tbuckley/cabot-search huggingface dataset:
Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study
Authors: Blánaid M Hicks, Kristian B Filion, Hui Yin, Lama Sakr, Jacob A Udell, Laurent Azoulay
Journal: BMJ (2018)

Abstract Objective To determine whether the use of angiotensin converting enzyme inhibitors (ACEIs), compared with use of angiotensin receptor blockers, is associated with an increased risk of lung cancer. Design Population based cohort study. Setting United Kingdom Clinical Practice Research Datalink. Participants A cohort of 992 061 patients newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2015 was identified and followed until 31 December 2016. Main outcome measures Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident lung cancer associated with the time varying use of ACEIs, compared with use of angiotensin receptor blockers, overall, by cumulative duration of use, and by time since initiation. Results The cohort was followed for a mean of 6.4 (SD 4.7) years, generating 7952 incident lung cancer events (crude incidence 1.3 (95% confidence interval 1.2 to 1.3) per 1000 person years). Overall, use of ACEIs was associated with an increased risk of lung cancer (incidence rate 1.6 v 1.2 per 1000 person years; hazard ratio 1.14, 95% confidence interval 1.01 to 1.29), compared with use of angiotensin receptor blockers. Hazard ratios gradually increased with longer durations of use, with an association evident after five years of use (hazard ratio 1.22, 1.06 to 1.40) and peaking after more than 10 years of use (1.31, 1.08 to 1.59). Similar findings were observed with time since initiation. Conclusions In this population based cohort study, the use of ACEIs was associated with an increased risk of lung cancer. The association was particularly elevated among people using ACEIs for more than five years. Additional studies, with long term follow-up, are needed to investigate the effects of these drugs on incidence of lung cancer.
BRIDGING THE GAP – BENEFITS OF NEUROSURGICAL TISSUE FOR PRE-CLINICAL RESEARCH
Authors: Aminul Ahmed, Paul Grundy, Girish Vajramani, Mariana Vargas-Caballero, Sandrine Willaime-Morawek, Diederik Bulters
Journal: Neuro-Oncology (2018)

The use of primary human neural tissue for research provides an invaluable insight into human neural function that cannot be achieved in any other way. Despite this it is successfully collected and used in only a small minority of units. We have established a collaboration between the Wessex Neurological Centre and the University of Southampton that allows us to study using human tissue resected during neurosurgery, and have used this tissue for over a decade. Tissue is most commonly collected from oncological, epilepsy and vascular operations. Here we share our experiences of the practicalities of working with live human glioma tissue and try to provide some insights for practicing neuro-oncology surgeons. We discuss the ethical considerations and practical difficulties of the co-ordination of the clinical and academic teams, and challenge of optimization of the tissue for the research. We will present the mechanisms in place to optimize the study of human neural tissue. We will review the progression from resection of tissue from glioma surgery to epilepsy surgery to any neurosurgical procedure in which the normal brain is resected and tissue discarded. We discuss the different models that can be used and the application locally to glioma stem cells, pathways activated in TBI, tissue damage from haemoglobin, the electrophysiology of the normal brain and with age and the inflammatory response of microglia. We will present examples of the value of human tissue studies. Firstly we will show the importance of primary glioma tissue compared to established glioma cell lines. Secondly, we will demonstrate some electrophysiological differences between humans and rodent that could only be investigated through the use of live human tissue obtained at operation. We will also demonstrate how we have moved to streamline tissue collection and propose a move to establish a national framework for such experiments.
Synthetic DNA-Encoded Monoclonal Antibody Delivery of Anti–CTLA-4 Antibodies Induces Tumor Shrinkage<i>In Vivo</i>
Authors: Elizabeth K. Duperret, Aspen Trautz, Regina Stoltz, Ami Patel, Megan C. Wise, Alfredo Perales-Puchalt, Trevor Smith, Kate E. Broderick, Emma Masteller, J. Joseph Kim, Laurent Humeau, Kar Muthumani, David B. Weiner
Journal: Cancer Research (2018)

