tRFtarget 2.0: expanding the targetome landscape of transfer RNA-derived fragments.

tRFtarget 1.0 (http://trftarget.net/) is a platform consolidating both computationally predicted and experimentally validated binding sites between transfer RNA-derived fragments (tRFs) and target genes (or transcripts) across multiple organisms. Here, we introduce a newly released version of tRFtarget 2.0, in which we integrated 6 additional tRF sources, resulting in a comprehensive collection of 2614 high-quality tRF sequences spanning across 9 species, including 1944 Homo sapiens tRFs and one newly incorporated species Rattus norvegicus. We also expanded target genes by including ribosomal RNAs, long non-coding RNAs, and coding genes >50 kb in length. The predicted binding sites have surged up to approximately 6 billion, a 20.5-fold increase than that in tRFtarget 1.0. The manually curated publications relevant to tRF targets have increased to 400 and the gene-level experimental evidence has risen to 232. tRFtarget 2.0 introduces several new features, including a web-based tool that identifies potential binding sites of tRFs in user's own datasets, integration of standardized tRF IDs, and inclusion of external links to contents within the database. Additionally, we enhanced website framework and user interface. With these improvements, tRFtarget 2.0 is more user-friendly, providing researchers a streamlined and comprehensive platform to accelerate their research progress.

diseaseGPS: auxiliary diagnostic system for genetic disorders based on genotype and phenotype.

SUMMARY: The next-generation sequencing brought opportunities for the diagnosis of genetic disorders due to its high-throughput capabilities. However, the majority of existing methods were limited to only sequencing candidate variants, and the process of linking these variants to a diagnosis of genetic disorders still required medical professionals to consult databases. Therefore, we introduce diseaseGPS, an integrated platform for the diagnosis of genetic disorders that combines both phenotype and genotype data for analysis. It offers not only a user-friendly GUI web application for those without a programming background but also scripts that can be executed in batch mode for bioinformatics professionals. The genetic and phenotypic data are integrated using the ACMG-Bayes method and a novel phenotypic similarity method, to prioritize the results of genetic disorders. diseaseGPS was evaluated on 6085 cases from Deciphering Developmental Disorders project and 187 cases from Shanghai Children's hospital. The results demonstrated that diseaseGPS performed better than other commonly used methods. AVAILABILITY AND IMPLEMENTATION: diseaseGPS is available to freely accessed at https://diseasegps.sjtu.edu.cn with source code at https://github.com/BioHuangDY/diseaseGPS.

Fetal overgrowth and weight trajectories during infancy and adiposity in early childhood.

BACKGROUND: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood. Little is known about how infancy growth trajectories affect adiposity in early childhood in LGA. METHODS: In the Shanghai Birth Cohort, we followed up 259 LGA (birth weight >90th percentile) and 1673 appropriate-for-gestational age (AGA, 10th-90th percentiles) children on body composition (by InBody 770) at age 4 years. Adiposity outcomes include body fat mass (BFM), percent body fat (PBF), body mass index (BMI), overweight/obesity, and high adiposity (PBF >85th percentile). RESULTS: Three weight growth trajectories (low, mid, and high) during infancy (0-2 years) were identified in AGA and LGA subjects separately. BFM, PBF and BMI were progressively higher from low- to mid-to high-growth trajectories in both AGA and LGA children. Compared to the mid-growth trajectory, the high-growth trajectory was associated with greater increases in BFM and the odds of overweight/obesity or high adiposity in LGA than in AGA children (tests for interactions, all P < 0.05). CONCLUSIONS: Weight trajectories during infancy affect adiposity in early childhood regardless of LGA or not. The study is the first to demonstrate that high-growth weight trajectory during infancy has a greater impact on adiposity in early childhood in LGA than in AGA subjects. IMPACT: Large-for-gestational age (LGA), a marker of fetal overgrowth, has been linked to obesity in adulthood, but little is known about how weight trajectories during infancy affect adiposity during early childhood in LGA subjects. The study is the first to demonstrate a greater impact of high-growth weight trajectory during infancy (0-2 years) on adiposity in early childhood (at age 4 years) in subjects with fetal overgrowth (LGA) than in those with normal birth size (appropriate-for-gestational age). Weight trajectory monitoring may be a valuable tool in identifying high-risk LGA children for close follow-ups and interventions to decrease the risk of obesity.

