tbuckley/cabot-search huggingface dataset:
Inhibitory Regulation of Skin Fibrosis in Systemic Sclerosis by Apelin/APJ Signaling
Authors: Yoko Yokoyama, Akiko Sekiguchi, Chisako Fujiwara, Akihiko Uchiyama, Akihito Uehara, Sachiko Ogino, Ryoko Torii, Osamu Ishikawa, Sei‐ichiro Motegi
Journal: Arthritis & Rheumatology (2018)

Objective Apelin/ APJ signaling has been determined to regulate cardiac and arterial fibrosis and to be involved in the pathogenesis of pulmonary arterial hypertension. Our objective was to elucidate the role of apelin in skin fibrosis in systemic sclerosis ( SS c). Methods Expression of apelin/ APJ in normal and SS c fibroblasts was compared. Effects of small interfering RNA depletion and the addition of apelin in fibroblasts were analyzed. The effect of apelin injections on bleomycin‐induced dermal fibrosis in mice was investigated. We analyzed the effects of the biased agonist of APJ , MM 07, on skin fibrosis in vitro and in vivo. Results The expression of apelin in SS c fibroblasts was significantly lower than that in normal fibroblasts. Serum apelin levels were negatively correlated with the modified Rodnan skin thickness score in SS c patients. Stimulation with transforming growth factor β1 ( TGF β1) inhibited apelin expression in fibroblasts, suggesting that activation of TGF β1 signaling in SS c might be responsible for reduced apelin expression in SS c fibroblasts. Small interfering RNA depletion of apelin from fibroblasts significantly enhanced fibrosis‐related gene expression, and treatment with apelin protein significantly inhibited TGF β1 signaling in fibroblasts. Administration of apelin significantly inhibited bleomycin‐induced dermal fibrosis in mice. We demonstrated that MM 07 had greater potential than apelin to inhibit fibrosis in vivo and in vitro. Conclusion Collectively, TGF β1 signaling and apelin signaling may counteract each other in the fibrotic process of SS c. Inhibitory regulation of TGF β1‐induced skin fibrosis by apelin/ APJ signaling may be involved in the pathogenesis of SS c and could be a therapeutic target for fibrosis in SS c patients.
Spatial systems lipidomics reveals nonalcoholic fatty liver disease heterogeneity
Authors: K. Scupakova, Z. Soons, G. Ertaylan, K.A. Pierzchalski, G.B. Eijkel, S.R. Ellis, J.W. Greve, A. Driessen, T.M. De Kok, S. Rensen, S.O. Damink, R.M.A. Heeren
Journal: Journal of Hepatology (2018)
Developmental Delay, Treatment-Resistant Psychosis, and Early-Onset Dementia in a Man With 22q11 Deletion Syndrome and Huntington’s Disease
Authors: Martilias Farrell, Maya Lichtenstein, James J. Crowley, Dawn M. Filmyer, Gabriel Lázaro-Muñoz, Rita A. Shaughnessy, Ian R. Mackenzie, Veronica Hirsch-Reinshagen, Robert Stowe, James P. Evans, Jonathan S. Berg, Jin Szatkiewicz, Richard C. Josiassen, Patrick F. Sullivan
Journal: American Journal of Psychiatry (2018)
Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts early occurrence of hepatocellular carcinoma in SVR achieved hepatitis C patients with interferon-free treatment
Authors: Y. Yasui, M. Kurosaki, T. Nobuharu, Y. Komiyama, H. Takada, K. Watakabe, M. Okada, W. Wan, T. Shimizu, Y. Kubota, M. Higuchi, K. Takaura, K. Tsuchiya, H. Nakanishi, J. Itakura, N. Izumi
Journal: Journal of Hepatology (2018)
Abstract 18468: The Healthy Weights Initiative
Authors: Mark Lemstra
Journal: Circulation (2015)

