tbuckley/cabot-search huggingface dataset:
Abstract P046: Psychosocial Measures In Relation To Smartwatch Device Alerts For Atrial Fibrillation Detection Post Stroke: The Pulsewatch Study
Authors: Andreas Filippaios, Khanh-van T Tran, Jordy Mehawej, Eric Ding, Jane Saczynski, Darleen Lessard, Tenes Paul, Edith Mensah Otabil, Kamran Noorishirazi, Syed Naeem, Shiksha Joshi, Apurv Soni, David D McManus
Journal: Circulation (2022)

Background: Atrial fibrillation (AF) is a major stroke risk factor and rhythm monitoring post stroke is recommended. Wearable smartwatches with different device alert systems have been increasingly popular. Anxiety and perceived confidence in physicians, particularly in older stroke survivors, in relation to alerts delivered from AF detection devices remain to be elucidated. Objectives: Assess the associations between smartwatch alerts for detected atrial fibrillation in older post stroke patients and self-reported anxiety and perceived confidence in physicians. Methods: Data were used from Phase I of the Pulsewatch study, a randomized controlled trial, which enrolled patients (≥50 years) from the UMass Memorial Health System with a history of a stroke or transient ischemic attack (TIA), CHA 2 DS 2 -VASc ≥ 2 and no contraindications to anticoagulation. Intervention participants wore a cardiac patch monitor, a smartwatch, and were given a smartphone installed with the Pulsewatch applications, while control participants only wore the cardiac patch monitor for 14 days. Intervention participants were grouped into those receiving at least one alert versus those who did not receive any alerts from the smartwatch. Generalized Anxiety Disorder-7 Scale and Perceived Efficacy in Patient-Physician Interactions Questionnaire were utilized at baseline and 14 days to assess anxiety and perceived confidence in physicians, respectively. Logistic regression was used to examine anxiety and perceived confidence in physicians in relation to alerts amongst smartwatch users. Results: A total of 68 participants (on average 65.2 ± 9.2 years of age, 41.2% [28 of 68] were women, 83.8% [57 of 68] were non-Hispanic white) were included in the intervention arm; 10 of which received at least one alert. Reception of alerts was not significantly associated with increased anxiety (adjusted OR [aOR] 0.98, 95% CI 0.13 - 7.6) or decreased perceived confidence in physicians (aOR 1.86, 95% CI 0.26 - 13.4), adjusting for the corresponding baseline outcome. Conclusions: Our study shows that smartwatch devices prescribed for AF detection in stroke survivors are not significantly associated with increased anxiety or decreased perceived confidence in physicians. Further studies are needed to explore their potential as methods for AF monitoring in older patients post stroke.
Abstract P141: Infant Mortality Risk In Hypertensive Disorders Of Pregnancy
Authors: Angela M Malek, Dulaney A Wilson, Julio Mateus, Tanya N Turan, Daniel T Lackland, Kelly J Hunt
Journal: Circulation (2022)

Introduction: Hypertensive disorders of pregnancy (HDP) increase the risk of infant and maternal morbidity and mortality, disproportionately affecting racial and ethnic minority groups. Less is known about disparities in infant mortality by mother’s HDP status. We assessed the relationships between HDP and pre-pregnancy hypertension and other pregnancy and delivery characteristics with infant mortality. Methods: This retrospective cohort study included 667,359 live, singleton deliveries (mother’s race/ethnicity: non-Hispanic White [NHW; 56.5%], non-Hispanic Black [NHB; 32.2%)], Hispanic [9.0%], other race/ethnicity [2.2%]) in South Carolina (2004-2016) to women aged 12-49 years. HDP (pre-eclampsia, eclampsia, gestational hypertension) and pre-pregnancy hypertension were defined by hospitalization/emergency department (ED) visit data or birth certificates. Infant mortality within one year (n=2,431) was defined by death certificates. Logistic regression models controlled for covariates. Results: Deliveries to women with pre-pregnancy hypertension with superimposed HDP (2.1%), HDP (16.9%), pre-pregnancy hypertension without superimposed HDP (0.3%), and neither condition (80.6%) were described. Infant mortality was increased for women with HDP with and without pre-pregnancy hypertension. Also associated with higher odds of infant mortality were NHB mothers, with high school education or less, Medicaid, higher pre-pregnancy BMI, no prenatal care, increasing number of prior pregnancies, prior Cesarean section, prior preterm birth, and women smoking during pregnancy; with the odds lower for increasing maternal age, Hispanic mothers, and female sex of baby. Discussion: The odds of infant mortality were increased 48% in women with HDP and 83% in women with both HDP and pre-pregnancy hypertension than women with neither condition after adjusting for pregnancy and delivery characteristics. Future studies are needed to identify social or other factors contributing to differences.
Imaging of Tumor Hypoxia With 18F-EF5 PET/MRI in Cervical Cancer
Authors: Sara I. Narva, Marko P. Seppänen, Juho R.H. Raiko, Sarita J. Forsback, Katri J. Orte, Johanna M. Virtanen, Johanna Hynninen, Sakari Hietanen
Journal: Clinical Nuclear Medicine (2021)

