Disentangling the directionality among cultural stressors and psychosocial outcomes in recently immigrated Hispanic families: A random intercept cross-lagged panel model approach.

Research shows the impact of cultural stressors (e.g. perceived discrimination, bicultural stressors, negative context of reception) on adolescents' psychosocial outcomes. Given the presence of multiple cultural stressors in many Hispanic adolescents' lives, it is essential to examine the (a) developmental sequencing of cultural stressors among recent immigrant youth and (b) predictive effects of cultural stressors on adolescents' psychosocial outcomes. We employed a random intercept cross-lagged panel model to examine the longitudinal interplay among cultural stressors and their effects on youth outcomes using longitudinal data with six waves among 302 recently immigrated Hispanic adolescents (47% girls, Mage = 14.51, SD = .88). We observed bidirectional within-person relations and between-person associations among cultural stressors. At the within-person level, bidirectional cross-lagged effects emerged between perceived discrimination and bicultural stress, between perceived discrimination and negative context of reception, and between negative context of reception and bicultural stress. At the between-person level, bidirectional cross-lagged effects emerged only between perceived discrimination and bicultural stressors. Our findings indicate that cultural stressors explain heterogeneity in psychosocial outcomes: self-esteem was inversely predicted by all cultural stressors, whereas depressive symptoms were predicted only by perceived discrimination. In addition, optimism was predicted only by bicultural stressors, and externalizing behavior was predicted by both bicultural stressors and perceived discrimination. These results suggest that the longitudinal relationships among cultural stressors are (partly) bidirectional. Additionally, cultural stressors demonstrated differential predictive effects on psychosocial outcomes, indicating the added value of considering multiple cultural stressors and their longitudinal effects on adolescents' psychosocial outcomes.

Vaping Devices with Video Games.

The United States Food and Drug Administration (FDA) and other agencies have warned e-cigarette to companies to stop selling vaping products that look like toys because these products could attract youth to nicotine use. The vaping industry has gone a step further, producing vaping devices that are fully functional video games. We have observed several new vaping devices that contain youth-oriented video games such as Pac-Man, Tetris, Mario, Q*bert, and virtual pets. Some of these games reward users for each puff of nicotine. The incorporation of video games into vaping devices raises public health concerns regarding the potential appeal to younger users and the potential to escalate nicotine use and dependence. It is crucial to address these devices through robust policy, educational initiatives, and enforcement of existing policies.

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction: A Randomized Clinical Trial.

Importance: Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. Objective: To compare HF and CF PMRT outcomes after implant-based reconstruction. Design, Setting, and Participants: This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Interventions: Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. Main Outcomes and Measures: The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Results: Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). Conclusions and Relevance: In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. Trial Registration: ClinicalTrials.gov Identifier: NCT03422003.

The differential impacts of COVID-19 mortality on mental health by residential geographic regions: The Los Angeles Pandemic Surveillance Cohort Study.

OBJECTIVE: This study examines the association between changes in mental health before and during the COVID-19 pandemic and COVID-19 mortality across geographic areas and by race/ethnicity. METHODS: A cross-sectional survey was conducted in Los Angeles County between April and May 2021. The study used the Patient Health Questionnaire-2 to assess major depression risk. Participants' home ZIP codes were classified into low, middle, and high COVID-19 mortality impacted areas (CMIA). RESULTS: While there were existing mental health disparities due to differences in demographics and social determinants of health across CMIA in 2018, the pandemic exacerbated the disparities, especially for residents living in high CMIA. Non-White residents in high CMIA reported the largest deterioration in mental health. Differences in mental health by CMIA persisted after controlling for resident characteristics. CONCLUSIONS: Living in an area with higher COVID-19 mortality rates may have been associated with worse mental health, with Non-White residents reporting worse mental health outcomes in the high mortality area. POLICY IMPLICATIONS: It is crucial to advocate for greater mental health resources in high COVID-19 mortality areas especially for racial/ethnic minorities.

Hepatitis C virus NS5A and core protein induce fibrosis-related genes regulation on Huh7 cells through activation of LX2 cells.

