The complete and fully-phased diploid genome of a male Han Chinese.

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.

Dexmedetomidine alleviates osteoarthritis inflammation and pain through the CB2 pathway in rats.

As a common joint disease, osteoarthritis (OA) is often associated with chronic pain. Synovial inflammation is correlated with OA progression and pain. Synovial inflammation can produce a series of destructive substances, such as inflammatory factors and pain mediators, which aggravate cartilage injury and further accelerate the progression of OA. Although many studies investigated the effects of synovial inflammation on the onset and progression of OA, there are limited reports regarding slowing the progression of OA and relieving pain by modulating synovial inflammation. Therefore, there is an urgent need to search for safe and effective drugs to alleviate synovial inflammation. Dexmedetomidine, a selective α2 agonist, has been shown to have anti-inflammatory and analgesic effects. However, its role and mechanism in OA remain unclear. Here, the effects and mechanisms of dexmedetomidine in OA synovial inflammation were investigated both in vivo and in vitro. We observed that dexmedetomidine stunted LPS-induced migration and invasion of FLSs and the expression of inflammatory factors by upregulating cannabinoid receptor type 2 (CB2) expression. Surprisingly, the application of AM630 (CB2 antagonist) reversed this therapeutic effect. The results of the animal experiments showed that dexmedetomidine reduced synovial inflammation and increased the pain threshold in an OA rat model. These preliminary results imply that dexmedetomidine may be an effective compound for OA treatment.

eSMC: a statistical model to infer admixture events from individual genomics data.

BACKGROUND: Inferring historical population admixture events yield essential insights in understanding a species demographic history. Methods are available to infer admixture events in demographic history with extant genetic data from multiple sources. Due to the deficiency in ancient population genetic data, there lacks a method for admixture inference from a single source. Pairwise Sequentially Markovian Coalescent (PSMC) estimates the historical effective population size from lineage genomes of a single individual, based on the distribution of the most recent common ancestor between the diploid's alleles. However, PSMC does not infer the admixture event. RESULTS: Here, we proposed eSMC, an extended PSMC model for admixture inference from a single source. We evaluated our model's performance on both in silico data and real data. We simulated population admixture events at an admixture time range from 5 kya to 100 kya (5 years/generation) with population admix ratio at 1:1, 2:1, 3:1, and 4:1, respectively. The root means the square error is [Formula: see text] kya for all experiments. Then we implemented our method to infer the historical admixture events in human, donkey and goat populations. The estimated admixture time for both Han and Tibetan individuals range from 60 kya to 80 kya (25 years/generation), while the estimated admixture time for the domesticated donkeys and the goats ranged from 40 kya to 60 kya (8 years/generation) and 40 kya to 100 kya (6 years/generation), respectively. The estimated admixture times were concordance to the time that domestication occurred in human history. CONCLUSION: Our eSMC effectively infers the time of the most recent admixture event in history from a single individual's genomics data. The source code of eSMC is hosted at https://github.com/zachary-zzc/eSMC .

COVID-19-Related Health Inequalities Induced by the Use of Social Media: Systematic Review.

Background: COVID-19-related health inequalities were reported in some studies, showing the failure in public health and communication. Studies investigating the contexts and causes of these inequalities pointed to the contribution of communication inequality or poor health literacy and information access to engagement with health care services. However, no study exclusively dealt with health inequalities induced by the use of social media during COVID-19. Objective: This review aimed to identify and summarize COVID-19-related health inequalities induced by the use of social media and the associated contributing factors and to characterize the relationship between the use of social media and health disparities during the COVID-19 pandemic. Methods: A systematic review was conducted on this topic in light of the protocol of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. Keyword searches were performed to collect papers relevant to this topic in multiple databases: PubMed (which includes MEDLINE [Ovid] and other subdatabases), ProQuest (which includes APA PsycINFO, Biological Science Collection, and others), ACM Digital Library, and Web of Science, without any year restriction. Of the 670 retrieved publications, 10 were initially selected based on the predefined selection criteria. These 10 articles were then subjected to quality analysis before being analyzed in the final synthesis and discussion. Results: Of the 10 articles, 1 was further removed for not meeting the quality assessment criteria. Finally, 9 articles were found to be eligible and selected for this review. We derived the characteristics of these studies in terms of publication years, journals, study locations, locations of study participants, study design, sample size, participant characteristics, and potential risk of bias, and the main results of these studies in terms of the types of social media, social media use-induced health inequalities, associated factors, and proposed resolutions. On the basis of the thematic synthesis of these extracted data, we derived 4 analytic themes, namely health information inaccessibility-induced health inequalities and proposed resolutions, misinformation-induced health inequalities and proposed resolutions, disproportionate attention to COVID-19 information and proposed resolutions, and higher odds of social media-induced psychological distress and proposed resolutions. Conclusions: This paper was the first systematic review on this topic. Our findings highlighted the great value of studying the COVID-19-related health knowledge gap, the digital technology-induced unequal distribution of health information, and the resulting health inequalities, thereby providing empirical evidence for understanding the relationship between social media use and health inequalities in the context of COVID-19 and suggesting practical solutions to such disparities. Researchers, social media, health practitioners, and policy makers can draw on these findings to promote health equality while minimizing social media use-induced health inequalities.

