tbuckley/cabot-search huggingface dataset:
Frequent <i>Met</i> Oncogene Amplification in a <i>Brca1/Trp53</i> Mouse Model of Mammary Tumorigenesis
Authors: Gromoslaw A. Smolen, Beth Muir, Gayatry Mohapatra, Anne Barmettler, Woo J. Kim, Miguel N. Rivera, Sara M. Haserlat, Ross A. Okimoto, Eunice Kwak, Sonika Dahiya, Judy E. Garber, Daphne W. Bell, Dennis C. Sgroi, Lynda Chin, Chu-Xia Deng, Daniel A. Haber
Journal: Cancer Research (2006)

Abstract In a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brca1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driven by loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in human breast cancers, the identification of a dominant somatic genetic lesion in the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist in BRCA1-initiated human breast cancer. (Cancer Res 2006; 66(7): 3452-5)
Mechanically Robust, Negative‐Swelling, Mussel‐Inspired Tissue Adhesives
Authors: Devin G. Barrett, Grace G. Bushnell, Phillip B. Messersmith
Journal: Advanced Healthcare Materials (2012)

Abstract Most synthetic polymer hydrogel tissue adhesives and sealants swell considerably in physiologic conditions, which can result in mechanical weakening and adverse medical complications. This paper describes the synthesis and characterization of mechanically tough zero‐ or negative‐swelling mussel‐inspired surgical adhesives based on catechol‐modified amphiphilic poly(propylene oxide)‐poly(ethylene oxide) block copolymers. The formation, swelling, bulk mechanical, and tissue adhesive properties of the resulting thermosensitive gels were characterized. Catechol oxidation at or below room temperature rapidly resulted in a chemically cross‐linked network, with subsequent warming to physiological temperature inducing a thermal hydrophobic transition in the PPO domains and providing a mechanism for volumetric reduction and mechanical toughening. The described approach can be easily adapted for other thermally sensitive block copolymers and cross‐linking strategies, representing a general approach that can be employed to control swelling and enhance mechanical properties of polymer hydrogels used in a medical context.
Effect of Bariatric Surgery Versus Intensive Medical Management on Diabetic Ophthalmic Outcomes
Authors: Rishi P. Singh, Richard Gans, Sangeeta R. Kashyap, Rumneek Bedi, Kathy Wolski, Stacy A. Brethauer, Steven E. Nissen, Deepak L. Bhatt, Philip Schauer
Journal: Diabetes Care (2015)

Glycemic control improves immediately after gastric bypass in patients with type 2 diabetes mellitus (T2DM) (1). The American Diabetes Association defines complete remission of diabetes as a return to normal glucose levels (HbA1c < 6%, fasting glucose <5.6 mmol/L) without glucose-lowering medication for at least 1 year after bariatric surgery (2). Prior studies have indicated that a rapid improvement in glycemic control is known to worsen diabetic retinopathy in cases of intense insulin control (3). However, few studies have examined whether undergoing bariatric surgery would significantly alter the prognosis of diabetes microvascular complications in patients with T2DM.

The Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial observed the effect of bariatric surgery versus intensive medical management on patients with diabetes and examined the ophthalmic outcomes at 2 years (4). This was a prospective, randomized, nonblinded clinical trial that enrolled 150 patients with the primary outcome of examining the efficacy of intensive medical therapy alone versus surgical management with either Roux-en-Y gastric bypass or sleeve gastrectomy for the management of T2DM. As a secondary end point of the trial, patients were assessed with biomicroscopic fundus exam by …
Opposing Effects of Pigment Epithelium–Derived Factor on Breast Cancer Cell versus Neuronal Survival: Implication for Brain Metastasis and Metastasis-Induced Brain Damage
Authors: Daniel P. Fitzgerald, Preeti Subramanian, Monika Deshpande, Christian Graves, Ira Gordon, Yongzhen Qian, Yeva Snitkovsky, David J. Liewehr, Seth M. Steinberg, José D. Paltán-Ortiz, Mary M. Herman, Kevin Camphausen, Diane Palmieri, S. Patricia Becerra, Patricia S. Steeg
Journal: Cancer Research (2012)

