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Michael Woodward,1,* Venkatasubramanian Ramasubramanian,2 Adeeba Kamarulzaman,3 Terapong Tantawichien,4 Minggui Wang,5 Joon Young Song,6 Won Suk Choi,7 Samsuridjal Djauzi,8 Rontgene Solante,9 Wen-Sen Lee,10 Kazuhiko Tateda,11 HongXing Pan,12 Ning-Chi Wang,13 Tikki Pang14,* 1Aged Care Research, Austin Health, Melbourne, VIC, Australia; 2Department of Infectious Diseases, HIV & Tropical Medicine, Apollo Hospitals, Chennai, TN, India; 3Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia; 4Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 5Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, SH, People’s Republic of China; 6Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 7Division of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korean University College of Medicine, Ansan, Korea; 8Allergy and Clinical Immunology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 9Adult Infectious Diseases and Tropical Medicine, San Lazaro Hospital, Manila, NCR, Philippines; 10Division of Infectious Diseases, Department of Internal Medicine, New Taipei City Hospital, New Taipei, Taiwan; 11Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University, Tokyo, Japan; 12Institution of Vaccine Clinical Trials, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, JS, People’s Republic of China; 13Department of Medicine, Tri-Service Hospital, Taipei, Taiwan; 14Centre for Behavioural and Implementation Science Interventions, Yong Loo Lin School of Medicine, National University of Singapore, Singapore*These authors contributed equally to this workCorrespondence: Tikki Pang, Centre for Behavioural and Implementation Science Interventions, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, 117597, Singapore, Tel +65 6516 1048, Email mdctep@nus.edu.sgAbstract: The impact of vaccinating the older population against vaccine-preventable diseases in terms of health, social and economic benefits has been increasingly recognised. However, there is a gap in the utilisation of vaccines worldwide. The population is ageing at an unprecedented pace in the Asia-Pacific (APAC) region, with the number of persons older than 65 years set to double by 2050 to around 1.3 billion. More than 18% of the population in Japan, Hong Kong, and China is over the age of 65 years. This highlights the importance of prioritising resources to address societal obligations toward the needs of the ageing generation. This review provides an overview of the challenges to adult vaccination in APAC, drivers to increase vaccination coverage, vaccination insights gained through the COVID-19 pandemic, and potential measures to increase the uptake of adult vaccines in the region.Keywords: adult vaccination, vaccine-preventable diseases, VPD, adult vaccines, COVID-19 vaccination

Sun S Kim,1 Somporn Sitthisongkram,1 Kunsook Bernstein,2 Hua Fang,3 Won S Choi,4 Douglas Ziedonis5 1Department of Nursing, College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA, 2Hunter-Bellevue School of Nursing, Hunter College, City University of New York, New York, NY, 3Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, 4Department of Preventive Medicine and Public Health, University of Kansas Medical Center, Kansas City, KS, 5Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA Introduction: Korean women are reluctant to pursue in-person smoking cessation treatment due to stigma attached to women smokers and prefer treatment such as telephone and online smoking cessation programs that they can access secretively at home. However, there is some evidence that face-to-face interaction is the most helpful intervention component for them to quit smoking.Methods: This study is a pilot clinical trial that examined the acceptability and feasibility of a videoconferencing smoking cessation intervention for Korean American women and compared its preliminary efficacy with a telephone-based intervention. Women of Korean ethnicity were recruited nationwide in the United States and randomly assigned at a ratio of 1:1 to either a video arm or a telephone arm. Both arms received eight 30-minute weekly individualized counseling sessions of a deep cultural smoking cessation intervention and nicotine patches for 8 weeks. Participants were followed over 3 months from the quit day. Results: The videoconferencing intervention was acceptable and feasible for Korean women aged

Background: African Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers (use ≤10 cigarettes per day). African Americans have been under-represented in smoking cessation research, and few studies have evaluated treatment for light smokers. This paper describes the study design, measures, and baseline characteristics from Kick It at Swope III (KIS-III), the first treatment study of bupropion for African American light smokers.Methods: Five hundred forty African American light smokers were randomly assigned to receive bupropion (150mg bid) (n = 270) or placebo (n = 270) for 7 weeks. All participants received written materials and health education counseling. Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up.Results: Of 2,628 individuals screened, 540 were eligible, consented, and randomized to treatment. Participants had a mean age of 46.5 years and 66.1% were women. Participants smoked an average of 8.0 cigarettes per day, had a mean exhaled carbon monoxide of 16.4ppm (range 1-55) and a mean serum cotinine of 275.8ng/ml. The mean Fagerström Test for Nicotine Dependence was 3.2, and 72.2% of participants smoked within 30 minutes of waking. The average number of quit attempts in the past year was 3.7 and 24.2% reported using pharmacotherapy in their most recent quit attempt. Motivation and confidence to quit were high.Conclusion: KIS-III is the first study designed to examine both nicotine and bupropion metabolism, evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors, in the context of treatment of African American light smokers. Of 1629 smokers screened for study participation, only 18 (1.1%) were ineligible to participate in the study because they refused blood draws, demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses. Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers. © 2011 Cox et al; licensee BioMed Central Ltd.