Chinese Version of the Mobile Health App Usability Questionnaire: Translation, Adaptation, and Validation Study.

BACKGROUND: The usability of mobile health (mHealth) apps needs to be effectively evaluated before they are officially approved to be used to deliver health interventions. To this end, the mHealth App Usability Questionnaire (MAUQ) has been designed and proved valid and reliable in assessing the usability of mHealth apps. However, this English questionnaire needs to be translated into other languages, adapted, and validated before being utilized to evaluate the usability of mHealth apps. OBJECTIVE: This study aims to improve, further adapt, and validate the Chinese version of the MAUQ (C-MAUQ; interactive for patients) on Left-handed Doctor, one of the most popular "reaching out to patients" interactive mHealth apps with chatbot function in China, to test the reliability and cross-cultural adaptability of the questionnaire. METHODS: The MAUQ (interactive for patients) has been translated into Chinese and validated for its reliability on Good Doctor, one of the most influential "reaching out to patients" mHealth apps without chatbot function in China. After asking for the researchers' approval to use this Chinese version, we adjusted and further adapted the C-MAUQ by checking it against the original English version and improving its comprehensibility, readability, idiomaticity, and cross-cultural adaptability. Following a trial survey completed by 50 respondents on wenjuanxing, the most popular online questionnaire platform in China, the improved version of the C-MAUQ (I-C-MAUQ) was finally used to evaluate the usability of Left-handed Doctor through an online questionnaire survey (answered by 322 participants) on wenjuanxing, to test its internal consistency, reliability, and validity. RESULTS: The I-C-MAUQ still retained the 21 items and 3 dimensions of the original MAUQ: 8 items for usability and satisfaction, 6 items for system information arrangement, and 7 items for efficiency. The translation problems in the C-MAUQ, including (1) redundancy, (2) incompleteness, (3) misuse of parts of speech, (4) choice of inappropriate words, (5) incomprehensibility, and (6) cultural difference-induced improper translation, were improved. As shown in the analysis of data obtained through the online survey, the I-C-MAUQ had a better internal consistency (ie, the correlation coefficient between the score of each item and the total score of the questionnaire determined within the range of 0.861-0.938; P<.01), reliability (Cronbach α=.988), and validity (Kaiser-Meyer-Olkin=0.973), compared with the C-MAUQ. It was effectively used to test the usability of Left-handed Doctor, eliciting over 80% of informants' positive attitudes toward this mHealth app. CONCLUSIONS: The I-C-MAUQ is highly reliable and valid for Left-handed Doctor, and suitable for testing the usability of interactive mHealth apps used by patients in China. This finding further confirms the cross-cultural validity, reliability, and adaptability of the MAUQ. We identified certain factors influencing the perceived usability of mHealth apps, including users' age, gender, education, profession, and possibly previous experience with mHealth apps and the chatbot function of such apps. Most notably, we found a wider acceptance of this new technology among young Chinese female college students who were more engaged in the interaction with health care chatbots. The age-, gender-, and profession-induced preference for new digital health interventions in China aligns with the findings in other similar studies in America and Malaysia. This preference identifies areas for further research on the social, cultural, and gender adaptation of health technologies.

Language Use in Conversational Agent-Based Health Communication: Systematic Review.