INTRODUCTION AND OBJECTIVES: Liver fibrosis remains a complication derived from a chronic Hepatitis C Virus (HCV) infection even when it is resolved, and no liver antifibrotic drug has been approved. Molecular mechanisms on hepatocytes and activation of hepatic stellate cells (HSCs) play a central role in liver fibrogenesis. To elucidate molecular mechanisms, it is important to analyze pathway regulation during HSC activation and HCV infection. MATERIALS AND METHODS: We evaluate the fibrosis-associated molecular mechanisms during a co-culture of human HSCs (LX2), with human hepatocytes (Huh7) that express HCV NS5A or Core protein. We evaluated LX2 activation induced by HCV NS5A or Core expression in Huh7 cells during co-culture. We determined a fibrosis-associated gene expression profile in Huh7 that expresses NS5A or Core proteins during the co-culture with LX2. RESULTS: We observed that NS5A induced 8.3-, 6.7- and 4-fold changes and that Core induced 6.5-, 1.8-, and 6.2-fold changes in the collagen1, TGFß1, and timp1 gene expression, respectively, in LX2 co-cultured with transfected Huh7. In addition, NS5A induced the expression of 30 genes while Core induced 41 genes and reduced the expression of 30 genes related to fibrosis in Huh7 cells during the co-culture with LX2, compared to control. The molecular pathways enriched from the gene expression profile were involved in TGFB signaling and the organization of extracellular matrix. CONCLUSIONS: We demonstrated that HCV NS5A and Core protein expression regulate LX2 activation. NS5A and Core-induced LX2 activation, in turn, regulates diverse fibrosis-related gene expression at different levels in Huh7, which can be further analyzed as potential antifibrotic targets during HCV infection.

Increase in forest structural complexity along a precipitation gradient is mediated by partial harvests in temperate Patagonian forests.

Increasing forest structural complexity is becoming a common goal in forestry worldwide. However, the lack of empirical quantification clouds its implementation. Here we quantified the long-term effects (> 30 y) of partial harvest on stand structural complexity and net primary productivity using the east-west precipitation gradient (318-2508 mm, mean annual precipitation-MAP) of western Patagonian as a study system. In this gradient, pairs of 1-ha plots on 20 sites (20 plots harvested and 20 plots unharvested) were installed. In each plot terrestrial laser scanning was used to quantify the stand structural complexity index (SSCI), and Sentinel satellite images to obtain the Enhanced Vegetation Index (EVI: proxy of net primary productivity). Generalized linear mixed-effect models were used to relate SSCI to MAP and EVI to SSCI, with harvesting as indicator variable, and site as random variable (two plots nested to same precipitation). Results showed that harvested plots on mesic-to-humid sites (but not on dry sites) had higher SSCI and EVI values compared to unharvested plots, likely due to a greater vertical canopy packing. These results show the influence of precipitation on SSCI, which resulted in a more diversified stand structure and higher EVI. Such insights support site-specific management aimed to increase forest structural complexity.

Functional antibody responses targeting the Spike protein of SARS-CoV-2 Omicron XBB.1.5 in elderly nursing home residents following Wuhan-Hu-1-based mRNA booster vaccination.

The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group.

Probing Hydrodynamic Fluctuation-Induced Forces with an Oscillating Robot.

We study the dynamics of an oscillating, free-floating robot that generates radially expanding gravity-capillary waves at a fluid surface. In open water, the device does not self-propel; near a rigid boundary, it can be attracted or repelled. Visualization of the wave field dynamics reveals that when near a boundary, a complex interference of generated and reflected waves induces a wave amplitude fluctuation asymmetry. Attraction increases as wave frequency increases or robot-boundary separation decreases. Theory on confined gravity-capillary wave radiation dynamics developed by Hocking in the 1980s captures the observed parameter dependence due to these "Hocking fields." The flexibility of the robophysical system allows detailed characterization and analysis of locally generated nonequilibrium fluctuation-induced forces [M. Kardar and R. Golestanian, Rev. Mod. Phys. 71, 1233 (1999)RMPHAT0034-686110.1103/RevModPhys.71.1233].

Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease.