Factors Influencing the Sharing of Personal Health Data Based on the Integrated Theory of Privacy Calculus and Theory of Planned Behaviors Framework: Results of a Cross-Sectional Study of Chinese Patients in the Yangtze River Delta.

BACKGROUND: The health care system in China is fragmented, and the distribution of high-quality resources remains uneven and irrational. Information sharing is essential to the development of an integrated health care system and maximizing its benefits. Nevertheless, data sharing raises concerns regarding the privacy and confidentiality of personal health information, which affect the willingness of patients to share information. OBJECTIVE: This study aims to investigate patients' willingness to share personal health data at different levels of maternal and child specialized hospitals in China, to propose and test a conceptual model to identify key influencing factors, and to provide countermeasures and suggestions to improve the level of data sharing. METHODS: A research framework based on the Theory of Privacy Calculus and the Theory of Planned Behavior was developed and empirically tested through a cross-sectional field survey from September 2022 to October 2022 in the Yangtze River Delta region, China. A 33-item measurement instrument was developed. Descriptive statistics, chi-square tests, and logistic regression analyses were conducted to characterize the willingness of sharing personal health data and differences by sociodemographic factors. Structural equation modeling was used to assess the reliability and validity of the measurement as well as to test the research hypotheses. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies was applied for reporting results. RESULTS: The empirical framework had a good fit with the chi-square/degree of freedom (χ2/df)=2.637, root-mean-square residual=0.032, root-mean-square error of approximation=0.048, goodness-of-fit index=0.950, and normed fit index=0.955. A total of 2060 completed questionnaires were received (response rate: 2060/2400, 85.83%). Moral motive (ß=.803, P<.001), perceived benefit (ß=.123, P=.04), and perceived effectiveness of government regulation (ß=.110, P=.001) had a significantly positive association with sharing willingness, while perceived risk (ß=-.143, P<.001) had a significant negative impact, with moral motive having the greatest impact. The estimated model explained 90.5% of the variance in sharing willingness. CONCLUSIONS: This study contributes to the literature on personal health data sharing by integrating the Theory of Privacy Calculus and the Theory of Planned Behavior. Most Chinese patients are willing to share their personal health data, which is primarily motivated by moral concerns to improve public health and assist in the diagnosis and treatment of illnesses. Patients with no prior experience with personal information disclosure and those who have tertiary hospital visits were more likely to share their health data. Practical guidelines are provided to health policy makers and health care practitioners to encourage patients to share their personal health information.

