tbuckley/cabot-search huggingface dataset:
Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer
Authors: Anita K. Mehta, Emily M. Cheney, Christina A. Hartl, Constantia Pantelidou, Madisson Oliwa, Jessica A. Castrillon, Jia-Ren Lin, Katie E. Hurst, Mateus de Oliveira Taveira, Nathan T. Johnson, William M. Oldham, Marian Kalocsay, Matthew J. Berberich, Sarah A. Boswell, Aditi Kothari, Shawn Johnson, Deborah A. Dillon, Mikel Lipschitz, Scott Rodig, Sandro Santagata, Judy E. Garber, Nadine Tung, José Yélamos, Jessica E. Thaxton, Elizabeth A. Mittendorf, Peter K. Sorger, Geoffrey I. Shapiro, Jennifer L. Guerriero
Journal: Nature Cancer (2020)
7P Peripheral blood-based biomarkers of prognosis and treatment response in patients with non-small cell lung cancer treated with PD-1 inhibitors
Authors: I. Tourkantonis, D. Grapsa, A. Charpidou, I. Gkiozos, H. Gogas, D. Psyrri, K. Syrigos
Journal: Annals of Oncology (2020)
Covid-19: Pfizer-BioNTech vaccine is rolled out in US
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

<h3>Objective</h3> Patients with type 2 diabetes mellitus (T2DM) often experience hypoglycaemia and weight gain due to treatment side effects. Sulfonylureas (SU) and the combination of SU and metformin (SU+MET) were the most common monotherapy and combination therapies used in Thailand tertiary care hospitals. This study aimed to assess the glycaemic goal attainment rates, hypoglycaemic episodes, weight gain and treatment compliance among patients with T2DM receiving SU or SU+MET. <h3>Research design and methods</h3> A multicentre cross-sectional survey and retrospective review was conducted in five tertiary care hospitals, Thailand. Patients with T2DM aged ≥30 years were included consecutively during a 12-month period. Glycaemic control, experiences of hypoglycaemia, weight gain and compliance were evaluated. Glycaemic goal attainment was defined by HbA<sub>1c</sub> level less than 7%. <h3>Results</h3> Out of the 659 patients (mean age (±SD)), 65.5 (10.0) years and median duration of T2DM (IQR), 10 (5–15) years), 313 (47.5%) achieved the glycaemic goal. HbA<sub>1c</sub> levels in the patients with goal attainment was significantly lower compared with those without (6.3%±0.5% vs 8.1%±1.2%, p&lt;0.001). Goal attainment was significantly lower among patients treated with SU+MET than those treated with SU alone (43.5% vs 63.0%; OR 0.45, 95% CI 0.31, 0.66, p&lt;0.001). A third of patients reported experiencing hypoglycaemia (30.7%) and weight gain (35.4%). Weight gain in the SU+MET group was lower than those receiving SU alone (33.1% vs 44.6%, p=0.015), but there was no difference in hypoglycaemic events. Major events in the previous 12 months were experienced by 68 patients, most commonly congestive heart failure and ischaemic heart disease. Approximately half of the patients (52.2%) reported not always taking their medication as prescribed. <h3>Conclusions</h3> Among patients with T2DM receiving SU or SU+MET, only about half of the patients achieved glycaemic goal and compliance with the treatment. Hypoglycaemia and weight gain posed a significant burden with risk of weight gain higher in the SU group.
Correspondence on ‘Clinical characteristics and genetic analyses of 187 patients with undefined autoinflammatory diseases’
Authors: Gonçalo Boleto, Carolla El Chamieh, Lucie Biard, Isabelle Koné-Paut, Veronique Hentgen, Guilaine Boursier, Guillaume Sarrabay, Patrice Cacoub, Isabelle Touitou, David Saadoun
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article by Ter Haar et al 1 who describe the clinical characteristics, treatment response and genetic findings in a cohort of patients (n=187) with undefined systemic autoinflammatory diseases (sAIDs). The authors observed that patients with pericarditis were older at disease onset and had milder disease whereas patients with intellectual impairment were younger at disease onset and often had affected relatives. Of note, among patients with recurrent disease course, 30% (n=53/180) had aphthous stomatitis. Moreover, after complete gene screening, screening of most relevant exons or screening of most relevant point mutations, 9.4% (n=15/159) of patients carried likely pathogenic variants or variants of uncertain significance. Our recent French multicentre study on targeted next-generation sequencing (NGS) gives further insight into the clinical characteristics and genetic findings in patients with sAIDs associated with recurrent aphthous stomatitis (RAS).

