tbuckley/cabot-search huggingface dataset:
Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies
Authors: Aixa E. Soyano, Bhagirathbhai Dholaria, Julian A. Marin-Acevedo, Nancy Diehl, David Hodge, Yan Luo, Rami Manochakian, Saranya Chumsri, Alex Adjei, Keith L. Knutson, Yanyan Lou
Journal: Journal for ImmunoTherapy of Cancer (2018)

Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies.We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed.We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24-3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17-2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54-4.05; P < 0.001), even after a multivariate analysis (HR, 2.31; P = 0.002), compared to those with lower ratio.Increased baseline ANC: ALC ratio and M: L ratio before initiation of anti-PD1 antibodies were associated with poor PFS and OS in advanced NSCLC patients. The potential predictive value of these readily available biomarkers might help with risk stratification and treatment strategies. These findings warrant further investigation in a larger, prospective study.
Checkpoint Inhibitors Augment CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia
Authors: Amanda M. Li, George E Hucks, Amanda M. Dinofia, Alix E. Seif, David T Teachey, Diane Baniewicz, Colleen Callahan, Christina Fasano, Beth McBride, Vanessa Gonzalez, Farzana Nazimuddin, David L. Porter, Simon F Lacey, Carl H June, Stephan A. Grupp, Shannon L. Maude
Journal: Blood (2018)
Electronic cigarettes: a task force report from the European Respiratory Society
Authors: Robert Bals, Jeanette Boyd, Susanna Esposito, Robert Foronjy, Pieter S. Hiemstra, Carlos A. Jiménez-Ruiz, Paraskevi Katsaounou, Anne Lindberg, Carlos Metz, Wolfgang Schober, Avrum Spira, Francesco Blasi
Journal: European Respiratory Journal (2018)

There is a marked increase in the development and use of electronic nicotine delivery systems or electronic cigarettes (ECIGs). This statement covers electronic cigarettes (ECIGs), defined as "electrical devices that generate an aerosol from a liquid" and thus excludes devices that contain tobacco. Database searches identified published articles that were used to summarise the current knowledge on the epidemiology of ECIG use; their ingredients and accompanied health effects; second-hand exposure; use of ECIGs for smoking cessation; behavioural aspects of ECIGs and social impact; in vitro and animal studies; and user perspectives.ECIG aerosol contains potentially toxic chemicals. As compared to conventional cigarettes, these are fewer and generally in lower concentrations. Second-hand exposures to ECIG chemicals may represent a potential risk, especially to vulnerable populations. There is not enough scientific evidence to support ECIGs as an aid to smoking cessation due to a lack of controlled trials, including those that compare ECIGs with licenced stop-smoking treatments. So far, there are conflicting data that use of ECIGs results in a renormalisation of smoking behaviour or for the gateway hypothesis. Experiments in cell cultures and animal studies show that ECIGs can have multiple negative effects. The long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term. Based on current knowledge, negative health effects cannot be ruled out.
Identification of breast cancer by differences in urinary iodine
Authors: Bernard A. Eskin, Waqas Anjum, Guy E. Abraham, Frederick Stoddard, Ann A. Prestrud, Ari D. Brooks
Journal: Cancer Research (2005)

2150  Introduction: Iodine is involved metabolically in normal, nursing, and neoplastic breast tissues. Our objective was to evaluate differences in urinary iodine levels in women with benign and malignant breast changes. Methods: Ninety-eight women with a median age of 47 years (range 15-87) presenting with benign or malignant breast diagnoses to the university breast center participated in this study. Women with a history of hyper/ hypothyroidism were excluded. Urine specimens were collected following informed consent. Urine was quantified by chromatography/anion exchange resin. Values are reported as micrograms (mcg) iodine or milligrams (mg) bromide per liter by ion selective electrode assay. A t-test was used to compare means. Results: Our final cohort included 20 women with cancer (DCIS =6; invasive cancer=14), 20 women who were smokers and 42 who were post menopausal. A significant difference in iodine excretion between women with cancer (105 mcg/l) versus non-cancer (141 mcg/l, p
Visualization and quantification of mitochondrial structure in the endothelium of intact arteries
Authors: Matthew J Durand, Karima Ait-Aissa, Vladislav Levchenko, Alexander Staruschenko, David D Gutterman, Andreas M Beyer
Journal: Cardiovascular Research (2018)

