Pretreatment mortality risk prediction model in patients with polymyositis/dermatomyositis-associated interstitial lung disease.

OBJECTIVES: Risk prediction for patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) is challenging due to heterogeneity in the disease course. We aimed to develop a mortality risk prediction model for PM/DM-ILD. METHODS: This prognostic study analysed patients with PM/DM-ILD admitted to Nanjing Drum Hospital from 2016 to 2021. The primary outcome was mortality within 1 year. We used a least absolute shrinkage and selection operator (LASSO) logistic regression model to identify predictive laboratory indicators. These indicators were used to create a laboratory risk score, and we developed a mortality risk prediction model by incorporating clinical factors. The evaluation of model performance encompassed discrimination, calibration, clinical utility and practical application for risk prediction and prognosis. RESULTS: Overall, 418 patients with PM/DM-ILD were enrolled and randomly divided into development (n=282) and validation (n=136) cohorts. LASSO logistic regression identified four optimal features in the development cohort, forming a laboratory risk score: C reactive protein, lactate dehydrogenase, CD3+CD4+ T cell counts and PO2/FiO2. The final prediction model integrated age, arthralgia, anti-melanoma differentiation-associated gene 5 antibody status, high-resolution CT pattern and the laboratory risk score. The prediction model exhibited robust discrimination (area under the receiver operating characteristic: 0.869, 95% CI 0.811 to 0.910), excellent calibration and valuable clinical utility. Patients were categorised into three risk groups with distinct mortality rates. The internal validation, sensitivity analyses and comparative assessments against previous models further confirmed the robustness of the prediction model. CONCLUSIONS: We developed and validated an evidence-based mortality risk prediction model with simple, readily accessible clinical variables in patients with PM/DM-ILD, which may inform clinical decision-making.

Leveraging functional genomic annotations and genome coverage to improve polygenic prediction of complex traits within and between ancestries.

We develop a method, SBayesRC, that integrates genome-wide association study (GWAS) summary statistics with functional genomic annotations to improve polygenic prediction of complex traits. Our method is scalable to whole-genome variant analysis and refines signals from functional annotations by allowing them to affect both causal variant probability and causal effect distribution. We analyze 50 complex traits and diseases using ∼7 million common single-nucleotide polymorphisms (SNPs) and 96 annotations. SBayesRC improves prediction accuracy by 14% in European ancestry and up to 34% in cross-ancestry prediction compared to the baseline method SBayesR, which does not use annotations, and outperforms other methods, including LDpred2, LDpred-funct, MegaPRS, PolyPred-S and PRS-CSx. Investigation of factors affecting prediction accuracy identifies a significant interaction between SNP density and annotation information, suggesting whole-genome sequence variants with annotations may further improve prediction. Functional partitioning analysis highlights a major contribution of evolutionary constrained regions to prediction accuracy and the largest per-SNP contribution from nonsynonymous SNPs.

Added Value of Frequency of Imaging Markers for Prediction of Outcome After Intracerebral Hemorrhage: A Secondary Analysis of Existing Data.

BACKGROUND: Frequency of imaging markers (FIM) has been identified as an independent predictor of hematoma expansion in patients with intracerebral hemorrhage (ICH), but its impact on clinical outcome of ICH is yet to be determined. The aim of the present study was to investigate this association. METHODS: This study was a secondary analysis of our prior research. The data for this study were derived from six retrospective cohorts of ICH from January 2018 to August 2022. All consecutive study participants were examined within 6 h of stroke onset on neuroimaging. FIM was defined as the ratio of the number of imaging markers on noncontrast head tomography (i.e., hypodensities, blend sign, and island sign) to onset-to-neuroimaging time. The primary poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months. RESULTS: A total of 1253 patients with ICH were included for final analysis. Among those with available follow-up results, 713 (56.90%) exhibited a poor neurologic outcome at 3 months. In a univariate analysis, FIM was associated with poor prognosis (odds ratio 4.36; 95% confidence interval 3.31-5.74; p < 0.001). After adjustment for age, Glasgow Coma Scale score, systolic blood pressure, hematoma volume, and intraventricular hemorrhage, FIM was still an independent predictor of worse prognosis (odds ratio 3.26; 95% confidence interval 2.37-4.48; p < 0.001). Based on receiver operating characteristic curve analysis, a cutoff value of 0.28 for FIM was associated with 0.69 sensitivity, 0.66 specificity, 0.73 positive predictive value, 0.62 negative predictive value, and 0.71 area under the curve for the diagnosis of poor outcome. CONCLUSIONS: The metric of FIM is associated with 3-month poor outcome after ICH. The novel indicator that helps identify patients who are likely within the 6-h time window at risk for worse outcome would be a valuable addition to the clinical management of ICH.

