tbuckley/cabot-search huggingface dataset:
Alginate nanobeads interspersed fibrin network as in situ forming hydrogel for soft tissue engineering
Authors: S. Deepthi, R. Jayakumar
Journal: Bioactive Materials (2017)

Hydrogels are a class of materials that has the property of injectability and in situ gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200-500 nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the in situ injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19 kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed in situ forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.
Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results
Authors: Robert J. Motzer, Alain Ravaud, Jean-Jacques Patard, Hardev S. Pandha, Daniel J. George, Anup Patel, Yen-Hwa Chang, Bernard Escudier, Frede Donskov, Ahmed Magheli, Giacomo Carteni, Brigitte Laguerre, Piotr Tomczak, Jan Breza, Paola Gerletti, Mariajose Lechuga, Xun Lin, Michelle Casey, Lucile Serfass, Allan J. Pantuck, Michael Staehler
Journal: European Urology (2017)
The pruritogenic mediator endothelin‐1 shifts the dendritic cell–T‐cell response toward Th17/Th1 polarization
Authors: T. Nakahara, M. Kido‐Nakahara, F. Ohno, D. Ulzii, T. Chiba, G. Tsuji, M. Furue
Journal: Allergy (2017)

Abstract Endothelin‐1 ( ET ‐1) is associated with skin diseases such as atopic dermatitis ( AD ) and psoriasis. ET ‐1 is enhanced in the skin of patients AD and psoriasis. In addition, plasma levels of ET ‐1 are elevated in AD and psoriasis. Although both AD and psoriasis are T‐cell–mediated skin diseases, the association between ET ‐1 and the T‐cell immune response has not been clarified. To evaluate the role of ET ‐1 in inflammatory skin disease, we sought to investigate the effects of ET ‐1 on the functions of dendritic cells ( DC s) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET ‐1 in the epidermis of patients with AD or psoriasis. ET ‐1 directly induced phenotypic maturation of bone marrow‐derived DC s ( BMDC s). In addition, ET ‐1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDC s. Interestingly, ET ‐1–activated BMDC s primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET ‐1 polarizes the DC –T‐cell response toward Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.
Updated results of phase 1b study of tarextumab (TRXT, anti-Notch2/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC).
Authors: Anne C. Chiang, Charles M. Rudin, Alexander I. Spira, Robert M. Jotte, Shirish M. Gadgeel, Alain C. Mita, Lowell L. Hart, William Larry Gluck, Stephen V. Liu, Ann M. Kapoun, Lu Xu, Dawn Hill, Lei Zhou, Jakob Dupont, David R. Spigel
Journal: Journal of Clinical Oncology (2016)

8564 Background: Notch signaling is implicated in cancer stem cell self-renewal and proliferation, thus it is an appealing target in the treatment of SCLC. TRXT, a fully human IgG2 antibody targeting Notch2 and 3 receptors, has shown preclinical efficacy in SCLC models in combination with cisplatin. This Phase Ib study explores the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of TRXT with EP in chemo-naive ED-SCLC. Here we report updated safety and efficacy data. Methods: Cohorts of 3 to 6 pts were treated at each dose level using a standard 3+3 design. TRXT was given IV on Day 1 of each 21 day cycle with etoposide 100 mg/m2 (Days 1- 3) and cisplatin 80 mg/m2 or carboplatin at AUC 5 (Day 1). After 6 cycles, those pts without disease progression or unacceptable toxicities continued TRXT alone every 21 days. Once the MTD of TRXT with etoposide and cisplatin was established, the MTD of TRXT plus etoposide and carboplatin was evaluated in a cohort of 6 subjects. Results: As of November 17, 2015, 27 pts were treated with TRXT doses ranging from 5 mg/kg to 15 mg/kg. The MTD was not reached and TRXT 15 mg/kg was determined to be the Phase 2 dose. Frequently reported ( ≥ 15%) TRXT-related adverse events were: diarrhea (63%), fatigue (44.4%), nausea (37%), anemia (33.3%), decreased appetite (29.6%), vomiting (29.6%), alopecia (22.2%) and thrombocytopenia (22.2%); most were Grade 1 or 2, and reversible.The median number of TRXT doses received was 6. The overall response rate was 73%. By January 12, 2016, the mOS was 10.3 months with median follow up of 9.8 months for all pts. The mOS was 16.0 months for pts receiving TRXT doses at ≥ 12.5 mg/kg, and 7.6 months for pt at < 12 mg/kg. Conclusions: TRXT with EP was well tolerated. Dose dependent antitumor activity was seen. Updated PK/PD, safety, and efficacy data as well as exploratory predictive biomarker data and correlation with clinical response will be presented. A randomized placebo-controlled phase 2 study with this regimen is ongoing. Clinical trial information: NCT01859741.
“No convincing evidence” that QOF improves care of patients with long term illness
Authors: Matthew Limb
Journal: BMJ (2017)