Few community-based obesity reduction programs have been evaluated. After 153 community consultations, the city of Moose Jaw, Saskatchewan, Canada decided to initiate a free comprehensive program. The initiative included 71 letters of support from the Mayor, every family physician, cardiologist and internist in the city and every relevant community group including the Heart and Stroke Foundation, the Canadian Cancer Society and the Public Health Agency of Canada. The objective was to promote strong adherence while positively influencing a wide range of physical and mental health variables measured through objective assessment or validated surveys. The only inclusion criteria was that the individuals must be obese adults (BMI &gt;30). Participants were requested to sign-up with a “buddy” who was also obese and identify three family members or friends to sign a social support contract. During the initial 12 weeks, each individual received 60 group exercise sessions, 12 group cognitive behaviour therapy sessions and 12 group dietary sessions with licensed professionals. During the second 12 week period, maintenance therapy included 12 group exercise sessions. To date, 243 people have been referred with 229 starting. Among those who started, 183 completed the program (79.9%) while 15 quit for medical reasons and 31 quit for personal reasons. Mean objective reductions included 31.0 pounds of body fat, 3.9 percent body fat, 2.9 inches from the waist, 2.3 inches from the hip, blood cholesterol by 0.5 mmol/L, systolic blood pressure by 5.9 mmHg and diastolic blood pressure by 3.2 mmHg (all p&lt;.000). There were no changes in blood sugar levels. There was also statistically significant differences in aerobic fitness, self-report health, quality of life measured by SF-36 and depressed mood measured by CES-D (all p&lt;.000). An independent risk factor for not completing the program was not having a family member or friend sign a social support contract (OR 2.91; 95% CI 1.01-8.34, p=.047). Education level was a confounder. Comprehensive obesity reduction programs can be effective when there is extensive consultation at the community level and social support at the individual level.
Cholesterol negatively regulates IL-9–producing CD8+ T cell differentiation and antitumor activity
Authors: Xingzhe Ma, Enguang Bi, Chunjian Huang, Yong Lu, Gang Xue, Xing Guo, Aibo Wang, Maojie Yang, Jianfei Qian, Chen Dong, Qing Yi
Journal: The Journal of Experimental Medicine (2018)

CD8+ T cells can be polarized into IL-9–secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8+ or CD4+ T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function.
Rapid in vitro evaluation of immune responses to tumor-derived organoids as an adjunct to immunotherapy trials.
Authors: Robert George Ramsay
Journal: Journal of Clinical Oncology (2017)

3573 Background: Cancer immunotherapy has made rapid advances with the development of agents that subvert the negative arm of the immune system. This has been important because patients can mount anti-tumor immune responses. In the case of colorectal cancer (CRC), the presence of tumour infiltrating lymphocytes (TILs) appears to have predictive power regarding outcome. Nevertheless, assays that directly evaluate the quality, phenotype and anti-tumor activity of TILs are lacking. Here a novel immune assay platform is presented that measures the kinetics of TIL killing which correlates with pathological tumour response after treatment. Methods: Treatment naïve fresh cancer biopsies were processed to generate organoids and TILs from patients (n = 12) with pathological complete response (pCR) verses non-responding tumours (NRT). These were co-cultured with TILs to organoid ratios of 1:1, 5:1 and 10:1 for 48 hs and TILs function were measured by cytokine release and mean fluorescence intensity (MFI) based upon activated caspase activity. Additionally, TILs from patients with metastatic CRC (n = 20) have also been evaluated. Results: Ten thousand+ organoids are routinely cultured while millions of TILs are retrieved and expanded from biopsies. TIL-mediated killing of patient-matched tumor organoid confirm CD8+ve specific killing. At 24hrs MFI was significantly higher in pCR organoid indicative of immune-mediated cell death compared to NRT organoids at a ratio of 1:1. The efficiency of TIL killing was further enhanced as the ratio increased to 5:1 and 10:1. Gamma interferon production by cytotoxic (CD8+) T-cell is a robust measure of TIL activation state and was also significantly higher by pCR TILs compared to NRT TILs. Substantive differences in TIL subsets were also found in mCRC-derived samples compared to primary CRC. Conclusions: This is a novel functional immune assay and the first of its kind that successfully demonstrated the differences in patient-matched TIL killing between non-responding and responding CRC. This assay can be performed within in two weeks and thus it has translational potential that may change clinical management in the future and immunotherapy strategy design.
Follow-up of Patients with Clear-Cell Adenocarcinoma of the Vagina and Cervix
Authors: Dezheng Huo, Diane Anderson, Arthur L Herbst
Journal: New England Journal of Medicine (2018)