Is the frequency of imaging markers still a predictor for revised intracerebral hemorrhage expansion?

INTRODUCTION: Frequency of imaging markers (FIM) has been described as a novel predictor for hematoma expansion after intracerebral hemorrhage (ICH). A revised definition of hematoma expansion that incorporates intraventricular hemorrhage (IVH) growth, that is, revised hematoma expansion (RHE), has also been proposed. Nevertheless, the associations between FIM and IVH growth or RHE remains unexplored. The objective of this study was to assess the influence and performance of the FIM on two types. MATERIALS AND METHODS: Patient selection and variables were based on our published protocol. FIM was defined as the ratio of the number of imaging markers to the onset-to-neuroimaging time. The association between FIM and two definitions was tested by multivariate analysis. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the FIM on two definitions were also evaluated. RESULTS: There were 303 (20.36%) and 583 (39.18%) subjects in the IVH growth and RHE, respectively. Multivariate analysis demonstrated that FIM was associated with both IVH growth and RHE (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.60-2.39; OR = 15.01, 95% CI = 10.51-21.43, respectively). The optimal cutoff points for FIM to predict IVH growth and RHE were 0.63 and 0.62, with AUC, sensitivity, specificity, PPV, and NPV of 0.66, 0.50, 0.78, 0.36, and 0.86 versus 0.80, 0.60, 0.93, 0.84, and 0.78, respectively. DISCUSSION AND CONCLUSION: FIM was not only a predictor of IVH growth, but also of RHE. These findings may have important clinical implications for decision-making based on risk stratification of patients with ICH.

Combining Non-Contrast CT Signs With Onset-to-Imaging Time to Predict the Evolution of Intracerebral Hemorrhage.

OBJECTIVE: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). MATERIALS AND METHODS: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. RESULTS: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87-13.40]), IVHG (3.64 [2.15-6.24]), and RHE (7.90 [4.93-12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52-0.66]), IVHG (0.72 [0.64-0.81]), and RHE (0.61 [0.54-0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36-15.30] and 10.10 [7.10-14.60], respectively, for the blend sign and 2.75 [1.64-4.67] and 2.62 [1.60-4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. CONCLUSION: Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

The frequency of imaging markers adjusted for time since symptom onset in intracerebral hemorrhage: A novel predictor for hematoma expansion.

BACKGROUND: Hematoma expansion (HE) is common in patients with intracerebral hemorrhage (ICH) and associated with a worse outcome. Imaging makers and shorter time from symptom onset are both associated with HE, but prognostic scores based on these parameters individually have not been satisfactory. We hypothesized that a score including both imaging markers of expansion, and time of onset, would improve prediction. METHODS: Patients with supratentorial ICH within 6 h after onset were consecutively recruited from six centers between January 2018 and August 2022. Three markers were used: hypodensities, the blend sign, and the island sign. We first defined frequency of imaging markers (FIM) as the relationship between the number of imaging markers and onset-to-CT time (OCT). The time-adjusted FIM was defined as the ratio of the number of imaging markers to the onset-to-initial imaging time. Multivariate analysis was performed to determine the relationship between FIM and HE. Receiver operating curve analysis was used to identify potential threshold values of FIM that optimally predict HE. In addition, the sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and the area under the curve (AUC) of the optimal cut-off in predicting HE were calculated. RESULTS: In total, 1488 patients were eligible for inclusion, of whom 418 had incident HE. Multivariate analysis showed that age, male sex, baseline Glasgow Coma Scale score, presence of intraventricular hemorrhage, and FIM were independent predictors of HE (odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.97-0.99; OR = 1.73, 95% CI = 1.28-2.35; OR = 0.87, 95% CI = 0.83-0.92; OR = 0.42, 95% CI = 0.28-0.62; OR = 7.82, 95% CI = 5.86-10.42, respectively). The optimal cut-off point for FIM in predicting HE was 0.63, with sensitivity, specificity, PPV, NPV, and AUC values of 0.69, 0.89, 0.71, 0.88, and 0.83, respectively. CONCLUSION: The FIM adjusted for time since symptom onset is a significant predictor of HE. Its use may allow improved prediction of those patients with ICH who develop HE, and the score may be clinically applicable in the management of patients with ICH.

A Systematic Study on the Processing Strategy in Femtosecond Laser Scribing via a Two-Temperature Model.

