tbuckley/cabot-search huggingface dataset:
Abstract 13209: Law Enforcement-Initiated Cardiopulmonary Resuscitation in the Care of Out-of-Hospital Cardiac Arrest
Authors: Luke A Wohlford, Bruce J Barnhart, Daniel W Spaite, Joshua B Gaither, Amber D Rice, Gail Bradley, Robyn McDannold, Samuel Keim, Chengcheng Hu
Journal: Circulation (2021)

Background: Little is known about the provision of care by law enforcement (LE) personnel within modern EMS systems. We evaluated LE performance of bystander CPR (BCPR) and associated outcomes in OHCA across Arizona. Methods: A total of 5,654 OHCA cases (1/1/2019-12/31/2019) were evaluated using the Save Hearts in Arizona Registry and Education (SHARE) cardiac arrest registry. Data were abstracted from all EMS patient care records (PCRs). If two parties provided BCPR, the first to give compressions was considered the provider for this analysis. Cases identified as “Stranger” or “Unknown” BCPR were manually evaluated for narrative data to identify BCPR provider when possible. Results: BCPR was provided in 2285 cases [48.8%; (95% CIs 47.4%, 50.3%)] after excluding 850 cases that occurred in healthcare facilities where personnel are duty-bound to provide CPR. LE provided BCPR in 444 patients [19.4% (17.8%, 21.1%)], second only to family/spouse [1143 pts; 50.0% (48.0%, 52.1%)]. Overall, 279 patients survived to hospital discharge [12.2%, (10.9%, 13.6%)]. The Table shows the rates of BCPR in each provider category and the associated rates of survival. Of note is that the rate of bystander AED use was more than four times higher in LE BCPR [6.3% (4.23%, 8.99%)] than family-provided BCPR [1.5% (0.87%, 2.37%; p &lt; 0.0001)], but was still very low. Conclusions: In this statewide study that included more than 130 EMS agencies from frontier to urban settings, LE personnel were frequently involved in the care of OHCA patients within the 911 system response. To our knowledge, this magnitude of provision of BCPR by LE (nearly one in five BCPR cases) has not been reported previously. Furthermore, the consequential rate of LE response to OHCA provides the opportunity to significantly increase AED use. Our findings support the widespread and intentional training of LE in CPR and AED use and has the potential to improve survival in diverse settings.
36P Alterations in tumour-promoting cytokines in cancer patients after SARS-CoV-2 infection
Authors: F.H. De Winter, A. Hotterbeekx, M. Huizing, A. Konnova, B. 's Jongers, R.K. Jairam, P. Moons, E. Roelant, D. Le Blon, W. Vanden Berghe, A. Janssens, W. Lybaert, L. Croes, C. Vulsteke, S. Malhotra-Kumar, H. Goossens, Z. Berneman, M. Peeters, P. Van Dam, S. Kumar-Singh
Journal: Annals of Oncology (2021)
DNMT3A-Mutant Leukemia Cells Primed to “Fork It Over” under DNA Damage
Authors: Aaron D. Viny
Journal: Clinical Cancer Research (2021)

Mutations in the gene DNMT3A have been identified in various hematopoietic conditions, including clonal hematopoiesis, myelodysplastic syndrome, and acute myeloid leukemia. The clinical significance of this early mutation and the resultant enhanced clonal fitness have been a focus for therapeutic intervention. See related article by Venugopal et al., p. 756.
Alterations of human skin microbiome and expansion of antimicrobial resistance after systemic antibiotics
Authors: Jay-Hyun Jo, Catriona P. Harkins, Nicole H. Schwardt, Jessica A. Portillo, Matthew D. Zimmerman, Claire L. Carter, Md Amir Hossen, Cody J. Peer, Eric C. Polley, Véronique Dartois, William D. Figg, Niki M. Moutsopoulos, Julia A. Segre, Heidi H. Kong
Journal: Science Translational Medicine (2021)

Use of systemic antibiotics induces substantial changes in the microbiome and expansion of antimicrobial resistant bacteria.
Anticipating the ageing trajectories of superheroes in the Marvel cinematic universe
Authors: Sarah T Fox, Natasha Reid, Ida Tornvall, Shavini Weerasekera, Emily Gordon, Ruth E Hubbard
Journal: BMJ (2021)

