tbuckley/cabot-search huggingface dataset:
Health experts urge MPs to back decriminalisation of prostitution
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Public health experts have backed a recent call from MPs for changes to the law over prostitution, and have urged them to consider full decriminalisation of sex work.

MPs on the home affairs committee recently published a report1 that recommended that the Home Office change existing legislation so that soliciting is no longer an offence and brothel keeping provisions allow sex workers to share premises, without losing the ability to prosecute those who use brothels to control or exploit sex workers.

The report said that treating soliciting as an offence was having an adverse impact in terms of stopping sex workers from seeking help to exit prostitution because having a …
Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping
Authors: Elaine Rutherford, Mohammed A. Talle, Kenneth Mangion, Elizabeth Bell, Samuli M. Rauhalammi, Giles Roditi, Christie McComb, Aleksandra Radjenovic, Paul Welsh, Rosemary Woodward, Allan D. Struthers, Alan G. Jardine, Rajan K. Patel, Colin Berry, Patrick B. Mark
Journal: Kidney International (2016)

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking-derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.
Abstract 2748: Targeting DNA repair deficient cancers with the cell-penetrating autoantibody 3E10
Authors: Audrey L. Turchick, Peter M. Glazer
Journal: Cancer Research (2016)

Abstract There is growing evidence that many solid tumors have defective DNA repair pathways and cell cycle checkpoints. This has spurred development of therapeutics to specifically target cancer cells with defective DNA repair, but few have been successful outright due to problems such as general toxicity. One novel anti-cancer agent of interest to us is 3E10, a unique cell-penetrating, anti-DNA autoantibody. This molecule is non-toxic to normal cells on its own but has deleterious effects on cells with DNA repair deficiencies. Specifically, 3E10 has been shown to be synthetically lethal in BRCA2-deficient human cancer cells, to be synergistic with radiation and other commonly used DNA damaging therapies, and to reduce the efficiency of Rad51 mediated strand exchange and thus homologous recombination (HR). The goal of this project is to better understand how 3E10 can be used as a new paradigm for cancer treatment. New evidence suggests that 3E10 inhibits Exo1 exonuclease activity. Additionally, preliminary data shows that 3E10 physically interacts with Rad51, ultimately inhibiting Rad51 nuclear localization and foci formation. Additionally, a point mutation in 3E10 that confers increased DNA binding mediates increased cell death in BRCA2-deficient human cancer cells. Furthermore, studies investigating the potential therapeutic effect of 3E10 in patient derived primary melanoma cell lines show that 3E10 is synthetically lethal with PTEN deficiency. This data suggests that 3E10 inhibits HR by binding to DNA at double strand breaks and occupying sites normally processed by core repair machinery, as well as by physically interacting with Rad51. Overall, 3E10 holds great promise as a novel therapeutic agent for various cancers, including PTEN deficient melanomas. Reference: Hansen, J. et al. Targeting cancer with a lupus autoantibody. Science Translational Medicine 4, (2012) Citation Format: Audrey L. Turchick, Peter M. Glazer. Targeting DNA repair deficient cancers with the cell-penetrating autoantibody 3E10. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2748.
ERCC1 status in patients with locally advanced cervical cancer treated with RT or CRT: A multicenter clinicopathologic analysis.
Authors: C. M. Doll, A. W. Fyles, C. Aquino-Parsons, M. Pintilie, A. Klimowicz, S. Petrillo, M. Milosevic, S. P. Lees-Miller, B. A. Clarke, A. M. Magliocco
Journal: Journal of Clinical Oncology (2010)

