tbuckley/cabot-search huggingface dataset:
Policy change eliminating body checking in non-elite ice hockey leads to a threefold reduction in injury and concussion risk in 11- and 12-year-old players
Authors: Amanda M Black, Alison K Macpherson, Brent E Hagel, Maria A Romiti, Luz Palacios-Derflingher, Jian Kang, Willem H Meeuwisse, Carolyn A Emery
Journal: British Journal of Sports Medicine (2015)

Background In ice hockey, body checking is associated with an increased risk of injury. In 2011, provincial policy change disallowed body checking in non-elite Pee Wee (ages 11–12 years) leagues. Objective To compare the risk of injury and concussion between non-elite Pee Wee ice hockey players in leagues where body checking is permitted (2011–12 Alberta, Canada) and leagues where policy change disallowed body checking (2011–12 Ontario, Canada). Method Non-elite Pee Wee players (lower 70%) from Alberta (n=590) and Ontario (n=281) and elite Pee Wee players (upper 30%) from Alberta (n=294) and Ontario (n=166) were recruited to participate in a cohort study. Baseline information, injury and exposure data was collected using validated injury surveillance. Results Based on multiple Poisson regression analyses (adjusted for clustering by team, exposure hours, year of play, history of injury/concussion, level of play, position and body checking attitude), the incidence rate ratio (IRR) associated with policy allowing body checking was 2.97 (95% CI 1.33 to 6.61) for all game injury and 2.83 (95% CI 1.09 to 7.31) for concussion. There were no differences between provinces in concussion [IRR=1.50 (95% CI 0.84 to 2.68)] or injury risk [IRR=1.22 (95% CI 0.69 to 2.16)] in elite levels of play where both provinces allowed body checking. Conclusions The rate of injury and concussion were threefold greater in non-elite Pee Wee ice hockey players in leagues where body checking was permitted. The rate of injury and concussion did not differ between provinces in elite levels, where body checking was allowed.
Use of Human Immunoglobulins in Secondary Immunodeficiencies Associated with Hematological Malignancy in Real-Life Practice: Which Patients, Which Treatment?
Authors: Omar Benbrahim, Bernard Grosbois, Jean-François Viallard, Sylvain Choquet, Bruno Royer, Brigitte Dreyfus, Emmanuel Fleck, Miguel Carreiro, Pierre Clerson, Jean Charles Crave, Jean-christophe Delain, Vincent Levy
Journal: Blood (2014)
First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors
Authors: Albiruni R. Abdul Razak, Morten Mau-Soerensen, Nashat Y. Gabrail, John F. Gerecitano, Anthony F. Shields, Thaddeus J. Unger, Jean R. Saint-Martin, Robert Carlson, Yosef Landesman, Dilara McCauley, Tami Rashal, Ulrik Lassen, Richard Kim, Lee-Anne Stayner, Mansoor R. Mirza, Michael Kauffman, Sharon Shacham, Amit Mahipal
Journal: Journal of Clinical Oncology (2016)

