tbuckley/cabot-search huggingface dataset:
Stem cell-based retina models
Authors: Kevin Achberger, Jasmin C. Haderspeck, Alexander Kleger, Stefan Liebau
Journal: Advanced Drug Delivery Reviews (2018)

From the early days of cell biological research, the eye-especially the retina-has evoked broad interest among scientists. The retina has since been thoroughly investigated and numerous models have been exploited to shed light on its development, morphology, and function. Apart from various animal models and human clinical and anatomical research, stem cell-based models of animal and human cells of origin have entered the field, especially during the last decade. Despite the observation that the retina of different species comprises endogenous stem cells, most stem cell-related research in the human retina is now based on pluripotent stem cell models. Herein, systems of two-dimensional (2D) cultures and co-cultures of distinctly differentiated retinal subtypes revealed a variety of cellular aspects but have in many aspects been replaced by three-dimensional (3D) structures-the so-called retinal organoids. These organoids not only contain all major retinal cell subtypes compared to the physiological situation, but also show a distinct layering in close proximity to the in vivo morphology. Nevertheless, all these models have inherent advantages and disadvantages, which are expounded and summarized in this review. Finally, we discuss current application aspects of stem cell-based retina models and the specific promises they hold for the future.
RNA-Seq profiling of circular RNAs in human laryngeal squamous cell carcinomas
Authors: Cheng Lu, Xi Shi, Amanda Y. Wang, Yuan Tao, Zhenxiao Wang, Chaoping Huang, Yuehua Qiao, Hongyi Hu, Liangfa Liu
Journal: Molecular Cancer (2018)

Abnormal expression of non-coding circular RNAs (circRNAs) have been reported in many types of tumors. circRNA have been suggested to be an ideal candidate biomarker for diagnostic and therapeutic implications in cancers. The aim of this study was to assess the circRNA expression profile of laryngeal squamous cell carcinomas (LSCC). The biopsy samples from patients with LSCC were obtained intra-operatively. The circRNA expression was performed using secondary sequencing. Among 10 patients with LSCC, 2 were well differentiated, 3 were moderately differentiated and 5 were adjunctive samples with normal and LSCC tissues. A total of 21,444 distinct circRNA candidates were detected. Among them, we defined the statistical criteria for selecting aberrant-expressed circRNA using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. A total of 29 circRNA were upregulated and 19 circRNA were downregulated significantly in the LSCC tissues. The intersection of these dysregulated circRNAs of normal-well differentiated set and normal-moderately differentiated set was then assessed to narrow the upregulated and downregulated circRNAs down to 18 and 5 respectively. Furthermore, an association of the circRNA-miRNA-mRNA was investigated, showing that 20 dysregulated circRNA successfully predicted an interaction with several cancer-related miRNAs. Finally, a further KEGG analysis showed that PPAR, Axon guidance, Wnt and Cell cycle signaling pathway were key putative pathways in the process of LSCC. hsa_circ:chr20:31876585–31,897,648 was found to be able to differentiate most of LSCC from the matching normal tissues. This observational study demonstrated dysregulation of circRNA in LSCC, which may have an impact on development of potential biomarkers in this disease. Validation of down-regulation of hsa_circ:chr20:31876585–31,897,648 in LSCC compared to each adjunctive tissue by Q-RT-PCR, indicating that hsa_circ:chr20:31876585–31,897,648 may be a novel promising tumor suppresser in LSCC.
Abstract 17378: Atheroprotective Laminar Flow Represses the H3k27me3 Epigenetic Mark in Human Endothelial Cells Through Down-regulation of Ezh2
Authors: Suowen Xu, Meimei Yin, Yanni Xu, Marina Koroleva, Zheng Gen Jin
Journal: Circulation (2016)

