tbuckley/cabot-search huggingface dataset:
Curbing Firearm Violence
Authors: Robert B. Sklaroff
Journal: Annals of Internal Medicine (2016)

Letters20 December 2016Curbing Firearm ViolenceRobert B. Sklaroff, MDRobert B. Sklaroff, MDFrom Nazareth Hospital, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0541 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Weinberger's editorial (1) with interest. As was the case 2 years ago (2), “because public health research predictably guides a generation of public policy, it is necessary to scrutinize the political science underlying the paired [article] and editorial on gun control.” Inasmuch as the term “gun control” carries divergent meanings to liberals (restricting firearm access) and conservatives (aiming firearms properly), it is necessary to recognize that editorialization—particularly in a scientific journal—is most effective when devoid of proselytizing.Weinberger claims that physicians “have a broader societal obligation to improve population health” and, thus, “to inform and ...References1. Weinberger SE. Curbing firearm violence: identifying a specific target for physician action. Ann Intern Med. 2016;165:221-2. [PMID: 27183475]. doi:10.7326/M16-0968 LinkGoogle Scholar2. Sklaroff RB. Guns, suicide, and homicide [Letter]. Ann Intern Med. 2014;160:876-7. [PMID: 24935495]. doi:10.7326/L14-5012-2 LinkGoogle Scholar3. Wintemute GJ, Betz ME, Ranney ML. Yes, you can: physicians, patients, and firearms. Ann Intern Med. 2016;165:205-13. [PMID: 27183181]. doi:10.7326/M15-2905 LinkGoogle Scholar4. Electronic Frontier Foundation. National security and medical information. 2016. Accessed at www.eff.org/issues/national-security-and-medical-information on 5 August 2016. Google Scholar5. Anonymous. The role of HIPAA in gun control. Scripted Blog. 2016. Accessed at www.scripted.com/writing-samples/the-role-of-hipaa-in-gun-control on 5 August 2016. Google Scholar Author, Article, and Disclosure InformationAffiliations: From Nazareth Hospital, Philadelphia, Pennsylvania.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0541. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCurbing Firearm Violence: Identifying a Specific Target for Physician Action Steven E. Weinberger Curbing Firearm Violence Steven Weinberger Metrics Cited byFirearm Research Must Not Presuppose Outcome 20 December 2016Volume 165, Issue 12Page: 893-894KeywordsBehaviorConflicts of interestDisclosureFirearm injuriesInformation storage and retrievalPrevention, policy, and public healthPublic policy ePublished: 20 December 2016 Issue Published: 20 December 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Gene Expression Profiling Identifies Similar CD4+ and CD8+ T Cell Defects in TCL1 Transgenic Mice after Development of CLL to Those Observed in Patients with CLL.
Authors: Vassiliki Rizouli, David Zahrieh, Gullu Gorgun, Tobias A.W. Holderried, Carlo Croce, John G. Gribben
Journal: Blood (2004)
PTH-319 Is there a useful relationship between pelvimetry and operative or oncological outcome after low rectal cancer surgery?: Abstract PTH-319 Table 1
Authors: P Waterland, G Lafaurie, D Macarthur, S Karandikar
Journal: Gut (2015)

