Surface protein profiling and subtyping of extracellular vesicles in body fluids reveals non-CSF biomarkers of Alzheimer's disease.

Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD-associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD-associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD.

Recent Progress on Microfluidics Integrated with Fiber-Optic Sensors for On-Site Detection.

This review introduces a micro-integrated device of microfluidics and fiber-optic sensors for on-site detection, which can detect certain or several specific components or their amounts in different samples within a relatively short time. Fiber-optics with micron core diameters can be easily coated and functionalized, thus allowing sensors to be integrated with microfluidics to separate, enrich, and measure samples in a micro-device. Compared to traditional laboratory equipment, this integrated device exhibits natural advantages in size, speed, cost, portability, and operability, making it more suitable for on-site detection. In this review, the various optical detection methods used in this integrated device are introduced, including Raman, ultraviolet-visible, fluorescence, and surface plasmon resonance detections. It also provides a detailed overview of the on-site detection applications of this integrated device for biological analysis, food safety, and environmental monitoring. Lastly, this review addresses the prospects for the future development of microfluidics integrated with fiber-optic sensors.

3D Multimodal Fusion Network with Disease-induced Joint Learning for Early Alzheimer's Disease Diagnosis.

Multimodal neuroimaging provides complementary information critical for accurate early diagnosis of Alzheimer's disease (AD). However, the inherent variability between multimodal neuroimages hinders the effective fusion of multimodal features. Moreover, achieving reliable and interpretable diagnoses in the field of multimodal fusion remains challenging. To address them, we propose a novel multimodal diagnosis network based on multi-fusion and disease-induced learning (MDL-Net) to enhance early AD diagnosis by efficiently fusing multimodal data. Specifically, MDL-Net proposes a multi-fusion joint learning (MJL) module, which effectively fuses multimodal features and enhances the feature representation from global, local, and latent learning perspectives. MJL consists of three modules, global-aware learning (GAL), local-aware learning (LAL), and outer latent-space learning (LSL) modules. GAL via a self-adaptive Transformer (SAT) learns the global relationships among the modalities. LAL constructs local-aware convolution to learn the local associations. LSL module introduces latent information through outer product operation to further enhance feature representation. MDL-Net integrates the disease-induced region-aware learning (DRL) module via gradient weight to enhance interpretability, which iteratively learns weight matrices to identify AD-related brain regions. We conduct the extensive experiments on public datasets and the results confirm the superiority of our proposed method. Our code will be available at: https://github.com/qzf0320/MDL-Net.

A Portable Array Visualization Device Integrating Sample Preparation and Detection All-in-One for the On-Site Analysis of Complex Samples.

A gas membrane separation/array fluorescence visualization (GMS/AFV) device is developed by integrating hydrazine-based carbonized copolymer dots (PD-N2H4) for visual on-site analysis. The novel PD-N2H4 was synthesized using a "polymer template" approach, exhibiting strong blue fluorescence capable of visual sensing. The GMS/AFV device integrates sample preparation and detection all-in-one, consisting of a smartphone, a sample pretreatment system, and an optical system. In the detection procedure, the samples will be treated in the sample pretreatment system to create volatile gases. Therefore, any gas samples as well as solid and liquid samples that potentially produce volatile gases can be visually detected on-site by the device. H2S was utilized as a model analyte to test the practicality of the GMS/AFV device. The entire analysis can be finished in 3 min, and the limit of detection of H2S is as low as 3.4 µg/L. Surprisingly, the device is also capable of high-throughput sample detection, which can process 48 samples simultaneously in about 20 min. The device offers a quick, easy, cheap, and environmentally friendly way to analyze volatile gases, and it creates new opportunities for on-site detection of complex samples.

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study.

OBJECTIVE: Perampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4-18 years) with epilepsy. METHOD: A multicenter prospective observational study was performed on children and adolescents (age, 4-18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. RESULTS: In this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. CONCLUSION: The overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.

The Effect of Aerobic Exercise on Cognitive Function in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis.

