tbuckley/cabot-search huggingface dataset:
Benefit of Postoperative Radiotherapy for Patients With Nonmetastatic Adrenocortical Carcinoma: A Population-Based Analysis
Authors: Kan Wu, Xu Liu, Zhihong Liu, Yiping Lu, Xianding Wang, Xiang Li
Journal: Journal of the National Comprehensive Cancer Network (2021)

Adrenocortical carcinoma (ACC) is an aggressive cancer with high recurrence rates and poor prognosis, even after radical surgery. The survival benefit of adjuvant radiotherapy (RT) in patients with ACC has not been well explored. The aim of this study was to evaluate the effect of adjuvant RT on the survival outcome of patients with ACC.All patients with nonmetastatic ACC who underwent complete resection were identified from the SEER database (2004-2016). Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival.Of 365 patients with nonmetastatic ACC, 55 (15.1%) received adjuvant RT and the remainder underwent surgery alone. Patient characteristics were similar between the 2 groups, but those with a higher disease stage were more likely to receive adjuvant RT. Overall, patients receiving RT seemed to have better survival compared with the non-RT group (3-year OS rate, 63.1% vs 52.8%; P<.062). After adjustment for confounding factors, adjuvant RT was indeed associated with a 48% decreased risk of death (hazard ratio, 0.52; 95% CI, 0.29-0.91; P=.023) for all patients. In addition, adjuvant RT may confer a survival benefit only in patients with a high risk of recurrence (3-year OS rate, 55.1% vs 40.0%; P=.048) rather than in those with low/moderate-risk ACC (P=.559).Our findings suggest that adjuvant RT may be associated with improved survival in patients with nonmetastatic ACC who underwent radical surgery, especially those with high risk of recurrence.
Contribution of socioeconomic risk factors within a diverse mycosis fungoides cohort from Detroit, Michigan
Authors: Connor R Buechler, Ethan Sagher, Aaron Tisack, Gordon Jacobsen, Henry W Lim, Chauncey McHargue, Ben J Friedman, Qing-Sheng Mi, David M Ozog, Jesse Veenstra
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 13013: Survival After In-Hospital Cardiopulmonary Resuscitation for Cardiac Arrest in Patients With COVID-19: An Updated Meta-Analysis
Authors: Archana Pattupara, Devika Aggarwal, Kirtipal S Bhatia, Olga Gomez-Rojas, vardhmaan jain, Kam Ho, Avinash Singh, Arieh Fox, Arman Qamar, Joseph Mathew
Journal: Circulation (2021)