The aim of this study was to evaluate the distribution of hypoxia using 18F-EF5 as a hypoxia tracer in cervical cancer patients with PET/MRI. We investigated the association between this 18F-EF5-PET tracer and the immunohistochemical expression of endogenous hypoxia markers: HIF1α, CAIX, and GLUT1.Nine patients with biopsy-proven primary squamous cell cervix carcinoma (FIGO 2018 radiological stages IB1-IIIC2r) were imaged with dual tracers 18F-EF5 and 18F-FDG using PET/MRI (Int J Gynaecol Obstet. 2019;145:129-135). 18F-EF5 images were analyzed by calculating the tumor-to-muscle ratio to determine the hypoxic tissue (T/M ratio >1.5) and further hypoxic subvolume (HSV) and percentage hypoxic area. These 18F-EF5 hypoxic parameters were correlated with the size and localization of tumors in 18F-FDG PET/MRI and the results of hypoxia immunohistochemistry.All primary tumors were clearly 18F-FDG and 18F-EF5 PET positive and heterogeneously hypoxic with multiple 18F-EF5-avid areas in locally advanced cancer and single areas in clinically stage I tumors. The location of hypoxia was detected mainly in the periphery of tumor. Hypoxia parameters 18F-EF5 max T/M ratio and HSV in primary tumors correlated independently with the advanced stage (P = 0.036 and P = 0.040, respectively), and HSV correlated with the tumor size (P = 0.027). The location of hypoxia in 18F-EF5 imaging was confirmed with a higher hypoxic marker expression HIF1α and CAIX in tumor fresh biopsies.The 18F-EF5 imaging has promising potential in detecting areas of tumor hypoxia in cervical cancer.
Abstract 11445: Safety and Efficacy of Cryoballoon Ablation for Atrial Fibrillation Performed at Community Hospitals with Low to Medium Case Numbers: Acute and First Long Term Results of The German "Regional" Registry
Authors: Jochen Michaelsen, Ulli Parade, Hansjoerg Bauerle, Klaus-Dieter Winter, Ulrich Rauschenbach, Karl Mischke, Carl Schaefer, Klaus-Juergen Gutleben, Tobias Willich, Ole-Alexander A Breithardt, Stefan Middendorf, Rainer Grove, Joerg Mosa, Joachim Krug, Rainer Hoffmann
Journal: Circulation (2021)

