tbuckley/cabot-search huggingface dataset:
Abstract P5-13-20: Overall survival of women with breast cancer treated with newly approved targeted drugs in Manitoba: A population based study
Authors: S Devgan, O Bucher, M Geirnaert, S Niraula
Journal: Cancer Research (2019)

Abstract Background: Cancer drugs are approved based on the results of clinical trials in selected, rigorously monitored groups of participants. The ultimate goal of new cancer drug approvals is to improve outcomes, preferably overall survival, at population level compared to existing standard of care. Methods: We conducted a population based study using data from the provincial Manitoba cancer registry, Manitoba Health, and electronic patient records. We collected data on patient demographics, toxicity outcomes, and efficacy outcomes including recurrence and Overall Survival (OS) of patients who were treated with the 10 most frequently used new targeted cancer drugs between January 2005 and December 2017 in Manitoba. Patient demographics were reported using descriptive statistics. Toxicity events were reported in frequency, and Kaplan-Meier curves were used for time-to-event outcomes. Results: Four breast cancer drugs – Trastuzumab Emtansine (T-DM1), pertuzumab, fulvestrant, and palbociclib qualified for inclusion. During the timeframe, 71 women were treated with T-DM1, 100 with pertuzumab, 102 with Fulvestrant, and 21 with palbociclib. Patient demographics, disease stage, and line of therapy were comparable to those reported in pivotal trials leading to approval of these drugs. Median OS was 15.82 months for T-DM1, 25.34 months for pertuzumab, 14.65 months for fulvestrant, and not assessable for palbociclib – of note, these were consistently about half the median OS duration reported in pivotal trials leading to approval of the respective drugs. [For example, median OS in pivotal trials was 55.6 months for pertuzumab, 29.9 months for T-DM1, up to 26.4 months for fulvestrant, and 37.5 months (one trial) for palbociclib]. Serious toxicities were observed more frequently than reported in the literature – detailed results will be presented. Conclusion: Despite impressive improvements in outcomes reported in clinical trials leading to approval of new targeted therapies for breast cancer, such agents only yield modest OS at population level which was often worse than even the control groups used in pivotal clinical trials. Given the main aim of new interventions are to improve outcomes at population level, future research should explore causes, and identify solutions to minimize such efficacy-effectiveness gaps. Cautious patient selection, early identification and management of toxicities, and increasing resources available to individual patients may minimize such gaps. Citation Format: Devgan S, Bucher O, Geirnaert M, Niraula S. Overall survival of women with breast cancer treated with newly approved targeted drugs in Manitoba: A population based study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-20.
Author Correction: Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration
Authors: Rinki Ratnapriya, Olukayode A. Sosina, Margaret R. Starostik, Madeline Kwicklis, Rebecca J. Kapphahn, Lars G. Fritsche, Ashley Walton, Marios Arvanitis, Linn Gieser, Alexandra Pietraszkiewicz, Sandra R. Montezuma, Emily Y. Chew, Alexis Battle, Gonçalo R. Abecasis, Deborah A. Ferrington, Nilanjan Chatterjee, Anand Swaroop
Journal: Nature Genetics (2019)
Widespread Utilization of Peptide Communication in Phages Infecting Soil and Pathogenic Bacteria
Authors: Avigail Stokar-Avihail, Nitzan Tal, Zohar Erez, Anna Lopatina, Rotem Sorek
Journal: Cell Host & Microbe (2019)