Background: Diabetes, a chronic disease metabolic disorder, commonly affects people. It is well-documented that aerobic exercise significantly reduces blood glucose in diabetic conditions. This study aimed to demonstrate the role of aerobic exercise on T2DM patients and cognitive impairment. Methods: We selected studies that published random controlled trials (RCTs) on the effects of aerobic exercise on cognitive function in patients with T2DM. However, the animal trials were we excluded in this study. We retrieved the data of random controlled trials from 8 databases based on the influences of aerobic exercise on cognitive function in patients with type 2 diabetes mellitus (T2DM). We utilized RevMan 5.3 software to analyze the data after evaluating the literature. Results: We selected 685 studies based on the information in the abstract and title after deleting the duplicate references. Then, we investigated the full text of 15. After full-text evaluation,we selected 10 random controlled trials to perform this comprehensive meta-analysis. We found that 10 studies derived the information of cognitive function between the test and the control groups and the cognitive function is significantly higher in the experimental group (SMD: 1.88; 95% Cl: 0.91,2.84; P < .01) than the control group. Moreover, the experimental group showed significantly higher minimum mental state examination (MMSE) (SMD: 2.06; 95% Cl: 0.96,3.14; P < .01) and Montreal Cognitive Assessment (MoCA) (SMD:1.62; 95% Cl: 0.54, 2.69; P < .01) than the normal group. Conclusion: Our findings demonstrated that aerobic exercise is crucially potent in T2DM patients and cognitive impairment, as evidenced by total cognitive function, MMSE, and MoCA. The above results should be warranted to verify with sophisticated clinical trials. In the future, aerobic exercise is suggested to guide patients'srecovery.

The association between creatinine to body weight ratio and the risk of progression to diabetes from pre-diabetes: a 5-year cohort study in Chinese adults.

OBJECTIVE: Evidence on the association between the creatinine to body weight (Cre/BW) ratio and the risk of pre-diabetes to diabetes development remains limited. Our study aimed to examine the association between the Cre/BW ratio and incident diabetes in pre-diabetic patients. METHODS: This retrospective cohort study included 24,506 pre-diabetic participants who underwent health checks from 2010 to 2016 in China. We used the Cox proportional-hazards regression model to explore the relationship between baseline Cre/BW ratio and diabetes risk in pre-diabetes patients. Using a Cox proportional hazards regression with cubic spline function and smooth curve fitting (cubical spline smoothing), we were able to determine the non-linear relationship between them. We also carried out a number of subgroup and sensitivity analyses. RESULTS: The age range of the participants included in this study was 20-99 years, with a majority of 16,232 individuals (66.24%) being men. The mean baseline Cre/BW ratio was 1.06 (SD 0.22) umol/L/kg. 2512 (10.25%) participants received a diabetes final diagnosis over a median follow-up period of 2.89 years. After adjusting for covariates, the Cre/BW ratio had a negative association with incident diabetes in participants with pre-diabetes, per umol/L/kg increase in Cre/BM ratio was accompanied by a 55.5% decrease in diabetes risk (HR = 0.445, 95%CI 0.361 to 0.548). The Cre/BW ratio and risk of diabetes had a non-linear connection, with 1.072 umol/L/kg serving as the ratio's inflection point. The HR were 0.294 (95%CI:0.208-0.414) and 0.712 (95%CI:0.492-1.029), respectively, on the left and right sides of the inflection point. The sensitivity analysis demonstrated the robustness of these results. Subgroup analyses indicated that the Cre/BW ratio was strongly associated with the risk of diabetes among participants who were younger than 50 years, as well as among those with diastolic blood pressure (DBP) < 90 mmHg and triglyceride (TG) < 1.7 mmol/L. In contrast, among participants 50 years of age or older, those with DBP ≥ 90 mmHg, and those with TG ≥ 1.7 mmol/L, the relationship between the Cre/BW ratio and the risk of diabetes was attenuated. CONCLUSION: This study demonstrates a negative, non-linear relationship between the Cre/BW ratio and the risk of diabetes among the Chinese population with pre-diabetes. From a therapeutic standpoint, it is clinically meaningful to maintain the Cre/BW ratio levels above the inflection point of 1.072 umol/L/kg.

