tbuckley/cabot-search huggingface dataset:
Oesophageal cancer incidence in 20-year follow-up in a population-based sample of 12 000 middle-age men with or without <i>Helicobacter pylori</i> infection in Finland
Authors: Ilkka Juhani Vohlonen, Matti Hakama, Matti Härkönen, Nea Malila, Eero Pukkala, Veli Koistinen, Pentti Sipponen
Journal: Gut (2017)

Two consensus reports on Helicobacter pylori (Hp), published recently in Gut , summarise the role of Hp gastritis in upper GI diseases, including gastric cancer (GCA).1 2 Although Hp gastritis definitely increases the risk of GCA as suggested in both reports, Hp is, on the other hand, also associated with a notable low incidence of oesophageal cancer (EC), of both adenomatous and squamous type.

In our earlier 15-year follow-up of a large population-based sample of males aged 50–65 years (n=12 016) from two Finnish cities, with or without Hp, diagnosed in 1994–1996 by serological (IgG) Hp test (Biohit HealthCare, Helsinki, Finland), 57 GCA cases were recorded in the study population by the nationwide Cancer Registry during the follow-up.3 Of these cancers, 50 were in men and seven in those with and without Hp, respectively. The relative standardised incidence ratio (RR) of GCA incidence in Hp positive compared with that in Hp-negative men, calculated with the Altman’s procedure, was 6.0 (95%CI 2.3 to 19.0).

In …
Injectable Mussel‐Inspired Immobilization of Platelet‐Rich Plasma on Microspheres Bridging Adipose Micro‐Tissues to Improve Autologous Fat Transplantation by Controlling Release of PDGF and VEGF, Angiogenesis, Stem Cell Migration
Authors: Shaolong Zhou, Qiang Chang, Feng Lu, Malcolm Xing
Journal: Advanced Healthcare Materials (2017)

Abstract Platelets‐rich plasma (PRP) can produce growth factors (GFs) to improve angiogenesis. However, direct injection of PRP does not lead to highly localized GFs. The current study employs a mussel‐inspired polydopamine to immobilize PRP on gelatin microspheres (GMs) with the purpose of bridging adipose micro‐tissues to help implanted fat survive (GM‐pDA‐PRP). Enhanced PRP adhesion leads to a prolonged and localized production of GFs, which is verified by platelet counting and by ELISA of vascular endothelial growth factors (VEGFs) and of platelet derived growth factors (PDGFs). The GM‐pDA‐PRP “hatches” a microenvironment for the proliferation of adipose‐derived stem cells. After the adipose micro‐tissue has bridged with GM‐pDA‐PRP after 16 weeks, triple‐fluorescence staining reveals that the mature adipocytes, blood vessels, and capillaries are arranged like in normal adipose tissue. The survival fat increases significantly compared to that in control, PRP, and GM‐PRP groups (84.8 ± 11.4% versus 47.8 ± 8.9%, 56.9 ± 9.7%, and 60.2 ± 10.5%, respectively). Both histological assessments and CD31 immunofluorescence indicate that the improvement of angiogenesis in GM‐pDA‐PRP is higher than in the fat graft group (6.4‐fold in quantitative CD31 positive cells). The CD34 positive cells in the GM‐pDA‐PRP group are around 3.5‐fold the amount in the fat graft group, which suggests that more stem cells migrate to the implant area. Cell proliferation staining shows that the number of Ki67 positive cells is around five times as high as that in the fat graft group.
No Association Between Normalization of VWF Levels and Bleeding Phenotype in Patients with Type 1 VWD - from the Win Study
Authors: Johan Boender, Jeroen Eikenboom, Karin Fijnvandraat, Waander van Heerde, Karina Meijer, Evelien Mauser-Bunschoten, Marjon Cnossen, Joke de Meris, Britta Laros-van Gorkom, Anske van der Bom, Frank W.G. Leebeek
Journal: Blood (2016)
Clinical outcomes in adult patients with aplastic anemia: A single institution experience
Authors: Prajwal Boddu, Guillermo Garcia‐Manero, Farhad Ravandi, Gautam Borthakur, Elias Jabbour, Courtney DiNardo, Nitin Jain, Naval Daver, Naveen Pemmaraju, Paolo Anderlini, Simrit Parmar, Devendra KC, Mary Akosile, Sherry A. Pierce, Richard Champlin, Jorge Cortes, Hagop Kantarjian, Tapan Kadia
Journal: American Journal of Hematology (2017)