Introduction: It is now clear that coronavirus disease 19 (COVID-19) severity is associated with a dysregulated immune response, but the relative contributions of different immune cells is still not fully understood. SARS CoV-2 infection triggers marked changes in NK cell populations, but there are contradictory reports as to whether these effector lymphocytes play a protective or pathogenic role in immunity to SARS-CoV-2. Methods: To address this question we have analysed differences in the phenotype and function of NK cells in SARS-CoV-2 infected individuals who developed either very mild, or life-threatening COVID-19 disease. Results: Although NK cells from patients with severe disease appeared more activated and the frequency of adaptive NK cells was increased, they were less potent mediators of ADCC than NK cells from patients with mild disease. Further analysis of peripheral blood NK cells in these patients revealed that a population of NK cells that had lost expression of the activating receptor NKG2D were a feature of patients with severe disease and this correlated with elevated levels of cell free NKG2D ligands, especially ULBP2 and ULBP3 in the plasma of critically ill patients. In vitro, culture in NKG2DL containing patient sera reduced the ADCC function of healthy donor NK cells and this could be blocked by NKG2DL-specific antibodies. Discussion: These observations of reduced NK function in severe disease are consistent with the hypothesis that defects in immune surveillance by NK cells permit higher levels of viral replication, rather than that aberrant NK cell function contributes to immune system dysregulation and immunopathogenicity.

Young Adults' Exposure to and Engagement With Tobacco-Related Social Media Content and Subsequent Tobacco Use.

INTRODUCTION: Nicotine/tobacco social media content may increase young people's risk for use. This study examined prospective associations between exposure to and engagement with nicotine/tobacco-related social media content and nicotine/tobacco use among young adults. AIMS AND METHODS: Young adults (N = 2080) originally recruited from Southern California high schools for a prospective cohort study reported frequency of viewing and posting nicotine/tobacco content on four social media platforms (Facebook, Instagram, Twitter, and YouTube). Participants also reported frequency of seeing nicotine/tobacco posts from friends, seeing nicotine/tobacco posts from influencers or celebrities, and liking nicotine/tobacco posts. Within subsamples of nicotine/tobacco never users (n = 794), past users (n = 897) and current users (n = 389), analyses examined associations of baseline (May-October 2020) social media content exposure and engagement with follow-up (January-June 2021) tobacco use initiation (among never users), resumption (among past users), and continuation (among current users), adjusting for sociodemographic and socioenvironmental characteristics. RESULTS: Never users who saw nicotine/tobacco posts from friends (Adjusted Odds Ratio [AOR] = 2.91 [95% Confidence Interval [CI]: 1.46, 5.82], p = .002) or from celebrities or influencers (AOR = 2.77 [1.32, 5.84], p = .007) were significantly more likely to initiate nicotine/tobacco use than their peers. Among past users, posting nicotine/tobacco content at baseline was associated with use resumption (AOR = 1.77 [1.12, 2.80], p = .014). Content exposure and engagement were not associated with nicotine/tobacco use continuation among current users (p-values > .05). CONCLUSIONS: Seeing nicotine/tobacco posts from friends, influencers, or celebrities was associated with greater odds of tobacco use initiation, but not resumption or continuation, 6 months later. Young adults with past nicotine/tobacco use who post about nicotine/tobacco may be at elevated risk for resuming use. IMPLICATIONS: Young adults with exposure to nicotine/tobacco social media content were more likely than their peers to initiate nicotine/tobacco use 6 months later. Past nicotine/tobacco users who reported posting about nicotine/tobacco on social media at baseline were more likely than their peers to resume nicotine/tobacco use. Among young adults with current nicotine/tobacco use at baseline, social media activity did not predict odds of nicotine/tobacco use continuation at follow-up. Nicotine/tobacco content on social media should be restricted to reduce young people's chances of nicotine/tobacco use initiation or resumption.

SARS-CoV-2 membrane protein-specific antibodies from critically ill SARS-CoV-2-infected individuals interact with Fc receptor-expressing cells but do not neutralize the virus.