To quantify the mitochondrial structure of ECs in intact arteries vs. cultured cells.Cre-stop mito-Dendra2 mice, expressing the fluorescent protein Dendra2 in the mitochondrial matrix only, were used to label EC mitochondria using Cre-recombinase under the control of the VE-cadherin promoter. Conduit arteries, resistance arterioles and veins were fixed, mounted on glass slides and fluorescent images were obtained using a laser scanning confocal microscope (ex 488 nm; em 550 nm). ImageJ was used to calculate form factor (FF) and aspect ratio (AR) of the mitochondrial segments. Mitochondrial fragmentation count (MFC) was calculated by counting non-contiguous mitochondrial particles and dividing by the number of pixels which comprise the mitochondrial network. Primary aortic EC cultures (48 h on culture plates) were generated to compare the mitochondrial structure of cultured ECs vs. intact arteries. Aortic segments were also exposed to high glucose overnight (33 mM) ex vivo, and separate groups of mice were either infused with a high-glucose saline solution (300 mM) via tail vein catheter for 1 h or injected with streptozotocin (STZ; 50 mg/kg) to cause hyperglycaemia. Compared with cultured ECs, the mitochondria of ECs from the intact aorta were more fragmented (MFC: 6.4 ± 2.5 vs. 18.6 ± 9.4, respectively; P < 0.05). The mitochondrial segments of ECs within the aorta were more circular in shape (FF: 3.5 ± 0.75 vs. 1.8 ± 0.30, respectively; P < 0.05) and had less branching (AR: 2.9 ± 0.60 vs. 2.0 ± 0.25, respectively; P < 0.05) compared with cultured ECs. Ex vivo exposure of the intact aorta to high glucose overnight caused mitochondrial fission compared with normal glucose conditions (5 mM; MFC: 25.5 ± 11.1 high glucose vs. 11.0 ± 3.6 normal glucose; P < 0.05). Both 1-h infusion of high glucose saline (MFC: 22.4 ± 4.3) and STZ treatment (MFC: 40.3 ± 14.2) caused mitochondrial fission compared with freshly fixed aortas from control mice (MFC: 18.6 ± 9.4; P < 0.05 vs. high-glucose infusion and STZ treatment).Using a novel mouse model, we were able to, for the first time, obtain high resolution images of EC mitochondrial structure in intact arteries. We reveal the endothelial mitochondrial network is more fragmented in the intact aorta compared with cultured ECs, indicating that mitochondria assume a more elongated and branched phenotype in cell culture.
Molecular Profiling of Cohorts of Tumor Samples to Guide Clinical Development of Pembrolizumab as Monotherapy
Authors: Mark Ayers, Michael Nebozhyn, Razvan Cristescu, Terrill K. McClanahan, Rodolfo Perini, Eric Rubin, Jonathan D. Cheng, David R. Kaufman, Andrey Loboda
Journal: Clinical Cancer Research (2018)

Molecular profiling of large databases of human tumor gene expression profiles offers novel opportunities for informing decisions in clinical development programs.Gene expression profile of programmed death ligand 1 (PD-L1) was explored in a dataset of 16,000 samples, including approximately 4,000 metastatic tumors, across >25 tumor types prevalent in the United States, looking for new indications for the programmed death 1 (PD-1) inhibitor pembrolizumab. PD-L1 expression was highly concordant with several genomic signatures indicative of immune-inflamed tumor microenvironment. Prevalence of activated immune-inflamed tumors across all tumor types was explored and used to rank tumor types for potential response to pembrolizumab monotherapy.The analysis yielded 3 tiers of indications in which high levels of PD-L1 and immune-inflamed signatures were found in up to 40% to 60%, 20% to 40%, and 0% to 20% of tumors. Tier 1 contained novel indications known at the time of analysis to be responsive to PD-1 checkpoint blockade in the clinic (such as melanoma and non-small cell lung cancer), as well as indications not studied in the clinic previously, including microsatellite instability-high colorectal, head and neck, bladder, and triple-negative breast cancers. Complementary analysis of an Asian/Pacific cancer dataset (gastric cancer) revealed high prevalence of immune-inflamed tumors in gastric cancer. These data contributed to prioritization of these indications for clinical development of pembrolizumab as monotherapy.Data highlight the value of molecular profiling in identifying populations with high unmet needs with potentially favorable response characteristics and accelerating development of novel therapies for these patients.See related commentary by Mansfield and Jen, p. 1443.
Twenty-metre shuttle run: (mis)representation, (mis)interpretation and (mis)use
Authors: Neil Armstrong, Jo Welsman
Journal: British Journal of Sports Medicine (2018)

