A dual-acting DNASE1/DNASE1L3 biologic prevents autoimmunity and death in genetic and induced lupus models.

A defining feature of systemic lupus erythematosus (SLE) is loss of tolerance to self-DNA, and DNASE1L3 deficiency, the main enzyme responsible for chromatin degradation in blood, is also associated with SLE. This association includes an ultra-rare pediatric population with DNASE1L3 deficiency who develop SLE, adult patients with loss of function variants of DNASE1L3 who are at a higher risk for SLE, and patients with sporadic SLE who have neutralizing autoantibodies to DNASE1L3. To mitigate the pathogenic effects of inherited and acquired DNASE1L3 deficiencies, we engineered a long-acting enzyme biologic with dual DNASE1/DNASE1L3 activity that is resistant to DNASE1 and DNASE1L3 inhibitors. Notably, we found that the biologic prevented the development of lupus in Dnase1-/-/Dnase1L3-/- double knockout mice and rescued animals from death in pristane-induced lupus. Finally, we confirmed that the human isoform of the enzyme biologic was not recognized by autoantibodies in SLE and efficiently degrades genomic and mitochondrial cell free DNA, as well as microparticle DNA, in SLE plasma. Our findings suggest that autoimmune diseases characterized by aberrant DNA accumulation, such as SLE, can be effectively treated with a replacement DNASE tailored to bypass pathogenic mechanisms, both genetic and acquired, that restrict DNASE1L3 activity.

Public Support for Tobacco Endgame Policies: A Systematic Review and Meta-analysis.

INTRODUCTIONS: An increasing number of countries are adopting the tobacco endgame goal. High levels of public support can accelerate momentum towards implementing tobacco endgame policies. We aimed to conduct a systematic review of public support for tobacco endgame policies and to examine the geographical distribution of studies, support among key populations (adolescents and young adults, people who smoke), and the association between survey design and support. METHODS: We searched Embase, PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2013 onwards. Google was used to search the grey literature. The reference lists of included articles were hand-searched. Studies were included if they reported the proportions of people supporting one or more endgame policies. Risk of bias was assessed using the JBI checklist for prevalence studies. RESULTS: Forty-seven articles were included. Aotearoa/New Zealand and the United States were the countries with the most studies (n=11, respectively). Three-level meta-analyses showed the highest support for mandating a very low nicotine content in tobacco products (76%, 95% CI 61-87%). Meta-regressions were performed to assess the associations of population subgroup and survey design with support levels. The level of support was lower among people who smoke compared to the general population (ß range: -1.59 to -0.51). Support for some policies was lower when neutral or don't know response options were included. CONCLUSIONS: Public support for most tobacco endgame policies was high. IMPLICATIONS: Assessing public support can assist with progressing tobacco endgame policies. Policies that are widely supported by the public may be more politically feasible to implement. Qualitative studies and trial studies can further inform communication and implementation strategies for tobacco endgame policies.

Discourse Production Across the Adult Lifespan: Microlinguistic Processes.

Successful spoken discourse requires a speaker to be informative to deliver a coherent, meaningful message. The informativeness of discourse can be conveyed by the variety of vocabulary produced (i.e., lexical diversity [LD]), the typicality of vocabulary items used (i.e., core lexicon [CL]), and the amount of relevant content produced (i.e., information units). Yet, it is well documented that older adults produce less informative content compared to younger adults despite relatively subtle changes to LD. The typicality of core lexical items has not been assessed in healthy aging. Paradoxically, these results indicate that some aspects of discourse informativeness remain stable or even improve across the adult lifespan, while other aspects decline. The purpose of the current study is to understand how microlinguistic processes of informativeness change across the adult lifespan. The cross-sectional study included narrative language samples from two wordless picture books collected from 420 healthy participants between 20 and 89 years old. LD and percent of correct information units (%CIUs) were analyzed, as well as CL nouns and verbs. The results indicate that %CIUs and CL nouns demonstrate a quadratic decline starting around the ages of 40 and 60, respectively. LD shows a slight linear decline as a function of age. CL verbs are resistant to age-related changes but are influenced greater by education. The differing findings across the microlinguistic measures can be explained by the weakened connections within the language system and the differential characteristics of the measures. The findings contribute to the aging literature by systematically identifying the trajectory of how variables of informativeness change with age.

