tbuckley/cabot-search huggingface dataset:
MicroRNA-214-3p in the Kidney Contributes to the Development of Hypertension
Authors: Yong Liu, Kristie Usa, Feng Wang, Pengyuan Liu, Aron M. Geurts, Junhui Li, Anna Marie Williams, Kevin R. Regner, Yiwei Kong, Han Liu, Jing Nie, Mingyu Liang
Journal: Journal of the American Society of Nephrology (2018)

In spite of extensive study, the mechanisms for salt sensitivity of BP in humans and rodent models remain poorly understood. Several microRNAs (miRNAs) have been associated with hypertension, but few have been shown to contribute to its development.
Clinical significance following breast conservation surgery with or without postoperative irradiation in Japanese women with breast cancer.
Authors: Kentaro Tamaki, Nobumitsu Tamaki, Yoshihiko Kamada, Kanou Uehara, Minoru Miyashita, Takanori Ishida, Hironobu Sasano
Journal: Journal of Clinical Oncology (2012)

e11530 Background: Postoperative irradiation or radiotherapy following breast conservation surgery has been reported to be clinically effective in terms of prevention of local breast cancer recurrences. However, it is also true that its local recurrence rate was only 5% to 10%, suggestive of the lack of its clinical benefits in the great majority of the cases. The purpose of this study was to investigate the significance of post-operative radiotherapy in breast conservation surgery by comparing the groups with or without irradiation. Methods: We retrospectively evaluated 1197 Japanese female breast cancer patients (598 irradiation cases and 599 non-irradiation cases). Radiation was administered in a dose of 50 Gy for all conserved breast and additional 10 Gy in those with positive margins or carcinoma within 5mm from surgical margin. We examined the local recurrence rates in those with or without post-operative irradiation according to the status of surgical margin, ER and HER2 in breast cancer tissues. Results: RFS in the irradiated groups were significantly higher than non-irradiated ones in surgical margin positive (P=0.001, HR: 0.334, 95%CI: 0.14-0.79), negative (P=0.015, 0.362, 95%CI: 0.15-0.82), ER positive (P&lt;0.001, HR: 0.249, 95%CI: 0.11-0.54), HER2 negative (P=0.002, HR: 0.316, 95%CI: 0.15-0.65) and non-triple negative patients (P=0.001, HR: 0.382, 95%CI: 0.21-0.69). However, no significant differences were detected between these two groups in ER negative (P=0.288, HR: 0.586, 95%CI: 0.22-1.57), HER2 positive (P=0.969, HR: 0.971, 95%CI: 0.22-4.24) and triple negative (P=0.336, HR: 0.282, 95%CI: 0.02-3.72) patients. Conclusions: Results of our present study could provide clinically inert information as to the selection of the breast cancer patients following conserve surgery.
Response to: ‘Can we further SPARkle the SPAR model?’ by Kavadichanda<i>et al</i>
Authors: Wanlong Wu, Suzana Jordan, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2018)

Thank you very much for your interest in our article ‘Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model’1 and your precious questions ‘Can we further SPARkle the SPAR model’.2 We are glad to respond as below.

Musculoskeletal manifestations in scleroderma are commonly treated with methotrexate. The progress/worsening of ILD by methotrexate has been widely contested across various disease groups. Hence, could it be possible that the subset of patients with arthritis ended up receiving methotrexate, which in turn was responsible for ILD progression? 

The causative role of methotrexate (MTX) in inducing or exacerbating interstitial lung disease (ILD) is quite controversial, especially in non-rheumatoid arthritis autoimmune diseases.3 Furthermore, Avouac et al 4 reported that the presence of joint synovitis was an independent predictor for disease progression in systemic sclerosis (SSc), suggesting that arthritis by itself is associated with organ manifestations independent …
Digital health in rheumatology
Authors: Vinod Ravindran, Suchitra Kataria
Journal: Annals of the Rheumatic Diseases (2018)

We read with interest the article by Dr Burmester on the digital technologies which have the potential to deeply impact healthcare delivery in rheumatology too.1 Technology has always been integral to modern medicine and without doubt it has played a big role in advanced diagnostics, drug development, treatment and rehabilitation. However, the personalised data-led approach is a recent phenomenon which is poised to change the way medicine has been practised traditionally since its evolution, as highlighted by Dr Burmester. In this context, some other aspects and concerns as we have outlined below may also be considered.