PURPOSE: This double-blind randomized crossover study compared the analgesic efficacy of pre- and postoperative administration of oral pregabalin 75 mg using a postsurgical dental pain model. MATERIALS AND METHODS: Patients requiring third molar surgery in 2 separate stages under local anesthesia were recruited. They were given pregabalin 75 mg either 1 hour before or after their first surgical extraction. They then received the same dose of pregabalin at their second surgical extraction, but those who received it before surgery received it postsurgery, and vice versa. Postoperative analgesic effects were assessed at postoperative hours 2, 4, 8, 12, 24, 48, and 72. Time to first analgesic, analgesic consumption and adverse events were also evaluated. RESULTS: Forty patients were recruited, and 34 completed the study. The area under curves for numerical rating scale pain scores 1 to 24 hours were significantly lower at rest but not during mouth opening for patients receiving postoperative pregabalin (P < .048). Pain relief was similar for the period of 24 to 72 hours. No significant difference was found in time to first analgesic, total analgesic consumption, and side effects between preoperative and postoperative groups. No difference in the incidence of adverse events was noticed in relation to the timing of pregabalin administration. CONCLUSIONS: Postoperative administration of oral pregabalin 75 mg appears to offer better analgesic efficacy than preoperative administration after third molar surgery under local anesthesia. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effects of resveratrol, a natural polyphenol with neuroprotective properties, on retinal neuronal cell death mediated by diabetes-induced activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII).Research Design and Methods: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received buffer. All mice were killed 2 months after the injections, and the extent of neuronal cell death, CaMKII, and phospho-CaMKII protein expression levels and CaMKII kinase activity were examined in the retinas. To assess the role of CaMKII in the death of retinal neurons, a small-interfering RNA (siRNA) or specific inhibitor of CaMKII was injected into the right vitreous humor, and vehicle only was injected into the left vitreous humor, 2 days before death. Resveratrol (20 mg/kg) was administered by oral gavage daily for 4 weeks, beginning 1 month after the fifth injection of either STZ or buffer.Results: The death of retinal ganglion cells (RGCs), CaMKII, phospho-CaMKII protein levels, and CaMKII activity were all greatly increased in the retinas of diabetic mice compared with controls, 2 months after induction of diabetes. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive signals co-localized with CaMKII- and phospho-CaMKII immunoreactive RGCs. However, in addition to CaMKII knockdown and inhibition by siRNA or a specific inhibitor, respectively, resveratrol provided complete protection from diabetes-induced retinal cell death.Conclusions: In the present study, resveratrol prevented diabetes-induced RGC death via CaMKII downregulation, implying that resveratrol may have potential therapeutic applications for prevention of diabetes-induced visual dysfunction. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Interleukin-32 (IL-32) is a recently discovered cytokine that appears to play a critical role in human rheumatoid arthritis (RA). It is highly expressed in synovium and fibroblast-like synoviocytes (FLS) from RA patients, but not in patients with osteoarthritis (OA). This study was undertaken to assess IL-32 levels in RA synovial fluid (SF) and to investigate the secretion and regulation of IL-32 in RA FLS. METHODS: FLS and SF were obtained from the joints of RA patients. The secretion and expression of IL-32 and activation of signaling molecules were examined by enzyme-linked immunosorbent assay, immunoblotting, immunoprecipitation, reverse transcriptase-polymerase chain reaction, and small interfering RNA (siRNA) transfection. RESULTS: IL-32 levels were high in RA SF compared with OA SF. Furthermore, RA FLS expressed and secreted IL-32 when stimulated with tumor necrosis factor alpha (TNFalpha). TNFalpha-induced expression of IL-32 was significantly suppressed, in a dose-dependent manner, by inhibitors of Syk, protein kinase Cdelta (PKCdelta), and JNK and by knockdown of these kinases and c-Jun with siRNA. We also observed that PKCdelta mediated the activation of JNK and c-Jun, and experiments using specific inhibitors and siRNA demonstrated that Syk was the upstream kinase for the activation of PKCdelta. CONCLUSION: The present findings suggest that IL-32 may be a newly identified prognostic biomarker in RA, thereby adding valuable knowledge to the understanding of this disease. The results also demonstrate that the production of IL-32 in RA FLS is regulated by Syk/PKCdelta-mediated signaling events. [ABSTRACT FROM AUTHOR]

