tbuckley/cabot-search huggingface dataset:
A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy
Authors: Ruby Maharjan, Jeong Uk Choi, Seho Kweon, Rudra Pangeni, Na Kyeong Lee, Seong Jin Park, Kwan-Young Chang, Jin Woo Park, Youngro Byun
Journal: Biomaterials (2021)

In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment.
Reproductive value and the evolution of altruism
Authors: António M.M. Rodrigues, Andy Gardner
Journal: Trends in Ecology & Evolution (2021)

Altruism is favored by natural selection provided that it delivers sufficient benefits to relatives. An altruist's valuation of her relatives depends upon the extent to which they carry copies of her genes - relatedness - and also on the extent to which they are able to transmit their own genes to future generations - reproductive value. However, although relatedness has received a great deal of attention with regard to altruism, reproductive value has been surprisingly neglected. We review how reproductive value modulates patterns of altruism in relation to individual differences in age, sex, and general condition, and discuss how social partners may manipulate each other's reproductive value to incentivize altruism. This topic presents opportunities for tight interplay between theoretical and empirical research.
Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist
Authors: Martin Bossart, Michael Wagner, Ralf Elvert, Andreas Evers, Thomas Hübschle, Tim Kloeckener, Katrin Lorenz, Christine Moessinger, Olof Eriksson, Irina Velikyan, Stefan Pierrou, Lars Johansson, Gabriele Dietert, Yasmin Dietz-Baum, Thomas Kissner, Irene Nowotny, Christine Einig, Christelle Jan, Faiza Rharbaoui, Johann Gassenhuber, Hans-Peter Prochnow, Inoncent Agueusop, Niels Porksen, William B. Smith, Almut Nitsche, Anish Konkar
Journal: Cell Metabolism (2021)

Unimolecular triple incretins, combining the activity of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG), have demonstrated reduction in body weight and improved glucose control in rodent models. We developed SAR441255, a synthetic peptide agonist of the GLP-1, GCG, and GIP receptors, structurally based on the exendin-4 sequence. SAR441255 displays high potency with balanced activation of all three target receptors. In animal models, metabolic outcomes were superior to results with a dual GLP-1/GCG receptor agonist. Preclinical in vivo positron emission tomography imaging demonstrated SAR441255 binding to GLP-1 and GCG receptors. In healthy subjects, SAR441255 improved glycemic control during a mixed-meal tolerance test and impacted biomarkers for GCG and GIP receptor activation. Single doses of SAR441255 were well tolerated. The results demonstrate that integrating GIP activity into dual GLP-1 and GCG receptor agonism provides improved effects on weight loss and glycemic control while buffering the diabetogenic risk of chronic GCG receptor agonism.
Abstract 12789: Development of the Tool to EMPOwer Surrogate Decision Makers of Comatose Survivors of Cardiac Arrest
Authors: Sarah M Perman, Bonnie J Siry-Bove, Benjamin Abella, Stacie L Daugherty, Edward Havranek, Dan D Matlock
Journal: Circulation (2021)