A burst of big data and the artificial neural network-powered artificial intelligence is already empowering the clinicians, patients and the care …
Increased Extracellular Vesicles Mediate WNT5A Signaling in Idiopathic Pulmonary Fibrosis
Authors: Aina Martin-Medina, Mareike Lehmann, Olivier Burgy, Sarah Hermann, Hoeke A. Baarsma, Darcy E. Wagner, Martina M. De Santis, Florian Ciolek, Thomas P. Hofer, Marion Frankenberger, Michaela Aichler, Michael Lindner, Wolfgang Gesierich, Andreas Guenther, Axel Walch, Christina Coughlan, Paul Wolters, Joyce S. Lee, Jürgen Behr, Melanie Königshoff
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by lung epithelial cell injury, increased (myo)fibroblast activation, and extracellular matrix deposition. Extracellular vesicles (EVs) regulate intercellular communication by carrying a variety of signaling mediators, including WNT (wingless/integrated) proteins. The relevance of EVs in pulmonary fibrosis and their potential contribution to disease pathogenesis, however, remain unexplored.Objectives: To characterize EVs and study the role of EV-bound WNT signaling in IPF.Methods: We isolated EVs from BAL fluid (BALF) from experimental lung fibrosis as well as samples from IPF, non-IPF interstitial lung disease (ILD), non-ILD, and healthy volunteers from two independent cohorts. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Primary human lung fibroblasts (phLFs) were used for EV isolation and analyzed by metabolic activity assays, cell counting, quantitative PCR, and Western blotting upon WNT gain- and loss-of-function studies.Measurements and Main Results: We found increased EVs, particularly exosomes, in BALF from experimental lung fibrosis as well as from patients with IPF. WNT5A was secreted on EVs in lung fibrosis and induced by transforming growth factor-β in primary human lung fibroblasts. The phLF-derived EVs induced phLF proliferation, which was attenuated by WNT5A silencing and antibody-mediated inhibition and required intact EV structure. Similarly, EVs from IPF BALF induced phLF proliferation, which was mediated by WNT5A.Conclusions: Increased EVs function as carriers for signaling mediators, such as WNT5A, in IPF and thus contribute to disease pathogenesis. Characterization of EV secretion and composition may lead to novel approaches to diagnose and develop treatments for pulmonary fibrosis.
Carfilzomib Weekly Plus Melphalan and Prednisone in Newly Diagnosed Elderly Multiple Myeloma (IFM 2012-03)
Authors: Xavier Leleu, Lionel Karlin, Brigitte Kolb, Mourad Tiab, Carla Araujo, Nathalie Meuleman, Thierry De Revel, Pascal Bourquard, Pascal Lenain, Murielle Roussel, Arnaud Jaccard, Marie-Odile Petillon, Karim Belhadj-Merzoug, Gerard Lepeu, Marie-Lorraine Chretien, Jean Fontan, Philippe Rodon, Anna Schmitt, Fritz Offner, Laurent Voillat, Sophie Cereja, Frederique Kuhnowski, Sophie Rigaudeau, Olivier Decaux, Catherine Humbrecht-Kraut, Jamile Frayfer, Olivier Fitoussi, Damien Roos Weil, Jean Claude Eisenmann, Veronique Dorvaux, Eric G. Voog, Cyrille Hulin, Michel Attal, Philippe Moreau, Thierry Facon
Journal: Blood (2015)
Factors associated with additional anterior cruciate ligament reconstruction and register comparison: a systematic review on the Scandinavian knee ligament registers
Authors: Eleonor Svantesson, Eric Hamrin Senorski, Angelo Baldari, Olufemi R. Ayeni, Lars Engebretsen, Francesco Franceschi, Jon Karlsson, Kristian Samuelsson
Journal: British Journal of Sports Medicine (2018)

Objective To present an overview of the Scandinavian knee ligament registers with regard to factors associated with additional ACL reconstruction, and studies comparing the Scandinavian registers with other knee ligament registers. Design Systematic review. Data sources Four electronic databases: PubMed, EMBASE, the Cochrane Library and AMED were searched, and 157 studies were identified. Two reviewers independently screened titles, abstracts and full-text studies for eligibility. A modified version of the Downs and Black checklist was applied for quality appraisal. Eligibility criteria for selecting studies Eligible studies were those published since the establishment of the Scandinavian registers in 2004, which reported factors associated with additional ACL reconstruction and compared data from other registers. Results Thirty-one studies met the inclusion criteria and generally displayed good reporting quality. Adolescent age (&lt;20 years) was the most common factor associated with additional ACL reconstruction. The choice of hamstring tendon graft compared with patella tendon, transportal femoral tunnel drilling, smaller graft diameter and utilisation of suspensory fixation devices were associated with additional ACL reconstruction. Concomitant cartilage injury decreased the likelihood of additional ACL reconstruction. Patient sex alone did not influence the likelihood. The demographics of patients undergoing ACL reconstruction in the Scandinavian registers are comparable to registers in other geographical settings. However, there are differences in surgical factors including the presence of intra-articular pathology and graft choice. Summary The studies published from the Scandinavian registers in general have a high reporting quality when regarded as cohort studies. Several factors are associated with undergoing additional ACL reconstruction. The results from the registers may help facilitate treatment decisions.
Acellular Cauda Equina Allograft as Main Material Combined with Biodegradable Chitin Conduit for Regeneration of Long‐Distance Sciatic Nerve Defect in Rats
Authors: Xun Sun, Yu Wang, Zhiyuan Guo, Bo Xiao, Zhen Sun, Heyong Yin, Haoye Meng, Xiang Sui, Qing Zhao, Quanyi Guo, Aiyuan Wang, Wenjing Xu, Shuyun Liu, Yaojun Li, Shibi Lu, Jiang Peng
Journal: Advanced Healthcare Materials (2018)