Cordyceps sinensis, one of the well-known fungi used in traditional Chinese medicine, is recognized to play a role in the metabolic process of inflammation and immunity. The purpose of this study was to evaluate the effects of water extracts of C. sinensis on the immune function of mesenteric lymph node (MLN) lymphocytes in C57Bl/6N mice. C. sinensis-treated mice were administered the respective extract by oral gavage for 4 weeks. Immunoglobulin E concentrations in serum and MLN lymphocytes were significantly lower in C. sinensis-treated mice than in control mice. In contrast, the immunoglobulin A concentration from the C. sinensis group was higher than that in control mice. C. sinensis increased the proportion of CD4(+) and CD8(+) T cells in MLN lymphocytes. C. sinensis significantly decreased interleukin-4 and interleukin-10 cytokine concentrations. Therefore, water extracts of C. sinensis modulate immune parameters through regulation of immunoglobulin production resulting from decreased T-lymphocyte helper 2 cytokine secretion and reduce cytokine secretion in MLN lymphocytes. [ABSTRACT FROM AUTHOR]

AIM: Approximately 50% of African American smokers are light smokers (smoke < or = 10 cigarettes a day). The prevalence of light smoking in the United States is increasing, yet there has not been a single smoking cessation clinical trial targeting light smokers. The purpose of this 2 x 2 factorial, randomized clinical trial was to evaluate the efficacy of nicotine gum (2 mg versus placebo) and counseling (motivational interviewing versus health education) for African American light smokers. DESIGN: Participants were assigned randomly to one of four study arms: 2 mg nicotine gum plus health education (HE); 2 mg nicotine gum plus motivational interviewing (MI); placebo gum plus HE; and placebo gum plus MI. PARTICIPANTS AND SETTING: A total of 755 African American light smokers (66% female, mean age = 45) were enrolled at a community health center over a 16-month period. INTERVENTION AND MEASUREMENTS: Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study. Biochemical measures included expired carbon monoxide (CO) and serum and salivary cotinine. FINDINGS: Seven-day quit rates for nicotine gum were no better than for the placebo group (14.2% versus 11.1%, P = 0.232) at 6 months. However, a counseling effect emerged, with HE performing significantly better than MI (16.7% versus 8.5%, P < 0.001). These results were consistent across outcome time-points (weeks 1, 8, and 26). CONCLUSIONS: Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation. Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit. [ABSTRACT FROM AUTHOR]

We studied the relationship between reading nutrition labels and percent calorie intake from fat. In adolescent boys, reading nutrition labels was associated with higher fat intake. In girls, fat intake did not differ by frequency of nutrition label reading. Nutrition label reading does not translate into healthier diet in adolescents. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY: Gastrodia elata (GE) Blume (Orchidaceae) has been traditionally used as a folk medicine in Oriental countries since centuries for their variety of therapeutic benefits. This study is an attempt to investigate the protective effects of GE extract against MPP(+)-induced cytotoxicity in human dopaminergic SH-SY5Y cells and explore the neuroprotective mechanisms involved. MATERIALS AND METHODS: Human dopaminergic SH-SY5Y cells were used to demonstrate the protective effects of GE against multiple parameters such as MPP(+)-induced cell viability, oxidative damage, expression of Bcl-2 and Bax, caspase-3 and poly(ADP-ribose) polymerase proteolysis. RESULTS: GE effectively attenuated the cytotoxicity and improved cell viability in a dose-dependent manner. GE was effective in inhibiting both, the increased production of reactive oxygen species (ROS) and increase in Bax/Bcl-2 ratio, cleaved caspase-3 and PARP proteolysis. CONCLUSION: Data from this study suggests the protective effects of GE on MPP(+)-induced cytotoxicity in dopaminergic cells, which may be ascribed to its significant anti-oxidative and anti-apoptotic properties, thus, GE might prove to be a valuable therapeutic agent for the treatment of various neurodegenerative diseases including progressive Parkinson's disease (PD). [ABSTRACT FROM AUTHOR]