Introduction: Surrogate decision makers (SDMs) for comatose survivors of cardiac arrest are often charged with making time-sensitive complex decisions with regard to life-sustaining therapies in a sudden critical illness. We describe the development of a decision aid for SDMs of comatose survivors of cardiac arrest. Methods: Applying recommendations from the International Patient Decision Aid Standards, we developed this decision aid iteratively with the purpose to educate families on post-arrest care and evidence based decision-making. We obtained feedback from stakeholders, including surrogate decision makers, patients, caregivers, nurses and physicians, in focus groups and semi-structured interviews. Results: Informed by interviews with SDMs and the AHA Guidelines, we designed a prototype of the decision aid. Each iteration resulted in a refined version of the aid (Figure). Step 1 included feedback from the Shared Decision-Making Core at the Adult and Child Consortium on Outcomes Research and Delivery Science (ACCORDS). Step 2 incorporated feedback from the ACCORDS Community Engagement Stakeholder group. Step 3 consisted of 10 semi-structured interviews with informal caregivers and patient pairs within the Advanced Heart Failure or Seniors clinics. The document was then reviewed by a team of expert cardiac arrest stakeholders. The aid includes key definitions, a timeline of post-arrest care, factors that support decisions to discontinue or pursue life sustaining therapies, commonly asked questions and an illustration of a patient undergoing post-arrest treatment. The decision aid, entitled T ool to EMPO wer (TEMPO) Surrogate Decision Makers, is written at a 7 th grade reading level. Conclusions: Through a robust iterative process, we designed a decision aid for SDMs of comatose survivors of cardiac arrest. The aid is intended to support the decision to pursue or forego further life-sustaining therapy and to be informative about post-arrest care.
Editorial Board
Authors: Zuhair Ballas, Iowa City, Iowa Deputy, David Huston, Rachel Miller, New York, N Associate, Andrea Apter, Leonard Philadelphia, Nashville Bacharier, Claus Bachert, Joshua Boyce, Javier Chinen, Raif Geha, Johann Gudjonsson, Ann Arbor, Mich Kenji Kabashima, Corinne Keet, Chapel Hill, Carole Ober, Wanda Phipatanakul, Harald Renz, Marburg Germany, Marc Rothenberg, Cincinnati Ohio, Hirohisa Saito, Stefan Vieths, Langen Germany, Stephan Weidinger
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 14213: Injury Characteristics of Chest Compressions in a Swine Model of Infant Asphyxial Cardiac Arrest Using Either 1.5 inch or 1/3 Anterior-Posterior Diameter Depth Targets
Authors: David D Salcido, Allison C Koller, Ericka L Fink, Robert A Berg, James J Menegazzi
Journal: Circulation (2021)