5055 Background: ERCC1 expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites. However, it has not been well studied in cervical cancer. Purpose: To determine the impact of tumoral ERCC1 expression in patients with locally advanced cervical cancer treated with radiotherapy (RT) or chemoradiotherapy (CRT), in a large multicenter cohort. Methods: 463 patients with locally advanced cervical cancer, treated with radical RT or CRT (cisplatin-based) from 3 major Canadian cancer centers (BCCA, Vancouver (n = 90); TBCC, Calgary (n = 225); PMH, Toronto (n = 148) between 1986-2004 were evaluated. 308 patients (66%) were in the CRT cohorts and 155 (33%) were in the RT cohorts. Pretreatment FFPE tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) protein expression was measured using AQUA technology, and nuclear/cytoplasmic (n/c) ratio was calculated for standardization. The association of clinical factors and ERCC1 status with PFS and OS was determined at 3 years. Results: The majority of patients had FIGO stage II disease (53%); median tumor size was 5 cm. Median patient age was 52 years. Median follow-up was 5 years. Overall survival was 70% for the CRT cohorts, and 63% for the RT alone cohort (p = 0.076); PFS was 58% for both treatment cohorts (p = 0.54). OS was associated with age (HR 1.02, p = 0.0005), tumor size (HR 1.2, p < 0.0001), pre-treatment hemoglobin (Hgb) status (HR 2.63, p < 0.0001), and chemotherapy (HR 0.54, p = 0.0003). In addition, ERCC1 status was associated with OS (HR 2.44 [1.08-5.52], p = 0.03) and PFS (HR 2.08 [1.00-4.33], p = 0.05) in the CRT cohorts. No significant association between ERCC1 status and outcome was seen in the RT alone cohort. In the CRT cohorts ERCC1 status was not significant when the model was adjusted for the clinical factors: for OS (HR 1.84 [0.78-4.33], p = 0.16); for PFS (HR 1.55 [0.71-3.39] p = 0.27). Conclusions: Tumor size and pretreatment Hgb status were significantly associated with OS and PFS in patients treated with RT or CRT. ERCC1 status appears to have prognostic impact on univariate analysis in patients treated in the CRT cohorts, but was not independently associated with outcome. No significant financial relationships to disclose.
Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia
Authors: Laura Gragnani, Marcella Visentini, Elisa Fognani, Teresa Urraro, Adriano De Santis, Luisa Petraccia, Marie Perez, Giorgia Ceccotti, Stefania Colantuono, Milica Mitrevski, Cristina Stasi, Martina Del Padre, Monica Monti, Elena Gianni, Alessandro Pulsoni, Massimo Fiorilli, Milvia Casato, Anna Linda Zignego
Journal: Hepatology (2016)

Hepatitis C virus (HCV)‐associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, but conventional therapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir‐based direct‐acting antiviral therapy, individually tailored according to the latest guidelines, in a cohort of 44 consecutive patients with HCV‐associated MC. In two patients MC had evolved into an indolent lymphoma with monoclonal B‐cell lymphocytosis. All patients had negative HCV viremia at week 12 (SVR12) and at week 24 (SVR24) posttreatment, at which time all had a clinical response of vasculitis. The mean (±standard deviation) Birmingham Vasculitis Activity Score decreased from 5.41 (±3.53) at baseline to 2.35 (±2.25) ( P &lt; 0.001) at week 4 on treatment to 1.39 (±1.48) ( P &lt; 0.001) at SVR12 and to 1.27 (±1.68) ( P &lt; 0.001) at SVR24. The mean cryocrit value fell from 7.2 (±15.4)% at baseline to 2.9 (±7.4)% ( P &lt; 0.01) at SVR12 and to 1.8 (±5.1)% ( P &lt; 0.001) at SVR24. Intriguingly, in the 2 patients with MC and lymphoma there was a partial clinical response of vasculitis and ∼50% decrease of cryocrit, although none experienced a significant decrease of monoclonal B‐cell lymphocytosis. Adverse events occurred in 59% of patients and were generally mild, with the exception of 1 patient with ribavirin‐related anemia requiring blood transfusion. Conclusion: Interferon‐free, guideline‐tailored therapy with direct‐acting antivirals is highly effective and safe for HCV‐associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention‐to‐treat basis, opens the perspective for curing the large majority of these so far difficult‐to‐treat patients. (H epatology 2016;64:1473‐1482)
Improving Lentiviral Transduction Efficiency with Microfluidic Systems
Authors: Reginald Tran, David R Myers, Jordan E Shields, Byungwook Ahn, Yongzhi Qiu, Caroline Hansen, Yumiko Sakurai, Robert Moot, H. Trent Spencer, Christopher B Doering, Wilbur A Lam
Journal: Blood (2015)
Haploidentical Transplantation (HAPLO) with Post-Transplant High-Dose Cyclophosphamide for Graft Vs Host Disease (GVHD) Prevention in the Treatment of High Risk Hematological Neoplasms
Authors: Jorge Gayoso, Mi Kwon, David Serrano, Pascual Balsalobre, Javier Anguita, Cristina Pascual, Ana Pérez-Corral, Ismael Buno, Carolina Martinez-Laperche, Cristina Castilla-Llorente, Inmaculada Heras, Maria Jesus Pascual, Dolores Caballero, Jose Luis Diez-Martin
Journal: Blood (2012)
Pain as a Predictor of Opioid Use Disorder in a Nationally Representative Sample
Authors: Carlos Blanco, Melanie M. Wall, Mayumi Okuda, Shuai Wang, Miren Iza, Mark Olfson
Journal: American Journal of Psychiatry (2016)

