Does Patient Blood Management Affect Outcomes in Metastatic Spine Tumour Surgery? A Review of Current Concepts.

STUDY DESIGN: Narrative review. OBJECTIVE: The spine is the most common site of metastases, associated with decreased quality of life. Increase in metastatic spine tumour surgery (MSTS) has caused us to focus on the management of blood, as blood loss is a significant morbidity in these patients. However, blood transfusion is also not without its own risks, and hence this led to blood conservation strategies and implementation of a concept of patient blood management (PBM) in clinical practise focusing on these patients. METHODS: A narrative review was conducted and all studies that were related to blood management in metastatic spine disease as well as PBM surrounding this condition were included. RESULTS: A total of 64 studies were included in this review. We discussed a new concept of patient blood management in patients undergoing MSTS, with stratification to pre-operative and intra-operative factors, as well as anaesthesia and surgical considerations. The studies show that PBM and reduction in blood transfusion allows for reduced readmission rates, lower risks associated with blood transfusion, and lower morbidity for patients undergoing MSTS. CONCLUSION: Through this review, we highlight various pre-operative and intra-operative methods in the surgical and anaesthesia domains that can help with PBM. It is an important concept with the significant amount of blood loss expected from MSTS. LEVEL OF EVIDENCE: Not applicable.

Daily life activities of young adults with obesity living in highly accessible and compact urban environments in Seoul, South Korea: a spatiotemporal qualitative study protocol.

INTRODUCTION: Amid the growing global concern about obesity, young adults in South Korea are particularly affected, with 30.8% of people aged 19-34 classified as obese. Given the urban-centric lifestyle of Korean youth, understanding the relationship between daily life activities and the urban environment holds great promise for effective interventions. This study aims to explore the daily life activities of young adults with obesity in Seoul, a city known for its highly accessible and compact environment. The research questions explore the interaction between daily life activities and the neighbourhood environment and consider weight management in an urban context. METHODS AND ANALYSIS: This study uses an extended qualitative geographic information system approach to explore a district in Seoul with a highly accessible and compact urban environment. The sample comprises young adults with obesity (aged 19-34) residing in the study area, with recruitment targeting up to 51 participants for data saturation. A qualitative, multimethod approach combines descriptive and spatiotemporal data collection. Descriptive data are being collected, including in-depth interviews and photographs of daily food consumption. Spatial data collection involves field observations, cognitive mapping and mobile Global Positioning System tracking. Temporal data is gathered through participants drawing round timetables, detailing their daily schedules. Data analysis will entail thematic analysis of the interview data and content analysis of the spatiotemporal data. For the integrated analysis, pattern finding will be used to synthesise the data. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of Seoul National University on 11 July 2022. Data collection and curation are currently underway, and the results of the analysis will be shared with the scientific community at international conferences and peer-reviewed journals. We are planning an open seminar to share our research findings with relevant policy-makers, community organisations and health professionals.

Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1.

Plant defensins are a large family of small cationic proteins with diverse functions and mechanisms of action, most of which assert antifungal activity against a broad spectrum of fungi. The partial mechanism of action has been resolved for a small number of members of plant defensins, and studies have revealed that many act by more than one mechanism. The plant defensin Ppdef1 has a unique sequence and long loop 5 with fungicidal activity against a range of human fungal pathogens, but little is known about its mechanism of action. We screened the S. cerevisiae non-essential gene deletion library and identified the involvement of the mitochondria in the mechanism of action of Ppdef1. Further analysis revealed that the hyperpolarisation of the mitochondrial membrane potential (MMP) activates ROS production, vacuolar fusion and cell death and is an important step in the mechanism of action of Ppdef1, and it is likely that a similar mechanism acts in Trichophyton rubrum.

In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma.

Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over extracellular localization of therapeutic proteins. A critical gap therefore remains the need to develop and incorporate methodologies that allow for posttranslational control over expression dynamics, localization, and stability of nucleic acid-generated protein therapeutics. To address this, we explored how the body's endogenous machinery controls protein localization through signal peptides (SPs), including how these motifs could be incorporated modularly into therapeutics. SPs serve as a virtual zip code for mRNA transcripts that direct the cell where to send completed proteins within the cell and the body. Utilizing this signaling biology, we incorporated secretory SP sequences upstream of mRNA transcripts coding for reporter, natural, and therapeutic proteins to induce secretion of the proteins into systemic circulation. SP sequences generated secretion of various engineered proteins into the bloodstream following intravenous, intramuscular, and subcutaneous SP mRNA delivery by lipid, polymer, and ionizable phospholipid delivery carriers. SP-engineered etanercept/TNF-α inhibitor proteins demonstrated therapeutic efficacy in an imiquimod-induced psoriasis model by reducing hyperkeratosis and inflammation. An SP-engineered anti-PD-L1 construct mediated mRNA encoded proteins with longer serum half-lives that reduced tumor burden and extended survival in MC38 and B16F10 cancer models. The modular nature of SP platform should enable intracellular and extracellular localization control of various functional proteins for diverse therapeutic applications.

Tobacco Product Use Among U.S. Middle and High School Students - National Youth Tobacco Survey, 2023.

Tobacco product use during adolescence increases the risk for lifelong nicotine addiction and adverse health consequences. CDC and the Food and Drug Administration analyzed data from the 2023 National Youth Tobacco Survey to assess tobacco product use patterns among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2023, 10.0% of middle and high school students (2.80 million) reported current (i.e., past 30-day) use of any tobacco product. Current use of any tobacco product by high school students declined by an estimated 540,000, from 2.51 million in 2022 to 1.97 million in 2023. From 2022 to 2023, current e-cigarette use among high school students declined from 14.1% to 10.0%. Among middle and high school students, e-cigarette products were the most used tobacco product in 2023 (7.7%; 2.13 million), followed by cigarettes (1.6%), cigars (1.6%), nicotine pouches (1.5%), smokeless tobacco (1.2%), other oral nicotine products (1.2%), hookahs (1.1%), heated tobacco products (1.0%), and pipe tobacco (0.5%). Among students who had ever used an e-cigarette, 46.7% reported current use. In 2023, among students reporting current e-cigarette use, 89.4% used flavored products and 25.2% used an e-cigarette daily; the most commonly reported brands were Elf Bar, Esco Bars, Vuse, JUUL, and Mr. Fog. Given the number of middle and high school students that use tobacco products, sustained efforts to prevent initiation of tobacco product use among young persons and strategies to help young tobacco users quit are critical to reducing U.S. youth tobacco product use.

Graft-derived cfDNA Monitoring in Plasma and Bile During Normothermic Machine Perfusion in Liver Transplantation Is Feasible and a Potential Tool for Assessing Graft Viability.

BACKGROUND: Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study. METHODS: Serial plasma and bile samples were collected during NMP for 10 consecutive grafts, at 15 min post-machine reperfusion and then 2-h intervals. Digital polymerase chain reaction was used to quantify gdcfDNA at each time point. RESULTS: Five grafts were suitable for LT, there were no cases of primary nonfunction or death in the recipients. gdcfDNA was quantified in all bile and plasma samples (n > 100). In plasma, gdcfDNA concentrations climbed post-machine reperfusion until 4.25 h (median 2.25 h = 15.98 × 106 copies/mL, 4.25 h = 40.21 × 106 copies/mL). gdcfDNA levels then diverged significantly when comparing the viable and non-viable graft groups (6.25 h, median viable: 117.15 × 106 copies/mL versus non-viable: 16.72 × 106 copies/mL, P = 0.01). These opposing trends correlated in each graft and in all cases with the viable/non-viable outcome. There was a trend of gradual decline in bile gdcfDNA from viable grafts post-machine reperfusion; discarded grafts showed more variable patterns of release. CONCLUSIONS: gdcfDNA analysis during NMP is a feasible and potential tool to inform viability assessment during NMP for LT. Bile gdcfDNA monitoring offers the prospect of an objective means to assess the degree of biliary injury associated with organ procurement.

Novel insecticidal proteins from ferns resemble insecticidal proteins from Bacillus thuringiensis.

Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis (Bt) in crop plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to Bt proteins has highlighted an urgent need for new insecticidal proteins with different modes or sites of action. We discovered a new family of insecticidal proteins from ferns. The prototype protein from Pteris species (Order Polypodiales) and variants from two other orders of ferns, Schizaeales and Ophioglossales, were effective against important lepidopteran pests of maize and soybean in diet-based assays. Transgenic maize and soybean plants producing these proteins were more resistant to insect damage than controls. We report here the crystal structure of a variant of the prototype protein to 1.98 Å resolution. Remarkably, despite being derived from plants, the structure resembles the 3-domain Cry proteins from Bt but has only two out of three of their characteristic domains, lacking the C-terminal domain which is typically required for their activities. Two of the fern proteins were effective against strains of fall armyworm that were resistant to Bt 3-domain Cry proteins Cry1Fa or Cry2A.127. This therefore represents a novel family of insecticidal proteins that have the potential to provide future tools for pest control.

Cross-Cultural Adaptation of Lung Cancer Screening Health Belief Scale in Chinese Americans: A Methodological Study.

Background and Purpose: The purpose of this study is to report the process of adapting the existing Lung Cancer Screening Health Belief Scale to be used in Chinese Americans. Methods: Guided by Flaherty et al.'s cross-cultural equivalency model, the methodology used in the adaptation process consists of four steps, including preliminary modification after a comprehensive literature review, forward and backward translation, expert review, and cognitive interviews among participants. Results: The modified culturally fitted Lung Cancer Screening Health Belief Scale included 57 items and 6 subscales, which proved highly reliable and valid through the expert review and participants' review. Conclusions: This study provided an example for a novice cross-cultural researcher to adapt an instrument to be used in another population with a different language. Further research is needed to work out a standard guideline for cross-cultural instrument adaptation.

Effectiveness of a nurse-led decision counselling programme on hepatocellular carcinoma screening uptake among patients with hepatitis B: A randomised controlled trial.

BACKGROUND: The globally endemic hepatocellular carcinoma induced by hepatitis B highlights the need for an ultrasonography-based screening strategy to reduce the tumour burden. However, patient non-adherence due to unawareness and complex decisions in weighting uncertainties of hepatocellular carcinoma screening has continuously challenged its continuum. OBJECTIVE: To examine the effectiveness and process of a nurse-led decision counselling programme for improving hepatocellular carcinoma screening among patients with hepatitis B. DESIGN: Single-blind randomised controlled trial. SETTING AND PARTICIPANTS: Between 12 March and 19 July 2021, 178 patients with hepatitis B were recruited from six inpatient wards of a university-affiliated hospital in northern China. METHODS: Participants were randomly allocated to receive usual care (n = 89) or usual care plus a nurse-led decision counselling programme (n = 89). Underpinned by the preventive health model, the programme consisted of health education, tailored information, and values clarification exercises to elicit informed and value-based preferences for hepatocellular carcinoma screening. Screening barriers were explored and addressed through procedural problem-solving. Hepatocellular carcinoma screening rate at six months post-baseline was the primary outcome. Secondary outcomes (knowledge, perceptions, and decision conflicts regarding hepatocellular carcinoma screening) were measured at baseline (T0), immediately after the intervention (T1), and the six-month follow-up (T2). A Medical Research Council framework-guided process evaluation was conducted by drawing on data from intervention documentation, WeChat discussions, and interviews with stakeholders (n = 13). RESULTS: With a mean age of 47.32 (8.78) years, participants mostly occupied rural residences (63.5 %). Compared with the control group, the intervention group had significantly higher hepatocellular carcinoma screening rates (75.6 % vs. 42.1 %, p < 0.001) and displayed greater improvements in the scores of hepatocellular carcinoma screening knowledge (ß = 3.643, 95 % confidence interval [CI] = 3.030, 4.255), salience and coherence (ß = 0.410, 95 % CI = 0.234, 0.586), response efficacy (ß = 0.327, 95 % CI = 0.181, 0.473), and perceived susceptibility (ß = 0.214, 95 % CI = 0.040, 0.388) at T1. Improvement in perceived susceptibility was not maintained, whereas a higher decrease of the decision conflict score was found at T2 (ß = -4.156, 95 % CI = -7.851, -0.461). The process evaluation revealed potential intervention mechanisms and contextual factors affecting intervention effectiveness, such as living status and natural disasters. CONCLUSION: The programme was effective in improving hepatocellular carcinoma screening and showed that nurses could play a decision counselling role in optimising the screening among patients with hepatitis B. TRIAL REGISTRATION: ClinicalTrials.govNCT04659005. Registration date: 9 December, 2020. TWEETABLE ABSTRACT: Nurse-led decision counselling improves hepatocellular carcinoma screening in patients with hepatitis B.

Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor-Positive Breast Cancer.

Hormone receptor-positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2-positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

BACKGROUND: Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. OBJECTIVE: The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. METHODS: A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. RESULTS: Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). CONCLUSION AND RELEVANCE: Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing.

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane-localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport-independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.

Trends and Associations of Past-30-Day Cigar Smoking in the U.S. by Age, Race/Ethnicity, and Sex, NSDUH 2002-2020.

Cigar smoking remains a public health issue in the United States (U.S.), with a heterogeneous prevalence based on sociodemographic characteristics. Nationally representative data suggest changes in cigar smoking over time, with some evidence for sociodemographic differences. Using data from the 2002-2019 National Survey on Drug Use and Health (NSDUH), the prevalence of past-30-day cigar smoking was examined overall and stratified by sociodemographic characteristics; joinpoint regression examined the trends. Logistic regression analyses identified the correlates of cigar smoking using 2020 NSDUH data. From 2002 to 2004, the prevalence of cigar smoking remained stable (5.33-5.73%), but declined from 2004 to 2019 (5.73-4.29%). Cigar smoking declined in some periods between 2002-2019 among the non-Hispanic White, Hispanic, ages 12-17, ages 18-20, ages 21-25, age ≥ 35, and male subgroups, but remained unchanged among the non-Hispanic Other, ages 26-34, and female subgroups. Cigar smoking increased among non-Hispanic Black persons overall from 2002 to 2019 (6.67-8.02%). Past-30-day cigarette smoking and drug or alcohol use disorder was associated with an increased likelihood of cigar use, while female sex was associated with a decreased likelihood of cigar use, across all age groups. Though a decline in the prevalence of past-30-day cigar smoking is seen in the general population, the same is not evident among all sociodemographic subgroups. Our findings have the potential to inform tobacco cessation efforts within clinical practice, as well as regulatory efforts to reduce cigar use.

Cancer Screening Rates Among Asian Americans: A Cross-Sectional Secondary Data Analysis Study.

PURPOSE: This study aims 1) to investigate recent cancer screening rates among Asian Americans and 2) to test the relationship between race/ethnicity and cancer screening rates. METHODS: This is a cross-sectional secondary data analysis study using data from the 2019 National Health Interview Survey. The screening rates of prostate cancer, colorectal cancer, cervical cancer, and breast cancer among non-Hispanic (NH) Asian Americans, Hispanics, NH Whites, NH African Americans, and NH American Indian and Alaska Natives (AIAN) were analyzed in July 2022. The variables were recoded and analyzed using descriptive analysis and chi-square test. The SPSS version 27 software was used. RESULTS: Descriptive analysis showed a general low screening rate of cancers among Asian Americans, which ranged from 40.5% to 67.5%. The chi-square test suggested significant associations between race/ethnicity and the screening rates of colorectal cancer (P = .002), cervical cancer (P < .01), and breast cancer (P = .021), but not the prostate cancer (P = .472). CONCLUSION: Necessary intervention programs should be designed to increase the uptake rates of cancer screening among Asian Americans.

Multiple Tobacco Product Use Among Youth E-Cigarette Users: National Youth Tobacco Survey, 2020.