Inflammatory response in dairy cows caused by heat stress and biological mechanisms for maintaining homeostasis.

Climate change increases global temperatures, which is lethal to both livestock and humans. Heat stress is known as one of the various livestock stresses, and dairy cows react sensitively to high-temperature stress. We aimed to better understand the effects of heat stress on the health of dairy cows and observing biological changes. Individual cows were divided into normal (21-22 °C, 50-60% humidity) and high temperature (31-32 °C, 80-95% humidity), respectively, for 7-days. We performed metabolomic and transcriptome analyses of the blood and gut microbiomes of feces. In the high-temperature group, nine metabolites including linoleic acid and fructose were downregulated, and 154 upregulated and 72 downregulated DEGs (Differentially Expressed Genes) were identified, and eighteen microbes including Intestinimonas and Pseudoflavonifractor in genus level were significantly different from normal group. Linoleic acid and fructose have confirmed that associated with various stresses, and functional analysis of DEG and microorganisms showing significant differences confirmed that high-temperature stress is related to the inflammatory response, immune system, cellular energy mechanism, and microbial butyrate production. These biological changes were likely to withstand high-temperature stress. Immune and inflammatory responses are known to be induced by heat stress, which has been identified to maintain homeostasis through modulation at metabolome, transcriptome and microbiome levels. In these findings, heat stress condition can trigger alteration of immune system and cellular energy metabolism, which is shown as reduced metabolites, pathway enrichment and differential microbes. As results of this study did not include direct phenotypic data, we believe that additional validation is required in the future. In conclusion, high-temperature stress contributed to the reduction of metabolites, changes in gene expression patterns and composition of gut microbiota, which are thought to support dairy cows in withstanding high-temperature stress via modulating immune-related genes, and cellular energy metabolism to maintain homeostasis.

Sunflower seed extract supplementation reduces body fat in adults with obesity: A double-blind, randomized, placebo-controlled trial.

Obesity is an important public health problem and socioeconomic burden. We hypothesized that an intake of sunflower seed extract (SUN-CA) would decrease body fat and then investigated the effects and safety of SUN-CA intake on body fat in adults with obesity as an option for obesity treatment. In this double-blind, randomized, placebo-controlled study, 100 adults with body mass indices of 25 to 31.9 kg/m2 were assigned to groups that received SUN-CA (n = 50) or a placebo (n = 50) and received 1 tablet/day containing 500 mg of SUN-CA or the placebo over a 12-week period. The primary endpoint was the change in mass and percentage of body fat. The group that received SUN-CA daily showed decreases in body fat mass greater than those in the placebo group (-0.9 ± 1.8 kg vs. -0.1 ± 1.4 kg, P = .043). In addition, body weight, body mass index, and hip circumference improved after the intake of SUN-CA relative to the changes in the placebo group. There was no intergroup differences in the prevalence of adverse events. The accumulation of excess body fat improved through the intake of 500 mg/day of SUN-CA containing 100 mg of chlorogenic acids for 12 weeks in adults with obesity without causing serious adverse side effects. SUN-CA could be an effective and safe management option for obesity. The trial was registered at Clinical Research Information Service (CRIS: https://cris.nih.go.kr/cris/index/index.do) as KCT0005733.

Decrease in household secondhand smoking among Korean adolescents associated with smoke-free policies: grade-period-cohort and interrupted time series analyses.

