tbuckley/cabot-search huggingface dataset:
Use of thrombopoietin receptor agonists for immune thrombocytopenia in pregnancy: results from a multicenter study
Authors: Marc Michel, Marco Ruggeri, Tomas Jose Gonzalez-Lopez, Salam Alkindi, Stéphane Cheze, Waleed Ghanima, Tor Henrik Anderson Tvedt, Mikael Ebbo, Louis Terriou, James B. Bussel, Bertrand Godeau
Journal: Blood (2020)
Covid-19: £8.4m announced to fund new immune response research in UK
Authors: Elisabeth Mahase
Journal: BMJ (2020)

UK research bodies have committed £8.4m (€9.4m; $11.1m) to fund three new studies examining immune responses to covid-19.

Two studies will focus on key questions about covid-19 immunity, including how long it lasts, cross immunity, and the role of antibodies in immunity. A third study will examine covid-19’s effects on vital organs.

The funding has been provided by UK Research and Innovation and the National Institute for Health Research. It will allow researchers to develop better tests to define immunity and to understand why some people suffer from life threatening covid-19 while others have mild or asymptomatic infections but can still transmit the virus.

The studies will also look at reinfection. This comes after the …
High-flow nasal oxygen: a safe, efficient treatment for COVID-19 patients not in an ICU
Authors: Tiphaine Guy, Audrey Créac'hcadec, Charles Ricordel, Alexandre Salé, Baptiste Arnouat, Jean-Louis Bizec, Marie Langelot, Christine Lineau, David Marquette, Françoise Martin, Mathieu Lederlin, Stéphane Jouneau
Journal: European Respiratory Journal (2020)

<b>SARS-CoV-2 infected patients with nonhypercapnic acute hypoxaemic respiratory failure can benefit from high-flow nasal oxygen outside an ICU. The technique appears to be safe for healthcare workers and could well liberate critical ICU resources.</b>https://bit.ly/2Xq80iu
Residential Greenness and Cardiovascular Disease Incidence, Readmission, and Mortality
Authors: Hong Chen, Richard T. Burnett, Li Bai, Jeffrey C. Kwong, Dan L. Crouse, Eric Lavigne, Mark S. Goldberg, Ray Copes, Tarik Benmarhnia, Sindana D. Ilango, Aaron van Donkelaar, Randall V. Martin, Perry Hystad
Journal: Environmental Health Perspectives (2020)

Background: Living in greener areas of cities was linked to increased physical activity levels, improved mental well-being, and lowered harmful environmental exposures, all of which may affect human health. However, whether living in greener areas may be associated with lower risk of cardiovascular disease incidence, progression, and premature mortality is unclear. Objectives: We conducted a cohort study to examine the associations between residential green spaces and the incidence of acute myocardial infarction (AMI) and heart failure (HF), post-AMI and HF hospital readmissions, and mortality. Methods: We simultaneously followed four large population-based cohorts in Ontario, Canada, including the entire adult population, adults free of AMI and HF, and survivors of AMI or HF from 2000 to 2014. We estimated residential exposure to green spaces using satellite-derived observations and ascertained health outcomes using validated disease registries. We estimated the associations using spatial random-effects Cox proportional hazards models. We conducted various sensitivity analyses, including further adjusting for property values and performing exploratory mediation analysis. Results: Each interquartile range increase in residential greenness was associated with a 7% [95% confidence interval (CI): 4%, 9%] decrease in incident AMI and a 6% (95% CI: 4%, 7%) decrease in incident HF. Residential greenness was linked to a ∼10% decrease in cardiovascular mortality in both adults free of AMI and HF and the entire adult population. These associations remained consistent in sensitivity analyses and were accentuated among younger adults. Additionally, we estimated that the decreases in AMI and HF incidence associated with residential greenness explained ∼53% of the protective association between residential greenness and cardiovascular mortality. Conversely, residential greenness was not associated with any delay in readmission or mortality among AMI and HF patients. Conclusions: Living in urban areas with more green spaces was associated with improved cardiovascular health in people free of AMI and HF but not among individuals who have already developed these conditions. https://doi.org/10.1289/EHP6161
Use of CDK6 oncogene amplification and 17q gain to predict poor clinical risk groups in adult medulloblastoma
Authors: S. M. Pfister, M. Remke, A. Benner, W. Werft, F. Mendrzyk, W. Scheurlen, A. Kulozik, P. Lichter, A. Korshunov
Journal: Journal of Clinical Oncology (2009)