Background: Current AHA guidelines for the delivery of chest compressions (CC) for infants and children are largely consensus based, and recommended depths of 1.5 inches or 1/3 anterior-posterior chest diameter (APD). It is unclear whether these have equal potential for injury. Objectives: We sought to examine and compare injury characteristics of CC delivered at 1.5 inches or 1/3 APD in an infant-sized model of asphyxial OHCA. Methods: Thirty-six juvenile swine weighing 10.6kg +/- 0.84 (approximating the 50 th percentile for a 12-month-old) were anesthetized, paralyzed, intubated, and mechanically ventilated (FiO2 21%). APD was measured and by two investigators via a sliding T-square. After instrumentation, the endotracheal tube was manually occluded to induce asphyxia, and occlusion was maintained for 9 minutes. Animals with an organized rhythm after 8 minutes 45 seconds of asphyxia received a single, 3-second transthoracic shock to induce ventricular fibrillation. At 9 minutes, each was then randomized to receive CC with a depth of 1.5 inches (Group 1) or 1/3 APD (Group 2), both with a rate of 100 per minute. ALS drugs were administered after 13 minutes, followed by initial defibrillation attempt at 14 minutes. Resuscitation continued until return of spontaneous circulation (ROSC) or 20 minutes of failed resuscitation. Survivors were sacrificed with KCl after 20 minutes of observation. Veterinary staff blinded to group assignment conducted necropsies to assess lung injury, rib fracture, hemothorax, airway bleeding, great vessel dissection, and heart/liver/spleen contusion. Characteristics were compared via Chi-Squared test or Mann-Whitney U-test using an alpha = 0.05. Results: Group 1 had n=18 and Group 2 had n=18 animals. Mean (SD) APD overall was 5.58 (0.22) inches, yielding a mean 1/3 APD depth of 1.86 inches. APD did not differ between groups. ROSC rates did not differ between groups (Group 1: 66.7% vs Group 2: 83.33%; p = 0.248. No injury characteristics differed significantly between groups. Airway bleeding rates were noteworthy though not different between groups (Group 1: 18.8% vs Group 2: 42.1%; p = 0.219). Conclusions: In a swine model of infant OHCA and resuscitation, both CC depth strategies had similar injury characteristics.
Association Between Area-Level Socioeconomic Deprivation and Diabetes Care Quality in US Primary Care Practices
Authors: Shaheen Shiraz Kurani, Michelle A. Lampman, Shealeigh A. Funni, Rachel E. Giblon, Jonathan W. Inselman, Nilay D. Shah, Summer Allen, David Rushlow, Rozalina G. McCoy
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Diabetes management operates under a complex interrelationship between behavioral, social, and economic factors that affect a patient's ability to self-manage and access care. <h3>Objective</h3> To examine the association between 2 complementary area-based metrics, area deprivation index (ADI) score and rurality, and optimal diabetes care. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed the electronic health records of patients who were receiving care at any of the 75 Mayo Clinic or Mayo Clinic Health System primary care practices in Minnesota, Iowa, and Wisconsin in 2019. Participants were adults with diabetes aged 18 to 75 years. All data were abstracted and analyzed between June 1 and November 30, 2020. <h3>Main Outcomes and Measures</h3> The primary outcome was the attainment of all 5 components of the D5 metric of optimal diabetes care: glycemic control (hemoglobin A<sub>1c</sub>&lt;8.0%), blood pressure (BP) control (systolic BP &lt;140 mm Hg and diastolic BP &lt;90 mm Hg), lipid control (use of statin therapy according to recommended guidelines), aspirin use (for patients with ischemic vascular disease), and no tobacco use. The proportion of patients receiving optimal diabetes care was calculated as a function of block group–level ADI score (a composite measure of 17 US Census indicators) and zip code–level rurality (calculated using Rural-Urban Commuting Area codes). Odds of achieving the D5 metric and its components were assessed using logistic regression that was adjusted for demographic characteristics, coronary artery disease history, and primary care team specialty. <h3>Results</h3> Among the 31 934 patients included in the study (mean [SD] age, 59 [11.7] years; 17 645 men [55.3%]), 13 138 (41.1%) achieved the D5 metric of optimal diabetes care. Overall, 4090 patients (12.8%) resided in the least deprived quintile (quintile 1) of block groups and 1614 (5.1%) lived in the most deprived quintile (quintile 5), while 9193 patients (28.8%) lived in rural areas and 2299 (7.2%) in highly rural areas. The odds of meeting the D5 metric were lower for individuals residing in quintile 5 vs quintile 1 block groups (odds ratio [OR], 0.72; 95% CI, 0.67-0.78). Patients residing in rural (OR, 0.84; 95% CI, 0.73-0.97) and highly rural (OR, 0.81; 95% CI, 0.72-0.91) zip codes were also less likely to attain the D5 metric compared with those in urban areas. <h3>Conclusions and Relevance</h3> This cross-sectional study found that patients living in more deprived and rural areas were significantly less likely to attain high-quality diabetes care compared with those living in less deprived and urban areas. The results call for geographically targeted population health management efforts by health systems, public health agencies, and payers.
Mature dendritic cell-derived dendrosomes swallow oxaliplatin-loaded nanoparticles to boost immunogenic chemotherapy and tumor antigen-specific immunotherapy
Authors: Xing Chen, Xiang Ling, Jiaxuan Xia, Ying Zhu, Longlong Zhang, Yuwei He, Anni Wang, Guolong Gu, Bo Yin, Jianxin Wang
Journal: Bioactive Materials (2021)

The cytomembrane-derived delivery platform represents a promising biomimetic strategy in oncotherapy. To achieve durable and reliable tumor inhibition, mature dendrosomes (mDs), which were isolated from bone marrow-derived dendritic cells undergoing CT26 tumor antigen (TA) stimulation, were fused with redox-responsive nanoparticles (NPs) that were composed of poly(disulfide ester amide) polymers with an intensified disulfide density and hydrophobic oxaliplatin (OXA) prodrugs with the ability to potentiate immunogenicity.
Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts
Authors: Elin Almstedt, Emil Rosén, Marleen Gloger, Rebecka Stockgard, Neda Hekmati, Katarzyna Koltowska, Cecilia Krona, Sven Nelander
Journal: Neuro-Oncology (2021)