Newer treatment modalities are being investigated to improve upon historical outcomes with standard immunosuppressive therapy (IST) in aplastic anemia (AA). We analyzed outcomes of adult patients with AA treated with various combinatorial anti-thymoglobulin-based IST regimens in frontline and relapsed/refractory (R/R) settings. Pretreatment and on-treatment clinical characteristics were analyzed for relationships to response and outcome. Among 126 patients reviewed, 95 were treatment-naïve (TN) and 63, R/R (including 32 from the TN cohort); median ages were 49 and 50 years, respectively. Overall survival (OS) was superior in IST responders (P < .001). Partial response to IST was associated with shorter relapse-free survival (RFS), as compared with complete response (P = .03). By multivariate analysis, baseline platelet and lymphocyte count predicted for IST response at 3 and 6 months, respectively. While additional growth factor interventions led to faster count recovery, there were no statistically significant differences in RFS or OS across the various frontline IST regimens (i.e., with/without G-CSF or eltrombopag). While marrow cellularity did not correlate with peripheral-blood counts at 3 months, cytomorphological assessment revealed dyspoietic changes in all nonresponders with hypercellular-marrow indices. Covert dysplasia, identified through early bone marrow assessment, has implications on future therapy choices after IST failure. Salvage IST response depended upon prior response to ATG: prior responders (46%) vs. primary refractory (0%) (P < .01). In the R/R setting, there was no survival difference between IST and allogeneic stem cell transplant groups, with a trend toward superior OS in the former. Transplant benefits in the R/R setting may be underrealized due to transplant-related mortality.
Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions
Authors: C A van der Weyden, S A Pileri, A L Feldman, J Whisstock, H M Prince
Journal: Blood Cancer Journal (2017)

CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target. The efficacy of naked anti-CD30 antibodies in practice was, however, modest. Moreover, combinations with bacterial toxins and radioimmunoconjugates have also had limited success. The development of the antibody-drug compound brentuximab vedotin (BV), however, has rejuvenated interest in CD30 as a tumor target. Phase I and II clinical trials in Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T cell lymphoma, and even CD30-expressing B-cell lymphomas, have shown the compound is well tolerated, but more importantly, able to deliver meaningful disease control even in patients with multiply relapsed or refractory disease. FDA approval has been granted for its use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. A recent phase III trial of BV in cutaneous T-cell lymphoma has confirmed its superiority to standard of care therapies. In this manuscript, we explore the history of CD30 as a tumor marker and as a therapeutic target, both in the laboratory and in the clinic, with a view to understanding future avenues for further study.
樹状細胞によるIL‐6の交差提示は,病原性Th17細胞の感作に必要である
Authors: Heink Sylvia, Yogev Nir, Garbers Christoph, Herwerth Marina, Aly Lilian, Gasperi Christiane, Husterer Veronika, Croxford Andrew L, Moeller‐Hackbarth Katja, Bartsch Harald S, Sotlar Karl, Krebs Stefan, Regen Tommy, Blum Helmut, Hemmer Bernhard, Misgeld Thomas, Wunderlich Thomas F, Hidalgo Juan, Oukka Mohamed, Rose‐John Stefan, Schmidt‐Supprian Marc, Waisman Ari, Korn Thomas
Journal: Nature Immunology (2017)
歯科インプラント用の高耐摩耗性と生体適合性炭素ナノ複合材料被覆【Powered by NICT】
Authors: V Penkov Oleksiy, E Pukha Vladimir, L Starikova Svetlana, Khadem Mahdi, V Starikov Vadym, V Maleev Maxim, Kim Dae-Eun
Journal: Biomaterials (2016)
Clinical and genomic characterization of metastatic small cell/neuroendocrine prostate cancer (SCNC) and intermediate atypical prostate cancer (IAC): Results from the SU2C/PCF/AACRWest Coast Prostate Cancer Dream Team (WCDT).
Authors: Eric Jay Small, Rahul Raj Aggarwal, Jiaoti Huang, Artem Sokolov, Li Zhang, Joshi J. Alumkal, Jack Youngren, Charles J. Ryan, Adam Foye, Robert Evan Reiter, Christopher P. Evans, Martin Gleave, Owen Witte, Josh Stuart, Theodore C. Goldstein, George V. Thomas, Lawrence D. True, Himisha Beltran, Mark A. Rubin, Tomasz M. Beer
Journal: Journal of Clinical Oncology (2016)

