tbuckley/cabot-search huggingface dataset:
Overuse injuries are prevalent in children’s competitive football: a prospective study using the OSTRC Overuse Injury Questionnaire
Authors: Mari Leppänen, Kati Pasanen, Benjamin Clarsen, Pekka Kannus, Roald Bahr, Jari Parkkari, Heidi Haapasalo, Tommi Vasankari
Journal: British Journal of Sports Medicine (2018)

Objectives To investigate the prevalence and burden of overuse injuries in children’s football as well as player characteristics and their association with overuse injury risk. Methods This investigation is based on the control arm (10 clubs) of a randomised controlled trial investigating prevention of injuries in youth football. We conducted a prospective 20-week follow-up study on overuse injuries among Finnish football players (n=733, aged 9–14 years). Each week, we sent a text message to players’ parents to ask if the player had sustained any injury during the past week. Players with overuse problem were interviewed over the phone using an overuse injury questionnaire. The main outcome measures were prevalence of all overuse injuries and substantial overuse injuries (those leading to moderate or severe reductions in participation or performance) and injury severity. Results The average response rate was 95%. In total, 343 players (46.8%) reported an overuse problem while in the study. The average weekly prevalence of all overuse problems and substantial overuse problems was 12.8% and 6.0%, respectively. Injuries affecting the knee had the highest weekly prevalence (5.7% and 2.4% for all and substantial knee problems, respectively). Girls had a higher likelihood of knee problems (OR 2.70; 95% CI 1.69 to 4.17), whereas boys had a higher likelihood of heel problems (OR 2.82; 95% CI 1.07 to 7.44). The likelihood of reporting an overuse problem increased with age (OR 1.21; 95% CI 1.00 to 1.47). Conclusion Overuse injuries are prevalent in children’s competitive football. Knee overuse injuries represent the greatest burden on participation and performance. Trial registration number ISRCTN14046021 .
Abstract 3705: Targeted anticancer drug delivery to Ewing's sarcoma using human anti-CD99 targeted hybrid polymerization liposomal nanoparticles
Authors: Hyunggyoo Kang, Jon Nagy, Timothy Triche
Journal: Cancer Research (2018)

Abstract Most anticancer therapies are unspecific and therefore inevitably lead to off-target toxicity. To overcome these shortcomings, targetable hybrid polymerization liposomal nanoparticles (HPLNs) have been invented. Multiple innovative and proprietary technologies have been developed to enable creation of this unique form of nanoparticle therapy, including the use of cross linked lipids to improve both stability and bioavailability, modified polyethylene glycol (PEG) for both ‘stealthiness' (to prevent immune response to the nanoparticle) and for covalent attachment of targeting molecules such as tumor specific antibodies or peptides. Our present study showed the superior efficacy of human anti-CD99 targeted HPLNs in the treatment of Ewing sarcoma. Human monoclonal anti-CD99 antibody-targeted HPLNs encapsulating irinotecan (CD99-HPLN/Ir) can efficiently reach implanted Ewing sarcoma tumors in xenograft mice and dramatically reduce and/or eliminate the tumor burden. Complete tumor ablation has been observed at doses as low as 1 mg irinotecan/kg, treated twice per week. In other cases, animals who failed untargeted (HPLN/Ir) treatment showed complete tumor ablation after ‘salvage' treatment with CD99-HPLN/Ir. Our CD99 targeted HPLN/irinotecan formulation, termed NV103 showed much better efficacy than the commercial untargeted liposomal irinotecan (Onivyde™) and doxorubicin (Doxil™). Toxic side effects, normally associated with systemic administration of free irinotecan, were minimized or undetectable. Our nanoparticles showed excellent bioavailability. Even the untargeted HPLN/Ir improve drug bioavailability six-fold in a comparison experiment with the drug in liposome form (Onivyde™), with no discernable systemic toxicity. Antibody targeting of the HPLN irinotecan formulation (NV103) improves the efficacy 12-fold, over the untargeted liposome form. In conclusion, this formulation may be effective for treatment of other CD99-expressing tumors like certain leukemias, lymphomas and glioma. Ultimately, after development of other tumor-specific targeting agents and varied encapsulated therapeutics, this technology can be usefully adapted for the treatment of other cancers as well. Citation Format: Hyunggyoo Kang, Jon Nagy, Timothy Triche. Targeted anticancer drug delivery to Ewing's sarcoma using human anti-CD99 targeted hybrid polymerization liposomal nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3705.
Abstract PL02-04: Decoding patient genomes through the hierarchical pathway architecture of the cancer cell
Authors: Trey Ideker
Journal: Cancer Research (2018)

