tbuckley/cabot-search huggingface dataset:
Evaluating Litigation as a Structural Strategy for Addressing Bias-Based Bullying Among Youth
Authors: Mark L. Hatzenbuehler, Sarah McKetta, Robert Kim, Solomon Leung, Seth J. Prins, Stephen T. Russell
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> Homophobic bullying—which is motivated by actual or perceived sexual orientation—is a common experience among youth and is more strongly associated with adverse outcomes than bullying unrelated to bias. Yet current approaches to reducing homophobic bullying either lack empirical evidence or encounter significant obstacles. Thus, the field requires the identification of strategies that hold promise for reducing homophobic bullying. <h3>Objective</h3> To examine whether litigation is associated with reductions in homophobic bullying. <h3>Design, Setting, and Participants</h3> In this quasi-experimental study, difference-in-difference analysis was used to estimate the association between litigation and homophobic bullying, comparing students in schools that experienced litigation with students in schools that did not experience litigation, controlling for individual and school characteristics, study year, and county. Survey responses came from high school students from 499 schools participating in the California Healthy Kids Survey, the largest statewide survey of youth risk behaviors and protective factors, between 2001 and 2016. Legal data were collected from September 2018 to September 2019, and data were analyzed from February 2020 to April 2021. <h3>Exposures</h3> Outcomes of litigation related to sexual orientation–based harassment and discrimination in California schools occurring after 2000. <h3>Main Outcomes and Measures</h3> Student reports of homophobic bullying. <h3>Results</h3> Of 1 448 778 included participants, 706 258 (48.7%) were male, 563 973 (38.9%) were White, and the mean (SD) age was 14.6 (1.7) years. For cases where the plaintiff (student) secured monetary and/or injunctive relief through settlement or court decision, there was a 23% reduction in the ratio of odds ratios (ROR) of homophobic bullying in schools directly involved in the litigation relative to schools that did not experience litigation (ROR, 0.77; 95% CI, 0.68-0.86). These benefits of litigation spilled over into schools in the same district as the schools experiencing litigation (ROR, 0.76; 95% CI, 0.70-0.81). However, homophobic bullying slightly increased in the school and district where the defendant (school) avoided adverse legal consequences, suggesting potential backlash. <h3>Conclusions and Relevance</h3> Litigation seeking to address alleged violations of the rights of students who are (or are perceived to be) lesbian, gay, bisexual, or transgender under laws prohibiting harassment or discrimination may lead to reductions in rates of homophobic bullying, with effect sizes comparable with that of resource-intensive school-based bullying interventions. These findings set the stage for future studies to evaluate the consequences of different litigation efforts aimed at redressing stigma-based harms among youth.
P48.05 Is Relapse-Free Survival at 2-Years an Appropriate Surrogate for Overall Survival at 5-Years in EGFR-mutated Resected NSCLC?
Authors: M. Garcia, S. Schmid, K. Hueniken, L. Zhan, K. Balaratnam, K. Khan, A. Fares, S. Chan, E. Smith, R. Aggarwal, M.C. Brown, D. Patel, A. Sacher, P. Bradbury, F.A. Shepherd, N. Leighl, G. Liu
Journal: Journal of Thoracic Oncology (2021)
Rapid synaptic plasticity contributes to a learned conjunctive code of position and choice-related information in the hippocampus
Authors: Xinyu Zhao, Ching-Lung Hsu, Nelson Spruston
Journal: Neuron (2021)

To successfully perform goal-directed navigation, animals must know where they are and what they are doing—e.g., looking for water, bringing food back to the nest, or escaping from a predator. Hippocampal neurons code for these critical variables conjunctively, but little is known about how this "where/what" code is formed or flexibly routed to other brain regions. To address these questions, we performed intracellular whole-cell recordings in mouse CA1 during a cued, two-choice virtual navigation task. We demonstrate that plateau potentials in CA1 pyramidal neurons rapidly strengthen synaptic inputs carrying conjunctive information about position and choice. Plasticity-induced response fields were modulated by cues only in animals previously trained to collect rewards based on available cues. Thus, we reveal that gradual learning is required for the formation of a conjunctive population code, upstream of CA1, while plateau-potential-induced synaptic plasticity in CA1 enables flexible routing of the code to downstream brain regions.
Catecholamines Mediate Psychologic Stress–Induced Cancer Progression
Authors: Daniel G. Bernabé
Journal: Cancer Research (2021)