Abstract Autologous nerve grafting (ANG), the gold standard treatment for peripheral nerve defects, still has many restrictions. In this study, the acellular cauda equina allograft (ACEA), which consists of biodegradable chitin conduit and acellular cauda equina, is developed. The cauda equina is able to complete decellularization more quickly and efficiently than sciatic nerves under the same conditions, and it is able to reserve more basal lamina tube. In vitro, ACEA shows superior guidance capacity for the regeneration of axons and migration of Schwann cells compared to acellular sciatic nerve allograft (ASNA) in dorsal root ganglion culture. In vivo, ACEA is used to bridge 15 mm long‐distance defects in rat sciatic nerves. On day 21 after transplantation, the regenerative distance of neurofilaments in the grafting segment is not significantly different between the ACEA and ANG groups. At week 12, ACEA group shows better sciatic nerve repair than chitin conduit only and ASNA groups, and the effect is similar to that in the ANG group as determined by gait analysis, neural electrophysiological, and histological analyses. The above results suggest that the ACEA has the potential to become a new biological material as a replacement for autografting in the treatment of long‐distance nerve defects.
Retrospective clinical case series study in 2017 identifies Plasmodium knowlesi as most frequent Plasmodium species in returning travellers from Thailand to Germany
Authors: Guenter Froeschl, Hans Dieter Nothdurft, Frank von Sonnenburg, Gisela Bretzel, Roman Polanetz, Inge Kroidl, Michael Seilmaier, Hans Martin Orth, Sabine Jordan, Peter Kremsner, Sabine Vygen-Bonnet, Michael Pritsch, Michael Hoelscher, Camilla Rothe
Journal: Eurosurveillance (2018)

Febrile illnesses are common in travellers returning from south-east Asia. However, malaria is a rare diagnosis in this population. A series of Plasmodium knowlesi infections was noted in German travellers returning from Thailand since 2012. Infectious disease and tropical medicine facilities registered by the German Society for Tropical Medicine and International Health were contacted in March 2017, and asked to report previous P. knowlesi cases. In addition, surveillance data from the Robert Koch-Institute were analysed. The facilities reported a total of six P. knowlesi -positive cases, all were returning travellers from Thailand. The P. knowlesi -positive cases made up 6/9 of all diagnosed malaria cases imported from Thailand in the time period 2012 to 2017. In 4/5 of cases where a malaria rapid diagnostic test had been applied it revealed a negative result. P. knowlesi is an important differential diagnosis in travellers returning from south-east Asia with itineraries that include Thailand. This study highlights the importance of this Plasmodium species in this patient subgroup. Whenever malaria is suspected in a returning traveller from Thailand, P. knowlesi should be taken into consideration and a differential PCR be executed as currently the unequivocal diagnosis of P. knowlesi is based on nuclear amplification techniques.
Association Between Midlife Risk Factors and Late-Onset Epilepsy
Authors: Emily L. Johnson, Gregory L. Krauss, Alexandra K. Lee, Andrea L. C. Schneider, Jennifer L. Dearborn, Anna M. Kucharska-Newton, Juebin Huang, Alvaro Alonso, Rebecca F. Gottesman
Journal: JAMA Neurology (2018)