Abstract Antibody-based immune therapies targeting the T-cell checkpoint molecules CTLA-4 and PD-1 have affected cancer therapy. However, this immune therapy requires complex manufacturing and frequent dosing, limiting the global use of this treatment. Here, we focused on the development of a DNA-encoded monoclonal antibody (DMAb) approach for delivery of anti–CTLA-4 monoclonal antibodies in vivo. With this technology, engineered and formulated DMAb plasmids encoding IgG inserts were directly injected into muscle and delivered intracellularly by electroporation, leading to in vivo expression and secretion of the encoded IgG. DMAb expression from a single dose can continue for several months without the need for repeated administration. Delivery of an optimized DMAb encoding anti-mouse CTLA-4 IgG resulted in high serum levels of the antibody as well as tumor regression in Sa1N and CT26 tumor models. DNA-delivery of the anti-human CTLA-4 antibodies ipilimumab and tremelimumab in mice achieved potent peak levels of approximately 85 and 58 μg/mL, respectively. These DMAb exhibited prolonged expression, with maintenance of serum levels at or above 15 μg/mL for over a year. Anti-human CTLA-4 DMAbs produced in vivo bound to human CTLA-4 protein expressed on stimulated human peripheral blood mononuclear cells and induced T-cell activation in a functional assay ex vivo. In summary, direct in vivo expression of DMAb encoding checkpoint inhibitors serves as a novel tool for immunotherapy that could significantly improve availability and provide broader access to such therapies. Significance: DNA-encoded monoclonal antibodies represent a novel technology for delivery and expression of immune checkpoint blockade antibodies, thus expanding patient access to, and possible clinical applications of, these therapies. Cancer Res; 78(22); 6363–70. ©2018 AACR.
Challenges in Defining Inappropriate Medication Use in Parkinson Disease Dementia
Authors: Christopher W. Hess, Michael S. Okun, Adolfo Ramirez-Zamora
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Association of Sexual Harassment and Sexual Assault With Midlife Women’s Mental and Physical Health
Authors: Rebecca C. Thurston, Yuefang Chang, Karen A. Matthews, Roland von Känel, Karestan Koenen
Journal: JAMA Internal Medicine (2018)

Sexual harassment and sexual assault are prevalent experiences among women. However, their association with health indices is less well understood.To investigate the association of history of sexual harassment and sexual assault with blood pressure, mood, anxiety, and sleep among midlife women.Nonsmoking women without cardiovascular disease were recruited from the community to undergo physical measurements (blood pressure, height, weight), medical history, and questionnaire psychosocial assessments (workplace sexual harassment, sexual assault, depression, anxiety, sleep).Sexual harassment and sexual assault.Blood pressure, depressive symptoms, anxiety, and sleep characteristics.Among the 304 nonsmoking women aged 40 to 60 years who participated in the study, all were free of clinical cardiovascular disease, and the mean (SD) age was 54.05 (3.99) years. A total of 19% reported a history of workplace sexual harassment (n = 58), and 22% reported a history of sexual assault (n = 67). Sexual harassment was related to significantly greater odds of stage 1 or 2 hypertension among women not taking antihypertensives (odds ratio [OR], 2.36; 95% CI, 1.10-5.06; P = .03) as well as clinically poor sleep (OR, 1.89; 95% CI, 1.05-3.42; P = .03), after adjusting for covariates. Sexual assault was associated with significantly greater odds of clinically elevated depressive symptoms (OR, 2.86; 95% CI, 1.42-5.77; multivariable P = .003), clinically relevant anxiety (OR, 2.26; 95% CI, 1.26-4.06; P = .006), and clinically poor sleep (OR, 2.15; 95% CI, 1.23-3.77; multivariable P = .007), after adjusting for covariates.Sexual harassment and sexual assault are prevalent experiences among midlife women. Sexual harassment was associated with higher blood pressure and poorer sleep. Sexual assault was associated with poorer mental health and sleep. Efforts to improve women's health should target sexual harassment and assault prevention.
Abstract 12206: Endothelial-derived Mif Contributes to Pulmonary Endothelial Cell Proliferation in Human Pulmonary Arterial Hypertension
Authors: Morane Le Hiress, Ly Tu, Carole Phan, Raphaël Thuillet, Nicolas Ricard, Andrei Seferian, Etienne-Marie Jutant, Elie Fadel, Gerald Simonneau, Alice Huertas, Yuichi Tamura, Marc Humbert, Christophe Guignabert
Journal: Circulation (2015)