OBJECTIVES: Smoke-free areas have expanded and related campaigns have been implemented since 1995 in Korea. As a result, household secondhand smoke (SHS) exposure has decreased over the past 15 years. We assessed the cohort effect, the effect of a 2008 campaign on household SHS exposure, and the impact of a complete smoking ban in public places along with increased penalties, as implemented in December 2011. METHODS: Nationally representative cross-sectional 15-wave survey data of Korean adolescents were used. The 810,516 participants were classified into 6 grade groups, 15 period groups, and 20 middle school admission cohorts. An age-period-cohort analysis, conducted with the intrinsic estimator method, was used to assess the cohort effect of household SHS exposure, and interrupted-time series analyses were conducted to evaluate the effects of the smoke-free policy and the campaign. RESULTS: For cohorts who entered middle school from 2002 to 2008, the risk of household SHS exposure decreased among both boys and girls. Immediately after implementation of the smoke-free policy, the prevalence of household SHS exposure by period decreased significantly for boys (coefficient, -8.96; p<0.05) and non-significantly for girls (coefficient, -6.99; p=0.07). After the campaign, there was a significant decrease in household SHS exposure by cohort among boys, both immediately and post-intervention (coefficient, -4.84; p=0.03; coefficient, -1.22; p=0.02, respectively). CONCLUSIONS: A school-admission-cohort effect was found on household SHS exposure among adolescents, which was associated with the smoke-free policy and the campaign. Anti-smoking interventions should be implemented consistently and simultaneously.

A preliminary investigation on core lexicon analysis in dementia of the Alzheimer's type.

BACKGROUND: Core lexicon (CL) analysis is a time efficient and possibly reliable measure that captures discourse production abilities. For people with aphasia, CL scores have demonstrated correlations with aphasia severity, as well as other discourse and linguistic measures. It was also found to be clinician-friendly and clinically sensitive enough to capture longitudinal changes in aphasia. To our knowledge, CL has never been investigated in individuals with neurologically progressive disease. AIMS: As a preliminary investigation, we sought to investigate (1) whether CL scores correlate with dementia severity, (2) whether CL scores correlate with measures of discourse quality, and (3) whether CL scores correlate with other measures of lexical/semantic access. METHODS & PROCEDURES: Twelve participants with a cognitive impairment associated with dementia of the Alzheimer's type (DAT) completed several measures of language and cognitive ability, as well as provide a language sample from the wordless picture book, Picnic. RESULTS & CONCLUSION: Results are informative, as they provide insight into characteristics of CL and provide support for potential use of CL in individuals with neurologically progressive disease. The results indicated that CL scores do correlate with dementia severity and several measures of language ability, indicating they may provide a useful measure of language abilities in DAT, but more research is needed. WHAT THIS PAPER ADDS: What is already known on the subject Core lexicon (CL) analysis is an assessment measure of discourse ability, most closely related to informativeness or productivity, used in aphasiology that is easier to use and less time consuming than previous measures of informativeness, such as correct information units or type-token ratio (TTR). For people with aphasia, CL analysis correlates with aphasia severity, measures of informativeness, as well as other measures of discourse quality. It has also been shown to be faster and more reliable between scorers than other informativeness measures. What this study adds Core lexicon analysis is a new simple and online method for assessing the informativeness of a discourse sample without the need to record or transcribe the language sample. CL is receiving a lot of attention in aphasia, correlating with everything from aphasia severity to measures of productivity and lexical access, as well as measures of informativeness. Unfortunately, no one has investigated CL analysis in dementia. The study demonstrates the first evidence that CL analysis may be a useful measure for determining dementia severity and language quality in people with dementia. What are the clinical implications of this work? Core lexicon analysis may provide clinicians and researchers with an easy method for assessing the discourse of people with a cognitive impairment associated with dementia of the Alzheimer's type. This will improve initial assessment, as well as improve ongoing language assessment that may provide clues into their functional ability to communicate effectively.

The complete mitochondrial genome of the bait worm, Marphysa victori (Annelida; Polychaeta; Eunicida; Eunicidae).

The complete mitochondrial genome of Marphysa victori Lavesque, Daffe, Bonifácio & Hutchings, 2017, was 15,891 bp in length with a GC content of 41%, comprising 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. The maximum-likelihood tree showed the closest relationship between M. victori and M. sanguinea.

Physical Activity Pattern of Adults With Metabolic Syndrome Risk Factors: Time-Series Cluster Analysis.