Abstract Brain metastases are a significant cause of morbidity and mortality for patients with cancer, yet preventative and therapeutic options remain an unmet need. The cytokine pigment epithelium–derived factor (PEDF) is downregulated in resected human brain metastases of breast cancer compared with primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here, we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression, as supported by in vitro analyses as well as direct intracranial implantation. Notably, the suppressive effects of PEDF were not only rapid but independent of the effects of this factor on angiogenesis. Paralleling its cytotoxic effects on breast cancer cells, PEDF also exerted a prosurvival effect on neurons that shielded the brain from tumor-induced damage, as indicated by a relative 3.5-fold reduction in the number of dying neurons adjacent to tumors expressing PEDF. Our findings establish PEDF as both a metastatic suppressor and a neuroprotectant in the brain, highlighting its role as a double agent in limiting brain metastasis and its local consequences. Cancer Res; 72(1); 144–53. ©2012 AACR.
An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient
Authors: Laurent Brochard, Fekri Abroug, Matthew Brenner, Alain F. Broccard, Robert L. Danner, Miquel Ferrer, Franco Laghi, Sheldon Magder, Laurent Papazian, Paolo Pelosi, Kees H. Polderman
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Section:ChooseTop of pageAbstract <<CONTENTSEXECUTIVE SUMMARYMETHODSI. HOW CAN WE IDENTIFY AC...II. WHAT CAN WE DO TO PRO...III. CAN WE PREVENT ACUTE...IV. HOW SHOULD WE MANAGE ...V. WHAT IS THE IMPACT OF ...SUMMARYReferencesCITING ARTICLES
Plasmon‐Coupled Gold Nanospheres for Two‐Photon Imaging and Photoantibacterial Activity
Authors: Peiyan Yuan, Xin Ding, Zhenping Guan, Nengyue Gao, Rizhao Ma, Xiao‐Fang Jiang, Yi Yan Yang, Qing‐Hua Xu
Journal: Advanced Healthcare Materials (2014)

Positively charged Au nanospheres are found to form aggregates on the bacterial surface, resulting in significantly enhanced two-photon photoluminescence (TPPL). The enhanced TPPL is successfully utilized to image bacterial cells in the NIR region. In addition, these Au nanospheres effectively eradicate the bacterial cells by laser pulses in the same NIR region due to the photothermal effect. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A Review of Unintentional Injuries in Adolescents
Authors: David A. Sleet, Michael F. Ballesteros, Nagesh N. Borse
Journal: Annual Review of Public Health (2010)

Unintentional injuries are the largest source of premature morbidity and mortality and the leading cause of death among adolescents 10–19 years of age. Fatal injury rates of males are twice those of females, and racial disparities in injury are pronounced. Transportation is the largest source of these injuries, principally as drivers and passengers, but also as cyclists and pedestrians. Other major causes involve drowning, poisonings, fires, sports and recreation, and work-related injuries. Implementing known and effective prevention strategies such as using seat belts and bicycle and motorcycle helmets, installing residential smoke alarms, reducing misuse of alcohol, strengthening graduated driver licensing laws, promoting policy change, using safety equipment in sports and leisure, and protecting adolescents at work will all contribute to reducing injuries. The frequency, severity, potential for death and disability, and costs of these injuries, together with the high success potential of prevention strategies, make injury prevention a key public health goal to improve adolescent health in the future.
Tpl2 regulates intestinal myofibroblast HGF release to suppress colitis-associated tumorigenesis
Authors: Vasiliki Koliaraki, Manolis Roulis, George Kollias
Journal: Journal of Clinical Investigation (2012)