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum morifolium Ramat (Asteraceae) has (CM) long been used in Korean and Chinese traditional herbal medicines with numerous therapeutic applications. AIM OF THE STUDY: To evaluate the neuroprotective activities of Chrysanthemum morifolium (CM) extract against 1-methyl-4-phenylpridinium ions (MPP(+)), Parkinsonian toxin through oxidative stress and impaired energy metabolism, in human SH-SY5Y neuroblastoma cells and the underlying mechanisms. MATERIALS AND METHODS: The effects of CM against MPP(+)-induced cytotoxicity and neuronal cell viability, oxidative damage, the expression of Bcl-2 and Bax, caspase-3 and poly(ADP-ribose) polymerase (PARP) proteolysis were evaluated by using SH-SY5Y neuroblastoma cells. RESULTS: CM effectively inhibited the cytotoxicity and improved cell viability. CM also attenuated the elevation of reactive oxygen species (ROS) level, increase in Bax/Bcl-2 ratio, cleavage of caspase-3 and PARP proteolysis. CONCLUSION: These results demonstrate that CM possesses potent neuroprotective activity and therefore, might be a potential candidate in neurodegenerative diseases such as Parkinson's disease. [ABSTRACT FROM AUTHOR]

Purpose: Recruitment is often the rate-limiting step in conducting clinical trials among ethnic minorities. Little is known about participants who consent and enroll into a trial, but do not return for randomization. Why participants fail to return for randomization is largely unknown.Methods: We compared 287 enrolled African American smokers who did not return for randomization, to the 500 who returned and were randomized to participate in a clinical trial for smoking cessation in African Americans. Analyses were conducted to identify variables associated with not returning for randomization.Results: Univariate comparisons found the nonrandomized group to be significantly different from those randomized. Logistic regression showed younger age, less readiness to quit, having been proactively recruited, lacking a regular source of health care, believing that they will be smoking in 6 months, less church attendance, and a lower literacy level to be jointly related with not returning for randomization.Conclusions: African American participants who did not return for randomization into a clinical trial were different from those who did. Better understanding of these factors may allow researchers to target recruitment efforts resulting in enhanced accrual in clinical trials and increased efficiency. [ABSTRACT FROM AUTHOR]

Infinite-layer transition metal oxides with two-dimensional oxygen coordination exhibit intriguing electronic and magnetic properties due to strong in-plane orbital hybridization. The synthesis of this distinctive structure has primarily relied on kinetically controlled reduction of oxygen-rich phases featuring three-dimensional polyhedral oxygen coordination. Here, using in situ atomic-resolution electron microscopy, we scrutinize the intricate atomic-scale mechanisms of oxygen conduction leading to the transformation of SrFeO 2.5 to infinite-layer SrFeO 2 . The oxygen release is highly anisotropic and governed by the lattice reorientation aligning the fast diffusion channels towards the outlet, which is facilitated by cooperative yet shuffle displacements of iron and oxygen ions. Accompanied with the oxygen release, the three-dimensional to two-dimensional reconfiguration of oxygen is facilitated by the lattice flexibility of FeO x polyhedral layers, adopting multiple discrete transient states following the sequence determined by the least energy-costing pathways. Similar transformation mechanism may operate in cuprate and nickelate superconductors, which are isostructural with SrFeO 2 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: We evaluated the radiologic, pulmonary functional, and antibody statuses of coronavirus disease 2019 (COVID-19) patients 6 and 18 months after discharge, comparing changes in status and focusing on risk factors for residual computed tomography (CT) abnormalities., Methods: This prospective cohort study was conducted on COVID-19 patients discharged between April 2020 and January 2021. Chest CT, pulmonary function testing (PFT), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements were performed 6 and 18 months after discharge. We evaluated factors associated with residual CT abnormalities and the correlation between lesion volume in CT (lesion volume ), PFT, and IgG levels., Results: This study included 68 and 42 participants evaluated 6 and 18 months, respectively, after hospitalizations for COVID-19. CT abnormalities were noted in 22 participants (32.4%) at 6 months and 13 participants (31.0%) at 18 months. Lesion volume was significantly lower at 18 months than 6 months ( P < 0.001). Patients with CT abnormalities at 6 months showed lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), and patients with CT abnormalities at 18 months exhibited lower FVC. FVC significantly improved between 6 and 18 months of follow-up (all P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with CT abnormalities at 6 and 18 months ( P < 0.001). At 18-month follow-up assessments, age was associated with CT abnormalities (odds ratio, 1.17; 95% confidence interval, 1.03-1.32; P = 0.01), and lesion volume showed a positive correlation with IgG level ( r = 0.643, P < 0.001)., Conclusion: At 18-month follow-up assessments, 31.0% of participants exhibited residual CT abnormalities. Age and higher SARS-CoV-2 IgG levels were significant predictors, and FVC was related to abnormal CT findings at 18 months. Lesion volume and FVC improved between 6 and 18 months., Trial Registration: Clinical Research Information Service Identifier: KCT0008573., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra -/- ) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD., (© 2024. The Author(s).)