Purpose This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. Patients and Methods In total, 189 patients with advanced solid tumors received selinexor (3 to 85 mg/m 2 ) in 21- or 28-day cycles. Pre- and post-treatment levels of XPO1 mRNA in patient-derived leukocytes were determined by reverse transcriptase quantitative polymerase chain reaction, and tumor biopsies were examined by immunohistochemistry for changes in markers consistent with XPO1 inhibition. Antitumor response was assessed according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. Results The most common treatment-related adverse events included fatigue (70%), nausea (70%), anorexia (66%), and vomiting (49%), which were generally grade 1 or 2. Most commonly reported grade 3 or 4 toxicities were thrombocytopenia (16%), fatigue (15%), and hyponatremia (13%). Clinically significant major organ or cumulative toxicities were rare. The maximum-tolerated dose was defined at 65 mg/m 2 using a twice-a-week (days 1 and 3) dosing schedule. The recommended phase II dose of 35 mg/m 2 given twice a week was chosen based on better patient tolerability and no demonstrable improvement in radiologic response or disease stabilization compared with higher doses. Pharmacokinetics were dose proportional, with no evidence of drug accumulation. Dose-dependent elevations in XPO1 mRNA in leukocytes were demonstrated up to a dose level of 28 mg/m 2 before plateauing, and paired tumor biopsies showed nuclear accumulation of key tumor-suppressor proteins, reduction of cell proliferation, and induction of apoptosis. Among 157 patients evaluable for response, one complete and six partial responses were observed (n = 7, 4%), with 27 patients (17%) achieving stable disease for ≥ 4 months. Conclusion Selinexor is a novel and safe therapeutic with broad antitumor activity. Further interrogation into this class of therapy is warranted.
Feline Oncornavirus-Associated Cell Membrane Antigen. IV. Antibody Titers in Cats With Naturally Occurring Leukemia, Lymphoma, and Other Diseases&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Essex, S M Cotter, W D Hardy, P Hess, W Jarrett, O Jarrett, L Mackey, H Laird, L Perryman, R G Olsen, D S Yohn
Journal: JNCI Journal of the National Cancer Institute (1975)

Cats with naturally occurring leukemia and lymphoma had low or negative humoral antibody titers to the feline oncornavirus-associated cell membrane antigen (FOCMA). Geographic differences were seen in the relative frequencies of various forms of lymphoproliferative neoplasms. Lymphatic leukemia and thymic lymphoma were most common in Boston, whereas alimentary lymphoma was most frequent in Glasgow. No significant differences were found in geometric mean FOCMA antibody titers for the various forms of leukemia-lymphoma or for feline leukemia virus (FeLV)-positive as compared to FeLV-negative cats. Approximately 70% of 76 Boston cats with nonregenerative anemias were FeLV gs antigen (gsa) positive; this was similar to the percentage with leukemia-lymphoma from the same population that was positive. Fifty-five to 62% of the Boston cats with other infectious diseases, such as peritonitis and septicemia, were gsa positive. We postulate that this is due to a predisposition to infectious diseases by the immunosuppressive action of FeLV. Young cats from the Boston population that developed lymphoma, infectious peritonitis, and certain other diseases were more likely to be FeLV gsa positive than older cats with the same diseases.
Prognostic significance of isolated tumor cells in regional lymph nodes in patients with T2-T3 stage gastric cancer.
Authors: Sung-Ho Jin, Soo-Youn Cho, Kyu-Jae Lee, Sunhoo Park, Hang-Jong Yu, Ho-Yoon Bang, Jong-Inn Lee
Journal: Journal of Clinical Oncology (2012)

8 Background: The prognostic impact of isolated tumor cells (ITCs) in regional lymph nodes is unclear. This study was aimed to evaluate the prognostic significance of ITCs in subpopulation with T2-T3 gastric cancer by adopting the standard definition for ITC (≤ 0.2 mm, detected by H&amp;E or IHC) and micrometastsis (≤ 2 mm, detected by H&amp;E or IHC) in 7 th AJCC staging. Methods: A total of three hundred eleven patients diagnosed as pT2-3/N0-2/M0 gastric carcinoma after curative surgery at Korea Cancer Center Hospital between January 1996 and December 2000 was retrospectively studied. All tumor and lymph node specimens by H&amp;E received reexaminations, and 5,825 lymph nodes from 191 patients without macrometastasis (&gt; 2.0 mm) were re-evaluated after IHC staining with anti-cytokeratin (AE1/AE3). And N stage was reclassified into pN0(i-), pN0(i+), pN1mi, pN1, and pN2. Survival analyses were performed using Kaplan-Meier method with Log-rank test and Cox regression model. Results: According to original N stage, 5-year overall survival rates were estimated as 80.5% in N0, 79.3% in N1, 68.8% in N2 without statistical difference between N0 and N1 (p=0.790). Whereas according to reclassified pN stage, survival rates were estimated as 92.3% in pN0(i-), 75.5% in pN0(i+), 84.4% in pN1mi, 76.1% in pN1, and 69.0% in pN2, and significant difference was found between pN0(i-) and pN0(i+) (p=0.034). In the multivariate Cox model with backward conditional method, reclassified pN stage was remained as an independent prognostic factor along with age and tumor location while excluding original N stage, and the hazard ratio (95% CI) of pN0(i+) compared to pN0(i-) was 3.60 (1.08-12.00). Conclusions: The result demonstrates that ITCs in regional lymph nodes is a bad prognostic factor, even after adjusting for other prognostic factors. So we suggest that ITCs should be classified separately from the N0 in gastric cancer staging.
Impact of HLA‐Mismatch in Unrelated Donor Hematopoietic Stem Cell Transplantation: A Meta‐Analysis
Authors: Natasha Kekre, Kimberley S. Mak, Konrad H. Stopsack, Moritz Binder, Kazusa Ishii, Elsa Brånvall, Corey S. Cutler
Journal: American Journal of Hematology (2016)