Ruth Hubbard and colleagues examine the personal traits and health behaviours of five of Marvel9s superheroes and envisage the challenges this extraordinary cohort might experience during ageing
Fine particulate matter components and interstitial lung disease in rheumatoid arthritis
Authors: Naizhuo Zhao, Ziyad Al-Aly, Boyang Zheng, Aaron van Donkelaar, Randall V. Martin, Christian A. Pineau, Sasha Bernatsky
Journal: European Respiratory Journal (2021)

Background Exposure to ambient fine particulate matter with an aerodynamic diameter &lt;2.5 μg·m −3 (PM 2.5 ) is a risk factor for pulmonary and systemic autoimmune diseases; however, evidence on which PM 2.5 chemical components are more harmful is still scant. Our goal is to investigate potential associations between major PM 2.5 components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA). Methods New-onset RA subjects identified from a US healthcare insurance database (MarketScan) were followed for new onset of RA-associated ILD (RA-ILD) from 2011 to 2018. Annual concentrations of ambient PM 2.5 chemical components ( i.e. sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to 1 year before ILD onset or end of study were assigned to subjects based on their core-based statistical area or metropolitan division codes. A novel time-to-event quantile-based g (generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM 2.5 chemical components adjusting for age, sex and prior chronic obstructive pulmonary disease (as a proxy for smoking). Results We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% CI 1.47–1.63) per every decile increase in all seven exposures. Ammonium, mineral dust and black carbon contributed more to ILD risk than the other PM 2.5 components. Conclusion Exposure to components of PM 2.5 , particularly ammonium, increases ILD risk in RA.
A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction
Authors: Jasper Tromp, Wouter Ouwerkerk, Dirk J. van Veldhuisen, Hans L. Hillege, A. Mark Richards, Peter van der Meer, Inder S. Anand, Carolyn S.P. Lam, Adriaan A. Voors
Journal: JACC Heart Failure (2021)
Immunogenic ferroptosis and where to find it?
Authors: Robin Demuynck, Iuliia Efimova, Faye Naessens, Dmitri V Krysko
Journal: Journal for ImmunoTherapy of Cancer (2021)

Ferroptosis is a recently discovered form of regulated cell death that is morphologically, genetically, and biochemically distinct from apoptosis and necroptosis, and its potential use in anticancer therapy is emerging. The strong immunogenicity of (early) ferroptotic cancer cells broadens the current concept of immunogenic cell death and opens up new possibilities for cancer treatment. In particular, induction of immunogenic ferroptosis could be beneficial for patients with cancers resistant to apoptosis and necroptosis. However, ferroptotic cancer cells may be a rich source of oxidized lipids, which contribute to decreased phagocytosis and antigen cross-presentation by dendritic cells and thus may favor tumor evasion. This could explain the non-immunogenicity of late ferroptotic cells. Besides the presence of lactate in the tumor microenvironment, acidification and hypoxia are essential factors promoting ferroptosis resistance and affecting its immunogenicity. Here, we critically discuss the crucial mediators controlling the immunogenicity of ferroptosis that modulate the induction of antitumor immunity. We emphasize that it will be necessary to also identify the tolerogenic (ie, immunosuppressive) nature of ferroptosis, which can lead to tumor evasion.
Guidelines on how to manage basal cell carcinoma in adults
Journal: British Journal of Dermatology (2021)

Basal cell carcinoma (BCC) is the most common type of skin cancer. It is usually caused by long‐term ultraviolet light exposure from the sun and/or sunbeds. It is particularly common on the sun‐exposed areas of the skin, especially in people with lightly pigmented skin types. It can also occur as part of rare inherited conditions (such as Gorlins syndrome). It does not generally spread internally to other parts of the body but if left untreated will slowly grow and can cause significant disfiguring damage.
Structural alignment guides oriented migration and differentiation of endogenous neural stem cells for neurogenesis in brain injury treatment
Authors: Yi Chai, He Zhao, Shuhui Yang, Xiaohan Gao, Zheng Cao, Jiaju Lu, Qingling Sun, Wei Liu, Zhe Zhang, Junyi Yang, Xuelin Wang, Tuoyu Chen, Xiangdong Kong, Antonios G. Mikos, Xiaohua Zhang, Yuqi Zhang, Xiumei Wang
Journal: Biomaterials (2021)
Why may citrate sodium significantly increase the effectiveness of transarterial chemoembolization in hepatocellular carcinoma?
Authors: Philippe Icard, Luca Simula, Zherui Wu, Diana Berzan, Philippe Sogni, Anthony Dohan, Raphael Dautry, Antoine Coquerel, Hubert Lincet, Mauro Loi, David Fuks
Journal: Drug Resistance Updates (2021)
mTEC damage risks immune recovery
Authors: Yousuke Takahama
Journal: The Journal of Experimental Medicine (2021)

