tbuckley/cabot-search huggingface dataset:
ACTR-16. RESULTS OF THE OPARATIC TRIAL: A PHASE I DOSE ESCALATION STUDY OF OLAPARIB IN COMBINATION WITH TEMOZOLOMIDE (TMZ) IN PATIENTS WITH RELAPSED GLIOBLASTOMA (GBM)
Authors: Anthony Chalmers, Garth Cruickshank, Laurence Dunn, Sara Erridge, Lisa Godfrey, Christopher Herbert, Sarah Jefferies, Juanita Lopez, Catherine McBain, Marc Pittman, Rebecca Sleigh, Colin Watts, Mark Webster-Smith, Sarah Halford
Journal: Neuro-Oncology (2017)

Olaparib, a small molecule inhibitor of poly(ADP-ribose) polymerase (PARP), may improve GBM outcomes by enhancing the cytotoxic effects of ionising radiation and TMZ. Clinical development of PARP inhibitors in combination with chemotherapy has been restricted by exacerbation of haematological toxicity. We investigated tumour pharmacokinetics (PK) of olaparib and safety and tolerability of its combination with TMZ. Dose escalation explored different schedules of olaparib with daily low dose TMZ. A dose expansion cohort evaluated the maximum tolerated schedule. Olaparib exposure was measured in tumour core, tumour margin and plasma following four doses prior to neurosurgical resection. 48 patients were recruited (median age 51 (18–68); 29 male, 19 female) of whom 27 underwent surgery and 35 received olaparib/TMZ and were evaluable. Olaparib was detected in 73 of 74 tumour core specimens from 27 patients. The mean concentration was 588nM (97-1374nM), similar to breast cancer data. Olaparib was also detected in 27 of 28 tumour margin specimens from 10 patients; mean concentration 500nM (97-1237nM), mean margin:core ratio 1.2 (0. 2–3.9). Although plasma exposure was dose-dependent, no correlation between dose and tumour exposure was seen and tumour:plasma ratios ranged from 0.01 to 0.9 (mean 0.25). Olaparib dosing on days 1–5 was hindered by myelosuppression (3grade 3 in up to 51% of evaluable patients). The expansion cohort dose was defined as TMZ 75mg/m2 daily plus olaparib 150mg (OD) days 1–3 weekly. In the expansion cohort 9/13 patients completed cycle 1, 2/13 completed cycle 2 and 2/13 completed cycle 3. 39% of evaluable (efficacy) patients remained progression-free at 6 months. Olaparib penetrates both core and margins of recurrent GBM despite failing to penetrate the intact blood brain barrier. Combination with low dose TMZ is safe and tolerated, yielding encouraging 6 month progression-free survival rates. Intermittent olaparib dosing is required to mitigate haematological toxicity.
Anastomose hépatico-gastrique guidée sous échoendoscopie: nouvelle voie d'accès aux voies biliaires
Authors: E Bories, C Pesenti, F Caihol, O Jeanniard, M Giovannini
Journal: Endoscopy (2006)

Le but de ce travail était d'évaluer rétrospectivement la faisabilité et l'efficacité du drainage des voies biliaires par voie trans-gastrique sous échoendoscopie en cas d'échec du cathétérisme rétrograde endoscopique.
Pharmacogenetic biomarkers associated with paclitaxel response in Mexican women with locally advanced breast cancer.
Authors: Andric Christopher Perez-Ortiz, Cynthia Villarreal-Garza, Antonio Villa-Romero, Juan Carlos Cruz Lopez, Israel Ramirez-Sanchez, Alexandra Luna-Angulo, Juan Carlos Guerrero-Solorzano, Juan Antonio Matus, José Díaz-Chávez, Brenda Angelica Garcia-Alvarez, Ismar Angelica Rosado-Arenas, Laura Sanchez-Chapul, Francisco Javier Estrada-Mena
Journal: Journal of Clinical Oncology (2016)