The authors sought to ascertain the relationship between moderate and more severe pain and prescription opioid use disorders in the noninstitutionalized U.S.A structural equation model was used to assess prospectively the interdependency of pain and prescription opioid use disorder at waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Pain was measured with a 5-point scale of pain-related interference in daily activities and dichotomized as "no pain" (no or little interference) or "pain" (moderate to extreme interference). Prescription opioid use disorder was assessed with a structured interview (the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version). Other covariates included age, sex, anxiety or mood disorders, and family history of drug, alcohol, and behavioral problems.In the structural equation model, pain and prescription opioid use disorders were significantly associated with one another at baseline and at 3-year follow-up. However, whereas pain at baseline was also significantly associated with prescription opioid use disorder at follow-up, prescription opioid use disorder at baseline was not associated with pain at follow-up. These associations were independent of several background demographic and clinical characteristics. The path for pain interference was associated with a 41% relative increase in the risk of developing a prescription opioid use disorder.Painful conditions contribute to the risk of prescription opioid use disorders. To help reduce the incidence of prescription opioid abuse and dependence among adults with moderate to severe pain, careful monitoring and consideration of nonopioid alternative treatments is warranted.
Determinants of survival in adolescents and young adults with urothelial cancer: Results from the California Cancer Registry.
Authors: Joshua David Lara, Ann Brunson, Ralph de Vere White, Chong-xian Pan, Stanley A Yap, Jay R. Balagtas
Journal: Journal of Clinical Oncology (2015)