Effects of a Nonwearable Digital Therapeutic Intervention on Preschoolers With Autism Spectrum Disorder in China: Open-Label Randomized Controlled Trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause difficulty with communication and social interactions as well as complicated family dynamics. Digital health interventions can reduce treatment costs and promote healthy lifestyle changes. These therapies can be adjunctive or replace traditional treatments. However, issues with cooperation and compliance prevent preschool patients with ASD from applying these tools. In this open-label, randomized controlled trial, we developed a nonwearable digital therapy called virtual reality-incorporated cognitive behavioral therapy (VR-CBT). OBJECTIVE: The aim of this study was to assess the adjunctive function of VR-CBT by comparing the effects of VR-CBT plus learning style profile (LSP) intervention with those of LSP-only intervention in preschool children with ASD. METHODS: This trial was performed in China on 78 preschool children (age 3-6 years, IQ>70) diagnosed with ASD who were randomized to receive a 20-week VR-CBT plus LSP intervention (intervention group, 39/78, 50%) or LSP intervention only (control group, 39/78, 50%). The primary outcome was the change of scores from baseline to week 20, assessed by using the parent-rated Autism Behavior Checklist (ABC). Secondary outcomes included the Childhood Autism Rating Scale (CARS), Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV), and behavioral performance data (accuracy and reaction time) in go/no-go tasks. All primary and secondary outcomes were analyzed in the intention-to-treat population. RESULTS: After the intervention, there was an intervention effect on total ABC (ß=-5.528; P<.001) and CARS scores (ß=-1.365; P=.02). A similar trend was observed in the ABC subscales: sensory (ß=-1.133; P=.047), relating (ß=-1.512; P=.03), body and object use (ß=-1.211; P=.03), and social and self-help (ß=-1.593; P=.03). The intervention also showed statistically significant effects in improving behavioral performance (go/no-go task, accuracy, ß=2.923; P=.04). Moreover, a significant improvement of ADHD hyperactivity-impulsivity symptoms was observed in 53 children with comorbid ADHD based on ADHD-RS-IV (ß=-1.269; P=.02). No statistically significant intervention effect was detected in the language subscale of ABC (ß=-.080; P=.83). Intervention group girls had larger improvements in ABC subscales, that is, sensory and body and object use and in the CARS score and accuracy of go/no-go task (all P<.05) than the control group girls. Statistically significant intervention effects could be observed in hyperactivity-impulsivity symptoms in the intervention group boys with comorbid ADHD compared with those in the control group boys (ß=-1.333; P=.03). CONCLUSIONS: We found potentially positive effects of nonwearable digital therapy plus LSP on core symptoms associated with ASD, leading to a modest improvement in the function of sensory, motor, and response inhibition, while reducing impulsivity and hyperactivity in preschoolers with both ASD and ADHD. VR-CBT was found to be an effective and feasible adjunctive digital tool. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053165; http://www.chictr.org.cn/showproj.aspx?proj=137016.

Higher greenspace exposure is associated with a decreased risk of childhood asthma in Shanghai - A megacity in China.

Inconsistent evidence exists about whether exposure to greenspace benefits childhood asthma. Previous studies have only focused on residential or school greenspace, and no research has combined greenspace exposures at both homes and schools to determine their link with childhood asthma. A population-based cross-sectional study was conducted among 16,605 children during 2019 in Shanghai, China. Self-reported questionnaires were used to collect information on childhood asthma and demographic, socioeconomic and behavioural factors. Environmental data including ambient temperature, particulate matter with aerodynamic diameter less than 1 µm (PM1), enhanced vegetation index (EVI), and normalized difference vegetation index (NDVI) were collected from satellite data. Binomial generalized linear models with a logit link were carried out to evaluate the association between greenspace exposure and children's asthma, as well as the effect modifiers. An interquartile range increment of whole greenspace (NDVI500, NDVI250, EVI500, and EVI250) exposure was associated with a reduced odds ratio of children's asthma (0.88, 95% CI: 0.78, 0.99; 0.89, 95% CI: 0.79, 1.01; 0.87, 95% CI: 0.77, 0.99; and 0.88, 95% CI: 0.78, 0.99, respectively) after controlling potential confounders. Low temperature, low PM1, males, vaginal delivery, suburban/rural area, and without family history of allergy appeared to enhance the greenspace-asthma association. Increased greenspace exposure was associated with a lower risk of childhood asthma, and the association was modified by a range of socio-environmental factors. These findings add to the body of evidence on the benefits of biodiversity and supporting the promotion of urban greenspace to protect children's health.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants.

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU µL-1 (18 fM spike protein), with a linear range of 250-10,000 TU µL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

Pediococcus pentosaceus CECT 8330 protects DSS-induced colitis and regulates the intestinal microbiota and immune responses in mice.