Recent publications in the British Journal of Sports Medicine ( BJSM) (mis)represent and (mis)interpret young people’s cardiorespiratory fitness (CRF) and potentially (mis)inform health promotion and clinical practice. 1 2 The papers recognise peak VO2as the criterion measure of CRF but base their estimations of peak VO2 on performances in 20 m shuttle runs (20mSRT). Moreover, and of serious concern to us, estimated peak VO2 is (mis)represented and (mis)interpreted in ratio with body mass (ie, in mL/kg/min).

The papers identify a few of the limitations of shuttle running but a recent meta-analysis succinctly summarised the issues. It demonstrated that with children, over half of correlation coefficients between 20mSRT scores and peak VO2 explain less than 50% of the variance in peak VO2. The meta-analysis reported that the criterion-related validity of the 20mSRT with children was only ‘ moderate ’ and concluded, ‘testers must be aware that the performance score of the 20MSR test is simply estimation and not a direct measure of cardiorespiratory fitness’.3

An example of specious interpretation of 20mSRT scores is the assertion that …
Abstract 16047: Insulin-Like Growth Factor-1 Upregulates Junction Proteins in Vascular Endothelial Cells: Potential Mechanisms for Anti-Atherogenic Effect of Insulin-Like Growth Factor-1
Authors: Svitlana Danchuk, Zhaohui Li, Sergiy Sukhanov, Patrice Delafontaine, Yusuke Higashi
Journal: Circulation (2017)

Endothelial cells (ECs) provide a barrier function to the vasculature, which is supported by intercellular junctions between ECs. Two types of endothelial cell intercellular junctions, namely tight...
Age and Sex as Independent Risk Factors for Stroke Among Patients With Atrial Fibrillation—Reply
Authors: Yujiro Kida
Journal: JAMA (2003)

To the Editor: Dr Wang and colleagues derived a risk score for predicting stroke and death in patients with new-onset atrial fibrillation (AF). The authors found that female sex decreased the 5-year risk of stroke. It is possible, however, that age may interact with sex in predicting risk. For example, Hart et al have reported that women with AF had a much higher rate of stroke compared with men among patients aged 75 years or older, but that there was no difference in risk among those younger than 75 years. Those authors concluded that this difference was due to differences in use of postmenopausal hormone therapy (HT). It is controversial whether HT really increases the risk of ischemic stroke. Thus, it remains uncertain whether female sex is a risk factor for stroke among women younger than 75 years.
Abstract 16343: Cardiac Troponin I Provides Superior Prognostic Information to C-Reactive Protein in the General Population: Data From The Nord-Trøndelag Health Study
Authors: Fjola D Sigurdardottir, Magnus N Lyngbakken, Oddgeir L Holmen, Håvard Dalen, Kristian Hveem, Helge Røsjø, Torbjørn Omland
Journal: Circulation (2017)

Background: Both C-reactive protein (CRP) and cardiac troponin I (cTnI) measured with high-sensitivity assays have been associated with risk of fatal and nonfatal cardiovascular events in the gener...
Joint Prevalence of Sitting Time and Leisure-Time Physical Activity Among US Adults, 2015-2016
Authors: Emily N. Ussery, Janet E. Fulton, Deborah A. Galuska, Peter T. Katzmarzyk, Susan A. Carlson
Journal: JAMA (2018)

differentially affect activities during different types of plays during competitions and hence would not bias this analysis.Confounding by player or game characteristics changing over time and surveillance bias are possible.The action taken by Ivy League leadership based on epidemiologic evidence demonstrates how targeted policy changes can reduce sport-related concussion.Although these results may not generalize beyond the Ivy League, they may inform the NCAA as it considers adjusting the kickoff rules in football in all collegiate conferences.
Legal representation at tribunals slashes risk of erasure, figures show
Authors: Clare Dyer
Journal: BMJ (2018)

Doctors who face medical practitioner tribunals without legal representation are at much greater risk of being struck off than those who have lawyers appearing for them, new figures show.