e15543 Background: Urothelial cancer (UC) is the 6thmost common malignancy in the United States and is often diagnosed in the elderly: median age at diagnosis is 73 years. Previous studies have reported racial disparities in survival outcomes in UC patients but have not focused on a younger demographic. We sought to identify factors influencing cancer-specific survival (CSS) in adolescents and young adults (AYA, ages 15-39) with UC using the California Cancer Registry (CCR). Methods: Patients diagnosed with UC between 1998 through 2012 and reported to the CCR as of October 2013 were included. The primary outcome measure was CSS. Cox regression models were used to evaluate predictors of improved CSS in AYA patients with UC, adjusted for potential confounders, including race and socioeconomic status (SES, scaled from lowest to highest, 1 to 5). Results: Of 111,800 cases of UC, we identified 1,753 AYA patients. Age distribution (n, %) was as follows: 15-19 (47, 2.7%), 20-24 (113, 6.4%), 25-29 (216, 12.3%), 30-34 (456, 26.0%), & 35-39 (921, 52.5%). Most were male (1,284, 73.2%), white (1,162, 66.3%), had in situ/localized stage (1,549, 88.3%), and had transitional cell histology (1,608, 91.7%). Bivariate analysis showed worse CSS in females (Hazard Ratio [HR] 1.64, p = 0.007), blacks (HR 2.9, p < 0.001), and distant stage (HR 278.2, p < 0.001), among others. Multivariate analysis demonstrated that black race (HR 2.9, p = 0.001), distant stage (HR 192.9, p < 0.001), and low SES (HR 2.5, p = 0.002) were significant predictors of poor CSS. Interaction analysis showed that blacks in the lowest SES groups (i.e., SES 1-3) had significantly worse CSS (HR 5.0, p = 0.05) than white patients, but there was no difference between race groups at the higher SES groups. Conclusions: This is among the largest analyses of survival outcomes in AYA patients with UC ever reported. Significant racial and socioeconomic disparities exist in AYA patients with UC diagnosed in California. Potential causes of these disparities could include genetic differences and/or lack of access to quality cancer care. Further studies are warranted to further identify the underlying causes in order to overcome these disparities.
Abstract 2923: Preclinical validation of Omomyc cell-penetrating peptides as a viable in vivo anti-Myc therapy
Authors: LAURA SOUCEK.
Journal: Cancer Research (2016)

Abstract Deregulated Myc is associated with most human cancers suggesting that its inhibition would be a useful therapeutic strategy. Indeed, we have shown that Myc inhibition displays extraordinary therapeutic benefit in various transgenic mouse models of cancer (i.e. skin, lung, pancreatic cancer and glioma), without eliciting resistance to therapy, and causes only mild, well-tolerated and reversible side effects in normal tissues. For these studies we employed a dominant negative inhibitor of Myc, called Omomyc, which is an effective inhibitor of Myc transactivation function both in vitro and in vivo. Omomyc has so far been utilized exclusively as a transgene and served as a successful proof of principle. Here we present our current results based on the direct use of Omomyc itself as a peptide displaying unexpected and efficient cell-penetrating activity (OmomycCPP). When tested in vitro, OmomycCPP causes growth arrest and/or death of several cancer cell lines. In vivo, upon intranasal administration, it rapidly biodistributes to the lung and brain, as well as to other tissues of the animals, and - like its transgenic counterpart before - has a notable therapeutic impact on KRasG12D-driven Non-small Cell Lung Cancer (NSCLSC). In summary, our results show that OmomycCPP represents a novel and viable pharmacological strategy to inhibit Myc in vivo, a strategy that has the potential to be translated rapidly to the clinic. Citation Format: LAURA SOUCEK. Preclinical validation of Omomyc cell-penetrating peptides as a viable in vivo anti-Myc therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2923.
Re: Cost-Effectiveness of Cervical Cancer Screening With Human Papillomavirus DNA Testing and HPV-16,18 Vaccination
Authors: Paolo Giorgi Rossi, Marco Zappa
Journal: JNCI Journal of the National Cancer Institute (2008)

Goldhaber-Fiebert et al. (1) presented a convincing model for the natural history of cervical cancer. The results of this study should be considered by all policy makers in taking decisions about the preventive strategies for cervical cancer.

The evaluation of this model was made by comparing the observed incidence curve by age of cervical cancer onset with the predicted incidence curve. In industrialized countries, this incidence curve is the result of a complex interaction involving the clinical history of the disease, sexual behaviors, and the screening habits of the different cohorts of women. The model reproduces the observed curve perfectly, and this reproduction is the result of a mixture of five populations with different cervical cancer screening behaviors and age distributions. The sum of these five populations produces the observed figures of screening behaviors by age in the United States and the number of invasive cancers that occurred (2).

The preventive strategies proposed are based mainly on two interventions: vaccination and screening. Both of these interventions have two main factors that determine their effectiveness: the technical characteristics of vaccine and screening test (ie, the protection against infection and the types of human papillomaviruses that the vaccine is directed against and the sensitivity and specificity of the test) and the compliance of the population (ie, the vaccine coverage and test uptake).