5019 Background: SCNC and a novel pathologic subtype, IAC, comprise a growing proportion of mCRPC patients resistant to androgen signaling inhibitors such as Abiraterone (Abi) or Enzalutamide (Enz). We sought to characterize these non-adenocarcinoma (adeno) subtypes in a prospective biopsy study. Methods: Eligible mCRPC pts underwent a metastasis biopsy (bx), and were followed for clinical outcomes. Tissue was both frozen and formalin fixed/paraffin embedded (FFPE). Independent review of FFPE specimens was undertaken by 3 pathologists. Frozen specimens underwent laser capture micro-dissection prior to RNA sequencing (seq). Machine learning was used to derive histology-specific expression signatures. Signature accuracy was evaluated with leave-pair-out cross-validation and application to an independent data set. Results: 226 of 300 planned mCRPC pts (74% resistant to Abi and/or Enz) have undergone bx (including 123 bone, 61 node, and 23 liver bx) with a 78% evaluable biopsy rate. Adeno was identified in 39%, non-adeno in 41% (SCNC in 12%, IAC in 29%), with other mixtures in the remaining 20%. Median overall survival (OS) from time of biopsy for pts with non-adeno histologies was 12.8 months (mos) [ IAC OS = 19.1 mos; SCNC OS = 12.8 mos] versus 25.8 mos in adeno pts (p=0.023). RNAseq data are available from 94 bx. Transcriptional signatures were developed which accurately distinguish adeno, SCNC and IAC. IAC appears to have a signature intermediate between adeno and SCNC. When applied to an independent data set (Beltran et al, Ca Disc 2011), these transcriptional signatures identified SCNC with 100% accuracy, and predict for IAC differentiation in a subset of non-SCNC tumors. Conclusions: A majority of CRPC metastases exhibit non-adenocarcinoma features, which are associated with a shortened survival. IAC and SCNC are genomically distinct, and newly derived transcriptional signatures based on these bx can be used to identify SCNC in an independent data set. Integration of whole exome with RNA-seq data are ongoing to identify pathways up-regulated in IAC and SCNC.
Developing a situation analysis tool to assess containment of antimicrobial resistance in South East Asia
Authors: Manish Kakkar, Anuj Sharma, Sirenda Vong
Journal: BMJ (2017)

SYNOPSIS A method of constructing pherograms is described.The study of electrophoretic patterns shown on pherograms of tumour tissue from man and animals is claimed to offer a new approach to the identification and classification of tumour tissues.
Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure
Authors: Bram Rochwerg, Laurent Brochard, Mark W. Elliott, Dean Hess, Nicholas S. Hill, Stefano Nava, Paolo Navalesi, Massimo Antonelli, Jan Brozek, Giorgio Conti, Miquel Ferrer, Kalpalatha Guntupalli, Samir Jaber, Sean Keenan, Jordi Mancebo, Sangeeta Mehta, Suhail Raoof
Journal: European Respiratory Journal (2017)

Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, de novo hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort
Authors: Cécile Gaujoux-Viala, Nathalie Rincheval, Maxime Dougados, Bernard Combe, Bruno Fautrel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. <h3>Objective</h3> To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. <h3>Methods</h3> Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. <h3>Results</h3> Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. <h3>Conclusion</h3> Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.
Effect of zymosan and poly (I:C) adjuvants on responses to microneedle immunization coated with whole inactivated influenza vaccine
Authors: Ju-Hyung Shin, Jin-Yong Noh, Kwon-Ho Kim, Jae-Keun Park, Ji-Ho Lee, Seong Dong Jeong, Dae-Yoon Jung, Chang-Seon Song, Yeu-Chun Kim
Journal: Journal of Controlled Release (2017)
Obesity, but Not Physical Activity, Is Associated With Higher Prevalence of Asymptomatic Diverticulosis
Authors: Rouzbeh Mashayekhi, Danielle R. Bellavance, Samantha M. Chin, Benjamin Maxner, Kyle Staller, Ramnik J. Xavier, Daniel C. Chung, Hamed Khalili
Journal: Clinical Gastroenterology and Hepatology (2017)
Phase I dose escalation study of CVM-1118, a novel anti-vascular mimicry agent, in patients with advanced cancers.
Authors: Anthony W. Tolcher, Wu-Chou Su, Nehal Lakhani, John Gutheil, Teresa J. Melink, Yi-Wen Chu, Yen-Ling Chen, Du-Shieng Chien
Journal: Journal of Clinical Oncology (2017)