2030 Background: While in children medulloblastoma comprises the most common malignant brain tumor, it accounts for only 1% of intracranial malignancies in adults. The infrequent appearance of MB in adults poses the question, whether these tumors are the same in adults and children in terms of biological and clinical peculiarities. Methods: Array-CGH was performed for a total 34 adult medulloblastoma samples (&gt;18 years) and results were compared with data from 101 pediatric patients. Selected genomic regions were further investigated by FISH analysis in an independent cohort of 415 samples (112 adult and 303 pediatric). All 146 adult patients received a standard treatment regimen consisting of tumor resection, irradiation of the neuroaxis with 36 Gy, a boost of 20–23 Gy to the posterior fossa, and eight cycles of vincristin, lomustine, and cisplatin. To identify novel prognostic markers, DNA copy-number information was correlated with survival data using log rank and chi-square tests. Results: Copy-number gains of chromosome 17q as well as high-level amplifications of CDK6 were identified as significant adverse prognostic markers in adult medulloblastoma. Apart from one exception, CDK6 amplifications were only observed in adult patients (9% in adults versus 0.2 % in children), whereas amplifications of MYC or MYCN were significantly overrepresented in the pediatric cohort, but when present were also associated with dismal prognosis in adults. Monosomy of chromosome 6, in contrast to the pediatric cohort, was not significantly associated with good prognosis, although nuclear ß-catenin accumulation was detected in most cases (r = 0.68). Based on these results, we propose a molecular staging system for adult medulloblastoma: i) cases with oncogene amplification (10% of cases, 5-year OS = 0%); ii) cases with chromosome 17q gain without oncogene amplification (25% of cases, 5-year-OS = 35%); and iii) cases without oncogene amplification or 17q gain (65% of cases, 5-year OS = 92%). Conclusions: We report on the largest cohort of adult medulloblastoma investigated for genomic imbalances to date. We propose a model for the molecular risk stratification of adult medulloblastoma comprising three distinct genomic risk groups with significantly different survival and tumor biology. No significant financial relationships to disclose.
Poly-dopamine, poly-levodopa, and poly-norepinephrine coatings: Comparison of physico-chemical and biological properties with focus on the application for blood-contacting devices
Authors: Xing Tan, Peng Gao, Yalong Li, Pengkai Qi, Jingxia Liu, Ru Shen, Lianghui Wang, Nan Huang, Kaiqin Xiong, Wenjie Tian, Qiufen Tu
Journal: Bioactive Materials (2020)

Thanks to its simplicity, versatility, and secondary reactivity, dopamine self-polymerized coatings (pDA) have been widely used in surface modification of biomaterials, but the limitation in secondary molecular grafting and the high roughness restrain their application in some special scenarios. Therefore, some other catecholamine coatings analog to pDA have attracted more and more attention, including the smoother poly-norepinephrine coating (pNE), and the poly-levodopa coating (pLD) containing additional carboxyl groups. However, the lack of a systematic comparison of the properties, especially the biological properties of the above three catecholamine coatings, makes it difficult to give a guiding opinion on the application scenarios of different coatings. Herein, we systematically studied the physical, chemical, and biological properties of the three catecholamine coatings, and explored the feasibility of their application for the modification of biomaterials, especially cardiovascular materials. Among them, the pDA coating was the roughest, with the largest amount of amino and phenolic hydroxyl groups for molecule grafting, and induced the strongest platelet adhesion and activation. The pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory response. The pNE coating was the smoothest, with the best hemocompatibility and histocompatibility, and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle cells. To sum up, the pNE coating may be a better choice for the surface modification of cardiovascular materials, especially those for vascular stents and grafts, but it is still not widely recognized.
Re: Variability of the Positive Predictive Value of PI-RADS for Prostate MRI Across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel
Authors: Anwar R. Padhani, Jelle Barentsz, Jeffrey Weinreb, Ivo Schoots, Clare Tempany
Journal: European Urology (2020)
Maximising the impact of global and national physical activity guidelines: the critical role of communication strategies
Authors: Karen Milton, Adrian E Bauman, Guy Faulkner, Gerard Hastings, William Bellew, Chloë Williamson, Paul Kelly
Journal: British Journal of Sports Medicine (2020)