BACKGROUND: Compelling evidences demonstrated that gut microbiota dysbiosis plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Therapies for targeting the microbiota may provide alternative options for the treatment of IBD, such as probiotics. Here, we aimed to investigate the protective effect of a probiotic strain, Pediococcus pentosaceus (P. pentosaceus) CECT 8330, on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were administered phosphate-buffered saline (PBS) or P. pentosaceus CECT 8330 (5 × 108 CFU/day) once daily by gavage for 5 days prior to or 2 days after colitis induction by DSS. Weight, fecal conditions, colon length and histopathological changes were examined. ELISA and flow cytometry were applied to determine the cytokines and regulatory T cells (Treg) ratio. Western blot was used to examine the tight junction proteins (TJP) in colonic tissues. Fecal short-chain fatty acids (SCFAs) levels and microbiota composition were analyzed by targeted metabolomics and 16S rRNA gene sequencing, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of orthologous groups of proteins (COG) pathway analysis were used to predict the microbial functional profiles. RESULTS: P. pentosaceus CECT 8330 treatment protected DSS-induced colitis in mice as evidenced by reducing the weight loss, disease activity index (DAI) score, histological damage, and colon length shortening. P. pentosaceus CECT 8330 decreased the serum levels of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), and increased level of IL-10 in DSS treated mice. P. pentosaceus CECT 8330 upregulated the expression of ZO-1, Occludin and the ratio of Treg cells in colon tissue. P. pentosaceus CECT 8330 increased the fecal SCFAs level and relative abundances of several protective bacteria genera, including norank_f_Muribaculaceae, Lactobacillus, Bifidobacterium, and Dubosiella. Furthermore, the increased abundances of bacteria genera were positively correlated with IL-10 and SCFAs levels, and negatively associated with IL-6, IL-1ß, and TNF-α, respectively. The KEGG and COG pathway analysis revealed that P. pentosaceus CECT 8330 could partially recover the metabolic pathways altered by DSS. CONCLUSIONS: P. pentosaceus CECT 8330 administration protects the DSS-induced colitis and modulates the gut microbial composition and function, immunological profiles, and the gut barrier function. Therefore, P. pentosaceus CECT 8330 may serve as a promising probiotic to ameliorate intestinal inflammation.

Discovery of novel 3-butyl-6-benzyloxyphthalide Mannich base derivatives as multifunctional agents against Alzheimer's disease.

Based on the multitarget-directed ligands strategy, a series of 3-butyl-6-benzyloxyphthalide Mannich base derivatives were designed, synthesized and identified for Alzheimer's disease (AD). Biological activity studies demonstrated that the designed hybrids showed multitarget activities toward AD. Among them, compound 7d was the most potent agent with excellent inhibitory activities on EeAChE (IC50 = 0.087 µM), HuAChE (IC50 = 0.041 µM) and MAO-B (IC50 = 0.30 µM). Furthermore, molecular docking studies were conducted to investigate the interaction mode with enzymes. Besides, 7d also possessed good effects of Cu2+ chelation, ameliorate oxidative stress, and anti-neuroinflammation, desirable BBB permeability and eligible drug-like properties. Altogether, the multifunctional profiles of 7d prove that it deserves further investigation as a novel drug candidate for AD treatment.

6-Benzyloxyphthalides as selective and reversible monoamine oxidase B inhibitors with antioxidant and anti-neuroinflammatory activities for Parkinson's disease treatment.

A series of 6-benzyloxyphthalides were designed and synthesized as potent monoamine oxidase B inhibitors with antioxidant and anti-neuroinflammatory activities. The representative compounds 8f and 14a exhibited excellent selective MAO-B inhibition activity (IC50 = 1.33 nM, SI = 865; IC50 = 0.02 nM, SI = 40250, respectively) and moderate antioxidant activity (0.34 and 0.36 Trolox equivalent, respectively). Further studies showed that they were competitive and quasi-reversible MAO-B inhibitors. In cellular experiments, they could significantly decrease the production of NO and TNF-α in LPS-stimulated BV-2 cells to perform their in vitro anti-neuroinflammatory activities. Moreover, BBB permeability study and the predicted physicochemical properties indicated they were suitable for the CNS. Finally, in in vivo acute and subacute MPTP-induced mice model of PD, 8f and 14a could significantly improve most behavioral disorders, restore the DA content and decrease the MDA content in the mice striatum, exhibiting better anti-PD effects than clinically used safinamide. Hence, compounds 8f and 14a are identified in our studies as prospective prototype in the research of innovative multifunctional drugs for Parkinson's disease treatment.