Introduction: Several small studies have reported variable outcomes following in-hospital cardiac arrest (IHCA) in patients with COVID-19. A clear estimate is important in prognostication and guiding resuscitation efforts and policies for these patients. Methods: A search of PubMed, Embase, and Scopus databases was conducted to identify studies reporting outcomes after IHCA in adult patients with confirmed COVID-19. The cumulative characteristics of the patients were described. The primary outcome studied was survival at 30 days or at hospital discharge (short term survival). Additional outcomes of interest were proportional prevalence of the initial rhythm at arrest, return of spontaneous circulation (ROSC), and neurological recovery (defined as Cerebral Performance Category Score of 1-2 ). Metanalysis of proportions was performed utilizing the Metaprop command. A random effects model was chosen to account for interstudy variance. Results: A total of 13 eligible studies were identified and included in the analyses. Out of all the hospitalized patients with COVID-19, 1,618 underwent advanced cardiac resuscitation after an IHCA. Patients who had a cardiac arrest had a median age between 50-69 years. IHCA occurred predominantly in men, and in the ICU setting. Shockable rhythms were identified in 8% (95% CI 5-10%, I2; 56%) and non-shockable rhythms in 89% (95% CI 85-94% I2; 84%) of patients (Fig. 1a). ROSC was achieved in 40% (95% CI 31-48% I2; 90%) (Fig. 1b). Only 7 % ( 95% CI 3-12% I2; 86%) of patients survived at 30 days/hospital discharge (Fig. 1c). Neurological recovery was seen in 5% (95% CI 3-9% I2; 67%) of patients who suffered a IHCA (Fig. 1d). Conclusions: Our meta-analysis demonstrates the majority of the cardiac arrests in patients with COVID-19 have non-shockable rhythms. Survival rate in these patients is low, and neurological recovery is unfavorable. This study provides further insight in guiding resuscitation efforts in these patients.
Comparison of Stress and Suicide-Related Behaviors Among Korean Youths Before and During the COVID-19 Pandemic
Authors: So Young Kim, Hye-Rim Kim, Bumjung Park, Hyo Geun Choi
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The COVID-19 pandemic has had a substantial psychological effect on young people. A quantitative assessment of the association between the pandemic and stress and suicidality in youths is needed. <h3>Objective</h3> To investigate the association of the COVID-19 pandemic with self-reported stress and suicide-related behaviors in youths. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the the Korea Youth Risk Behavior Web-based Survey (KYRBWS) conducted in 2019 and 2020 with youths aged 12 to 18 years. Statistical analysis was performed from January to February 2021. <h3>Main Outcomes and Measures</h3> The odds ratios (ORs) with 95% CIs for subjective stress level, sadness or despair, suicidal thoughts, suicide planning, and suicide attempts among 2020 participants were compared with those of the 2019 participants using multiple logistic regression analysis with complex sampling using weighted values. <h3>Results</h3> The 48 443 youths in the 2019 KYRBWS (24 917 male youths [51.3%]; mean [SD] age, 15.0 [1.7] years) and the 44 216 youths in the 2020 KYRBWS (23 103 male youths [52.5%]; mean [SD] age, 15.1 [1.7] years) were compared. The degree of subjective stress was lower in the 2020 participants than in the 2019 participants (severe stress: adjusted OR [aOR], 0.90 [95% CI, 0.83-0.97]; very severe stress: aOR, 0.65 [95% CI, 0.60-0.72]). Sadness or despair was also lower in the 2020 participants than in the 2019 participants (aOR, 0.81 [95% CI, 0.78-0.84]). There were fewer suicide-related behaviors, including suicidal thoughts, suicide planning, and suicide attempts, among the 2020 participants than among the 2019 participants (suicidal thoughts: aOR, 0.77 [95% CI, 0.73-0.80]; suicide planning: aOR = 0.88 [95% CI, 0.81-0.96]; suicide attempts: aOR, 0.64 [95% CI, 0.58-0.70]). <h3>Conclusions and Relevance</h3> This cross-sectional study found that severe stress, sadness or despair and suicide-related behaviors had inverse associations with the early COVID-19 pandemic in Korean youths. These findings suggest that levels of high stress decreased among Korean youths in the early period of the pandemic compared with prepandemic levels.
1O Dynamic circulating tumour DNA (ctDNA) response to neoadjuvant (NA) atezolizumab (atezo) and surgery (surg) and association with outcomes in patients (pts) with NSCLC
Authors: M.G. Kris, J.M. Grindheim, J.E. Chaft, J.M. Lee, B.E. Johnson, V.W. Rusch, P.A. Bunn, H. Pass, E. Schum, J. Carlisle, M. Weyant, A. Nicholas, A. Johnson, D. Shames, I.I. Wistuba, D.P. Carbone, K. Schulze, D.J. Kwiatkowski
Journal: Annals of Oncology (2021)
Facts and Hopes in Prediction, Diagnosis, and Treatment of Immune-Related Adverse Events
Authors: James W. Smithy, David M. Faleck, Michael A. Postow
Journal: Clinical Cancer Research (2021)