2580 Background: CVM-1118 is an oral NCE that demonstrated potent anti-tumor effects in several tumor xenograft models, via multiple MOAs including induction of cancer cell cycle arrest and apoptosis, and reducing vasculogenic mimicry (VM) network formation in cancer cells, providing a promising therapeutic means in the treatment of malignant tumors that have metastatic potential. Methods: Patients with advanced tumors are being enrolled into 2 ongoing open-label Phase I dose escalation studies in both US (CVM-001) and Taiwan (CVM-002) to evaluate ethnic differences in drug responses. CVM-1118 capsules are administrated orally QD/BID in a 28-day cycle for 4 cycles. The primary objectives are to evaluate the safety, tolerability and pharmacokinetics (PK) and establish the Recommended Phase 2 Dose (RP2D). The secondary objective is to evaluate the therapeutic response after receiving treatment. Beyond 4 cycles, patients showing clinical benefit with CVM-1118 may enter extension cohort to continue the treatment. Results: To date, 28 pts (16 M/12 F)received CVM-1118 across 6 dose levels (50 to 800 mg daily). Median number of days was 52 (range 2 to 135). For CVM-001, 2 DLTs (grade 5 dehydration and grade 3 fatigue) were reported at cohort 6 (800 mg/daily) and the MTD is currently under evaluation. For CVM-002, 3 cohorts (100 to 400 mg/daily) have been completed without DLT. Enrolment to cohort 5 (600 mg/daily) is in progress. From both studies, the most common drug-related AEs included manageable diarrhea, nausea, and vomiting. Rapid oral absorption was observed with Tmax &lt; 2 hr. Bioconversion to active metabolite, CVM-1125, occurred rapidly and the drug exposure increased with increasing dose levels. However, patients in US study showed higher drug exposure than those in Taiwan study. Two patients at 200 mg/daily cohort in Taiwan completing 4-cycle treatment and showing stable disease continued into extension cohort with higher dose. Conclusions: In this ongoing study, Asian patients in Taiwan appear to have better tolerance for CVM-1118 than those in US, likely due to lower drug exposure at same dose level, and some patients have experienced clinical benefit. Clinical trial information: NCT02507544; NCT02703298.
in vitroのマクロファージ取り込みおよびゼブラフィッシュにおける循環に基づく腫瘍でのナノ粒子のin vivo蓄積の予測
Authors: Chang Hyeyoun, Yhee Ji Young, Jang Gun Hyuk, You Dong Gil, Ryu Ju Hee, Choi Yongwhan, Na Jin Hee, Park Jae Hyung, Lee Kwan Hyi, Choi Kuiwon, Kim Kwangmeyung, Kwon Ick Chan
Journal: Journal of Controlled Release (2016)
Chemogenomic Landscape of <i>RUNX1</i>-mutated AML Reveals Importance of <i>RUNX1</i> Allele Dosage in Genetics and Glucocorticoid Sensitivity
Authors: Laura Simon, Vincent-Philippe Lavallée, Marie-Eve Bordeleau, Jana Krosl, Irène Baccelli, Geneviève Boucher, Bernhard Lehnertz, Jalila Chagraoui, Tara MacRae, Réjean Ruel, Yves Chantigny, Sébastien Lemieux, Anne Marinier, Josée Hébert, Guy Sauvageau
Journal: Clinical Cancer Research (2017)

Purpose:RUNX1-mutated (RUNX1mut) acute myeloid leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Toward this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup.Experimental Design: RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML.Results: We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the glucocorticoid receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that coassociating mutations as well as GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells.Conclusions: Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Clin Cancer Res; 23(22); 6969-81. ©2017 AACR.
Multiple productive IGH rearrangements denote oligoclonality even in immunophenotypically monoclonal CLL
Authors: K Brazdilova, K Plevova, H Skuhrova Francova, H Kockova, M Borsky, V Bikos, J Malcikova, A Oltova, J Kotaskova, B Tichy, Y Brychtova, J Mayer, M Doubek, S Pospisilova
Journal: Leukemia (2017)

Multiple productive IGH rearrangements denote oligoclonality even in immunophenotypically monoclonal CLL
Erratum. Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial. Diabetes Care 2017;40:1096–1102
Authors: Gregory P. Forlenza, Sunil Deshpande, Trang T. Ly, Daniel P. Howsmon, Faye Cameron, Nihat Baysal, Eric Mauritzen, Tatiana Marcal, Lindsey Towers, B. Wayne Bequette, Lauren M. Huyett, Jordan E. Pinsker, Ravi Gondhalekar, Francis J. Doyle, David M. Maahs, Bruce A. Buckingham, Eyal Dassau
Journal: Diabetes Care (2017)

In the above-mentioned article, the supplementary data had the incorrect figure listed for …
Hunt’s war of words with Hawking has gone too far, says former health secretary
Authors: Abi Rimmer
Journal: BMJ (2017)

The secretary of state for health’s current dispute with the eminent scientist Stephen Hawking has gone too far, a former health secretary has said.

Andy Burnham, mayor for Greater Manchester and former Labour cabinet member, told The BMJ he thought that the current health secretary, Jeremy Hunt, was wrong to repeatedly dispute Hawking’s views on the evidence for seven day NHS services.

Hunt and Hawking have been in an ongoing …
紙ベース3D細胞培養系における放射に対する肺癌細胞の代謝応答【Powered by NICT】
Authors: A Simon Karen, Mosadegh Bobak, Minn Kyaw Thu, R Lockett Matthew, R Mohammady Marym, M Boucher Diane, B Hall Amy, M Hillier Shawn, Udagawa Taturo, K Eustace Brenda, M Whitesides George
Journal: Biomaterials (2016)