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Amyloid-β (Aβ) and hyperphosphorylated tau protein are targets for Alzheimer's Disease (AD) immunotherapies, which are generally focused on single epitopes within Aβ or tau. However, due to the complexity of both Aβ and tau in AD pathogenesis, a multipronged approach simultaneously targeting multiple epitopes of both proteins could overcome limitations of monotherapies. Herein, we propose an active AD immunotherapy based on a nanoparticle vaccine comprising two Aβ peptides (1-14 and pyroglutamate pE3-14) and three tau peptides (centered on phosphorylated pT181, pT217 and pS396/404). These correspond to both soluble and aggregated targets and are displayed on the surface of immunogenic liposomes in an orientation that maintains reactivity with epitope-specific monoclonal antibodies. Intramuscular immunization of mice with individual epitopes resulted in minimally cross-reactive antibody induction, while simultaneous co-display of 5 antigens ("5-plex") induced antibodies against all epitopes without immune interference. Post-immune sera recognized plaques and neurofibrillary tangles from human AD brain tissue. Vaccine administration to 3xTg-AD mice using a prophylactic dosing schedule inhibited tau and amyloid pathologies and resulted in improved cognitive function. Immunization was well tolerated and did not induce antigen-specific cellular responses or persistent inflammatory responses in the peripheral or central nervous system. Antibody levels could be reversed by halting monthly vaccinations. Altogether, these results indicate that active immune therapies based on nanoparticle formulations of multiple Aβ and tau epitopes warrant further study for treating early-stage AD., Competing Interests: Declaration of Competing Interest J.F.L. and W-C.H. hold interest in POP Biotechnologies. W-C.H. and M.W. are employees of POP Biotechnologies. Other 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 Inc. All rights reserved.)

Drowsy driving among college students is a critical public health issue due to its significant impact on road safety. This cross-sectional study aimed to investigate the determinants of stopping drowsy driving behavior among college students using the multi-theory model (MTM) of health behavior change. Data for this study were collected from September to October 2023 via a 42-item psychometric valid, web-based survey disseminated via Qualtrics, involving 725 students from a large southwestern university. Nearly half of the participants (49.38%) reported drowsy driving in the past month. Hierarchical multiple regression analysis revealed that participatory dialogue ( p = 0.0008) and behavioral confidence ( p < 0.0001) significantly predicted the initiation of refraining from drowsy driving, with the final model explaining 36.4% of the variance. Similarly, emotional transformation ( p < 0.0001) and practice for change ( p = 0.0202) significantly predicted the sustenance of behavior change, with the final model accounting for 40.6% of the variance. These findings underscore the importance of targeted MTM-based interventions focusing on enhancing students' awareness and confidence in managing drowsiness to mitigate drowsy driving, ultimately improving road safety and student well-being.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu 5 Cl 3 (TMPP)]Cl 5  ⋅ xSol (denoted as Cu-TMPP; H 2 TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu 8 Cl 6 ] 10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl - -based octahedron are capped by eight Cu 2+ . Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl - counterions can be exchanged by BF 4 - , PF 6 - , and NO 3 - . The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1 O 2 on light irradiation (650 nm; 25 mW cm -2 ). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases., (© 2024 Wiley-VCH GmbH.)

Inoculation of arbuscular mycorrhizal fungi (AMF) or biochar (BC) application can improve photosynthesis and promote plant growth under saline-alkali stress. However, little is known about the effects of the two combined on growth and physiological characteristics of switchgrass under saline-alkali stress. This study examined the effects of four treatments: (1) no AMF inoculation and no biochar addition (control), (2) biochar (BC) alone, (3) AMF (Rhizophagus irregularis, Ri) alone, and (4) the combination of both (BC+Ri) on the plant biomass, antioxidant enzymes, chlorophyll, and photosynthetic parameters of switchgrass under saline-alkali stress. The results showed that the above-ground, belowground and total biomass of switchgrass in the BC+Ri treatment group was significantly higher (+136.7%, 120.2% and 132.4%, respectively) than in other treatments compared with Control. BC+Ri treatment significantly increased plant leaves' relative chlorophyll content, antioxidant enzyme activity, and photosynthesis parameters. It is worth noting that the transpiration rate, stomatal conductance, net photosynthetic rate, PSII efficiency and other photosynthetic-related indexes of the BC+Ri treatment group were the highest (38% to 54% higher than other treatments). The fitting results of light response and CO 2 response curves showed that the light saturation point, light compensation point, maximum carboxylation rate and maximum electron transfer rate of switchgrass in the Ri+BC treatment group were the highest. In conclusion, biochar combined with Ri has potential beneficial effects on promoting switchgrass growth under saline-alkali stress and improving the activity of antioxidant enzymes and photosynthetic characteristics of plants., (© 2024 Scandinavian Plant Physiology Society.)

Background: Diabetes mellitus (DM) increases the risk for cognitive impairment and Alzheimer's disease (AD). Diabetic ketoacidosis (DKA), a serious complication of DM, may also cause brain damage and further AD, but the underlying molecular mechanisms remain unclear., Objective: Our objective was to understand how DKA can promote neurodegeneration in AD., Methods: We induced DKA in rats through intraperitoneal injection of streptozotocin, followed by starvation for 48 hours and investigated AD-related brain alterations focusing on tau phosphorylation., Results: We found that DKA induced hyperphosphorylation of tau protein at multiple sites associated with AD. Studies of tau kinases and phosphatases suggest that the DKA-induced hyperphosphorylation of tau was mainly mediated through activation of c-Jun N-terminal kinase and downregulation of protein phosphatase 2A. Disruption of the mTOR-AKT (the mechanistic target of rapamycin-protein kinase B) signaling pathway and increased levels of synaptic proteins were also observed in the brains of rats with DKA., Conclusions: These results shed some light on the mechanisms by which DKA may increase the risk for AD., Competing Interests: KI and CXG are Editorial Board Members of this journal but were not involved in the peer-review process for this article and did not have access to any information regarding its peer review. KI is cofounder and Chief Scientific Officer of Phanes Biotech, Inc. This company is in the process of developing biomarkers and therapeutics of Alzheimer’s disease and related disorders. CXG serves in the Scientific Advisory Board of Alectos Therapeutics., (© 2024 – The authors. Published by IOS Press.)

