Search

Background The role of social environment, that is, the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. Methods We developed a novel polysocial risk score for dementia based on 19 SDOH among 5 199 participants in the Health and Retirement Study, United States, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006–2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. Results The study participants (mean age = 73.4 years, SD  = 8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1 089 participants developed dementia. Every 1-point increase in the polysocial risk score (ranging from 0 to 10) was associated with a 21.6% higher risk (adjusted hazard ratio [aHR] = 1.21, 95% confidence intervals [95% CI] = 1.15–1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43%–60% lower risk of developing dementia (p  < .001). In addition, African Americans were 1.3 times (aHR = 2.28, 95% CI = 1.96–2.66) more likely to develop dementia than European Americans, other things being equal. Conclusion An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia. [ABSTRACT FROM AUTHOR]

The automotive industry appears to be a particularly attractive application case for blockchain technology adoption. Blockchain is one of the innovations that has much potential to change current business processes in German original equipment manufacturers (OEMs) and enable new services for their customers. This paper combines collective case study and in-depth interviews to explore the potentials and existing challenges of blockchain technology-based applications at German OEMs. The results suggest that blockchain applications have advantages in aggregating product information, securing transaction information, and establishing a reliable supply chain. Based on the TOE (technology, organisation and environment) model, our case study shows that the biggest obstacles for blockchain technology adoption in the automotive supply chain include: technology immaturity, lack of guidance and industry standards, non-cooperation of chain members, and legislative ambiguity. Based on auto manufacturers investigated, blockchain technology is perceived to have great potentials in reducing process costs, ensure product quality, and enhance the automotive supply chain's visibility and digitisation. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake. [ABSTRACT FROM AUTHOR]

Background: Root resorption of adjacent teeth due to impacted canines is common, and orthodontic treatment often leads to secondary resorption or even loss of adjacent roots. Clinical reports of long-term stability after treatment are rare. Case presentation: This study reports two cases of maxillary impacted canines resulting in severe root resorption of the adjacent lateral incisors. Surgical exposure, orthodontic retraction, and alignment of the impacted canines were successful in both cases, and the resorbed lateral incisors were stable with no significant loosening and normal pulp vitality after treatment and at the 5- and 10-year follow-up appointments. Conclusions: Light orthodontic force may be used to move adjacent teeth with root resorption due to tooth obstruction. The path and direction in which the teeth are moved must be specifically designed so that the adjacent roots are not resorbed and so long-term stability can be achieved. [ABSTRACT FROM AUTHOR]

This study aimed to understand Bangladeshi users' satisfaction with their assistive devices, including (a) device characteristics, e.g., size, weight, safety, ease of use, comfort, and effectiveness, and (b) availability of parts and repair services. We also described how frequently individuals with disabilities living in the community used assistive devices in their daily activities and how the use of assistive devices promoted individuals' wellbeing. We conducted a cross-sectional survey with assistive device users or their guardians (if under 18) in Bangladesh about their experience and satisfaction with their assistive device 6 months after receiving it. The research team developed a survey questionnaire consisting of both closed and open-ended questions. All data were collected via telephone interviews. We employed descriptive statistics to analyse quantitative data and inductive analysis for the qualitative data. We found that out of the 376 participants, nearly 95% used assistive devices on a regular basis, and their satisfaction with the devices was high. Participants reported that assistive devices improved mobility, independence, and wellbeing of persons with disabilities. A few participants (6.4%) reported that their devices were damaged. Some participants identified concerns with their assistive devices, including (i) inappropriate size of ankle-foot orthoses, manual self-propelled wheelchairs, and prostheses, (ii) back slabs (a type of brace) being too short, and (iii) walking frames being too large. Several participants noted pain and discomfort when they used their assistive device. Additionally, some participants stated that environmental factors (e.g., muddy roads) contributed to the disrepair of their assistive devices. Finally, participants recounted that repair services were limited in rural areas of Bangladesh. These findings indicate that the provision of assistive devices requires accommodating individuals' needs and ensuring appropriate environments in which to function. The results support the need for follow-up services after distributing assistive devices. Further research could explore the impact of assistive devices on the family quality of life of persons with disabilities. It is essential for rehabilitation professionals to conduct follow-up services after distributing assistive devices among persons with disabilities. There is a need for the government of Bangladesh to revisit the Rights and Protection of Persons with Disability Act of 2013 and provide further clarity about their commitment to the provision of assistive devices and associated services (e.g., repair services) and its subsequent implementation. Policymakers in Bangladesh must be proactive to translate policy commitments into practice, as it relates to building an accessible environment for people using assistive devices. Further, government efforts are needed to educate policy implementers in all relevant ministries so that all responsible bodies are fully familiar with their national and international commitments regarding the rights of persons with disabilities. Future research could (i) include user's satisfaction with the service delivery process and (ii) measure the impact of assistive devices on family quality of life of persons with disabilities. [ABSTRACT FROM AUTHOR]

