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Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease.

Human mucosal-associated invariant T (MAIT) cells are characterized by their expression of an invariant TCR α chain Vα7.2-Jα33/Jα20/Jα12 paired with a restricted TCR β chain. MAIT cells recognize microbial peptides presented by the highly conserved MHC class I-like molecule MR1 and bridge the innate and acquired immune systems to mediate augmented immune responses. Upon activation, MAIT cells rapidly proliferate, produce a variety of cytokines and cytotoxic molecules, and trigger efficient antitumor immunity. Administration of a representative MAIT cell ligand 5-OP-RU effectively activates MAIT cells and enhances their antitumor capacity. In this review, we introduce MAIT cell biology and their importance in antitumor immunity, summarize the current development of peripheral blood mononuclear cell-derived and stem cell-derived MAIT cell products for cancer treatment, and discuss the potential of genetic engineering of MAIT cells for off-the-shelf cancer immunotherapy.

The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation. Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration. This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and γδT cells. This study also assesses the antitumor ability of CAR-engineered innate T cells, evaluating their potential adoption for clinical therapies. The in vitro trials presented in this study demonstrate the considerable TAM-killing abilities of all three innate T cell types, and confirm the enhanced antitumor abilities of CAR-engineered innate T cells. The tumor- and TAM-targeting capacity of these innate T cells suggest their potential for antitumor therapy that supplements cytotoxicity with remediation of tumor microenvironment (TME)-immunosuppression.

Happiness and other emotions spread between people in direct contact, but it is unclear whether massive online social networks also contribute to this spread. Here, we elaborate a novel method for measuring the contagion of emotional expression. With data from millions of Facebook users, we show that rainfall directly influences the emotional content of their status messages, and it also affects the status messages of friends in other cities who are not experiencing rainfall. For every one person affected directly, rainfall alters the emotional expression of about one to two other people, suggesting that online social networks may magnify the intensity of global emotional synchrony.

Husiraci Environmental health specialists often perform environmental assessments (EAs) when a suspected or confirmed foodborne illness outbreak is linked to a food establishment. Information from EAs helps officials determine the cause of the outbreak and develop strategies to prevent future outbreaks; however, EAs are not always conducted. To determine facilitators and barriers to conducting EAs, we analyzed open-ended responses reported to the National Environmental Assessment Reporting System about these assessments. We found that EAs were conducted most often when illness was identified, a jurisdiction had a policy to investigate illnesses, and there were resources for such a response. EAs were not conducted in instances such as limited resources, insufficient training, uncooperative facility personnel, or if the establishment fell outside of health department jurisdiction. Identifying the facilitators and barriers to conducting EAs can enable health departments to develop strategies that improve their ability to conduct EAs., Introduction Foodborne illness is a significant public health problem in the U.S. (Angelo, Nisler, Hall, Brown, & Gould, 2017; Centers for Disease Control and Prevention [CDC], 2013; Gould et al., [...]

Researchers often face the problem of needing to protect the privacy of subjects while also needing to integrate data that contains personal information from diverse data sources. The advent of computational social science and the enormous amount of data about people that is being collected makes protecting the privacy of research subjects ever more important. However, strict privacy procedures can hinder the process of joining diverse sources of data that contain information about specific individual behaviors. In this paper we present a procedure to keep information about specific individuals from being "leaked" or shared in either direction between two sources of data without need of a trusted third party. To achieve this goal, we randomly assign individuals to anonymous groups before combining the anonymized information between the two sources of data. We refer to this method as the Yahtzee procedure, and show that it performs as predicted by theoretical analysis when we apply it to data from Facebook and public voter records.

Every year, roughly 1 in 6 Americans (48 million people) get sick, 128,000 are hospitalized, and 3,000 die of foodborne diseases (Centers for Disease Control and Prevention [CDC], 2016). Furthermore, [...]

Human behaviour is thought to spread through face-to-face social networks, but it is difficult to identify social influence effects in observational studies (9-13), and it is unknown whether online social [...]

Objectives: We determined how often emergency physician pediatric musculoskeletal (MSK) radiograph interpretations were discordant to that of a radiologist and led to an adverse event (AE). We also established the variables independently associated with this outcome. Methods: This prospective cohort study was conducted in an urban, tertiary care children's emergency department (ED). We enrolled children who presented to an ED with an extremity injury and received radiographs. ED physicians documented their radiograph interpretation, which was compared to a radiology reference standard. Patients received telephone follow‐up and had institutional medical records reviewed in 3 weeks. An AE occurred if there were clinical sequelae and/or repeat health care visits due to a delay in correct radiograph interpretation. Results: We enrolled 2,302 children (mean [±SD] age = 9.0 [4.4] years; 1,288 (56.0%) male]. Of these, 180 (7.8%; 95% confidence interval = 6.8 to 9.0) ED physician discordant interpretations resulted in an AE. Specifically, there were no negative clinical outcomes; however, relative to cases diagnosed correctly at the index ED, patients whose fracture was not initially identified encountered 77.2% more subsequent ED visits, while those falsely diagnosed with a fracture experienced 41.5% additional orthopedic clinic visits. Odds of an ED discrepant interpretation was significantly higher if a physician's pretest probability of a fracture was ≤ 20% versus> 20% (adjusted odds ratio [aOR] = 1.6), patient's pain score was ≤ 2 versus> 2 (aOR = 1.6), and injury was located in a joint versus other location (aOR = 1.7). Conclusions: Emergency physician discordant pediatric MSK radiograph interpretations that resulted in an AE occurred with regular frequency in a pediatric ED setting. AEs were primarily an increase in subsequent health care visits. Importantly, a low clinical suspicion for a fracture or injury located in the joint were risk factors for ED physician discordant interpretations. [ABSTRACT FROM AUTHOR]

Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease. [ABSTRACT FROM AUTHOR]