BACKGROUND: Given the growing significance of conversational agents (CAs), researchers have conducted a plethora of relevant studies on various technology- and usability-oriented issues. However, few investigations focus on language use in CA-based health communication to examine its influence on the user perception of CAs and their role in delivering health care services. OBJECTIVE: This review aims to present the language use of CAs in health care to identify the achievements made and breakthroughs to be realized to inform researchers and more specifically CA designers. METHODS: This review was conducted by following the protocols of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. We first designed the search strategy according to the research aim and then performed the keyword searches in PubMed and ProQuest databases for retrieving relevant publications (n=179). Subsequently, 3 researchers screened and reviewed the publications independently to select studies meeting the predefined selection criteria. Finally, we synthesized and analyzed the eligible articles (N=11) through thematic synthesis. RESULTS: Among the 11 included publications, 6 deal exclusively with the language use of the CAs studied, and the remaining 5 are only partly related to this topic. The language use of the CAs in these studies can be roughly classified into six themes: (1) personal pronouns, (2) responses to health and lifestyle prompts, (3) strategic wording and rich linguistic resources, (4) a 3-staged conversation framework, (5) human-like well-manipulated conversations, and (6) symbols and images coupled with phrases. These derived themes effectively engaged users in health communication. Meanwhile, we identified substantial room for improvement based on the inconsistent responses of some CAs and their inability to present large volumes of information on safety-critical health and lifestyle prompts. CONCLUSIONS: This is the first systematic review of language use in CA-based health communication. The results and limitations identified in the 11 included papers can give fresh insights into the design and development, popularization, and research of CA applications. This review can provide practical implications for incorporating positive language use into the design of health CAs and improving their effective language output in health communication. In this way, upgraded CAs will be more capable of handling various health problems particularly in the context of nationwide and even worldwide public health crises.

Chromosome-Level Haplotype Assembly for Equus asinu.

Background: Haplotype provides significant insights into understanding genomes at both individual and population levels. However, research on many non-model organisms is still based on independent genetic variations due to the lack of haplotype. Results: We conducted haplotype assembling for Equus asinu, a non-model organism that plays a vital role in human civilization. We described the hybrid single individual assembled haplotype of the Dezhou donkey based on the high-depth sequencing data from single-molecule real-time sequencing (×30), Illumina short-read sequencing (×211), and high-throughput chromosome conformation capture (×56). We assembled a near-complete haplotype for the high-depth sequenced Dezhou donkey individual and a phased cohort for the resequencing data of the donkey population. Conclusion: Here, we described the complete chromosome-scale haplotype of the Dezhou donkey with more than a 99.7% phase rate. We further phased a cohort of 156 donkeys to form a donkey haplotype dataset with more than 39 million genetic variations.

Interventions in Chinese Undergraduate Students' Mental Health: Systematic Review.

BACKGROUND: Over 30% of university students from 8 countries were afflicted with mental distress according to a World Health Organization survey. Undergraduate students in increasing numbers in China have also been reported to suffer from different mental problems. Various psychological distresses significantly impact their academic and daily life, thereby causing role impairments and unsatisfactory academic achievements. While the prevalence of, diverse underlying factors for, and interventions of social support in college students' mental health have extensively been investigated in China, there is no study exclusively focusing on the impact of interventions on their psychological well-being. OBJECTIVE: The aim of this review was to identify and synthesize the interventions in the mental health concerns of Chinese undergraduate students studying in China reported in the literature to inform educational authorities, college and university management, students' affairs counselors, and mental health providers. METHODS: We performed a systematic review and reported the research findings of previous studies according to the protocol of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. First, based on the predefined search strategy, keyword searches were performed in the PubMed and ProQuest databases to retrieve relevant studies. Subsequently, we screened the candidate articles based on predefined inclusion and exclusion criteria. Finally, we analyzed the included papers for qualitative synthesis. RESULTS: We retrieved a total of 675 studies from the PubMed and ProQuest databases using the search strategy on March 15, 2022. Among these candidate studies, 15 that were not written in English, 76 duplicates, and 149 studies of other document types were removed before screening. An additional 313 studies were excluded in the screening process, with 73 articles ruled out for being not relevant to interventions, not related to mental health, or not focused on undergraduate students in the full-text review. As a result, 49 papers were eligible and included in this systematic review. In the qualitative synthesis, we divided the interventions reported in the selected studies into two categories: (1) social support from government authorities, university authorities, students' affairs counselors and teachers, family members, health care authorities and professionals, and the media (various online platforms), and (2) various coping strategies adopted by undergraduate students themselves. We identified further research on mental health interventions that may be delivered by digital medical platforms, conversational agents (eg, chatbots), and researchers. CONCLUSIONS: This was the first systematic review of interventions to address the mental health concerns of Chinese undergraduate students studying in China. The categorization of reported interventions and the identification of new intervention channels can effectively inform stakeholders. Interventions for undergraduate students' mental health is a research topic worth further investigation.