Introduction: In idiopathic pulmonary arterial hypertension (iPAH), pulmonary-endothelial cells (P-ECs) display phenotypic abnormalities including a greater proliferative response to growth factors and apoptosis resistance; however, the precise underlying mechanisms remain obscure. Excessive MIF (macrophage migration-inhibitory factor) expression during the initial stages of tumor contributes to endothelial proliferation, tumor growth and progression. Hypothesis: We therefore hypothesized that MIF could function as a growth/survival factor promoting the altered P-EC phenotype in iPAH and disease progression. Methods: We examined the expression and the role of MIF in human lung tissues and in cultured pulmonary endothelial cells of control and idiopathic patients. In addition, two complementary animal models of pulmonary hypertension (PH) have been studied: the monocrotaline (MCT) and SU5416 plus chronic hypoxia (SuHx) rat models. Results: In distal pulmonary arteries (PAs) of patients with iPAH, we found a strong immunoreactivity for MIF in the endothelium compared with PAs from control patients. This aberrant endothelial MIF expression is also found in the two experimental models of PH. These in situ observations were replicated in vitro , with cultures P-ECs from patients with iPAH exhibiting increased MIF expression and release compared with control P-ECs. Decreasing MIF expression and signaling by RNA interference or a specific MIF inhibitor called ISO-1 decreased proliferation and induced apoptosis of iPAH P-ECs. Finally, we found that daily treatment of rats with ISO-1 for 2 weeks started 1 week after a subcutaneous monocrotaline injection partially reverses development of pulmonary hypertension. Conclusions: We report here that the pulmonary endothelium of iPAH patients represents a local abnormal source of MIF that could contribute to the hyperproliferative and apoptosis-resistant phenotype of iPAH endothelial cells.
Alopecia Universalis and Chronic Graft-vs-Host Disease Treated With Ruxolitinib
Authors: Michelle A. Borg, Reem A. Shalabi, Richard Childs, Brian C. Wells
Journal: JAMA Dermatology (2018)

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EXPLORING ALIGNMENT-FREE SEQUENCE COMPARISON METHODS TO ELUCIDATE PATTERNS OF EVOLUTION AND HETEROGENEITY IN LONGITUDINAL GLIOMA PATIENT COHORTS
Authors: Aideen Roddy, Anna Jurek, David Gonzalez, Manuel Salto-Tellez, Kevin Prise, Darragh McArt
Journal: Neuro-Oncology (2018)

Longitudinal glioma patient samples can reveal critical information relating to gliomagenesis, tumour evolution and therapy resistance. Previous studies examining tumour heterogeneity and evolution in these cohorts have focused solely on the limited information retained after applying stringent alignment and variant calling pipelines. Here, we propose the use of alignment-free methods to obtain an unsupervised view of the relationships between longitudinal tumour samples. Alignment-free (AF) sequence comparison is a novel methodology that has been heavily implemented in protein sequencing comparison and assessing evolutionary relationships between organisms but has not yet been applied to cancer research. Unsupervised AF methods can result in shorter computational times and may offer wider information for studying tumour heterogeneity and evolution in cancer research. In this study, we have identified a cohort of longitudinal glioma samples (Johnson et al.) for which we have whole exome-sequencing for germline, multiple spatial samples from an initial grade II glioma and spatial samples from a subsequent recurrent tumour for each patient. We developed an AF software to produce unrooted neighbour-joining trees for each patient, for which a matched least-square minimum-evolution tree produced from non-synonymous, somatic SNPs present in each of the samples is available from the original publication. Results demonstrate clear similarities when comparing the results from AF analysis to the trees produced using alignment-based approaches, however, clear and possibly fundamental differences were identified. These may be a result of the compounded effect of unassessed structural variants, larger indels or passenger synonymous variants which are also contributing to the tumours mutational landscape and therefore effecting the evolutionary pathway of gliomas. We hypothesise that this presents an opportunity to identify early and late events in evolution as well as highlight potential therapy-resistant subclones of the initial tumour which then give rise to a subsequent recurrent tumour.
The Bawa-Garba principle for medical error
Authors: Deen M Mirza
Journal: BMJ (2018)