The magnitude of risk associated with 9/10 mismatched unrelated donor (MMURD) hematopoietic stem cell transplantation and that of mismatches at the individual HLA loci remain unclear. We performed a meta-analysis to assess the difference in clinical outcomes between matched unrelated donor (MUD) and MMURD transplantation. A comprehensive search of Medline and Embase for manuscripts regarding transplantation outcomes in primarily adult patients with hematologic malignancies was performed. The pooled effect estimates were calculated using DerSimonian-Laird random effects models. A total of 13 studies were included, reporting on 13,446 transplants. 9/10 MMURD transplantation was associated with worse overall survival compared to 10/10 MUD transplantation (pooled HR: 1.27, 95% CI: 1.12-1.45; n = 7 studies). Mismatch at HLA-A, -B, or -C was associated with significantly worse overall survival compared to MUD transplantation, while there was no significant difference associated with -DQ or -DPB1 mismatch. Inferior survival associated with HLA-DRB1 mismatch could not be ruled out. Data on acute and chronic graft-versus-host disease were scarce but favored MUD transplantation. In summary, this meta-analysis of the available literature favored MUD over MMURD transplantation in hematologic malignancies and further quantifies the risks associated with specific HLA-allele mismatches. Am. J. Hematol. 91:551-555, 2016. © 2016 Wiley Periodicals, Inc.
Treatment of Eosinophilic Fasciitis With Sirolimus
Authors: Vikash S. Oza, Rabina Walsh, Jeffrey North, Timothy G. Berger, Jenny E. Murase
Journal: JAMA Dermatology (2016)

The patient was diagnosed with stage 2B MF and treated first with local radiation therapy and then with oral bexarotene, 75 mg, twice daily.After 4 months there was a complete response.Discussion | The occurrence of lipodermatosclerosis mimicking MF has been poorly described in the literature, with only 1 other case reported to our knowledge. 1Several clinical morphological and textural features should be considered when evaluating similar lesions on the legs.Lipodermatosclerosis often presents as a localized, painful, indurated plaque with erythema and hyperpigmentation on the lower legs in a setting of venous insufficiency.The chronic form is said to resemble an "inverted champagne bottle."The typical presentation of MF is erythematous patches, plaques, or tumors with fine scale that favor sun protected areas. 2 Treatments for MF are based on the stage of the disease and include topical corticosteroids, topical nitrogen mustard, total skin electron beam therapy, oral retinoids, subcutaneous interferon alfa, histone deacetylase inhibitors, alemtuzumab, psoralen plus UV-A photochemotherapy (PUVA), and extracorporeal photopheresis.Lipodermatosclerosis is the result of chronic venous insufficiency.Both septal and lobular panniculitis as well as lipomembranous changes are seen on pathologic analysis.Mainstay treatments include compression, leg elevation, topical and/or intralesional corticosteroids, and anabolic steroids for recalcitrant disease. 3 Mycosis fungoides should be included in the differential diagnosis of any cutaneous patch or plaque that does not respond to first-and second-line treatments.A low threshold for obtaining biopsy should be the rule for any patient with a chronic, recalcitrant eruption.
Should a pregnancy test be required before scuba diving?
Authors: Françoise Damnon, Maud de Rham, David Baud
Journal: British Journal of Sports Medicine (2016)