Physical activity guidelines are evidence-based statements on recommended physical activity levels for good health. Guidelines, in isolation, are unlikely to increase population levels of physical activity; appropriate and effective communication is fundamental to maximising their impact. The aim of this paper is to provide a planning framework for physical activity guideline communication, including an overview of key audiences, aims and approaches.All authors considered and agreed on the three broad issues to address by consensus. We identified key sources of evidence through scoping of the literature and our knowledge of the research area.Whether guidelines are global or national, communication of the physical activity guidelines should be informed by: (1) a situational analysis that considers the context in which the communication will take place and (2) a stakeholder analysis to determine the key target audiences for the communication and their values, needs and preferences. Audiences include policy-makers within and outside the health sector, other key stakeholders, the general public, specific population subgroups, health professionals and non-health professionals with a role in physical activity promotion. The aims and approach to communication will differ depending on the target audience.Communication to raise awareness and knowledge of the physical activity guidelines must be supported by policies, environments and opportunities for physical activity. Besides the intrinsic value of the physical activity guidelines, it is essential that substantial effort is put in to diligently planning, funding and implementing their communication from the outset.
Ultra-rapid flow cytometry assay for colistin MIC determination in Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii
Authors: Daniela Fonseca e Silva, Ferdinando F. Andrade, Rosário Gomes, Ana Silva-Dias, Inês Martins-Oliveira, Blanca Pérez-Viso, Maria Helena Ramos, Acácio G. Rodrigues, Rafael Cantón, Cidália Pina-Vaz
Journal: Clinical Microbiology and Infection (2020)
Nano-micrometer surface roughness gradients reveal topographical influences on differentiating responses of vascular cells on biodegradable magnesium
Authors: Ke Zhou, Yutong Li, Lei Zhang, Liang Jin, Feng Yuan, Jinyun Tan, Guangyin Yuan, Jia Pei
Journal: Bioactive Materials (2020)

Distinctively directing endothelial cells (ECs) and smooth muscle cells (SMCs), potentially by surface topography cue, is of central importance for enhancing bioefficacy of vascular implants. For the first time, surface gradients with a broad range of nano-micrometer roughness are developed on Mg, a promising next-generation biodegradable metal, to carry out a systematic study on the response of ECs and SMCs. Cell adhesion, spreading, and proliferation are quantified along gradients by high-throughput imaging, illustrating drastic divergence between ECs and SMCs, especially in highly rough regions. The profound role of surface topography overcoming the biochemical cue of released Mg2+ is unraveled at different roughness ranges for ECs and SMCs. Further insights into the underlying regulatory mechanism are gained at subcellular and gene levels. Our work enables high-efficient exploration of optimized surface morphology for modulating favored cell selectivity of promoting ECs and suppressing SMCs, providing a potential strategy to achieve rapid endothelialization for Mg.
OC-070 Endoscopic mucosal resection in the elderly
Authors: A Gaglia, T Skouras, A Bond, MJ Lim, L Bonnet, S Sarkar
Journal: Gut (2017)

Introduction  Endoscopic mucosal resection (EMR) is an invaluable and effective technique of resecting colorectal (CR) polyps. However, the outcomes and usefulness in elderly patients is unknown.  The aim of the study was to determine the outcomes of elderly persons undergoing EMR of CR polyps and to quantify the survival and predictors of mortality  Method  Retrospective cohort study of persons aged ≥75 years old who underwent EMR over 10 years (2005–2014) at a tertiary university centre. Age, gender, Charlson score (comorbidity index), repeat colonoscopies and polyp characteristics were investigated to identify potential predictors of post EMR survival.  Results  208 patients (mean age 80.9±3.67 years; 114 male, 94 female) with median Charlson score 1 (IQR 0–2) were included. The median size of the polyps was 20 mm (range 10–150 mm). There were 50 deaths (24%) during the follow up period. All patients but one, who died from colorectal cancer, died from their comorbidities. The mean overall survival was 6.7±0.3 years (median 7.25 years). The complication rate was low at 2.5% and included 2 cases (0.9%)of post EMR bleeding with no need for re-intervention and no perforations. The 7 day readmission rate was 5.3% and the 30 day mortality post procedure was 0%.  Predictors of Survival: Table 1 shows only the statistical significant factors of the univariate and multivariate analysis. Age≥80, Charson score ≥3 and histology of high grade dysplasia were predictors of significantly shorter survival. Repeat procedures had a survival benefit.  Patients with a Charlson Index of   Conclusion  EMR appeared to be a safe procedure in this cohort of elders. Age≥80 and Charlson score ≥3 were independent predictors of death. The latter is not normally recorded in routine assessment for endoscopy and may be important to the individualised decision making when considering an EMR in the Elderly.  Disclosure of Interest  None Declared
Systematic Analyses of Clinically Relevant Single Nucleotide Polymorphisms (SNPs) of NR3C1 in Patients from the Italian Registry of Diamond Blackfan Anemia
Authors: Jiawen Li, Mayte Suarez-Farinas, Stuart Scott, Lilian Varricchio, Carolyn F. Whitsett, Ugo Ramenghi, Irma Dianzani, Anna Rita Migliaccio
Journal: Blood (2017)
Efficacy of venlafaxine for the prevention and relief of acute neurotoxicity of oxaliplatin: Results of EFFOX, a randomized, double-blinded, placebo-controlled prospective study
Authors: J. P. Durand, G. Deplanque, J. Gorent, V. Montheil, E. Raymond, F. Scotte, E. Mitry, F. Goldwasser
Journal: Journal of Clinical Oncology (2009)