e13004 Background: The response to treatment of locally advanced breast cancer (LABC) with paclitaxel varies from 21% to 86%. Potential biomarkers in protein coding genes have been explored this in resistant cancer cell lines. Two of these (SGCD, SNTG1) belong to the dystrophin-associated protein complex (DAPC). This complex is present in normal breast tissue but decreased or absent in benign breast disease. Moreover it colocalizes with subunits of the tubulin. We aim to determine the association between these biomarkers of eight genes, not yet evaluated in patients, with the treatment response. Methods: 94 women with LABC, all naive to any chemotherapy, were initially treated with paclitaxel (80 mg/m2 q12 Weeks). Objective response was documented with digital mammography and/or gammagraphy and assessed with the RECIST criteria 1.1 adapted for this study. Genotyping was performed with TaqMan probes on RT-PCR. We obtained proteins from core biopsies for western-blot. Data was analyzed with SPSS 21. Results: The minor allele of the SGCD gene (AA, AG) (rs7715464) was significantly associated (p=0.02) with stable or progressive disease in LABC patients, in contrast to the rs7731517 (GG or GT) associated with partial or complete response to paclitaxel (p=0.03). Similarly, two SNPs of ROBO1 gene, behave in the same manner, the rs997274 alleles (CC, CT) confers risk no response (p=0.03), contrary to the rs1355983 (GG, GT), trending towards significance (p=0.055) (See Table). In regards of protein expression both δ-sarcoglycan (SGCD) (p=0.046) and γ-1-syntrophin (SNTG1) (p=0.032), levels were significantly decreased compared with controls. Conclusions: Four novel SNPs in two no-cytochrome genes (SGCD and ROBO1) are associated with tumor response to paclitaxel (not to toxicity). Moreover there is a decrease in expression of the DAPC in breast cancer tissue samples that might explain the above. Taken all together, we propose these SNPs as potential response biomarkers in LABC. Significantly associated SNPs. rsID p OR IC95 SGCD rs7715464 0.0242 3.6480 (1.175 —11.329) SGCD rs7731517 0.0305 0.3115 (0.116— 0.838) ROBO1 rs997274 0.0392 3.4560 (1.107—10.786) ROBO1 rs1355983 0.0559 0.3644 (0.138— 0.964)
Patient awareness and expectations of tumor genomic profiling (TGP) may predict willingness-to-pay (WTP) in a diverse patient sample.
Authors: John M. Kaczmar, Elizabeth Handorf, Julie Woods, Jennifer Madeline Matro, Yu-Ning Wong, Yana Chertock, Mary Beryl Daly, Michael J. Hall
Journal: Journal of Clinical Oncology (2016)

e13021 Background: TGP has emerged as an increasingly routine part of treatment planning for cancer. Patients’ awareness and attitudes toward TGP, and the value they place on its impact remain uncertain. Understanding patients’ views and potential barriers to pursuit of TGP is important as they may directly impact uptake of TGP-guided therapies. Methods: A survey examining patient attitudes and knowledge of TGP was administered in the outpatient clinic to a convenience sample of cancer patients at our center. Baseline WTP an OOP cost ( ≤ 200, $500, and ≥ $1000), were presented previously (ASCO 2015, Abstract #1545). Here, hypothetical scenarios describing varying degrees of TGP predictive power (20% vs 80%) were presented to patients and impact on WTP was assessed. Distance patients were willing to travel to obtain an experimental targeted agent was also assessed. Statistical analyses performed to determine associations with WTP. Results: 88 patients with diverse cancers completed surveys. Mean age was 58.9 yrs, 62% were male, 20% non-white, 37% income < $50,000, and 60% were on ≥ 2nd line of therapy. African Americans and those with higher educational attainment held more negative views of TGP and were less likely to think a targetable mutation identified by TGP would impact tumor growth (all p = 0.01). Those with high school education, lower income, and non-private insurance all demonstrated significantly decreased (p < 0.05) WTP for TGP if not covered by insurance. Those with private insurance (p = 0.015) were much more likely to be willing to travel farther to obtain treatment suggested by TGP. In hypothetical scenarios white (0.053), more educated (0.067) and patients with greater awareness of TGP (0.051) were more likely to increase WTP as the predictive power of TGP increased. Conclusions: Differences in income, educational attainment, baseline knowledge of TGP and race gave rise to markedly different expectations of TGP and WTP for testing. As TGP becomes routine practice, improved insurance coverage and/or interventions to better inform patients about TGP may be needed to mitigate disparities and lead to more uniform application of this increasingly important diagnostic tool.
EFFECTS OF ADDITIONAL PERTURBATION ON NEUROMUSCULAR TRUNK ACTIVATION PATTERN DURING CORE-SPECIFIC SENSORIMOTOR EXERCISE
Authors: Juliane Mueller, Omar Baritello, Josefine Stoll, Steffen Mueller, Frank Mayer
Journal: British Journal of Sports Medicine (2017)