Abstract Over the past decade, the use of immune checkpoint inhibitors (ICI) has expanded across a wide spectrum of oncology indications. Immune-related adverse events (irAE) from ICIs represent a significant source of morbidity, and in rare instances, can lead to treatment-related mortality. There are significant opportunities to better identify patients at increased risk for immune-related toxicity, diagnose irAEs more accurately and earlier in their course, and develop more individualized therapeutic strategies once complications arise. Clinical characteristics, germline and somatic genetic features, microbiome composition, and circulating biomarkers have all been associated with higher risk of developing irAEs in retrospective series. Many of these data suggest that both antitumor and anti-host ICI-associated immune reactions may be driven by common features of either the tumor or the patient's preexisting immune milieu. While irAE diagnosis is currently based on clinical history, exclusion of alternative etiologies, and sometimes pathologic confirmation, novel blood-based and radiographic assays are in development to identify these complications more precisely. Anecdotal reports and small case series have highlighted the potential role of targeted immunomodulatory agents to treat irAEs, though further prospective investigation is needed to evaluate more rigorously their use in these settings. In this review, we highlight the current state of knowledge about predicting, diagnosing, and treating irAEs with a translational focus and discuss emerging strategies which aim to improve each of these domains.
Near‐Infrared Responsive Membrane Nanovesicles Amplify Homologous Targeting Delivery of Anti‐PD Immunotherapy against Metastatic Tumors
Authors: Ya‐Nan Tan, Jian‐Dong Huang, Yong‐Peng Li, Shan‐Shan Li, Min Luo, Jie Luo, Anne Wing‐Mui Lee, Li Fu, Fu‐Qiang Hu, Xin‐Yuan Guan
Journal: Advanced Healthcare Materials (2021)

The major obstacles of anti-PD therapy in metastatic tumors are limited drug delivery in primary tumors and metastatic foci, and the lack of tumor-infiltrating lymphocytes (TILs). Here, the authors constructed a novel cellular membrane nanovesicles platform (M/IR NPs) based on homologous targeting and near-infrared (NIR) responsive release strategy to potentiate PD-1/PD-L1 blockade therapy against metastatic tumors. In tumor-bearing mice, biomimetic M/IR NPs targeted both primary tumors and their lung metastases. Upon laser irradiation, M/IR NPs reduced cancer-associated fibroblasts (CAFs) in tumor microenvironment, thus increasing the penetration of TILs. When shed from homologous tumor cell membranes, positively charged nanoparticles (IR NPs) core can capture released tumor-associated antigens, thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. When the photothermal conversion temperature under NIR-laser is higher than 42 °C, M/IR NPs initiated the rupture of cell membranes and the responsive release of PD-1/PD-L1 inhibitor BMS, which significantly attenuated tumor-associated immunosuppression and synergistically induced T cellular immunity to inhibit the tumor growth and metastasis. Overall, biomimetic M/IR NPs can improve the targeting and therapeutic efficacy of anti-PD therapy in primary tumors and metastases, opening up a new avenue for the diagnosis and treatment of metastatic tumors in the future.
Abstract 9764: Prevalence of Inappropriate Defibrillation Attempts During Pediatric In-Hospital Cardiac Arrest
Authors: James M Gray, Tia T Raymond, Dianne L Atkins, Ken Tegtmeyer, Dana E Niles, Vinay M Nadkarni, Maya Dewan
Journal: Circulation (2021)

Introduction: Shockable rhythms (ventricular fibrillation [VF] and ventricular tachycardia [VT]) occur in &lt;25% of pediatric in-hospital cardiac arrest (IHCA) events, yet the prevalence of inappropriate defibrillation attempts for non-VF/VT rhythms is unknown. We aim to describe the prevalence of inappropriate shocks across a large, multi-national pediatric cardiac arrest network. Methods: We included children &lt;18y reported to the pedi atric RES uscitation- Q uality (pediRES-Q) network from 2015-2019 with complete defibrillator files who received defibrillation attempts during IHCA (ZOLL R-Series, MA). Two pediatric cardiologists independently classified rhythms immediately prior to shock as: 1) appropriate (VF or wide complex ≥ 150/min), 2) indeterminate (narrow complex ≥150/min or wide complex 100-149/min), or 3) inappropriate (asystole, sinus, narrow complex &lt;150/min, or wide complex &lt;100/min). Rhythms that were undecipherable due to artifact were excluded from analysis (n=22). Disagreements were resolved by arbitration and consensus. Results: Of 896 IHCA events, 124 (14%) had defibrillation attempts. A total of 303 shocks were delivered: 87 (29%) in age &lt;1y, 84 (28%) in 1-8y, and 132 (44%) in 9-17y. Of shocks delivered, 206 (68%) were appropriate, 12 (4%) indeterminate, and 85 (28%) inappropriate. There was no difference in inappropriate shock delivery by age category: &lt;1y (24/87, 28%), 1-8y (26/84, 31%), 9-17y (35/132, 27%) ( p =0.4). Conclusions: Across a multi-national pediatric cardiac arrest network, a large proportion (28%) of defibrillation attempts were inappropriate, suggesting significant opportunity for improvement in rhythm identification in pediatric cardiac arrest. There was no difference in inappropriate shock delivery across age groups. Figure 1. Representation of rhythm classification and appropriateness of defibrillation attempts with exemplar rhythms.
Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma: Erratum
Authors: Libin Yan, Beichen Ding, Haoran Liu, Yangjun Zhang, Jin Zeng, Junhui Hu, Weimin Yao, Gan Yu, Ruihua An, Zhiqiang Chen, Zhangqun Ye, Jinchun Xing, Kefeng Xiao, Lily Wu, Hua Xu
Journal: Theranostics (2021)