Background: Breastfeeding provides several positive health benefits for the newborn child, yet breastfeeding rates remain low in the United States (US). Theory-based approaches have the potential to improve breastfeeding promotion interventions. Hence, the study examined the correlates of intention to breastfeed among US pregnant women based on the multi-theory model (MTM) of health behavior change., Methods: Using a cross-sectional design, a 36-item online survey was administered to a nationally representative sample of 315 pregnant women in the US. The instrument was psychometrically validated for face, content, and construct validity by a panel of six experts over two rounds. Further, construct validation was done by confirmatory factor analysis (CFA). Hierarchical regression modeling was employed to explain the intention to start breastfeeding and sustain exclusive breastfeeding for up to six months and with complementary foods for up to 24 months., Results: Internal consistency using Cronbach's alpha was found to be acceptable. It was found that behavioral confidence and changes in the physical environment positively affected the initiation of breastfeeding ( P <0.01; adjusted R2=0.478). All three constructs of MTM namely practice for change, emotional transformation, and changes in the social environment were significant predictors for the sustenance of breastfeeding at six months ( P <0.01; adjusted R2=0.591) and at 24 months ( P <0.01; adjusted R2=0.347)., Conclusion: Based on the findings of this study it is essential for educators and healthcare providers to design MTM-based interventions to promote breastfeeding among pregnant women in the US., Competing Interests: The Authors declare no conflict of interest., (© 2024 The Author(s).)

Introduction: Risky alcohol use patterns, characterized by heavy episodic drinking (HED) and alcohol-induced blackout, are prevalent in college students. However, it is not clear if experiencing HED and blackout among college-attending cannabis users heightens risk for adverse cannabis use consequences. The purpose of this study was to examine whether heavy episodic drinking and blackout episodes moderate the relationship between cannabis consumption and cannabis use consequences among college students., Methods: Undergraduate college students ( n = 4331) were recruited from a Midwest University in 2021. This analysis used a subset of data from past 6-month cannabis users ( n = 772; 17.8% of the full sample). Among cannabis users, 64.5% identified as female and 87.8% were White with an average age of 19.99 ( SD =2.88). A linear regression was conducted with two two-way interactions of cannabis consumption and HED frequency as well as cannabis consumption and alcohol-induced blackout episodes., Results: Results showed a statistically significant positive association between cannabis consumption and cannabis use consequences (B=0.73, p <.001), adjusting for the other variables in the model. Blackout, but not HED, was a significant moderator (B=0.19, p =.003)., Discussion: The findings of this study indicate that blackout experiences amplify the relationship between cannabis use and cannabis-related consequences among college students. This underscores that blackouts not only signal a risk of problematic drinking but also exacerbate the association between cannabis use and its negative consequences., Conclusion: Findings may inform college campus interventions targeting cannabis and alcohol concurrent-users who experience alcohol-induced blackouts to reduce their additional risk for cannabis-related consequences., Competing Interests: The authors declare no conflicts of interest., (© 2023 Authors et al.)

Eating outside-of-home (EOH) is one of the main changes in lifestyle that occurred worldwide in the past few decades. Given that EOH behavior is influenced by individual and contextual factors, the utilization of a theory seems to be suitable in analyzing this health behavior. The fourth-generation theory multi-theory model (MTM) is designed exclusively for health behavior change at the individual and community levels. Therefore, the purpose of this analytical cross-sectional study was to investigate EOH behavior by using the MTM among a nationally representative sample in the United States (US). Data for this study were collected from April-May 2023 via a 61-item psychometric valid, web-based, structured survey disseminated via Qualtrics. Chi-square/Fisher's exact tests were used to compare categorical data, whereas the independent-samples t -test was used to compare the mean scores of MTM constructs across groups. Pearson correlation analysis was performed for the intercorrelation matrix between the MTM constructs and hierarchical regression models were built to predict the variance in the initiation and sustenance by certain predictor variables beyond demographic characteristics. The p values in the multiple comparisons were calculated by using adjusted residuals. Among a total of 532 survey respondents, 397 (74.6%) indicated being engaged in EOH at least twice a week, whereas 135 (25.4%) reported not being engaged in EOH. People who were engaged in EOH were younger (mean age = 42.25 ± 17.78 years vs. 55.89 ± 19.43 years) African American, (15.9% vs. 6.7%, p = 0.01), single or never married, (34.0% vs. 23.0%, p = 0.02), had a graduate degree (9.6% vs. 3.7%, p = 0.03), and were employed (72.0% vs. 34.8%, p < 0.001) as opposed to those who reported not being engaged in eating outside the home. Among the MTM constructs of initiation, "behavioral confidence" and "changes in the physical environment" were the significant predictors of initiating a reduction in EOH behavior and explained 48% of the variance in initiation. Among the MTM constructs of sustenance, "emotional transformation" and "changes in the social environment" were the significant predictors of sustaining a reduction in EOH behavior and explained 50% of the variance in sustenance. This study highlights a need to design MTM-based educational interventions that promote in-home eating instead of frequent EOH for health, family bonding, economic, and other reasons.

