tbuckley/cabot-search huggingface dataset:
Soy Protein/Cellulose Nanofiber Scaffolds Mimicking Skin Extracellular Matrix for Enhanced Wound Healing
Authors: Seungkuk Ahn, Christophe O. Chantre, Alanna R. Gannon, Johan U. Lind, Patrick H. Campbell, Thomas Grevesse, Blakely B. O'Connor, Kevin Kit Parker
Journal: Advanced Healthcare Materials (2018)

Abstract Historically, soy protein and extracts have been used extensively in foods due to their high protein and mineral content. More recently, soy protein has received attention for a variety of its potential health benefits, including enhanced skin regeneration. It has been reported that soy protein possesses bioactive molecules similar to extracellular matrix (ECM) proteins and estrogen. In wound healing, oral and topical soy has been heralded as a safe and cost‐effective alternative to animal protein and endogenous estrogen. However, engineering soy protein‐based fibrous dressings, while recapitulating ECM microenvironment and maintaining a moist environment, remains a challenge. Here, the development of an entirely plant‐based nanofibrous dressing comprised of cellulose acetate (CA) and soy protein hydrolysate (SPH) using rotary jet spinning is described. The spun nanofibers successfully mimic physicochemical properties of the native skin ECM and exhibit a high water retaining capability. In vitro, CA/SPH nanofibers promote fibroblast proliferation, migration, infiltration, and integrin β1 expression. In vivo, CA/SPH scaffolds accelerate re‐epithelialization and epidermal thinning as well as reduce scar formation and collagen anisotropy in a similar fashion to other fibrous scaffolds, but without the use of animal proteins or synthetic polymers. These results affirm the potential of CA/SPH nanofibers as a novel wound dressing.
Abstract P1-01-10: Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth
Authors: ER Sauter, B Li, J Hao, M Kong
Journal: Cancer Research (2018)

Abstract Background: Obesity increases the risk of many types of cancer, including breast cancer. The underlying mechanisms that drive obesity-related breast cancer remain unclear. Fatty Acid Binding Proteins (FABPs) are a family of cytosolic proteins which are organ specific and coordinate lipid transportation. Adipocyte FABP (A-FABP) is highly expressed in adipose tissues and may provide a link to obesity-associated breast cancer risk. We previously observed that A-FABP serum levels were associated with obesity, and decreased with surgically induced weight loss. In this report, we evaluate the role of A-FABP in promoting obesity-associated mammary tumor growth. Hypothesis: Deficiency of A-FABP in mice decreases obesity-associated mammary tumor progression. Methods: Weaned wild type control and A-FABP-deficient (genetically depleted A-FABP-/-) female mice (n=15/group) were randomly grouped and fed either a high fat diet (HFD) (60% fat) or a low fat diet (LFD) (10% fat). After 6 months on the diets, serum was collected from the tail vein and measured for levels of circulating A-FABP by ELISA. E0771 mammary tumor cells (0.5x106/mouse) were injected into the mammary fat pad and tumor volume measured at 3-day intervals. The student's t-test was used to compare A-FABP levels and ANOVA to compare tumor sizes in the lean and obese mice. Results: HFD-fed control mice exhibited a significant increase in body weight (31.5±2.13g) compared to LFD-fed control mice (19.86±0.36) (p&amp;lt;0.01). Serum levels of A-FABP were correspondingly elevated in obese (104.9±8.3 ng/ml) vs. lean controls (31.8±5.4 ng/ml) (p&amp;lt;0.01). Interestingly, although A-FABP deficient mice fed a HFD were more obese than HFD-fed control mice (final body weight 43.4g vs. 31.5 g) (p&amp;lt;0.05), tumor growth in the A-FABP deficient mice was significantly less than in controls (p&amp;lt;0.0001), suggesting that A-FABP expression is critical for obesity-associated mammary tumor growth. Long term tumor growth in lean A-FABP deficient vs. control mice was not significantly different. Thus, A-FABP deficiency appears to uncouple obesity and mammary tumor growth in HFD-induced obese mice. Impact: A-FABP is associated with obesity related breast/mammary cancer, and appears to be an important driver of tumor development. Downregulation of this protein may be useful to prevent and/or treat these tumors. Citation Format: Sauter ER, Li B, Hao J, Kong M. Expression of adipocyte fatty acid binding protein promotes obesity-associated mammary tumor growth [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-10.
LOW FLOW, LOW GRADIENT SEVERE MITRAL STENOSIS: HEMODYNAMICS, CLINICAL CHARACTERISTICS AND OUTCOMES
Authors: Abdallah El Sabbagh, Yogesh Reddy, Sergio Barros-Gomes, Barry Borlaug, William Miranda, Sorin Pislaru, Rick A. Nishimura, Patricia Pellikka
Journal: Journal of the American College of Cardiology (2018)
SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways
Authors: Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Journal: Cancer Research (2018)

Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.Significance: Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg Cancer Res; 78(9); 2305-17. ©2018 AACR.
Global proteome and phosphoproteome analysis of meningiomas
Authors: Jemma Dunn, Sara Ferluga, Edwin Lasonder, Oliver Hanemann
Journal: Neuro-Oncology (2018)

Meningiomas are common brain tumours arising from meningeal tissue. Despite the majority of them displaying benign features, they can cause mild to severe morbidity. The current main therapeutic approach is complete tumour resection commonly with adjunct radiation therapy. However, tumour location can hamper complete resection and chemotherapies are ineffective. In this study we aim to elucidate dysregulated pathways in meningioma pathogenesis and identify novel molecular targets by deciphering the proteome and phosphoproteome of different grades of meningiomas. Tumour lysates were collected from grade I, II and III frozen meningioma specimens and three normal healthy human meninges. Phosphoprotein purification was performed using Qiagen® PhosphoProtein Purification Kit. Proteins were separated by SDS-PAGE followed by in-gel tryptic digestion. Extracted peptides were purified and analysed by electrospray ionization LC-MS/MS. Raw mass spectrometry files were analysed using MaxQuantTM. Expression data was validated by Western blot and functionally annotated using Ingenuity® Pathway Analysis (IPA®) and DAVID 6.8. We have quantified 3888 proteins and 3074 phosphoproteins across all grades of meningioma and normal meninges. Comparative analysis confirmed 181 proteins and 338 phosphoproteins to be commonly significantly upregulated (log2 fold-change≥1.5; p<0.05) among all grades vs. normal meninges. We have successfully validated the expression data of several upregulated proteins and phosphoproteins. Gene Ontology revealed biological processes including EFGR and VEGFR signalling to be enriched in the phosphoproteome. Grade-wise comparisons identified 667 proteins and 769 phosphoproteins to be differentially expressed (p<0.05) between grade III meningiomas compared to grade II and I. We have performed a comparative proteomic analysis across all meningioma grades and identified changes in proteomic profiles between these tumours and normal healthy meninges. We will use this data to define novel targets common to all grades and specific to a grade of meningioma for future therapies.
NHS finance staff don’t feel appreciated by clinicians
Authors: Matthew Limb
Journal: BMJ (2016)

Many NHS finance staff have said that they feel they are not valued by clinicians, and many think that non-finance colleagues are lacking in financial literacy, a survey has found.

In a survey of 500 NHS finance staff in England, 46% said that they felt valued by clinicians in their organisation. This compared with 48% who felt valued by their boards and 78% who felt valued by their line managers.

The survey showed that 60% of respondents thought that better communication between finance and non-finance staff was …
Two thirds of junior doctors worry about lack of support from seniors, survey finds
Authors: Abi Rimmer
Journal: BMJ (2014)

As over 7000 foundation year 1 doctors begin their rotations in hospitals, the fears of new doctors have again been highlighted in poll findings.