[This corrects the article DOI: 10.7150/thno.37628.].
Abstract 11763: The impact of the Australian Warning Signs Campaign on Emergency Medical Service Use for Acute Coronary Syndrome and Unspecified Chest Pain
Authors: Kathryn J Eastwood, Stuart Howell, Ziad Nehme, Judith Finn, Karen L Smith, Peter Cameron, Dion Stub, Janet Bray
Journal: Circulation (2021)

Background: Between 2009 and 2013, the National Heart Foundation of Australia ran mass media campaigns to improve Australian’s awareness of Acute Coronary Syndrome (ACS) symptoms and the need to call emergency medical services (EMS). This study examined the impact of this campaign on emergency department (ED) presentations and EMS use in Victoria, Australia. Methods: The Victorian Department of Health and Human Services provided data for adult Victorian patients presenting to public hospitals with an ED diagnosis of ACS or unspecified chest pain (U-CP). We modelled changes in the incidence of ED presentations, and the association between the campaign period and 1) EMS arrival and 2) referred to ED by a general practitioner (GP). Models were adjusted for increasing population size, ACS subtype and demographics. Results: Between 2003 and 2015, there were 124,632 eligible ED presentations with ACS and 536,148 with U-CP. In ACS patients, the campaign period was associated with an increase in ED presentations (Incidence Rate Ratio: 1.11; 95% CI: 1.07-1.15), a decrease in presentations via a GP (Adjusted Odds Ratio [AOR]: 0.77; 95% CI: 0.70-0.86), and an increase in EMS use (AOR: 1.10; 95%CI: 1.05-1.17). Similar, but smaller associations were seen in U-CP. Conclusions: The Warning Signs Campaign was associated with improvements in treatment seeking in ACS patients -including increased EMS use. The increase in ACS ED presentations corresponds with a decrease in out-of-hospital cardiac arrest over this time. Future education need to focus on improving EMS use in ACS patient groups where use remains low.
When to suspect contamination rather than colonization – lessons from a putative fetal sheep microbiome
Authors: Simone Bihl, Marcus de Goffau, Daniel Podlesny, Nicola Segata, Fergus Shanahan, Jens Walter, W. Florian Fricke
Journal: Gut Microbes (2021)

There is an ongoing controversy around the existence of a prenatal, fetal microbiome in humans, livestock, and other animals. The 'in utero microbial colonization' hypothesis challenges the clinical paradigm of the 'sterile womb' but has been criticized for its reliance on DNA-based evidence to detect microbiomes and the failure to conciliate the routine experimental derivation of germ-free animals from surgically resected embryos with a thriving fetal microbiome. In order to avoid the propagation of misinformation in the scientific literature, a critical assessment and careful review of newly published studies, particularly those that challenge the convincing current clinical dogma of the sterile womb, is of critical importance.We read with interest a recent publication that postulated the presence of a fetal microbiome in sheep, but questioned the plausibility of the reported findings and their meaningfulness to prove "microbial colonisation of the fetal gut […] in utero". We reanalyzed the published metagenomic and metatranscriptomic sequence data from the original publication and identified evidence for different types of contamination that affected all samples alike and could explain the reported findings without requiring the existence of a fetal microbiome.Our reanalysis challenges the reported findings as supportive of a prenatal fetal lamb microbiome. The shortcomings of the original analysis and data interpretation highlight common problems of low-biomass microbiome projects. We propose genomic independence of separate biological samples, i.e. distinctive profiles at the microbial strain level, as a potential new microbiome marker to increase confidence in metagenomics analyses of controversial low-biomass microbiomes.
Need to Clarify Mechanisms Explaining the Effect of Screen Time on Recovery From Concussion—Reply
Authors: Theodore Macnow, Rebekah Mannix
Journal: JAMA Pediatrics (2021)