Chemokines were originally defined as cytokines that affect the movement of immune cells. In recent years, due to the increasing importance of immune cells in the tumor microenvironment (TME), the role of chemokines has changed from a single "chemotactic agent" to a key factor that can regulate TME and affect the tumor phenotype. CXCL6, also known as granulocyte chemoattractant protein-2 (GCP-2), can recruit neutrophils to complete non-specific immunity in the process of inflammation. Cancer-related genes and interleukin family can promote the abnormal secretion of CXCL6, which promotes tumor growth, metastasis, epithelial mesenchymal transformation (EMT) and angiogenesis in the TME. CXCL6 also has a role in promoting fibrosis and tissue damage repair. In this review, we focus on the regulatory network affecting CXCL6 expression, its role in the progress of inflammation and how it affects tumorigenesis and progression based on the TME, in an attempt to provide a potential target for the treatment of diseases such as inflammation and cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Cinobufagin is a natural active ingredient isolated from the traditional Chinese medicine Venenum Bufonis (Chinese: Chansu), which is the dried secretion of the postauricular gland or skin gland of the Bufo gargarizans Cantor or Bufo melanostictus Schneider. There is increasing evidence indicating that cinobufagin plays an important role in the treatment of cancer. This article is to review and discuss the antitumor pharmacological effects and mechanisms of cinobufagin, along with a description of its toxicity and pharmacokinetics., Methods: The public databases including PubMed, China National Knowledge Infrastructure and Elsevier were referenced, and 'cinobufagin', 'Chansu', 'Venenum Bufonis', 'anticancer', 'cancer', 'carcinoma', and 'apoptosis' were used as keywords to summarize the comprehensive research and applications of cinobufagin published up to date., Key Findings: Cinobufagin can induce tumour cell apoptosis and cycle arrest, inhibit tumour cell proliferation, migration, invasion and autophagy, reduce angiogenesis and reverse tumour cell multidrug resistance, through triggering DNA damage and activating the mitochondrial pathway and the death receptor pathway., Conclusions: Cinobufagin has the potential to be further developed as a new drug against cancer., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Colorectal cancer is the third most common cancer worldwide and is the second leading cause of cancer-associated deaths. While colorectal cancer is on the decline in the United States (US), disparities still exist, despite the non-invasive screening modalities, such as stool-based tests have shown themselves to be effective in the detection of colorectal cancer. Many of the existing stool-based test interventions lack the use of a contemporary theory-based approach. Given the paucity of theory-based interventions intended to promote stool-based tests, this cross-sectional study utilizes the multi-theory model (MTM) of health behavior change to explain the seeking of stool-based tests for colorectal cancer (CRC) screening. An online 57-item questionnaire with an established psychometric validity was used to collect responses from the US-based sample ( n = 640) of adults aged 45-75 years old. The data were analyzed using bivariate and multivariate statistical methods. Structural equation modeling (SEM) was conducted to test the construct validity of the survey instrument. In this nationwide sample, 39.2% ( n = 251) of participants reported having received some form of a stool-based test. Among the participants who did not undergo stool-based CRC screening, the MTM subscales, including "participatory dialogue", "behavioral confidence", and "changes in the social environment", were significant predictors of initiating screening behavior and explained 48% of the variance in the initiation among this group (R 2 = 0.579, F = 5.916, p < 0.001; adjusted R 2 = 0.481). The MTM may be a useful framework with which to design educational, mass media, social media, and clinical interventions for the promotion of stool-based CRC screening among adults aged 45-75 years old.

The highly conserved ribosomal protein L34 ( RPL34 ) has been reported to play an essential role in the progression of diverse malignancies. RPL34 is aberrantly expressed in multiple cancers, although its significant in colorectal cancer (CRC) is currently unclear. Here, we demonstrated that RPL34 expression was higher in CRC tissues than in normal tissues. Upon RPL34 overexpression, the ability of proliferation, migration, invasion, and metastasis of CRC cells were significantly enhanced in vitro and in vivo . Furthermore, high expression of RPL34 accelerated cell cycle progression, activated the JAK2/STAT3 signaling pathway, and induced the epithelial-to-mesenchymal transition (EMT) program. Conversely, RPL34 silencing inhibited the CRC malignant progression. Utilizing immunoprecipitation assays, we identified the RPL34 interactor, the cullin-associated NEDD8-dissociated protein 1 ( CAND1 ), which is a negative regulator of cullin-RING ligases. CAND1 overexpression reduced the ubiquitin level of RPL34 and stabilized RPL34 protein. CAND1 silencing in CRC cells resulted in a decrease in the ability of proliferation, migration, and invasion. CAND1 overexpression promoted CRC malignant phenotypes and induced EMT, and RPL34 knockdown rescued CAND1 -induced CRC progression. In summary, our study indicates that RPL34 acts as a mediator, is stabilized by CAND1 , and promotes proliferation and metastasis, in part, through the activation of the JAK2/STAT3 signaling pathway and induction of EMT in CRC.

During college years, perceived stress is the top reported hindrance to well-being and academic success. Data on the acceptance and perceived benefits of yoga among college students are limited. A purposive sample of college students (n = 79) from a course centered on Vinyasa Yoga and Mindfulness Meditation were recruited. Comprehensive yoga journaling data were collected, and a directed content analysis along the constructs of the multi-theory model (MTM) of health behavior change was utilized. The advantages of yoga that emerged were improved physical performance, reduced perceived stress, acceptance of oneself, better well-being, and improved coping. The identified disadvantages were time commitment, lack of motivation, and other competing interests. Learning through small steps, modifications, and identifying multiple sources of confidence helped build behavioral confidence. Practicing at home or at a yoga studio was a common theme for support in the physical environment. Directing negative emotions into purposes was helpful in maintaining the yoga practice. Sustained commitment to the practice also helped maintain the regular performance of yoga. Finally, social support from family, friends, and instructors was vital for continued practice. The study has important ramifications for the development of survey tools for descriptive studies and designing behavior-change yoga interventions in this target population.

The design, fabrication, and measurement of a microelectromechanical system (MEMS) three-axis magnetic field sensor (MFS) based on the commercial complementary metal oxide semiconductor (CMOS) process are investigated. The MFS is a magnetic transistor type. The performance of the MFS was analyzed employing the semiconductor simulation software, Sentaurus TCAD. In order to decrease the cross-sensitivity of the three-axis MFS, the structure of the MFS is planed to accommodate two independent sensing components, a z-MFS utilized to sense magnetic field (M-F) in the z-direction and a y/x-MFS composed of a y-MFS and a x-MFS to be utilized to sense M-F in the y- and x-directions. The z-MFS incorporates four additional collectors to increase its sensitivity. The commercial 1P6M 0.18 μm CMOS process of the Taiwan Semiconductor Manufacturing Company (TSMC) is utilized to manufacture the MFS. Experiments depict that the MFS has a low cross-sensitivity of less than 3%. The sensitivities of z-, y-, and x-MFS are 237 mV/T, 485 mV/T, and 484 mV/T, respectively.

Tau pathology is essential in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Tau immunotherapy aimed at reducing the progression of tau pathology provides a potential therapeutic strategy for treating these diseases. By screening monoclonal antibodies 43D, 63B, 39E10, and 77G7 that recognize epitopes ranging from tau's N-terminus to C-terminus, we found the 77G7, which targets the microtubule-binding domain promoted tau clearance in a dose-dependent manner by entering neuronal cells in vitro. Intra-cerebroventricular injection of 77G7 antibody reduced tau levels in the wild-type FVB mouse brain. Without influencing the levels of detergent-insoluble and aggregated tau, intravenous injection of 77G7 reduced tau hyperphosphorylation in the brain and improved novel object recognition but not spatial learning and memory in 15-18-month-old 3xTg-AD mice. These studies suggest that epitopes recognized by tau antibodies are crucial for the efficacy of immunotherapy. Immunization with antibody 77G7 provides a novel potential opportunity for tau-directed immunotherapy of AD and related tauopathies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this work, enzymatic doped/undoped poly-silicon nanowire sensors with different lengths were fabricated using a top-down technique to measure glucose concentration. The sensitivity and resolution of these sensors correlate well with the dopant property and length of nanowire. Experimental results indicate that the resolution is proportional to the nanowire length and dopant concentration. However, the sensitivity is inversely proportional to the nanowire length. The optimum resolution can be better than 0.02 mg/dL for a doped type sensor with length of 3.5 μm. Furthermore, the proposed sensor was demonstrated for 30 applications with similar current-time response and showed good repeatability.