Balancing quality and productivity, especially deciding on the optimal matching strategy for multiple process parameters, is challenging in ultrashort laser processing. In this paper, an economical and new processing strategy was studied based on the laser scribing case. To reveal the temperature evolution under the combination of multiple process parameters in the laser scribing process, a two-temperature model involving a moving laser source was developed. The results indicated that the peak thermal equilibrium temperature between the electron and lattice increased with the increase in the laser fluence, and the temperature evolution at the initial position, influenced by subsequent pulses, was strongly associated with the overlap ratio. The thermal ablation effect was strongly enhanced with the increase in laser fluence. The groove morphology was controllable by selecting the overlap ratio at the same laser fluence. The removal volume per joule (i.e., energy utilization efficiency) and the removal volume per second (i.e., ablation efficiency) were introduced to analyze the ablation characteristics influenced by multiple process parameters. The law derived from statistical analysis is as follows; at the same laser fluence with the same overlap ratio, the energy utilization efficiency is insensitive to changes in the repetition rate, and the ablation efficiency increases as the repetition rate increases. As a result, a decision-making strategy for balancing quality and productivity was created.

Familial co-aggregation and shared genetics of cardiometabolic disorders and traits: data from the multi-generational Lifelines Cohort Study.

BACKGROUND: It is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study. METHODS: We used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λR) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h2), shared environment, and genetic correlation (rg) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age2, and sex. RESULTS: Individuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λFDR of 1.23 (95% CI 1.20-1.25) for hypertension to λFDR of 2.48 (95% CI 2.15-2.86) for T2D. Most of these were higher than in spouses (λSpouses < λFDR), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h2CRP: 0.26 to h2HDL: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λFDR obesity-MetS: 1.28 (95% CI 1.24-1.32) to λFDR MetS-T2D: 1.61 (95% CI 1.52-1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from rg HDL-Triglycerides: - 0.53 to rg LDL-Apolipoprotein B: 0.94). CONCLUSIONS: There is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.

Fresnel zone plate sculptured out of diamond by femtosecond laser for harsh environments.

With the rapid development of micro-optical applications, there is an increasing demand for micro-optical elements that can be made with minimal processing steps. Current research focuses on practical functionalities of optical performance, lightweight, miniaturization, and easy integration. As an important planar diffractive optical element, the Fresnel zone plate (FZP) provides a compact solution for focusing and imaging. However, the fabrication of FZPs with high quality out of hard and brittle materials remains challenging. Here, we report on the fabrication of diamond FZP by femtosecond laser direct writing. FZPs with the same outer diameter and different focal lengths of 250-1000 µm were made via ablation. The fabricated FZPs possess well-defined geometry and excellent focusing and imaging ability in the visible spectral range. Arrays of FZPs with different focal lengths were made for potential applications in imaging, sensing, and integrated optical systems.

Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety.

It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a variety of stress-related exposures on depression and anxiety. We included 41,810 participants with both genome-wide genetic data and measurements of depression and anxiety in the Lifelines Cohort Study. Current depression and anxiety were measured by the MINI International Neuropsychiatric Interview. Stress-related exposures included long-term difficulties, stressful life events, reduced social support, childhood trauma, and loneliness, which were measured by self-report questionnaires. PRSs were calculated based on recent large genome-wide association studies for depression and anxiety. We used linear mixed models adjusting for family relationships to estimate the interactions between PRSs and stress-related exposures. Nine of the ten investigated interactions between the five stress-related exposures and the two PRSs for depression and anxiety were significant (Ps < 0.001). Reduced social support, and higher exposure to long-term difficulties, stressful life events, and loneliness amplified the genetic effects on both depression and anxiety. As for childhood trauma exposure, its interaction with the PRS was significant for depression (P = 1.78 × 10-05) but not for anxiety (P = 0.32). Higher levels of stress-related exposures significantly amplify the effects of genetic susceptibility on depression and anxiety. With a large sample size and a comprehensive set of stress-related exposures, our study provides powerful evidence on the presence of polygenic risk-by-environment interactions in relation to depression and anxiety.

Predicting Hemorrhage Progression in Deep Intracerebral Hemorrhage: A Multicenter Retrospective Cohort Study.