PURPOSE: Limited information exists on multiple tobacco product use, particularly among youth. This study assessed the prevalence of current youth use of e-cigarettes with other tobacco products and their associated characteristics using 2020 National Youth Tobacco Survey data. METHODS: Prevalence estimates were calculated for current e-cigarette users, by multiple tobacco product use status and product combination. Demographic characteristics, e-cigarette use behaviors, age at first combustible tobacco use, and tobacco dependence symptoms were compared between current users of both e-cigarettes and combustible tobacco (dual users) and current exclusive e-cigarette users. RESULTS: In 2020, 61.1% of all current e-cigarette users reported exclusive e-cigarette use, and 38.9% used e-cigarettes with other tobacco products. Among those who used e-cigarettes with other tobacco products, 85.0% used combustible tobacco, with cigarettes being the most commonly used other tobacco product. Compared with current exclusive e-cigarette users, higher proportions of dual users reported the following: frequent e-cigarette use; obtaining e-cigarettes from gas stations, persons other than a family member/friend, vape shops, or the internet; and having any tobacco dependence symptoms. Among dual users, 31.2% reported first combustible product use after e-cigarette initiation, and 34.3% reported first combustible product use prior to e-cigarette initiation. DISCUSSION: Approximately four in 10 youth current e-cigarette users reported using multiple tobacco products, with a majority using combustible tobacco. Frequent e-cigarette use and tobacco dependence symptoms were more prevalent among dual users of e-cigarettes and combustible tobacco.

Race/ethnicity-stratified fine-mapping of the MHC locus reveals genetic variants associated with late-onset asthma.

Introduction: Asthma is a chronic disease of the airways that impairs normal breathing. The etiology of asthma is complex and involves multiple factors, including the environment and genetics, especially the distinct genetic architecture associated with ancestry. Compared to early-onset asthma, little is known about genetic predisposition to late-onset asthma. We investigated the race/ethnicity-specific relationship among genetic variants within the major histocompatibility complex (MHC) region and late-onset asthma in a North Carolina-based multiracial cohort of adults. Methods: We stratified all analyses by self-reported race (i.e., White and Black) and adjusted all regression models for age, sex, and ancestry. We conducted association tests within the MHC region and performed fine-mapping analyses conditioned on the race/ethnicity-specific lead variant using whole-genome sequencing (WGS) data. We applied computational methods to infer human leukocyte antigen (HLA) alleles and residues at amino acid positions. We replicated findings in the UK Biobank. Results: The lead signals, rs9265901 on the 5' end of HLA-B, rs55888430 on HLA-DOB, and rs117953947 on HCG17, were significantly associated with late-onset asthma in all, White, and Black participants, respectively (OR = 1.73, 95%CI: 1.31 to 2.14, p = 3.62 × 10-5; OR = 3.05, 95%CI: 1.86 to 4.98, p = 8.85 × 10-6; OR = 19.5, 95%CI: 4.37 to 87.2, p = 9.97 × 10-5, respectively). For the HLA analysis, HLA-B*40:02 and HLA-DRB1*04:05, HLA-B*40:02, HLA-C*04:01, and HLA-DRB1*04:05, and HLA-DRB1*03:01 and HLA-DQB1 were significantly associated with late-onset asthma in all, White, and Black participants. Conclusion: Multiple genetic variants within the MHC region were significantly associated with late-onset asthma, and the associations were significantly different by race/ethnicity group.

Functional interrogation of lymphocyte subsets in alopecia areata using single-cell RNA sequencing.

Alopecia areata (AA) is among the most prevalent autoimmune diseases, but the development of innovative therapeutic strategies has lagged due to an incomplete understanding of the immunological underpinnings of disease. Here, we performed single-cell RNA sequencing (scRNAseq) of skin-infiltrating immune cells from the graft-induced C3H/HeJ mouse model of AA, coupled with antibody-based depletion to interrogate the functional role of specific cell types in AA in vivo. Since AA is predominantly T cell-mediated, we focused on dissecting lymphocyte function in AA. Both our scRNAseq and functional studies established CD8+ T cells as the primary disease-driving cell type in AA. Only the depletion of CD8+ T cells, but not CD4+ T cells, NK, B, or γδ T cells, was sufficient to prevent and reverse AA. Selective depletion of regulatory T cells (Treg) showed that Treg are protective against AA in C3H/HeJ mice, suggesting that failure of Treg-mediated immunosuppression is not a major disease mechanism in AA. Focused analyses of CD8+ T cells revealed five subsets, whose heterogeneity is defined by an "effectorness gradient" of interrelated transcriptional states that culminate in increased effector function and tissue residency. scRNAseq of human AA skin showed that CD8+ T cells in human AA follow a similar trajectory, underscoring that shared mechanisms drive disease in both murine and human AA. Our study represents a comprehensive, systematic interrogation of lymphocyte heterogeneity in AA and uncovers a novel framework for AA-associated CD8+ T cells with implications for the design of future therapeutics.

