González-Suárez
Journal: Endoscopy (2015)

Introducción: La Enteroscopia de Monobalón (EM) es una alternativa diagnóstica y terapéutica en el estudio del intestino delgado. Los datos actuales acerca de esta técnica parecen ser comparables a los resultados de la Enteroscopia de Doble Balón (EDB) aunque la experiencia es más limitada.
Using episodic memory to gauge implicit and/or indeterminate social commitments
Authors: John Michael, Marcell Székely, Wayne Christensen
Journal: Behavioral and Brain Sciences (2018)

Abstract In discussing Mahr &amp; Csibra's (M&amp;C's) observations about the role of episodic memory in grounding social commitments, we propose that episodic memory is especially useful for gauging cases of implicit commitment and cases in which the content of a commitment is indeterminate. We conclude with some thoughts about how commitment may relate to the evolution of episodic memory.
Sequence-dependent combination effect of NK012, a novel micellar nanoparticle of SN-38, with 5-fluorouracil in mouse colon cancer model.
Authors: Takeshi Onda, Hiroko Mashiba, Chieko Seno, Shin-ichi Matsumoto, Eiji Ichimura, Takemitsu Nagahata, Kazuya Okamoto, Kiyohiro Nishikawa
Journal: Cancer Research (2008)

5626  Irinotecan hydrochloride (CPT-11) is widely used for the treatment of advanced colorectal cancer in combination with 5-fluorouracil (5-FU), but its low conversion rate to an active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), and low retention in tumor tissue limit the antitumor effect. To exploit therapeutic potential of SN-38 by optimizing its pharmacokinetic properties, we have successfully developed NK012, SN-38-encapsulated nanoparticle, and reported that NK012 drastically improved intratumoral SN-38 delivery and exhibited the superior antitumor activity to CPT-11 in liver metastatic tumor model of colorectal cancer (2007 AACR Annual Meeting, #1495). In the present study, we evaluated the combination effect of NK012 and 5-FU in mouse Colon 26 cancer model. First, we compared the effect of administration sequences of 10 mg/kg of NK012 (20% of MTD, iv) and 80 mg/kg of 5-FU (50% of MTD, iv) in the following three combination: (a) simultaneous administration, (b) 5-FU followed by NK012 on the next day, and (c) NK012 followed by 5-FU on the next day, starting when the tumor reached 100-200 mm3 in size. The time requiring to reach 4 times of the initial tumor volume was determined for each group and its delay over control group produced treatment was calculated as TGD as the ratio of control. The TGD were 118%, 118%, and 178% for the sequence of (a), (b) and (c), respectively, indicating that a sequence of NK012 followed by 5-FU is superior to the concurrent administration or the reverse sequence. Next, combination effect of NK012 (25 mg/kg) followed by 5-FU (80 mg/kg) was compared with that of CPT-11 (67 mg/kg) and 5-FU. The higher dose combination of NK012 and 5-FU produced superior antitumor efficacy (TGD = 437%) to that of CPT-11 and 5-FU (TGD = 153%). These results indicate that NK012 maximizes combined therapeutic benefit of SN-38 over CPT-11 in combination with 5-FU. The improved efficacy of NK012 might be accounted for by the prolonged exposure time to SN-38 released from the micellar NK012, which specifically accumulated in tumor tissue due to leakiness of tumor blood vessel to nanosize molecules.
A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis
Authors: F Passamonti, T Giorgino, B Mora, P Guglielmelli, E Rumi, M Maffioli, A Rambaldi, M Caramella, R Komrokji, J Gotlib, J J Kiladjian, F Cervantes, T Devos, F Palandri, V De Stefano, M Ruggeri, R T Silver, G Benevolo, F Albano, D Caramazza, M Merli, D Pietra, R Casalone, G Rotunno, T Barbui, M Cazzola, A M Vannucchi
Journal: Leukemia (2017)