Introduction: Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is a guideline recommended treatment for symptomatic paroxysmal and persistent atrial fibrillation. Little is known on performance data of CBA in low to medium volume hospitals. Hypothesis: To determine safety and efficacy of PVI using CBA performed at community hospitals with limited annual case numbers. Methods: This prospective registry included 1004 consecutive patients (pts) who had CBA performed for symptomatic paroxysmal (n=563) or persistent AF (n=441) at 20 hospitals, each with &lt;100 PVI / year. CBA procedures were performed according to local standards. Procedural data, efficacy and complication rates were determined. Results: The mean number of CBA / year / center was 59±25. CBA was performed by a total of 22 operators (1.1/center), 12/20 operators were board certified for invasive electrophysiology. Average procedure time was 90.1±31.6 min, fluoroscopy time was 19.2±11.4 min. Isolation of all pulmonary veins was reached in 97.9% of pts, the most frequent reason for not achieving complete isolation was development of phrenic nerve palsy (PNP). No hospital deaths were observed. 2 pts (0.2%) suffered a clinical stroke. Pericardial effusion occurred in 6 pts (0.6%), 2 (0.2%) required pericardial drainage. Vascular complications occurred in 24 pts (2.4%), 2 pts (0.2%) underwent vascular surgery. PNP occurred in 48 pts (4.8%) and persisted up to discharge in 6 pts (0.6%). The results were independant for board certification status of the operator and independant for the number of enrolled patients per center (if &gt; or &lt; 60 pts). Follow up data at 12 months were available from 14 centers and 75,2 % of their pts so far. Recurrent atrial arrhythmias after a 3 months blanking period were found in 177/536 pts. (33%), 152 (85,9%) were symptomatic. 71 (40%) pts with recurrence were still on antiarrhythmic drugs, 42 (23.7%) underwent Re-PVI. One phrenic nerve palsy persisted, there were no further access site complications and no esophago-atrial fistula. Conclusions: PVI for paroxysmal or persistant AF using CBA can be safely performed at community hospitals with high acute efficacy, low complication rates and good recurrence data after 1 year despite low and moderate annual case numbers.
CLINICAL MANIFESTATION AND PROGNOSIS OF DIFFERENT CARDIOMYOPATHIES ON THE BASE OF GENETIC BACKGROUND (GEN-PHEN)
Authors: Alessia Paldino, Matteo Dal Ferro, Davide Stolfo, Marta Gigli, Kristen Medo, Sharon Louise Graw, Matthew R. Taylor, Ilaria Gandin, Gianfranco Sinagra, Luisa Mestroni
Journal: Journal of the American College of Cardiology (2022)
CTNI-01. A PHASE 1-2 CLINICAL TRIAL OF EO1001 (APL-122), A NOVEL IRREVERSIBLE PAN-ERBB INHIBITOR WITH PROMISING BRAIN PENETRATION
Authors: Sophia Frentzas, Gary Richardson, Jeffrey Bacha, Sarath Kanekal, Neil Sankar, Wang Shen, Sanjeev Redkar, Chinglin Lai, Peony Yu, Ian Nisbet, Kathy Skoff, Helen Wheeler, Harry Pedersen, Wang Zhen Zhong, Dennis Brown
Journal: Neuro-Oncology (2021)

Abstract CNS metastases are a prominent driver of cancer morbidity and mortality, especially as targeted therapies have improved systemic outcomes. Mutations in the ErbB/HER kinase family are known oncodrivers in many cancers. Extensive crosstalk among ErbB/HER receptors suggests that inhibition of multiple family members may benefit treatment and limit drug resistance. There is a desperate need for new agents that are more tolerable and effective in treating CNS metastases. EO1001 (APL-122) is a first-in-class, oral, irreversible pan-ErbB inhibitor targeting ErbB1, ErbB2 and ErbB4 with promising CNS penetration in preclinical models. Preclinical data suggests a favorable pharmacokinetic and safety profile and activity against ErbB-driven cancers in patient-derived xenograft models. We report on a first-in-human Phase 1-2 clinical trial in progress. Adult participants with confirmed ErbB-positive cancer, including patients with CNS involvement, who have progressed after standard-of-care, with adequate bone marrow, renal and liver function are eligible. ESCALATION: One subject per dose cohort is enrolled in an accelerated dose-escalation design until drug-related toxicity (≥G2) is observed in the first cycle, after which dose escalation will revert to a 3 + 3 design to determine the maximum tolerated dose (MTD). Cycle 1: Patients receive a single oral dose of EO1001 on day 1; single-dose pharmacokinetics are measured. Beginning on day 8, EO1001 is administered once daily for 21 days; multi-dose pharmacokinetics are measured. Cycles 2-6: EO1001 is administered once daily in continuous 28-day cycles for up to 20 weeks. EXPANSION: EO1001 will be administered once daily to 20 patients at the MTD in continuous 28-day cycles for up to 6 cycles to determine a recommended Phase 2 dose (RP2D) for further study. Toxicity is assessed based on NCI CTCAEv5 and tumor response is assessed by RECIST 1.1. CNS exposure is evaluated in patients via CSF collection with confirmed CNS disease involvement.
The stimulus-response crisis
Authors: Robyn Wilford, Juan Ardila-Cifuentes, Edward Baggs, Michael L. Anderson
Journal: Behavioral and Brain Sciences (2022)