One of the key lessons from the Bawa-Garba case1 is the need to articulate to the public how system failure leads to medical error. This concept is not new to medicine.2 But under pressure from the media and public opinion, our regulators can buckle, ignoring the systemic factors that predispose to error and instead scapegoating those …
Abstract 11009: Serum Cholesterol Efflux Capacity is an Independent Predictor of All-cause and Cardiovascular Mortality in Patients With Coronary Artery Disease
Authors: Chaoqun Liu, Yuan Zhang, Ding Ding, Dongliang Wang, Xinrui Li, Yunou Yang, Qing Li, Yuanzhu Zheng, Wenhua Ling
Journal: Circulation (2015)

Objective To investigate the association between serum cholesterol efflux capacity and all-cause and cardiovascular mortality in patients with coronary artery disease. Design Prospective cohort study. Setting Guangdong Coronary Artery Disease Cohort, established in 2008-2011. Participants 1 765 patients with coronary artery disease were followed-up for a median of 3.9 years. Main outcome measures Primary outcome was the association of baseline serum cholesterol efflux capacity with the risks of all-cause and cardiovascular mortality. Results: During 6 778 person-years of follow-up, 170 deaths were registered, 126 of which were caused by cardiovascular diseases. After multivariate adjustment for factors related to cardiovascular diseases, the hazard ratios (95% confidence intervals) across quartiles of serum cholesterol efflux capacity were 1.00, 0.75 (0.51-1.10), 0.51 (0.33-0.81) and 0.43 (0.25-0.73) for all-cause mortality ( P = 0.003), and 1.00, 0.76 (0.49-1.18), 0.37 (0.21-0.65), and 0.25 (0.12-0.52) for cardiovascular mortality ( P &lt; 0.001). Adding serum cholesterol efflux capacity to a model containing traditional cardiovascular risk factors significantly increases its discriminatory power and predictive ability for all-cause (area under receiver operating characteristic curve 0.68 versus 0.61, P &lt; 0.001; net reclassification improvement 14.5%, P = 0.001) and cardiovascular (area under receiver operating characteristic curve 0.71 versus 0.63, P &lt; 0.001; net reclassification improvement 18.4%, P &lt; 0.001) death, respectively. Conclusions: Serum cholesterol efflux capacity may serve as an independent measure for predicting all-cause and cardiovascular mortality in patients with coronary artery disease.
Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus
Authors: Maria Dall'Era, Mariela L. Pauli, Kelly Remedios, Keyon Taravati, Priscila M. Sandova, Amy L. Putnam, Angela Lares, Anna Haemel, Qizhi Tang, Marc Hellerstein, Marc Fitch, James McNamara, Beverly Welch, Jeffrey A. Bluestone, David Wofsy, Michael D. Rosenblum
Journal: Arthritis & Rheumatology (2018)

Adoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease.We describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment.Deuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon-γ pathway and a reciprocal augmentation of the interleukin-17 (IL-17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL-17 production.We report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses.
P3.16-30 The Impact of the Surgical Approach on Lymph Node Upstaging in Curative Intent Lung Cancer Surgery
Authors: K. Mardanzai, D. Cheufou, B. Hegedus, T. Plönes, M. Zaatar, D. Theegarten, K. Darwiche, C. Aigner
Journal: Journal of Thoracic Oncology (2018)
Immune-checkpoint inhibitors in previously treated patients with urothelial carcinoma: A systematic review and meta-analysis
Authors: E. De Luca, V. Di Nunno, C. Buttigliero, M. Tucci, F. Vignani, C. Zichi, A. Ardizzoni, F. Massari, M. Di Maio
Journal: Annals of Oncology (2018)
Abstract 18891: Impact of Type 2 Diabetes on Optimal Target LDL-C Level for Secondary Prevention of Cardiovascular Disease in Patients With Acute Coronary Syndrome: A Subanalysis of HIJ-PROPER
Authors: Haruki Sekiguchi, Erisa Kawada-Watanabe, Hiroyuki Arashi, Junichi Yamaguchi, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Circulation (2017)