Association of childhood asthma with intra-day and inter-day temperature variability in Shanghai, China.

OBJECTIVES: Short-term temperature variability (TV) is associated with the exacerbation of asthma, but little is known about the relative effects of intra- and inter-day TV. We aimed to assess the relative impacts of intra- and inter-day TV on childhood asthma and to explore the modification effects by season. METHODS: A quasi-Poisson generalized linear regression model combined with a distributed lag nonlinear model was adopted to evaluate the nonlinear and lagged effects of TV on childhood asthma in Shanghai from 2009 to 2017. Intra- and inter-day TV was measured with diurnal temperature range (DTR) and temperature changes between neighboring days (TCN), respectively. RESULTS: Increased DTR was associated with the elevated relative risk (RR) of daily outpatient visits for childhood asthma (DOVCA) in both the whole year (RRlag0-14 for the 99th percentile: 1.264, 95% confidence interval (CI): 1.052, 1.518) and cold season (RRlag0-12 for the 99th percentile: 1.411, 95% CI: 1.053, 1.889). Higher TCN in the warm season was associated with the increased RR of DOVCA (RRlag0-14 for the 99th percentile: 2.964, 95% CI: 1.636, 5.373). The number and fraction of DOVCA attributed to an interquartile range (IQR) increase of TCN were higher than those attributed to DTR in both the whole year period and warm season. However, the number and fraction of DOVCA attributed to an IQR increase of DTR were greater than those attributed to TCN in the cold season. CONCLUSIONS: Our results provide novel evidence that both intra- and inter-day TV might be a trigger of childhood asthma. Higher DTR appeared to have greater impacts on childhood asthma in the cold season while an increase in TCN seemed to have bigger effects in the warm season.

Environmental Exposure and Childhood Atopic Dermatitis in Shanghai: A Season-Stratified Time-Series Analysis.

BACKGROUND: Childhood atopic dermatitis (AD) is an inflammatory skin disease which sometimes predisposes to allergies. Environmental factors (low humidity, irritants, etc.) are prominent causative triggers of AD. OBJECTIVES: This study aims to explore the effects of both meteorological factors and air pollutants on childhood AD, and the modification effects by season in Shanghai, China. METHODS: Quasi-Poisson generalized linear regression model, combined with a distributed lag nonlinear model was used to examine the nonlinear and lagged effects of environmental factors on childhood AD from 2009 to 2017 in Shanghai. We also performed a season-stratified analysis to determine the modification effects of environmental exposure by season on childhood AD. RESULTS: There were 1,043,240 outpatient visits for childhood AD in total, at 3 major pediatric hospitals. Low temperature and relative humidity (RH), and high daily temperature difference (DTD) and air pollutants (i.e., NO2) increased the relative risks (RRs) of outpatient visits for childhood AD in the whole year. In the cold season, an increased risk of outpatient visits for childhood AD was associated with low RH (RR 2.26, 95% CI 1.69-3.02) and high NO2 (1.11, 95% CI 1.06-1.17). In the warm season, outpatient visits for childhood AD were associated with low temperature (3.49, 95% CI 3.22-3.77), low RH (1.89, 95% CI 1.74-2.06), high DTD (1.41, 95% CI 1.31-1.53), and high NO2 (1.05, 95% CI 1.03-1.06). CONCLUSIONS: This study suggests that environmental exposure may be a key trigger for outpatient visits for childhood AD with apparent seasonal effects. Tailored preventive strategies to avoid environmental triggers of childhood AD should be developed.

PhenoModifier: a genetic modifier database for elucidating the genetic basis of human phenotypic variation.