The Medical Defence Union (MDU) conducted a survey of 704 junior doctors and medical students. It found that 60% of newly qualified and trainee doctors …
REGγ Controls Hippo Signaling and Reciprocal NF-κB–YAP Regulation to Promote Colon Cancer
Authors: Qingwei Wang, Xiao Gao, Tong Yu, Lei Yuan, Jie Dai, Weicang Wang, Geng Chen, Chan Jiao, Wang Zhou, Quan Huang, Long Cui, Pei Zhang, Robb E. Moses, Jianhua Yang, Fengyuan Chen, Junjiang Fu, Jianru Xiao, Lei Li, Yongyan Dang, Xiaotao Li
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Colorectal cancer is one of the most commonly diagnosed cancers closely associated with inflammation and hyperactive growth. We previously demonstrated a regulatory circuit between the proteasome activator REGγ and NF-kappaB (NF-κB) during colon inflammation, known to be important in the development of colitis-associated cancer as well as sporadic colorectal cancer. How the inflammatory microenvironment affects the Hippo pathway during colorectal cancer development is largely unknown. Experimental Design: Here, we used REGγ-deficient colon cancer cell lines, REGγ knockout mice, and human colorectal cancer samples to identify the novel molecular mechanism by which REGγ functions as an oncoprotein in the development of colorectal cancer. Results: REGγ can directly interact with Lats1 and promote its degradation, which facilitates Yes-associated protein (YAP) activation in colon cancer cells. REGγ deficiency significantly attenuated colon cancer growth, associated with decreased YAP activity. Suppression of tumor growth due to REGγ depletion was overcome by constitutively active YAP. Surprisingly, reciprocal activation of the YAP and NF-κB pathways was observed in human colon cancer cells. REGγ overexpression was found in over 60% of 172 colorectal cancer specimens, highly correlating with the elevation of YAP and p65. Postoperative follow-up revealed a significantly lower survival rate in patients with concomitantly high expression of REGγ, YAP, and p-p65. Conclusions: REGγ could be a master regulator during colorectal cancer development to promote YAP signaling and reinforce cross-talks between inflammation and growth pathways, and REGγ might be a new marker for prognosis of colorectal cancer patients. Clin Cancer Res; 24(8); 2015–25. ©2018 AACR.
Abstract P5-03-06: Novel targets of breast cancer associated with inflammatory tumor microenvironment
Authors: RK Tiwari, G Ben Rahoma, N Tuli, R Bednarczyk, RR Maniyar, S Chakraborty, S Singh, A Mittelman, J Geliebter
Journal: Cancer Research (2018)

Abstract Breast cancer affects one in eight women in the USA. Considerable progress in the identification of genetic lesions and their modulation has resulted in newer therapies making breast cancer a manageable disease. However, triple negative breast cancer is still difficult to treat and warrants a search for newer targets. To this end, we focused our attention towards the modulation of the breast cancer epithelium by other cell types such as the endothelial cells and the macrophages. The migratory macrophages and the estrogen sensitive migratory endothelial progenitor cells (EPCs) constitute the cellular milieu within the tumor microenvironment which continuously modulates breast cancer epithelium. We analyzed the interactions of the breast cancer cell lines (MCF-7 and MDA-MB-231) with the highly proliferative human umbilical cord derived CD133+/CD34+/VEGFR-2+ EPCs and M1 polarized macrophages (activated THP-1 cell line) in two separate in vitro studies. The readouts were cell proliferation, changes in epithelial to mesenchymal transition (EMT), and cellular differentiation. We observed morphological and cellular growth changes in the EPCs on treatment with conditioned medium (CM) generated from breast cancer cells, consistent with vasculogenesis and in vitro tubulogenesis. Both, MDA-MB-231 and MCF-7 CM, treatments resulted in enhanced EPCs proliferation and differentiation. However, the differentiation patterns were distinct, with MCF-7 CM increasing the number of cell clusters, whereas MDA-MB-231 CM increasing the number of adherent spindle shaped cells. The paracrine interaction was also assessed with M1 polarized macrophages. We observed decreased cell viability in MCF-7 and MDA-MB-231 cells following activated THP-1 CM and exosome treatments. Analysis of exosomes from activated THP-1 indicated an upregulation of 13 miRNAs compared to unactivated THP-1. The miRNA hsa-miR-146a-5p had the highest upregulation (44 fold increase). This specific miRNA has been observed in senescent cell and it inhibits cell proliferation, suggesting a possible mechanism for exosome-associated growth inhibition. The analysis of the paracrine interactive mediators between breast cancer cells, EPCs, and M1 polarized macrophages is likely to yield viable novel clinically translatable therapeutic targets. Citation Format: Tiwari RK, Ben Rahoma G, Tuli N, Bednarczyk R, Maniyar RR, Chakraborty S, Singh S, Mittelman A, Geliebter J. Novel targets of breast cancer associated with inflammatory tumor microenvironment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-03-06.
Introducing Ronald J. Sokol, M.D.—our 2018 AASLD president
Authors: Cara L. Mack
Journal: Hepatology (2018)

1Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Digestive Health Institute, Children's Hospital ColoradoUniversity of Colorado School of MedicineAuroraCO *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Cara L. Mack, M.D.Section of Gastroenterology, Hepatology and Nutrition, Department of PediatricsDigestive Health Institute, Children's Hospital ColoradoUniversity of Colorado School of MedicineAurora, CO 80045E‐mail: [email protected]Tel: +1‐720‐271‐0830
Impaired Proteasomal Function in Human Osteoarthritic Chondrocytes Can Contribute to Decreased Levels of <scp>SOX</scp>9 and Aggrecan
Authors: Ramon L. Serrano, Liang‐Yu Chen, Martin K. Lotz, Ru Liu‐Bryan, Robert Terkeltaub
Journal: Arthritis & Rheumatology (2018)

Osteoarthritis (OA) chondrocytes exhibit impairment of autophagy, one arm of the proteostasis network that coordinates proteome and organelle quality control and degradation. Deficient proteostasis impacts differentiation and viability, and inflammatory processes in aging and disease. The present study was undertaken to assess ubiquitin proteasome system proteasomal function in OA chondrocytes.We evaluated human knee cartilage by immunohistochemistry, and assessed proteasomal function, levels of proteasomal core subunits and chaperones, and autophagy in cultured chondrocytes. Assays included Western blotting, quantitative reverse transcription-polymerase chain reaction, proteasomal protease activity assessment, and cell immunofluorescence analysis.Human knee OA cartilage exhibited polyubiquitin accumulation, with increased ubiquitin K48-linked polyubiquitinated proteins in situ, suggesting proteasomal impairment. Cultured OA chondrocytes demonstrated accumulation of K48 polyubiquitinated proteins, significantly reduced 20S proteasome core protease activity, and decreased levels of phosphorylated FOXO4 and proteasome 26S subunit, non-ATPase 11 (PSMD11), a FOXO4-inducible promoter of proteasomal activation. Levels of proteasome subunit β type 3 (PSMB3), PSMB5, PSMB6, and proteasome assembly chaperone 1 were not decreased in OA chondrocytes. In normal chondrocytes, PSMD11 small interfering RNA knockdown stimulated certain autophagy machinery elements, increased extracellular nitric oxide (NO) levels, and reduced chondrocytic master transcription factor SOX9 protein and messenger RNA (mRNA) and aggrecan (AGC1) mRNA. PSMD11 gain-of- function by transfection increased proteasomal function, increased levels of SOX9-induced AGC1 mRNA, stimulated elements of the autophagic machinery, and inhibited extracellular levels of interleukin-1-induced NO and matrix metalloproteinase 13 in OA chondrocytes.Deficient PSMD11, associated with reduced phosphorylated FOXO4, promotes impaired proteasomal function in OA chondrocytes, dysregulation of chondrocytic homeostasis, and decreased levels of SOX9 mRNA, SOX9 protein, and AGC1 mRNA. Chondrocyte proteasomal impairment may be a therapeutic target for OA.
COMPARISON OF CLINICAL OUTCOMES BETWEEN MAGMARIS (DREAMS 2G) AND ORSIRO DRUG ELUTING STENTS: POOLED PATIENT LEVEL ANALYSIS FROM BIOSOLVE II-III AND BIOFLOW II TRIALS
Authors: Alexandre Hideo-Kajita, Hector Garcia Garcia, Viana Azizi, Hüseyin Ince, Stephan Kische, Alexandre Abizaid, Ralph Töelg, Pedro Lemos, Nicolas Van Mieghem, Stefan Verheye, Clemens von Birgelen, Evald Christiansen, Willem Wijns, Thierry Lefèvre, Stephan Windecker, Ron Waksman, Michael Haude
Journal: Journal of the American College of Cardiology (2018)
Behaviors Related to Unintentional, Intentional Injuries, High School Students—United States, 1991
Journal: JAMA (1992)