Use of Health Care Chatbots Among Young People in China During the Omicron Wave of COVID-19: Evaluation of the User Experience of and Satisfaction With the Technology.

BACKGROUND: Long before the outbreak of COVID-19, chatbots had been playing an increasingly crucial role and gaining growing popularity in health care. In the current omicron waves of this pandemic when the most resilient health care systems at the time are increasingly being overburdened, these conversational agents (CA) are being resorted to as preferred alternatives for health care information. For many people, especially adolescents and the middle-aged, mobile phones are the most favored source of information. As a result of this, it is more important than ever to investigate the user experience of and satisfaction with chatbots on mobile phones. OBJECTIVE: The objective of this study was twofold: (1) Informed by Deneche and Warren's evaluation framework, Zhu et al's measures of variables, and the theory of consumption values (TCV), we designed a new assessment model for evaluating the user experience of and satisfaction with chatbots on mobile phones, and (2) we aimed to validate the newly developed model and use it to gain an understanding of the user experience of and satisfaction with popular health care chatbots that are available for use by young people aged 17-35 years in southeast China in self-diagnosis and for acquiring information about COVID-19 and virus variants that are currently spreading. METHODS: First, to assess user experience and satisfaction, we established an assessment model based on relevant literature and TCV. Second, the chatbots were prescreened and selected for investigation. Subsequently, 413 informants were recruited from Nantong University, China. This was followed by a questionnaire survey soliciting the participants' experience of and satisfaction with the selected health care chatbots via wenjuanxing, an online questionnaire survey platform. Finally, quantitative and qualitative analyses were conducted to find the informants' perception. RESULTS: The data collected were highly reliable (Cronbach α=.986) and valid: communalities=0.632-0.823, Kaiser-Meyer-Olkin (KMO)=0.980, and percentage of cumulative variance (rotated)=75.257% (P<.001). The findings of this study suggest a considerable positive impact of functional, epistemic, emotional, social, and conditional values on the participants' overall user experience and satisfaction and a positive correlation between these values and user experience and satisfaction (Pearson correlation P<.001). The functional values (mean 1.762, SD 0.630) and epistemic values (mean 1.834, SD 0.654) of the selected chatbots were relatively more important contributors to the students' positive experience and overall satisfaction than the emotional values (mean 1.993, SD 0.683), conditional values (mean 1.995, SD 0.718), and social values (mean 1.998, SD 0.696). All the participants (n=413, 100%) had a positive experience and were thus satisfied with the selected health care chatbots. The 5 grade categories of participants showed different degrees of user experience and satisfaction: Seniors (mean 1.853, SD 0.108) were the most receptive to health care chatbots for COVID-19 self-diagnosis and information, and second-year graduate candidates (mean 2.069, SD 0.133) were the least receptive; freshmen (mean 1.883, SD 0.114) and juniors (mean 1.925, SD 0.087) felt slightly more positive than sophomores (mean 1.989, SD 0.092) and first-year graduate candidates (mean 1.992, SD 0.116) when engaged in conversations with the chatbots. In addition, female informants (mean 1.931, SD 0.098) showed a relatively more receptive attitude toward the selected chatbots than male respondents (mean 1.999, SD 0.051). CONCLUSIONS: This study investigated the use of health care chatbots among young people (aged 17-35 years) in China, focusing on their user experience and satisfaction examined through an assessment framework. The findings show that the 5 domains in the new assessment model all have a positive impact on the participants' user experience and satisfaction. In this paper, we examined the usability of health care chatbots as well as actual chatbots used for other purposes, enriching the literature on the subject. This study also provides practical implication for designers and developers as well as for governments of all countries, especially in the critical period of the omicron waves of COVID-19 and other future public health crises.