Some 78% of doctors who were erased from the UK medical register from March 2015 to March 2018 had no legal representation. In the same period 80% of those who received no sanction and were able to continue practising …
Neoadjuvant chemotherapy + concurrent chemoradiotherapy versus concurrent chemoradiotherapy ± adjuvant chemotherapy for locoregionally advanced NPC: An update meta-analysis and efficacy-toxicity joint analysis
Authors: S. Liu, D. Xie, S. Zhou, C. Xu, Z. Ye, S. Liu, G. Wang, S. Ding, Y. Xia
Journal: Annals of Oncology (2018)
FRI0094 The applicability of the american college of rheumatology nomenclature and case definition for neuropsychiatric lupus syndromes. analysis of 527 patients
Authors: LT Costallat, MB Bertolo, S Appenzeller
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The American College of Rheumatology Nomenclature for neuropsychiatric lupus provides case definitions for 19 neuropsychiatric syndromes seen in SLE with reporting standards and recommendations for laboratory and imaging tests. <h3>Objectives</h3> To test the new ACR case definitions in a cohort of 527 SLE previously analysed for neuropsychiatric lupus. <h3>Methods</h3> Only patients with definite SLE (ACR &gt; = 4) were included. The 19 case definitions established by ACR including diagnostic criteria, important exclusions and methods of ascertainment were utilised for the cohort. Clinical, serologic and imaging data were retrospectively reviewed. The secondary neuropsychiatric manifestations were excluded. A short neuropsychological test battery for the diagnosis of cognitive deficits, and specific tests and questionnaire for headache, mood and anxiety disorders were realised in 40 patients from the cohort and compared to normals. Patients under 14 or older than 65 were not included in this evaluation. <h3>Results</h3> Seizures was observed in 39 patients, psychosis in 28, polyneuropathy in 20, acute confusional state in 15, cerebrovascular disease in 13, cranial neuropathy in 8, mononeuropathy in 7, myelopathy in 6, chorea in 4, asseptic meningitis in 2, Guillan- Barré, demyelinating syndrome and myasthenia gravis in one case each. Autonomic disorders and plexopathy were not observed. Specific tests applied in 40 patients revealed 75% of cognitive disturbs,75% of mood disorders and 70% of anxiety disorders. Headache occurred in 62.5%.of these patients. <h3>Conclusion</h3> The ACR nomenclature and case definitions for neuropsychiatric lupus is useful for facilitate clinical research, in special multicentric studies and series with a great number of patients. Headache was a common symptom in SLE, however some conditions such as plexopathy or autonomic disorders were rare. Specific battery tests and questionnaire are necessary for cognitive disturbs, mood and anxiety disorders diagnostic but they are not practical for routine testing because are time consuming. <h3>Reference</h3> ACR AD HOC Comitte on neuropsychiatric lupus nomenclature. The American College of Rheumatology nomenclature and case definition for neuropsychiatric syndromes. Arthritis Rheum. 1999;42(4):599–608
Abstract 17679: Chronotropic Incompetence in a Rat Model of Heart Failure With Preserved Ejection Fraction
Authors: Jae Hyung Cho, Lilian Grigorian, Russell G Rogers, Joshua I Goldhaber, Eduardo Marban, Eugenio Cingolani
Journal: Circulation (2017)

Introduction: Exercise intolerance and impaired heart rate response have been regarded as major functional impairments in patients affected by heart failure with preserved ejection fraction (HFpEF)...
Abstract 19452: Long-term Outcomes in Adults With Congenital Heart Disease Evaluated for Heart Transplantation
Authors: Gavin Hickey, Andrea Elliott, Morgan Hindes, Tim Maul, Ravi Ramani, Michael Mathier, Stephen Cook
Journal: Circulation (2015)