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Population Histories and Genomic Diversity of South American Natives
Authors: Marcos Araújo Castro e Silva, Tiago Ferraz, Cainã M Couto-Silva, Renan B Lemes, Kelly Nunes, David Comas, Tábita Hünemeier
Journal: Molecular Biology and Evolution (2021)

South America is home to one of the most culturally diverse present-day native populations. However, the dispersion pattern, genetic substructure, and demographic complexity within South America are still poorly understood. Based on genome-wide data of 58 native populations, we provide a comprehensive scenario of South American indigenous groups considering the genomic, environmental, and linguistic data. Clear patterns of genetic structure were inferred among the South American natives, presenting at least four primary genetic clusters in the Amazonian and savanna regions and three clusters in the Andes and Pacific coast. We detected a cline of genetic variation along a west-east axis, contradicting a hard Andes-Amazon divide. This longitudinal genetic variation seemed to have been shaped by both serial population bottlenecks and isolation by distance. Results indicated that present-day South American substructures recapitulate ancient macroregional ancestries and western Amazonia groups show genetic evidence of cultural exchanges that led to language replacement in precontact times. Finally, demographic inferences pointed to a higher resilience of the western South American groups regarding population collapses caused by the European invasion and indicated precontact population reductions and demic expansions in South America.
BACH2 inhibition reverses β cell failure in type 2 diabetes models
Authors: Jinsook Son, Hongxu Ding, Thomas B. Farb, Alexander M. Efanov, Jiajun Sun, Julie L. Gore, Samreen K. Syed, Zhigang Lei, Qidi Wang, Domenico Accili, Andrea Califano
Journal: Journal of Clinical Investigation (2021)

Type 2 diabetes (T2D) is associated with defective insulin secretion and reduced β cell mass. Available treatments provide a temporary reprieve, but secondary failure rates are high, making insulin supplementation necessary. Reversibility of β cell failure is a key translational question. Here, we reverse engineered and interrogated pancreatic islet-specific regulatory networks to discover T2D-specific subpopulations characterized by metabolic inflexibility and endocrine progenitor/stem cell features. Single-cell gain- and loss-of-function and glucose-induced Ca2+ flux analyses of top candidate master regulatory (MR) proteins in islet cells validated transcription factor BACH2 and associated epigenetic effectors as key drivers of T2D cell states. BACH2 knockout in T2D islets reversed cellular features of the disease, restoring a nondiabetic phenotype. BACH2-immunoreactive islet cells increased approximately 4-fold in diabetic patients, confirming the algorithmic prediction of clinically relevant subpopulations. Treatment with a BACH inhibitor lowered glycemia and increased plasma insulin levels in diabetic mice, and restored insulin secretion in diabetic mice and human islets. The findings suggest that T2D-specific populations of failing β cells can be reversed and indicate pathways for pharmacological intervention, including via BACH2 inhibition.
Fetal Growth and Brain Development—One Data Point Is Worth a Thousand Words, But Growth Trajectories Are Worth a Million
Authors: Patrícia Pelufo Silveira
Journal: JAMA Network Open (2021)

Carolina C. V. Silva, MD; Hanan El Marroun, PhD; Sara Sammallahti, MD, PhD; Meike W. Vernooij, MD, PhD; Ryan L. Muetzel, PhD; Susana Santos, PhD; Vincent W. V. Jaddoe, MD, PhD