Thermosensitive poly(N-isopropylacrylamide) hydrogel/highly internal phase emulsion porous polymer tube tip solid-phase extraction for the determination of methylimidazoles in beverage.

Poly(N-isopropylacrylamide) thermosensitive hydrogel tube tip solid-phase extraction/ultra-high liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed for analysis of methylimidazoles in beverages. Thermosensitive poly(N-isopropylacrylamide) (PNIPA) hydrogel solid-phase extraction (SPE) medium was prepared on the surface of highly internal phase emulsion (HIPE) porous polymer by thermally initiated polymerization in a tube tip. The temperature sensitive SPE medium has the characteristics of high porosity and high specific surface area. When the temperature is higher than 30.0℃, it can well adsorb polar molecular, and could quickly desorb polar molecular when the temperature was less than 20.0℃. The tube tip SPE coupled with UPLC-MS/MS method was established for the determination of three polar molecules including 1-methylimidazole, 4-methylimidazole and 2-methylimidazole, with linear ranges of 2.50 - 240 µg/L, and detection limits of 1.20, 1.20 and 0.65 µg/L, respectively. The method was applied to the determination of three methylimidazoles in beverages with the spiked recoveries of 81.5%-115.5% and the RSD of 0.6%-5.0%, and the relative errors of the results with the national standard UPLC-MS/MS method were in the range of -8.5%-8.9%.

[Surface-modified microchip electrophoretic separation and analysis of functional components in health care products].

Microchip electrophoresis (MCE) is widely applied in food, environment, medicine, and other fields, owing to its high separation efficiency, low consumption of reagents and samples, and ease of integrating multiple operating units. Polymer microchip materials like cycloolefin copolymer (COC) are low-cost and easy to fabricate. However, their practical applications are limited by the non-specific adsorption on channel surface during electrophoresis and the instability of electroosmotic flow. These shortcomings can be solved by COC surface modification. In this study, a static coating and dynamic/static coating combined strategy was used to develop a channel-surface-modified COC microchip. Combined with laser-induced fluorescence (LIF) detection, a MCE-LIF separation and analysis method was developed for detecting functional components in health care products. The separation performance of MCE was improved by the static coating microchannel surface modification method. The static coating was constructed by hydrophobic amino acid adsorption, glutaraldehyde immobilization, and hydrophilic amino acid functionalization on the COC microchannel surface. The separation performance of MCE was improved by microchannel surface modification combined with dynamic/static coating. The static coating was constructed by valine adsorption, carboxyl activation, and ethylenediamine functionalization on the COC microchannel surface. The dynamic coating is automatically formed by introducing a buffer solution containing hydroxypropyl methylcellulose and sodium dodecyl sulfate into the microchannel. The physical and chemical properties of surface-modified microchannels and the factors governing electrophoretic separation were studied. Combined with LIF detection, the MCE-LIF separation and analysis of lysine and γ-aminobutyric acid present in children's health care products, as well as aspartic acid and taurine in sport drinks, were developed. The recoveries of lysine and γ-aminobutyric acid in children's health care products were 84.8%-118%, and the relative standard deviations (RSDs) were less than 7.2% (n=3). The recoveries of aspartic acid and taurine in sport drinks were 97.5%-118%, and the RSDs were less than 6.4% (n=3). The analysis results are consistent with the HPLC results, and the method has potential for application in the separation and analysis of anionic amino acids in health care products.

Workplace violence against COVID-19 front-line healthcare workers versus non-front-line in Hangzhou, China: a cross-sectional study.