<h3>Introduction</h3> Bony pelvimetry varies between the sexes and has been found to be a possible factor in predicting operating time, quality of histological total mesorectal excision (TME) grade and positivity of circumferential resection margin (CRM) after rectal cancer surgery. Low pelvic dissection is anecdotally more difficult in narrow and deep pelves. This observational study aimed to identify any relationship between magnetic resonance (MR) bony pelvimetry measurements and operative or oncological outcome in patients undergoing rectal cancer surgery. <h3>Method</h3> A prospective database of patients undergoing anterior resection was maintained including demographics, operating time, tumour characteristics and oncological outcomes. MR pelvimetry recordings were performed by a surgeon ‘blinded’ to outcome. Chosen endpoints were local recurrence (LR), disease free survival (DFS), overall survival (OS) and operating time (OT). Binary logistic regression and Pearson’s correlation coefficient were performed for statistical analysis. <h3>Results</h3> A total of 171 patients underwent surgery (58 abdomino-perineal resection, 113 anterior resection) between 01/2009 and 05/2014. Median operating time was 318 min (range 91–421). Median follow-up was 25 months. There were 10(5.8%) patients with positive CRM, 10(5.8%) patients with LR, and 28(16.3%) deaths during follow-up period. There was no significant correlation between individual MR pelvimetry measurements and LR, DFS, OS or OT. However, the distance between the tip of the coccyx to the sacral promentory, and the tip of the coccyx to the body of S3 were strongly correlated with operating time, with the former also being closest to significance in correlation with LR. <h3>Conclusion</h3> Our study does not demonstrate any statistically significant relationship between bony pelvimetry and outcome after low rectal cancer surgery. A deep pelvis is correlated non-significantly with local recurrence and prolonged operating time. Further follow-up is required for complete five year oncological data. <h3>Disclosure of interest</h3> None Declared.
KetoCal®, a novel ketogenic diet therapy for brain cancer
Authors: Weihua Zhou, Purna Mukherjee, Michael A. Kiebish, John G. Mantis, Kristen N. Gorham, Tiernan J. Mulrooney, William T. Markis, Thomas N. Seyfried
Journal: Cancer Research (2006)

3887  The ketogenic diet (KD) is a high fat/low carbohydrate diet that has been used for decades to manage epileptic seizures in children. Our recent findings suggest that the bioenergetic transition from glucose to ketone bodies will metabolically target brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. This study evaluated the efficacy of KetoCal®, a new specially formulated commercial ketogenic diet for children, on the growth and angiogenic properties of a mouse astrocytoma (CT-2A) and a human glioma (U87-MG) that were orthotopically implanted in C57BL/6J and BALBc/J (SCID) mice, respectively. KetoCal®was administered to the mice in a restricted amount to maintain body weight at approximately 80% of the standard (high carbohydrate) chow-fed control group. Circulating glucose and ketone body levels were monitored as measures of energy consumption. Protein and gene expressions for succinyl-CoA-acetoacetate-CoA transferase (SCOT) and betahydroxybutyrate dehydrogenase (β-OHBDH), key enzymes for ketone metabolism, were investigated in tumors and contra-lateral normal brain tissue. The tumors were analyzed for microvessel density (Factor VIII) as a marker for tumor angiogenesis. KetoCal® significantly decreased the intracerebral CT-2A and U87-MG growth by about 70% and 35%, respectively, and significantly enhanced survival relative to the control groups. The diet significantly reduced blood glucose while elevated β-hydroxybutyrate dehydrogenase levels. SCOT and β-OHBDH expressions were significantly lower in the tumors than in the brain suggesting that the brain tumor cells have impaired ability to metabolize ketone bodies for energy. Microvessel density was significantly lower in the KetoCal® groups than in the control groups. These results indicate that KetoCal® has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors, and should have clinical efficacy for managing malignant human brain cancer. Supported by the National Institutes of Health grants (HD39722) and (CA102135), and a grant from the American Institute of Cancer Research.
541. Increased Integration of Lentiviral Vector Carrying a D167H Integrase Relies on the Presence of LEDGF/p75
Authors: Che Serguera, Noelle Dufour, ALexis P. Bemelmans
Journal: Molecular Therapy (2015)

HIV-1 vectors derive from a virus specialized of host human cells whose replication relies on a dynamic interplay between viral and cellular proteins. Critical for HIV-1 replication is the integration of its genome in the host cellular chromatin, a feature exploited by lentiviral vectors to ensure persistent transgene expression across generations in proliferating cells. To reach to that point the RNA genome of HIV must first ensure its reverse transcription as it is transported to the nucleus. During this early step of transduction the vector particle undergoes successive structural transformation from the reverse transcription complex (RTC), where the vector DNA is synthesized, to the preintegration complex (PIC) which is an assembly of vector and cellular factors able to catalyze vector genome integration into cellular DNA. The viral protein integrase (IN), in addition to catalyze viral DNA integration, also participates in the structure and function of these dynamic complexes through timely interactions with itself and with other viral and cellular proteins. We have previously shown that a HIV vector carrying a mutant integrase (D167H) had improved integration capabilities as compared to particles with wild type integrase. Here we show that such improvement is dependent on the presence of the cellular factor LEDGF/p75 and that this protein is required at integration step but is dispensable for nuclear translocation of the PIC.
306. Characterization of a Novel Adeno-Associated Viral Vector with Preferential Oligodendrocyte Tropism
Authors: Sara K. Powell, Nadia Khan, Christina Parker, R. Jude Samulski, Glenn Matsushima, Steven J. Gray, Thomas J. McCown
Journal: Molecular Therapy (2015)