From clinical observations to large-scale sequencing studies, the phenotypic impact of genetic modifiers is evident. To better understand the full spectrum of the genetic contribution to human disease, concerted efforts are needed to construct a useful modifier resource for interpreting the information from sequencing data. Here, we present the PhenoModifier (https://www.biosino.org/PhenoModifier), a manually curated database that provides a comprehensive overview of human genetic modifiers. By manually curating over ten thousand published articles, 3078 records of modifier information were entered into the current version of PhenoModifier, related to 288 different disorders, 2126 genetic modifier variants and 843 distinct modifier genes. To help users probe further into the mechanism of their interested modifier genes, we extended the yeast genetic interaction data and yeast quantitative trait loci to the human and we also integrated GWAS data into the PhenoModifier to assist users in evaluating all possible phenotypes associated with a modifier allele. As the first comprehensive resource of human genetic modifiers, PhenoModifier provides a more complete spectrum of genetic factors contributing to human phenotypic variation. The portal has a broad scientific and clinical scope, spanning activities relevant to variant interpretation for research purposes as well as clinical decision making.

Investigating Patients' Continuance Intention Toward Conversational Agents in Outpatient Departments: Cross-sectional Field Survey.

BACKGROUND: Conversational agents (CAs) have been developed in outpatient departments to improve physician-patient communication efficiency. As end users, patients' continuance intention is essential for the sustainable development of CAs. OBJECTIVE: The aim of this study was to facilitate the successful usage of CAs by identifying key factors influencing patients' continuance intention and proposing corresponding managerial implications. METHODS: This study proposed an extended expectation-confirmation model and empirically tested the model via a cross-sectional field survey. The questionnaire included demographic characteristics, multiple-item scales, and an optional open-ended question on patients' specific expectations for CAs. Partial least squares structural equation modeling was applied to assess the model and hypotheses. The qualitative data were analyzed via thematic analysis. RESULTS: A total of 172 completed questionaries were received, with a 100% (172/172) response rate. The proposed model explained 75.5% of the variance in continuance intention. Both satisfaction (ß=.68; P<.001) and perceived usefulness (ß=.221; P=.004) were significant predictors of continuance intention. Patients' extent of confirmation significantly and positively affected both perceived usefulness (ß=.817; P<.001) and satisfaction (ß=.61; P<.001). Contrary to expectations, perceived ease of use had no significant impact on perceived usefulness (ß=.048; P=.37), satisfaction (ß=-.004; P=.63), and continuance intention (ß=.026; P=.91). The following three themes were extracted from the 74 answers to the open-ended question: personalized interaction, effective utilization, and clear illustrations. CONCLUSIONS: This study identified key factors influencing patients' continuance intention toward CAs. Satisfaction and perceived usefulness were significant predictors of continuance intention (P<.001 and P<.004, respectively) and were significantly affected by patients' extent of confirmation (P<.001 and P<.001, respectively). Developing a better understanding of patients' continuance intention can help administrators figure out how to facilitate the effective implementation of CAs. Efforts should be made toward improving the aspects that patients reasonably expect CAs to have, which include personalized interactions, effective utilization, and clear illustrations.

Pitt-Hopkins syndrome: phenotypic and genotypic description of four unrelated patients and structural analysis of corresponding missense mutations.

Pitt-Hopkins syndrome is an underdiagnosed neurodevelopmental disorder which is characterized by specific facial features, early-onset developmental delay, and moderate to severe intellectual disability. The genetic cause, a deficiency of the TCF4 gene, has been established; however, the underlying pathological mechanisms of this disease are still unclear. Herein, we report four unrelated children with different de novo mutations (T606A, K607E, R578C, and V617I) located at highly conserved sites and with clinical phenotypes which present variable degrees of developmental delay and intellectual disability. Three of these four missense mutations have not yet been reported. The patient with V617I mutation exhibits mild intellectual disability and has attained more advanced motor and verbal skills, which is significantly different from other cases reported to date. Molecular dynamics simulations are used to explore the atomic level mechanism of how missense mutations impair the functions of TCF4. Mutations T606A, K607E, and R578C are found to affect DNA binding directly or indirectly, while V617I only induces subtle conformational changes, which is consistent with the milder clinical phenotype of the corresponding patient. The study expands the mutation spectrum and phenotypic characteristics of Pitt-Hopkins syndrome, and reinforces the genotype-phenotype correlation and strengthens the understanding of phenotype variability, which is helpful for further investigation of pathogenetic mechanisms and improved genetic counseling.