Abstract Catecholamines, which are involved in response to physical or emotional stress, have emerged as one of the main mediators of the relationship between chronic stress and cancer progression. The study in this issue of Cancer Research by Liu and colleagues reveals a new mechanism by which psychologic stress stimulates cancer progression through the D2 dopamine receptor and activation of the oxygen-independent HIF1α pathway. Although most investigations so far have focused on the action of the stress-related catecholamines norepinephrine and epinephrine on tumor cells, this study shows that dopamine and its receptor can be a potential therapeutic target. The findings broaden the understanding of the interaction of catecholamines with the tumor microenvironment and reinforces the need to look at psychologic stress as a modulator of cancer progression. See related article by Liu et al., p. 5353
MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice
Authors: Mingming Song, Shiyao Zhang, Zixuan Tao, Jianning Li, Yujie Shi, Yonghong Xiong, Wenxiang Zhang, Chang Liu, Siyu Chen
Journal: Biomaterials (2021)

The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.
Strategies for Antibiotic Administration for Bowel Preparation Among Patients Undergoing Elective Colorectal Surgery
Authors: John C. Woodfield, Kari Clifford, Barry Schmidt, Gregory A. Turner, Mohammad A. Amer, John L. McCall
Journal: JAMA Surgery (2021)

There are discrepancies in guidelines on preparation for colorectal surgery. While intravenous (IV) antibiotics are usually administered, the use of mechanical bowel preparation (MBP), enemas, and/or oral antibiotics (OA) is controversial.
P24.08 Lung Cancer Diagnosis in Absence of Adequate Tissue Molecular Analysis in Metastatic Disease by NGS Analysis of Plasma cfDNA
Authors: C. Steendam, P. Atmodimedjo, C. Van Der Leest, K. Van Loenhout, S. Van'T Westeinde, D. Dumoulin, W. Hanselaar, E. De Jonge, R. Van Schaik, J. Von Der Thüsen, J. Aerts, A. Dingemans, H. Dubbink
Journal: Journal of Thoracic Oncology (2021)
P10.14 ctDNA and Real-World Response (rwR) in Patients With Lung Cancer From A Prospective Real-World Clinico-Genomic (PCG) Study
Authors: A. Vanderwalde, M. Lu, S. Maund, M. Huntley, D. Incerti, A. Fine, K. Tolba, D. Jin, A. Bourla, A. Sondhi, M. Tromanhauser, D. Daniel, J. Tilford, J. Mcfarlane, S. Lakhanpal, G. Oxnard, K. Schulze
Journal: Journal of Thoracic Oncology (2021)
P26.02 A Phase II Trial of Neoadjuvant Osimertinib for Surgically Resectable EGFR-Mutant Non-Small Cell Lung Cancer: Updated Results
Authors: C. Blakely, A. Urisman, D. Kerr, W. Wu, B. Bacaltos, J. Rotow, M. Gubens, K. Jones, T. Bivona, S. Joo, J. Riess, D. Aisner, R. Doebele, T. Patil, E. Schenk, J. Kratz, D. Jablons
Journal: Journal of Thoracic Oncology (2021)
Abstract 16575: Arterial Tortuosity is Present in Multiple Genetic Conditions Associated With Aortopathy, a Study From the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)
Authors: Shaine A Morris, Kalyan Kancherla, Seitaro Oda, Federico M Asch, Sarah Sami, William A Payne, Nicholas A Dodd, Kim A Eagle, Claudia Pedroza, Reed E Pyeritz, William Ravekes, Mary J Roman, Kathryn W Holmes, Jon E Tyson, Ron Lacro, Scott A LeMaire, Rajesh Krishnamurthy, Dianna M Milewicz
Journal: Circulation (2015)