Probabilistic Prediction of Nonadherence to Psychiatric Disorder Medication from Mental Health Forum Data: Developing and Validating Bayesian Machine Learning Classifiers.

Background: Medication nonadherence represents a major burden on national health systems. According to the World Health Organization, increasing medication adherence may have a greater impact on public health than any improvement in specific medical treatments. More research is needed to better predict populations at risk of medication nonadherence. Objective: To develop clinically informative, easy-to-interpret machine learning classifiers to predict people with psychiatric disorders at risk of medication nonadherence based on the syntactic and structural features of written posts on health forums. Methods: All data were collected from posts between 2016 and 2021 on mental health forum, administered by Together 4 Change, a long-running not-for-profit organisation based in Oxford, UK. The original social media data were annotated using the Tool for the Automatic Analysis of Syntactic Sophistication and Complexity (TAASSC) system. Through applying multiple feature optimisation techniques, we developed a best-performing model using relevance vector machine (RVM) for the probabilistic prediction of medication nonadherence among online mental health forum discussants. Results: The best-performing RVM model reached a mean AUC of 0.762, accuracy of 0.763, sensitivity of 0.779, and specificity of 0.742 on the testing dataset. It outperformed competing classifiers with more complex feature sets with statistically significant improvement in sensitivity and specificity, after adjusting the alpha levels with Benjamini-Hochberg correction procedure. Discussion. We used the forest plot of multiple logistic regression to explore the association between written post features in the best-performing RVM model and the binary outcome of medication adherence among online post contributors with psychiatric disorders. We found that increased quantities of 3 syntactic complexity features were negatively associated with psychiatric medication adherence: "dobj_stdev" (standard deviation of dependents per direct object of nonpronouns) (OR, 1.486, 95% CI, 1.202-1.838, P < 0.001), "cl_av_deps" (dependents per clause) (OR, 1.597, 95% CI, 1.202-2.122, P, 0.001), and "VP_T" (verb phrases per T-unit) (OR, 2.23, 95% CI, 1.211-4.104, P, 0.010). Finally, we illustrated the clinical use of the classifier with Bayes' monograph which gives the posterior odds and their 95% CI of positive (nonadherence) versus negative (adherence) cases as predicted by the best-performing classifier. The odds ratio of the posterior probability of positive cases was 3.9, which means that around 10 in every 13 psychiatric patients with a positive result as predicted by our model were following their medication regime. The odds ratio of the posterior probability of true negative cases was 0.4, meaning that around 10 in every 14 psychiatric patients with a negative test result after screening by our classifier were not adhering to their medications. Conclusion: Psychiatric medication nonadherence is a large and increasing burden on national health systems. Using Bayesian machine learning techniques and publicly accessible online health forum data, our study illustrates the viability of developing cost-effective, informative decision aids to support the monitoring and prediction of patients at risk of medication nonadherence.

Detecting Symptom Errors in Neural Machine Translation of Patient Health Information on Depressive Disorders: Developing Interpretable Bayesian Machine Learning Classifiers.

Background: Due to its convenience, wide availability, low usage cost, neural machine translation (NMT) has increasing applications in diverse clinical settings and web-based self-diagnosis of diseases. Given the developing nature of NMT tools, this can pose safety risks to multicultural communities with limited bilingual skills, low education, and low health literacy. Research is needed to scrutinise the reliability, credibility, usability of automatically translated patient health information. Objective: We aimed to develop high-performing Bayesian machine learning classifiers to assist clinical professionals and healthcare workers in assessing the quality and usability of NMT on depressive disorders. The tool did not require any prior knowledge from frontline health and medical professionals of the target language used by patients. Methods: We used Relevance Vector Machine (RVM) to increase generalisability and clinical interpretability of classifiers. It is a typical sparse Bayesian classifier less prone to overfitting with small training datasets. We optimised RVM by leveraging automatic recursive feature elimination and expert feature refinement from the perspective of health linguistics. We evaluated the diagnostic utility of the Bayesian classifier under different probability cut-offs in terms of sensitivity, specificity, positive and negative likelihood ratios against clinical thresholds for diagnostic tests. Finally, we illustrated interpretation of RVM tool in clinic using Bayes' nomogram. Results: After automatic and expert-based feature optimisation, the best-performing RVM classifier (RVM_DUFS12) gained the highest AUC (0.8872) among 52 competing models with distinct optimised, normalised features sets. It also had statistically higher sensitivity and specificity compared to other models. We evaluated the diagnostic utility of the best-performing model using Bayes' nomogram: it had a positive likelihood ratio (LR+) of 4.62 (95% C.I.: 2.53, 8.43), and the associated posterior probability (odds) was 83% (5.0) (95% C.I.: 73%, 90%), meaning that approximately 10 in 12 English texts with positive test are likely to contain information that would cause clinically significant conceptual errors if translated by Google; it had a negative likelihood ratio (LR-) of 0.18 (95% C.I.: 0.10,0.35) and associated posterior probability (odds) was 16% (0.2) (95% C.I: 10%, 27%), meaning that about 10 in 12 English texts with negative test can be safely translated using Google.