Hesitancy toward the COVID-19 vaccine has hindered its rapid uptake among the Hispanic and Latinx populations. The study aimed to use the Multi-Theory Model (MTM) for health behavior change to explain the intention of initiating and sustaining the behavior of COVID-19 vaccination among the Hispanic and Latinx populations that expressed and did not express hesitancy towards the vaccine in Nevada. Using a quantitative cross-sectional and survey-based research study design, data were collected using a 50-item questionnaire and analyzed using multiple linear regression modeling. Of 231 respondents, participatory dialogue (b = 0.113, p < 0.001; b = 0.072, p < 0.001) and behavioral confidence (b = 0.358, p < 0.001; b = 0.206, p < 0.001) displayed significant associations with the initiation of COVID-19 vaccine acceptance among vaccine-hesitant and non-vaccine-hesitant individuals. Emotional transformation (b = 0.087, p < 0.001; b = 0.177, p < 0.001) displayed a significant association with the sustenance of COVID-19 vaccine acceptance among vaccine-hesitant and non-vaccine-hesitant individuals. Results from this study provide evidence that the MTM is a useful tool in predicting COVID-19 vaccine acceptance behavior among Hispanics and Latinxs in Nevada, and it should be used in intervention designs and messaging to promote vaccine uptake.

Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. Gene therapy may offer an efficient method to ameliorate the symptoms of this disorder. Methods An AAVphp.eb-hSyn-mFMR1IOS7 vector and an empty control were injected into the tail vein of adult Fmr1 knockout (KO) mice and wildtype (WT) controls. The KO mice were injected with 2 × 10 13 vg/kg of the construct. The control KO and WT mice were injected with an empty vector. Four weeks following treatment, the animals underwent a battery of tests: open field, marble burying, rotarod, and fear conditioning. The mouse brains were studied for levels of the Fmr1 product FMRP. Results: No significant levels of FMRP were found outside the CNS in the treated animals. The gene delivery was highly efficient, and it exceeded the control FMRP levels in all tested brain regions. There was also improved performance in the rotarod test and partial improvements in the other tests in the treated KO animals. Conclusion: These experiments demonstrate efficient, brain-specific delivery of Fmr1 via peripheral administration in adult mice. The gene delivery led to partial alleviation of the Fmr1 KO phenotypical behaviors. FMRP oversupply may explain why not all behaviors were significantly affected. Since AAV.php vectors are less efficient in humans than in the mice used in the current experiment, studies to determine the optimal dose using human-suitable vectors will be necessary to further demonstrate feasibility.

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells., Competing Interests: None

Background: Coronavirus disease 2019 (COVID-19) vaccine hesitancy has remained a significant concern among adults worldwide. However, not much is known about parental vaccine hesitancy for getting children vaccinated for COVID-19 in the U.S. Thus, the purpose of this study was to conduct a national assessment of parents' preferences for COVID-19 vaccination of children using the evidence-based Multi-Theory Model (MTM) and explore the predictors of vaccine hesitancy. Methods: To participate in this study, a national random sample of parents (n=263) took a valid and reliable online questionnaire based on the MTM. Independent samples t test, chi-square test, multiple logistic regression was utilized to analyze data. Results: More than two-fifths (42%) of the participating parents were not willing to get their children vaccinated for COVID-19. Parental vaccination status, booster dose acceptance, education, and political affiliation were significant predictors of willingness to get children vaccinated for COVID-19. In the multiple logistic regression analyses, behavioral confidence and participatory dialogue (i.e., perceived advantages versus disadvantages) were statistically significant predictors of COVID-19 vaccination hesitancy for children among the participating parents. Conclusion: Given the multiple factors that were found influential in parental hesitancy for COVID-19 vaccination among children, multimodal and evidence-based interventions are needed to increase the uptake of COVID-19 vaccines among children by influencing the parents' perceptions, increasing their confidence, dispelling misinformation, and reducing constraints for vaccination. Such interventions should emphasize communication and messaging that is truthful, interactive, scientifically correct, and to be delivered in a variety of community-based settings., (© 2022 The Author(s).)

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that eventually leads to dementia and death of the patient. Currently, no effective treatment is available that can slow or halt the progression of the disease. The gut microbiota can modulate the host immune system in the peripheral and central nervous system through the microbiota-gut-brain axis. Growing evidence indicates that gut microbiota dysbiosis plays an important role in the pathogenesis of AD, and modulation of the gut microbiota may represent a new avenue for treating AD. Immunotherapy targeting Aβ and tau has emerged as the most promising disease-modifying therapy for the treatment of AD. However, the underlying mechanism of AD immunotherapy is not known. Importantly, preclinical and clinical studies have highlighted that the gut microbiota exerts a major influence on the efficacy of cancer immunotherapy. However, the role of the gut microbiota in AD immunotherapy has not been explored. We found that immunotherapy targeting tau can modulate the gut microbiota in an AD mouse model. In this article, we focused on the crosstalk between the gut microbiota, immunity, and AD immunotherapy. We speculate that modulation of the gut microbiota induced by AD immunotherapy may partially underlie the efficacy of the treatment.