Background: Physical activity plays a crucial role in maintaining a healthy lifestyle, and wrist-worn wearables, such as smartwatches and smart bands, have become popular tools for measuring activity levels in daily life. However, studies on physical activity using wearable devices have limitations; for example, these studies often rely on a single device model or use improper clustering methods to analyze the wearable data that are extracted from wearable devices. Objective: This study aimed to identify methods suitable for analyzing wearable data and determining daily physical activity patterns. This study also explored the association between these physical activity patterns and health risk factors. Methods: People aged >30 years who had metabolic syndrome risk factors and were using their own wrist-worn devices were included in this study. We collected personal health data through a web-based survey and measured physical activity levels using wrist-worn wearables over the course of 1 week. The Time-Series Anytime Density Peak (TADPole) clustering method, which is a novel time-series method proposed recently, was used to identify the physical activity patterns of study participants. Additionally, we defined physical activity pattern groups based on the similarity of physical activity patterns between weekdays and weekends. We used the χ2 or Fisher exact test for categorical variables and the 2-tailed t test for numerical variables to find significant differences between physical activity pattern groups. Logistic regression models were used to analyze the relationship between activity patterns and health risk factors. Results: A total of 47 participants were included in the analysis, generating a total of 329 person-days of data. We identified 2 different types of physical activity patterns (early bird pattern and night owl pattern) for weekdays and weekends. The physical activity levels of early birds were less than that of night owls on both weekdays and weekends. Additionally, participants were categorized into stable and shifting groups based on the similarity of physical activity patterns between weekdays and weekends. The physical activity pattern groups showed significant differences depending on age (P=.004) and daily energy expenditure (P<.001 for weekdays; P=.003 for weekends). Logistic regression analysis revealed a significant association between older age (≥40 y) and shifting physical activity patterns (odds ratio 8.68, 95% CI 1.95-48.85; P=.007). Conclusions: This study overcomes the limitations of previous studies by using various models of wrist-worn wearables and a novel time-series clustering method. Our findings suggested that age significantly influenced physical activity patterns. It also suggests a potential role of the TADPole clustering method in the analysis of large and multidimensional data, such as wearable data.

Corrigendum: Modeling the future of tobacco control: Using SimSmoke to explore the feasibility of the tobacco endgame in Korea.

[This corrects the article DOI: 10.18332/tid/174127.].

Modeling the future of tobacco control: Using SimSmoke to explore the feasibility of the tobacco endgame in Korea.

INTRODUCTION: We used a simulation model to assess the feasibility of reaching the tobacco endgame target (reducing the smoking prevalence to below 5% by 2050) and explored potential implementation strategies. METHODS: The impact of strengthened tobacco-control policies on smoking prevalence was analyzed using Korea SimSmoke, a discrete-time Markov process. We considered the effects of various scenarios from 2023 and predictions were conducted until 2050. To confirm the stability of the results, deterministic and probabilistic sensitivity analyses were carried out by increasing and decreasing parameter estimates. RESULTS: The implementation of tobacco-control policies in accordance with the WHO MPOWER (Μonitor tobacco use and prevention policies; Protect people from tobacco smoke; Offer help to quit tobacco smoking; Warn of the dangers of tobacco; Enforce bans on tobacco advertising, promotion, and sponsorship; Raise taxes on tobacco) measures were insufficient to achieve the tobacco endgame objective of 5% by 2050. The overall predicted smoking prevalence in 2050 is 4.7% if all policies are fully implemented in accordance with the FCTC guidelines together with a complete ban on the sale of cigarettes to people born after 2003 and annual 10% increases in price. Sensitivity analyses using the varying policy effect assumptions demonstrated the robustness of the simulation results. CONCLUSIONS: For a substantive reduction in smoking prevalence, it is essential to strongly implement the MPOWER strategy. Beyond this foundational step, the eradication of smoking requires a paradigm shift in the perception of conventional tobacco-control policies, including a tobacco-free generation strategy and radical increases in the price of tobacco products.

Core lexicon in aphasia: A longitudinal study.