An AAV vector with oligodendrocyte-centric tropism would provide a valuable tool for research or for gene therapy in the treatment of demyelinating neurological disorders, such as ALS and multiple sclerosis. Using AAV capsid DNA shuffling we created a library of novel AAV vectors. The primary recovered AAV capsid clone (Olig001) exhibited a novel >95% tropism for rat, striatal oligodendrocytes when a chicken beta actin (CBH) promoter drove GFP expression. Furthermore, when Olig001 is administered intravenously it is highly detargeted from peripheral tissues such as the liver. Surprisingly, Olig001 shares 99.3% homology (7 amino acid differences) with AAV8 within the VP3 coding region (aa204-738 using VP1 numbering); however, AAV8-CBH-GFP vectors are predominantly neurotropic. While AAV8 has some minimal tropism for oligodendrocytes, our in vitro studies using primary mixed glia cultures showed that Olig001 binds to oligodendrocytes with much higher affinity than AAV8, thus Olig001 exhibits a true gain-of-function. We sought to identify which amino acid(s) of Olig001 contribute to the oligodendrocyte-preferring tropism. Mutation of some or all of the four C-terminal amino acids of Olig001 (downstream of aa343 using VP1 numbering) back to AAV8 still produced an oligodendrocyte-preferring capsid. The N-terminal, mostly VP1/VP2-specific, portion of the capsid is a chimeric mixture of AAV1, 2, 6, and 9, and our results suggest that this region of the capsid is conferring the oligodendrocyte preferring phenotype. In summary, we report the generation of a novel AAV capsid with a tropism and biodistribution profile distinct from any naturally-occuring AAV capsids. Moreover, our results suggest that the N-terminus of the capsid specific to VP1/VP2 is the major contributor to this unique oligodendrocyte tropism. Work supported by Michel J. Fox Foundation and Target ALS grants to TJM.
Two Strategies of Stem Cells Mobilization Using Plerixafor and Comparison of Grafts Obtained with and without It. Is Plerixafor Only a Mobilization Agent?
Authors: Michal Zwiewka, Zdenka Stefanikova, Katarína Masárová, Ján Martinka, Mikuláš Hrubiško, Hana Pribulová, Jolana Hapalová, Eva Bojtárová, Martin Mistrik
Journal: Blood (2011)
Choriocarcinoma - An Indian Experience
Authors: G. K, L. Kumar
Journal: Journal of Clinical Oncology (2004)

5127 Background: Choriocarcinoma (Cc) is in the malignant end of the spectrum of gestational trophoblastic diseases (GTD). Appropriate therapy results in excellent survival and preserved fertility. Methods:In the last decade, we have seen 31 cases of clinical/radiological and /or histopathologically confirmed cases of Cc. The current study is a retrospective audit of these cases. Results:The mean age was 27.4 +/- 1.0 years; five (16 %) were older than 35 years. Three forth had abortion as the antecedent event while the rest had term pregnancy. The common presenting symptoms were vaginal bleeding (87.1%) and abdominal pain (45.2%). Focal neurological deficits or seizures were seen in 5 cases. Metastases were noted in 29 (93.5%) patients and the common sites were lungs (84%), liver (19.3%), brain (16.4%) and one each in kidney, pancreas and peritoneum. The mean serum beta HCG was a 148000 mIU/ml. Raised serum HCG level beyond 6 months was seen in half the cases. Seven cases had neither National Cancer Institute (NCI) risk factor. Metastatic good risk group was the most common seen in 15 (48.4%) followed by the poor risk group (45.2%). The median modified WHO scores was 13 (range: 3–23), with 4 in the low risk and the rest in high-risk category. Suction curettage was the initial diagnostic/therapeutic modality in most while hysterectomy was performed in 6 cases. All except one, received chemotherapy with either methotrexate/leucovorin (64.3%) or EMA/CO regimen (18%) or others (14.3%). Eleven (36.6 %) with first line and 7 (23.3%) with second line chemotherapy (overall 60%) achieved complete remission and continue to remain in remission at last visit. Three cases received whole brain radiotherapy for brain secondaries and salvage surgery (2 hysterectomy and 1 lung metastatectomy) was performed in 3 cases. Two patients died of extensive disease while the others never achieved remission at last follow-up. Of the eligible 23 cases, 15 had normal menstruation, 3 had normal delivery while 2 had recurrent molar pregnancy subsequently. Conclusions:Our patients had higher tumor burden, advanced stage at diagnosis and higher prognostic scores, but with comparable survival. No significant financial relationships to disclose.
206. Determining the Effect of Endogenous PD-1 Expression on the Co-Stimulatory Potential of the PD1:CD28 Chimera
Authors: Megan E. Keys, Jonathan Arroyo, Bridgette Kielhack, Megan Prosser
Journal: Molecular Therapy (2016)