RAS (ie, adult onset, association with other features such as fever and malaise) can represent a diagnostic challenge. RAS especially when associated with fever, pharyngitis and lymphadenopathy may be the first presentation of sAIDs.2 sAIDs arise from impaired inflammatory responses due to variants in gene coding proteins …
MODL-20. A BIOBANK OF ~100 PATIENT-DERIVED MODELS REPRESENTING BIOLOGICAL HETEROGENEITY AND DISTINCT THERAPEUTIC DEPENDENCIES IN PAEDIATRIC HIGH GRADE GLIOMA AND DIPG
Authors: Diana Carvalho, Alan Mackay, Sara Temelso, Elisa Izquierdo, Elisabet Potente Fernandez, Rebecca Rogers, Jessica Boult, Janat Fazal Salom, Natalie Simon, Matthew Clarke, Valeria Molinari, Ketty Kessler, Anna Burford, Lynn Bjerke, Mariama Fofana, Michael Hubank, Jane Pears, Andrew Moore, Angel Montero Carcaboso, Lynley Marshall, Fernando Carceller, Simon Robinson, Darren Hargrave, Maria Vinci, Chris Jones
Journal: Neuro-Oncology (2020)

Abstract Paediatric high-grade glioma comprise multiple biological and clinical subgroups, the majority of which urgently require novel therapies. Patient-derived models represent useful tools for mechanistic and preclinical investigations based upon their retention of key genetic/epigenetic features and their amenability to high-throughput approaches. We have collected ~100 in vitro models representing multiple subtypes (H3.3/H3.2/H3.1K27M, H3.3G34R/V, BRAF, MYCN_amp, NTRK_fusion, hypermutator, others) established under 2D (laminin) and/or 3D (neurosphere) conditions, credentialed by phenotypic (growth, invasion/migration) and molecular (methylation array, DNA sequencing, RNAseq) comparison to the original tumour sample. These were derived from patients at our local hospitals (n=29), as part of national co-clinical trials (n=19), from international collaborating centres (n=11), or shared directly by research groups worldwide (n=45). These have variously been subjected to pharmacological (approved/experimental drug libraries) and/or genetic screening (whole-genome CRISPR) to identify specific biological dependencies. Many have been established as orthotopic xenografts in vivo (PDX), with detailed pathological and radiological correlations with the clinical disease, and with tumorigenic latencies ranging from 48–435 days. This resource has allowed us to identify genotype-specific synthetic lethalities and responses to targeted inhibitors, including olaparib (PARP) with ATRX, nutlin-3 (MDM2) with PPM1D, AZD1775 (WEE1) with TP53, and CYC065 (CDK9) with MYCN-amplification. Combinatorial screening highlighted synergies in ACVR1-mutant DIPG between novel ALK2 inhibitors and ONC201 (DRD2). Rapid screening allows for feedback of drug sensitivities to treating clinicians at relapse, whilst mechanistic underpinning of these interactions and use of the models to identify specific mediators of resistance will allow for rational future trial design.