Clear-Cell Adenocarcinoma and DES Exposure Among 695 women with clear-cell carcinoma of the vagina and cervix who were followed for a median of nearly 23 years, 5-year survival was 86% among women with documented diethylstilbestrol exposure and 81% among those without such exposure.
Listening in on the Microbubble Crowd: Advanced Acoustic Monitoring for Improved Control of Blood-Brain Barrier Opening with Focused Ultrasound
Authors: Catherine M. Gorick, Natasha D. Sheybani, Colleen T. Curley, Richard J. Price
Journal: Theranostics (2018)

Non-invasive drug and gene delivery to the brain to treat central nervous system pathologies has long been inhibited by the blood-brain barrier.The activation of microbubbles with focused ultrasound has emerged as a promising non-invasive approach to circumvent this obstacle, by transiently disrupting the blood-brain barrier and permitting passage of systemically administered therapeutics into the tissue.Clinical trials are underway to evaluate the safety of this technique; however, concerns remain regarding the potential for the treatment to induce sterile inflammation or petechiae.In this issue of Theranostics, Jones et al. [1] address these concerns through the development of an advanced three-dimensional imaging system for monitoring acoustic emissions from oscillating microbubbles.When subharmonic emissions are detected with this system, focused ultrasound pressure is reduced by 50% for the remainder of the treatment.This serves to transiently open the blood-brain barrier without generating adverse effects.While the ideal configuration of the transducer array for treatment and monitoring still presents an area for further optimization, the approach indicates that the acoustic signature of microbubble behavior within the skull can be used to ensure safe and effective blood-brain barrier opening using focused ultrasound.
Criteria to Determine Reliability of Noninvasive Assessment of Liver Fibrosis With Virtual Touch Quantification
Authors: Jerome Boursier, Christophe Cassinotto, Gilles Hunault, Sarah Shili, Jerome Lebigot, Bruno Lapuyade, Adrien Lannes, Jean-Baptiste Hiriart, Victoire Cartier, Brigitte Le Bail, Sophie Michalak, Amaury Mouries, Frederic Oberti, Faiza Chermak, Isabelle Fouchard-Hubert, Paul Cales, Christophe Aube, Victor de Ledinghen
Journal: Clinical Gastroenterology and Hepatology (2018)
Extracellular vesicles from mice with alcoholic liver disease carry a distinct protein cargo and induce macrophage activation through heat shock protein 90
Authors: Banishree Saha, Fatemeh Momen‐Heravi, Istvan Furi, Karen Kodys, Donna Catalano, Anwesha Gangopadhyay, Reka Haraszti, Abhishek Satishchandran, Arvin Iracheta‐Vellve, Adeyinka Adejumo, Scott A. Shaffer, Gyongyi Szabo
Journal: Hepatology (2017)