Temperate phages can adopt either a lytic or lysogenic lifestyle within their host bacteria. It was recently shown that Bacillus-subtilis-infecting phages of the SPbeta group utilize a peptide-based communication system called arbitrium to coordinate the lysogeny decision. The occurrence of peptide-based communication systems among phages more broadly remains to be explored. Here, we uncover a wide array of peptide-based communication systems utilized by phages for lysogeny decisions. These arbitrium-like systems show diverse peptide codes and can be detected in numerous genetically distant phage types and conjugative elements. The pathogens Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are commonly infected by arbitrium-carrying mobile elements, which often carry toxins essential for pathogenicity. Experiments with phages containing these arbitrium-like systems demonstrate their involvement in lysogeny decisions. Finally, our results suggest that the peptide-based decision is executed by an antisense RNA that controls the regulator of the lysogenic state.
Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study
Authors: Johanna C Wiersum-Osselton, Barbee Whitaker, Sharran Grey, Kevin Land, Gabriela Perez, Srijana Rajbhandary, Chester Andrzejewski, Paula Bolton-Maggs, Harriet Lucero, Philippe Renaudier, Pierre Robillard, Matilde Santos, Martin Schipperus
Journal: The Lancet Haematology (2019)
Responsiveness of Serum C‐Reactive Protein, Interleukin‐17A, and Interleukin‐17F Levels to Ustekinumab in Psoriatic Arthritis: Lessons From Two Phase III, Multicenter, Double‐Blind, Placebo‐Controlled Trials
Authors: Stefan Siebert, Kristen Sweet, Bidisha Dasgupta, Kim Campbell, Iain B. McInnes, Matthew J. Loza
Journal: Arthritis & Rheumatology (2019)

Objective To evaluate the associations of C‐reactive protein (CRP) and circulating Th17‐associated cytokine levels with psoriatic arthritis (PsA) disease activity and therapeutic response to ustekinumab. Methods Interleukin‐17A (IL‐17A), IL‐17F, IL‐23, and CRP concentrations were measured in serum samples collected as part of the 2 PSUMMIT phase III studies of ustekinumab in PsA (n = 927). In post hoc analyses, relationships of IL‐17A, IL‐17F, and CRP levels at baseline, week 4, and week 24 with baseline skin and joint disease activity and response to therapy were evaluated using generalized linear models and Pearson's product‐moment correlation tests. Results Baseline serum levels of IL‐17A and IL‐17F were positively correlated with baseline skin disease scores (r = 0.39–0.62). IL‐23 levels were correlated with skin disease scores to a lesser extent (r = 0.26–0.31). No significant correlations were observed between these cytokine or CRP levels and baseline joint disease activity. There was no significant association of baseline levels of IL‐17A, IL‐17F, IL‐23, or CRP with therapeutic response to ustekinumab in either the skin or joints. Significant reductions from baseline in levels of IL‐17A, IL‐17F, and CRP were seen in patients treated with ustekinumab compared to those treated with placebo. Ustekinumab‐treated patients in whom 75% improvement in the Psoriasis Area and Severity Index score or 20% improvement according to the American College of Rheumatology criteria was achieved after 24 weeks of treatment had greater reductions in CRP level (geometric mean decreases of 51–58% versus 32–33%; P &lt; 0.05), but not IL‐17A or IL‐17F levels, than nonresponders. Conclusion Baseline serum IL‐23/IL‐17 levels correlated with skin, but not joint, disease activity, suggesting tissue‐specific variation. However, neither baseline Th17‐associated cytokine levels nor CRP level were predictive of therapeutic response to ustekinumab in the skin or joints, despite rapid reductions in their levels following ustekinumab therapy.
Abstract P3-12-06: TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation
Authors: A Clément-Zhao, M-L Tanguy, P Cottu, B De La Lande, P Bontemps, C Lemanski, P Baumann, C Levy, K Peignaux, A Reynaud-Bougnoux, A Gobillion, Y Kirova
Journal: Cancer Research (2019)

Abstract Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer. Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy. Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size &amp;lt;2cm (50%) and nodal status negative (63.8%). Median total dose of B was 15000 mg (13200 – 18550) and median duration was 11.2 months (11-12.6). No grade ≥3 toxicity was observed. Only 16 patients had grade 1-2 toxicities (8 treated with B and RT, 8 with RT alone): n=4 (3.8%) had grade 1 pain, n=5 (4.8%) had grade 1-2 fibrosis, n=1 (1%) had grade 2 telangiectasia and n=5 (4.8%) had grade 1-2 lymphoedema. No significant difference between the 2 arms was observed. One patient of 46 evaluated had Left Ventricular Ejection Fraction inferior to 50%. At 5 years, overall survival was 93.8%, disease free-survival 89% and locoregional free-survival 93.1 %. Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed. Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-06.
Associations between exposure to takeaway food outlets, takeaway food consumption, and body weight in Cambridgeshire, UK: population based, cross sectional study
Authors: Neil Chanchlani, James R Goodhand
Journal: BMJ (2014)

