tbuckley/cabot-search huggingface dataset:
US to Increase Efforts to Reduce Rural Cancer Toll
Authors: Jeff Lyon
Journal: JAMA (2017)

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Anti-CD 19 and Anti- CD 20 Chimeric Antigen Receptor-Modified T Cells for B-Cell Malignancies: A Systematic Review and Meta-Analysis
Authors: Irbaz Bin Riaz, Muhammad Husnain, Muhammad Umar Kamal, Ali McBride, Anh Hua, Laeth Geoge, Auon Abbas Hamadani, Bushra Rahman, Zeeshan Ali, Qurat-ul-Ain Riaz Sipra, Umar Zahid, Ammad Raina, Ahlam Saleh, Faiz Anwer
Journal: Blood (2016)
Comparing three‐year extension of early intervention service to regular care following two years of early intervention service in first‐episode psychosis: a randomized single blind clinical trial
Authors: Ashok Malla, Ridha Joober, Srividya Iyer, Ross Norman, Norbert Schmitz, Thomas Brown, Danyael Lutgens, Eric Jarvis, Howard C. Margolese, Nicola Casacalenda, Amal Abdel‐Baki, Eric Latimer, Sally Mustafa, Sherezad Abadi
Journal: World Psychiatry (2017)

This study aimed to determine if, following two years of early intervention service for first‐episode psychosis, three‐year extension of that service was superior to three years of regular care. We conducted a randomized single blind clinical trial using an urn randomization balanced for gender and substance abuse. Participants were recruited from early intervention service clinics in Montreal. Patients (N=220), 18‐35 years old, were randomized to an extension of early intervention service (EEIS; N=110) or to regular care (N=110). EEIS included case management, family intervention, cognitive behaviour therapy and crisis intervention, while regular care involved transfer to primary (community health and social services and family physicians) or secondary care (psychiatric outpatient clinics). Cumulative length of positive and negative symptom remission was the primary outcome measure. EEIS patients had a significantly longer mean length of remission of positive symptoms (92.5 vs. 63.6 weeks, t=4.47, p&lt;0.001), negative symptoms (73.4 vs. 59.6 weeks, t=2.84, p=0.005) and both positive and negative symptoms (66.5 vs. 56.7 weeks, t=2.25, p=0.03) compared to regular care patients. EEIS patients stayed in treatment longer than regular care patients (mean 131.7 vs. 105.3 weeks, t=3.98, p&lt;0.001 through contact with physicians; 134.8 ± 37.7 vs. 89.8 ± 55.2, t=6.45, p&lt;0.0001 through contact with other health care providers) and received more units of treatment (mean 74.9 vs. 39.9, t=4.21, p&lt;0.001 from physicians, and 57.3 vs. 28.2, t=4.08, p&lt;0.001 from other health care professionals). Length of treatment had an independent effect on the length of remission of positive symptoms (t=2.62, p=0.009), while number of units of treatment by any health care provider had an effect on length of remission of negative symptoms (t=−2.70, p=0.008) as well as total symptoms (t=−2.40, p=0.02). Post‐hoc analysis showed that patients randomized to primary care, based on their better clinical profile at randomization, maintained their better outcome, especially as to remission of negative symptoms, at the end of the study. These data suggest that extending early intervention service for three additional years has a positive impact on length of remission of positive and negative symptoms compared to regular care. This may have policy implications for extending early intervention services beyond the current two years.
Media: Scottish fears over PFI
Authors: B. Christie
Journal: BMJ (1999)

Few ideas can be more assured to work the press into a lather than the notion of taxpayers' hard earned money being used to swell the coffers of rich private conglomerates. And so it has proved to be with the issue of the private finance initiative (PFI)—a scheme introduced by the Conservative government and adopted by the present Labour administration, which involves private companies building hospitals and schools and then leasing them back to the state over a 20 or 30 year period. The buildings may never revert to public ownership, prompting the Scottish National Party (SNP) to dub PFI “Privatisation For Infinity.” It has become one of the most fiercely fought over issues in the election for the first Scottish parliament for 300 years, generating many column inches in the newspapers over the past few weeks.