Whether autologous hematopoietic stem cell transplantation is free from graft-versus-host disease is controversial. Alawam et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211239) now demonstrate that prolonged damage in thymic medullary epithelial cells causes the failure in self-tolerance in newly generated T cells and provokes post-transplant autoimmunity.
How Compensatory Mechanisms and Adaptive Rewiring Have Shaped Our Understanding of Therapeutic Resistance in Cancer
Authors: Johann S. Bergholz, Jean J. Zhao
Journal: Cancer Research (2021)

Abstract Therapeutic resistance to targeted therapies by tumor cells is a common and serious problem in the clinic. Increased understanding of the molecular mechanisms that underly resistance is necessary for the rational design and improvement of effective pharmacologic treatment strategies. The landmark study by O'Reilly and colleagues published in Cancer Research in 2006 provided valuable insights into nongenomic adaptive rewiring and compensatory mechanisms responsible for mediating resistance to targeted inhibition of the PI3K–AKT–mTOR pathway, and how tumor cells regulate signaling pathways via negative feedback loops. These findings have proven fundamental for guiding current efforts to develop effective combination treatments and provided a blueprint for research studies aimed at understanding the intricacies of cellular signaling. See related article by O'Reilly and colleagues, Cancer Res 2006;66:1500–8
Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials
Authors: Qingyang Shi, Yang Wang, Qiukui Hao, Per Olav Vandvik, Gordon Guyatt, Jing Li, Zhe Chen, Shishi Xu, Yanjiao Shen, Long Ge, Feng Sun, Ling Li, Jiajie Yu, Kailei Nong, Xinyu Zou, Siyi Zhu, Cong Wang, Shengzhao Zhang, Zhi Qiao, Zhongyu Jian, Ya Li, Xinyi Zhang, Kerun Chen, Furong Qu, Yuan Wu, Yazhou He, Haoming Tian, Sheyu Li
Journal: The Lancet (2021)
Response by Trifan et al to Letter Regarding Article, “Efficacy and Safety of Using Dual Versus Monotherapy Antiplatelet Agents in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials”
Authors: Gabriela Trifan, Philip B. Gorelick, Fernando D. Testai
Journal: Circulation (2021)

In Response:We thank Hu et al for taking the time to read our article and for their comments.The authors raise 3 main concerns.The first one is related to heterogeneity and its effect on the reliability of our results.In their letter, they cite the Cochrane Handbook for Systematic Reviews of Interventions and indicate that, by excluding the study from Yi et al, the heterogeneity decreases from 57% (as we reported) to 48%, with a P value for the overall effect of 0.06.Based on this observation, they conclude that "compared to monotherapy of aspirin, short term (≤30 days) treatment with aspirin plus clopidogrel did not significantly decrease the risk of stroke recurrence." Several thresholds have been used to measure heterogeneity.The Cochrane Handbook for Systematic Reviews and Interventions referenced by Hu et al uses overlapping ranges.To this end, heterogeneity (as measured by the I 2 ) may be not important (0% to 40%), moderate (30% to 60%), substantial (50% to 90%), or considerable (70% to 100%). 1 Based on these ranges, the heterogeneity of 57% estimated for the comparison of dual antiplatelet therapy with aspirin plus clopidogrel to aspirin monotherapy for the prevention of recurrent stroke falls between moderate and substantial, not considerable as Hu et al indicate in their letter.As indicated in our article, however, we used the benchmarks suggested by Higgins and Thompson.These were also included in the American Heart Association Methodological Standards for In comparison with the Cochrane referenced by the authors, Higgins and Thompson recommend using I 2 threshold values of 25%, 50%, and 75% for low, moderate, and high degrees of inconsistency or statistical heterogeneity, respectively.3 It is important to bear in mind that arbitrary I 2 thresholds, although convenient for discussing results, are not meant to be used to draw dogmatic
Personalized DNA Vaccine Tamps Down HCC
Journal: Cancer Discovery (2021)

In a phase I/II trial, the personalized DNA vaccine GNOS-PV02 combined with pembrolizumab and plasmid-encoded IL12 yielded a response rate of 25% in patients with advanced hepatocellular carcinoma. The vaccine encoded up to 40 patient-specific neoantigens and had a manageable safety profile.
Respiratory tract infection and risk of bleeding in oral anticoagulant users: self-controlled case series
Authors: Haroon Ahmed, Heather Whitaker, Daniel Farewell, Julia Hippisley-Cox, Simon Noble
Journal: BMJ (2021)