Introduction: Neurofibrillary tangle (NFT) of hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and related tauopathies. Tau lesion starts in the trans-entorhinal cortex, from where it spreads to limbic regions, followed by neocortical areas. The regional distribution of NFTs associates with the progression of AD. Accumulating evidence suggests that proteopathic tau can seed tau aggregation in a prion-like fashion in vitro and in vivo. Inhibition of tau seeding activity could provide a potential therapeutic opportunity to block the propagation of tau pathology in AD and related tauopathies., Aims: In the present study, we investigated the role of 77G7, a monoclonal tau antibody to the microtubule-binding repeats, in repressing the seeding activity of proteopathic tau., Results: We found that 77G7 had a higher affinity toward aggregated pathological tau fractions than un-aggregated tau derived from AD brain. 77G7 inhibited the internalization of tau aggregates by cells, blocked AD O-tau to capture normal tau, and to seed tau aggregation in vitro and in cultured cells. Tau pathology induced by hippocampal injection of AD O-tau in 3xTg-AD mice was suppressed by mixing 77G7 with AD O-tau. Intravenous administration of 77G7 ameliorated site-specific hyperphosphorylation of tau induced by AD O-tau in the hippocampi of Tg/hTau mice., Conclusion: These findings indicate that 77G7 can effectively suppress the seeding activity of AD O-tau and thus could be developed as a potential immunotherapeutic drug to inhibit the propagation of tau pathology in AD and related tauopathies., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Adolescents from minority groups are particularly susceptible to poor oral hygiene behaviors, including lack of daily flossing. This cross-sectional study aimed to conduct an exploratory behavioral research to identify evidence-based (theory-based) approaches to promote flossing behavior among African American/Black and Latinx/Hispanic (minority) adolescents. A 39-item psychometrically valid web-based questionnaire was used to collect responses from a nationwide sample of minority adolescents aged 10-17 years residing in the United States. The data were analyzed using bivariate and multivariate statistical methods. Of 520 minority adolescents (260 African American/Black and 260 Latinx/Hispanic adolescents), the proportion of flossing was nearly equally split in the sample. A significantly higher proportion of minority adolescents who were flossing had access to floss as opposed to those who were not flossing (86.8% vs. 69.8%, p < 0.001). A significantly higher proportion of minority adolescents who were not flossing did not visit the dentist over the past year as opposed to those who floss (25.2% vs. 14.7%, p < 0.001). Among the participants who were not flossing, gender, grade level, instruction in school regarding flossing, and multi-theory model (MTM) of health behavior change constructs were the significant predictors ( p < 0.001) of initiating and sustaining flossing. The findings of this study will serve as baseline data for developing and evaluating effective evidence-based interventions using the MTM.

Variation in the blood metabolome is intimately related to human health. However, few details are known about the interplay between genetics and the microbiome in explaining this variation on a metabolite-by-metabolite level. Here, we perform analyses of variance for each of 930 blood metabolites robustly detected across a cohort of 1,569 individuals with paired genomic and microbiome data while controlling for a number of relevant covariates. We find that 595 (64%) of these blood metabolites are significantly associated with either host genetics or the gut microbiome, with 69% of these associations driven solely by the microbiome, 15% driven solely by genetics and 16% under hybrid genome-microbiome control. Additionally, interaction effects, where a metabolite-microbe association is specific to a particular genetic background, are quite common, albeit with modest effect sizes. This knowledge will help to guide targeted interventions designed to alter the composition of the human blood metabolome., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Numerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable., Objective: To assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning., Methods: Forty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT)., Results: Eleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up., Conclusion: RNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Long noncoding RNAs (lncRNAs) participate in a variety of biological processes and diseases. However, the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed. In this study of right side hemisection of the spinal cord at T10, we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed. We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2, the two expression trends with the most significant difference. Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury. There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25. The co-expression network showed that the co-expressed genes were mainly enriched in cell division, inflammatory response, FcγR-mediated cell phagocytosis signaling pathway, cell cycle and apoptosis. The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury. There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2. The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction. The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways. These findings provide a new direction for the clinical treatment of spinal cord injury., Competing Interests: None

Purpose: Given the increased exposure to e-cigarettes and nicotine among young adults, difficulty in quitting vaping is likely, which supports the need for effective behavioral interventions. Therefore, this cross-sectional study aims to assess the testability of the contemporary multi-theory model of health behavior change in predicting the vaping quitting behavior among young adults in the United States., Methods: A nationally representative sample of 619 young adults engaged in vaping behavior and aged 18-24 years was recruited to complete a 49-item web-based survey. A structural equation model was used to test relationships between MTM constructs. Hierarchical multiple regression was utilized to predict the variance in the initiation and sustenance of vaping quitting behavior by predictor variables, such as demographic characteristics, history of behaviors, and MTM constructs., Results: Of 619 respondents, over 75% were White and nearly 70% had educational attainment equal to high school or some college. In total, 62% of respondents were using nicotine, followed by 33.3% were using cannabis. About 80% of the respondents reported being engaged in drinking alcohol, and nearly 45% were engaged in cigarette smoking. The predictive effect of all MTM constructs on vaping quitting initiation (adjusted R 2 = 0.417, F (23, 595) = 20.215, p < 0.001) and sustenance (adjusted R 2 = 0.366, F (23, 595) = 16.533, p < 0.001) was statistically significant., Conclusions: The findings of this study point to the usability and applicability of MTM in operationalizing and developing vaping quitting behavior interventions targeting young adults.

This study develops a TEMH (thermoelectric energy micro harvester) chip utilizing a commercial 0.18 μm CMOS (complementary metal oxide semiconductor) process. The chip contains a TEMH and temperature sensors. The TEMH is established using a series of 54 thermocouples. The use of the temperature sensors monitors the temperature of the thermocouples. One temperature sensor is set near the cold part of the thermocouples, and the other is set near the hot part of the thermocouples. The performance of the TEMH relies on the TD (temperature difference) at the CHP (cold and hot parts) of the thermocouples. The more the TD at the CHP of the thermocouples increases, the higher the output voltage and output power of the TEMH become. To obtain a higher TD, the cold part of the thermocouples is designed as a suspended structure and is combined with cooling sheets to increase heat dissipation. The cooling sheet is constructed of a stack of aluminum layers and is mounted above the cold part of the thermocouple. A finite element method software, ANSYS, is utilized to compute the temperature distribution of the TEMH. The TEMH requires a post-process to obtain the suspended thermocouple structure. The post-process utilizes an RIE (reactive ion etch) to etch the two sacrificial materials, which are silicon dioxide and silicon substrate. The results reveal that the structure of the thermocouples is completely suspended and does not show any injury. The measured results reveal that the output voltage of the TEMH is 32.5 mV when the TD between the CHP of the thermocouples is 4 K. The TEMH has a voltage factor of 8.93 mV/mm 2 K. When the TD between the CHP of the thermocouples is 4 K, the maximum output power of the TEMH is 4.67 nW. The TEMH has a power factor of 0.31 nW/mm 2 K 2 .