The paper

Abstract

Objectives To examine the association between environmental exposure to takeaway food outlets, takeaway food consumption, and body weight, while accounting for home, work place, and commuting route environments.

Design Population based, cross sectional study, using data on individual participants’ diet and weight, and objective metrics of food environment exposure.

Participants Working adults participating in the Fenland Study, Cambridgeshire, UK (n=5442, aged 29-62 years), who provided home and work addresses and commuting preferences. Takeaway food outlet exposure was derived using data from local authorities for individual environmental domains (at home, at work, and along commuting routes (the shortest route between home and work)), and for exposure in all three domains combined. Exposure was divided into quarters (Q); Q1 being the least exposed and Q4 being the most exposed.

Main outcome measures Self reported consumption of takeaway type food (g/day; pizza, burgers, fried foods, and chips) using food frequency questionnaires, measured body mass index, and cut-offs for body mass index as defined by the World Health Organization.

Results In multiple linear regression models, exposure to takeaway food outlets was positively associated with consumption of takeaway food. Among domains at home, at work, and along commuting routes, associations were strongest in work environments (Q4 v Q1; β coefficient=5.3 g/day, 95% confidence interval 1.6 to 8.7; P<0.05), with evidence of a dose-response effect. Associations between exposure in all three domains combined and consumption were greater in magnitude across quarters of exposure (Q4 v Q1; 5.7 g/day, 2.6 to 8.8; P<0.001), with evidence of a dose-response effect. Combined exposure was especially strongly associated with increased body mass index (Q4 v Q1; …
CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes
Authors: Moritz Rapp, Maximilian W.M. Wintergerst, Wolfgang G. Kunz, Viola K. Vetter, Max M.L. Knott, Dominik Lisowski, Sascha Haubner, Stefan Moder, Raffael Thaler, Stephan Eiber, Bastian Meyer, Natascha Röhrle, Ignazio Piseddu, Simon Grassmann, Patrick Layritz, Benjamin Kühnemuth, Susanne Stutte, Carole Bourquin, Ulrich H. von Andrian, Stefan Endres, David Anz
Journal: The Journal of Experimental Medicine (2019)

Chemokines have crucial roles in organ development and orchestration of leukocyte migration. The chemokine CCL22 is expressed constitutively at high levels in the lymph node, but the functional significance of this expression is so far unknown. Studying a newly established CCL22-deficient mouse, we demonstrate that CCL22 expression by dendritic cells (DCs) promotes the formation of cell–cell contacts and interaction with regulatory T cells (T reg) through their CCR4 receptor. Vaccination of CCL22-deficient mice led to excessive T cell responses that were also observed when wild-type mice were vaccinated using CCL22-deficient DCs. Tumor-bearing mice with CCL22 deficiency showed prolonged survival upon vaccination, and further, CCL22-deficient mice had increased susceptibility to inflammatory disease. In conclusion, we identify the CCL22–CCR4 axis as an immune checkpoint that is crucial for the control of T cell immunity.
Abstract 12070: Long-term Prognostic Value of Cardiac Power Index in Patients Admitted With Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Satoh, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Circulation (2015)

