Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes.

In tumors, a subset of CD8+ T cells expressing the transcription factor TCF-1 drives the response to immune checkpoint blockade. We examined the mechanisms that maintain these cells in an autochthonous model of lung adenocarcinoma. Longitudinal sampling and single-cell sequencing of tumor-antigen specific TCF-1+ CD8+ T cells revealed that while intratumoral TCF-1+ CD8+ T cells acquired dysfunctional features and decreased in number as tumors progressed, TCF-1+ CD8+ T cell frequency in the tumor draining LN (dLN) remained stable. Two discrete intratumoral TCF-1+ CD8+ T cell subsets developed over time-a proliferative SlamF6+ subset and a non-cycling SlamF6- subset. Blocking dLN egress decreased the frequency of intratumoral SlamF6+ TCF-1+ CD8+ T cells. Conventional type I dendritic cell (cDC1) in dLN decreased in number with tumor progression, and Flt3L+anti-CD40 treatment recovered SlamF6+ T cell frequencies and decreased tumor burden. Thus, cDC1s in tumor dLN maintain a reservoir of TCF-1+ CD8+ T cells and their decrease contributes to failed anti-tumor immunity.

Human Genetic Variation in F3 and Its Impact on Tissue Factor-Dependent Disease.

Tissue factor (TF) is the primary initiator of blood coagulation in humans. As improper intravascular TF expression and procoagulant activity underlie numerous thrombotic disorders, there has been longstanding interest in the contribution of heritable genetic variation in F3, the gene encoding TF, to human disease. This review seeks to comprehensively and critically synthesize small case-control studies focused on candidate single nucleotide polymorphisms (SNPs), as well as modern genome-wide association studies (GWAS) seeking to discover novel associations between variants and clinical phenotypes. Where possible, correlative laboratory studies, expression quantitative trait loci, and protein quantitative trait loci are evaluated to glean potential mechanistic insights. Most disease associations implicated in historical case-control studies have proven difficult to replicate in large GWAS. Nevertheless, SNPs linked to F3, such as rs2022030, are associated with increased F3 mRNA expression, monocyte TF expression after endotoxin exposure, and circulating levels of the prothrombotic biomarker D-dimer, consistent with the central role of TF in the initiation of blood coagulation.

Transportation and language access as crucial pillars for an immigrant-inclusive 21st-century food security program.

Though food insecurity has long been recognised to impact health, population-specific determinants of food insecurity have recently been studied systematically as an important public health concern. Indeed, while immigrant populations face particular challenges to equitable access to the food system, many of these concerns have not been systematically described. To this end, we critically review recent work that demonstrates the importance of transportation and language access as independent determinants of access to food for immigrant populations. Furthermore, we highlight proposals to mitigate barriers to access, including both academic and community-driven approaches to create overlapping institutional commitments for inclusive policymaking that meets the specific needs of diverse populations.

Rationing, Responsibility, and Vaccination during COVID-19: A Conceptual Map.

Throughout the COVID-19 pandemic, shortages of scarce healthcare resources consistently presented significant moral and practical challenges. While the importance of vaccines as a key pharmaceutical intervention to stem pandemic scarcity was widely publicized, a sizable proportion of the population chose not to vaccinate. In response, some have defended the use of vaccination status as a criterion for the allocation of scarce medical resources. In this paper, we critically interpret this burgeoning literature, and describe a framework for thinking about vaccine-sensitive resource allocation using the values of responsibility, reciprocity, and justice. Although our aim here is not to defend a single view of vaccine-sensitive resource allocation, we believe that attending critically with the diversity of arguments in favor (and against) vaccine-sensitivity reveals a number of questions that a vaccine-sensitive approach to allocation should answer in future pandemics.

Highlighting State Innovation to Close Coverage Gaps in Perinatal Care for Noncitizens.

This Viewpoint highlights several key steps that states could take to expand perinatal care coverage for noncitizens.

Regulating Direct-to-Consumer Polygenic Risk Scores.

This Viewpoint discusses the possible harms associated with direct-to-consumer polygenic risk scores and advocates for federal regulation.

Simple and compelling biomimetic metal-organic framework catalyst for the degradation of nerve agent simulants.

Inspired by biology, in which a bimetallic hydroxide-bridged zinc(II)-containing enzyme is utilized to catalytically hydrolyze phosphate ester bonds, the utility of a zirconium(IV)-cluster-containing metal-organic framework as a catalyst for the methanolysis and hydrolysis of phosphate-based nerve agent simulants was examined. The combination of the strong Lewis-acidic Zr(IV) and bridging hydroxide anions led to ultrafast half-lives for these solvolysis reactions. This is especially remarkable considering that the actual catalyst loading was a mere 0.045 % as a result of the surface-only catalysis observed.