Transcatheter Aortic Valve Implantation: A Snapshot From the United Kingdom⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Alec Vahanian, Dominique Himbert, Bernard Iung
Journal: Journal of the American College of Cardiology (2011)
Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity
Authors: Marco Mannes, Arthur Dopler, Oliver Zolk, Sophia J. Lang, Rebecca Halbgebauer, Britta Höchsmann, Arne Skerra, Christian K. Braun, Markus Huber-Lang, Hubert Schrezenmeier, Christoph Q. Schmidt
Journal: Blood (2020)
Abstract P306: Racial/Ethnic Differences In Self-reported Sedentary Time Are Related To Differential Risk For Prevalent Hypertension: NHANES 2011-2016
Authors: Jennifer L Mattingly, Megan E Petrov
Journal: Circulation (2020)

Introduction: Evidence suggests there are racial/ethnic differences in lifestyle behaviors that may affect cardiovascular health outcomes such as physical activity engagement, diet, and sleep duration. However, the literature on racial/ethnic differences in sedentary time (ST) and whether these differences may be related differentially to cardiovascular health is limited. The goals of this study are to investigate racial/ethnic differences in self-reported ST, and examine if the modifying effect of ST with race/ethnicity will be associated with hypertension (HTN) prevalence. Methods: Adults (N=15903, age ≥20 yrs) from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 reported their race/ethnicity (Mexican American [MA], Other Hispanic [OH], non-Hispanic White [NHW], non-Hispanic Black [NHB], non-Hispanic Asian, Other or mixed race [OM]), ST on a typical day (median split at 6 hrs: Low vs. High ST), and history of physician diagnosed HTN (yes/no). Weighted logistic regression models were conducted to examine the association between race/ethnic groups and ST, and combined racial/ethnic-ST groups (reference group: NHW with Low ST) on HTN prevalence while controlling for age, sex, education, body mass index, smoking status, moderate-vigorous physical activity min/wk, and history of diabetes, cardiovascular (i.e., heart failure, myocardial infarction, stroke, coronary heart disease) and kidney conditions. Results: There was a significant association between race/ethnic groups and ST (Wald F [5,43]=23.4, p &lt;0.001) such that compared to NHW, MA (OR=.43, 95%CI:.36,.51) OH (OR=.51, 95%CI:.42,.62), and OM (OR=.71, 95%CI:.55,.91) had lower odds for High ST. Weighted percent of the sample with HTN was 32.6%. There was a significant effect of combined race by ST groups on HTN (Wald F [11,37] = 9.8, p &lt;0.001). Compared to NHW with Low ST, MA (OR=.70, 95%CI: .54,.90) and OH (OR=.79, 95%CI: .64,.97) with Low ST had lower odds for HTN, whereas NHB with Low ST (OR=1.58, 95%CI: 1.34,1.87) and High ST (OR=1.76, 95%CI: 1.50,2.07) had increased odds of HTN. Conclusion: In a large national cohort, daily ST differed by race/ethnicity, and ST modified the association between race/ethnicity and odds for HTN such that compared to more active NHW, more active Hispanic groups had decreased odds for HTN, but NHB regardless of ST had increased risk for HTN. ST may be a key modifiable risk factor in addressing race/ethnic disparities in cardiovascular health.
LINC-43. FACTORS LEADING TO DIAGNOSTIC DELAY FOR CHILDREN WITH PRIMARY TUMORS OF CENTRAL NERVOUS SYSTEM (CNS) IN QATAR
Authors: Tayseer Yousif, Ayman Saleh, Ata Maaz
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Median time to diagnosis for primary CNS tumors for children in Qatar has been reported to be 28 days. However, a wide variation in diagnostic times is seen. This study was undertaken to analyze the factors leading to delay in diagnosis. METHODS Data were retrospectively analyzed for children who had diagnostic delay (more than 28 days) from September 2006 to February 2020. Presenting symptoms, number and type of healthcare contacts and presenting symptom interval (PSI) were reviewed. Parental delay (PSI-1) was defined as the date of onset of first symptom to the date of first healthcare contact. Healthcare delay (PSI-2) was defined as date of first healthcare contact to the date of diagnostic scan. RESULTS Twenty-four patients were identified with diagnostic delay. Median age at diagnosis was 48.2 (range 5.4–171.6) months with an equal sex distribution. Fifteen (62.5%) patients were older than 3 years, 13(54%) patients had low grade glioma, 16 (66.7%) had supratentorial tumors and 12 (50%) presented with raised intracranial pressure. Diagnosis was made after a median 3 (range 1–8) healthcare contacts. Nineteen (79%) patients presented to primary care. Median PSI was 132 (31–783) days. Parental delay (PSI-1) was 35 (0–496) days, while healthcare delay (PSI-2) was 41 (0–562) days. Endocrine (241 days) and oculo-visual (184 days) symptoms were associated with the longest PSI. CONCLUSIONS There was no significant difference between parental and healthcare delay. Endocrine and oculo-visual symptoms were associated with longest PSI. Increased awareness is required for early recognition of signs suggestive of CNS tumors.