Background Sensorimotor exercises (SE) are evident to enhance neuromuscular activity of the trunk muscles (TM). However, it is unclear if an additional unexpected perturbation leads to higher muscular activity and therefore enhances training efficacy. Objective To analyse effects of additional unexpected perturbations on trunk neuromuscular activation pattern during SE. Design Cross-sectional design. Setting University Outpatient Clinic, Sports Medicine Centre. Participants Ten healthy, normal active participants (5 m/5 f; 29±2 yrs; 177±7 cm, 74±12 kg) were included. Assessment of Risk Factors All participants were prepared with a bilateral 12-lead trunk EMG (Mm. rectus abdominis (RA), external obliquus (EO), internal obliquus (IO), latissimus dorsi (LD), thoracic (UES) and lumbar erector spinae (LES)). Warm-up on an isokinetic dynamometer (extension/flexion; 30 rep; 60°sec) was followed by maximum voluntary isometric contraction measurements (MVC, 5 sec). Next, a (right-armed) side plank on stable surface (SP; 30 sec) and 2 different instable conditions were randomly assigned (SP plus pad under the elbow (SPP), SPP plus perturbation (SPP+P)). Main Outcome Measurements Root mean square (RMS) normalized to MVC (%MVC) was calculated during the whole exercise. Muscles were grouped to ventral right/left (VR;VL=mean of RA, IO, EO), and dorsal right/left (DR;DL=mean of LD, UES, LES). Differences between conditions were calculated for muscle groups, Ventral:Dorsal (V:D) and Side-Right/Side-Left ratio (S R ;S L ) (repeated-measures ANOVA; α=0.05). Results SPP+P showed highest EMG-RMS (e.g,VR: 81±9%; DR: 55±12%) for all muscle groups except DL with significant differences (p&lt;0.05) between conditions SP and SPP+P in VR, VL and DR muscle groups. No differences were found between SPP (e.g.,VR: 71±11%) and SPP+P (e.g.,VR: 81±9%)(p&gt;0.05). Statistically significant higher V:D ratios was found in SPP+P compared to SP (p&lt;0.05). S R :S L ratio did not show any differences (p&gt;0.05). Conclusions The use of additional perturbations during core stability training is superior to enhance trunk neuromuscular activity and should be implemented into sensorimotor exercises addressing the trunk.
Phytochemical study of Illicium angustisepalum and its biological activities
Authors: Karina M. Szymulanska-Ramamurthy, Ming Zhao, Chun-Tao Che
Journal: Acta Pharmaceutica Sinica B (2017)

Sixteen compounds, including two new natural products (1 and 2), were obtained from the twigs of Illicium angustisepalum. The structures were elucidated based on NMR, MS, IR data and optical rotation values. Compounds 4, 5, 6 and 8 displayed moderate antibacterial activities against clinical isolates; compounds 4, 5, 8, 9 and 15 protected neural cells against oxidative stress; and compounds 10 and 14 exhibited anti-acetylcholinesterase activity.
RECRUITMENT OF BICEPS FEMORIS MUSCLE REGIONS AT DIFFERENT RUNNING SPEEDS
Authors: András Hegyi, Basílio Gonçalves, Taija Finni, Neil Cronin
Journal: British Journal of Sports Medicine (2017)