Introduction:  Atherosclerosis is an epigenetic disease, in which pro-atherosclerotic factors, such as low-density lipoprotein (LDL), oxidized LDL, high glucose, disturbed flow (oscillatory shear stress), and homocysteine impacts DNA methylation and histone modifications on specific gene loci in vascular cells. However, it remains largely unknown whether atheroprotective laminar flow regulates endothelial function by modifying histone methylation. Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme and the catalytic subunit of the polycomb repressive complex 2 (PRC2), which methylates lysine-27 (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.   Hypothesis:  Laminar flow affects EZH2 mediated histone methylation and downregulation of EZH2/H3K27me3 mediates the atheroprotective effects of laminar flow.   Methods:  Western blot, real time PCR, en face staining, ChIP aasay, RNA-sequencing.   Results:  Here we report that laminar flow decreases the H3K27me3 epigenetic mark in human endothelial cells (ECs) through down-regulation of EZH2, which in part mediates laminar flow atheroprotective action. In vivo, EZH2 expression and activity (H3K27me3) was significantly diminished in laminar flow area of mouse aorta. In vitro, EZH2 expression and activity (H3K27me3) was reduced in cultured human ECs subjected to laminar flow . Moreover, laminar flow decreased expression of EZH2 via flow-responsive miR101. RNA sequencing (RNA-Seq) profiling in EZH2-depleted ECs reveals that EZH2 regulates a cohort of genes relevant to vascular inflammation. Like laminar flow, siRNA-mediated EZH2 depletion or pharmacological inhibition of EZH2 activity reduced TNF-α induced monocyte adhesion to human ECs.   Conclusions:  Collectively, our results demonstrate that laminar flow modulates the EZH2/H3K27me3 pathway in ECs. Our findings also suggest that EZH2 critically regulates the inflammatory status in endothelium and pharmacological inhibition of EZH2 may therefore be a promising strategy for treating atherosclerotic vascular disease.
Abstract 18169: Thromboelastography Predicts Peri-Operative Bleeding Outcomes in Pediatric Patients Undergoing Cardiac Surgery
Authors: Sirisha Emani, David Zurakowski, Michelle Mulone, James DiNardo, Juan Ibla, Sitaram M Emani
Journal: Circulation (2016)

Introduction:  Peri-operative bleeding is the most common morbidity in pediatric patients undergoing cardiac surgery. Although thromboelastography (TEG) has been utilized in select patients, its ability to predict bleeding in this population has not been established.   Hypothesis:  We hypothesize that TEG parameters predict bleeding outcomes peri-operatively in pediatric patients undergoing cardiac surgery.   Methods:  TEG was performed in 450 pediatric patients undergoing complex cardiac surgery requiring cardiopulmonary bypass (CPB). TEG was performed at baseline (T0), post-protamine in the OR (T1), during the first ICU labs (T2), and 24-hours post-surgery (T3). TEG values from all time points were compared in patients with and without perioperative bleeding. Bleeding was defined by several methods - objective (transfusion requirements, need for re-exploration) or subjective (time spent controlling bleeding in OR, and caregiver assessment).   Results:  Although none of the TEG parameters were significantly different between bleeding and non-bleeding patients at the T0, T2, or T3 time points, significantly higher ADP-induced platelet inhibition at T0 was observed in bleeding patients (37.6%) compared to non-bleeding patients (13.5%) (p   Conclusions:  Inhibition of platelet function pre-surgery may predict peri-operative bleeding. Abnormal TEG MA is associated with perioperative bleeding. Prophylactic platelet transfusion in the OR may not be useful to prevent bleeding in the ICU when patients are not bleeding and with normal MA.
Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells
Authors: Miroslav Hons, Aglaja Kopf, Robert Hauschild, Alexander Leithner, Florian Gaertner, Jun Abe, Jörg Renkawitz, Jens V. Stein, Michael Sixt
Journal: Nature Immunology (2018)
Multifunctional Smart Skin Adhesive Patches for Advanced Health Care
Authors: Insol Hwang, Hong Nam Kim, Minho Seong, Sang‐Hyeon Lee, Minsu Kang, Hoon Yi, Won Gyu Bae, Moon Kyu Kwak, Hoon Eui Jeong
Journal: Advanced Healthcare Materials (2018)

Abstract A skin adhesive patch is the most fundamental and widely used medical device for diverse health‐care purposes. Conventional skin adhesive patches have been mainly utilized for routine medical purposes such as wound management, fixation of medical devices, and simple drug release. In contrast to traditional skin adhesive patches, recently developed patches incorporate multiple key functions of bulky medical devices into a thin, flexible patch based on emerging nanomaterials and flexible electronic technologies. Consequently, the meaning of the term “skin adhesive patch” becomes broader and smarter compared to the traditional term. This review summarizes recent efforts undertaken in the development of multifunctional advanced skin adhesive patches, and briefly describes future directions and challenges toward the next generation of smart skin adhesive patches for ubiquitous personalized health care.
Negligible import of enteric pathogens by newly arrived asylum seekers and no impact on incidence of notified Salmonella and Shigella infections and outbreaks in Rhineland-Palatinate, Germany, January 2015 to May 2016
Authors: Lutz Ehlkes, Maja George, Donald Knautz, Florian Burckhardt, Klaus Jahn, Manfred Vogt, Philipp Zanger
Journal: Eurosurveillance (2018)