Backgrounds: Cardiac power is the rate of hydraulic work done by the heart. It has recently been shown that cardiac power index (CPI) provided prognostic independent and incremental prediction in adverse outcomes beyond traditional hemodynamic parameters in ambulatory patients with advanced heart failure. However, there is little information available on the long-term prognostic value of CPI in patients with acute decompensated heart failure (ADHF). Methods and Results: We studied 209 patients admitted for ADHF, who underwent right heart catheterization at the admission and were discharged with survival. CPI was calculated by: CPI W/m 2 = ([mean arterial pressure(mmHg) - [right arterial pressure(mm Hg)] x cardiac output [L/min] x K)/ (BSA m 2 ) where K = 0.0022. During a mean follow-up period of 4.4±3.3 yrs, 50 patients had cardiovascular death (CVD). CPI was significantly lower in patients with than without CVD (0.407±0.138 vs 0.550±0.258 W/m 2 , p=0.0002). Multivariate Cox regression analysis revealed that CPI (hazard ratio 0.092 [95%CI 0.017-0.497], p=0.005) was significantly associated with CVD, independently of body mass index, BUN and serum sodium levels, after adjustment for age, systolic blood pressure, pulmonary vascular resistance, and serum creatinine, albumin, and hemoglobin levels. Patients with low CPI (lowest tertile&lt;0.395 W/m 2 ) had a significantly higher CVD risk than those with middle CPI(0.395-0.565 W/m 2 ) and high CPI (highest tertile: &gt;0.565 W/m 2 ) (41%(28/69) vs 22%(15/70) vs 10%(10/70), p&lt;0.0001, respectively). The adjusted hazard ratio in patients with low CPI was 3.40 (95%CI 1.46-7.92). Conclusions: CPI could provide the long-term prognostic information in patients admitted with ADHF.
Abstract ES6-2: PI3K in breast cancer, glutamine changes and methionine addiction
Authors: A Toker
Journal: Cancer Research (2019)

Abstract Mutations in the PI 3-kinase and AKT signaling pathway are highly prevalent in breast cancer. In luminal, estrogen receptor-positive breast cancer patients, oncogenic mutations in PIK3CA, the gene that encodes the catalytic subunit of class 1a PI3K occur with a frequency of approximately 40%. By contrast, inactivating mutations and loss of heterozygosity in the tumor suppressors PTEN and INPP4B that normally terminate PI3K signaling, are found more frequently in basal-like, triple negative breast tumors. Regardless, in all cases the net result is hyperactivation of PI3K/AKT signaling leading to induction of phenotypes associated with malignancy. In spite of the frequency of genetic lesions in the PI3K pathway and the development of potent and specific small molecule inhibitors targeting the PI3K pathway, results from clinical trials with these inhibitors have been disappointing most often due to dose-limiting on-target toxicities. Consequently, numerous combination trials with PI3K inhibitors and other targeted therapies are underway. Separate pre-clinical and clinical efforts have also been initiated targeting PI3K oncogene addition with therapies that impact cellular states and programs, including metabolic pathways and enzymes. The concept that metabolic reprogramming is a feature of all cancer cells, and not merely a byproduct of accelerated growth, goes back to the days of Otto Warburg who in the 1920s proposed that increased levels of aerobic glycolysis followed by lactate fermentation occurs in tumor cells undergoing rapid growth. This so-called 'Warburg effect' spurred the recent development of numerous drugs that target glycolysis in human tumors, many of which are in clinical trials. Equally promising are strategies that target non-essential amino acid metabolism. The concept of metabolic starvation, whereby one or more metabolite is limiting or removed has gained traction in the field, with the finding that certain non-essential amino acids, particularly glutamine, can be synthesized by normal cells, whereas tumor cells rely on an extracellular supply to the extent that glutamine deprivation sensitizes tumor cells to death. Glutamine is the most widely studied nutrient, other than glucose, in the field of tumor metabolism. The presentation will focus on the intersection of PI3K, AKT and glutamine metabolism in breast cancer, as well as how these pathways modulate methionine dependency in breast cancers that display PI3K pathway hyperactivation. A greater understanding of the mechanisms by which glutamine and methionine sustain cancer cells may lead to the development or repurposing of other successful targeted metabolic therapies and use of the pathway enzymes and metabolites as biomarkers. Citation Format: Toker A. PI3K in breast cancer, glutamine changes and methionine addiction [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES6-2.
Abstract MP057: Subclinical Cerebrovascular Disease is Associated with Worsening Gait and Balance in an Elderly Multi-Ethnic Population: The Northern Manhattan Study (NOMAS)
Authors: Joshua Z Willey, Yeseon Park Moon, Janet DeRosa, Erin Kulick, Sandino Cespedes, Ahmet Bagci, Noam Alperin, Ying K Cheung, Clinton B Wright, Ralph L Sacco, Mitchell S Elkind
Journal: Circulation (2017)