Antibacterial coordination compounds have attracted tremendous attention ascribed to their excellent designability. However, how the morphological evolution of these complexes influences their antibacterial and physicochemical properties has never been investigated based on proposed mechanisms. Thus, a series of Co–HOAT coordination compounds synthesized from inorganic to organic cobalt sources were prepared. We propose that with the same HOAT ligand, inorganic Co–HOAT nanosheets possess higher sterilization rates compared with organic Co–HOAT nanoparticles. This is explained by the different steric hindrance of cobalt sources. Relatively small steric hindrance could lead to ample active positions for inorganic cobalt ions to coordinate with both N and O atoms in HOAT. Meanwhile, organic Co2+ ions could only unite with N atoms in HOAT. Furthermore, by theoretical calculation, cobalt ions with adequate coordination sites are beneficial for developing nanosheet morphologies. Meanwhile, the Co–HOAT complexes with a lower density of electron clouds present higher sterilization rates due to the anchoring effect of electrostatic attraction. The proposed mechanism is that Co2+ released from compounds could cause multiple toxic effects to bacteria anchored by Co–HOATs. Finally, Co–HOATs' behaviors have excellent antimicrobial properties without environmental limitations. In conclusion, the Co–HOATs appear to be a potential antibacterial catalyst in the antimicrobial field. [ABSTRACT FROM AUTHOR]

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2‐related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch‐like ECH‐associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1‐Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1‐Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2. [ABSTRACT FROM AUTHOR]

Impacts occur everywhere, and they pose a serious threat to human health and production safety. Flexible materials with efficient cushioning and energy absorption are ideal candidates to provide protection from impacts. Despite the high demand, the cushioning capacity of protective materials is still limited. In this study, an integrated bionic strategy is proposed, and a bioinspired structural composite material with highly cushioning performance is developed on the basis of this strategy. The results demonstrated that the integrated bionic material, an S‐spider web‐foam, has excellent energy storage and dissipation as well as cushioning performance. Under impact loading, S‐spider web‐foam can reduce peak impact forces by a factor of 3.5 times better than silicone foam, achieving unprecedented cushioning performance. The results of this study deepen the understanding of flexible cushioning materials and may provide new strategies and inspiration for the preparation of high‐performance flexible cushioning materials. [ABSTRACT FROM AUTHOR]

Background: Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young‐onset T2DM and T2DM patients with lean phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2) at T2DM diagnosis in 56 countries. Methods: Descriptive cross‐sectional analysis of WHO STEPS surveys. We analysed adults (25–69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five‐year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories. Results: There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25–29 years and 8.5% were 30–34 years old; in women, 8.6% and 12.5% were 25–29 years and 30–34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category. Conclusions: A non‐negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus (COVID-19) became a global pandemic in March 2020 and impacted nations worldwide not only because of the disease but also because the containment measures-imposed created ripple effects for the populations in each country. The COVID-19 pandemic disproportionately affected vulnerable groups, such as persons with disabilities. This study aimed to understand the impact of COVID-19 on the function of Community-Based Rehabilitation (CBR)/Community-Based Inclusive Development (CBID) across nations and for their target communities—persons with disabilities. The current article also described some measures CBR/CBID programs took in light of service closure to facilitate access to needed services for persons with disabilities. Methods: We conducted a secondary analysis of qualitative data to understand the impact of COVID-19 on the functioning of CBR/CBID programs and their target communities. The original qualitative data were collected through online dialogues among CBR/CBID partners across five regions of the world, facilitated for understanding of their practices on five other topics. Findings: COVID-19 significantly impacted the function of CBR/CBID programs across the world. Many services were halted due to public health measures, such as maintaining social distancing or lockdowns. The COVID-19 pandemic also had a negative impact on access to health, education and livelihood support for persons with disabilities. Additionally, many people with disabilities did not have access to COVID-19 related information and services like vaccines. However, we found that technology played a significant role in revitalizing CBR/CBID programs during COVID-19. CBR/CBID service providers across five regions used online platforms to disseminate information about COVID-19. Professionals also used technology to provide rehabilitation and educational services to people with disabilities through online platforms. Conclusion: Our findings suggest that technology can play a vital role in continuing many services (e.g., CBR/CBID) that cannot be offered in person during crises like COVID-19. However, it is important to remember that technology may not be accessible to many individuals with disabilities, specifically those who reside in rural areas and who experience adverse situations like financial constraints. Additionally, many persons with disabilities may not have the necessary knowledge and skills to use technology. CBR personnel must consider that before adopting technology to provide services under CBR programs. [ABSTRACT FROM AUTHOR]