In intelligent manufacturing and robotic technology, various sensors must be integrated with equipment. In addition to traditional sensors, stretchable sensors are particularly attractive for applications in robotics and wearable devices. In this study, a piezoresistive stretchable strain sensor based on laser-induced graphene (LIG) was proposed and developed. A three-dimensional, porous LIG structure fabricated from polyimide (PI) film using laser scanning was used as the sensing layer of the strain sensor. Two LIG pattern structures (parallel and vertical) were fabricated and integrated within the LIG strain sensors. Scanning electron microscopy, an X-ray energy dispersive spectrometer, and Raman scattering spectroscopy were used to examine the microstructure of the LIG sensing layer. The performance and strain sensing properties of the parallel and vertical stretchable LIG strain sensors were investigated in tensile tests. The relative resistance changes and the gauge factors of the parallel and vertical LIG strain sensors were quantified. The parallel strain sensor achieved a high gauge factor of 15.79 in the applied strain range of 10% to 20%. It also had high sensitivity, excellent repeatability, good durability, and fast response times during the tensile experiments. The developed LIG strain sensor can be used for the real-time monitoring of human motions such like finger bending, wrist bending, and throat swallowing.

Characterizing complex microbial communities with single-cell resolution has been a long-standing goal of microbiology. We present Microbe-seq, a high-throughput method that yields the genomes of individual microbes from complex microbial communities. We encapsulate individual microbes in droplets with microfluidics and liberate their DNA, which we then amplify, tag with droplet-specific barcodes, and sequence. We explore the human gut microbiome, sequencing more than 20,000 microbial single-amplified genomes (SAGs) from a single human donor and coassembling genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe microbial interactions, reconstructing the horizontal gene transfer (HGT) network and observing HGT between 92 species pairs; we also identify a significant in vivo host-phage association between crAssphage and one strain of Bacteroides vulgatus . Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.

Background: Hypoxia and ferroptosis are crucial in the occurrence and development of hepatocellular carcinoma (HCC), and they both affect the immune status of the tumor microenvironment. Previous studies have also shown a link between hypoxia and ferroptosis., Patients and Methods: In all, 814 HCC cases from The Cancer Genome Atlas and Gene Expression Omnibus databases were used as the discovery cohort, and 230 HCC cases from the International Cancer Genome Consortium database were used as the validation cohort. Hypoxia subtypes and ferroptosis subtypes were identified by consensus cluster analysis according to 174 hypoxia-related genes and 193 ferroptosis-related genes. The prognostic signature was constructed using the Cox and LASSO regression analyses, and two risk groups were identified. A comprehensive analysis of the clinical and immune characteristics between the two risk groups was further performed., Results: Two hypoxia subtypes and two ferroptosis subtypes were distinguished and verified; subsequently, a five-gene prognostic signature was constructed and the risk score could be acquired by the following formula: risk score = 0.0604*Expression (CA9)-0.0714*Expression (ANXA10) + 0.1501*Expression (CDC20)-0.0853*Expression (CYP7A1) + 0.0530*Expression (SPP1). Compared with the low-risk group, the high-risk group had a worse prognosis. The high-risk group also showed a higher level of immune infiltration than the low-risk group, and immune checkpoints were generally upregulated in the high-risk group. The antigen presentation ability of the low-risk group was poor, which may be related to the immune escape mechanism. Drug sensitivity analysis indicated that the high- and low-risk groups were sensitive to tyrosine kinase inhibitors and chemotherapeutic drugs, respectively., Conclusion: The hypoxia-, ferroptosis-, and immune-associated prognostic signature we constructed could stratify patients with HCC and guide precise treatment., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The triple transgenic mouse model of Alzheimer's disease (3×Tg-AD) has gained popularity in Alzheimer's research owing to the progressive development of both amyloid- β and tau pathologies in its brain. Prior handling-habituation, a necessary preparation procedure that reduces anxiety and stress in rodents, was seldom described in the literature involving these mice and needs to be addressed., Objective: We sought to determine whether 3×Tg-AD mice differ from B6;129 genetic control mice in terms of tameness and prior habituation to handling., Methods: We devised hand-staying and hand-boarding assays to evaluate tameness in 3×Tg-AD and B6;129 genetic control mice at 2.5, 7, and 11.5 months of age, representing cognitively pre-symptomatic, early symptomatic and advanced symptomatic stages of the disease, respectively. We monitored the progress of handling-habituation across 8-15 daily handling sessions and assessed the animal behaviors in elevated plus maze., Results: We found that 3×Tg-AD mice were markedly tamer than age-matched control mice at the baseline. Whereas it took 2-3 days for 3×Tg-AD mice to reach the criteria for full tameness, it took an average of 7-9 days for young genetic control mice to do so. Prior handling-habituation enhanced risk assessment and coping strategy in mice in elevated plus maze. Completely handling-habituated mice exhibited comparable anxiety indices in the maze regardless of genotype and age., Conclusion: These findings collectively point to inherently heightened tameness and accelerated handling-habituation in 3×Tg-AD mice on a B6;129 genetic background. These traits should be carefully considered when behaviors are compared between 3×Tg-AD and the genetic control mice., Competing Interests: The authors have no conflict of interest to report., (© 2022 – The authors. Published by IOS Press.)

Background: Despite the availability of COVID-19 vaccines and the proven benefits of vaccinations outweighing the potential risks, hesitancy to accept vaccines and additional doses remains a persistent problem. Therefore, the purpose of the study was to investigate hesitancy, confidence, literacy, and the role of the multi-theory model (MTM) constructs in COVID-19 booster uptake. Methods: This cross-sectional study utilized a 52-item psychometric valid web-based survey conducted during the month of October 2021 to recruit a nationally representative sample of U.S. adults. Univariate, bivariate, and multivariate statistical tests were used to analyze the data. Results: Among the booster hesitant group (n = 209, 41.7%), a significantly larger proportion of respondents were unvaccinated with the primary series (43.5% vs. 11%, p < 0.001), were among 18−44 years age group (51.2% vs. 31.8%, p < 0.001), single or never married (33.0% vs. 24.3%, p = 0.04), had lower education with some high school (6.2% vs. 2.4%, p = 0.03), and identified themselves as Republicans (31.6% vs. 20.5%, p = 0.01). The hesitant group had lower mean scores of vaccine literacy, and vaccine confidence, and had 19% lower odds of behavioral confidence than their non-hesitant counterparts (adjusted odds ratio = 0.81, 95% CI: 0.71−0.92). Conclusions: The findings of this study underscore the need of raising public awareness through effective multi-theory-model-based communication campaigns.