Supporting Risk-Aware Use of Online Translation Tools in Delivering Mental Healthcare Services among Spanish-Speaking Populations.

Neural machine translation technologies are having increasing applications in clinical and healthcare settings. In multicultural countries, automatic translation tools provide critical support to medical and health professionals in their interaction and exchange of health messages with migrant patients with limited or non-English proficiency. While research has mainly explored the usability and limitations of state-of-the-art machine translation tools in the detection and diagnosis of physical diseases and conditions, there is a persistent lack of evidence-based studies on the applicability of machine translation tools in the delivery of mental healthcare services for vulnerable populations. Our study developed Bayesian machine learning algorithms using relevance vector machine to support frontline health workers and medical professionals to make better informed decisions between risks and convenience of using online translation tools when delivering mental healthcare services to Spanish-speaking minority populations living in English-speaking countries. Major strengths of the machine learning classifier that we developed include scalability, interpretability, and adaptability of the classifier for diverse mental healthcare settings. In this paper, we report on the process of the Bayesian machine learning classifier development through automatic feature optimisation and the interpretation of the classifier-enabled assessment of the suitability of original English mental health information for automatic online translation. We elaborate on the interpretation of the assessment results in clinical settings using statistical tools such as positive likelihood ratios and negative likelihood ratios.

Forecasting the Suitability of Online Mental Health Information for Effective Self-Care Developing Machine Learning Classifiers Using Natural Language Features.

BACKGROUND: Online mental health information represents important resources for people living with mental health issues. Suitability of mental health information for effective self-care remains understudied, despite the increasing needs for more actionable mental health resources, especially among young people. OBJECTIVE: We aimed to develop Bayesian machine learning classifiers as data-based decision aids for the assessment of the actionability of credible mental health information for people with mental health issues and diseases. METHODS: We collected and classified creditable online health information on mental health issues into generic mental health (GEN) information and patient-specific (PAS) mental health information. GEN and PAS were both patient-oriented health resources developed by health authorities of mental health and public health promotion. GENs were non-classified online health information without indication of targeted readerships; PASs were developed purposefully for specific populations (young, elderly people, pregnant women, and men) as indicated by their website labels. To ensure the generalisability of our model, we chose to develop a sparse Bayesian machine learning classifier using Relevance Vector Machine (RVM). RESULTS: Using optimisation and normalisation techniques, we developed a best-performing classifier through joint optimisation of natural language features and min-max normalisation of feature frequencies. The AUC (0.957), sensitivity (0.900), and specificity (0.953) of the best model were statistically higher (p < 0.05) than other models using parallel optimisation of structural and semantic features with or without feature normalisation. We subsequently evaluated the diagnostic utility of our model in the clinic by comparing its positive (LR+) and negative likelihood ratios (LR-) and 95% confidence intervals (95% C.I.) as we adjusted the probability thresholds with the range of 0.1 and 0.9. We found that the best pair of LR+ (18.031, 95% C.I.: 10.992, 29.577) and LR- (0.100, 95% C.I.: 0.068, 0.148) was found when the probability threshold was set to 0.45 associated with a sensitivity of 0.905 (95%: 0.867, 0.942) and specificity of 0.950 (95% C.I.: 0.925, 0.975). These statistical properties of our model suggested its applicability in the clinic. CONCLUSION: Our study found that PAS had significant advantage over GEN mental health information regarding information actionability, engagement, and suitability for specific populations with distinct mental health issues. GEN is more suitable for general mental health information acquisition, whereas PAS can effectively engage patients and provide more effective and needed self-care support. The Bayesian machine learning classifier developed provided automatic tools to support decision making in the clinic to identify more actionable resources, effective to support self-care among different populations.