Background: The prevalence of adult congenital heart disease (ACHD) patients with heart failure is increasing. No guidelines exist for evaluation and listing for heart transplant (HT) in ACHD. We sought to review the outcomes of HT committee decisions [accepted and transplanted (T), accepted awaiting transplant (A), deferred (D), ineligible (I)]. Methods: This was a retrospective analysis performed on ACHD (≥ 18 yrs) referred for HT between 2000-2014. Data on demographics, CHD severity, NYHA class, imaging, exercise testing, catheterization and HT committee decision were recorded. Primary outcome was all-cause mortality. Analysis was completed to identify variables that were statistically different amongst groups. Results: Sixty-two ACHD were included in analysis, A (n= 17) I (n=14) T (n=22) D (n=9), NYHA class III-IV (98%), CHD of great complexity (74%). Median time to HT, after listing, was 3 mo. (mean 5.5). Survival was significantly lower in the group awaiting transplant compared to all other groups (p&lt;0.001): A (18.6%) I (65.3%) T (78.3%) D (100%) ( Fig ). Among those who had not been transplanted, several variables were significantly different (p&lt;0.05) including: systolic BP, alb, BNP, Hct, right atrial pressure and peak oxygen consumption. For those awaiting transplant with pulmonary hypertension (PH) mortality was 100% but 40% for those without PH (p&lt;0.1). Conclusion: Waitlist mortality in the ACHD population is high. Given poor outcomes while on the waitlist, earlier listing may improve survival. Specific variables were statically different among patients not transplanted and there was a high mortality in those with PH. These may have contributed to the difference in survival among groups and may impact HT committees in the evaluation and listing for HT.
Tumors derived from clonal C57Bl/6 PyMT mammary tumor cell lines recapitulate microvascular densities characteristic of spontaneous tumors
Authors: Lesley Ellies, Dorothy Chan, Sylvia Shen, Robi Sircar, Malini Vangipuram
Journal: Cancer Research (2008)

459  Dissection of the contribution of epithelium and stroma to the development of tumor vasculature has proven challenging due to the number of different cell types involved in various tissues. By the time a tumor becomes established, so many interactions have taken place between the tumor cell and microenvironment that the relative importance of epithelial versus stromal signals becomes blurred. Effects of inflammatory stimuli on epithelial cells or stroma may also be important modulating factors. To determine the degree of autonomy mammary epithelial cells (MECs) have to influence tumor microvascular density (MVD) we have developed stable cell lines from wild type (Wt), inducible nitric oxide synthase (iNOS) deficient and p53 deficient polyomavirus middle T (PyMT) mammary tumors congenic in the C57Bl/6 background. These clonal MECs have characteristic growth rates and karyotypes. When injected into the cleared mammary fat pad of weanling mice, PyMT/Wt MECs produced highly vascular hyperplastic outgrowths indistinguishable from spontaneous hyperplasias that we have previously shown have a higher MVD than solid mammary tumors as assessed by quantitation of CD31 staining. Both PyMT/iNOS-/- and PyMT/p53-/- MECs produced solid tumors and the growth rates of all MECs correlated positively with their in vitro growth rates. PyMT/Wt and PyMT/p53-/- tumors were heavily infiltrated with tumor associated macrophages (TAMs), however, PyMT/iNOS-/- tumors showed a dramatic reduction in TAM recruitment, suggesting that iNOS production by mammary tumor cells is important in this process. The reduction in TAMs had no apparent affect on MVD in these tumors. When injected via the tail vein into wild type C57Bl/6 female recipients independent MEC lines developed similar numbers of lung metastases, suggesting that a similar proportion of cells within each line had the capacity to initiate a tumor. The tumors within each line were uniform in size and exhibited characteristic microvascular densities. The results showed that all MEC lines produced multiple well-differentiated mammary tumors of uniform size in the lungs or fat pad. Each MEC line was associated with a particular tumor growth rate that was reproducible between animals and experiments. Furthermore the MVD of tumors was clearly influenced by the MEC line. The same cells injected into different hosts had similar tumor MVDs and MVDs varied with cell line and stage of tumor development. These studies demonstrate that mammary epithelial cells can instruct the host stroma to develop a vascular network to support tumor growth. iNOS production by MECs is important for TAM recruitment, but the effect of TAMs on MVD in this model remains to be elucidated. Thus, these cell lines provide useful tools for the analysis of epithelial stromal interactions in mammary tumorigenesis.
Neuromedin U Does Not Act as a Decretin in Rats
Authors: Rune Ehrenreich Kuhre, Charlotte Bayer Christiansen, Seyed Mojtaba Ghiasi, Maria Buur Nordskov Gabe, Patricia Almine Skat-Rørdam, Ida Marie Modvig, Thomas Mandrup-Poulsen, Reidar Albrechtsen, Mette Marie Rosenkilde, Bolette Hartmann, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst
Journal: Cell Metabolism (2018)