The Scottish press has variously described the private finance initiative as “the only practical means of providing patients and staff with first class treatment facilities”; “a poor deal for taxpayers, who will pay huge …
Abstract 17319: All-extremity Aerobic Exercise Training Does Not Improve Aortic Wave Reflection Characteristics and Wasted Left Ventricular Energy in Sedentary Older Adults
Authors: Han-Kyul Kim, Chueh-Lung Hwang, Jeung-Ki Yoo, Moon-Hyon Hwang, Eileen M Handberg, Wilmer W Nichols, Demetra D Christou
Journal: Circulation (2016)

Introduction: Aging is associated with early return of reflected pressure waves from the lower body to the heart which augments central blood pressure and increases wasted left ventricular energy, ...
Early-Life Phthalate Exposure and Adiposity at 8 Years of Age
Authors: Jessica Shoaff, George D. Papandonatos, Antonia M. Calafat, Xiaoyun Ye, Aimin Chen, Bruce P. Lanphear, Kimberly Yolton, Joseph M. Braun
Journal: Environmental Health Perspectives (2017)

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022
Randomized trial of a smartphone mobile app for adherence to oral chemotherapy.
Authors: Jamie M. Jacobs, Nicole Pensak, Lauren Ellen Nisotel, Joel N Fishbein, James J MacDonald, Molly Ream, Charn-Xin Fuh, Joanne S. Buzaglo, Alona Muzikansky, Inga Tolin Lennes, Steven A. Safren, William F. Pirl, Jennifer S. Temel, Joseph Greer
Journal: Journal of Clinical Oncology (2017)

230 Background: As patients with cancer are increasingly prescribed oral chemotherapy, they share greater responsibility for ensuring adherence and monitoring side effects. The aim of this study was to test the effect of a smartphone mobile app to improve adherence and symptom management in patients prescribed oral chemotherapy. Methods: From 2/15 to 12/16, 181 patients with diverse cancers prescribed oral chemotherapy at an urban cancer center were randomized to receive either the smartphone mobile app or standard care. The mobile app included a medication treatment plan with alerts, symptom reporting module, education library, and cancer-specific resources. The primary outcome was adherence, measured by electronic pill cap (MEMS) and self-report (Morisky Medication Adherence Scale; MMAS). To assess symptoms, mood, and quality of life, participants completed the MD Anderson Symptom Inventory, Hospital Anxiety &amp; Depression Scale (HADS); and Functional Assessment of Cancer Therapy-General (FACT-G) at baseline and 12 weeks. General linear models were used to assess intervention effects on patient outcomes. Results: Study groups did not differ across outcome measures from baseline to week 12, except patients in the mobile app group had less of a reduction in social well-being (FACT-G) over time (Mean Diff = 1.67, 95% CI = -3.12, -0.21, p = .025). Secondary analyses showed that baseline adherence (MMAS) and anxiety (HADS) were moderators of intervention effects on self-reported and electronically monitored adherence. Among patients who reported adherence problems, those assigned to the mobile app had better average MEMS adherence (Mean Diff = -22.30, 95% CI = -42.82, -1.78, p = .034) compared to standard care. Similarly, among patients with higher baseline anxiety, those in the mobile app group had better average MEMS adherence (Mean Diff = -16.08, 95% CI = -31.74, -0.41, p = .044) and reported fewer adherence problems on the MMAS at 12 weeks (4.3% vs 32%, OR = 0.06, 95% CI = 0.003, 0.96, p = .047) compared to standard care. Conclusions: A patient-centered, smartphone mobile app designed to improve adherence to oral chemotherapy may be especially useful for patients with certain risk factors, such as those struggling with adherence or anxiety. Clinical trial information: NCT02157519.
Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery
Authors: Dongxi Xiang, Sarah Shigdar, Andrew G Bean, Matthew Bruce, Wenrong Yang, Motilal Mathesh, Tao Wang, Wang Yin, Phuong Ha-Lien Tran, Hadi Al Shamaileh, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Aina He, Wei Duan
Journal: Theranostics (2017)

Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei. Treatment of tumour-bearing xenograft mice with Apt-DOX resulted in at least 3-fold more inhibition of tumour growth and longer survival as well as a 30-fold lower frequency of CSC and a prolonged longer tumourigenic latency compared with those receiving the same dose of free DOX. Our data demonstrate that a CSC-targeting aptamer is able to transform a conventional chemotherapeutic agent into a CSC-killer to overcome drug resistance in solid tumours.
AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both
Authors: Beverley J Shea, Barnaby C Reeves, George Wells, Micere Thuku, Candyce Hamel, Julian Moran, David Moher, Peter Tugwell, Vivian Welch, Elizabeth Kristjansson, David A Henry
Journal: BMJ (2017)