Abstract Objective To estimate the association between untreated, community acquired, respiratory tract infections and bleeding in oral anticoagulant users. Design Self-controlled case series. Setting General practices in England contributing data to the Clinical Practice Research Datalink GOLD. Participants 1208 adult users of warfarin or direct oral anticoagulants with a general practice or hospital admission record of a bleeding event between January 2010 and December 2019, and a general practice record of a consultation for a community acquired respiratory tract infection for which immediate antibiotics were not prescribed (that is, untreated). Main outcome measures Relative incidence of major bleeding and clinically relevant non-major bleeding in the 0-14 days after an untreated respiratory tract infection, compared to unexposed time periods. Results Of 1208 study participants, 58% (n=701) were male, median age at time of first bleed was 79 years (interquartile range 72-85), with a median observation period of 2.4 years (interquartile range 1.3-3.8). 292 major bleeds occurred during unexposed time periods and 41 in the 0-14 days after consultation for a respiratory tract infection. 1003 clinically relevant non-major bleeds occurred during unexposed time periods and 81 in the 0-14 days after consultation for a respiratory tract infection. After adjustment for age, season, and calendar year, the relative incidence of major bleeding (incidence rate ratio 2.68, 95% confidence interval 1.83 to 3.93) and clinically relevant non-major bleeding (2.32, 1.82 to 2.94) increased in the 0-14 days after an untreated respiratory tract infection. Findings were robust to several sensitivity analyses and did not differ by sex or type of oral anticoagulant. Conclusions This study observed a greater than twofold increase in the risk of bleeding during the 0-14 days after an untreated respiratory tract infection. These findings have potential implications for how patients and clinicians manage oral anticoagulant use during an acute intercurrent illness and warrant further investigation into the potential risks and how they might be mitigated.
CSF3R T618I Collaborates with RUNX1-RUNX1T1 to Expand Human Haematopoietic Stem and Progenitor Cells
Authors: Anja Swoboda, Roland Windisch, Paul Kerbs, Enric Redondo Monte, Johannes W. Bagnoli, Linping Chen-Wichmann, Alessandra Caroleo, Monica Cusan, Wolfgang Enard, Tobias Herold, Christian Wichmann, Philipp A. Greif
Journal: Blood (2021)
Sizes, ratios, approximations: On what and how the ANS represents
Authors: Brian Ball
Journal: Behavioral and Brain Sciences (2021)

Clarke and Beck propose that the approximate number system (ANS) represents rational numbers. The evidence cited supports only the view that it represents ratios (and positive integers). Rational numbers are extensive magnitudes (i.e., sizes), whereas ratios are intensities. It is also argued that WHAT a system represents and HOW it does so are not as independent of one another as the authors assume.
NIMG-25. IMPROVING THE NONINVASIVE CLASSIFICATION OF GLIOMA GENETIC SUBTYPE WITH DEEP LEARNING AND DIFFUSION-WEIGHTED IMAGING
Authors: Julia Cluceru, Joanna Phillips, Annette Molinaro, Yannet Interian, Tracy Luks, Paula Alcaide-Leon, Devika Nair, Marisa LaFontaine, Anny Shai, Pranathi Chunduru, Valentina Pedoia, Javier Villanueva-Meyer, Susan Chang, Janine Lupo
Journal: Neuro-Oncology (2021)