Abstract Although cancer is governed by complex molecular systems, the composition and modular organization of these systems remains poorly understood. I will describe efforts by the Cancer Cell Map Initiative (CCMI) to generate large protein interaction maps of tumor cells, which we are integrating with existing molecular and structural data to assemble a comprehensive multiscale map of cancer cell biology. The current draft map contains a hierarchy of ~250 systems covering both known hallmarks and unexpected components. Integration with tumor mutation profiles suggests that the modules under strongest selective pressure in cancer are often not genes, but extend upwards in scale to include protein complexes, broad cellular processes, and organelles. This observation suggests a classification of cancer based on convergence of mutations at key bottlenecks in the hierarchy of cellular systems. Citation Format: Trey Ideker. Decoding patient genomes through the hierarchical pathway architecture of the cancer cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr PL02-04.
Trends in opioid use in commercially insured and Medicare Advantage populations in 2007-16: retrospective cohort study
Authors: Molly Moore Jeffery, W Michael Hooten, Henry J Henk, M Fernanda Bellolio, Erik P Hess, Ellen Meara, Joseph S Ross, Nilay D Shah
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To describe trends in the rate and daily dose of opioids used among commercial and Medicare Advantage beneficiaries from 2007 to 2016. <h3>Design</h3> Retrospective cohort study of administrative claims data. <h3>Setting</h3> National database of medical and pharmacy claims for commercially insured and Medicare Advantage beneficiaries in the United States. <h3>Participants</h3> 48 million individuals with any period of insurance coverage between 1 January 2007 and 31 December 2016, including commercial beneficiaries, Medicare Advantage beneficiaries aged 65 years and over, and Medicare Advantage beneficiaries under age 65 years (eligible owing to permanent disability). <h3>Main endpoints</h3> Proportion of beneficiaries with any opioid prescription per quarter, average daily dose in milligram morphine equivalents (MME), and proportion of opioid use episodes that represented long term use. <h3>Results</h3> Across all years of the study, annual opioid use prevalence was 14% for commercial beneficiaries, 26% for aged Medicare beneficiaries, and 52% for disabled Medicare beneficiaries. In the commercial beneficiary group, quarterly prevalence of opioid use changed little, starting and ending the study period at 6%; the average daily dose of 17 MME remained unchanged since 2011. For aged Medicare beneficiaries, quarterly use prevalence was also relatively stable, ranging from 11% at the beginning of the study period to 14% at the end. Disabled Medicare beneficiaries had the highest rates of opioid use, the highest rate of long term use, and the largest average daily doses. In this group, both quarterly use rates (39%) and average daily dose (56 MME) were higher at the end of 2016 than the low points observed in 2007 for each endpoint (26% prevalence and 53 MME). <h3>Conclusions</h3> Opioid use rates were high during the study period of 2007-16, with the highest rates in disabled Medicare beneficiaries versus aged Medicare beneficiaries and commercial beneficiaries. Opioid use and average daily dose have not substantially declined from their peaks, despite increased attention to opioid abuse and awareness of their risks.
Abstract 2361: Big data analysis allows the identification of long non-coding RNAs with therapeutic potential against hepatocellular carcinoma
Authors: Juan P. Unfried, Guillermo Serrano, Beatriz Suárez, Valeria Ferretti, Paloma Sangro, Celia Prior, Loreto Boix, Jordi Bruix, Bruno Sangro, Victor Segura, Puri Fortes
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) is a disease associated with high morbidity and mortality for which there is currently no curative treatment and therapeutic targeting remains ineffective. To search for new therapeutic targets, we have evaluated the coding and non-coding transcriptome of all RNA-Seq data from TCGA, comprising over 10000 patients and 34 different tumors with HCC among them. To this, we have added the transcriptomes of additional 10000 samples from 53 human tissues from the GTEx project. Using neural networks and bioinformatics analyses we have identified coding and non-coding genes with preferential and differential expression and obtained a more precise location of HCC in the human transcriptional landscape. The analyses of tumor-deregulated gene expression indicated that coding genes have a high tumor promiscuity. Non-coding genes, on the contrary, showed higher tissue specificity and their expression was altered in a more tumor-specific manner, predictive of a therapeutic target with fewer secondary effects. We have identified 7321 long non-coding RNAs (lncRNAs) deregulated in at least one tumor type. In HCC, we found 1128 deregulated lncRNAs of which 138 were specific of HCC. Bioinformatic functional predictions indicated a positive relationship of deregulated lncRNAs with cell proliferation and motility while immune response was negatively associated. Ten lncRNAs with oncogenic potential were selected and their expression was validated in two independent cohorts of HCC patients. Most tumor samples showed high expression levels of these lncRNAs when compared to their paired peritumoral sample. Furthermore, several candidates were found to be expressed at very low levels in healthy liver. When expression of 2 of them was inhibited with antisense drugs in HCC cells, a drastic stall in proliferation was observed. Proliferation was recovered after restoring lncRNA expression. We think these candidates may play a key role in the proliferation and motility of cancer cells and show great potential as therapeutic targets. Our studies suggest that big data analyses can give a much-needed boost to HCC target search and to personalized medicine against cancer and other diseases. Citation Format: Juan P. Unfried, Guillermo Serrano, Beatriz Suárez, Valeria Ferretti, Paloma Sangro, Celia Prior, Loreto Boix, Jordi Bruix, Bruno Sangro, Victor Segura, Puri Fortes. Big data analysis allows the identification of long non-coding RNAs with therapeutic potential against hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2361.
Abstract 11606: Critical Pathway for Elderly Patients With Heart Failure Based on Physical Activity Reduces Length of Hospital Stay
Authors: NaoyaKakutani, ArataFukushima, RisakoNakamura, ShigekiMori, TatsuyaOikawa, RowIshimoto, IchiroYoshida
Journal: Circulation (2014)