The number of published systematic reviews of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions. Systematic reviews are subject to a range of biases and increasingly include non-randomised studies of interventions. It is important that users can distinguish high quality reviews. Many instruments have been designed to evaluate different aspects of reviews, but there are few comprehensive critical appraisal instruments. AMSTAR was developed to evaluate systematic reviews of randomised trials. In this paper, we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic reviews, including those based on non-randomised studies of healthcare interventions<i>.</i>
Which exercise prescriptions improve quality of life and physical function in patients with cancer during and following treatment? A systematic review and meta-analysis of randomised controlled trials
Authors: Maike G Sweegers, Teatske M Altenburg, Mai J Chinapaw, Joeri Kalter, Irma M Verdonck-de Leeuw, Kerry S Courneya, Robert U Newton, Neil K Aaronson, Paul B Jacobsen, Johannes Brug, Laurien M Buffart
Journal: British Journal of Sports Medicine (2017)

Certain exercise prescriptions for patients with cancer may improve self-reported quality of life (QoL) and self-reported physical function (PF). We investigated the effects of exercise on QoL and PF in patients with cancer and studied differences in effects between different intervention-related and exercise-related characteristics.We searched four electronic databases to identify randomised controlled trials investigating exercise effects on QoL and PF in patients with cancer. Pooled effects (Hedges' g) were calculated using Comprehensive Meta-Analysis software. Subgroup analyses were conducted based on intervention dimensions, including timing, duration and delivery mode, and exercise dimensions, including frequency, intensity, type and time (FITT factors).We included 74 exercise arms. Patients who were randomised to exercise interventions had significantly improved QoL (g=0.15, 95% CI (0.10 to 0.20), n=67 exercise arms) and PF (g=0.21, 95% CI (0.15 to 0.27), n=59 exercise arms) compared with patients in control groups. We found a significant between-group difference for exercise delivery mode, with significant beneficial effects for supervised exercise interventions (g=0.20, 95% CI (0.14 to 0.26) for QoL and g=0.27, 95% CI (0.20 to 0.33) for PF), but not for unsupervised interventions (g=0.04, 95% CI (-0.06 to 0.13) for QoL and g=0.09, 95% CI (-0.01 to 0.19) for PF). No statistically significant differences in intervention effects were found for variations in intervention timing, duration or exercise FITT factors. Unsupervised exercise with higher weekly energy expenditure was more effective than unsupervised exercise with lower energy expenditure (z=2.34, p=0.02).Exercise interventions, especially when supervised, have statistically significant and small clinical benefit on self-reported QoL and PF in patients with cancer. Unsupervised exercise intervention effects on PF were larger when prescribed at a higher weekly energy expenditure.
Victims of blood contamination win right to sue government
Authors: Clare Dyer
Journal: BMJ (2017)

The High Court in London has made a group litigation order potentially allowing 400 or more victims of the scandal involving contaminated blood products in the 1970s and 1980s to come together to sue the UK government for damages.

Many people with haemophilia were infected with HIV and hepatitis C after receiving blood clotting products factor 8 and factor 9, …
Chronic E. coli infection and inflammation induce prostatic intraepithelial neoplasia in mice
Authors: Johny E. Elkahwaji, Weixiong Zhong, Lindsay M. Janda, Walter J. Hopkins
Journal: Cancer Research (2005)