IntroductionThe 2015 refugee crisis raised concerns about an import of infectious diseases affecting the German population. Aims: To evaluate public and individual health benefits of stool screening, and explore whether importation of enteric pathogens by newly-arrived asylum seekers impacts on the host population. Methods: We used data from mandatory stool screening to determine the overall, age, sex, and country-specific prevalence of enteric bacteria and helminths. We used surveillance data to assess whether the number of incoming asylum seekers influenced notifications of salmonellosis and shigellosis in Rhineland-Palatinate. Results: Salmonella were found in 0.2% (95% confidence interval (CI) 0.2-0.3%) of 23,410 samples collected from January 2015 to May 2016. Prevalence was highest in children under 5 years (0.8%; 95% CI: 0.5-1.3%). No Shigella or invasive Salmonella spp. were detected. In a subset of 14,511 samples, the prevalence of helminth infestation was 2.4% (95% CI: 2.1-2.6%), with highest proportions detected in adolescents (4.6%; 95% CI 3.8-5.4%) and among Eritreans (9.3%; 95% CI: 7.0-12.0%); in the latter particularly Schistosoma mansoni and Taenia spp. The increase in asylum applications did not increase notifications of salmonellosis and shigellosis. No transmission from asylum seekers to German residents was notified. Conclusion: Public health risk associated with imported enteric pathogens is very low overall. Addressing individual and public health risks, we recommend replacing stool screening of all newly-arrived asylum seekers by a targeted approach, with target groups and approaches being adapted if necessary. Target groups supported by our data are children, adolescents, and Eritreans.
Validation of the 16-Gene Recurrence Score in Patients with Locoregional, High-Risk Renal Cell Carcinoma from a Phase III Trial of Adjuvant Sunitinib
Authors: Brian I. Rini, Bernard Escudier, Jean-Francois Martini, Ahmed Magheli, Christer Svedman, Margarita Lopatin, Dejan Knezevic, Audrey D. Goddard, Phillip G. Febbo, Rachel Li, Xun Lin, Olga Valota, Michael Staehler, Robert J. Motzer, Alain Ravaud
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Adjuvant sunitinib prolonged disease-free survival (DFS; HR, 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC after nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored the association of RS results with prediction of sunitinib benefit. Patients and Methods: The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer–specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and those without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 [95% confidence interval (CI), 2.15–39.24; P &amp;lt; 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy. Clin Cancer Res; 24(18); 4407–15. ©2018 AACR.
<i>TP53, STK11</i>, and <i>EGFR</i> Mutations Predict Tumor Immune Profile and the Response to Anti–PD-1 in Lung Adenocarcinoma
Authors: Jérôme Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, François Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène Blons, Diane Damotte
Journal: Clinical Cancer Research (2018)

Purpose: By unlocking antitumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed.Experimental Design: We performed in-depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry, and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and PD-L1 expression, and a public clinical database was used to validate the results obtained.Results: We showed that distinct combinations of STK11, EGFR, and TP53 mutations were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations (TP53-mut/STK11-EGFR-WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T-cell density and PD-L1 expression. In this tumor subtype, pathways related to T-cell chemotaxis, immune cell cytotoxicity, and antigen processing were upregulated. Finally, a prolonged progression-free survival (PFS: HR = 0.32; 95% CI, 0.16-0.63, P < 0.001) was observed in anti-PD-1-treated patients harboring TP53-mut/STK11-EGFR-WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression.Conclusions: Our study reveals that different combinations of TP53, EGFR, and STK11 mutations, together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade. Clin Cancer Res; 24(22); 5710-23. ©2018 AACR.
Dietary Fiber Confers Protection against Flu by Shaping Ly6c− Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism
Authors: Aurélien Trompette, Eva S. Gollwitzer, Céline Pattaroni, Isabel C. Lopez-Mejia, Erika Riva, Julie Pernot, Niki Ubags, Lluis Fajas, Laurent P. Nicod, Benjamin J. Marsland
Journal: Immunity (2018)
<i>Notes from the Field:</i> Acute Poisonings from a Synthetic Cannabinoid Sold as Cannabidiol — Utah, 2017–2018
Authors: Roberta Z. Horth, Barbara Crouch, B. Zane Horowitz, Amelia Prebish, Matthew Slawson, Jennifer McNair, Chris Elsholz, Stephen Gilley, Jenny Robertson, Ilene Risk, Mary Hill, Linnea Fletcher, Wei Hou, Dallin Peterson, Karlee Adams, Dagmar Vitek, Allyn Nakashima, Angela Dunn
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
Transplant-Free Survival and Interventions at 6 Years in the SVR Trial
Authors: Jane W. Newburger, Lynn A. Sleeper, J. William Gaynor, Danielle Hollenbeck-Pringle, Peter C. Frommelt, Jennifer S. Li, William T. Mahle, Ismee A. Williams, Andrew M. Atz, Kristin M. Burns, Shan Chen, James Cnota, Carolyn Dunbar-Masterson, Nancy S. Ghanayem, Caren S. Goldberg, Jeffrey P. Jacobs, Alan B. Lewis, Seema Mital, Christian Pizarro, Aaron Eckhauser, Paul Stark, Richard G. Ohye
Journal: Circulation (2018)