The membrane (M) glycoprotein of SARS-CoV-2 is one of the key viral proteins regulating virion assembly and morphogenesis. Immunologically, the M protein is a major source of peptide antigens driving T cell responses, and most individuals who have been infected with SARS-CoV-2 make antibodies to the N-terminal, surface-exposed peptide of the M protein. We now report that although the M protein is abundant in the viral particle, antibodies to the surface-exposed N-terminal epitope of M do not appear to neutralize the virus. M protein-specific antibodies do, however, activate antibody-dependent cell-mediated cytotoxicity and cytokine secretion by primary human natural killer cells. Interestingly, while patients with severe or mild disease make comparable levels of M antigen-binding antibodies, M-specific antibodies from the serum of critically ill patients are significantly more potent activators of antibody-dependent cell-mediated cytotoxicity than antibodies found in individuals with mild or asymptomatic infection.

Proximity to Cannabis Retailers and Recent Cannabis Use among a Diverse Sample of California Adolescents.

Background: As of May 2023, 23 states and Washington, DC have legalized the sale of cannabis for adults aged 21+, and 38 states, three territories, and D.C. have legalized medical cannabis. Exposure to cannabis retailers could increase adolescent cannabis use. Few studies have examined the impact of residential proximity to cannabis retailers on adolescent cannabis use, and previous findings are inconsistent. Methods: This study examined associations between proximity to cannabis retailers and past 30-day cannabis use. Data were from Project Cal Teens, a statewide survey of California adolescents regarding cannabis-related opinions/behaviors (N = 1406, mean age = 15.5 years, 48% female, 38% Hispanic/Latinx, 33% White, 15% Asian/Pacific Islander, 10% Black/African American, 5% Other/Multiracial). Participants were recruited via schools/social media in 2018-2020. Results: For every additional 5 driving miles to the nearest cannabis retailer, the risk of past 30-day cannabis use was reduced by 3.6% [IRR: 0.964; 95% CI: 0.935-0.994]. For every additional 5 miles from a licensed retailer, the risk of past 30-day cannabis use was reduced by 4.3% [IRR: 0.957; 95% CI: 0.926-0.989]. Interaction analyses revealed that among Hispanic/Latinx students, every 5 miles from a licensed retailer was associated with an 11.9% reduction in the risk of past 30-day cannabis use [IRR: 0.881; 95% CI: 0.820-0.945]. Conclusions: As the number of cannabis retailers in the U.S. increases with the continued legalization of adult cannabis use, research examining the effects of these policies on underage use is crucial. Interventions could include enforcement of zoning laws in/near residential areas to reduce accessibility of adolescents to cannabis retailers.

Surveying Adolescents During a Pandemic: Comparison of Adolescents Recruited via Social Media vs. Schools.

School-based surveys of adolescents can be logistically difficult and exclude students who do not attend school. Social media recruitment could be a promising strategy to recruit representative samples of adolescents. However, few studies have compared adolescent survey data collected via different methodologies. Our team was conducting a school-based survey when the COVID-19 pandemic closed all schools, necessitating a shift to online adolescent recruitment. To achieve our goal of obtaining a sample of high school students throughout California, we placed ads on social media. We compared the adolescents recruited in schools with those recruited on social media on demographic characteristics, mental health, and substance use. The sample of students recruited in schools (N = 737) and adolescents recruited via social media (N = 953) did not differ significantly on gender or substance use. However, compared with school-based recruitment, social media recruitment yielded a higher proportion of boys, whites, and Asians and a lower proportion of girls, Hispanic/Latinx adolescents, and those who spoke other languages at home. The social media sample had significantly higher levels of depression and anxiety symptoms and perceived stress than the school-based sample. Results indicate that social media can be useful for recruiting adolescents for survey research, especially if strategies such as Spanish-language social media ads are used to recruit and consent Hispanic/Latinx adolescents and those with non-English-speaking parents. This method could potentially replace school-based surveys in cases where schools are unwilling to participate in research, or it could be used to supplement school-based samples. Advantages and disadvantages of both methods are discussed.

Spanish-language tobacco-related posts on Twitter: content analysis.