Automatic Diagnosis of Mental Healthcare Information Actionability: Developing Binary Classifiers.

We aimed to develop a quantitative instrument to assist with the automatic evaluation of the actionability of mental healthcare information. We collected and classified two large sets of mental health information from certified mental health websites: generic and patient-specific mental healthcare information. We compared the performance of the optimised classifier with popular readability tools and non-optimised classifiers in predicting mental health information of high actionability for people with mental disorders. sensitivity of the classifier using both semantic and structural features as variables achieved statistically higher than that of the binary classifier using either semantic (p < 0.001) or structural features (p = 0.0010). The specificity of the optimized classifier was statistically higher than that of the classifier using structural variables (p = 0.002) and the classifier using semantic variables (p = 0.001). Differences in specificity between the full-variable classifier and the optimised classifier were statistically insignificant (p = 0.687). These findings suggest the optimised classifier using as few as 19 semantic-structural variables was the best-performing classifier. By combining insights of linguistics and statistical analyses, we effectively increased the interpretability and the diagnostic utility of the binary classifiers to guide the development, evaluation of the actionability and usability of mental healthcare information.

Forecasting Erroneous Neural Machine Translation of Disease Symptoms: Development of Bayesian Probabilistic Classifiers for Cross-Lingual Health Translation.

BACKGROUND: Machine translation (MT) technologies have increasing applications in healthcare. Despite their convenience, cost-effectiveness, and constantly improved accuracy, research shows that the use of MT tools in medical or healthcare settings poses risks to vulnerable populations. OBJECTIVES: We aimed to develop machine learning classifiers (MNB and RVM) to forecast nuanced yet significant MT errors of clinical symptoms in Chinese neural MT outputs. METHODS: We screened human translations of MSD Manuals for information on self-diagnosis of infectious diseases and produced their matching neural MT outputs for subsequent pairwise quality assessment by trained bilingual health researchers. Different feature optimisation and normalisation techniques were used to identify the best feature set. RESULTS: The RVM classifier using optimised, normalised (L2 normalisation) semantic features achieved the highest sensitivity, specificity, AUC, and accuracy. MNB achieved similar high performance using the same optimised semantic feature set. The best probability threshold of the best performing RVM classifier was found at 0.6, with a very high positive likelihood ratio (LR+) of 27.82 (95% CI: 3.99, 193.76), and a low negative likelihood ratio (LR-) of 0.19 (95% CI: 0.08, 046), suggesting the high diagnostic utility of our model to predict the probabilities of erroneous MT of disease symptoms to help reverse potential inaccurate self-diagnosis of diseases among vulnerable people without adequate medical knowledge or an ability to ascertain the reliability of MT outputs. CONCLUSION: Our study demonstrated the viability, flexibility, and efficiency of introducing machine learning models to help promote risk-aware use of MT technologies to achieve optimal, safer digital health outcomes for vulnerable people.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility.

The COVID-19 pandemic has accounted for millions of infections and hundreds of thousand deaths worldwide in a short-time period. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed interindividual phenotypic variability. Here, we report the first host genetic study in the Chinese population by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People's Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe, and critical ill patients after the correction of potential confounding factors. Pedigree analysis suggested a potential monogenic effect of loss of function variants in GOLGA3 and DPP7 for critically ill and asymptomatic disease demonstration. Genome-wide association study suggests the most significant gene locus associated with severity were located in TMEM189-UBE2V1 that involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We identified that the HLA-A*11:01, B*51:01, and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial genomic study of Chinese patients provides genetic insights into the phenotypic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.

Tailoring local coordination structure of the Er3+ ions for tuning the up-conversion multicolor luminescence.