Background: Arterial tortuosity is emerging as an imaging marker of adverse events in aortopathy, but quantification has focused on patients with Marfan and Loeys-Dietz syndromes. Our objective was to characterize vertebral artery tortuosity among a variety of aortopathy phenotypes and genotypes. Methods: We performed a retrospective analysis of patients ≤50 years old with at least one of the following: aortic dilation or dissection, bicuspid aortic valve (BAV), or a genotype associated with aortopathy. Patients included were either enrolled in GenTAC or were cared for at our institution, and had undergone a magnetic resonance or computed tomography angiogram that included the vertebral arteries. The disease-causing gene mutation was available for a subset of the patients. The vertebral artery tortuosity index (VTI) was utilized to quantify tortuosity, and was compared among phenotypes and genotypes. Increased tortuosity was defined as ≥2SD above the mean VTI of previously reported controls undergoing evaluation to exclude arrhythmogenic right ventricular dysplasia (mean 4.5±2.5, cutoff=10.5). Results: We included 456 patients, of median age 29 years (IQR 15-40 years), and 58% male. The figure shows VTI by phenotype and genotype. VTI was higher in all phenotypic groups than controls (p ≤0.01 for all). All genotypes (for which n&gt;1) had increased VTI compared to controls (p≤0.01 for all). Patients with TGFBR2 mutations had significantly greater VTI (median 59, IQR 20-85) than those with FBN1 mutations (median 25, IQR 13-51, p=0.01); there was no difference in VTI between TGFBR1 (median 19, IQR 12-64) and FBN1 mutations (p=0.79). There was no overall correlation between age and VTI; when evaluated by diagnosis, there was a weak correlation in MFS (Spearman's rho=0.213, p=0.01). Conclusions: Increased arterial tortuosity as measured by VTI is present in many phenotypes and genotypes associated with aortopathy, and is not limited to those with mutations in TGFBR1/2.
P46.06 Response of an Advanced Lung Cancer Mass to Targeted Therapy
Authors: P.A. Schulze, M. Iglesias, T. Menegaz, A.C. Gelatti, V. Lorandi, B. Hochhegger, M.T. Tsukazan, J.A. Figueiredo Pinto
Journal: Journal of Thoracic Oncology (2021)
Pregnancy Outcomes in Women With Psoriatic Arthritis in Relation to Presence and Timing of Antirheumatic Treatment
Authors: Katarina Remaeus, Kari Johansson, Fredrik Granath, Olof Stephansson, Karin Hellgren
Journal: Arthritis & Rheumatology (2021)

To evaluate pregnancy outcomes in relation to antirheumatic treatment before and during pregnancy, as a proxy of disease severity in pregnant women with psoriatic arthritis (PsA), compared to those without PsA.Our study focused on a Swedish nationwide registry-based cohort study that included 921 PsA pregnancies and 9,210 non-PsA pregnancies occurring between 2007 and 2017 (matched 1:10 based on maternal age, year of delivery, and parity). We estimated adjusted odds ratios (ORs) overall, with 95% confidence intervals (95% CIs), and stratified by presence, timing, and type of antirheumatic treatment. Adjustments were made for maternal body mass index, smoking, education level, and country of birth. The outcome of preterm birth was also stratified by parity.Pregnant women with PsA versus those without PsA were more obese, more often smokers, and more frequently had a diagnosis of pregestational hypertension and diabetes mellitus. Increased risks in PsA pregnancies versus non-PsA pregnancies were primarily preterm birth (adjusted OR 1.69 [95% CI 1.27-2.24]) and cesarean delivery (adjusted OR 1.77 [95% CI 1.43-2.20] for elective delivery, and adjusted OR 1.42 [95% CI 1.10-1.84] for emergency delivery). The risks differed according to the presence, timing, and type of antirheumatic treatment, with the most increased risk in PsA pregnancies (versus non-PsA) occurring with antirheumatic treatment during pregnancy (adjusted OR 2.30 [95% CI 1.49-3.56] for preterm birth). The corresponding adjusted OR for preterm birth in women with PsA who were exposed specifically to biologic treatment during pregnancy was 4.49 [95% CI 2.60-7.79]. Risk of preterm birth was primarily increased in first pregnancies.Compared to non-PsA pregnancies, risks of preterm birth and cesarean delivery were mostly increased in those exposed to antirheumatic treatment during pregnancy, especially biologic treatments. As parity influences the risk of preterm birth in women with PsA, special attention to first pregnancies is warranted. Women with PsA should receive individualized monitoring during pregnancy.
Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment
Authors: Shuang Wang, Feng Li, Tong Ye, Jianghua Wang, Chengliang Lyu, Shuang Qing, Zhaowen Ding, Xiaoyong Gao, Rongrong Jia, Di Yu, Jun Ren, Wei Wei, Guanghui Ma
Journal: Science Translational Medicine (2021)