Background The majority of hamstring strain injuries (HSIs) occur in the late swing phase of high-speed running when hamstrings work eccentrically. The proximal region of the biceps femoris (BF) seems to be the most common site of injury. Elongation of the fascicles in eccentric contractions is higher in the proximal region compared to the distal region of BF, but the neural background to this phenomenon is not clear. Objective To examine the region-specificity of BF muscle activity at different running speeds. Design Observational study. Running speeds were randomized. Setting Laboratory, amateur level. Participants Football players without acute injury/illness, and without HSI history were recruited. Data collection is ongoing; six players have been measured and analysed so far. Assessment After warm-up, players ran on a treadmill at 12, 15, 18 km/h, and maximum speed. Electromyographic activity (EMG) along the BF and joint angular displacements were recorded with a 16-channel high-density EMG array and 3-D motion analysis, respectively. EMG data were normalized to maximal voluntary isometric contraction. Main Outcome Measures Normalized root-mean-square activity was calculated in the proximal, middle and distal muscle regions, and BF elongation was calculated using musculoskeletal modelling. Results Higher BF elongation and activity were observed in all regions with increasing speed. Activity in the proximal region was lower compared to the distal region at 15, 18 km/h and maximum speed, by 12, 18, and 35%, respectively. Conclusions Lower relative activity in the proximal region and greater proximal-distal differences in activity with increasing speed may indicate why HSIs occur at higher speeds, and mainly in the proximal region. Lower proximal activity may be associated with the higher elongation in this region during eccentric contractions that has been reported previously. Future studies are needed to examine whether players with higher within-muscle heterogeneity in muscle recruitment are at higher risk for HSI.
Conventional Polysomnography Is Not Necessary for the Management of Most Patients with Suspected Obstructive Sleep Apnea. Noninferiority, Randomized Controlled Trial
Authors: Jaime Corral, Maria-Ángeles Sánchez-Quiroga, Carmen Carmona-Bernal, Ángeles Sánchez-Armengol, Alicia Sánchez de la Torre, Joaquín Durán-Cantolla, Carlos J. Egea, Neus Salord, Carmen Monasterio, Joaquín Terán, M. Luz Alonso-Alvarez, Jesús Muñoz-Méndez, Eva M. Arias, Marta Cabello, Josep M. Montserrat, Mónica De la Peña, José C. Serrano, Ferran Barbe, Juan F. Masa, Ricardo Pereira, Estefanía Garcia-Ledesma, Francisco J. Gómez de Terreros, Miguel Merchan, Pedro Mañas, M. Isabel Asensio-Cruz, Silvia Gómez, Anunciación Cortijo, Ainhoa Álvarez-Ruiz de Larrinaga, Jaime Marcos Cabrero, Mercé Gasa, Sandra Pérez-Ramos, Estrella Ordax, Trinidad Díaz-Cambriles, M. Ángeles Martínez-Martínez, Olga Cantalejo, Marta Torres, Nuria Toledo-Pons, Ángel Ortega-González, F. Javier Barca
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Home respiratory polygraphy may be a simpler alternative to in-laboratory polysomnography for the management of more symptomatic patients with obstructive sleep apnea, but its effectiveness has not been evaluated across a broad clinical spectrum.To compare the long-term effectiveness (6 mo) of home respiratory polygraphy and polysomnography management protocols in patients with intermediate-to-high sleep apnea suspicion (most patients requiring a sleep study).A multicentric, noninferiority, randomized controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in 12 tertiary hospitals in Spain. Sequentially screened patients with sleep apnea suspicion were randomized to respiratory polygraphy or polysomnography protocols. Moreover, both arms received standardized therapeutic decision-making, continuous positive airway pressure (CPAP) treatment or a healthy habit assessment, auto-CPAP titration (for CPAP indication), health-related quality-of-life questionnaires, 24-hour blood pressure monitoring, and polysomnography at the end of follow-up. The main outcome was the Epworth Sleepiness Scale measurement. The noninferiority criterion was -2 points on the Epworth scale.In total, 430 patients were randomized. The respiratory polygraphy protocol was noninferior to the polysomnography protocol based on the Epworth scale. Quality of life, blood pressure, and polysomnography were similar between protocols. Respiratory polygraphy was the most cost-effective protocol, with a lower per-patient cost of 416.7€.Home respiratory polygraphy management is similarly effective to polysomnography, with a substantially lower cost. Therefore, polysomnography is not necessary for most patients with suspected sleep apnea. This finding could change established clinical practice, with a clear economic benefit. Clinical trial registered with www.clinicaltrials.gov (NCT 01752556).
The Prognostic Value of Fasting Plasma Glucose, Two-Hour Postload Glucose, and HbA1c in Patients With Coronary Artery Disease: A Report From EUROASPIRE IV
Authors: Bahira Shahim, Dirk De Bacquer, Guy De Backer, Viveca Gyberg, Kornelia Kotseva, Linda Mellbin, Oliver Schnell, Jaakko Tuomilehto, David Wood, Lars Rydén
Journal: Diabetes Care (2017)