Microbial enterotypes beyond genus level: <i>Bacteroides</i> species as a predictive biomarker for weight change upon controlled intervention with arabinoxylan oligosaccharides in overweight subjects
Authors: Lars Christensen, Claudia V. Sørensen, Frederikke U. Wøhlk, Louise Kjølbæk, Arne Astrup, Yolanda Sanz, Mads F. Hjorth, Alfonso Benítez-Páez
Journal: Gut Microbes (2020)

Recent studies indicate that microbial enterotypes may influence the beneficial effects of wholegrain enriched diets including bodyweight regulation. In a 4-week intervention trial, overweight subjects were randomized to consume either arabinoxylan-oligosaccharides (AXOS) (10.4 g/d) from wheat bran or polyunsaturated fatty acids (PUFA) (3.6 g/d). In the present study, we have stratified the subjects participating in the intervention (n = 29) according to the baseline Prevotella-to-Bacteroides (P/B) ratios through a post-hoc analysis and applied a linear mixed model analysis to identify the influence of this P/B ratio on the differences in weight changes in the intervention arms. Following AXOS consumption (n = 15), the high P/B group showed no bodyweight changes [−0.14 kg (95% CI: −0.67; 0.38, p = .59)], while the low P/B group gained 0.65 kg (95% CI: 0.16; 1.14, p = .009). Consequently, a difference of −0.79 kg was found between P/B groups (95% CI: −1.51; −0.08, p = .030). No differences were found between P/B groups following PUFA consumption (0.61 kg, 95% CI: −0.13; 1.35, p = .10). Among the Bacteroides species, B. cellulosilyticus relative abundance exhibited the highest positive rank correlation (Kendall’s tau = 0.51, FDR p = .070) with 4-week weight change on AXOS, and such association was further supported by using supervised classification methods (Random Forest). We outlined several carbohydrate-active enzyme (CAZy) genes involved in xylan-binding and degradation to be enriched in B. cellulosilyticus genomes, as well as multiple accessory genes, suggesting a supreme AXOS-derived glycan scavenging role of such species. This post-hoc analysis, ensuring species and strain demarcation at the human gut microbiota, permitted to uncover the predictive role of Bacteroides species over P/B enterotype in weight gain during a fiber-based intervention. The results of this pilot trial pave the way for future assessments on fiber fermentation outputs from Bacteroides species affecting lipid metabolism in the host and with direct impact on adiposity, thus helping to design personalized interventions.
Annals Consult Guys - Remote Physical Examination in Heart Failure: What Is the Evidence?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2020)

Web Exclusives15 December 2020Annals Consult Guys - Remote Physical Examination in Heart Failure: What Is the Evidence?FREEGeno J. Merli, MD, Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author, Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article and Disclosure Informationhttps://doi.org/10.7326/W19-0045 Eligible for CME Point-of-CareCME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys and special guest Dr. Jennifer Thibodeau review a strategy for assessing patients with heart failure during telemedicine encounters.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment The Consult GuysJefferson University4 June 2021 Author's response Our time for telehealth consultation is 30-40 minutes. The visit is scripted on questioning the patient. José TapiaHospital la Florida, Santiago, Chile29 May 2021 Time to evaluate a patient Hi consult guys, thanks a lot for this video, very interesting....one question: How much time you need (or have) for a telemedicine consult? Thanks, Jose Author, Article and Disclosure InformationDisclosures: Geno J. Merli, MD, and Howard H. Weitz, MD, report that they have no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Stephanie Chang, MD, MPH, Deputy Editor, reports employment with the Agency for Healthcare Research and Quality, travel compensation from the Guidelines International Network, and participation in the Patient-Centered Outcomes Research Institute methodology committee. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interests to disclose. Eliseo Guallar, MD, MPH, DrPH, Deputy Editor, Statistics, reports that he has no financial relationships or interests to disclose. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 2020Volume 173, Issue 12Page: CG1 ePublished: 15 December 2020 Issue Published: 15 December 2020 CopyrightCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development