OBJECTIVES: Workplace violence (WPV) against healthcare workers (HCWs) is a global issue. Our research aimed to elucidate the status and associated factors of WPV among front-line/non-front-line HCWs during the COVID-19 pandemic. DESIGN: This cross-sectional study was conducted among HCWs in Hangzhou City through multistage sampling from December 2020 to January 2021. PARTICIPANTS: This study included 14 909 valid samples (N=3748 front-line HCWs and N=11 161 non-front-line HCWs). PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed the WPV status by Chinese version of WPV questionnaire. Binary logistic regression model was established to examine the associated factors of front-line/non-front-line HCWs experiencing WPV. RESULTS: The total WPV prevalence equalled 37.25% for front-line HCWs and 27.73% for non-front-line HCWs. Among front-line HCWs, females were less likely to experience WPV (OR 0.837, 95% CI 0.710 to 0.988), while individuals who were undergraduate (OR 1.251, 95% CI 1.061 to 1.541) and had higher professional title (intermediate: OR 1.475, 95% CI 1.227 to 1.772; advanced: OR 1.693, 95% CI 1.294 to 2.216) were more likely to suffer from WPV; for non-front-line HCWs, individuals who aged over 50 years old (OR 0.721, 95% CI 0.563 to 0.969), had worked between 10 and 19 years (OR 0.847, 95% CI 0.749 to 0.958) and worked in the non-graded hospital (OR 0.714, 95% CI 0.614 to 0.832) had less chance to experience WPV, while individuals who had higher educational level (undergraduate: OR 1.323, 95% CI 1.179 to 1.484; ≥graduate: OR 1.519, 95% CI 1.217 to 1.895), were nurse (OR 1.142, 95% CI 1.031 to 1.265), and had higher professional title (intermediate: OR 1.458, 95% CI 1.297 to 638; advanced: OR 1.928, 95% CI 1.607 to 2.313) were more inclined to suffer from WPV (p all<0.05). CONCLUSIONS: This study indicates that the prevalence of WPV among front-line HCWs is significantly higher than among non-front-line HCWs. Policy-makers should prioritise COVID-19 front-line HCWs, especially those with high educational levels and professional titles.

[Advances in microchip electrophoresis for the separation and analysis of biological samples].

Microchip electrophoresis is a separation technology that involves fluid manipulation in a microchip; the advantages of this technique include high separation efficiency, low sample consumption, and fast and easy multistep integration. Microchip electrophoresis has been widely used to rapidly separate and analyze complex samples in biology and medicine. In this paper, we review the research progress on microchip electrophoresis, explore the fabrication and separation modes of microchip materials, and discuss their applications in the detection and analysis of biological samples. Research on microchip materials can be mainly categorized into chip materials, channel modifications, electrode materials, and electrode integration methods. Microchip materials research involves the development of silicon, glass, polydimethylsiloxane and polymethyl methacrylate-based, and paper electrophoretic materials. Microchannel modification research primarily focuses on the dynamic and static modification methods of microchannels. Although chip materials and fabrication technologies have improved over the years, problems such as high manufacturing costs, long processing time, and short service lives continue to persist. These problems hinder the industrialization of microchip electrophoresis. At present, few static methods for the surface modification of polymer channels are available, and most of them involve a combination of physical adsorption and polymers. Therefore, developing efficient surface modification methods for polymer channels remains a necessary undertaking. In addition, both dynamic and static modifications require the introduction of other chemicals, which may not be conducive to the expansion of subsequent experiments. The materials commonly used in the development of electrodes and processing methods for electrode-microchip integration include gold, platinum, and silver. Microchip electrophoresis can be divided into two modes according to the uniformity of the electric field: uniform and non-uniform. The uniform electric field electrophoresis mode mainly involves micro free-flow electrophoresis and micro zone electrophoresis, including micro isoelectric focusing electrophoresis, micro isovelocity electrophoresis, and micro density gradient electrophoresis. The non-uniform electric field electrophoresis mode involves micro dielectric electrophoresis. Microchip electrophoresis is typically used in conjunction with conventional laboratory methods, such as optical, electrochemical, and mass spectrometry, to achieve the rapid and efficient separation and analysis of complex samples. However, the labeling required for most widely used laser-induced fluorescence technologies often involves a cumbersome organic synthesis process, and not all samples can be labeled, which limits the application scenarios of laser-induced fluorescence. The applications of unlabeled microchip electrophoresis-chemiluminescence/dielectrophoresis are also limited, and simplification of the experimental process to achieve simple and rapid microchip electrophoresis remains challenging. Several new models and strategies for high throughput in situ detection based on these detection methods have been developed for microchip electrophoretic systems. However, high throughput analysis by microchip electrophoresis is often dependent on complex chip structures and relatively complicated detection methods; thus, simple high throughput analytical technologies must be further explored. This paper also reviews the progress on microchip electrophoresis for the separation and analysis of complex biological samples, such as biomacromolecules, biological small molecules, and bioparticles, and forecasts the development trend of microchip electrophoresis in the separation and analysis of biomolecules. Over 250 research papers on this field are published annually, and it is gradually becoming a research focus. Most previous research has focused on biomacromolecules, including proteins and nucleic acids; biological small molecules, including amino acids, metabolites, and ions; and bioparticles, including cells and pathogens. However, several problems remain unsolved in the field of microchip electrophoresis. Overall, microchip electrophoresis requires further study to increase its suitability for the separation and analysis of complex biological samples.