OBJECTIVE Three tests are recommended for identifying dysglycemia: fasting glucose (FPG), 2-h postload glucose (2h-PG) from an oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). This study explored the prognostic value of these screening tests in patients with coronary artery disease (CAD). RESEARCH DESIGN AND METHODS FPG, 2h-PG, and HbA1c were used to screen 4,004 CAD patients without a history of diabetes (age 18–80 years) for dysglycemia. The prognostic value of these tests was studied after 2 years of follow-up. The primary end point included cardiovascular mortality, nonfatal myocardial infarction, stroke, or hospitalization for heart failure and a secondary end point of incident diabetes. RESULTS Complete information including all three glycemic parameters was available in 3,775 patients (94.3%), of whom 246 (6.5%) experienced the primary end point. Neither FPG nor HbA1c predicted the primary outcome, whereas the 2h-PG, dichotomized as &amp;lt;7.8 vs. ≥7.8 mmol/L, was a significant predictor (hazard ratio 1.38, 95% CI 1.07–1.78; P = 0.01). During follow-up, diabetes developed in 78 of the 2,609 patients (3.0%) without diabetes at baseline. An FPG between 6.1 and 6.9 mmol/L did not predict incident diabetes, whereas HbA1c 5.7–6.5% and 2h-PG 7.8–11.0 mmol/L were both significant independent predictors. CONCLUSIONS The 2h-PG, in contrast to FPG and HbA1c, provides significant prognostic information regarding cardiovascular events in patients with CAD. Furthermore, elevated 2h-PG and HbA1c are significant prognostic indicators of an increased risk of incident diabetes.
A polymorphism in the interferon stimulated gene PKR is not associated with the persistence of hepatitis C viraemia in a homogenous population of irish females
Authors: DS Manning, M O'Brien, CP O'Brien, JE Hegarty, C O'Farrelly
Journal: Endoscopy (2006)

Aims: Complex host and viral factors interact to determine the outcome of Hepatitis C viral (HCV) infection. It has not been determined whether the signalling pathway and production of interferon alpha is defective in patients who fail to spontaneously clear HCV.
Serum Sphingolipids Level as a Novel Potential Indicator for Early Detection of Cardiac Ischemia
Authors: Egom Eea., M A Mamas, S Chacko, S E Stringer, V Charlton-Menys, M El-Omar, D Chirico, B Clarke, L Neyses, K J Cruickshank, M Lei, F Fath-Ordoubadi
Journal: Circulation (2010)
Health-Related Quality of Life and Costs Associated With Eosinophilic Esophagitis: A Systematic Review
Authors: Vincent Mukkada, Gary W. Falk, Christian S. Eichinger, Denise King, Lora Todorova, Nicholas J. Shaheen
Journal: Clinical Gastroenterology and Hepatology (2017)