In recent years, scuba diving has become accessible worldwide. The average age of female scuba divers is similar to their window of fertility, and many women dive annually without knowing their pregnancy status. These women seek advice concerning the potential teratogenicity of diving, and whether they can continue the pregnancy. Nevertheless, little is known about the consequences of scuba diving on pregnancy, and the scientific literature is poor1 (old studies,2 ,3 no controls,2 ,4 few participants2). Adverse pregnancy outcomes were observed in animal models, but were only conducted in late gestation.1 As a precaution principle, all international diving and medical organisations5 recommend avoiding scuba diving activity during pregnancy at any period of gestation. The aim of our study is to report …
A phase I-II trial of cisplatin and dichloromethotrexate in squamous cell cancer of the head and neck.
Authors: R H Wheeler, R B Natale, S G Roshon, S R Baker
Journal: Journal of Clinical Oncology (1984)

Dichloromethotrexate, a dihalogenated analog of methotrexate, is excreted and metabolized by the liver; therefore, blood levels are not dependent on renal function. The possibility that dichloromethotrexate could be given at its maximally tolerated dose in combination with high-dose cisplatin has been evaluated in 30 patients with advanced squamous cell cancer of the head and neck. Overall, this regimen was well tolerated, and 13 of 24 evaluable patients had an objective response to therapy (25% complete response and 29% partial response). The maximum dose of dichloromethotrexate that could be delivered was related to the serum albumin. Patients with an albumin less than 3.8 g/100 mL rarely tolerated doses of 500 mg/m2 or greater. Cisplatin plus dichloromethotrexate is an active drug combination in squamous cell cancer of the head and neck, and deserves further evaluation in randomized studies and in an adjuvant setting.
Molecular Portrait of Resected Gastric Cancer (Rgc) with Next Generation Sequencing (Ngs) According to a Clinical Biological Risk Model Considering Fhit, Apc and Her-2 Overexpression
Authors: E. Bria, M. Fassan, S. Pilotto, G. De Manzoni, S. Kinspergher, I. Sperduti, U. Peretti, M. Simbolo, P. Capelli, A. Tomezzoli, C. Luchini, A. Mafficini, G. Turri, G. Tortora, A. Scarpa
Journal: Annals of Oncology (2014)
Effect of miR-21 on resistance to 5-fluorouracil and regulation of MSH2.
Authors: N. Valeri, P. Gasparini, C. Braconi, F. Lovat, A. Paone, M. Fabbri, G. Nuovo, R. Fishel, C. M. Croce
Journal: Journal of Clinical Oncology (2011)