This study presents a framework for determining the prioritization of vaccine introduction in the National Immunization Program (NIP) of the Republic of Korea, with a focus on case examples assessed in 2021 and 2023. We describe the predefined criteria for evaluating the prioritization of vaccines in the NIP and the established process in the Republic of Korea. These criteria included disease characteristics, vaccine characteristics, rationality and efficiency of resource allocation, and the acceptance of immunization. The process of prioritizing NIP introduction involved several sequential steps: a demand survey, evidence collection, preliminary evaluation, priority evaluation, and decision making. In 2021 and 2023, 14 and 25 committee members participated in evaluating the prioritization of vaccines in the NIP, respectively. Overall, 13 and 19 NIP vaccine candidates were included in the 2021 and 2023 evaluations, respectively. Through the Delphi survey and consensus processes, the priority order was determined: vaccination against Rotavirus infection was the top priority in 2021, while Influenza 4v (for chronic disease patients) took precedence in 2023. This study demonstrates an evidence-based decision-making process within the healthcare field. The outlined approach may provide valuable guidance for policymakers in other countries seeking to prioritize the inclusion of new vaccines in their NIP.

HER2-enriched (HER2 + ) breast cancers express high levels of the growth-promoting HER2 protein. Although these cancers are treated with the HER2-targeted drug, trastuzumab, resistance to treatment is common. Retinoic acid (RA) is an anti-cancer agent that has been successfully used for the treatment of leukemia and holds promise for the treatment of solid cancers, including breast cancer. The HER2 gene is frequently co-amplified with RARA, a key determinant of RA sensitivity in breast cancers. It seems surprising, therefore, that HER2 + breast cancers are refractory to RA treatment. Here, we show that MYC mediates RA resistance by suppressing the expression of cellular retinoic acid binding protein 2 (CRABP2), resulting in RARα inactivation. CRABP2 is an intracellular RA transporter that delivers RA to the nuclear receptor RARα for its activation. Our results indicate that response to RA is enhanced by MYC depletion in HER2 + breast cancer cells and that RA treatment enhances trastuzumab responsiveness. Our findings support the use of RA and trastuzumab for the treatment of subsets of patients with breast cancers that are HER2-RARα co-amplified and have low levels of MYC., (© 2024 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1-deficient mice are resistant to metastasis and further protected by combined immune-checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF-β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK-target cell responses, which is dysregulated and hijacked by tumors during metastatic progression., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear., Methods: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points., Results: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4 + and CD8 + T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4 + T, CD8 + T EM , CD8 + T EMRA , and T FH cells, increased with age., Conclusions: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations., (© 2024. The Author(s).)

Introduction: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear., Methods: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike 1 ) and beta and gamma variant (Spike 2 ) were utilized., Results: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike 1 and Spike 2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike 2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05)., Conclusion: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Enhancing corporate accountability in areas such as environment, social, and governance (ESG) has solidified its role in the discussion on improving corporate resilience and growth. ESG management activities not only augment corporate sustainability and risk control but also influence the professional roles and personal lives of members through their perceived ESG. Historically, most ESG research has centered on the interrelation of corporate ESG endeavors and outcomes, while studies focusing on the influence of perceived ESG on members have been sparse. In this light, our investigation, rooted in the conservation of resources theory, aimed to delineate the mechanistic link between perceived ESG and members' psychological well-being. This study employed a stratified random sampling technique and collected data across three waves, each spaced four weeks apart. Our sample comprised 325 Korean employees working in administrative, technical, service, and sales roles. This study recruited 325 Korean employees across three time-lagged phases and found that ESG comprehension enhances job meaningfulness, subsequently amplifying psychological wellness. Intriguingly, as pay satisfaction escalates, the mediating role of job meaningfulness between perceived ESG and well-being intensifies. Our study underscores that for organizations to harness perceived ESG to boost psychological well-being via job meaningfulness, managing pay satisfaction is imperative. These findings highlight a crucial policy implication: policymakers must actively promote ESG awareness and incorporate it into employee compensation strategies. This integration is essential to cultivating a healthier, more engaged workforce and driving long-term organizational success.