Polygenic Scores in the Direct-to-Consumer Setting: Challenges and Opportunities for a New Era in Consumer Genetic Testing.

Direct-to-consumer (DTC) genetic tests have generated considerable scholarly attention and public intrigue. Although the current consumer genetic testing regime relies on the reporting of individual variants of interest to consumers, there has recently been interest in the possibility of integrating polygenic scores (PGS), which aggregate genetic liability for disease across the entire genome. While PGS have thus far been extensively explored as clinical and public health tools, the use of PGS in consumer genetic testing has not yet received systematic attention, even though they are already in use for some consumer genetic tests. In this narrative review, we highlight the ethical, legal, and social implications of the use of PGS in DTC genetic tests and synthesize existing solutions to these concerns. We organize these concerns into three domains: (1) industry variation; (2) privacy and commercialization; and (3) patient safety and risk. While previously expressed concerns in these domains will remain relevant, the emergence of PGS-based DTC genetic tests raises challenges that will require novel approaches.

Toward a new standard of health for immigrants in the United States.

The COVID-19 pandemic has caused massive disruptions in social life, created significant morbidity and mortality, and has exacerbated pre-existing disparities in health and welfare. In the United States, the pandemic has also catalyzed debate regarding how our health and social services infrastructure can be improved and bolstered going forward. An important part of these discussions revolves around the vulnerability experienced by immigrant populations during the pandemic. However, the debate has too often left unquestioned what fundamental standard of health is owed to immigrants. Here, we offer a set of proposals that can chart a course for a new standard of health for immigrants in the US, some of which, as a matter of statute, can ensure that the health of immigrant populations is not contingent on the policy prerogatives of various governmental administrations. Though these proposals would establish a novel standard for immigrant health, we argue that a broader approach is needed-encompassing local, state, and federal initiatives-to ensure that all members of society are provided fundamental resources and social support.

State Flexibility in Emergency Medicaid to Care for Uninsured Noncitizens.

This Viewpoint discusses how Emergency Medicaid offers an immediately available pathway for states to improve access to care for uninsured, lower-income noncitizens with serious health conditions.

Extramedullary plasmacytoma arising from the nasal septum.

We report a rare case of extramedullary plasmacytoma of the nasal septum in a 65-year-old woman. She presented with a 2-month history of left-sided nasal obstruction and intermittent blood-tinged nasal crusting. Nasal endoscopy revealed that a dark-red mass had arisen from the nasal septum; no evidence of invasion to adjacent tissues was seen. A biopsy specimen was diagnosed as a plasmacytoma (kappa light chain-type). Serum and urine electrophoresis failed to detect any myeloma component or Bence Jones protein. All other screening tests to rule out multiple myeloma were negative. These findings confirmed the diagnosis of extramedullary plasmacytoma. The mass was completely removed via an endoscopic approach. No recurrence was noted at the 2-year follow-up.

Cardiorespiratory and biomechanical responses to simulated recreational horseback riding in healthy children.

PURPOSE: The purpose of this study was to determine the reliability of cardiorespiratory and pelvic kinematic responses to simulated horseback riding (SHBR) and to characterize responses to SHBR relative to walking in apparently healthy children. METHOD: Fifteen healthy children (M(age) = 9.5 ± 2.6 years) completed SHBR on a commercially available simulator at low intensity (0.27 Hz) and high intensity (0.65 Hz) during 3 sessions on different occasions. Heart rate (HR), blood pressure, and respiratory gases were measured at rest and during steady-state exercise at both intensities. Pelvic displacement was measured during steady-state exercise. Rate of energy expenditure, mean arterial pressure, and rate pressure product (RPP) were calculated. Participants also walked on a treadmill for 26.8 m/min to 80.5 m/min in 13.4-m/min increments at 0% grade during 1 session to compare cardiorespiratory responses with those of SHBR. RESULTS: Physiological variables across all 3 SHBR sessions were similar at both intensities (p>.05 for all). Intraclass correlation coefficients (ICCs) and coefficients of variation indicate good to modest reliability of cardiorespiratory measures during SHBR (ICCs = .542-.996 for oxygen consumption, energy expenditure, and RPP). Cardiorespiratory variables, except for HR, were 2% to 19% greater, and pelvic displacement was up to 37% greater with high-intensity riding. Treadmill walking at all speeds elicited greater physiological responses compared with SHBR (p < .05). CONCLUSION: Cardiorespiratory responses and pelvic kinematics are reproducible with SHBR in young children, and these responses were lower than those elicited by slow treadmill walking.