A salient feature of alcoholic liver disease (ALD) is Kupffer cell (KC) activation and recruitment of inflammatory monocytes and macrophages (MØs). These key cellular events of ALD pathogenesis may be mediated by extracellular vesicles (EVs). EVs transfer biomaterials, including proteins and microRNAs, and have recently emerged as important effectors of intercellular communication. We hypothesized that circulating EVs from mice with ALD have a protein cargo characteristic of the disease and mediate biological effects by activating immune cells. The total number of circulating EVs was increased in mice with ALD compared to pair‐fed controls. Mass spectrometric analysis of circulating EVs revealed a distinct signature for proteins involved in inflammatory responses, cellular development, and cellular movement between ALD EVs and control EVs. We also identified uniquely important proteins in ALD EVs that were not present in control EVs. When ALD EVs were injected intravenously into alcohol‐naive mice, we found evidence of uptake of ALD EVs in recipient livers in hepatocytes and MØs. Hepatocytes isolated from mice after transfer of ALD EVs, but not control EVs, showed increased monocyte chemoattractant protein 1 mRNA and protein expression, suggesting a biological effect of ALD EVs. Compared to control EV recipient mice, ALD EV recipient mice had increased numbers of F4/80 hi cluster of differentiation 11b (CD11b) lo KCs and increased percentages of tumor necrosis factor alpha–positive/interleukin 12/23–positive (inflammatory/M1) KCs and infiltrating monocytes (F4/80 int CD11b hi ), while the percentage of CD206 + CD163 + (anti‐inflammatory/M2) KCs was decreased. In vitro , ALD EVs increased tumor necrosis factor alpha and interleukin‐1β production in MØs and reduced CD163 and CD206 expression. We identified heat shock protein 90 in ALD EVs as the mediator of ALD‐EV‐induced MØ activation. Conclusion: Our study indicates a specific protein signature of ALD EVs and demonstrates a functional role of circulating EVs containing heat shock protein 90 in mediating KC/MØ activation in the liver. (H epatology 2018;67:1986‐2000).
Mechanism for hypertriglyceridemia and effect of fibrate coadministration during acetyl-CoA carboxylase inhibitor treatment
Authors: L. Goedeke, J. Bates, D. Vatner, R. Perry, M.W. Ellis, T. Wang, M. Subramanian, R. Myers, A. Ray, G.I. Shulman
Journal: Journal of Hepatology (2018)
Histomorphologic spectrum of germline-related and sporadic BAP1-inactivated melanocytic tumors
Authors: Erin M. Garfield, Kara E. Walton, Victor L. Quan, Timothy VandenBoom, Bin Zhang, Betty Y. Kong, Maria Cristina Isales, Elnaz Panah, Gene Kim, Pedram Gerami
Journal: Journal of the American Academy of Dermatology (2018)
Matrix protein tenascin-C expands and reversibly blocks maturation of murine eosinophil progenitors
Authors: Ton C. Doan, Brian M. Jeong, Mackenzie E. Coden, Lucas F. Loffredo, Swati Bhattacharyya, Sergio E. Chiarella, John Varga, Hiam Abdala-Valencia, Sergejs Berdnikovs
Journal: Journal of Allergy and Clinical Immunology (2018)
Outbreak of acute hepatitis A involving young men in Lombardy Region, Italy: risk factors, clinical and virological characteristics
Authors: M. Iavarone, M. Viganò, C. Orcese, M. Coen, C. Oggioni, A. Spinetti, A. Soria, C. Galli, C. Tagliacarne, L. Scaramella, M. Merli, R. Rossotti, G.A. Gubertini, S. Merli, A. Piscitelli, V. Castelli, A. Comelli, D. Cereda, M. Gramegna, M. Puoti, A. Gori, M.G. Rumi, F. Castelli, P. Lampertico, L. Romanò
Journal: Journal of Hepatology (2018)
Estimating the Cost-Effectiveness of Lung Cancer Screening with Low-Dose Computed Tomography for High-Risk Smokers in Australia
Authors: Stephen Wade, Marianne Weber, Michael Caruana, Yoon-Jung Kang, Henry Marshall, Renee Manser, Shalini Vinod, Nicole Rankin, Kwun Fong, Karen Canfell
Journal: Journal of Thoracic Oncology (2018)
Intraparticle FRET for Enhanced Efficiency of Two‐Photon Activated Photodynamic Therapy
Authors: Hongqian Cao, Yang Yang, Yanfei Qi, Yue Li, Bingbing Sun, Ying Li, Wei Cui, Juan Li, Junbai Li
Journal: Advanced Healthcare Materials (2018)

Abstract Photodynamic therapy (PDT) still faces two main problems on cancer therapy. One is how to improve PDT efficiency against hypoxic environment of tumors. The other one is how to overcome the limit of short wavelength light to increase PDT treatment depth. In this work, an intraparticle fluorescence resonance energy transfer (FRET) platform is designed to address these problems together. The nanoparticles are doped with multicomponents, such as catalase, two‐photon dyes, and traditional photosensitizers, with a simple “one‐pot” and green method. On the one hand, catalase can catalyze intracellular H 2 O 2 into O 2 and promote PDT efficiency. One the other hand, photosensitizers can be excited indirectly by two‐photon lasers through an intraparticle FRET mechanism, which results in deeper tissue penetration for PDT. These properties are verified through the material induced cytotoxicity in light or in dark and in vivo blocking blood‐vessel experiment.
The association of circulating microRNAs (miRs) with liver fibrosis stage and the impact of selonsertib treatment in patients with NASH
Authors: M. Charlton, A.M. Diehl, N. Sarkar, B. LI, L. Wang, A. Billin, S. Djedjos, M. Subramanian, R. Myers, N. Afdhal, S. Caldwell, Z. Goodman, R. Loomba
Journal: Journal of Hepatology (2018)
Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies
Authors: Brandon Bumbaca, Wei Li
Journal: Acta Pharmaceutica Sinica B (2018)