Abstract Background Patient-derived xenograft (PDX) models of glioblastoma (GBM) are a central tool for neuro-oncology research and drug development, enabling the detection of patient-specific differences in growth, and in vivo drug response. However, existing PDX models are not well suited for large-scale or automated studies. Thus, here, we investigate if a fast zebrafish-based PDX model, supported by longitudinal, AI-driven image analysis, can recapitulate key aspects of glioblastoma growth and enable case-comparative drug testing. Methods We engrafted 11 GFP-tagged patient-derived GBM IDH wild-type cell cultures (PDCs) into 1-day-old zebrafish embryos, and monitored fish with 96-well live microscopy and convolutional neural network analysis. Using light-sheet imaging of whole embryos, we analyzed further the invasive growth of tumor cells. Results Our pipeline enables automatic and robust longitudinal observation of tumor growth and survival of individual fish. The 11 PDCs expressed growth, invasion and survival heterogeneity, and tumor initiation correlated strongly with matched mouse PDX counterparts (Spearman R = 0.89, p &amp;lt; 0.001). Three PDCs showed a high degree of association between grafted tumor cells and host blood vessels, suggesting a perivascular invasion phenotype. In vivo evaluation of the drug marizomib, currently in clinical trials for GBM, showed an effect on fish survival corresponding to PDC in vitro and in vivo marizomib sensitivity. Conclusions Zebrafish xenografts of GBM, monitored by AI methods in an automated process, present a scalable alternative to mouse xenograft models for the study of glioblastoma tumor initiation, growth, and invasion, applicable to patient-specific drug evaluation.
Impact of Cytokine Inhibitor Therapy on the Prevalence, Seroconversion Rate, and Longevity of the Humoral Immune Response Against <scp>SARS</scp>–<scp>CoV</scp>‐2 in an Unvaccinated Cohort
Authors: David Simon, Koray Tascilar, Arnd Kleyer, Filippo Fagni, Gerhard Krönke, Christine Meder, Peter Dietrich, Till Orlemann, Thorsten Kliem, Johanna Mößner, Anna‐Maria Liphardt, Verena Schönau, Daniela Bohr, Louis Schuster, Fabian Hartmann, Moritz Leppkes, Andreas Ramming, Milena Pachowsky, Florian Schuch, Monika Ronneberger, Stefan Kleinert, Axel J. Hueber, Karin Manger, Bernhard Manger, Raja Atreya, Carola Berking, Michael Sticherling, Markus F. Neurath, Georg Schett
Journal: Arthritis & Rheumatology (2021)

To investigate the impact of biologic disease-modifying antirheumatic drug (bDMARD) treatment on the prevalence, seroconversion rate, and longevity of the humoral immune response against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs).
Harmonization after the GDPR? Divergences in the rules for genetic and health data sharing in four member states and ways to overcome them by EU measures: Insights from Germany, Greece, Latvia and Sweden
Authors: Fruzsina Molnár-Gábor, Julian Sellner, Sophia Pagil, Santa Slokenberga, Olga Tzortzatou-Nanopoulou, Katarina Nyström
Journal: Seminars in Cancer Biology (2021)