Federated Domain Adaptation via Transformer for Multi-Site Alzheimer's Disease Diagnosis.

In multi-site studies of Alzheimer's disease (AD), the difference of data in multi-site datasets leads to the degraded performance of models in the target sites. The traditional domain adaptation method requires sharing data from both source and target domains, which will lead to data privacy issue. To solve it, federated learning is adopted as it can allow models to be trained with multi-site data in a privacy-protected manner. In this paper, we propose a multi-site federated domain adaptation framework via Transformer (FedDAvT), which not only protects data privacy, but also eliminates data heterogeneity. The Transformer network is used as the backbone network to extract the correlation between the multi-template region of interest features, which can capture the brain abundant information. The self-attention maps in the source and target domains are aligned by applying mean squared error for subdomain adaptation. Finally, we evaluate our method on the multi-site databases based on three AD datasets. The experimental results show that the proposed FedDAvT is quite effective, achieving accuracy rates of 88.75%, 69.51%, and 69.88% on the AD vs. NC, MCI vs. NC, and AD vs. MCI two-way classification tasks, respectively.

Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China.

Objective: This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC). Methods: This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups. Results: In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P < 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P < 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221). Conclusion: Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.

Enhancing doctor-patient relationships in community health care institutions: the Patient Oriented Four Habits Model (POFHM) trial-a stepped wedge cluster randomized trial protocol.

BACKGROUND: The poor relationship between doctors and patients is a long-standing, global problem. However, current interventions tend to focus on the training of physicians, while patient-targeted interventions still need to be improved. Considering that patients play a significant role in outpatient consultations, we developed a protocol to assess the effectiveness of the Patient Oriented Four Habits Model (POFHM) in improving doctor-patient relationships. METHODS: A cross-sectional incomplete stepped-wedge cluster randomized trial design will be conducted in 8 primary healthcare institutions (PHCs). Following phase I of "usual care" as control measures for each PHC, either a patient- or doctor-only intervention will be implemented in phase II. In phase III, both patients and doctors will be involved in the intervention. This study will be conducted simultaneously in Nanling County and West Lake District. The primary outcomes will be evaluated after patients complete their visit: (1) patient literacy, (2) sense of control and (3) quality of doctor-patient communication. Finally, a mixed-effects model and subgroup analysis will be used to evaluate the effectiveness of the interventions. DISCUSSION: Fostering good consultation habits for the patient is a potentially effective strategy to improve the quality of doctor-patient communication. This study evaluates the implementation process and develops a rigorous quality control manual using a theoretical domain framework under the collective culture of China. The results of this trial will provide substantial evidence of the effectiveness of patient-oriented interventions. The POFHM can benefit the PHCs and provide a reference for countries and regions where medical resources are scarce and collectivist cultures dominate. TRIAL REGISTRATION: AsPredicted #107,282 on Sep 18, 2022; https://aspredicted.org/QST_MHW.