431 Background: MicroRNAs are small non coding RNAs controlling cell homeostasis. Defects in mismatch repair (MMR) genes cause resistance to 5-fluorouracil (5FU). miR-21 is up-regulated in colorectal cancer (CRC) and is associated with poor benefit from adjuvant 5FU. We aimed at studying if miR-21 may induce 5FU resistance by down-regulating MSH2. Methods: Fresh frozen (32) and paraffin-embedded (50) cases of CRC and matched normal tissues were studied for miR-21 expression (Northern Blotting and in situ Hybridization) and MSH2 expression (Western Blotting and Immunohistochemistry). CRC Colo-320DM, SW620 and isogenic Lovo cells with [Lovo(MSH2+)] and without MSH2 [Lovo(MSH2-)] were used. Pre-miR-21 was used for over-expression experiments. Luciferase vectors with MSH2 (Luc-MSH2) and MSH6 (Luc-MSH6) 3'UTRs downstream of the Luciferase gene were used. Cell cycle modifications after 5FU (10uM) were assessed by FACS analysis. Lentiviral vectors encoding for miR-21 or siRNA to MSH2 or empty vectors were used for stable infection. Stable clones were injected in the flank of nude mice. Mice were treated with 5FU i.p. for 2 weeks. Tumor volume was measured once a week and calculated according to the formula Volume=LxW 2 /2. Results: A statistically significant inverse correlation between miR-21 and MSH2 expression was observed by Parson's test in the two CRC cohorts. miR-21 over-expression caused reduction in MSH2 and MSH6 protein expression and in Luciferase activity after transfection with Luc-MSH2 or Luc-MSH6 vectors confirming that miR-21 directly regulates MSH2 and MSH6. miR-21 up-regulation reduced 5FU induced apoptosis and G2/M arrest at the same extent of siRNA to MSH2 in all MMR proficient cells while no significant effect was observed in Lovo(MSH2-). Complementation experiments with plasmid encoding for MSH2 promoted 5FU induced apoptosis that was inhibited by co-transfection with miR-21. Xenograft tumors over-expressing miR-21 or siRNA anti MSH2 achieved the same response to 5FU and both showed to be less responsive to 5FU than controls. Conclusions: miR-21 causes resistance to 5FU in a MSH2 dependent manner and might be a useful marker in predicting therapeutic outcome in CRC patients. No significant financial relationships to disclose.
3-Iodothyronamine (T1AM), an endogenous fast acting thyroid hormone derivative: novel evidence for weight loss and glucose co-regulation by RNA gene expression
Authors: Fariba Assadi Porter, Grazia Chiellini, Riccardo Zucchi, Tonelli Marco, Reiland Hannah, Thomas S. Scanlan, Sandra Ghelardoni, Carnicelli Vittoria, Butz Dan
Journal: Endocrine Reviews (2013)
Abstract 16021: Contemporary Temporal Trends in Acute Coronary Syndrome in the Community by Age and Gender From 2008-2011: The Kaiser Permanente ACS Study
Authors: Matthew D Solomon, Thomas K Leong, Rachel E Perloff, Sue Hee Sung, Yaping Xu, Vanessa S Reddy, Susan M Begelman, Alan S Go
Journal: Circulation (2013)

Background: Limited data exist about the most recent population trends in the incidence of acute coronary syndrome (ACS) in the community and whether they vary by age and gender. Methods: We identi...
Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis
Authors: Martijn H. van den Bosch, Arjen B. Blom, Rik F. P. Schelbergen, Thomas Vogl, Johannes P. Roth, Annet W. Slöetjes, Wim B. van den Berg, Peter M. van der Kraan, Peter L. E. M. van Lent
Journal: Arthritis & Rheumatology (2015)

Objective Both alarmins S100A8/A9 and canonical Wnt signaling have been found to play active roles in the development of experimental osteoarthritis (OA). However, what activates canonical Wnt signaling remains unknown. This study was undertaken to investigate whether S100A8 induces canonical Wnt signaling and whether S100 proteins exert their effects via activation of Wnt signaling. Methods Expression of the genes for S100A8/A9 and Wnt signaling pathway members was measured in an experimental OA model. Selected Wnt signaling pathway members were overexpressed, and levels of S100A8/A9 were measured. Activation of canonical Wnt signaling was determined after injection of S100A8 into naive joints and induction of collagenase‐induced OA in S100A9‐deficient mice. Expression of Wnt signaling pathway members was tested in macrophages and fibroblasts after S100A8 stimulation. Canonical Wnt signaling was inhibited in vivo to determine if the effects of S100A8 injections were dependent on Wnt signaling. Results The alarmins S100A8/A9 and members of the Wnt signaling pathway showed coinciding expression in synovial tissue in an experimental OA model. Synovial overexpression of selected Wnt signaling pathway members did not result in increased expression of S100 proteins. In contrast, intraarticular injection of S100A8 increased canonical Wnt signaling, whereas canonical Wnt signaling was decreased after induction of experimental OA in S100A9‐deficient mice. S100A8 stimulation of macrophages, but not fibroblasts, resulted in increased expression of canonical Wnt signaling members. Overexpression of Dkk‐1 to inhibit canonical Wnt signaling decreased the induction of matrix metalloproteinase 3, interleukin‐6, and macrophage inflammatory protein 1α after injection of S100A8. Conclusion Our findings indicate that the alarmin S100A8 induces canonical Wnt signaling in macrophages and murine knee joints. The effects of S100A8 are partially dependent on activation of canonical Wnt signaling.
Tumor infiltrating lymphocytes associated with brain metastasis in breast cancer.
Authors: Nicole Olivia Williams, Cheryl L. Thompson, Shikha Parsai, Vinay Varadan, Kristy Miskimen, Jill Barnholtz-Sloan, Paula Silverman, Shaveta Vinayak, Lisa R. Rogers, Andrew E. Sloan, Lyndsay Harris, Hannah L. Gilmore
Journal: Journal of Clinical Oncology (2015)