Background: Heart failure (HF) is the most common cause of hospitalization in elderly patients and contributes to high morbidity, mortality, and economic cost. Physical activity is often restricted in elderly patients with HF, and closely related to prolonged hospital stay. Critical pathway has been developed and implemented to improve guideline compliance and save cost in patients with cardiovascular disease. However, little controlled research has been performed on the effectiveness of critical pathway for elderly HF patients. We thus investigated whether the physical activity-based critical pathway reduced the length of hospital stay in elderly HF patients. Methods: We developed critical pathway for HF patients aged 65 years and older categorized in 7 stages based on their physical activities (Figure 1). 114 inpatients with HF (83±8 years, NYHA functional class II-III) were randomly assigned to conventional care (control group, n=64) or care by critical pathway (pathway group, n=50) after the treatment...
Abstract 173: Adipocytes-derived collagen reorganization in microenvironment promotes breast cancer progression
Authors: Wei Xiaohui, He Jinyong, Li Sijing, Yuan Shengtao, Sun Li
Journal: Cancer Research (2018)

Abstract Purposes Breast cancer cells recruit surrounding stromal cells, such as cancer-associated fibroblasts (CAFs), to reorganize collagen and promote tumor metastasis. Adipocytes are the most abundant stromal partners in breast tissue, whether cancer-associated adipocytes (CAAs) involve in the collagen reorganization and ultimately promoting metastasis of breast cancer is still unknown. In this study, we seek to understand whether adipocytes involve in the extracellular matrix collagen reorganization in breast cancer and its underline mechanism. Methodology In vitro mature adipocytes and breast cancer transwell co-culture model and orthotopic xenograft mouse model of human breast tumor formation in vivo were used to study the crosstalk between adipocytes and breast cancer cells, and then using a combination of proteomics, database analysis and clinical breast cancer samples analysis to study the mechanism mediated adipocytes-derived collagen reorganization. Results Here, we found that CAAs co-cultured with breast cancer cells increased the linearly aligned type I collagen fibers deposition in vitro and in vivo, which accompanied with increasing collagen lysyl hydroxylation 2 (LH2) and lysyl oxidase (LOX) expression. Breast cancer cells migrated orderly along the CAAs-derived collagen, while randomly migrated through the mature adipocyte-derived collagen. Simultaneously, clinical breast cancer samples analysis showed LH2 was high expression in the areas where cancer cells infiltrated into fatty tissue, which accompanied with poor prognosis. It is well-known that interaction between adipocytes and cancer altered the secretion of cytokines. In the present study, proteomics analysis showed that IL-6, MIF-1, TECK, MCP-1, PAI-1, IGFBP-1, TIMP1 and TIMP2 are highly secreted in adipocytes-breast cancer system. And using agonist or antagonist of these cytokines showed that these cytokines might involve in the reorganization of adipocyte-derived