England’s incentives that pay GPs for performance have not delivered better care for people with long term conditions, a systematic review of evidence has found.1

The study said that there was “no convincing evidence” that the Quality and Outcomes Framework (QOF) influenced integration or coordination of care, self care or patients’ experiences, or improved any other outcomes for these patients. Rather, QOF may have “negative effects,” the reviewers said, and abolishing it may allow practices “to prioritise other activities which could lead to better care.”

But they warned that GPs would need to be assured of a stable income if the scheme were scrapped, to protect care of patients and practices’ recruitment.

Reacting to the study’s findings, Richard Vautrey, chair of the BMA’s …
Clinical benefit of systemic treatment in patients with advanced pancreatic and gastrointestinal neuroendocrine tumours according to ESMO-MCBS and ASCO framework
Authors: L.D. de Hosson, L.M. van Veenendaal, Y. Schuller, W.T. Zandee, W.W. de Herder, M.E.T. Tesselaar, H.J. Klümpen, A.M.E. Walenkamp
Journal: Annals of Oncology (2017)
The <i>CTRB1-CTRB2</i> risk allele for chronic pancreatitis discovered in European populations does not contribute to disease risk variation in the Chinese population due to near allele fixation
Authors: Xin-Ying Tang, Wen-Bin Zou, Emmanuelle Masson, Liang-Hao Hu, Claude Ferec, Jian-Min Chen, Zhao-Shen Li, Zhuan Liao
Journal: Gut (2017)

We read with great interest the article by Rosendahl et al 1 reporting the identification of CTRB1-CTRB2 (chymotrypsin B1 and chymotrypsin B2) as a new chronic pancreatitis (CP) risk locus by means of genome-wide association study, with the lead single nucleotide polymorphism (SNP) rs8055167 having an OR of 1.35. Moreover, they found that a previously reported 16.6 kb inversion in the CTRB1-CTRB2 locus2 was in linkage disequilibrium with the CP-associated SNPs and optimally tagged by rs8048956. Furthermore, they provided in silico and in vivo evidence showing that the inversion variant changes the expression ratio of the CTRB1 and CTRB2 isoforms, the major risk allele being associated with increased CTRB1 and decreased CTRB2 mRNA expression as compared with the minor allele. Finally, they provided in vitro evidence that CTRB1 was less efficient in degrading anionic trypsinogen (PRSS2) than CTRB2 (note that rapid degradation of PRSS2 conferred by a PRSS2 missense variant protects against CP).3 Taking together, Rosendahl and colleagues concluded that …
Association of Long-Term Exposure to Transportation Noise and Traffic-Related Air Pollution with the Incidence of Diabetes: A Prospective Cohort Study
Authors: Charlotte Clark, Hind Sbihi, Lillian Tamburic, Michael Brauer, Lawrence D. Frank, Hugh W Davies
Journal: Environmental Health Perspectives (2017)