Breastfeeding duration modified the effects of neonatal and familial risk factors on childhood asthma and allergy: a population-based study.

BACKGROUND: Childhood asthma and allergic diseases are a significant global problem. There are inconsistent findings on the associations of delivery mode, the number of children in the household and breastfeeding with childhood asthma and allergic diseases. We assessed these associations and examined whether breastfeeding modified the effects of neonatal and familial risk factors on childhood asthma and allergic diseases. METHODS: A population-based cross-sectional study was conducted in Shanghai, China. A total of 17 primary schools were randomly selected from 13 districts of Shanghai in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma and allergic diseases. Multivariable logistic regression models were used to evaluate the associations between neonatal and familial factors and childhood asthma and allergic diseases, and to examine the modification effects of breastfeeding on the associations assessed. RESULTS: Of 10,464 primary school children aged 6-11 years, the overall prevalence of childhood asthma, allergic rhinitis, urticaria, food allergy and drug allergy was 13.9, 22.7, 15.3, 8.1 and 4.6%, respectively. Male sex, high socioeconomic status, cesarean section delivery, only one child in the household and having family history of allergy were associated with increased odds ratio (OR) of childhood asthma and allergic diseases while longer breastfeeding duration (> 6 months) was inversely associated with these diseases. Longer breastfeeding duration also attenuated the OR of neonatal and familial risk factors on childhood asthma and allergic diseases. For instance, the adjusted OR of childhood asthma in the group of vaginal delivery and breastfeeding duration > 6 months was lowest (0.78, 95% confidence interval: 0.66, 0.92). CONCLUSIONS: Longer breastfeeding duration was inversely associated with childhood asthma and allergic diseases, and also reduced the OR of neonatal and familial risk factors on these diseases. Giving the prevalence of childhood asthma and allergic diseases is rapidly rising across the globe, these findings may have important clinical and public health implications.

Novel 3-benzylidene/benzylphthalide Mannich base derivatives as potential multifunctional agents for the treatment of Alzheimer's disease.

To discover novel multifunctional agents for the treatment of Alzheimer's disease, a series of 3-benzylidene/benzylphthalide Mannich base derivatives were designed, synthesized and evaluated. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound (Z)-13c raised particular interest because of its excellent multifunctional bioactivities. It displayed excellent EeAChE and HuAChE inhibition (IC50 = 9.18 × 10-5 and 6.16 × 10-4 µM, respectively), good MAO-B inhibitory activity (IC50 = 5.88 µM) and high antioxidant activity (ORAC = 2.05 Trolox equivalents). Additionally, it also exhibited good antiplatelet aggregation activity, moderate self- and Cu2+-induced Aß1-42 aggregation inhibitory potency, disaggregation ability on Aß1-42 fibrils, biometal chelating ability, appropriate BBB permeability and significant neuroprotective effect. Furthermore, (Z)-13c can also ameliorate the learning and memory impairment induced by scopolamine in mice. These multifunctional properties highlight compound (Z)-13c as a promising candidate for further development of multifunctional drug against AD.

Design, synthesis, and in vitro evaluation of 4-aminoalkyl-1(2H)-phthalazinones as potential multifunctional anti-Alzheimer's disease agents.