collagen. Mechanistic investigations demonstrated PI3K/AKT pathway and JAK/STAT3 signaling pathway involved in the rearrangement of adipocyte-derived collagen, which mediated by promoting forkhead-box(FOX) and phosphorylation STAT3(p-STAT3) translocate to the nucleus, respectively. Moreover, FOX and STAT3-dependent induction of LH2 expression further potentiated the adipocytes-derived collagen reorganization, which thus promoting breast cancer metastasis. Conclusion Collectively, our findings reveal new insights underlying increased breast cancer progression and offer new opportunities for stromal-targeted therapies in breast cancer. Citation Format: Wei Xiaohui, He Jinyong, Li Sijing, Yuan Shengtao, Sun Li. Adipocytes-derived collagen reorganization in microenvironment promotes breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 173.
Remarkable geographical variations between India and Europe in carriage of the staphylococcal surface protein-encoding sasX/sesI and in the population structure of methicillin-resistant Staphylococcus aureus belonging to clonal complex 8
Authors: S. De Backer, B.B. Xavier, L. Vanjari, J. Coppens, C. Lammens, L. Vemu, B. Carevic, W. Hryniewicz, P. Jorens, S. Kumar-Singh, A. Lee, S. Harbarth, J. Schrenzel, E. Tacconelli, H. Goossens, S. Malhotra-Kumar
Journal: Clinical Microbiology and Infection (2018)
A pH‐Mediated Electronic Wound Dressing for Controlled Drug Delivery
Authors: Gita Kiaee, Pooria Mostafalu, Mohamadmahdi Samandari, Sameer Sonkusale
Journal: Advanced Healthcare Materials (2018)

Abstract Topical administration of drugs in a timely manner according to the physiological need at the wound site can enhance the healing rate of chronic wounds. Herein, an electronic wound dressing that enables active topical drug delivery in response to electrically induced pH change is demonstrated for potential treatment of chronic wounds. In this platform, the pH of the dressing is controlled using an electrical field. This allows precise electrical control over the temporal profile of pH‐mediated drug release. This engineered dressing is comprised of microfabricated electrodes serving as anode and cathode, a pH sensitive hydrogel, and controlled electronic circuitry. The anode is coated with a pH sensitive poly(ethylene glycol)‐diacrylate/Laponite hydrogel layer containing drug loaded chitosan nanoparticles (ChPs). Applying a DC voltage between the electrodes results in a local change in pH near the electrodes. In basic environments found near the anode, the ChPs release their drug due to the dehydration process, while in acidic environments the release profile is negligible. Turning off the DC voltage results in immediate pH recovery and cessation of drug release. The biocompatibility of the dressing has also been confirmed—the pH shift resulting from application of DC voltage does not affect the wound pH significantly.
A 20-year comparison of definitive chemoradiation with 5-FU versus capecitabine in anal cancer patients treated at Stanford.
Authors: Yoanna S Pumpalova, Margaret M. Kozak, Rie von Eyben, George A. Fisher, Pamela L. Kunz, Daniel Tandel Chang, Sigurdis Haraldsdottir
Journal: Journal of Clinical Oncology (2018)