Adoptive immunotherapy is an emerging field of study involving genetic alteration of the immune system to enhance its effectiveness in eliminating cancer. A previous study created a novel chimera (PD1:CD28) containing the extracellular portion of an inhibitory molecule, Programmed Death 1 (PD-1), and the intracellular portion of a co-stimulatory molecule, CD28, resulting in tumor induced co-stimulation of T cells. Given that endogenous PD-1 expression is likely to up-regulate on T cells in the tumor microenvironment, the current study aims to determine whether the presence of PD-1 on the cell surface negatively impacts T cell stimulation by the PD1:CD28 chimera. Endogenous PD1 was tagged with a red fluorescent protein, mCherry, and PD1:CD28 with a green fluorescent protein, GFP. Fusion proteins were transfected into H9 cells and positive expression was detected via flow cytometric analysis and fluorescence microscopy. Stable cell lines expressing both PD1:mCherry and PD1:CD28:GFP fusion proteins are being examined for downstream signaling markers, proliferation, and cytokine expression following exposure to Programmed Death Ligand 1 (PD-L1), as compared to cells engineered to express only PD1:mCherry or PD1:CD28:GFP. This study will provide further insight into the ability of the PD1:CD28 chimera to overcome PD-1 mediated tumor immune evasion.
Abstract 14632: Effect of Obesity on Myocardial Strain Determined by Speckle Tracking Imaging
Authors: Meihua Zhu, Cole Streiff, Tao He, Muhammad Ashraf, Jiahui Zhang, Lydia Tam, David J Sahn
Journal: Circulation (2015)

Introduction: Obesity may affect cardiac function, which is hard to detect by traditional echocardiography in the early stages. Speckle tracking imaging (STI) is sensitive to subtle myocardial dysfunction. The aim of this study was to determine the influence of obesity on left ventricular (LV) myocardial function in diet-induced obesity (DIO) mice using two-dimensional (2D) speckle tracking echocardiography (STE). Hypothesis: 2D STE is useful to detect obesity-caused myocardial dysfunction. Methods: Twenty newborn mice were divided into two groups: a DIO group (high-fat diet) and a control group (regular-fat diet). 2D image loops were acquired at the end of each month for 6 months. Global longitudinal strain (GLS) and global circumferential strain (GCS) were analyzed at feeding periods over 3 months and 6 months, and compared between the two groups. Results: The control group gained 64% of its initial weight, while the DIO group gained 82% of its initial weight at the 3 month feeding period; and the two groups gained 88% (control) and 125% (DIO) respectively at 6 months. STE analysis revealed an insignificant decrease in strain values in the DIO mice after 3 months; however, after 6 months, the DIO group demonstrated a significant decrease in strain values (P&lt;0.05) despite normal ejection fractions in both groups. Conclusions: 2D STE is highly feasible to detect the myocardial dysfunction caused by obesity in earlier stage. These strain values appear to be related to the severity of obesity.
<i>MST1R</i> mutation as a genetic cause of Lady Windermere syndrome
Authors: Katharina L. Becker, Peer Arts, Martin Jaeger, Theodorus S. Plantinga, Christian Gilissen, Arjan van Laarhoven, Jakko van Ingen, Joris A. Veltman, Leo A.B. Joosten, Alexander Hoischen, Mihai G. Netea, Michael D. Iseman, Edward D. Chan, Frank L. van de Veerdonk
Journal: European Respiratory Journal (2016)