Background: The prevalence of high-risk pregnancy increased after the implementation of two-child policy in China, but the impact of this policy change on the burden and profile of multiple high-risk factors in pregnancy (MHFP) has been insufficiently explored. We hypothesised that the profile of MHFP might have changed after the two-child policy was implemented and aimed to estimate the prevalence, intercorrelation, and outcomes of MHFP before and after its introduction., Methods: We obtained data on the population of pregnant women before (2015) and after (2020/2021) the implementation of universal two-child policy in Huai'an. We then included 33 risk factors in our analysis based on the Five-Colour Management framework and defined MHFP as an individual having two or more of these factors. We also estimated the changes of the prevalence of each single factor and their coexistence. Lastly, we performed a network analysis to assess the intercorrelations across these factors and used logistic regression models to evaluate MHFP-related pregnancy outcomes., Results: We observed an increase in the prevalence of MHFP after the implementation of the universal two-child policy (25.8% in 2015 vs 38.4% in 2020/2021, P < 0.01). Chronic conditions (e.g. gestational diabetes mellitus, abnormal body mass index) had the largest increase among the included factors, while cardiovascular disease and hypertensive disorders were central factors of the network structures. The correlations of advanced maternal age with abnormal pregnancy histories and scarred uteri increased significantly from 2015 to 2020/2021. MHFP was associated with multiple pregnancy outcomes, including preterm birth (adjusted odds ratio (aOR) = 2.57; 95% confidence interval (CI) = 2.39-2.75), low birthweight (aOR = 2.77; 95% CI = 2.54-3.02), low Apgar score (aOR = 1.41; 95% CI = 1.19-1.67), perinatal death (aOR = 1.75; 95% CI = 1.44-2.12), and neonatal death (aOR = 1.76; 95% CI = 1.42-2.18). Moreover, an increasing number and certain combinations of MHFP were associated with higher odds of pregnancy outcomes. For example, the aOR of preterm birth increased from 1.67 (95% CI = 1.52-1.87) for one risk factor to 8.03 (95% CI = 6.99-9.22) for ≥4 risk factors., Conclusions: Chinese women experienced a higher burden of multiple high-risk factors after the introduction of the two-child policy, particularly those with advanced maternal age, obesity, and chronic conditions. Strategies targeting chronic conditions for women with MHFP should be prioritised and a shift to a multiple-factor-oriented framework is needed in the expanding Chinese maternal health care system., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Microbial fuel cells (MFCs) have the dual advantage of mitigating Cr(Ⅵ) wastewater ecological threats while generating electricity. However, the low electron transfer efficiency and the limited enrichment of active electrogens are barriers to MFCs advancement. This study describes the synthesis of the TP-PDA-RGO@CC negative electrode using tea polyphenol as a reducing agent and polydopamine-doped graphene, significantly enhances the roughness and hydrophilicity of the anode. The charge transfer resistance was reduced by 94%, and the peak MFC power was 1375.80 mW·m -2 . Under acidic conditions, the Cr(Ⅵ) reduction rate reached 92% within 24 h, with a 52% increase in coulombic efficiency. Biodiversity analysis shows that the TP-PDA-RGO@CC anode could enrich electrogens, thereby boosting the electron generation mechanism at the anode and enhancing the reduction efficiency of Cr(Ⅵ) in the cathode chamber. This work emphasizes high-performance anode materials for efficient pollutant removal, energy conversion, and biomass reuse., 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. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Ltd.)