Abstract Yarkoni correctly recognizes that one reason for psychology's generalizability crisis is the failure to account for variance within experiments. We argue that this problem, and the generalizability crisis broadly, is a necessary consequence of the stimulus-response paradigm widely used in psychology research. We point to another methodology, perturbation experiments, as a remedy that is not vulnerable to the same problems.
Re: Valentin H. Meissner, Isabel Rauscher, Kristina Schwamborn, et al. Radical Prostatectomy Without Prior Biopsy Following Multiparametric Magnetic Resonance Imaging and Prostate-specific Membrane Antigen Positron Emission Tomography. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2021.11.019
Authors: Hemamali Samaratunga, Brett Delahunt, Lars Egevad
Journal: European Urology (2022)
Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation
Authors: Alvaro Quintanal-Villalonga, Hirokazu Taniguchi, Yingqian A. Zhan, Maysun M. Hasan, Shweta S. Chavan, Fanli Meng, Fathema Uddin, Parvathy Manoj, Mark T.A. Donoghue, Helen H. Won, Joseph M. Chan, Metamia Ciampricotti, Andrew Chow, Michael Offin, Jason C. Chang, Jordana Ray-Kirton, Sam E. Tischfield, Jacklynn Egger, Umesh K. Bhanot, Irina Linkov, Marina Asher, Sonali Sinha, Joachim Silber, Christine A. Iacobuzio-Donahue, Michael H. Roehrl, Travis J. Hollmann, Helena A. Yu, Juan Qiu, Elisa de Stanchina, Marina K. Baine, Natasha Rekhtman, John T. Poirier, Brian Loomis, Richard P. Koche, Charles M. Rudin, Triparna Sen
Journal: Cancer Discovery (2021)

Lineage plasticity is implicated in treatment resistance in multiple cancers. In lung adenocarcinomas (LUAD) amenable to targeted therapy, transformation to small cell lung cancer (SCLC) is a recognized resistance mechanism. Defining molecular mechanisms of neuroendocrine (NE) transformation in lung cancer has been limited by a paucity of pre/posttransformation clinical samples. Detailed genomic, epigenomic, transcriptomic, and protein characterization of combined LUAD/SCLC tumors, as well as pre/posttransformation samples, supports that NE transformation is primarily driven by transcriptional reprogramming rather than mutational events. We identify genomic contexts in which NE transformation is favored, including frequent loss of the 3p chromosome arm. We observed enhanced expression of genes involved in the PRC2 complex and PI3K/AKT and NOTCH pathways. Pharmacologic inhibition of the PI3K/AKT pathway delayed tumor growth and NE transformation in an EGFR-mutant patient-derived xenograft model. Our findings define a novel landscape of potential drivers and therapeutic vulnerabilities of NE transformation in lung cancer. The difficulty in collection of transformation samples has precluded the performance of molecular analyses, and thus little is known about the lineage plasticity mechanisms leading to LUAD-to-SCLC transformation. Here, we describe biological pathways dysregulated upon transformation and identify potential predictors and potential therapeutic vulnerabilities of NE transformation in the lung. See related commentary by Meador and Lovly, p. 2962. This article is highlighted in the In This Issue feature, p. 2945.
Partitioning Mechanical Ventilator Duration in COVID-19–related Acute Respiratory Distress Syndrome
Authors: Ségolène Gendreau, Brice Benelli, Maxime Delière, Samuel Tuffet, Nicolas de Prost, Keyvan Razazi, Guillaume Carteaux, Armand Mekontso Dessap
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Circular RNA MTCL1 promotes advanced laryngeal squamous cell carcinoma progression by inhibiting C1QBP ubiquitin degradation and mediating beta-catenin activation
Authors: Zheng Wang, Anqi Sun, Aihui Yan, Jian Yao, Haibo Huang, Ziming Gao, Tao Han, Jia Gu, Ni Li, Huizhe Wu, Kai Li
Journal: Molecular Cancer (2022)