Background: Evidence for an association between transportation noise and cardiovascular disease has increased; however, few studies have examined metabolic outcomes such as diabetes or accounted for environmental coexposures such as air pollution, greenness, or walkability. Objectives: Because diabetes prevalence is increasing and may be on the causal pathway between noise and cardiovascular disease, we examined the influence of long-term residential transportation noise exposure and traffic-related air pollution on the incidence of diabetes using a population-based cohort in British Columbia, Canada. Methods: We examined the influence of transportation noise exposure over a 5-y period (1994–1998) on incident diabetes cases in a population-based prospective cohort study (n=380,738) of metropolitan Vancouver (BC) residents who were 45–85 y old, with 4-y of follow-up (1999–2002). Annual average transportation noise (Lden), air pollution [black carbon, particulate matter with aerodynamic diameter <2.5μm (PM2.5), nitrogen oxides], greenness [Normalized Difference Vegetation Index (NDVI)], and neighborhood walkability at each participant's residence were modeled. Incident diabetes cases were identified using administrative health records. Results: Transportation noise was associated with the incidence of diabetes [interquartile range (IQR) increase, 6.8 A-weighted decibels (dBA); OR=1.08 (95% CI: 1.05, 1.10)]. This association remained after adjustment for environmental coexposures including traffic-related air pollutants, greenness, and neighborhood walkability. After adjustment for coexposure to noise, traffic-related air pollutants were not associated with the incidence of diabetes, whereas greenness was protective. Conclusion: We found a positive association between residential transportation noise and diabetes, adding to the growing body of evidence that noise pollution exposure may be independently linked to metabolic health and should be considered when developing public health interventions. https://doi.org/10.1289/EHP1279
Portal pressure and liver stiffness measurements in the prediction of fibrosis regression after sustained virological response in recurrent hepatitis C
Authors: Ezequiel Mauro, Gonzalo Crespo, Carla Montironi, Maria‐Carlota Londoño, Virginia Hernández‐Gea, Pablo Ruiz, Lydia Sastre, Julissa Lombardo, Zoe Mariño, Alba Díaz, Jordi Colmenero, Antoni Rimola, Juan Carlos Garcia‐Pagán, Mercé Brunet, Xavier Forns, Miquel Navasa
Journal: Hepatology (2017)

Sustained virological response (SVR) improves survival in post-liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension (PH) post-SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after-SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and PH after viral clearance. We evaluated 112 hepatitis C virus-infected LT recipients who achieved SVR between 2001 and 2015. A liver biopsy was performed before treatment and 12 months post-SVR. Hepatic venous pressure gradient (HVPG), liver stiffness measurement (LSM), and Enhanced Liver Fibrosis (ELF) score were also determined at the same time points. Sixty-seven percent of the cohort presented fibrosis regression: 43% in recipients with cirrhosis and 72%-85% in the remaining stages (P = 0.002). HVPG, LSM, and ELF significantly decreased post-SVR. Liver function significantly improved, and survival was significantly better in patients achieving fibrosis regression. Baseline HVPG and LSM as well as decompensations before therapy were independent predictors of fibrosis regression. One year post-SVR, LSM had a high diagnostic accuracy to discard the presence of advanced fibrosis (AF) and clinically significant PH (AUROC, 0.902 and 0.888).In conclusion, SVR post-LT induces fibrosis regression in most patients, leading to significant clinical benefits. Pretreatment HVPG and LSM are significant determinants of the likelihood of fibrosis regression. Finally, LSM accurately predicts the presence of AF and PH 1 year after SVR and thus can be used to determine monitoring strategies. (Hepatology 2018;67:1683-1694).
JAVELIN Lung 100: updated design of a phase 3 trial of avelumab vs platinum doublet chemotherapy as first-line (1L) treatment for metastatic or recurrent PD-L1+ non-small-cell lung cancer (NSCLC)
Authors: M. Reck, C.-H. Yang, P.E. Postmus, F. Barlesi, E.F. Font, M. Thomas, T.M. Kim, M. Cobo Dols, H. Skuladottir, K. Park, R. Sullivan, A.L. Veatch, N. Pavlakis, L.M. Dreosti, M. Özgüroğlu, F. Morgillo, M. Schlichting, F. Teofilovici, V. Chand, V. Westeel
Journal: Annals of Oncology (2017)
Single‐Strain Versus Multistrain Probiotic Supplementation Treatment Strategy for Rheumatoid Arthritis: Comment on the Article by Marietta et al
Authors: Giancarlo Ceccarelli, Vincenzo Vullo, Gabriella d'Ettorre
Journal: Arthritis & Rheumatology (2017)

We read with interest the papers recently published by Marietta EV et al. on the gut microbial dysbiosis as a key factor in the pathogenesis of inflammatory diseases such as Rheumatoid arthritis (RA).1 Altered microbiota, well described in patients affected by RA, seems associated with perturbation of certain metabolic pathways and the therapies addressed to correct gut microbiome dysbiosis could help in the maintenance of immune homeostasis of the host.