Intractable lymphatic malformations (iLM) pose a significant threat to affected children, demonstrating limited responses to conventional treatments. Sirolimus, effectively inhibiting endothelial cell proliferation in lymphatic vessels, plays a crucial role in iLM treatment. However, the drug's narrow therapeutic window and substantial interindividual variability necessitate customized dosing strategies. This study aims to establish a Population Pharmacokinetic Model (PopPK model) for sirolimus in pediatric iLM patients, identifying quantitative relationships between covariates and sirolimus clearance and volume of distribution. Initial dosages are recommended based on a target concentration range of 5-15 ng/mL. Retrospective data from our institution, encompassing 53 pediatric patients with 275 blood concentration results over the past five years (average age: 4.64 ± 4.19 years), constituted the foundation of this analysis. The final model, adopting a first-order absorption and elimination single-compartment model, retained age as the sole covariate. Results indicated a robust correlation between apparent clearance (CL/F) at 5.56 L/h, apparent volume of distribution (V/F) at 292.57 L, and age. Monte Carlo simulation guided initial dosages for patients aged 0-18 years within the target concentration range. This study presents the first PopPK model using a large Therapeutic Drug Monitoring (TDM) database to describe personalized sirolimus dosing for pediatric iLM patients, contributing to pharmacokinetic guidance and potentially improving long-term clinical outcomes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated with an increased risk of developing such hallmark-related diseases., Methods: In this multicohort study, we included people aged 38-72 years with data on weight, height, and waist circumference measured during a clinical examination at baseline between March 13, 2006, and Oct 1, 2010, from the UK Biobank with follow-up until Nov 12, 2021. To test reproducibility of the findings (replication analysis), we used data from people aged 40 years or older included in the Finnish Public Sector study and the Finnish Health and Social Support study who responded to the study surveys, had data on BMI, and were successfully linked to electronic health records from national registers up to Dec 31, 2016. Obesity and clinical characteristics were assessed at baseline. Via linkage to national health records, participants were followed up for 83 diseases related to nine ageing hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication). Outcomes were the first instance of hallmark-related disease, in addition to co-occurrence of three or more hallmark-related diseases and mortality., Findings: 496 530 adults (mean age 57·0 years [SD 8·1]) from the UK Biobank were included in the primary analysis, and 83 249 (mean age 48·2 years [6·4]) adults from the Finnish cohorts were included in the replication analysis. Median follow-up was 12·7 years (IQR 12·0-13·4) in the UK Biobank and 14·0 years (8·0-15·0) in the Finnish cohorts. After adjusting for demographic characteristics, lifestyle factors, and depression, UK Biobank participants with obesity (BMI ≥30·0 kg/m 2 ) had a 1·40 (95% CI 1·38-1·41) times higher hazard ratio for the first hallmark-related disease than those with a healthy weight (BMI 18·5-24·9 kg/m 2 ). The corresponding hazard ratios for three co-occurring diseases were 2·92 (95% CI 2·64-3·22) for deregulated nutrient sensing, 2·73 (2·46-3·02) for telomere attrition, 2·33 (2·10-2·60) for epigenetic alterations, 2·30 (2·14-2·48) for mitochondrial dysfunction, 2·23 (2·04-2·45) for stem cell exhaustion, 2·02 (1·89-2·16) for altered intercellular communication, 2·01 (1·89-2·15) for cellular senescence, 1·83 (1·67-2·00) for loss of proteostasis, and 1·39 (1·27-1·52) for genomic instability. These findings were replicated in the Finnish cohorts. In both studies, the associations between other risk factors (low education, unhealthy dietary factors [available only in the UK Biobank], smoking, high alcohol consumption, physical inactivity, and depression) and hallmark-related diseases were weaker than those with obesity. 45-60% of the excess mortality in people with obesity was attributable to hallmark-related diseases., Interpretation: Obesity might have an important role in the development of diseases associated with cellular ageing. Tackling ageing mechanisms could potentially help to reduce the disease and mortality burden resulting from the obesity epidemic., Funding: Wellcome Trust, UK Medical Research Council, US National Institute on Aging, Academy of Finland, and Finnish Foundation for Cardiovascular Research., Translations: For the German and Finnish translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Pancreatic cancer (PC) continues to rank as one of the deadliest forms of cancer, with the majority of patients being diagnosed with unresectable disease. The implementation of cryoablation-based comprehensive treatment is expected to lead to a reduction in tumour size and potentially achieve complete resection. However, the availability of systematic and evidence-based treatment guidelines for cryoablation in pancreatic cancer is currently limited., Materials and Methods: A computerized search was conducted in the Medline, Embase, Cochrane Library databases, and Clinicaltrials to retrieve studies published from August 1987 to June 2023. The perioperative outcomes and long-term survival of patients with locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (mPC) who underwent cryosurgery were systematically collected. Heterogeneity was assessed using Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. Data were pooled and analyzed using Stata 14.0 software. The Newcastle-Ottawa Quality Assessment Form tool was employed for quality evaluation., Results: Nine studies, including 368 patients, were identified. The pooled overall incidence rate was 4% (95% CI: 0-14%; I²=54.06%) for acute pancreatitis, 0% (95% CI: 0-0%; I²=0.0%) for delayed gastric emptying, 0% (95% CI: 0-1%; I²=0.0%) for postoperative pancreatic fistula (POPF) or bile leakage, 2% (95% CI: 0-5%; I²=0.0%) for bleeding, and 4% (95% CI: 0-12%; I²=70.46%) for fever. The subgroup analysis revealed that the percutaneous treatment group had a lower incidence of complications compared to laparotomy but had higher incidences of POPF, bleeding, and pancreatitis than the intraoperative group. Median overall survival (OS) varied from 5 to 16.2 months. The median survival rates at 6, 12, 24, and 36 months for patients who underwent cryosurgery were as follows: 94.9%, 64.8% (range: 4.8-63.1%), 22.80%, and 9.5%, respectively., Conclusion: With the advancements in cryoablation and anti-tumour therapy, cryoablation has emerged as a promising treatment modality for patients with unresectable pancreatic cancer. According to existing literature, the combination of cryoablation with radioactive particle implantation or immunotherapy has demonstrated considerable efficacy and safety. However, while the majority of included data is derived from retrospective studies, it is imperative to conduct larger sample sizes or prospective trials for further validation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Android is undergoing unprecedented malicious threats daily, but the existing methods for malware detection often fail to cope with evolving camouflage in malware. To address this issue, we present Hawk, a new malware detection framework for evolutionary Android applications. We model Android entities and behavioral relationships as a heterogeneous information network (HIN), exploiting its rich semantic meta-structures for specifying implicit higher order relationships. An incremental learning model is created to handle the applications that manifest dynamically, without the need for reconstructing the whole HIN and the subsequent embedding model. The model can pinpoint rapidly the proximity between a new application and existing in-sample applications and aggregate their numerical embeddings under various semantics. Our experiments examine more than 80 860 malicious and 100 375 benign applications developed over a period of seven years, showing that Hawk achieves the highest detection accuracy against baselines and takes only 3.5 ms on average to detect an out-of-sample application, with the accelerated training time of 50× faster than the existing approach.