Despite its good initial response and significant survival benefit in patients with castration-resistant prostate cancer (CRPC), taxane therapy inevitably encounters drug resistance in all patients. Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression, and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics, indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.
Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment
Authors: Zhenqiang Sun, Shuaixi Yang, Quanbo Zhou, Guixian Wang, Junmin Song, Zhen Li, Zhiyong Zhang, Jizhong Xu, Kunkun Xia, Yuan Chang, Jinbo Liu, Weitang Yuan
Journal: Molecular Cancer (2018)

Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.
THE EFFICACY OF “HANDMADE MULTI-BENDING SYSTEM OF THE ENDOSCOPE” FOR ENDOSCOPIC SUBMUCOSAL DISSECTION OF THE DIFFICULT-TO-APPROACH SUPERFICIAL GASTRIC NEOPLASMS
Authors: K Yamamoto, K Tanaka, S Hayashi, N Tatsumi, T Michida, T Ito
Journal: Endoscopy (2018)

Maintaining good operative field is crucial in performing endoscopic submucosal dissection (ESD) for early stage gastrointestinal tumors, but it often requires high skill or special equipment depending on the lesion location. In ESD for the lesions at the lesser curvature of the gastric body, it is sometimes very difficult to approach the lesions, although early gastric cancers are often detected at this area. A multi-bending endoscope from Olympus is a very good option for such a situation, but it is difficult for most operators to prepare it at present due to its particularity. Therefore, we recently developed handmade multi-bending system and performed ESD using it for 10 lesions which were located at the lesser curvature of the gastric body and tended to be difficult to approach. Herein, we report its method and efficacy.
Antibiotics are the main cause of life threatening allergic reactions during surgery
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Antibiotics are the most frequent, and a growing, cause of life threatening anaphylaxis in the operating theatre, the largest prospective audit of anaphylaxis related to anaesthesia and surgery has found.1

The findings of the 6th National Audit Project of the Royal College of Anaesthetists (NAP6) contrast with those of previous studies which found the main culprit to be muscle relaxants.

Details of all cases of life threatening anaphylaxis that occurred in NHS hospitals during one year (5 November 2015 to 5 November 2016) were collected for the audit and 48% of the 266 cases …
<i>MIR142</i> Loss-of-Function Mutations Derepress ASH1L to Increase <i>HOXA</i> Gene Expression and Promote Leukemogenesis
Authors: Maria C. Trissal, Terrence N. Wong, Juo-Chin Yao, Rahul Ramaswamy, Iris Kuo, Jack Baty, Yaping Sun, Gloria Jih, Nishi Parikh, Melissa M. Berrien-Elliott, Todd A. Fehniger, Timothy J. Ley, Ivan Maillard, Pavan R. Reddy, Daniel C. Link
Journal: Cancer Research (2018)

Abstract Point mutations in the seed sequence of miR-142-3p are present in a subset of acute myelogenous leukemia (AML) and in several subtypes of B-cell lymphoma. Here, we show that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. Mir142 loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. During hematopoietic maturation, loss of Mir142 increased ASH1L protein expression and consequently resulted in the aberrant maintenance of Hoxa gene expression in myeloid-committed hematopoietic progenitors. Mir142 loss also enhanced the disease-initiating activity of IDH2-mutant hematopoietic cells in mice. Together these data suggest a novel model in which miR-142, through repression of ASH1L activity, plays a key role in suppressing HOXA9/A10 expression during normal myeloid differentiation. AML-associated loss-of-function mutations of MIR142 disrupt this negative signaling pathway, resulting in sustained HOXA9/A10 expression in myeloid progenitors/myeloblasts and ultimately contributing to leukemic transformation. Significance: These findings provide mechanistic insights into the role of miRNAs in leukemogenesis and hematopoietic stem cell function. Cancer Res; 78(13); 3510–21. ©2018 AACR.