This article is protected by copyright. All rights reserved.
Risk factors for admission to hospital with laboratory-confirmed influenza in young children: birth cohort study
Authors: Pia Hardelid, Maximiliane Verfuerden, Jim McMenamin, Ruth Gilbert
Journal: European Respiratory Journal (2017)

We determined risk factors for influenza hospital admission in children aged &lt;2 years to guide the design of paediatric vaccination programmes. We linked all singleton live births in Scotland from 2007 to 2015 to hospital administrative data and influenza laboratory reports. Cox proportional hazard models were used to identify birth and family risk factors for influenza admissions. There were 1115 influenza admissions among 424 048 children. 85.1% of admitted children were born at term and were not in a high-risk group. Presence of an older sibling was strongly associated with increased risk of influenza admission, particularly for children aged &lt;6 months: hazard ratio for second- <i>versus</i> first-born child was 2.02 (95% CI 1.52–2.69). Maternal age &lt;30 years and birth during autumn (age &lt;6 months) or spring (age 6–23 months) were also associated with admission risk. Targeting vaccination programmes to high-risk children will not prevent the vast majority of influenza admissions. Parents of children aged &lt;2 years should be advised that vaccination of older siblings will protect younger children against influenza infection. As evidence of the impact of the universal influenza vaccine programme emerges, there may be a need to reconsider universal influenza vaccination in children aged 6 months to 2 years in the UK.
Injectable Buprenorphine Halts Effects of Opioids and May Deter Abuse
Authors: Anita Slomski
Journal: JAMA (2017)

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Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish Group for Research on Sarcoma (GEIS)
Authors: J. Martin-Broto, A. Redondo, C. Valverde, M.A. Vaz, J. Mora, X. Garcia del Muro, A. Gutierrez, C. Tous, A. Carnero, D. Marcilla, A. Carranza, P. Sancho, J. Martinez-Trufero, R. Diaz-Beveridge, J. Cruz, V. Encinas, M. Taron, D.S. Moura, P. Luna, N. Hindi, A. Lopez-Pousa
Journal: Annals of Oncology (2017)
Nonmineralized and Mineralized Collagen Scaffolds Induce Differential Osteogenic Signaling Pathways in Human Mesenchymal Stem Cells
Authors: Qi Zhou, Xiaoyan Ren, David Bischoff, Daniel W. Weisgerber, Dean T. Yamaguchi, Timothy A. Miller, Brendan A. C. Harley, Justine C. Lee
Journal: Advanced Healthcare Materials (2017)

Abstract The instructive capabilities of extracellular matrix components in progenitor cell differentiation have recently generated significant interest in the development of bioinspired materials for regenerative applications. Previously, a correlation was described between the osteogenic capabilities of nanoparticulate mineralized collagen glycosaminoglycan scaffolds (MC‐GAG) and an autogenous activation of small mothers against decapentaplegic ( Smad1/5) in the canonical bone morphogenetic protein receptor (BMPR) pathway with a diminished extracellular signal regulated kinase 1/2 (ERK1/2) activation when compared to nonmineralized collagen glycosaminoglycan scaffolds (Col‐GAG). This work utilizes a canonical BMPR inhibitor (dorsomorphin homologue 1, DMH1) and an inhibitor of the mitogen activated protein kinase/ERK kinase (MEK)/(ERK) cascade (PD98059) to characterize the necessity of each pathway for osteogenesis. While DMH1 inhibits runt‐related transcription factor 2 (Runx2) and bone sialoprotein II (BSPII) gene expression of primary human mesenchymal stem cells (hMSCs) on MC‐GAG, PD98059 inhibits BSPII expression on Col‐GAG independent of Runx2 expression. DMH1 inhibits mineralization on both Col‐GAG and MC‐GAG, however, PD98059 only inhibits mineralization on Col‐GAG. DMH1 inhibits both Smad1/5 phosphorylation and Runx2 protein expression, whereas PD98059 inhibits ERK1/2 and c‐Jun amino‐terminal kinase 1/2 (JNK1/2) phosphorylation without affecting Runx2. Thus, activation of the canonical BMPR signaling is necessary for osteogenic differentiation and mineralization of hMSCs on Col‐GAG or MC‐GAG. The MEK/ERK cascade, intimately tied to JNK activation, is necessary for Runx2‐independent osteogenesis on Col‐GAG, while completely dispensable in osteogenesis on MC‐GAG.
The ABC-study: A randomized phase III study comparing one course of adjuvant bleomycin, etoposide, and cisplatin (BEP) and one course of carboplatin AUC7 in clinical stage I seminomatous testicular cancer.
Authors: Torgrim Tandstad, Olof Stahl, Olav Dahl, Ingrid Glimelius, Hege Sagstuen Haugnes, Asa Karlsdottir, Carl Wilhelm Langberg, Karin Soderstrom, Arne Solberg, Ulrika K. Stierner, Najme Wall, Gabriella Elisabeth Cohn-Cedermark
Journal: Journal of Clinical Oncology (2017)