Backgrounds: This study aimed to investigate the relationship between Cx43 expression and autophagy mediated by the AMPK-mTOR-Ulk1 signaling pathway in jaundice heart., Methods: In this study, a jaundice model was established in common bile duct ligation (CBDL) rats. Cardiac injury was assessed using various methods including myocardial injury indicators, echocardiography, TEM, HE staining, Masson staining, IHC, and IF. We investigated the regulatory relationship between Cx43, autophagy, and the AMPK-mTOR-ULK pathway in vivo by administering autophagy agonists (Rapa), autophagy inhibitors (3-MA), and Cx43 inhibitors (Gap 26). In vitro, we observed the relationship between autophagy and the AMPK-mTOR-ULK1 pathway in cells by exposing them to the AMPK inhibitor Compound C and the AMPK activator AICAR., Results: We found that CBDL induced autophagy through the AMPK-mTOR-ULK pathway, leading to the inhibition of myocardial dysfunction. Rapamycin pretreatment with CBDL3d exhibited a protective effect against myocardial injury and promoted autophagy. In contrast, 3-MA had no impact. Pretreatment with rapamycin at CBDL2w enhanced autophagy and aggravated cardiac injury; however, inhibition of autophagy using 3-MA attenuated cardiac injury. Cell viability was enhanced by AMPK inhibitors and inhibited by AMPK agonists. In addition, we observed that increased autophagy led to decreased Cx43 expression, which negatively affected cardiac function., Conclusions: CBDL induces myocardial injury in rats and activates autophagy through the AMPK-mTOR-ULK pathway, resulting in decreased Cx43 protein levels. A moderate increase in early autophagy in CBDL can improve cardiac injury, while late inhibition of autophagy can reduce myocardial injury., Competing Interests: CONFLICT OF INTEREST STATEMENT: None., (Copyright © 2024 by the Shock Society.)