Background: General consensus exists between clinicians as to the incorporation of discourse outcome measures into language assessment for persons with aphasia (PWA). The development of core lexicon measures (CoreLex) has enabled clinicians to reduce time and labor intensive preparatory work for discourse analysis, which has been considered as an alternative measure to quantify word retrieval ability in discourse in a clinical context. Although previous studies have investigated the quality of the measure, CoreLex has rarely been longitudinally explored. Aims: We aimed to investigate the adequacy of CoreLex to document linguistic changes in PWA over time. Specifically, we examined (1) whether natural language recovery from acute to chronic stages is manifested differentially by tasks and (2) the extent to which the ability to retrieve words in isolation predicts the ability to retrieve words in context. Methods: A total of 19 PWA participated in the study. They completed a language assessment including confrontation naming tasks (Boston Naming Test [BNT] and Hopkins Action Naming Assessment [HANA]) and a picture description task using the Cookie Theft picture at acute and chronic stages. Discourse samples from the picture description task were quantified using CoreLex. Results: We found significant differences across tasks and time-points by PWA. Moderate correlations between the confrontation naming tasks and CoreLex were found at the acute stage but not at the chronic stage. Additionally, McNemar's tests demonstrated a significant difference in PWA's performance in CoreLex from the acute to the chronic stages. Conclusions: Our findings show that performance by PWA improves over time on all tasks, but language gains are manifested differentially by tasks. Performance in confrontation naming moderately predicts word retrieval in context acutely. However, lack of correlations between confrontation naming tasks and CoreLex later endorse inadequacy of using confrontation naming tasks as a proxy measure for discourse-level performance and improvement for PWA.

Association between tobacco industry advertising expenses and tobacco advertising exposure among Korean adolescents.

INTRODUCTION: Monitoring the activities and impacts of tobacco industries is vital for tobacco control. Based on tobacco industry financial statements and a nationally representative survey of Korean adolescents, we examined the association between tobacco industry commercial advertising expenses and advertising exposure among Korean adolescents. METHODS: The commercial advertising expenses of three major tobacco industries in Korea (KT&G, Philip Morris Korea, and British and American Tobacco Korea) were identified in a repository (Data Analysis Retrieval and Transfer System) established by the Korean Financial Supervisory Service. The yearly advertising expenses were merged with data from the Korean Youth Risk Behavior Survey (2015-2018 and 2021, total N=309 190). We used logistic regression analyses to analyse the associations between tobacco industry advertising expenses and adolescent tobacco advertisement exposure. RESULTS: In 2021, the total advertising expenses of the three companies exceeded US$260 million, and the proportion of Korean adolescents exposed to tobacco advertisements ranged from 65.9% to 78.7% during 2015-2018 and 2021. Higher advertising expense sizes were associated with the risk of exposure to tobacco advertisements in both girls and boys, with OR of 1.009 (95% CI (1): 1.008 to 1.010) and 1.010 (95% CI: 1.009 to 1.011), respectively. CONCLUSION: Tobacco industry advertising expenses are associated with tobacco marketing exposure among adolescents. We used financial data to identify the reach of tobacco advertising among Korean adolescents. It is essential to increase tobacco industry surveillance using various data sources and to regulate tobacco advertising more strongly.

Genetic Diversity, Regional Distribution, and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome Virus in Gangwon Province, Korea, a Highly Prevalent Region, 2019-2021.

Severe fever with thrombocytopenia syndrome (SFTS) is an arthropod-borne viral disease with a high mortality rate with high fever and thrombocytopenia. We investigated the clinical and epidemiological characteristics and viral genotypes from 2019 to 2021 in Gangwon Province, Korea. Of the 776 suspected cases, 62 were SFTS. The fatality rate was 11.5-28.6% (average rate, 19.4%), and the frequent clinical symptoms were high fever (95.2%), thrombocytopenia (95.2%), and leukopenia (90.3%). Hwacheon had the highest incidence rate per 100,000 persons at 8.03, followed by Inje and Yanggu (7.37 and 5.85, respectively). Goseong, Yangyang, and Hoengseong had rates of 2 or higher; Samcheok, Hongcheon, Jeongsen, and Yeonwol were 1.70-1.98, and Wonju, Gangneung, and Donghae were slightly lower, ranging from 0.31 to 0.74. Of the 57 cases with identified genotypes, eight genotypes (A, B1, B2, B3, C, D, E, and F) were detected, and the B2 genotype accounted for 54.4% (31 cases), followed by the A genotype at 22.8% (13 cases). The B2 and A genotypes were detected throughout Gangwon Province, and other genotypes, B1, B3, C, D, and F, were discovered in a few regions. In particular, genotype A could be further classified into subtypes. In conclusion, SFTS occurred throughout Gangwon Province, and Hwacheon had the highest incidence density. Multiple genotypes of SFTS were identified, with B2 and A being the most common. These findings provide important insights for the understanding and management of SFTS in this region.