To better understand the role that each factor plays in determining effectiveness and also to have a valid target that is sensitive to the model characteristics, we believe that the proportion of cancer occurring in screened women, in unscreened people, and in vaccinated and unvaccinated women should be one of the most important outcomes to be presented for validation of a model for the natural history of cervical cancer. Given the structure of the model, it should be very easy to provide this output. Unfortunately, for the United States, there are few data on screening history for invasive cervical cancers (3,4) that could be used to validate the model; however, these data are available for other countries (5–7).

All of these studies conclude that lack of participation in screening is still a major risk factor for invasive cancer in industrialized countries. Will lack of participation still be the major failure for the future preventive programs?
Adipocyte-Derived Adiponectin Positively Regulates Exit from Quiescence of Hematopoietic Stem Cells By Potentiating mTORC1 Activation after Myelotoxic Injury
Authors: Yosuke Masamoto, Shunya Arai, Tomohiko Sato, Iseki Takamoto, Naoto Kubota, Takashi Kadowaki, Mineo Kurokawa
Journal: Blood (2015)
Abstract 3206: Programmed death receptor-1/programmed death receptor ligand-1 blockade improves priming of antitumor effector T cells after cytotoxic therapies
Authors: Miho Takahashi, Satoshi Watanabe, Ko Sato, Tomohiro Tanaka, Yu Saida, Junko Baba, Aya Ohtsubo, Miyuki Sato, Rie Kondo, Masaaki Okajima, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Toshiaki Kikuchi
Journal: Cancer Research (2016)

Abstract Cytotoxic lymphodepletion therapies, such as chemotherapy and radiotherapy, have been established to augment antitumor immunity. Naïve T cells elicit effector-like phenotypes and functions during recovery from lymphopenia. We and others have repeatedly demonstrated that transfer of naïve T cells into lymphopenic-tumor bearing mice delayed tumor growth. This enhancement of naïve T cells is required an activation through T-cell receptor (TCR). Programmed death receptor-1 (PD-1)/programmed death receptor ligand-1 (PD-L1) blockade therapy has been demonstrated to augment antitumor immunity. Previous studies have shown that PD-1/PD-L1 blockade therapy stimulates or restores the function of antitumor T cells in the effector phase. Because engagement of programmed death receptor-1 (PD-1) by ligand suppresses TCR signaling and inhibits T cell activation and function, there is a possibility that PD-1 regulates activation of T cells during recovery from lymphopenia after cytotoxic therapies. In the current study, we transferred naïve T cells into tumor-bearing mice following whole-body irradiation for lymphodepletion. These mice were further treated with anti-PD-1 antibodies. PD-1/PD-L1 blockade therapy after lymphodepletion significantly suppressed tumor progression. Next, we tested several kinds of cytotoxic agents to induce lymphopenia in mice. We found that the kind of cytotoxic agents affected the augmentation of antitumor efficacies of PD-1/PD-L1 blockade. Analyses of tumor-draining lymph-nodes (TDLNs) revealed that the number of tumor-specific effector T cells was significantly increased in mice treated with anti-PD-1 antibodies. By contrast, the number of effector T cells in spleens was not increased by PD-1/PD-L1 blockade therapy. These results indicate that PD-1 regulates a priming of antitumor effector T cells in TDLNs after cytotoxic lymphodepletion therapies. PD-1/PD-L1 blockade therapy is able to enhance antitumor T cell responses not only in the effector phase but also in the priming phase. Citation Format: Miho Takahashi, Satoshi Watanabe, Ko Sato, Tomohiro Tanaka, Yu Saida, Junko Baba, Aya Ohtsubo, Miyuki Sato, Rie Kondo, Masaaki Okajima, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Toshiaki Kikuchi. Programmed death receptor-1/programmed death receptor ligand-1 blockade improves priming of antitumor effector T cells after cytotoxic therapies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3206.