Nicotine Pouch Awareness and Use Among Youth, National Youth Tobacco Survey, 2021.

INTRODUCTION: This manuscript examines prevalence of awareness and use of nicotine pouches among U.S. middle and high school students by sociodemographic characteristics and other tobacco product use and characterizes nicotine pouch and other tobacco product use behaviors among current nicotine pouch users. AIMS AND METHODS: Data are from the 2021 National Tobacco Youth Survey, a cross-sectional, school-based survey of middle and high school students (N = 20 413; overall response rate: 44.6%), which included questions on nicotine pouches in 2021 for the first time. Prevalence estimates, 95% confidence intervals, and estimated population counts were assessed for nicotine pouch awareness, ever use, and current (past 30 days) use, and for use behaviors related to nicotine pouches (frequency of use, flavor(s) used) and other tobacco products (ever, current, frequency of use) among current nicotine pouch users. RESULTS: Over one-third of students (35.5%) had ever heard of nicotine pouches. An estimated 1.9% (490 000) reported ever using them, while 0.8% (200 000) reported current use. Among current nicotine pouch users, 61.6% reported flavored nicotine pouch use, 64.2% reported current e-cigarette use, and 52.6% used multiple (≥2) tobacco products. Current use of nicotine pouches was common among current smokeless tobacco users (41.3%). CONCLUSIONS: Overall, in 2021, while relatively few students had ever tried nicotine pouches or currently used them, more than one-third had heard of them. Current nicotine pouch users tended to use other tobacco products, particularly e-cigarettes and smokeless tobacco. Given previous rapid increases in youth uptake of e-cigarettes, it is important to continue monitoring nicotine pouch use among young people. IMPLICATIONS: This study's findings provide an important baseline for future monitoring of nicotine pouch awareness and use among middle and high school students. Emerging tobacco products, particularly those that are flavored, widely available, discreet, and inexpensive have the potential to attract youth. Given the potential of these products to appeal to young people, ongoing monitoring of nicotine pouch use behaviors is important to inform public health and regulatory efforts.

Development of a nurse-led decision counseling program for improving hepatocellular carcinoma screening: A typology-guided feasibility study.

Objective: Hepatocellular carcinoma (HCC) is frequently diagnosed late. Although ultrasound-based HCC screening is recommended, its effectiveness is restricted by underutilization. This study aimed to develop a nurse-led decision counseling program used to improve HCC screening in patients with hepatitis B and to evaluate its feasibility in terms of process, resources, management, and cultural acceptance. Methods: The nurse-led decision counseling program was developed following the Medical Research Council framework and the preventive health model. Its components were informed by a systematic review and a qualitative study that had explored empirical HCC screening barriers. Guided by typology of Tickle-Degnen, a feasibility study was conducted among twenty eligible patients with hepatitis B, who were randomized to receive the intervention plus usual care or usual care only. Multisets of feasibility data were collected from interviews, field notes, and minutes of discussions with participants, family members, and clinical specialists. Results: The program consists of health education, tailored information, values clarification exercises, and exploring and addressing barriers, which help to achieve informed and value-based HCC screening utilization. Feasibility assessments identified and improved process issues, such as restrictive inclusion criteria and cultural challenges, including (1) default mistrust, (2) discrimination and confidentiality concerns, (3) cultural reluctance to open discussions about HCC screening, and (4) social influence under a collectivist culture. Conclusions: The study informs an innovative feasibility typology for nursing interventions and contributes to a promising, feasible, and culturally relevant intervention to improve HCC screening and prevent advanced diagnosis in hepatitis B-induced HCC in China and other hepatitis B-prevalent Asian countries. Trial registration: Clinicaltrials.gov: NCT04659005.