Trends in adolescent secondhand smoke exposure at home over 15 years in Korea: Inequality by parental education level.

INTRODUCTION: Low parental education level and parental smoking are major risk factors for household secondhand smoke (SHS) exposure among adolescents. We investigated the trend in household SHS exposure according to sex, school, and parental education level to determine whether the decline in household SHS exposure over time depends on parental education level. METHODS: We used cross-sectional Korea Youth Risk Behavior datasets (2006-2020; 806829 subjects were eligible). We applied binary logistic regression to assess household SHS exposure trends and evaluated the interaction between period and parental education level. RESULTS: Household SHS exposure over 15 years has declined. The difference (0.121) was the smallest for male middle school students with low-educated parents. The slope for the estimated probability of household SHS exposure among students with high-educated parents was steeper than that for those with low-educated parents, except for female high school students (difference=0.141). Students with low-educated parents were at higher risk of household SHS exposure (male middle school students, adjusted odds ratio, AOR=1.52; 95% CI: 1.47-1.56; male high school students, AOR=1.42; 95% CI: 1.38-1.47; female middle school students, AOR=1.62; 95% CI: 1.58-1.67; female high school students, AOR=1.62; 95% CI: 1.57-1.67). The interaction between parental education level and period was significant. We also found a significant interaction between parental education level and parental smoking (other × present interaction, AOR=0.64; 95% CI: 0.60-0.67; low-low × present interaction, AOR=0.89; 95% CI: 0.83-0.95). CONCLUSIONS: Changes in parental education level over time mainly contributed to changes in adolescents' household SHS exposure. Adolescents with low-educated parents were at higher risk of household SHS exposure, with a slower decline. These gaps must be considered when creating and implementing interventions. Campaigns and community programs to prevent household SHS need to be emphasized among vulnerable adolescents.

Associations between Dietary Patterns and Metabolic Syndrome: Findings of the Korean National Health and Nutrition Examination Survey.

Metabolic syndrome (MetS) is a multifactorial cluster of metabolic disorders related to cardiovascular disease and type 2 diabetes mellitus. Diet and dietary patterns are significant factors in the development and management of MetS. The associations between dietary patterns (i.e., high-carbohydrate [HCHO], high-fat [HF], and high-protein [HP] diets) and the prevalence of MetS in Koreans were examined using data from the Korean National Health and Nutrition Examination Survey, collected between 2018 and 2020. The study included data from 9069 participants (3777 men and 5292 women). The percentage of participants with MetS was significantly higher in the HCHO diet group than in the normal diet group in women. Women with HCHO diet were positively associated with elevated blood pressure and triglyceride levels based on a comparison with the normal diet group (p = 0.032 and p = 0.005, respectively). Men with an HF diet were negatively associated with elevated fasting glucose levels based on a comparison with the normal diet group (p = 0.014). Our findings showed that HCHO intake was strongly associated with a higher risk of MetS, especially elevated blood pressure and triglyceride levels in women, and an HF diet was negatively associated with elevated fasting glucose levels in men. Further prospective studies of the impact of dietary carbohydrate, fat, and protein proportions on metabolic health are needed. The optimal types and proportions of these dietary components, as well as the underlying mechanisms through which suboptimal proportions can lead to MetS, should also be investigated.

Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

PURPOSE: This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect. RESULTS: Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1). CONCLUSION: The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

Resting-State Connectivity in Acute and Subacute Poststroke Aphasia: A Functional Near-Infrared Spectroscopy Pilot Study.