710 Background: Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for chemoradiation in rectal cancer. Few studies have compared the two agents in anal cancer. The objective of this retrospective study was to compare outcomes and toxicities in non-metastatic anal cancer patients undergoing definitive radiotherapy (RT) at Stanford combined with capecitabine/mitomycin (CM) versus 5-FU/mitomycin (FM). Methods: We included all non-metastatic anal cancer patients treated with definitive chemoradiation at Stanford from 1997 – 2016. Patients who received cisplatin or induction chemotherapy were excluded. Patient charts were reviewed and cause of death determined from the cancer registry. Fisher’s exact test was used to compare nominal parameters, Mann-Whitney U test for continuous variables. Gray’s test for equality was used to compare recurrence and colostomy incidence, and Log-rank test to compare disease-specific and overall survival. Results: Sixty-eight patients were treated at Stanford. Twenty-nine received FM and RT, 12 received standard 5-FU and 17 received low-dose continuous 5-FU; 39 patients received CM and RT. Median age was 59.5 years, and 56% were female. There was no difference in the 3-year overall and disease-specific survival between the FM and CM groups (81.5% v 90.5% p = 0.262; 88.1% v 96.0% p = 0.229). Incidence of recurrence was equivalent between the two groups (13.8% v 10.6%, p = 0.927) but patients in the combined FM group recurred earlier (6.9 v 20 months, p = 0.004) and distant recurrences were only seen in the CM group. Colostomy rates were higher in the FM group (14.6% v 2.8%, p = 0.082); all colostomies in the FM group were in patients receiving continuous 5-FU. Toxicities were similar between the two groups. The most common grade 2 or higher toxicities were dermatitis (77%), anal pain (77%), diarrhea (54%), stomatitis (19%), and nausea (22%). Conclusions: Overall and disease-specific survival and recurrence rates were equivalent between FM and CM groups. Recurrence patterns differed with loco-regional recurrences and higher colostomy rates in the FM group, while most recurrences in the CM group were distant.
Myocardin-Related Transcription Factor A Mediates OxLDL-Induced Endothelial Injury
Authors: FeiFang, YuyuYang, ZhibinYuan, YuqiGao, JiliangZhou, QiChen, YongXu
Journal: Circulation Research (2011)

Rationale:Atherosclerosis proceeds through a multistep reaction that begins with endothelial injury caused by a host of stress signals, among which oxidized low-density lipoprotein (oxLDL) plays a critical role. OxLDL disrupts normal functionality of the endothelium by upregulating adhesion molecules (eg, ICAM-1) and concomitantly downregulating endothelial nitric oxide synthase (eNOS) expression. The transcriptional modulator that mediates the cellular response to oxLDL remains largely obscure. Objective:Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, is responsible for the endothelial injury by oxLDL, and, if so, how MRTF-A promotes the proatherogenic agenda initiated by oxLDL. Methods and Results:OxLDL stimulated the expression of MRTF-A in endothelial cells as evidenced by Western blotting and immunofluorescence. Overexpression of MRTF-A synergistically enhanced the induction of...
Signaling Lymphocytic Activation Molecule Family Member 1 Engagement Inhibits T Cell–B Cell Interaction and Diminishes Interleukin‐6 Production and Plasmablast Differentiation in Systemic Lupus Erythematosus
Authors: Maria P. Karampetsou, Denis Comte, Abel Suárez‐Fueyo, Eri Katsuyama, Nobuya Yoshida, Michihito Kono, Vasileios C. Kyttaris, George C. Tsokos
Journal: Arthritis & Rheumatology (2018)

Objective Signaling lymphocytic activation molecule family member 1 ( SLAMF 1) homophilic interactions promote immunoglobulin production and T cell–B cell cross‐talk. SLAMF 1 is overexpressed on T and B cells in patients with systemic lupus erythematosus ( SLE ). This study was undertaken to determine the role of SLAMF 1 monoclonal antibody ( mA b) in modulating T cell–B cell interaction and B cell activation. Methods Anti‐IgM–prestimulated naive or total B cells from either healthy donors or patients with SLE were cocultured with autologous T cells under CD 3/ CD 28 stimulation, in the presence or absence of the SLAMF 1 mA b. Naive B cells were stimulated with anti‐IgM and CD 40L in the presence of the SLAMF 1 antibody. Cytokine production by CD 4+ T cells and B cells was examined by flow cytometry and/or quantitative polymerase chain reaction. Plasmablast formation and T cell and B cell conjugates were assessed by flow cytometry. IgG and antinuclear antibody production was determined by enzyme‐linked immunosorbent assay. Results SLAMF 1 ligation in a human peripheral blood T cell–B cell culture system reduced the following in both healthy controls and patients with SLE : conjugate formation, interleukin‐6 ( IL ‐6) production by B cells, IL ‐21 and IL ‐17A production by T cells, and Ig and autoantibody production. Whereas the SLAMF 1 mA b directly affected the function of isolated peripheral B cells by decreasing IL ‐6 and Ig production in vitro, it did not affect cytokine production by isolated T cells stimulated in vitro. Conclusion The SLAMF 1 antibody inhibits T cell–B cell interaction and suppresses B cell cytokine production and differentiation, thereby acting as a potential therapeutic tool in the treatment of patients with SLE .