Chiral phonons have recently been explored as a novel degree of freedom in quantum materials. The angular momentum carried by these quasiparticles is generated by the breaking of chiral degeneracy of phonons, owing to the chiral lattice structure or the rotational motion of ions of the material. In ferromagnets, a mechanism for generating non-equilibrium chiral phonons has been suggested, but their temporal evolution, which obeys Bose-Einstein statistics, remains unclear. Here we report the real-time dynamics of thermalized chiral phonons in an artificial superlattice composed of ferromagnetic metallic SrRuO 3 and non-magnetic insulating SrTiO 3 . Following the photo-induced ultrafast demagnetization in the SrRuO 3 layer, we observed the appearance of a magneto-optic signal in the superlattice, which is absent in the SrRuO 3 single films. This magneto-optic signal exhibits thermally driven dynamic properties and a clear correlation with the thickness of the non-magnetic SrTiO 3 layer, implying that it originates from thermalized chiral phonons. We use numerical calculations considering the magneto-elastic coupling in SrRuO 3 to validate our experimental observations and the angular momentum transfer mechanism between the lattice and spin systems in ferromagnetic systems and also to the non-magnetic system., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning., (© 2024. The Author(s).)

Maladaptive feeding behavior is the primary cause of modern obesity. While the causal influence of the lateral hypothalamic area (LHA) on eating behavior has been established in rodents, there is currently no primate-based evidence available on naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHA GABA ) neurons in eating using chemogenetics in three macaques. LHA GABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, predominantly for palatable food. Positron emission tomography and magnetic resonance spectroscopy validated chemogenetic activation. Resting-state functional magnetic resonance imaging revealed that the functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after LHA GABA neuron activation. Thus, our study elucidates the role of LHA GABA neurons in eating and obesity therapeutics for primates and humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Clinical trials powered to detect subgroup effects provide the most reliable data on heterogeneity of treatment effect among different subpopulations. However, pre-specified subgroup analysis is not always practical and post hoc analysis results should be examined cautiously. Bayesian hierarchical modelling provides grounds for defining a controlled post hoc analysis plan that is developed after seeing outcome data for the population but before unblinding the outcome by subgroup. Using simulation based on the results from a tobacco cessation clinical trial conducted among the general population, we defined an analysis plan to assess treatment effect among American Indians and Alaska Natives (AI/AN) enrolled in the study. Patients were randomized into two arms using Bayesian adaptive design. For the opt-in arm, clinicians offered a cessation treatment plan after verifying that a patient was ready to quit. For the opt-out arm, clinicians provided all participants with free cessation medications and referred them to a Quitline. The study was powered to test a hypothesis of significantly higher quit rates for the opt-out arm at one-month post randomization. Overall, one-month abstinence rates were 15.9% and 21.5% (opt-in and opt-out arm, respectively). For AI/AN, one-month abstinence rates were 10.2% and 22.0% (opt-in and opt-out arm, respectively). The posterior probability that the abstinence rate in the treatment arm is higher is 0.96, indicating that AI/AN demonstrate response to treatment at almost the same probability as the whole population.

Magnetic anisotropy in atomically thin correlated heterostructures is essential for exploring quantum magnetic phases for next-generation spintronics. Whereas previous studies have mostly focused on van der Waals systems, here we investigate the impact of dimensionality of epitaxially grown correlated oxides down to the monolayer limit on structural, magnetic, and orbital anisotropies. By designing oxide superlattices with a correlated ferromagnetic SrRuO 3 and nonmagnetic SrTiO 3 layers, we observed modulated ferromagnetic behavior with the change of the SrRuO 3 thickness. Especially, for three-unit-cell-thick layers, we observe a significant 1500% improvement of the coercive field in the anomalous Hall effect, which cannot be solely attributed to the dimensional crossover in ferromagnetism. The atomic-scale heterostructures further reveal the systematic modulation of anisotropy for the lattice structure and orbital hybridization, explaining the enhanced magnetic anisotropy. Our findings provide valuable insights into engineering the anisotropic hybridization of synthetic magnetic crystals, offering a tunable spin order for various applications.

Herpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi‑country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n  = 78) and physicians (general practitioners and specialists; n  = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.