The experiences of East Asian dementia caregivers in filial culture: a systematic review and meta-analysis.

Background: With the aging population in East Asia, the prevalence of dementia and the need for patient care is increasing. Family caregivers of people with dementia are at risk of physical and mental health problems. Filial piety culture regulates relationships within East Asian families and effects the well-being and behavior of dementia family caregivers (CGs). Objective: To systematically assess the experience of East Asian dementia caregivers in filial culture. Methods: Electronic databases, including MEDLINE, APA PsycINFO, CINAHL (via EBSCOhost), Web of Science, and Cochrane Library, were searched for relevant studies up to July 2021. Only original articles were included. Results: Thirteen eligible studies were included, of which eight were qualitative and five were quantitative. Meta-analysis showed a negative association (r = -0.18, 95%CI [-0.28, -0.08]) between filial culture and caregiver burden. The quantitative studies identified four themes related to dementia caregivers' experiences: (1) Recognition and understanding of filial piety as part of cultural identity, (2) Role transitions- from child to CG, (3) Filial piety's constraints on CGs; (4) CGs' self-compassion through changing cultural norms of filial practice. Conclusion: Filial culture influences the whole process behind caregiving for East Asian dementia caregivers. At the same time, cultural transition has also brought about new connotations and practices to filial culture.

Ag/Poly(N-isopropylacrylamide)-laponite Hydrogel Surface-Enhanced Raman Membrane Substrate for Rapid Separation, Concentration and Detection of Hydrophilic Compounds in Complex Sample All-in-One.

In this work, Ag nanoparticles (AgNPs) were embedded into a poly(N-isopropylacrylamide)-laponite (Ag/PNIP-LAP) hydrogel membrane for highly sensitive surface-enhancement Raman scattering (SERS) detection. In situ polymerization was initiated by UV light to encapsulate AgNPs in a PNIP-LAP hydrogel to prepare a highly active SERS membrane with a three-dimensional structure. Due to the surface plasmon resonance and high swelling/shrinkage ratio of the Ag/PNIP-LAP hydrogel SERS membrane, its network structure has a "sieving" effect, which makes it easier for hydrophilic small-molecule targets to enter the sterically confined hydrogel, and the AgNPs are close to each other to form a Raman "hot spot" through the shrinkage of the hydrogel, at the same time, the analyte is enriched in the confined space and close to the AgNPs to form a stronger SERS signal. The characterization of the SERS activity of the Ag/PNIP-LAP hydrogel showed that the prepared three-dimensional membrane had high detection sensitivity for urotropine, 2,5-dimethylpyrazine, pyrazinamide, and pyrazine; the detection limits (S/N = 3) were 17.4, 31.0, 53.1, and 1.11 µg/L, and the analytical time was 35 min. Due to the hydrophilicity of the Ag/PNIP-LAP hydrogel membrane, the small molecules can easily enter the SERS membrane, and the hydrophobic macromolecules are blocked outside the SERS membrane. The SERS method has good selectivity, stability, and reproducibility. The SERS method was applied to the detection of urotropine in dried bean curd sticks, 2,5-dimethylpyrazine in nuts and potato chips, and pyrazinamide in human plasma with recoveries of 81.8-116.8% and the relative standard deviation within 4.9-9.9%. The results matched well with that found by the corresponding chromatographic methods. The proposed method has the advantages of simple sample pretreatment, speediness, high sensitivity, and good selectivity to hydrophilic compounds and has potential application in the rapid on-site detection.

Chiral-Controlled Cyclic Chemiluminescence Reactions for the Analysis of Enantiomer Amino Acids.