Background: Understanding how brain function and language skills change during early (acute and subacute) stroke phases is critical for maximizing patient recovery, yet functional neuroimaging studies of early aphasia are scarce. In this pilot study, we used functional near-infrared spectroscopy (fNIRS) to investigate how resting-state functional connectivity (rs-FC) in early aphasia differs from neurologically healthy adults and is related to language deficits. Materials and Methods: Twenty individuals with aphasia (12 acute and 8 subacute phase) and 15 healthy controls underwent rs-fNIRS imaging with a 46-channel montage centered over bilateral perisylvian language areas. FC was computed using a prewhitening, autoregressive Pearson correlation routine applied to preprocessed oxyhemoglobin (HbO) data. Connections were classified as left intra-, right intra-, or interhemispheric. We then compared rs-FC between groups by connection type and examined Spearman correlations between rs-FC averages and language measures within patients. Results: Participants in the acute phase had significantly reduced global rs-FC across all HbO-based connections compared to healthy controls. No significant differences were found in rs-FC between controls and patients in the subacute phase. Controlling for days since stroke, stronger right intra- and interhemispheric rs-FC was related to milder aphasia across all patients. Exploratory correlations revealed that relationships between language measures and rs-FC differed between acute and subacute patient groups. Conclusion: This study provides preliminary evidence that fNIRS-based rs-FC measures may be a viable metric to index the early impacts of stroke in people with aphasia.

Performance evaluation of newly developed surrogate virus neutralization tests for detecting neutralizing antibodies against SARS-CoV-2.

We evaluated newly developed surrogate virus neutralization tests (sVNT) for detecting neutralizing antibodies (NAbs) against the receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VERI-Q SARS-CoV-2 Neutralizing Antibody Detection ELISA Kit (MiCo BioMed, Gyeonggi-do, Republic of Korea, hereafter, "eCoV-CN") is an enzyme-linked immunosorbent assay-based sVNT, and VERI-Q SARS-CoV-2 Neutralizing Antibody Rapid Test Kit (MiCo BioMed, hereafter, "rCoV-RN") is a point-of-care lateral-flow immunochromatography test with auto-scanner. A total of 411 serum samples were evaluated. Both evaluations used a 50% plaque reduction neutralization test (PRNT50) as the gold standard. Compared with PRNT50, the eCoV-CN showed 98.7% positive percent agreement (PPA), 96.8% negative percent agreement (NPA), 97.4% total percent agreement (TPA), with kappa values of 0.942. The rCoV-RN showed 98.7% PPA, 97.4% NPA, 97.8% TPA, and kappa values of 0.951, comparing to PRNT50. Neither assay indicated cross-reactivity for other pathogens, and the signal indexes were statistically significantly correlated to the PRNT50 titer. The two evaluated sVNTs show comparable performances to the PRNT50 with the advantages of technical simplicity, speed, and do not require cell culture facilities.

Tobacco consumption, sales, and output as monitoring indicators in the era of the tobacco endgame: a Korean example.

OBJECTIVES: The consumption, sales, and output of tobacco products each suggest different areas of intervention for tobacco control. In the era of the tobacco endgame, as increasingly stronger supply-side measures are implemented, multifaceted indicators that assess both supply and/or demand are required. We aimed to estimate the consumption of cigarette and heated tobacco products (HTPs) and sought agreement between the various indicators. METHODS: The annual cigarette and HTP consumption in 2014-2020 was calculated using the frequency and intensity of cigarette use from representative surveys of adults and adolescents by sex and age. Sales and output data were acquired from governmental sources. Spearman correlation coefficients and Bland-Altman plots were used to compare the indicators. RESULTS: Tobacco output, cigarette sales, and cigarette consumption were greatest in 2014. The HTP consumption calculated for 2020 was 292.28 million packs. Cigarette consumption and sales correlated significantly, as did tobacco output and tobacco sales. A Bland-Altman plot comparing the difference between cigarette consumption and sales showed that this difference was largest in 2014, immediately before cigarette prices increased. With the exception of a single year, all cigarette consumption values were within the limits of agreement for cigarette sales and tobacco output. CONCLUSIONS: Our analyses showed agreement between demand-side (tobacco consumption) and supply-side (sales and output) indicators. We recommend using all indicators to monitor the impacts of tobacco control on both demand and supply sides. The systematic use of various indicators is critical to achieve the end of the tobacco epidemic.