Epidemiologic research has increasingly acknowledged the importance of developmental origins of health and disease (DOHaD) and suggests that prior exposures can be transferred across generations. Multigenerational cohorts are crucial to verify the intergenerational inheritance among human subjects. We carried out this scoping review aims to summarize multigenerational cohort studies' characteristics, issues, and implications and hence provide evidence to the DOHaD and intergenerational inheritance. We adopted a comprehensive search strategy to identify multigenerational cohorts, searching PubMed, EMBASE, and Web of Science databases from the inception of each dataset to June 20th, 2022, to retrieve relevant articles. After screening, 28 unique multigenerational cohort studies were identified. We classified all studies into four types: population-based cohort extended three-generation cohort, birth cohort extended three-generation cohort, three-generation cohort, and integrated birth and three-generation cohort. Most cohorts ( n = 15, 53%) were categorized as birth cohort extended three-generation studies. The sample size of included cohorts varied from 41 to 167,729. The study duration ranged from two years to 31 years. Most cohorts had common exposures, including socioeconomic factors, lifestyle, and grandparents' and parents' health and risk behaviors over the life course. These studies usually investigated intergenerational inheritance of diseases as the outcomes, most frequently, obesity, child health, and cardiovascular diseases. We also found that most multigenerational studies aim to disentangle genetic, lifestyle, and environmental contributions to the DOHaD across generations. We call for more research on large multigenerational well-characterized cohorts, up to four or even more generations, and more studies from low- and middle-income countries.

Background: Angiogenesis response plays a crucial role in the occurrence and development of Crohn's disease (CD) and may involve the mechanism of infliximab non-response. However, the role of angiogenesis-related genes in Crohn's disease has not been comprehensively studied. This study aimed to explore the expression profiles of angiogenesis-related genes in CD patients and construct models for disease diagnosis and prediction of infliximab non-response., Methods: CD-related microarray datasets were collected from the GEO database. Unsupervised consensus clustering analysis was performed based on differentially expressed angiogenesis-related genes to divide CD samples into two distinct clusters. Weighted gene co-expression network analysis (WGCNA) was conducted on the clusters to identify angiogenesis-related module. Based on the differentially expressed genes in the module, machine learning algorithms were employed to further identify hub genes and construct a disease diagnostic model. Subsequently, treatment outcome-related genes were extracted from these hub genes, and a predictive model for infliximab non-response in CD patients was ultimately built., Results: Based on angiogenesis-related genes, we identified two distinct CD clusters (C1 and C2). Compared to C1, the metabolic pathways in C2 were significantly upregulated, and there was a higher abundance of cell clusters such as M1 macrophages and plasma cells. Additionally, C2 showed a poorer response to infliximab. Furthermore, a predictive model for infliximab non-response in CD patients was constructed based on the hub genes, and it was successfully validated using an external dataset., Conclusion: Comprehensive analysis of angiogenesis-related genes revealed different clusters of CD, which exhibited differential response rates to infliximab. The construction of models provides a reference for disease diagnosis and drug selection, aiding in clinical decision-making., 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 © 2024 Zheng, Chen, Ke, Xu, Wu and Jiang.)