2059 Background: Breast cancer represents the second most common cause of brain metastasis (BM). Though tumor-infiltrating lymphocytes (TILs) and immunotherapies have been studied in primary breast cancer, little is known about TILs in BM from breast cancer. The aim of this study is to characterize the immune response to BM in breast cancer. Methods: The cohort included 75 initial and recurrent BM samples and 20 matched primary breast tumors. Stromal (sTILs) were evaluated on H&E sections and scored according to international TILs working group guidelines and categorized as having no, low (1-5%), moderate (6-20%) or high ( > 20%) TILs. Tumor DNA/RNA was extracted on corresponding archival FFPE material. Gene expression profiling was performed using Affymetrix Human Transcriptome Array 2.0 microarrays. PAM50 subtypes were assigned by clustering samples using median-subtracted PAM50 gene expression levels. Gene expression levels of programmed cell death 1 (PD1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and forkhead box P3 (FOXP3) were compared in this cohort. Results: Of the 75 BM evaluated, 34 (45%) had no sTILs, 29 (39%) had low sTILs, 10 (13%) had moderate sTILS, and 1 (1%) had high sTILs. sTILs were significantly lower in the BM when compared with matched primary tumors (p = 0.0025). When comparing the level of BM sTILs in the PAM50 subtypes, the HER2-enriched subtype more commonly exhibited moderate to high sTILs compared luminal A, luminal B, and normal-like (p = 0.065). No association was seen between time to develop BM and % sTILs (p = 0.68). Though primary and BM were found to express both PD1 and FOXP3, only FOXP3 expression was found to be higher in primary tumors compared to BM (p = 0.0025). There was no association between PD1 and FOXP3 expression and PAM50 subtype or BM sTILS (p > 0.05). Significant PD-L1 and CTLA4 expression was not identified in primary tumors or BM. Conclusions: Overall, BM from breast cancer have relatively low sTILs expression. The expression of PD1 and FOXP3 in BM from breast cancer suggests that further investigation of the immune response in BM and clinical trials with immune checkpoint inhibitors should be considered for this poor prognosis population.
Altered Erythrocyte Osmotic Fragility in Mice With Ehrlich Ascites Tumor2
Authors: Allan E. Dumont, Martin S. Nachbar, Amalia B. Martelli
Journal: JNCI Journal of the National Cancer Institute (1977)

The osmotic fragility of erythrocytes from mice with Ehrlich ascites tumor was compared with that of erythrocytes from normal control animals. Erythrocytes collected from mice 15 days after the ip injection of tumor cells exhibited a uniform pattern of abnormal resistance to hemolysis in hypotonic saline, with 50% hemolysis occurring at an average saline concentration of 0.44% compared to an average of 0.49% for 11 controls a significant difference (P less than 0.0001). Erythrocytes from mice with this tumor apparently undergo an alteration in some component of the cell membrane that regulates either permeability to cations and water or distensibility of the cell.