The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear.To identify midlife vascular and lifestyle risk factors for late-onset epilepsy.The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018.Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors.Time to development of late-onset epilepsy (2 or more International Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures.Of the 10 420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E ε4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia.Potentially modifiable risk factors in midlife and the APOE ε4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.
Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study
Authors: Alessandro Vitale, Fabio Farinati, Giulia Noaro, Patrizia Burra, Timothy M. Pawlik, Laura Bucci, Edoardo G. Giannini, Chiara Faggiano, Francesca Ciccarese, Gian Lodovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Rodolfo Sacco, Giuseppe Cabibbo, Roberto Virdone, Fabio Marra, Martina Felder, Filomena Morisco, Luisa Benvegnù, Antonio Gasbarrini, Gianluca Svegliati‐Baroni, Francesco Giuseppe Foschi, Andrea Olivani, Alberto Masotto, Gerardo Nardone, Antonio Colecchia, Fabio Fornari, Massimo Marignani, Susanna Vicari, Emanuela Bortolini, Raffaele Cozzolongo, Alessandro Grasso, Camillo Aliberti, Mauro Bernardi, Anna Chiara Frigo, Mauro Borzio, Franco Trevisani, Umberto Cillo
Journal: Hepatology (2018)

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively).Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.
Anti–Glycoprotein VI Treatment Severely Compromises Hemostasis in Mice With Reduced α2β1 Levels or Concomitant Aspirin Therapy
Authors: SabineGrüner, MiroslavaProstredna, BarsomAktas, AlexandraMoers, ValerieSchulte, ThomasKrieg, StefanOffermanns, BeateEckes, BernhardNieswandt
Journal: Circulation (2004)

Background— Platelet inhibition is a major strategy to prevent arterial thrombosis, but it is frequently associated with increased bleeding because of impaired primary hemostasis. The activating platelet collagen receptor, glycoprotein VI (GP VI), may serve as a powerful antithrombotic target because its inhibition or absence results in profound protection against arterial thrombosis but no major bleeding in mice. Methods and Results— Mice lacking (−/−) or expressing half-levels (+/−) of the other major platelet collagen receptor, integrin α2β1, were injected with the anti–GP VI antibody JAQ1 and analyzed on day 5. Anti–GP VI treatment resulted in a marked hemostatic defect in α2−/− or α2+/− mice, as shown by dramatically prolonged tail bleeding times. Platelet adhesion to collagen was studied in an ex vivo whole-blood perfusion system under high shear conditions. Weak integrin activation by thromboxane A2 (TxA2) receptor stimulation restored defective adhesion of anti–GP VI–treated wild-type but not α2−/...
Rituximab maintenance therapy for mantle cell lymphoma: A systematic review and meta‐analysis
Authors: Talal Hilal, Zhen Wang, Diana Almader‐Douglas, Allison Rosenthal, Craig B. Reeder, Tania Jain
Journal: American Journal of Hematology (2018)

Mantle cell lymphoma is characterized by relapse and progressive disease, despite initial response to chemoimmunotherapy. We conducted a systematic review and meta-analysis to determine the efficacy of rituximab maintenance (RM) therapy in patients with mantle cell lymphoma. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials from database inception through November 1, 2017. Only full-text articles were included. Prespecified data elements were extracted from each trial. Outcomes of interest included progression-free survival (PFS) and overall survival (OS). The overall effect was pooled using the Der Simonian-Laird random effects model. Three randomized controlled trials and four observational studies met our inclusion criteria and were identified in the analyses. Six studies compared RM therapy to observation, and one compared RM therapy to interferon alfa. Meta-analysis evaluating outcomes of patients treated after ASCT revealed that RM improved for both PFS (HR = 0.33, 95% CI = 0.23-0.49) and OS (HR of death = 0.35, 95% CI = 0.17-0.69). A second meta-analysis of studies evaluating outcomes of patients who are ASCT-ineligible treated with anthracycline-based induction therapy revealed that RM improved PFS (HR = 0.38, 95% CI = 0.25-0.58). There is a paucity of data on the role of RM in ASCT-ineligible patients and those with relapsed disease. Overall, RM therapy appears to improve PFS and OS in previously untreated patients with mantle cell lymphoma who undergo induction chemoimmunotherapy followed by ASCT.
Recent Progress in Isolation and Detection of Extracellular Vesicles for Cancer Diagnostics
Authors: Wenshuo Wang, Jing Luo, Shutao Wang
Journal: Advanced Healthcare Materials (2018)

Abstract Extracellular vesicles (EVs) are emerging as one of the many new and promising biomarkers for liquid biopsy of cancer due to their loading capability of some specific proteins and nucleic acids that are closely associated with cancer states. As such, the isolation and detection of cancer‐derived EVs offer important information in noninvasive diagnosis of early‐stage cancer and real‐time monitoring of cancer development. In light of the importance of EVs, over the last decade, researchers have made remarkable innovations to advance the development of EV isolation and detection methods by taking advantage of microfluidics, biomolecule probes, nanomaterials, surface plasmon, optics, and so on. This review introduces the basic properties of EVs and common cancer‐derived EV ingredients, and provides a comprehensive overview of EV isolation and detection strategies, with emphasis on liquid biopsies of EVs for cancer diagnostics.