The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease is increasing [1]. The most commonly isolated disease-causing NTMs belong to the Mycobacterium avium complex [1]. Susceptibility to and clinical manifestation of NTM disease are largely governed by the immune status of a person. Disseminated or extrapulmonary NTM infections are strongly associated with severe immunosuppression, such as those with frank defects in the interferon (IFN)-γ–interleukin (IL)-12 axis [2]. Isolated pNTM is strongly associated with certain underlying conditions, such as cystic fibrosis, chronic obstructive pulmonary disease and primary ciliary dyskinesia [3, 4]. However, substantial numbers of pNTM patients have no apparent risk factors, and a significant proportion of them exhibit a body morphotype characterised by lifelong slender body habitus, pectus excavatum, scoliosis and mitral valve prolapse [5, 6], also called the Lady Windermere syndrome. A modest reduction in IFN-γ production and an increase in transforming growth factor (TGF)-β levels have been described [7–10]. Fowler et al. [11] quantified ciliary beat frequency of 58 pNTM patients and 40 controls and found reduced ciliary beat frequency in the pNTM patients. Szymanski et al. [12] performed whole-exome sequencing on patients with pNTM, their unaffected family members and a control group and concluded that pNTM is a multigenic disease, encompassing potential defects in proteins encoded by cilia genes, the cystic fibrosis transmembrane conductance regulator gene, connective tissue genes and certain immune-related genes. Susceptibility to NTM infections in patients with Lady Windermere syndrome is associated with MST1R variants <http://ow.ly/xKgX304uhse> We thank Melanie Wattenberg and Nicole Aalders for their great assistance in the tuberculosis lab and to Bart Loeys (all at Dept of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands) for helpful discussions. We are also grateful to all the patients for participating in the study. We thank Patricia Merkel and Vijaya Knight (National Jewish Health, Denver, CO, USA) for performing the Stat1a analysis.
Cytotoxic T Cells Specific for Adenovirus, BK Virus, Cytomegalovirus, Epstein Barr Virus and Varicella Zoster Virus Produced for Clinical Use In Immune Reconstitution Post Allogeneic Stem Cell Transplantation
Authors: Emily Blyth, Leighton Clancy, Shiva Gaundar, Renee Simms, David Gottlieb
Journal: Blood (2010)
Abstract 5297: Chromosomal instability as a prognostic marker in cervical cancer
Authors: Christine How, Jeff Bruce, Jonathan So, Melania Pintilie, Benjamin Haibe-Kains, Angela Hui, Blaise Clarke, David Hedley, Richard Hill, Michael Milosevic, Anthony Fyles, Kenneth W. Yip, Fei-Fei Liu
Journal: Cancer Research (2015)

Abstract Previous studies have demonstrated that chromosomal instability (CIN) is a consistent feature of the majority of solid tumors. In this current study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre (n = 79) and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients (n = 130). Patients with a high CIN70 score had a higher number of copy number alterations (Spearman's correlation coefficient (r) = 0.28, p&amp;lt;0.001), and a higher percentage of genome altered (r = 0.19, p = 0.016). According to Kaplan-Meier analysis, the CIN70 signature achieved borderline significance for para-aortic nodal or distant relapse, with a hazard ratio of 3.02 and Wald p-value of 0.05, but not significant for overall, disease-free survival, or local relapse. In summary, these findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer. Citation Format: Christine How, Jeff Bruce, Jonathan So, Melania Pintilie, Benjamin Haibe-Kains, Angela Hui, Blaise Clarke, David Hedley, Richard Hill, Michael Milosevic, Anthony Fyles, Kenneth W. Yip, Fei-Fei Liu. Chromosomal instability as a prognostic marker in cervical cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5297. doi:10.1158/1538-7445.AM2015-5297