Background: In the SVR trial (Single Ventricle Reconstruction), 1-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock–Taussig shunt in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups. Methods: Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial. Results: Transplant-free survival for the RVPAS versus modified Blalock–Taussig shunt groups did not differ at 6 years (64% versus 59%, P =0.25) or with all available follow-up of 7.1±1.6 years (log-rank P =0.13). The RVPAS versus modified Blalock–Taussig shunt treatment effect had nonproportional hazards ( P =0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before stage II surgery (HR, 0.66; 95% confidence interval, 0.48–0.92). The effect of shunt type on death or transplant was not statistically significant between stage II to Fontan surgery (HR, 1.36; 95% confidence interval, 0.86–2.17; P =0.17) or after the Fontan procedure (HR, 0.76; 95% confidence interval, 0.33–1.74; P =0.52). By 6 years, patients with RVPAS had a higher incidence of catheter interventions (0.38 versus 0.23/patient-year, P &lt;0.001), primarily because of more interventions between the stage II and Fontan procedures (HR, 1.72; 95% confidence interval, 1.00–3.03). Complications did not differ by shunt type; by 6 years, 1 in 5 patients had had a thrombotic event, and 1 in 6 had had seizures. Conclusions: By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS versus modified Blalock–Taussig shunt groups. Children assigned to the RVPAS group had 5% higher transplant-free survival, but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00115934.
Effects of mindfulness training programmes delivered by a self-directed mobile app and by telephone compared with an education programme for survivors of critical illness: a pilot randomised clinical trial
Authors: Christopher E Cox, Catherine L Hough, Derek M Jones, Anna Ungar, Wen Reagan, Mary D Key, Tina Gremore, Maren K Olsen, Linda Sanders, Jeffrey M Greeson, Laura S Porter
Journal: Thorax (2018)

Patients who are sick enough to be admitted to an intensive care unit (ICU) commonly experience symptoms of psychological distress after discharge, yet few effective therapies have been applied to meet their needs.Pilot randomised clinical trial with 3-month follow-up conducted at two academic medical centres. Adult (≥18 years) ICU patients treated for cardiorespiratory failure were randomised after discharge home to 1 of 3 month-long interventions: a self-directed mobile app-based mindfulness programme; a therapist-led telephone-based mindfulness programme; or a web-based critical illness education programme.Among 80 patients allocated to mobile mindfulness (n=31), telephone mindfulness (n=31) or education (n=18), 66 (83%) completed the study. For the primary outcomes, target benchmarks were exceeded by observed rates for all participants for feasibility (consent 74%, randomisation 91%, retention 83%), acceptability (mean Client Satisfaction Questionnaire 27.6 (SD 3.8)) and usability (mean Systems Usability Score 89.1 (SD 11.5)). For secondary outcomes, mean values (and 95% CIs) reflected clinically significant group-based changes on the Patient Health Questionnaire depression scale (mobile (-4.8 (-6.6, -2.9)), telephone (-3.9 (-5.6, -2.2)), education (-3.0 (-5.3, 0.8)); the Generalized Anxiety Disorder scale (mobile -2.1 (-3.7, -0.5), telephone -1.6 (-3.0, -0.1), education -0.6 (-2.5, 1.3)); the Post-Traumatic Stress Scale (mobile -2.6 (-6.3, 1.2), telephone -2.2 (-5.6, 1.2), education -3.5 (-8.0, 1.0)); and the Patient Health Questionnaire physical symptom scale (mobile -5.3 (-7.0, -3.7), telephone -3.7 (-5.2, 2.2), education -4.8 (-6.8, 2.7)).Among ICU patients, a mobile mindfulness app initiated after hospital discharge demonstrated evidence of feasibility, acceptability and usability and had a similar impact on psychological distress and physical symptoms as a therapist-led programme. A larger trial is warranted to formally test the efficacy of this approach.Results, NCT02701361.