TPS4593 Background: Clinical stage I seminomatous testicular cancer is by far the most frequent presentation of testicular cancer. Treatment options include surveillance or adjuvant treatment, internationally one course of adjuvant carboplatin (AUC7) is the preferred adjuvant treatment. Tumor size and stromal invasion in the rete testis can be used to identify patients with a higher risk of relapse. Recent data have showed only a modest effect of adjuvant carboplatin in preventing relapse, and more potent adjuvant therapies should be explored to this group of patients. Methods: The ABC-study is a investigator initiated randomized, open, phase III study comparing standard adjuvant chemotherapy in the form of one course carboplatin AUC7 to one course of BEP (Bleomycin, etoposide and cisplatin), in patients with one or two risk factors. Based on SWENOTECA data from one course of adjuvant carboplatin AUC7 we estimate the relapse rate in patients with one or two risk factors to be 9 %. We consider a reduction in relapse free survival of 7 % to be the minimum difference that will lead to routine use of one course of adjuvant BEP. To demonstrate an improvement in relapse rate from 9 to 2 % with an α = 0.05 and β = 0.80, 332 evaluable patients are required. We expect a dropout rate of maximum 5 %, and therefore intend to randomize a total of 348 patients. Enrollment in the study started in 2015, and as of February 1. 2017 a total of 66 patients have been enrolled. Accrual have been slower than expected, but the current accrual rate is about 6-7 patients a month. We invite institutions and collaboratory groups to participate in this study. NCT02341989. EUDRACT 2014-004075-23. Clinical trial information: NCT02341989.
Feasibility of a complete pancreatobiliary linear endoscopic ultrasound examination from the stomach
Authors: Vinay Dhir, Douglas Adler, Nonthalee Pausawasdi, Amit Maydeo, Khek Ho
Journal: Endoscopy (2017)

Abstract Background and study aims Linear endoscopic ultrasound (EUS) evaluation of the pancreaticobiliary system usually requires scanning from both the stomach and the duodenum. The feasibility of assessing the complete pancreaticobiliary system from the stomach alone has not been studied. We aimed to conceptualize a system-based approach (the railroad approach) for linear pancreaticobiliary EUS (PB-EUS) and evaluate whether the pancreaticobiliary anatomy could be assessed from the stomach alone. Patients and methods Three maneuvers were conceptualized and evaluated (the alpha maneuver in the stomach, and sigma and xi maneuvers in the duodenum). The maneuvers were prospectively evaluated in 100 consecutive patients requiring PB-EUS. Results The median procedure time for the three maneuvers was significantly higher than that for the alpha maneuver alone (12 vs. 6 minutes; P ≤ 0.001). The visualization rate of the hilum and common hepatic duct was significantly higher from the stomach than from the duodenum (100 % vs. 83.5 %; P ≤ 0.001), while rates for the head of the pancreas (100 % vs 100 %) and uncinate process (100 % vs 100 %) did not differ. The suprapancreatic common bile duct (CBD; 92 % vs 100 %; P = 0.006), retropancreatic CBD (95 % vs 100 %; P = 0.06), and pancreatic duct in the head (94 % vs 100 %; P = 0.03) were not completely visualized from the stomach, because of pancreatic calcification or shadow from the ligaments. The EUS diagnosis made from the stomach and duodenum did not differ after excluding body and tail lesions (pancreatic head neoplasms, 100 % vs 100 %; CBD stone, 100 % vs 84.6 %; pancreatic cysts in the head, 83.3 % vs 83.3 %, respectively). Conclusions Adequate anatomical and diagnostic information on the pancreaticobiliary system may be acquired by EUS scanning from the stomach alone and with a shorter procedure time.