The tumor microenvironment plays a significant role in colitis-associated cancer (CAC). Intestinal myofibroblasts (IMFs) are cells in the intestinal lamina propria secreting factors that are known to modulate carcinogenesis; however, the physiological role of IMFs and signaling pathways influencing CAC have remained unknown. Tumor progression locus 2 (Tpl2) is a MAPK that regulates inflammatory and oncogenic pathways. In this study we addressed the role of Tpl2 in CAC using complete and tissue-specific ablation of Tpl2 in mutant mice. Tpl2-deficient mice did not exhibit significant differences in inflammatory burdens following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration compared with wild-type mice; however, the mutant mice developed significantly increased numbers and sizes of tumors, associated with enhanced epithelial proliferation and decreased apoptosis. Cell-specific ablation of Tpl2 in IMFs, but not in intestinal epithelial or myeloid cells, conferred a similar susceptibility to adenocarcinoma formation. Tpl2-deficient IMFs upregulated HGF production and became less sensitive to the negative regulation of HGF by TGF-β3. In vivo inhibition of HGF-mediated c-Met activation blocked early, enhanced colon dysplasia in Tpl2-deficient mice, indicating that Tpl2 normally suppresses the HGF/c-Met pathway. These findings establish a mesenchyme-specific role for Tpl2 in the regulation of HGF production and suppression of epithelial tumorigenesis.
Improvement of the Therapeutic Index of Anticancer Drugs by the Superoxide Dismutase Mimic Mangafodipir
Authors: Jérôme Alexandre, Carole Nicco, Christiane Chéreau, Alexis Laurent, Bernard Weill, François Goldwasser, Frédéric Batteux
Journal: JNCI Journal of the National Cancer Institute (2006)

Anticancer drugs act by increasing intracellular hydrogen peroxide levels. Mangafodipir, a superoxide dismutase (SOD) mimic with catalase and glutathione reductase activities, protects normal cells from apoptosis induced by H2O2. We investigated its and other oxidative stress modulators' effects on anticancer drug activity in vitro and in vivo.Cell lysis and intracellular reactive oxygen species levels were assessed in vitro in human leukocytes from healthy subjects and in murine CT26 colon cancer cells. Cells were exposed to the chemotherapeutic agents paclitaxel, oxaliplatin, or 5-fluorouracil, either in the presence or absence of mangafodipir and other oxidative stress modulators. Cell viability was evaluated by the methylthiazoletetrazolium assay. The effects of mangafodipir and other oxidative stress modulators on peripheral blood counts and on tumor growth were studied in BALB/c mice that were implanted with CT26 tumors and treated with 20 mg/kg paclitaxel. Survival of BALB/c mice infected with Staphylococcus aureus was also examined by treatment group. Statistical tests were two-sided.In vitro lysis of leukocytes exposed to paclitaxel, oxaliplatin, or 5-fluorouracil in combination with mangafodipir was decreased by 46% (95% confidence interval [CI] = 44% to 48%), 30.5% (95% CI = 29% to 32%), and 15% (95% CI = 10% to 20%), compared with lysis of cells treated with anticancer agent alone. Mangafodipir also statistically significantly enhanced in vitro anticancer drug cytotoxicity toward CT26 cancer cells. In vivo, mangafodipir protected mice against paclitaxel-induced leukopenia. Moreover, the survival rate of mice infected with S. aureus and treated with paclitaxel was higher when mangafodipir was also administered (survival: 3 of 17 versus 14 of 17, P < .001). In addition, mangafodipir amplified the inhibitory effect of paclitaxel on CT26 tumor growth in mice.Mangafodipir decreased hematotoxicity and enhanced cytotoxicity of anticancer agents.
Targeting autoantigen to B cells prevents the induction of a cell-mediated autoimmune disease in rats.
Authors: M J Day, A G Tse, M Puklavec, S J Simmonds, D W Mason
Journal: The Journal of Experimental Medicine (1992)