Introduction: Age-related decline in gait and balance is a contributor to morbidity in the elderly. Subclinical cerebrovascular disease, seen on magnetic resonance imaging (MRI) as white matter hyperintensities (WMH) and silent brain infarcts (SBI), is associated with impaired mobility. Less is known about the association of WMH in specific brain regions and mobility impairment. We hypothesized that anterior WMH volume would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale associated with falls and mortality in the elderly. Methods: Participants in the Northern Manhattan Study MRI cohort had the SPPB measured a median of 5 years after enrollment. The SPPB has three domains with a maximum total score of 12: gait speed, chair stands, standing balance. Volumetric distributions for WMH volume across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter) were determined separately for each hemisphere by combining bimodal image intensity distribution and atlas based methods. Multi-variable linear regression was performed to examine the association between SBI and total and regional (frontal, parietal, occipital, temporal, anterior, posterior, and brainstem) head size-corrected WMH volumes, with the total SPPB score; models were adjusted for cardiovascular disease risk factors, osteo-arthritis, and grip strength. Results: Among 668 stroke-free participants with the SPPB available, mean age at the time of assessment was 74 ±9 years, 37% were male and 70% Hispanic; the mean SPPB score was 8.2 ± 2.9, interquartile range 7-10. Mean total WMHV was 0.55±0.75cc, mean anterior WMH volume 0.18±0.24cc, and 12% of participants had SBI. In multi-variable models, total WMHV was associated with a lower SPPB (beta = -0.3 per SD of logWMH, p=0.004), while SBI was not (beta= -0.12, p=0.7). For regional WMH volumes, only greater anterior periventricular WMHV was associated with SPPB (beta= -0.29 per SD, p=0.009). Conclusions: White matter hyperintensities, especially in the anterior cerebral regions, are associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical aging in the elderly.
Abstract 19691: Coronary Artery Disease Extent Among Patients With Human Immunodeficiency Virus Infection and the Role of Antiretroviral Therapy and Inflammatory Markers
Authors: Fadi Ghrair, Hassan Alkhawam, Amar Ashraf
Journal: Circulation (2017)

Background: Mortality rate in patients with Human immunodeficiency virus (HIV) infection has significantly decreased since the use of antiretroviral therapy (ART). However, the use of ART brought new concerns of metabolic disturbances including diabetes and dyslipidemia leading to coronary artery disease (CAD). Aim: To assess the effect of HIV disease on CAD, and to evaluate the role of ART and inflammatory markers. Methods: A retrospective study of 9,029 patients presented with chest pain and underwent cardiac catheterization between 01/01/2005 to 12/31/2016. Patients with documented HIV history were identified. We assessed variables related to HIV disease such as CD4 count, CRP and ESR. CAD extent was categorized into obstructive (left main stenosis of ≥50% or any stenosis of ≥70%), non-obstructive (≥1 stenosis ≥20%, but no stenosis ≥70%) and normal coronaries (no stenosis >20%). Results: Of 9,029 patients who had cardiac catheterization, 111 (1.2%) had documented HIV infection, of them 102 (92 %) had e...
Using a metallic ink pen to assist in the demarcation of skin lesions under reflectance confocal microscopy
Authors: Saud Aleissa, Cristian Navarrete-Dechent, Christina A. Banzhaf, Brian P. Hibler, Gary Peterson, Konstantinos Liopyris, Miguel Cordova, Anthony Rossi
Journal: Journal of the American Academy of Dermatology (2019)