9533 Background: Neurosensory toxicity of oxaliplatin is dose-limiting and presents as two distinct clinical syndromes: acute symptoms and cumulative peripheral neuropathy. Methods: From October 2005 to May 2008, patients (pts) presenting oxaliplatin-induced acute neurotoxicity were randomized in a double-blinded study, to receive either arm A: venlafaxine hydrochloride (Effexor, Wyeth Pharmaceuticals Inc.) 50 mg 1 hour prior oxaliplatin infusion and venlafaxine extended release 37.5 mg b.i.d. from day 2 to day 11, either arm B : placebo. The primary endpoint was percentage of pts without acute neuropathy. The study was designed to detect, with 54 pts, a difference of 25%. The neurotoxicity was evaluated using a numeric rating scale of symptoms relief and the Neuropathic Pain Symptom Inventory (Pain 2004;108(3):248–57). Results: 45 pts were included (male : 24; median age : 67.5). Most pts had colo-rectal cancer (75.6%). The two most used chemotherapy regimens were FOLFOX (82.2%) and GEMOX (11.1%). Median number of cycles administered at inclusion was 5. In January 2009, 16 pts out of 22 in arm A (venlafaxine) and 21 pts out of 23 in arm B (placebo) were evaluable. Venlafaxine reduced the incidence of neurosensory acute symptoms : 35.3 % in arm A vs 76.2% in arm B (p=.023, Fisher's exact test). Side effects were emesis (4 pts) and somnolence (3 pts). Conclusions: Venlafaxine is effective for prevention and relief of oxaliplatin-induced acute neurotoxicity. No significant financial relationships to disclose.
An update on the immune landscape in lung and head and neck cancers
Authors: Jennifer W. Carlisle, Conor E. Steuer, Taofeek K. Owonikoko, Nabil F. Saba
Journal: CA A Cancer Journal for Clinicians (2020)

Immunotherapy has dramatically changed the treatment landscape for patients with cancer. Programmed death-ligand 1/programmed death-1 checkpoint inhibitors have been in the forefront of this clinical revolution. Currently, there are 6 US Food and Drug Administration-approved checkpoint inhibitors for approximately 18 different histologic types of cancer. Lung cancer and head and neck squamous cell carcinoma (HNSCC) are 2 diseases that have led the way in the development of immunotherapy. Atezolizumab, durvalumab, nivolumab, and pembrolizumab are all currently used as part of standard-of-care treatment for different stages of lung cancer. Similarly, nivolumab and pembrolizumab have US regulatory approval as treatment for advanced metastatic HNSCC. This is significant because lung cancer represents the most common and most fatal cancer globally, and HNSCC is the sixth most common. Currently, most of the approvals for the use of immunotherapy agents are for patients diagnosed in the metastatic setting. However, research is ongoing to evaluate these drugs in earlier stage disease. There is plausible biological rationale to expect that pharmacologic activation of the immune system will be effective for early-stage and smaller tumors. In addition, selecting patients who are more likely to respond to immunotherapy and understanding why resistance develops are crucial areas of ongoing research. The objective of this review was to provide an overview of the current immune landscape and future directions in lung cancer and HNSCC.
Detection of early-stage pancreatic carcinoma
Authors: D. Gold, D. E. Modrak, G. Newsome, Z. Karanjawala, R. Hruban, M. Goggins, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2009)