INTRODUCTION: Twitter data has been used to surveil public sentiment about tobacco products, however, most tobacco-related Twitter research has been conducted with English-language posts. There is a gap in the literature on tobacco-related discussions on Twitter in languages other than English. This study summarized tobacco-related discussions in Spanish on Twitter. METHODS: A set of Spanish terms reflecting electronic cigarettes (e.g., cigarillos electrónicos), cigarettes (e.g., "pitillo"), and cigars (e.g., "cigaro") were identified. A content analysis of tweets (n=1,352) drawn from 2021 was performed to examine themes and sentiment. An initial codebook was developed in English then translated to Spanish and then translated back to English by a bilingual (Spanish and English) member of the research team. Two bilingual members of the research team coded the tweets into themes and sentiment. RESULTS: Themes in the tweets included 1) product promotion (n=168, 12.4%), 2) health warnings (n=161, 11.9%), 3) tobacco use (n=136, 10.1%), 4) health benefits of vaping (n=58, 4.3%), 5) cannabis use (n=50, 3.7%), 6) cessation (n=47, 3.5%), 7) addiction (n=33, 2.4%), 8) policy (n=27, 2.0%), and 9) polysubstance use (n=12, 0.9%). Neutral (n=955, 70.6%) was the most common category of sentiment observed in the data. CONCLUSIONS: Tobacco products are discussed in multiple languages on Twitter and can be summarized by bilingual research teams. Future research should determine if Spanish-speaking individuals are frequently exposed to pro-tobacco content on social media and if such exposure increases susceptibility to use tobacco among never users or sustained use among current users. IMPLICATIONS: Spanish-language pro-tobacco content exists on Twitter, which has implications for Spanish-speaking individuals who may be exposed to this content. Spanish-language pro-tobacco-related posts may help normalize tobacco use among Spanish-speaking populations. As a result, anti-tobacco tweets in Spanish may be necessary to counter areas of the online environment that can be considered pro-tobacco.

Characteristics associated with attitudes and behaviors towards mask wearing during the COVID-19 pandemic: The Trojan Pandemic Response Initiative.

BACKGROUND: Attitudes and behaviors towards mask wearing may influence the ability to reduce transmission of COVID-19 and other diseases. METHODS: University students, staff, and faculty (N = 9653) responded to an email invitation to complete electronic surveys (November 2021 and April 2022). Surveys included 19 items measuring attitudes and behaviors towards mask wearing from the Understanding America Study. Linear mixed models including variables for sex, age group, division, race and ethnicity, political affiliation, and history of COVID-19, were used to estimate the mean difference of the mean score for attitudes and behavior between Time 1 (November 2021) and Time 2 (April 2022). RESULTS: Participants were mostly female (62.1%), students (70.6%), White (39.5%) and Asian (34.7%). More than half identified their political affiliation as Democrat (65.5%). Characteristic variable-by-time interactions for difference in mean mask attitude scores difference were significant at Time 1 (T1) and Time 2 (T2) between Black and White participants (B = 0.18 (0.05), 95% CI: 0.07, 0.28, p = 0.001), Asian and White participants (B = 0.07 (0.02), 95% CI: 0.03-0.12, p = 0.001), participants with self-reported history of COVID-19 and no history of COVID-19 (B= -0.13 (0.02), 95% CI: -0.07, -0.18, p < 0.0001), females and males (B = 0.07 (0.02), 95% CI: 0.03, 0.11, p = 0.001), Republicans and Democrats (B= -0.18 (0.04), 95%CI: -0.26, -0.10, p < 0.0001) and Independents and Democrats (B= -0.10 (0.03), 95%CI: -0.15, -0.05, p < 0.0001). Mean difference in mean scores for mask behaviors at Time and Time 2 were significant between participants with COVID-19 and participants who did not have COVID-19 (B= -0.12 (0.04), 95% CI: -0.19, -0.04, p = 0.004), students compared to faculty and staff (B=-0.22 (0.05), -0.32, -0.12, p < 0.0001), between Republicans and Democrats (B-= -0.16 (0.07), 95% CI: -0.28, -0.03, p = 0.020, and between Independents and Democrats (B=-0.08 (0.04), 95% CI: -0.16, -0.002, p = 0.04). CONCLUSION: Race and ethnicity, political affiliation, and division may affect attitudes and behaviors in mask wearing. Further investigation into how characteristics influence public health measures such as mask wearing is needed to contain the spread of the COVID-19 virus, other infectious diseases, and future pandemics.