Introduction: Lipid-lowering therapy is essential for the secondary prevention of cardiovascular disease (CVD), especially in the setting of acute coronary syndrome (ACS). However, the impact of di...
Long noncoding RNA <i>lnc-TSI</i> inhibits renal fibrogenesis by negatively regulating the TGF-β/Smad3 pathway
Authors: Peng Wang, Man-Li Luo, Erwei Song, Zhanmei Zhou, Tongtong Ma, Jun Wang, Nan Jia, Guobao Wang, Sheng Nie, Youhua Liu, FanFan Hou
Journal: Science Translational Medicine (2018)

Transforming growth factor-β (TGF-β) is a well-established central mediator of renal fibrosis, a common outcome of almost all progressive chronic kidney diseases. Here, we identified a poorly conserved and kidney-enriched long noncoding RNA in TGF-β1-stimulated human tubular epithelial cells and fibrotic kidneys, which we termed TGF-β/Smad3-interacting long noncoding RNA (lnc-TSI). Lnc-TSI was transcriptionally regulated by Smad3 and specifically inhibited TGF-β-induced Smad3 phosphorylation and downstream profibrotic gene expression. Lnc-TSI acted by binding with the MH2 domain of Smad3, blocking the interaction of Smad3 with TGF-β receptor I independent of Smad7. Delivery of human lnc-TSI into unilateral ureteral obstruction (UUO) mice, a well-established model of renal fibrosis, inhibited phosphorylation of Smad3 in the kidney and attenuated renal fibrosis. In a cohort of 58 patients with biopsy-confirmed IgA nephropathy (IgAN), lnc-TSI renal expression negatively correlated with the renal fibrosis index (r = -0.56, P < 0.001) after adjusting for cofounders. In a longitudinal study, 32 IgAN patients with low expression of renal lnc-TSI at initial biopsy had more pronounced increases in their renal fibrosis index and experienced stronger declines in renal function at repeat biopsy at a mean of 48 months of follow-up. These data suggest that lnc-TSI reduced renal fibrogenesis through negative regulation of the TGF-β/Smad pathway.
A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis
Authors: Marjorie Z. Imperial, Payam Nahid, Patrick P. J. Phillips, Geraint R. Davies, Katherine Fielding, Debra Hanna, David Hermann, Robert S. Wallis, John L. Johnson, Christian Lienhardt, Rada M. Savic
Journal: Nature Medicine (2018)

Tuberculosis kills more people than any other infectious disease. Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins; however, approximately four-fifths of participants were cured. Through a pooled analysis of patient-level data with external validation, we identify populations eligible for 4-month treatment, define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes. In 3,405 participants included in analyses, baseline smear grade of 3+ relative to <2+, HIV seropositivity and adherence of ≤90% were significant risk factors for unfavorable outcome. Four-month regimens were non-inferior in participants with minimal disease defined by <2+ sputum smear grade or non-cavitary disease. A hard-to-treat phenotype, defined by high smear grades and cavitation, may require durations >6 months to cure all. Regimen duration can be selected in order to improve outcomes, providing a stratified medicine approach as an alternative to the 'one-size-fits-all' treatment currently used worldwide.
Attempts at assisted reproductive medical intervention in breast cancer patients who desire fertility preservation
Authors: Noriko Goda, Shinsuke Sasada, Keiko Kajitani, Mai Nishina, Satoshi Sueoka, Eri Suzuki, Akiko Emi, Norio Masumoto, Rumi Haruta, Ken Kataoka, Takayuki Kadoya, Eimi Rai, Tetsuaki Hara, Morihito Okada
Journal: Annals of Oncology (2018)