Purpose: Cellular responses following cerebral ischemia/reperfusion injury are critical to recovery and survival after ischemic stroke. Understanding of these cellular responses can help the design of therapies to protect brain tissue and promote recovery after stroke. One of these cellular responses may be mediated by the AKT (protein kinase B) signal transduction pathway. This study was aimed to investigate the cerebral ischemia-induced alterations of AKT signaling and the upstream molecular pathways., Methods: We modeled cerebral ischemia by middle cerebral artery occlusion in 2-3-month-old male C57BL/6J mice and then analyze the brain samples by using quantitative Western blots and phosphorylation/activation-dependent kinase antibodies. Cerebral ischemia was confirmed by staining of brain slices with 1% 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl, as well as neurological assessments of the mice 24 h after ischemia-reperfusion surgery., Results: We found marked downregulation of AKT within 12 h of cerebral ischemia/reperfusion, which leads to overactivation of glycogen synthase kinase-3β (GSK-3β). Furthermore, we found that the downregulation of AKT was mediated by downregulation of mTORC2 (the complex 2 of the mechanistic target of rapamycin) instead of its common upstream kinases, phosphatidylinositol 3-kinase and phosphoinositide-dependent kinase-1., Conclusion: Our findings provide new insight into the cellular responses to ischemia/reperfusion brain injury and will help develop new treatments targeting the AKT signaling pathway for the treatment of ischemic stroke., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 + T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies., Competing Interests: Declaration of interests J.R.H. and A.R. are founders and board members of PACT Pharma. J.R.H. is a board member of Isoplexis, and A.R. is the scientific advisor to Isoplexis. M.M.D. is a member of the Scientific Advisory Board of PACT Pharma. J.A.B. is a member of the Scientific Advisory Boards of Arcus, Solid, and VIR. J.A.B. is a member of the Board of Directors of Gilead and Provention. J.A.B. is the CEO of Sonoma Biotherapeutics. L.L.L. is on the scientific advisory boards of Alector, Atreca, Dragonfly, DrenBio, Nkarta, Obsidian Therapeutics, and SBI Biotech. R.G. has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, and Merck, has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and declares ownership in CellSpace Biosciences. P.D.G. is on the Scientific Advisory Board of Celsius, Earli, Elpiscience, Immunoscape, Rapt, and Nextech, was a scientific founder of Juno Therapeutics, and receives research support from Lonza. J.D.G. declared contracted research with Gilead, Lilly, and Regeneron. J.A.H. received consulting fees or honoraria from Gilead Sciences, Amplyx, Allovir, Allogene therapeutics, CRISPR therapeutics, CSL Behring, OptumHealth, Octapharma, and Takeda and research funding from Takeda, Allovir, Karius, and Gilead Sciences. Q.D., D.H.M., R.T., R.M.G., M.K., and T.M.S. have employment and equity ownership with Adaptive Biotechnologies. The remaining authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glial cells play an important role in signal transduction, energy metabolism, extracellular ion homeostasis and neuroprotection of the central nervous system. However, few studies have explained the potential effects of exosomes from glial cells on central nervous system health and disease. In this study, the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA sequencing. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Gene ontology analysis showed that extracellular exosome, mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group, while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia group. Next, combined with the screening of hub genes, the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance, whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative stress. Although there were differences in RNA expression between exosomes from astrocytes and microglia, the groups were related by the hub genes, ubiquitin B and heat shock protein family A (Hsp70) member 8. Ubiquitin B appeared to be involved in pleiotropic regulatory functions, including immune regulation, inflammation inhibition, protein catabolism, intracellular protein transport, exosomes and oxidative stress. The results revealed the clinical significance of exosomes from glia in neurodegenerative diseases. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. S20180102-152) on January 2, 2018., Competing Interests: None

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that eventually leads to dementia and death of the patient. Despite the enormous amounts of resources and efforts for AD drug development during the last three decades, no effective treatments have been developed that can slow or halt the progression of the disease. Currently available drugs for treating AD can only improve clinical symptoms temporarily with moderate efficacies. In recent years, the scientific community has realized these challenges and reconsidered the future directions of AD drug development. The most significant recent changes in AD drug development strategy include shifting from amyloid-based targets to other targets, such as tau, and efforts toward better designs for clinical trials. However, most AD drug development is still focused on a single mechanism or target, which is the conventional strategy for drug development. Although multifactorial mechanisms and, on this basis, multi-target strategies have been proposed in recent years, this approach has not been widely recognized and accepted by the mainstream of AD drug development. Here, we emphasize the multifactorial mechanisms of AD and discuss the urgent need for a paradigm shift in AD drug development from a single target to multiple targets, either with the multi-target-directed ligands approach or the combination therapy approach. We hope this article will increase the recognition of the multifactorial nature of AD and promote this paradigm shift. We believe that such a shift will facilitate successful development of effective AD therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gong, Dai, Liu and Iqbal.)

Background: Data on the characteristics of coronavirus disease 2019 (COVID-19) patients disaggregated by race/ethnicity remains limited. We evaluated the sociodemographic and clinical characteristics of patients across racial/ethnic groups and assessed their associations with COVID-19 outcomes., Methods: This retrospective cohort study examined 629 953 patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large health system spanning California, Oregon, and Washington between March 1 and December 31, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression., Results: A total of 570 298 patients with known race/ethnicity were tested for SARS-CoV-2, of whom 27.8% were non-White minorities: 54 645 individuals tested positive, with minorities representing 50.1%. Hispanics represented 34.3% of infections but only 13.4% of tests. Although generally younger than White patients, Hispanics had higher rates of diabetes but fewer other comorbidities. A total of 8536 patients were hospitalized and 1246 died, of whom 56.1% and 54.4% were non-White, respectively. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increased odds of testing positive and hospitalization were associated with all minority races/ethnicities. Hispanic patients also exhibited increased morbidity, and Hispanic race/ethnicity was associated with in-hospital mortality (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.14-1.70)., Conclusion: Major healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, required excess hospitalization and mechanical ventilation, and had higher odds of in-hospital mortality despite younger age. Targeted, culturally responsive interventions and equitable vaccine development and distribution are needed to address the increased risk of poorer COVID-19 outcomes among minority populations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A three-axis micro magnetic sensor (MS) is developed based on the standard 180 nm complementary metal oxide semiconductor (CMOS) technology. The MS designs two magnetic sensing elements (MSEs), which consists of an x/y-MSE and an z-MSE, to reduce cross-sensitivity. The x/y-MSE is constructed by an x-MSE and an y-MSE that are respectively employed to detect in the x- and y-direction magnetic field (MF). The z-MSE is used to sense in the z-direction MF. The x/y-MSE, which is constructed by two magnetotransistors, designs four additional collectors that are employed to increase the sensing current and to enhance the sensitivity of the MS. The Sentaurus TCAD software simulates the characteristic of the MS. The measured results reveal that the MS sensitivity is 534 mV/T in the x-direction MF, 525 mV/T in the y-direction MF and 119 mV/T in the z-axis MF.