Humoral immunity against SARS-CoV-2 evoked by heterologous vaccination groups using the CoronaVac (Sinovac) and BNT162b2 (Pfizer/BioNTech) vaccines in Chile.

Introduction: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]. Methods: We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2. Results: We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups. Discussion: These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.

Pneumonitis in Patients Receiving Thoracic Radiotherapy and Osimertinib: A Multi-Institutional Study.

Introduction: Thoracic radiotherapy (TRT) is increasingly used in patients receiving osimertinib for advanced NSCLC, and the risk of pneumonitis is not established. We investigated the risk of pneumonitis and potential risk factors in this population. Methods: We performed a multi-institutional retrospective analysis of patients under active treatment with osimertinib who received TRT between April 2016 and July 2022 at two institutions. Clinical characteristics, including whether osimertinib was held during TRT and pneumonitis incidence and grade (Common Terminology Criteria for Adverse Events version 5.0) were documented. Logistic regression analysis was performed to identify risk factors associated with grade 2 or higher (2+) pneumonitis. Results: The median follow-up was 10.2 months (range: 1.9-53.2). Of 102 patients, 14 (13.7%) developed grade 2+ pneumonitis, with a median time to pneumonitis of 3.2 months (range: 1.5-6.3). Pneumonitis risk was not significantly increased in patients who continued osimertinib during TRT compared with patients who held osimertinib during TRT (9.1% versus 15.0%, p = 0.729). Three patients (2.9%) had grade 3 pneumonitis, none had grade 4, and two patients had grade 5 events (2.0%, diagnosed 3.2 mo and 4.4 mo post-TRT). Mean lung dose was associated with the development of grade 2+ pneumonitis in multivariate analysis (OR = 1.19, p = 0.021). Conclusions: Although the overall rate of pneumonitis in patients receiving TRT and osimertinib was relatively low, there was a small risk of severe toxicity. The mean lung dose was associated with an increased risk of developing pneumonitis. These findings inform decision-making for patients and providers.

Antibody-dependent NK-cell and neutralizing antibody responses against the Spike protein of Wuhan-Hu-1 and Omicron BA.1 SARS-CoV-2 variants in vaccinated experienced and vaccinated naïve individuals.

Antibodies triggering Fc-mediated NK cell activity may contribute to protection against disease caused by SARS-CoV-2 infection in humans. However, how these Fc-mediated humoral responses compare between individuals displaying hybrid immunity (Vac-ex) and those fully vaccinated with no history of SARS-CoV-2 infection (Vac-n) and whether they correlate with neutralizing antibody (NtAb) responses remains largely undetermined. In this retrospective study serum samples from 50 individuals (median age, 44.5 years; range, 11-85; 25 males), 25 Vac-ex and 25 Vac-n were studied. A flow-cytometry-based antibody-mediated NK-cell activation assay was used to quantitate effector NK-cells stimulated to express LAMP1 (lysosomal associated membrane protein 1), MIP1 (Macrophage inflammatory protein 1), and interferon-γ (IFNγ); NK cells isolated from two donors (D1 and D2) were used. NtAb levels targeting the Spike protein of Wuhan-Hu-1 and Omicron BA.1 SARS-CoV-2 variants were quantitated using a SARS-CoV-2 S pseudotyped neutralization assay. Regardless of the SARS-CoV-2 variant S antigen used in the NK-cell activation assay, the frequency of NK cells stimulated to express LAMP-1, MIP1ß, and IFNγ was higher in Vac-ex compared with Vac-n (p values ranging from 0.07 to 0.006) for D1; this was only seen for BA.1 when NK cells from D2 were employed. The frequency of functional NK cells activated by antibody binding to either Wuhan-Hu-1 or Omicron BA.1 S protein was not significantly different for both VAC-ex and VAC-n. In contrast, NtAb titers against BA.1 were around 10-fold lower than that against Wuhan-Hu-1. Vac-ex displayed higher NtAb titers against both (sub)variants than Vac-n. NK-cell responses correlated poorly with NtAb titers (ρ ≤ 0.30). The data demonstrate higher cross-reactivity across variants of concern for antibodies triggering Fc-mediated NK cell than for NtAb. Moreover, Vac-Ex seemed to display more robust functional antibody responses as compared with Vac-n.