Abstract Background Circular RNAs (circRNAs) are involved in regulatory processes of ubiquitination and deubiquitination in various tumors at post-transcriptional epigenetic modification level. However, the underlying mechanism and its biological functions of circRNAs in the advanced laryngeal squamous cell carcinoma (LSCC) remain obscure. Methods RNA sequencing and quantitative real-time PCR (qRT-PCR) assays were applied to screen for circRNAs differentially expressed in LSCC tissues and cell lines. The candidate RNA-binding proteins and target signalling pathway were detected by RNA pull-down and mass spectrometry, in situ hybridization (ISH), immunohistochemistry (IHC), qRT-PCR assays, and bioinformatics analysis. The functional roles of these molecules were investigated using in vitro and in vivo experiments including EdU, transwell, wound healing, western blot assays, and the xenograft mice models. The molecular mechanisms were identified using RNA pull-down assays, RNA immunoprecipitation (RIP), Co-IP, ISH, Ubiquitination assay, bioinformatics analysis, and the rescue experiments. Results Here, we unveil that microtubule cross-linking factor 1 circRNA (circMTCL1, circ0000825) exerts its critical oncogenic functions by promoting complement C1q-binding protein (C1QBP)-dependent ubiquitin degradation and subsequently activating Wnt/ β -catenin signalling in laryngeal carcinoma initiation and development. Specifically, circMTCL1 was remarkably up-regulated in the paired tissues of patients with LSCC ( n = 67), which predicted a worse clinical outcome. Functionally, circMTCL1 exerted oncogenic biological charactersistics by promoting cell proliferative capability and invasive and migrative abilities. Ectopic circMTCL1 augumented cell proliferation, migration, and invasion of LSCC cells, and this effect could be reversed by C1QBP knocking down in vitro and in vivo. Mechanistically, circMTCL1 directly recruited C1QBP protein by harboring the specific recognized sequence (+ 159 − + 210), thereby accelerating the translation of C1QBP expression by inhibiting its ubiquitin–proteasome-mediated degradation. Importantly, the direct interaction of C1QBP with β -catenin protein was enhanced via suppressing the β -catenin phosphorylation and accelerating its accumulation in cytoplasm and nucleus. Conclusion Our findings manifested a novel circMTCL1-C1QBP- β -catenin signaling axis involving in LSCC tumorigenesis and progression, which shed new light on circRNAs-ubiquitous acidic glycoprotein mediated ubiquitin degradation and provided strategies and targets in the therapeutic intervention of LSCC.
A Potential Path to Universal Coverage With Medicare Advantage for All
Authors: Vincent Mor, David J. Meyers
Journal: JAMA (2022)

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Risk for Reinfection After SARS-CoV-2: A Living, Rapid Review for American College of Physicians Practice Points on the Role of the Antibody Response in Conferring Immunity Following SARS-CoV-2 Infection
Authors: Mark Helfand, Celia Fiordalisi, Jack Wiedrick, Katrina L. Ramsey, Charlotte Armstrong, Emily Gean, Kara Winchell, Irina Arkhipova-Jenkins
Journal: Annals of Internal Medicine (2022)

Background: The strength and duration of immunity from infection with SARS-CoV-2 are important for public health planning and clinical practice. Purpose: To synthesize evidence on protection against reinfection after SARS-CoV-2 infection. Data Sources: MEDLINE (Ovid), the World Health Organization global literature database, ClinicalTrials.gov, COVID19reviews.org, and reference lists. Study Selection: Longitudinal studies that compared the risk for reinfection after SARS-CoV-2 infection versus infection risk in individuals with no prior infection. Data Extraction: Two investigators sequentially extracted study data and rated quality. Data Synthesis: Across 18 eligible studies, reinfection risk ranged from 0% to 2.2%. In persons with recent SARS-CoV-2 infection compared with unvaccinated, previously uninfected individuals, 80% to 98% of symptomatic infections with wild-type or Alpha variants were prevented (high strength of evidence). In the meta-analysis, previous infection reduced risk for reinfection by 87% (95% CI, 84% to 90%), equaling 4.3 fewer infections per 100 persons in both the general population (risk difference, −0.043 [CI, −0.071 to −0.015]) and health care workers (risk difference, −0.043 [CI, −0.069 to −0.016]), and 26.6 fewer infections per 100 persons in care facilities (risk difference, −0.266 [CI, −0.449 to −0.083]). Protection remained above 80% for at least 7 months, but no study followed patients after the emergence of the Delta or Omicron variant. Results for the elderly were conflicting. Limitation: Methods to ascertain and diagnose infections varied. Conclusion: Before the emergence of the Delta and Omicron variants, persons with recent infection had strong protection against symptomatic reinfections for 7 months compared with unvaccinated, previously uninfected individuals. Protection in immunocompromised persons, racial and ethnic subgroups, and asymptomatic index case patients is unclear. The durability of protection in the setting of the Delta and Omicron variants is unknown. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098)