4613 Background: Invasive pancreatic carcinoma is a virtually lethal disease, mostly because of the failure to detect it at a sufficiently early timepoint for successful treatment. Our laboratory has identified a unique biomarker detected by MAb PAM4 that shows high specificity for a mucin glycoprotein expressed by pancreatic carcinoma (PC). While identified in almost 90% of PC and its precursor lesions, the antigen is not detectable in normal pancreas. We are investigating this biomarker for the early detection of PC. Methods: Both immunohistochemical (IHC) and enzyme immunoassay (EIA) were employed for detection and/or quantitation of PAM4-mucin in tissue and sera, respectively. Results: We have extended our prior IHC results with precursor lesions (Clin Cancer Res 2007;13:7380–7); PAM4 gave an intense, diffuse labeling pattern in 81% of mucinous cystic neoplasms (MCN), with an additional 11% showing a focal pattern (n=27). Thus, a total of 92% of MCN showed evidence of PAM4-antigen expression. Of interest, a difference in the labeling pattern was observed in association with the grade of dysplasia, providing easy identification of MCN with high- grade dysplasia. We previously reported use of an EIA for quantitation of PAM4-antigen in sera. The assay demonstrated a sensitivity and specificity of 77% and 95%, respectively, for identification of PC (J Clin Oncol, 2006;24:252–8). We have now confirmed these results in a set of serum specimens (n= 49 PC, 13 normal) for which staging information was available. Overall specificity and sensitivity were 82% and 85%, respectively, calculated by ROC curve analysis (AUC=0.878±0.045; 95% CI=0.769–0.947). Although only a small number of specimens were from patients with stage I disease (n=12), 92% of these were above the cutoff value for positive response. A correlation was observed for average concentration of antigen in the circulation with stage of disease (R2=0.988). Conclusions: IHC and EIA results indicate that PAM4 identifies a biomarker for PC that is present at the earliest stages of neoplastic transformation, thus warranting controlled analyses of larger specimen numbers. (Supported in part by USPHS grant CA096924 from the NIH.) [Table: see text]
Predictors of survival in patients with metastatic breast cancer (MBC) treated with high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT)
Authors: A. Von Drygalski, T. B. Tran, K. Messer, M. Pu, S. Corringham, C. Nelson, E. D. Ball, E. D. Ball
Journal: Journal of Clinical Oncology (2009)

e22086 Background: Individualized care in MBC requires predictors of survival for tailored treatment. Although HD-ASCT has not resulted in improved overall survival (OS), retrospective analyses may identify patients who benefited. We reviewed records of all patients (n=96) in the bone marrow transplant registry at UCSD treated with HD-ASCT for MBC between 1989 and 2000. Methods: Age, race, stage at diagnosis, histology, estrogen receptor (ER) and menopausal status, body mass index (BMI) in kg/m2, time to transplant and death, sites of metastasis, disease status prior to and after transplant, and days in hospital were extracted. Brookmeyer &amp; Crowley's 95% confidence intervals, Cox models for predictors of a time-to-event variable and Schoenfeld tests for proportional hazard assumptions were applied. Results: Median OS was 5.6 ys (CI 4.1–7.4) after initial diagnosis and 1.7 ys (CI 1.36–2.07) after transplant. OS after HD-ASCT at 12 ys was 8.2% and, although not statistically significant, 18.5% in ER- and 2.6% in ER+ patients, respectively. Stratified by ER status, stage at diagnosis was an independent predictor of OS. Patients with stage I at diagnosis were at lowest risk of death when compared to stage II-IV patients with HRs of 2.7 (II vs I CI 1.4–5.2), 4.6 (III vs I CI 2.1–10) and 17 (IV vs I CI 6.1- 47.8). Death risk was increased with BMI ≥ 30 (HR 3.1; CI 1.8–5.4), infiltrating lobular carcinoma (HR 2.5; CI 1.1–5.38) and visceral metastasis (HR 2.3; CI 1.3–4.1). Conclusions: The study highlights that ∼10% of patients experience ≥10 ys survival with HD- ASCT. Obesity, late stage at diagnosis, lobular infiltrating histology and visceral metastasis were independent negative predictors of OS. Surprisingly, ER- patients tended to live longer. Although survival was influenced by various disease characteristics, obesity was the only significant patient derived factor. How obesity negatively affects outcomes - whether affecting cancer growth or through associated morbidity - needs further study. These data may be useful stratification tools for future trials employing HD-ASCT as treatment modality in MBC. No significant financial relationships to disclose.