Despite multiple immunotherapeutic technologies that achieve potent T cell activation, effector T cells still lack efficiency because of the highly immunosuppressive conditions in the tumor microenvironment. Inspired by recent advances in nano-sized secreted vesicles known as exosomes as therapeutic agents and research revealing that circulating cancer cells have a “homing” capacity to return to the main tumor sites, we generated macrophage-tumor hybrid cells. We introduced nuclei isolated from tumor cells into activated M1-like macrophages to produce chimeric exosomes (aMT-exos). The aMT-exos were able to accumulate in both lymph nodes and diverse tumors of xenograft mice. They entered lymph nodes and primed T cell activation in both the classical antigen-presenting cell–induced immunostimulatory manner and a unique “direct exosome interaction” manner. aMT-exos also had strong “homing behavior” to tumor sites, where they ameliorated immunosuppression. They were effective in inducing tumor regression and extending survival in primary mouse models of lymphoma and breast and melanoma cancers. In addition, when combined with anti–programmed death 1 (a-PD1) treatment, aMT-exos were able to extend survival of metastatic and postsurgical tumor recurrence mouse models. Such a coactivation of the immune response and the tumor microenvironment enabled aMT-exos to confer efficient inhibition of primary tumors, tumor metastases, and postoperative tumor recurrence for personalized immunotherapy, which warrants further exploration in the clinical setting.
Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19
Authors: Felice D’Agnillo, Kathie-Anne Walters, Yongli Xiao, Zong-Mei Sheng, Kelsey Scherler, Jaekeun Park, Sebastian Gygli, Luz Angela Rosas, Kaitlyn Sadtler, Heather Kalish, Charles A. Blatti, Ruoqing Zhu, Lisa Gatzke, Colleen Bushell, Matthew J. Memoli, Steven J. O’Day, Trevan D. Fischer, Terese C. Hammond, Raymond C. Lee, J. Christian Cash, Matthew E. Powers, Grant E. O’Keefe, Kelly J. Butnor, Amy V. Rapkiewicz, William D. Travis, Scott P. Layne, John C. Kash, Jeffery K. Taubenberger
Journal: Science Translational Medicine (2021)

Lung epithelial and endothelial cell damage and defective lung tissue repair contribute to fatal COVID-19.
69P HER2 status in RAS and BRAF wild-type metastatic colorectal cancer: Portuguese study
Authors: M.J.P. de Sousa, T. Fraga, J. Correia Magalhães, R. Basto, J. Paulo, P. Jacinto, N. Bonito, J.P. Magalhães, P. Figueiredo, G. Sousa
Journal: Annals of Oncology (2021)
Abstract 16609: The Receptor for Advanced Glycation Endproducts (RAGE) Regulates Macrophage Cholesterol Efflux
Authors: Xiaoping Shen, Rosa Rosario, Shi Fang Yan, Ann Marie Schmidt
Journal: Circulation (2012)

RAGE plays a critical role in atherosclerosis via multiple mechanisms such as increased inflammation within the aortic wall; vascular endothelial dysfunction; monocytes/macrophages accumulation; an...
Low and High Ambient Temperatures during Pregnancy and Birth Weight among 624,940 Singleton Term Births in Israel (2010–2014): An Investigation of Potential Windows of Susceptibility
Authors: Xavier Basagaña, Yaron Michael, Itamar M. Lensky, Lisa Rubin, Itamar Grotto, Elyakom Vadislavsky, Yoav Levi, Eyal Amitai, Keren Agay-Shay
Journal: Environmental Health Perspectives (2021)