Abstract In contrast to the WHO 2016 guidelines that use genetic alterations to further stratify patients within a designated grade, new recommendations suggest that IDH mutation status, followed by 1p19q-codeletion, should be used before grade when differentiating gliomas. Although most gliomas will be resected and their tissue evaluated with genetic profiling, non-invasive characterization of genetic subgroup can benefit patients where surgery is not otherwise advised or a fast turn-around is required for clinical trial eligibility. Prior studies have demonstrated the utility of using anatomical images and deep learning to distinguish either IDH-mutant from IDH-wildtype tumors or 1p19q-codeleted from non-codeleted lesions separately, but not combined or using the most recent recommendations for stratification. The goal of this study was to evaluate the effects of training strategy and incorporation of Apparent Diffusion Coefficient (ADC) maps from diffusion-weighted imaging on predicting new genetic subgroups with deep learning. Using 414 patients with newly-diagnosed glioma (split 285/50/49 training/validation/test) and optimized training hyperparameters, we found that a 3-class approach with T1-post-contrast, T2-FLAIR, and ADC maps as inputs achieved the best performance for molecular subgroup classification, with overall accuracies of 86.0%[CI:0.839,1.0], 80.0%[CI:0.720,1.0], and 85.7%[CI:0.771,1.0] on training, validation, and test sets, respectively, and final test class accuracies of 95.2%(IDH-wildtype), 88.9%(IDH-mutated,1p19qintact), and 60%(IDHmutated,1p19q-codeleted). Creating an RGB-color image from 3 MRI images and applying transfer learning with a residual network architecture pretrained on ImageNet resulted in an 8% averaged increase in overall accuracy. Although classifying both IDH and 1p19q mutations together was overall advantageous compared with a tiered structure that first classified IDH mutational status, the 2-tiered approach better generalized to an independent multi-site dataset when only anatomical images were used. Including biologically relevant ADC images improved model generalization to our test set regardless of modeling approach, highlighting the utility of incorporating diffusion-weighted imaging in future multi-site analyses of molecular subgroup.
Macrophage-derived CXCL9 and CXCL11, T-cell skin homing, and disease control in mogamulizumab-treated CTCL patients
Authors: Adèle de Masson, Delphine Darbord, Gabor Dobos, Marie Boisson, Marie Roelens, Caroline Ram-Wolff, Charles Cassius, Hélène Le Buanec, Pierre de la Grange, Fanélie Jouenne, Baptiste Louveau, Aurélie Sadoux, Jean-David Bouaziz, Anne Marie-Cardine, Martine Bagot, Hélène Moins-Teisserenc, Samia Mourah, Maxime Battistella
Journal: Blood (2021)
Hidden biases in germline structural variant detection
Authors: Michael M. Khayat, Sayed Mohammad Ebrahim Sahraeian, Samantha Zarate, Andrew Carroll, Huixiao Hong, Bohu Pan, Leming Shi, Richard A. Gibbs, Marghoob Mohiyuddin, Yuanting Zheng, Fritz J. Sedlazeck
Journal: Genome biology (2021)

Abstract Background Genomic structural variations (SV) are important determinants of genotypic and phenotypic changes in many organisms. However, the detection of SV from next-generation sequencing data remains challenging. Results In this study, DNA from a Chinese family quartet is sequenced at three different sequencing centers in triplicate. A total of 288 derivative data sets are generated utilizing different analysis pipelines and compared to identify sources of analytical variability. Mapping methods provide the major contribution to variability, followed by sequencing centers and replicates. Interestingly, SV supported by only one center or replicate often represent true positives with 47.02% and 45.44% overlapping the long-read SV call set, respectively. This is consistent with an overall higher false negative rate for SV calling in centers and replicates compared to mappers (15.72%). Finally, we observe that the SV calling variability also persists in a genotyping approach, indicating the impact of the underlying sequencing and preparation approaches. Conclusions This study provides the first detailed insights into the sources of variability in SV identification from next-generation sequencing and highlights remaining challenges in SV calling for large cohorts. We further give recommendations on how to reduce SV calling variability and the choice of alignment methodology.
102P IMreal Cohort 2: First interim analysis of patient (pt) characteristics and safety data in pts with locally advanced or metastatic NSCLC (aNSCLC) receiving atezolizumab (atezo) under real-world conditions
Authors: N. Girard, S. Popat, S. Shoshkova, S. Fear, J.L. Perez Gracia
Journal: Annals of Oncology (2021)
Transcriptional modification of host cells harboring Toxoplasma gondii bradyzoites prevents IFN gamma-mediated cell death
Authors: Simona Seizova, Ushma Ruparel, Alexandra L. Garnham, Stefanie M. Bader, Alessandro D. Uboldi, Michael J. Coffey, Lachlan W. Whitehead, Kelly L. Rogers, Christopher J. Tonkin
Journal: Cell Host & Microbe (2021)
46MO Promoting functional persistence in solid tumor CAR T-cell therapy: Mesothelin-targeted CAR (M28z1XXPD1DNR) with T-cell intrinsic PD1 dominant negative receptor
Authors: P.S. Adusumilli, A.M. Amador, N. Chintala, Z. Hou, M. Offin, J. Pineda, B. Senechal, H.T. Quach, R. Bellis, S. Banerjee, J. Saini, A. Zhu, R.M. Daly, M. Sadelain, I. Rivière, M. Zauderer, R. O'Cearbhaill
Journal: Annals of Oncology (2021)