Immunization protocols that induce high levels of delayed-type hypersensitivity are often associated with low levels of antibody production, whereas alternative immunization strategies can produce the opposite effect. This reciprocal relationship appears to depend, at least in part, on the fact that T cell-derived lymphokines that are predominantly involved in one type of response inhibit the development of those T cells that promote the alternative one. Such a regulatory mechanism is likely to be bistable in that whenever one form of response is established, spontaneous development of the alternative one will be inhibited. We have applied this concept to the control of a cell-mediated autoimmune disease in rats. By covalently linking the autoantigen to anti-IgD antibody, we have targeted it to B cells for presentation to antigen-specific T cells. This form of presentation favors antibody production and may be expected to antagonize the cell-mediated disease-inducing response to the same antigen. To test this hypothesis, use was made of the fact that experimental allergic encephalomyelitis (EAE), when induced with the encephalitogenic peptide of guinea pig myelin basic protein, is purely a cell-mediated disease. The experiments show that Lewis rats, immunized with the peptide in its encephalitogenic form, were protected from disease when simultaneously injected with the peptide coupled to anti-IgD monoclonal antibodies. Control experiments showed that neither peptide nor anti-IgD alone were protective, and the peptide covalently coupled to irrelevant antibodies also failed to protect. Spleen cells from animals protected from disease by the anti-IgD-peptide conjugate, when activated in vitro with the encephalitogen, were able to transfer EAE to naive recipients. The results demonstrate that a cell-mediated immune response can be controlled by appropriate targeting of the specific antigen without inducing T cell anergy and suggest a potential strategy for preventing autoimmune diseases that are essentially cell-mediated in type.
Markers of Adenocarcinoma Characteristic of the Site of Origin: Development of a Diagnostic Algorithm
Authors: Jayne L. Dennis, Torgeir R. Hvidsten, Ernst C. Wit, Jan Komorowski, Alexandra K. Bell, Ian Downie, Jacqueline Mooney, Caroline Verbeke, Christopher Bellamy, W. Nicol Keith, Karin A. Oien
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Patients with metastatic adenocarcinoma of unknown origin are a common clinical problem. Knowledge of the primary site is important for their management, but histologically, such tumors appear similar. Better diagnostic markers are needed to enable the assignment of metastases to likely sites of origin on pathologic samples. Experimental Design: Expression profiling of 27 candidate markers was done using tissue microarrays and immunohistochemistry. In the first (training) round, we studied 352 primary adenocarcinomas, from seven main sites (breast, colon, lung, ovary, pancreas, prostate and stomach) and their differential diagnoses. Data were analyzed in Microsoft Access and the Rosetta system, and used to develop a classification scheme. In the second (validation) round, we studied 100 primary adenocarcinomas and 30 paired metastases. Results: In the first round, we generated expression profiles for all 27 candidate markers in each of the seven main primary sites. Data analysis led to a simplified diagnostic panel and decision tree containing 10 markers only: CA125, CDX2, cytokeratins 7 and 20, estrogen receptor, gross cystic disease fluid protein 15, lysozyme, mesothelin, prostate-specific antigen, and thyroid transcription factor 1. Applying the panel and tree to the original data provided correct classification in 88%. The 10 markers and diagnostic algorithm were then tested in a second, independent, set of primary and metastatic tumors and again 88% were correctly classified. Conclusions: This classification scheme should enable better prediction on biopsy material of the primary site in patients with metastatic adenocarcinoma of unknown origin, leading to improved management and therapy.
On Neuropathic Plica
Authors: J. F. Le Page
Journal: BMJ (1884)

the Dermatological Department of the Museum of the Royal College of Surgeons of England may be seen a specimen bearing the designation " neuropathic plica."It was presented by me to the Museum through, and at the kind suggestion of, Sir Erasmus Wilson; and I believe I am correct in saying that it is the only one in existence, at least, so far as I have been able to ascertain.At a time when the list of diseases of the nervous system is greatly in- creasing-pathological research having traced to that system as the fountain many not only so-called functional, but even organic dis- eases-to add a new name to the list appears to require some
Home mechanical ventilation (HMV) discontinuation: Mortality, adherence and transfer
Authors: Laura Swanton, Swapna Mandal, Michelle Ramsey, Rachel Harding, Nicholas Hart
Journal: European Respiratory Journal (2013)

Background: There is limited data in the literature reporting reasons for discontinuation of HMV. We investigated the specific causes for HMV removal. Methods: From a HMV database of prospectively entered data, we undertook retrospective data analysis of patients who discontinued HMV from January 2010 to December 2012. Results: There were 1167 patients on HMV. Over the 2 years, 205 had HMV withdrawn. In 61%, (125/205) death was the cause of removal. 22% were non-adherent to treatment, 17% were discharged. Of the 46 coded as non-adherent, 24% (11/46) stopped HMV due to interface issues, 11% due to disturbed sleep, 17% had limited clinical symptoms requiring HMV. 15% stopped HMV due to weight loss, 24% had no documentation for discontinuation and 9% gave other reasons.