A series of 4-aminoalkyl-1(2H)-phthalazinone derivatives was designed and synthesized as potential multifunctional agents for Alzheimer's disease (AD) treatment. In vitro biological assay results demonstrated that most synthesized compounds exhibited significant AChE inhibition, moderate to high MAOs inhibitory potencies and good anti-platelet aggregation abilities. Among them, compound 15b exhibited the highest inhibitory potencies towards MAO-B and MAO-A (IC50 = 0.7 µM and 6.4 µM respectively), moderate inhibition towards AChE (IC50 = 8.2 µM), and good activities against self- and Cu2+-induced Aß1-42 aggregation and platelet aggregation. Moreover, 15b also displayed antioxidant capacity, neuroprotective potency, anti-neuroinflammation and BBB permeability. These excellent results indicated that compound 15b could be worthy of further studies to be considered as a promising multifunctional candidate for the treatment of AD.

Evaluation Framework for Successful Artificial Intelligence-Enabled Clinical Decision Support Systems: Mixed Methods Study.

BACKGROUND: Clinical decision support systems are designed to utilize medical data, knowledge, and analysis engines and to generate patient-specific assessments or recommendations to health professionals in order to assist decision making. Artificial intelligence-enabled clinical decision support systems aid the decision-making process through an intelligent component. Well-defined evaluation methods are essential to ensure the seamless integration and contribution of these systems to clinical practice. OBJECTIVE: The purpose of this study was to develop and validate a measurement instrument and test the interrelationships of evaluation variables for an artificial intelligence-enabled clinical decision support system evaluation framework. METHODS: An artificial intelligence-enabled clinical decision support system evaluation framework consisting of 6 variables was developed. A Delphi process was conducted to develop the measurement instrument items. Cognitive interviews and pretesting were performed to refine the questions. Web-based survey response data were analyzed to remove irrelevant questions from the measurement instrument, to test dimensional structure, and to assess reliability and validity. The interrelationships of relevant variables were tested and verified using path analysis, and a 28-item measurement instrument was developed. Measurement instrument survey responses were collected from 156 respondents. RESULTS: The Cronbach α of the measurement instrument was 0.963, and its content validity was 0.943. Values of average variance extracted ranged from 0.582 to 0.756, and values of the heterotrait-monotrait ratio ranged from 0.376 to 0.896. The final model had a good fit (χ262=36.984; P=.08; comparative fit index 0.991; goodness-of-fit index 0.957; root mean square error of approximation 0.052; standardized root mean square residual 0.028). Variables in the final model accounted for 89% of the variance in the user acceptance dimension. CONCLUSIONS: User acceptance is the central dimension of artificial intelligence-enabled clinical decision support system success. Acceptance was directly influenced by perceived ease of use, information quality, service quality, and perceived benefit. Acceptance was also indirectly influenced by system quality and information quality through perceived ease of use. User acceptance and perceived benefit were interrelated.

Improvement in outpatient services using the WeChat calling system in the Shanghai Children's Hospital.

OBJECTIVES: We explored the utility of WeChat applet as part of the Outpatient Department (OPD) to provide patients with timely queuing information and compared it with the traditional calling system. METHODS: Data for the WeChat calling system was extracted for the period of May 2018 to September 2018. Data for the traditional system was extracted for the same period from the year 2017. We compared the effective patient waiting time and nurse idle time i.e. nonproductive time spent on factors outside of employees' control with the two systems. We also analyzed the relationship between the length of waiting time and conflicts between doctors and patients. RESULTS: The mean wait time for the traditional calling system was 126 minutes, while the average idle time for nurses was 96 minutes/day. On the other hand, the mean wait time for the WeChat calling system was 33 minutes, and the average idle time for nurses was 72 minutes/day. The incremental profit (cost of traditional calling system - cost of WeChat calling system) achieved from switching systems was 13,879 yuan/month. Behavioral observations showed that wait time (OR=2.745, 95%CI 1.936~3.892 P<0.0001) was a risk factor for staff-patient conflict. CONCLUSION: The cost of the WeChat calling system was significantly lower than the traditional system. Also, the traditional calling system was time-consuming. Longer waiting time was the main factor affecting OPD quality and caused conflicts between doctors and patients.