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal inflammation and dysfunction. Little is known about the humanistic and economic burden of the disease on patients, their caregivers, and the health care system. A systematic review was conducted to evaluate the existing literature on the disease burden of EoE for patients and their caregivers.The MEDLINE, Embase, and Evidence-Based Medicine Reviews databases and recent congresses were searched on March 23, 2017, for English-language publications describing the impact of EoE on health-related quality of life (HRQoL) in children and adults, and the economic burden associated with the disease.Of 676 articles identified, 22 met the inclusion criteria and were included in this analysis (HRQoL, 13; economic burden, 7; cost effectiveness, 2). The included studies showed that EoE is associated with a significant impact on HRQoL, resulting in disruption to and restrictions on daily life for patients, their caregivers, and, in some instances, their families. Treatment with topical corticosteroids, the 6-food elimination diet, or the cow's milk elimination diet significantly improved the HRQoL of patients with EoE. Symptom severity was associated strongly with the impact of EoE on HRQoL. Medical resource utilization costs for patients with EoE were significantly higher than those for healthy controls.EoE negatively impacts the HRQoL of patients and their families, and is a burden to the health care system. Although data are sparse, currently available treatments appear to improve HRQoL.
Abstract 1290: Impaired Re-Endothelialization Capacity of Endothelial Progenitor Cells (EPCs) and Endothelial Dysfunction in Patients with Pre-Hypertension
Authors: Giovanna Giannotti, Maja Mueller, Carola Doerries, Tibor Horvath, Sajosha Sorrentino, Kristina Sonnenschein, Costantina Manes, Nora Steenken, Helmut Drexler, Ulf Landmesser
Journal: Circulation (2007)
Efficacité de la Mitomycine C dans le traitement des récidives de sténoses courtes de l'oesophage chez l'enfant: résultats préliminaires
Authors: S Uhlen, P Fayoux, F Vachin, F Gottrand, L Michaud
Journal: Endoscopy (2005)

L'efficacité de l'application locale de Mitomycine C (antibiotique possédant une activité antimitotique similaire à celle des agents alkylants) a été démontrée dans le traitement des sténoses trachéales ou laryngées en ORL et suggérée, par quelques observations cliniques isolées dans la prévention des sténoses de l'œsophage après dilatation. Le but de cette étude était d'évaluer l'efficacité et la tolérance d'une application locale de Mitomycine C dans le traitement et la prévention de la récidive des sténoses courtes de l'œsophage chez l'enfant.
Individualized Prophylactic Treatment with Recombinant Factor VIII in Severe or Moderate Haemophilia a Patients. Association Between Pharmacokinetic Parameters and Clinical Variables
Authors: Juan Eduardo Megías-Vericat, María Remedios Marqués, Saturnino Haya, Ana Rosa Cid, Felipe Querol, Emilio Monte, María García-Dasí, Patricia Caunedo, Carmen Vila, Pau Bosch, Rafael Curats, Miguel Ángel Sanz, José Luis Poveda, Santiago Bonanad
Journal: Blood (2016)
From basal cell carcinoma morphogenesis to the alopecia induced by hedgehog inhibitors: connecting the dots
Authors: C. Dessinioti, C. Antoniou, A.J. Stratigos
Journal: British Journal of Dermatology (2017)

The deciphering of the hedgehog (Hh) signalling pathway implicated in the tumorigenesis of basal cell carcinoma (BCC) led to the development of targeted drug therapies, the Hh pathway inhibitors (HPIs) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles (HFs), where it is required for proliferation of the epithelium of HFs during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia underpin the central role of the Hh pathway in BCC formation, as well as hair cycling. Given the fact that BCC is a follicular‐driven tumour, it is a fine tuning of events that regulate hair cycling that may drive towards the formation of benign follicular hamartomas or malignant BCC neoplasms. Wnt/β‐catenin signalling interacts with the Hh signalling during HF morphogenesis, normal hair cycling and BCC development. The aim of this review is to present how key molecular events implicated in Hh pathway crosstalk in the HF are also involved in BCC pathogenesis and result in the alopecia developed by HPI treatment.