![Figure][1] 



Of the 34 coded as discharged, 22 (65%) had care transferred due to the commuting distance, 15% were discharged as they had no clinical symptoms but demonstrated compliance of 7(±2.6) hours a night, 12% had significant weight loss and did not require HMV. Conclusion: The primary reason for discontinuation of HMV was death, major causes of non-adherence are interface issues and sleep disruption. There is a small group with minimal symptoms but adhere to the ventilator prescription. The other major cause of HMV discontinuation is weight loss, albeit this can be discontinuation through non-adherence or clinical instruction.

 [1]: pending:yes
Effect of the Garrett Lee Smith Memorial Suicide Prevention Program on Suicide Attempts Among Youths
Authors: Lucas Godoy Garraza, Christine Walrath, David B. Goldston, Hailey Reid, Richard McKeon
Journal: JAMA Psychiatry (2015)

Youth suicide prevention is a major public health priority. Studies documenting the effectiveness of community-based suicide prevention programs in reducing the number of nonlethal suicide attempts have been sparse.To determine whether a reduction in suicide attempts among youths occurs following the implementation of the Garrett Lee Smith Memorial Suicide Prevention Program (hereafter referred to as the GLS program), consistent with the reduction in mortality documented previously.We conducted an observational study of community-based suicide prevention programs for youths across 46 states and 12 tribal communities. The study compared 466 counties implementing the GLS program between 2006 and 2009 with 1161 counties that shared key preintervention characteristics but were not exposed to the GLS program. The unweighted rounded numbers of respondents used in this analysis were 84 000 in the control group and 57 000 in the intervention group. We used propensity score-based techniques to increase comparability (on background characteristics) between counties that implemented the GLS program and counties that did not. We combined information on program activities collected by the GLS national evaluation with information on county characteristics from several secondary sources. The data analysis was performed between April and August 2014. P < .05 was considered statistically significant.Comprehensive, multifaceted suicide prevention programs, including gatekeeper training, education and mental health awareness programs, screening activities, improved community partnerships and linkages to service, programs for suicide survivors, and crisis hotlines.Suicide attempt rates for each county following implementation of the GLS program for youths 16 to 23 years of age at the time the program activities were implemented. We obtained this information from the National Survey on Drug Use and Health administered to a large national probabilistic sample between 2008 and 2011.Counties implementing GLS program activities had significantly lower suicide attempt rates among youths 16 to 23 years of age in the year following implementation of the GLS program than did similar counties that did not implement GLS program activities (4.9 fewer attempts per 1000 youths [95% CI, 1.8-8.0 fewer attempts per 1000 youths]; P = .003). More than 79 000 suicide attempts may have been averted during the period studied following implementation of the GLS program. There was no significant difference in suicide attempt rates among individuals older than 23 years during that same period. There was no evidence of longer-term differences in suicide attempt rates.Comprehensive GLS program activities were associated with a reduction in suicide attempt rates. Sustained suicide prevention programming efforts may be needed to maintain the reduction in suicide attempt rates.
Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes.
Authors: K W Wucherpfennig, I Catz, S Hausmann, J L Strominger, L Steinman, K G Warren
Journal: Journal of Clinical Investigation (1997)

Myelin basic protein (MBP) may be an important autoantigen in multiple sclerosis (MS), with the MBP(82-100) region being immunodominant for T cells and autoantibodies. The structural requirements for autoantibody recognition were compared to those previously defined for MBP-specific T cell clones. MBP autoantibodies were affinity-purified from central nervous system lesions of 11/12 postmortem cases studied. The MBP(83-97) peptide was immunodominant in all 11 cases since it inhibited autoantibody binding to MBP > 95%. Residues contributing to autoantibody binding were located in a 10-amino acid segment (V86-T95) that also contained the MHC/T cell receptor contact residues of the T cell epitope. In the epitope center, the same residues were important for antibody binding and T cell recognition. Based on the antibody-binding motif, microbial peptides were identified that were bound by purified autoantibodies. Autoantibody binding of microbial peptides required sequence identity at four or five contiguous residues in the epitope center. Microbial peptides previously found to activate T cell clones did not have such obvious homology to MBP since sequence identity was not required at MHC contacts. The similar fine specificity of B cells and T cells may be useful for tolerance induction to MBP in MS.