The EU member states' healthcare and health-related research sectors are both characterized by an emerging infrastructural coalescence on a national and European level. The culmination of this coalescence is the planned creation of a European Health Data Space, an EU-wide infrastructure for the processing of personal data for healthcare and for secondary uses such as scientific research. In contrast to growing technical interoperability, the legal framework for such integration is not yet defined in detail, particularly with regard to data protection law. Its development is accompanied by discussions about divergent member state implementations of the EU General Data Protection Regulation (GDPR) that affect data sharing between healthcare and scientific research actors and across various sectors driven by divergent processing purposes. The article presents four member states' main rules on data sharing based on the respective provision of the GDPR in six health-related contexts regarding data sharing across the healthcare and research sector and between the main actors of those sectors. The striking differences are then evaluated from the perspective of their factual effect on European data sharing depending on the legal characteristics of the GDPR provisions they rely on. Against this backdrop, the planned regulatory measures for the setup of the European Health Data Space are introduced and evaluated with regard to further harmonization between member states' laws and possibilities to overcome divergences in data protection rules relevant for European data sharing. The results of the analysis point to the conclusion that the destructive effect of divergent member state rules depends on the legal qualification of the EU provisions they rely on and that this qualification also determines which further EU regulatory measure would be the most effective to set the framework for the European Health Data Space.
Attenuated response to SARS-CoV-2 vaccine in patients with asymptomatic precursor stages of multiple myeloma and Waldenstrom macroglobulinemia
Authors: Yoshinobu Konishi, Romanos Sklavenitis-Pistofidis, Hong Yue, Federico Ferrari, Robert A Redd, Elizabeth D Lightbody, Massimiliano Russo, Jacqueline Perry, Erica Horowitz, Anna V Justis, Nader A Shayegh, Alexandra Savell, Julia Prescott, Shohreh Varmeh, Radosław P Nowak, Mark Hamilton, Daniel Auclair, Catherine R Marinac, Lorenzo Trippa, Eric S Fischer, Irene M Ghobrial
Journal: Cancer Cell (2021)
Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial
Authors: Mahir Karakas, Ibrahim Akin, Christoph Burdelski, Peter Clemmensen, Hanno Grahn, Dominik Jarczak, Mirjam Keßler, Paulus Kirchhof, Ulf Landmesser, Susanne Lezius, Diana Lindner, Alexandre Mebazaa, Axel Nierhaus, Anil Ocak, Wolfgang Rottbauer, Christoph Sinning, Carsten Skurk, Gerold Söffker, Dirk Westermann, Antonia Zapf, Elvin Zengin, Tanja Zeller, Stefan Kluge
Journal: The Lancet Respiratory Medicine (2021)
Out-of-Pocket Costs Among Patients With a New Cancer Diagnosis Enrolled in High-Deductible Health Plans vs Traditional Insurance
Authors: Sue J. Fu, Liam Rose, Aaron J. Dawes, Lisa M. Knowlton, Kathryn J. Ruddy, Arden M. Morris
Journal: JAMA Network Open (2021)

The financial burden of a cancer diagnosis is increasing rapidly with advances in cancer care. Simultaneously, more individuals are enrolling in high-deductible health plans (HDHPs) vs traditional insurance than ever before.To characterize the out-of-pocket costs (OOPCs) of cancer care for individuals in HDHPs vs traditional insurance plans.This retrospective cohort study used the administrative claims data of a single national insurer in the US for 134 826 patients aged 18 to 63 years with a new diagnosis of breast, colorectal, lung, or other cancer from 2008 to 2018 with 24 months or more of continuous enrollment. Propensity score matching was performed to create comparator groups based on the presence or absence of an incident cancer diagnosis.A new cancer diagnosis and enrollment in an HDHP vs a traditional health insurance plan.The primary outcome was OOPCs among individuals with breast, colon, lung, or all other types of cancer combined compared with those with no cancer diagnosis. A triple difference-in-differences analysis was performed to identify incremental OOPCs based on cancer diagnosis and enrollment in HDHPs vs traditional plans.After propensity score matching, 134 826 patients remained in each of the cancer (73 572 women [55%]; median age, 53 years [IQR, 46-58 years]; 110 071 non-Hispanic White individuals [82%]) and noncancer (66 619 women [49%]; median age, 53 years [IQR, 46-59 years]; 105 023 non-Hispanic White individuals [78%]) cohorts. Compared with baseline costs of medical care among individuals without cancer, a breast cancer diagnosis was associated with the highest incremental OOPC ($714.68; 95% CI, $664.91-$764.45), followed by lung ($475.51; 95% CI, $340.16-$610.86), colorectal ($361.41; 95% CI, $294.34-$428.48), and all other types of cancer combined ($90.51; 95% CI, $74.22-$106.79). Based on the triple difference-in-differences analysis, compared with patients without cancer enrolled in HDHPs, those with breast cancer paid $1683.36 in additional yearly OOPCs (95% CI, $1576.66-$1790.07), those with colorectal cancer paid $1420.06 more (95% CI, $1232.31-$1607.80), those with lung cancer paid $467.25 more (95% CI, $130.13-$804.37), and those with other types of cancer paid $550.87 more (95% CI, $514.75-$586.99).Patients with cancer and private insurance experienced sharp increases in OOPCs compared with those without cancer, which was amplified among those with HDHPs. These findings illustrate the degree to which HDHPs offer poorer protection than traditional insurance against unexpected health care expenses. Coupled with the increasing cost of cancer care, higher cost sharing in the form of increasing enrollment in HDHPs requires further research on the potential clinical consequences through delayed or foregone care.