4686  Background and objective: Prostate cancer (CaP) is a common cause of morbidity and mortality in men in the developed world. Epidemiological studies have linked chronic inflammation to cancer development in several organs, including the prostate. While the etiology of CaP remains largely unclear, we hypothesized that oxidative stress induced by chronic bacterial infection and inflammation may play a role in pre-neoplastic events within the prostate leading to an initiation and promotion of prostatic carcinogenesis. This hypothesis was tested using a mouse model of E. coli-induced prostatitis recently developed in our laboratory. Methods: Male C3H/HeOuJ mice 12 weeks old were anaesthetized with isoflurane and inoculated intraurethrally with 2x106E.coli 1677. Control mice were inoculated with PBS. Mice were sacrificed at five days and 12 weeks after inoculation. Prostate tissue sections were stained with hematoxylin and eosin and were evaluated by light microscopy for inflammatory responses and histologic changes. Also, the presence of oxidative DNA damage and cell proliferation was analyzed by immunohistochemistry using antibodies against 8-hydroxy-2’-deoxyguanosine (8-Oxo-dG) and Ki-67. Results: All infected mice developed acute prostatitis at five days and 12 weeks after inoculation. Control mice treated with PBS had no prostate infections or inflammation at either timepoint. Prostatic tissue sections showed acute inflammatory infiltrates in the prostate glands and the stroma five days following E.coli infection. At 12 weeks, the acute inflammation decreased and focal residual acute inflammation was present only in the prostatic glands. In addition, focal mild to moderate chronic inflammation was present in the stroma. Most significantly, prostatic glandular epithelium showed post-infection atypical hyperplasia with increased epithelial cell layers, cytological atypia, and dysplastic changes of glandular architecture. Some changes mimicked prostatic intraepithelial neoplasia or cancer like-lesions. Immunohistochemical analysis showed that atypical prostate glands had a stronger staining for the oxidative DNA damage marker 8-Oxo-dG than normal and simple hyperplastic glands. The atypical glands also showed a significant increase in epithelial nuclear labeling of the cell proliferation marker Ki-67. Conclusions: Our study showed that prostatic inflammation results in focal prostatic glandular atypia (e.g., PIN and dysplasia), a potential precursor of prostatic adenocarcinoma. In addition, our results suggest a clear relationship between chronic inflammation and oxidative DNA damage that may play a role in prostate carcinogenesis development. Further studies are needed to define the morphological and immunophenotypical changes within the prostate induced by chronic infection and to clarify a potential link between inflammation and etiology of prostate cancer.
Abstract 358: Impaired Function of Circulating Cd34 <sup>+</sup> Cd45 <sup>-</sup> Cells in Patients with Persistent Atrial Fibrillation Is Restored by the Calcium Channel Blocker Bepridil Hydrochloride
Authors: Youichi Katoh, Ryota Hashimoto, Gakuto Yozu, Hiroshige Yu-u, Miki Yamase, Yoshihisa Enjyoji, Yuji Nakazato
Journal: Circulation Research (2012)

Background: Despite accumulating evidence regarding the occurrence of endothelial dysfunction in persistent atrial fibrillation (PAF) patients, little is still known about the number and function of circulating endothelial progenitor cells (EPCs) in PAF. Bepridil hydrochloride (BEP) is a multiple ion channel blocker that has exhibited efficacy for the pharmacological conversion of PAF. Methods and Results: We evaluated both the number and functional properties of CD34 + CD45 - cells as EPCs in 12 consecutive patients with PAF. The number of circulating EPCs was determined by flow cytometry. BEP was administered beginning at a daily dose of 100 mg and was increased up to a maximum of 200 mg for 30 days. Higher levels of circulating CD34 + CD45 - cells were observed in patients with PAF in comparison to the control subjects [ 0.35 +0.04% vs 0.14 + 0.03% CD34 + CD45 - cells in the MNC fraction, p&lt;0.048]. However, the EPCs from patients with PAF exhibited an impaired migration towards SDF-1. Conclusion: The number of EPCs was observed to increase, but the EPC function was impaired in patients with persistent AF. BEP may have a beneficial effect on the pharmacological conversion of PAF by helping to restore the EPC function.
Membrane Fusion Mediated Intracellular Delivery of Lipid Bilayer Coated Mesoporous Silica Nanoparticles
Authors: Jian Yang, Jing Tu, Gerda E. M. Lamers, René C. L. Olsthoorn, Alexander Kros
Journal: Advanced Healthcare Materials (2017)

Protein delivery into the cytosol of cells is a challenging topic in the field of nanomedicine, because cellular uptake and endosomal escape are typically inefficient, hampering clinical applications. In this contribution cuboidal mesoporous silica nanoparticles (MSNs) containing disk-shaped cavities with a large pore diameter (10 nm) are studied as a protein delivery vehicle using cytochrome-c (cytC) as a model membrane-impermeable protein. To ensure colloidal stability, the MSNs are coated with a fusogenic lipid bilayer (LB) and cellular uptake is induced by a complementary pair of coiled-coil (CC) lipopeptides. Coiled-coil induced membrane fusion leads to the efficient cytosolic delivery of cytC and triggers apoptosis of cells. Delivery of these LB coated MSNs in the presence of various endocytosis inhibitors strongly suggests that membrane fusion is the dominant mechanism of cellular uptake. This method is potentially a universal way for the efficient delivery of any type of inorganic nanoparticle or protein into cells mediated by CC induced membrane fusion.