A design method and corresponding fabrication procedures are proposed for a dual frusto-conical reflector of a downlight luminaire. The profile of the dual frusto-conical reflector consists of two flat-slant reflective surfaces with slightly different slopes. The optimum dual frusto-conical reflector can be obtained with the proposed design method. The finished product of the dual frusto-conical reflector is fabricated by a 3D printer and followed by surface polishing and reflection paint spraying. The measurement results show that luminaires exhibited 70% optimum illuminance confined within an illumination area of 1.8 m 2 , and the optimum illumination intensity is at 252 lux. The optimum efficiency of the proposed luminaire can reach 158 lm/W for normal-white light-emitting diode (LED) and 119 lm/W for warm-white LED, respectively.

Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an 'omics-based' framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as 'current threats' (Rank I; 3%) - already present among pathogens - and 'future threats' (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 'current threat' ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II ('future threats'). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions., (© 2021. The Author(s).)

Globally, breast cancer is the most common malignancy affecting women. The incidence of breast cancer has been growing among Asian American women. Mammography is a screening procedure that provides early diagnosis for the timely treatment to reduce premature mortality due to breast cancer. However, there are no national data available that summarize the rates of mammography screening among Asian American women. Some small-scale studies have reported low rates of mammography uptake among Asian American women. This cross-sectional study utilized the fourth-generation, multi-theory model (MTM) of health behavior change to explain the correlates of mammography screening among Asian American women between the ages of 45-54 years. A 44-item instrument was evaluated for face, content, and construct validity (using structural equation modeling) and reliability (Cronbach's alpha) and administered electronically to a nationally representative sample of Asian American women ( n = 374). The study found that Asian American women who have had received mammograms in the past 12 months as per recommendations, all three constructs of MTM, namely, participatory dialogue (β = 0.156, p < 0.05), behavioral confidence (β = 0.236, p < 0.001), and changes in the physical environment (β = 0.426, p < 0.001) were statistically significant and crucial in their decision to initiate getting a mammogram, accounting for a substantial 49.9% of the variance in the decision to seek mammography. The study also found that the MTM constructs of emotional transformation (β = 0.437, p < 0.001) and practice for change (β = 0.303, p < 0.001) were significant for maintaining the repeated behavior of getting annual mammograms and were responsible for 53.9% of the variance. This evidence-based study validates the use of MTM in designing and evaluating mammography screening promotion programs among Asian American women aged 45-54 years.

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness., Competing Interests: Declaration of interests E.J.G.B. has received honoraria from Abbott CH, Angelini Italy, bioMérieux Inc, InflaRx GmbH, MSD Greece, and XBiotech Inc.; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux Inc, InflaRx GmbH, ThermoFisher Brahms GmbH, and XBiotech Inc; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). P.K. is a shareholder and a consultant to Inflammatix, Inc. Y.H.B. and Y.D.H. are employees of, and stockholders in, Inflammatix, Inc., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate., Aim: To investigate whether RL can improve the prognosis of patients with T1b GBC., Methods: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not., Results: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50)., Conclusion: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

A radio frequency microelectromechanical system switch (MSS) manufactured by the complementary metal oxide semiconductor (CMOS) process is presented. The MSS is a capacitive shunt type. Structure for the MSS consists of coplanar waveguide (CPW) lines, a membrane, and springs. The membrane locates over the CPW lines. The surface of signal line for the CPW has a silicon dioxide dielectric layer. The fabrication of the MSS contains a CMOS process and a post-process. The MSS has a sacrificial oxide layer after the CMOS process. In the post-processing, a wet etching of buffer oxide etch (BOE) etchant is employed to etch the sacrificial oxide layer, so that the membrane is released. Actuation voltage for the MSS is simulated using the CoventorWare software. The springs have a low stiffness, so that the actuation voltage reduces. The measured results reveal that actuation voltage for the MSS is 10 V. Insertion loss for the MSS is 0.9 dB at 41 GHz and isolation for the MSS is 30 dB at 41 GHz.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction., Objective: To explore strategies for early intervention to prevent Alzheimer's disease., Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated., Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice., Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

Background: Obesity remains among one of the greatest health care threats facing today's children and adolescents. Yoga has gained increased popularity in the United States and appears as a promising way to assist with weight loss and management in adults. However, research examining yoga programs targeting weight loss for children or adolescents are relatively scarce., Objective: The current study provided a systematic review of yoga-based interventions targeting weight loss among overweight or obese children and adolescents., Methodology: The authors conducted a systematic review of articles obtained from Alt HealthWatch, CINAHL, SPORTDiscus, PubMed, and Web of Science databases. Inclusion criteria were studies employed yoga as a primary component, targeted overweight or obese children or adolescents, measured body weight or BMI as an outcome, utilized any type of study design, and published in peer-reviewed journals in English language., Results: A total of nine studies met the inclusion criteria. Most studies were conducted in the United States (n = 5), and implemented in the school setting (n = 5). Among studies reviewed, three were randomized controlled trials, and two were with the attrition rates approaching 50%. A majority of the interventions were able to facilitate weight loss and relevant behaviors., Conclusion: The impact of yoga interventions on child and adolescent obesity was small but meaningful. Some of the limitations include small sample sizes, lack of follow-up assessment after posttest, lack of control groups, lack of utilization of behavioral theories, and lack of intervention targeting disadvantaged populations. Future interventions utilizing randomized controlled trials with large sample sizes are needed to assess the impact of yoga on child and adolescent obesity.