The regulation of the local structure around Er3+ ions is an important channel for adjusting the characteristic of up-conversion luminescence. In this paper, the cubic-phased Er3+:CaF2 crystals with different Er3+ doping concentrations were fabricated with temperature gradient technique (TGT) method and the effect of the local coordination structure of the Er3+ ions on its luminescence performance was investigated. The local coordination structure of Er3+ ions was simulated by density functional theory. The computational results show that clusters evolve from low order to high order with the increase of Er3+ ion doping concentration. In this evolution process, the local structure transforms from cubic structure to the co-existence of cubic and lower symmetric square anti-prism structures. Meanwhile, the distance between Er3+ ions in the cluster decreased first and then increased slightly, and in dimers and trimers this distance reached the minimum. Under 980 nm excitation, with the increase of Er3+ ion concentration, the intensity ratios of the red and green emissions of Er3+:CaF2 first increased from 0.61 to 42.03 and then decreased to 12.11. The corresponding up-conversion luminescence gamut was adjusted from monochrome green to red to red-yellow. This work provides a new thread for realizing upconversion multicolor luminescence by regulating the clusters of rare earth ions.

Suppression of WNK1-SPAK/OSR1 Attenuates Bone Cancer Pain by Regulating NKCC1 and KCC2.

Our preliminary experiment indicated the activation of with-nolysine kinases 1 (WNK1) in bone cancer pain (BCP) rats. This study aimed to investigate the underlying mechanisms via which WNK1 contributed to BCP. A rat model of BCP was induced by Walker-256 tumor cell implantation. WNK1 expression and distribution in the lumbar spinal cord dorsal horn and dorsal root ganglion were examined. SPS1-related proline/alanine-rich kinase (SPAK), oxidative stress-responsive kinase 1 (OSR1), sodium-potassium-chloride cotransporter 1 (NKCC1), and potassium-chloride cotransporter 2 (KCC2) expression were assessed. Pain behaviors including mechanical allodynia and movement-evoked pain were measured. BCP rats exhibited significant mechanical allodynia, with increased WNK1 expression in the dorsal horn and dorsal root ganglion neurons, elevated SPAK/OSR1 and NKCC1 expression in the dorsal root ganglion, and decreased KCC2 expression in the dorsal horn. WNK1 knock-down by small interfering alleviated mechanical allodynia and movement-evoked pain, inhibited WNK1-SPAK/OSR1-NKCC1 activities, and restored KCC2 expression. In addition, closantel (a WNK1-SPAK/OSR1 inhibitor) improved pain behaviors, downregulated SPAK/OSR1 and NKCC1 expression, and upregulated KCC2 expression in BCP rats. Activation of WNK1-SPAK/OSR1 signaling contributed to BCP in rats by modulating NKCC1 and KCC2 expression. Therefore, suppression of WNK1-SPAK/OSR1 may serve as a potential target for BCP therapy. PERSPECTIVE: Our findings demonstrated that the WNK1-SPAK/OSR1 signaling contributed to BCP in rats via regulating NKCC1 and KCC2. Suppressing this pathway reduced pain behaviors. Based on these findings, the WNK1-SPAK/OSR1 signaling may be a potential target for BCP therapy.

Color-tunable visible photoluminescence of Eu:CaF2 single crystals: variations of valence state and local lattice environment of Eu ions.

In this article, Eu-activated CaF2 single crystals were synthesized by Bridgman-Stockbarge method. The dependence of photoluminescence properties of Eu: CaF2 crystals in UV-Vis regions on EuF3 doping concentrations were investigated. While the EuF3 doping concentration is increased from 0.6% to 6.0%, the CIE (Commission Internationale de L'Eclairage) color coordinates of Eu: CaF2 crystals can be tuned from (0.28, 0.12) to (0.60, 0.38), corresponding to the luminescence color from blue to orange. XPS (X-ray Photoelectron Spectroscopy) measurements indicated that Eu2+ and Eu3+ ions both existed in the crystals. With EuF3 doping concentration increasing, the proportion of Eu3+ ions increase from 16.73% to 39.00%, while that of Eu2+ ions decrease from 83.27% to 61.00%. Moreover, the integrated intensity ratio (R) of the 614 nm to 593 nm of Eu3+ ions increase from 0.38 to 0.44, indicating the local lattice environment symmetry of Eu3+ ions become lower with higher EuF3 doping concentrations. Furthermore, the CIE chromaticity coordinates of Eu: CaF2 crystals greatly depend on the excitation wavelength. The warm white-light emission has been realized in 0.6%Eu: CaF2 crystal when the excitation wavelength is around 322 nm.