Background: Exposure to heat during pregnancy has been associated with reduced fetal growth. Less is known about associations with cold and the potential for critical time windows of exposure. Objectives: We aimed to evaluate, in a national retrospective cohort, critical windows of susceptibility during pregnancy to extreme temperatures (low and high) and fetal growth, among 624,940 singleton term births in Israel during the period 2010–2014. Methods: Temperature exposures were estimated using a spatially refined gridded climate data set with a 1-h and 1-km2 resolution. Percentiles of temperature were categorized by climatic zone for the entire pregnancy and by trimesters and weeks. Generalized additive models with the distributed lag nonlinear model framework were used to estimate unadjusted and adjusted associations between percentiles and categories of temperature and fetal growth markers: term [births after 36 weeks of gestational age (GA)] mean birth weight and term low birth weight (tLBW, term infants with birth weight below 2,500g). Results: After adjustment, extreme temperatures (percentiles) during the entire pregnancy were associated with a lower mean birth weight {≤10th vs. 41st–50th percentile: –56g [95% confidence interval (CI): –63g, –50g)]; >90th vs. 41st–50th percentile: –65g; 95% CI: –72g, –58g}. Similar inverse U-shaped patterns were observed for all trimesters, with stronger associations for heat than for cold and for exposures during the third trimester. For heat, results suggest critical windows between 3–9 and 19–34 GA-weeks, with the strongest association estimated at 3 GA-weeks (temperature >90th vs. 41st–50th percentiles: –3.8g; 95% CI: –7.1g, –0.4g). For cold, there was a consistent trend of null associations early in pregnancy and stronger inverse associations over time, with the strongest association at 36 GA-week (≤10th vs. 41st–50th percentiles: –2.9g; 95% CI: –6.5g, 0.7g). For tLBW, U-shape patterns were estimated for the entire pregnancy and third trimester exposures, as well as nonsignificant associations with heat for 29–36 GA-weeks. Generally, the patterns of associations with temperatures during the entire pregnancy were consistent when stratified by urbanicity and geocoding hierarchy, when estimated for daily minimum and maximum temperatures, when exposures were classified based on temperature distributions in 49 natural regions, and when estimated for all live births. Discussion: Findings from our study of term live births in Israel (2010–2014) suggest that exposure to extreme temperatures, especially heat, during specific time windows may result in reduced fetal growth. https://doi.org/10.1289/EHP8117
Association Between Hospital Performance Metrics and Market Share
Authors: August Oddleifson, Xiao Xu, Patrick Liu, Chengan Du, Erica Spatz, Nihar Desai
Journal: JAMA Network Open (2021)

This cross-sectional ecological study used hospital-level, risk-adjusted performance measures and patient volume for the following 3 conditions or procedures available in the Centers for Medicare and Medicaid Services' Hospital Care Compare database: acute myocardial infarction (AMI), coronary artery bypass graft (CABG), and hip and/or knee replacement.They were selected to exemplify nonelective, semielective, and mostly elective conditions or procedures, respectively.Performance measures included 30-day mortality rate and 30-day readmission rate for AMI and CABG and 90-day complication rate for hip and/or knee replacement for the 2019 report year, reflecting performance in July 1, 2015, through June 30, 2018.Each hospital's condition-or procedure-specific volume was obtained from the 2020 report year, reflecting patient volumes in July 1, 2016, through June 30, 2019. 4The performance score period preceded the volume period by 1 year to account for how consumers have access only to past, as opposed to contemporary, quality measurements.Market share was calculated by dividing the hospital's volume by the sum of the volume of all hospitals in the hospital referral region (HRR).Hospital and HRR characteristics were derived from the Hospital Care Compare database, the Dartmouth Atlas, 5 the American Community Survey, and the US Decennial Census. 6This research did not meet the National Institutes of Health definition of human subject research as specified in 45 CFR part 46, and was therefore exempt from institutional review board approval.We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.Fractional regressions via generalized linear models with binomial family and logit links were used to model hospital market share for each condition or procedure while adjusting for hospital and HRR characteristics.All estimates reflected marginal effects along with their 95% CIs.Variables adjusted for included number of beds (in tercile), HRR concentration, hospital type (acute care vs critical access), hospital ownership, teaching status, region, HRR population size (in tercile), HRR percentage of the non-White population (in tercile), HRR percentage of the population in rural area (in tercile), HRR percentage of the population with less than a high school education (in tercile), and HRR percentage of the population below the federal poverty level (in tercile).The reference level for tercile variables was the first (lowest) tercile.Terciles were calculated by measure.Two-tailed P < .05 was considered statistically significant.Analysis was conducted using RStudio, version 1.2 (RStudio PBC).The eMethods in the Supplement describes additional methodologic considerations.