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Children could keep the healthcare community on its toes
Authors: Sneha Rooh, Smita Asthana, Labani Satyanarayana
Journal: BMJ (2018)

Reading a scientific medical journal rarely makes one smile, but Wigley and colleagues’ article on what happens when you let children design patient information leaflets did just that.1

We wonder why information leaflets are filled with medical jargon; is it our fixation with brevity? The discomfort we inherit with …
Abstract 20192: Impact on Ejection Fraction and Major Adverse Cardiovascular Events in Heart Failure With Reduced Ejection Fraction Patients Undergoing Fractional Flow Reserve versus Angiography Guided Revascularization
Authors: Saad Sikanderkhel, Mohamed F Almahmoud, M. Waqas Choudhry, Hussain Ibrahim, Bao Nguyen, Russell Roark, Syed A Gilani, Wissam I Khalife
Journal: Circulation (2017)

Introduction: FFR has become the gold standard for assessing inducible myocardial ischemia in patients being evaluated for revascularization of intermediate grade coronary lesions. Outcomes in FFR ...
Understanding missed opportunities for more timely diagnosis of brain cancer – what can we learn from the BRACED qualitative interview study with adult glioma patients?
Authors: Clarissa Penfold, Alexis J Joannides, William Sage, Andrew Brodbelt, Michael D Jenkinson, Stephen Price, Colin Watts, Joyce Bell, Margaret Johnson, Willie Hamilton, Fiona M Walter
Journal: Neuro-Oncology (2018)

BRACED (The BRAin Cancer Early Detection study) is a qualitative study of patient perspectives on factors affecting timely diagnosis of primary brain tumours. Patient, doctor and health-care system-related factors can all contribute towards prolonged time to cancer diagnosis, impacting on patient experience, morbidity and mortality. To develop a richer understanding of adult glioma patients’ experiences and attributions of symptoms, and their routes to diagnosis. In-depth qualitative interviews with 20 patients with early analysis completed; a second phase of interviews is underway with another 20 patients, for a detailed exploration of early emerging themes. First phase participants were 14 men and 6 women, aged 22 - 76 (median 63) years. Participants reported varied routes and times to diagnosis, often involving more than one healthcare professional. Factors contributing to prolonged times to diagnosis were explored in analysis of patient narratives relating to initial assessment, diagnostic test performance and interpretation, and follow-up and coordination. There was evidence of challenges in presenting multiple and subtle symptoms in the context of a routine GP appointment. Some participants felt that their diagnosis may have been delayed in primary care by non-urgent referral to specialist care or ‘false’ reassurance following normal test results. Prolonged time to diagnosis was also suspected where: no CT or MRI scan was performed on emergency presentation despite being suggested by a clinician; a neurologist was called but did not see the patient prior to discharge; delays in reporting scan results occurred; or there was an apparent absence of ‘safety-netting’ advice to support patients in their ongoing appraisal of symptoms. Early findings identify a number of factors that may contribute to prolonged time to diagnosis after presentation, which could be minimised by improving guidance for both patients and clinicians.