The similarity and complexity of chiral amino acids (AAs) in complex samples remain a significant challenge in their analysis. In this work, the chiral metal-organic framework (MOF)-controlled cyclic chemiluminescence (CCL) reaction is developed and utilized in the analysis of enantiomer AAs. The chiral MOF of d-Co0.75Zn0.25-MOF-74 is designed and prepared by modifying the Co0.75Zn0.25-MOF-74 with d-tartaric acid. The developed chiral bimetallic MOF can not only offer the chiral recognize sites but also act as the catalyst in the cyclic luminol-H2O2 reaction. Moreover, a distinguishable CCL signal can be obtained on enantiomer AAs via the luminol-H2O2 reaction with the control of d-Co0.75Zn0.25-MOF-74. The amplified difference of enantiomer AAs can be quantified by the decay coefficient (k-values) which are calculated from the exponential decay fitting of their obtained CCL signals. According to simulation results, the selective recognition of 19 pairs of AAs is controlled by the pore size of the MOF-74 and their hydrogen-bond interaction with d-tartaric acid on the chiral MOF. Furthermore, the k-values can also be used to estimate the change of chiral AAs in complex samples. Consequently, this chiral MOF-controlled CCL reaction is applied to differentiate enantiomer AAs involved in the quality monitoring of dairy products and auxiliary diagnosis, which provides a new approach for chiral studies and their potential applications.

Depression and activities of daily living in elderly people applying for admission to public nursing facilities.

OBJECTIVE: The present study aims to (1) investigate the prevalence of positive screening for depression among elderly people applying for admission to public nursing facilities in Shenzhen and (2) to explore the correlation between depression and activities of daily living (ADL) among the elderly. METHODS: Visual and hearing acuity, ADL (obtained using the Barthel index), cognition and depression levels, and communication and social interaction skills were assessed in all elderly adults aged ≥60 years who applied for admission to public nursing facilities in Shenzhen between April 1, 2018, and December 31, 2019. RESULTS: A total of 1,113 elderly adults, 34.95% of whom were assessed as being depressed, were evaluated. Regarding dependence on the care of others, the ADL assessment results showed that 11.86% of the study subjects were fully dependent, 10.51% were severely dependent, 12.58% were moderately dependent, 42.86% were mildly dependent, and only 22.19% were fully capable of self-care. The univariate analysis suggested that gender, cognition level, visual and hearing acuity, and communication and social interaction skills were all correlated with the occurrence of depression. The prevalence of positive screening for depression was relatively high among subjects with an ADL score of ≤65; With an ADL score of ≤65, the prevalence of depression increased by 6% with every 1-point ADL score decrease. CONCLUSION: The prevalence of depression among elderly adults applying for admission to public nursing facilities in Shenzhen was high. For this reason, nursing facility caregivers should focus on screening elderly adults (especially subjects with impaired ADL function) for depression in order to improve their quality of life.

Multicenter and Multichannel Pooling GCN for Early AD Diagnosis Based on Dual-Modality Fused Brain Network.

For significant memory concern (SMC) and mild cognitive impairment (MCI), their classification performance is limited by confounding features, diverse imaging protocols, and limited sample size. To address the above limitations, we introduce a dual-modality fused brain connectivity network combining resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), and propose three mechanisms in the current graph convolutional network (GCN) to improve classifier performance. First, we introduce a DTI-strength penalty term for constructing functional connectivity networks. Stronger structural connectivity and bigger structural strength diversity between groups provide a higher opportunity for retaining connectivity information. Second, a multi-center attention graph with each node representing a subject is proposed to consider the influence of data source, gender, acquisition equipment, and disease status of those training samples in GCN. The attention mechanism captures their different impacts on edge weights. Third, we propose a multi-channel mechanism to improve filter performance, assigning different filters to features based on feature statistics. Applying those nodes with low-quality features to perform convolution would also deteriorate filter performance. Therefore, we further propose a pooling mechanism, which introduces the disease status information of those training samples to evaluate the quality of nodes. Finally, we obtain the final classification results by inputting the multi-center attention graph into the multi-channel pooling GCN. The proposed method is tested on three datasets (i.e., an ADNI 2 dataset, an ADNI 3 dataset, and an in-house dataset). Experimental results indicate that the proposed method is effective and superior to other related algorithms, with a mean classification accuracy of 93.05% in our binary classification tasks. Our code is available at: https://github.com/Xuegang-S.