Authors: Joan Font-Díaz, Alba Jiménez-Panizo, Carme Caelles, María dM Vivanco, Paloma Pérez, Ana Aranda, Eva Estébanez-Perpiñá, Antonio Castrillo, Mercedes Ricote, Annabel F. Valledor
Journal: Seminars in Cancer Biology (2020)
A Phase 2 Study of the LSD1 Inhibitor Img-7289 (bomedemstat) for the Treatment of Advanced Myelofibrosis
Authors: Harinder Gill, Abdulraheem Yacoub, Kristen M. Pettit, Terrence Bradley, Aaron T. Gerds, Maciej Tatarczuch, Jake Shortt, Natasha Joan Curtin, James M. Rossetti, Kate Burbury, Adam J. Mead, Joachim R. Göthert, Steffen Koschmieder, Amber Jones, Jennifer Peppe, Georges Natsoulis, Wan-Jen Hong, William S. Stevenson, Joanne Ewing, Claire N. Harrison, Alessandro Vannucchi, Justin Watts, David M Ross, Moshe Talpaz, Hugh Young Rienhoff
Journal: Blood (2021)
QOLP-28. PREOPERATIVE SLEEP DISTURBANCE AND ITS ASSOCIATION WITH QUALITY OF LIFE IN ADULT BRAIN TUMOR PATIENTS
Authors: Pin-Yuan Chen, Hsiao-Yean Chiu, Pei-Ching Lin
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Sleep disturbances are common complaints in adult brain tumor patients and impact their quality of life profoundly. The prevalence and pattern of preoperative sleep disturbances are still unknown. MATERIAL AND METHOD There were 36 adult patients with primary brain tumors who were recruited before craniotomy. All participants completed a battery of questionnaires, including the Athens Insomnia Scale, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Brief Fatigue Inventory, Hospital Anxiety, and Depression Scale, Morningness-Eveningness Questionnaire, and EORTC-QLQ-BN20. Actigraphy was put on a non-dominant wrist for obtaining objective sleep parameters, such as the dichotomy index. RESULT The prevalence of preoperative insomnia, poor sleep quality, excessive daytimes sleepiness, and circadian disruption were all high but similar between benign and malignant brain tumor groups. Patients with glioma had poorer quality of life. Insomnia was the only sleep disturbance that significantly associated with quality of life in a multivariate linear regression modal. CONCLUSION Sleep disturbances are common in adult brain tumor patients. Insomnia worse the quality of life of these patients. A further longitudinal investigation of sleep disturbances and quality of life in brain tumor patients is worthful.
TMOD-26. ESTABLISHING A PATIENT-DERIVED, IN-VITRO ORGANOTYPIC SLICE CULTURE MODEL OF GBM
Authors: Liam Rappoldt, Adrienne Weeks, Rodney Ouellete, Jeremy Roy, Catherine Taylor, Craig McCormick, Kathleen Attwood, Inhwa Kim
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma Multiforme (GBM) is the most common primary malignant brain tumour. This tumour is universally fatal with a median survival of 15 months. Driving this pathology is an extremely heterogeneic tumour and complex tumour microenvironment. GBM research is primarily conducted using immortalized or primary cell lines due to their practicality and reproducibility. However, these cell lines do not effectively recapitulate the tumour microenvironment. Mouse models address these shortcomings but are laborious and expensive. We propose to utilize a patient derived organotypic culture model of GBM as an intermediary. We have utilized this model to test genetic manipulation via lentiviral transduction and the feasibility of utilizing this model to understand patient derived extracellular vesicles (EVs). We have sectioned and cultured patient derived organotypic models for 14 days without loss of viability. To determine if these organotypic cultures are amenable to lentiviral manipulation, tissue sections were transduced with far-red fluorescent lentivirus and efficiency determined by confocal laser scanning microscopy (CLSM) and flow cytometry (FC). To determine feasibility as a model for EVs, media obtained from patient-derived organotypic cultures was analyzed by western blot, nanoparticle tracking analysis (NTA), and nanoFlow Cytometry (nFC). In the future these EVs will be compared to those found in patient serum. The model of GBM has been lentivirally transduced to express a far-red fluorescent vector in approximately 15% of the slice, quantified by CLSM and FC. EV-sized particles positive for canonical EV markers have been identified in the media by NTA, nFC and western blot. Using lentiviral-mediated genetic engineering and emerging EV science, this organotypic slice culture models yields exciting utility in GBM research. The established organotypic slice culture model will likely be a valuable tool in the study of GBM biology and EV dynamics.