BACKGROUND: Hemorrhage progression in deep intracerebral hemorrhage (ICH) involves not only the growth of parenchymal hematoma but also an increase in intraventricular hemorrhage (IVH). The search for methods that predict both the increased risk of parenchymal hematoma and IVH growth is warranted. METHODS: We conducted a retrospective cohort study at multiple centers. Participants with deep ICH were enrolled from January 2018 to December 2021. Prediction models based on logistic regression analysis included clinical as well as routine radiographic and radiomics variables, separately or in combination. The performance of each model was evaluated using discrimination measures (e.g., area under the curve [AUC]). Evaluation of clinical utility was performed using decision curve analysis (DCA). RESULTS: Overall, 647 individuals across 4 stroke centers were included. A total of 429 (66%) patients from 3 centers were assigned to the primary cohort and 218 (34%) from another center were placed in the validation cohort. Multivariate analysis showed that the Glasgow Coma Scale score, baseline ICH volume, IVH, blend sign, and radiomics score were associated with hemorrhage progression in the primary cohort. The clinical-radiomics model (AUC = 0.852 and 0.835) improved the prediction performance of hemorrhage progression compared to the Noncontrast computed tomography signs model (AUC = 0.666 and 0.618) in both the primary and validation cohorts, with similar results in the decision curve analysis curves. CONCLUSIONS: The clinical-radiomics model outperformed the routine Noncontrast computed tomography signs model in predicting the progression of deep ICH. The clinical benefit of screening patients using this model may assist in risk stratification.

Effect of Mechanical Vibration on the Mechanical Properties and Solidification Feeding in Low-Pressure Sand Casting of Al-Cu-Mn-Ti Alloy.

The shrinkage defects of Al-Cu-Mn-Ti alloy seriously hinder its application in high-performance engineering. In this study, mechanical vibration was introduced to low-pressure sand casting (LPSC) by a waveguide rod to eliminate shrinkage defects and improve mechanical properties. Four LPSC castings were performed by changing the solidification conditions: 20 kPa solidification pressure without and with 14 Hz vibration and 40 kPa without and with 24 Hz (the natural frequency of a casting system) vibration. The shrinkage defects, microstructures, and mechanical tensile properties at room temperature and at 2 mm/min tensile rate were investigated. X-ray detections showed that applying vibration was more effective than increasing solidification pressure in improving solidification feeding, while the most effective method was applying both simultaneously, which eliminated the shrinkage defects and increased the density by 2.7%. Microstructures exhibited that the average size of primary α-Al grains were reduced by 29.5%; mechanical tests showed that the ultimate tensile strength and the elongation increased by 21.7% and 7.8%, respectively, by applying vibration and increasing the solidification pressure simultaneously, as compared to the casting with 20 kPa solidification pressure without vibration. Mechanical vibration was conducive to mass feeding by refining the primary grains, to interdendritic feeding by reducing the threshold pressure gradient, and to burst feeding by collapsing the barrier.

Prediction model for the pretreatment evaluation of mortality risk in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease.

Background: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early. Methods: This prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model's performance was assessed in terms of discrimination, calibration, and clinical usefulness. Results: This study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846-0.957), good calibration (Hosmer-Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001). Conclusions: We developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.

Comprehensive Chemical Dust Suppressant Performance Evaluation and Optimization Method.

Chemical dust suppression is an effective dust control technology. A dust suppressant component evaluation method that facilitates a complete selection of safe, efficient, and economical chemical materials has not been explored. Considering dust suppression performance, environmental safety, and cost-effectiveness of chemical dust suppressant technology, this study constructs a comprehensive evaluation index system of chemical dust suppressant performance, including the wetting performance, hygroscopic performance, bonding performance, annual cost per unit area, pH value of dust suppression solution, chemical toxicity, and chemical corrosion. Among them, the index characterizing the wetting performance of the solution is the sedimentation wetting time, which is determined by the dust sedimentation experiment; the index characterizing the hygroscopic performance of the solution is the evaporation stability time, which is determined by the evaporation experiment of the solution on the dust surface; the index to characterize the bonding performance of the solution is the surface wind erosion rate, which is determined by the wind erosion experiment of the solution on the dust surface; the toxicity of the solution is evaluated by the LD50 of the solution; the index to characterize the corrosion performance of the solution is the Q235 monthly steel corrosion rate, which is determined by the Q235 steel corrosion test. Corresponding evaluation parameters are determined including sedimentation wetting time, evaporation stabilization time, surface wind erosion rate; annual average use cost per unit area; solution pH value, chemical acute toxicity classification, monthly corrosion rate of Q235 steel, and corresponding standard test methods are also provided. In order to evaluate the comparability of the results, according to the specific requirements of the evaluation index system and the distribution characteristics of the measurement data, the data of each evaluation and detection index are standardized by linear transformation, range transformation and other methods, so that the obtained results are comparable. Considering the differences in the actual performance requirements of dust suppressants in different usage scenarios, the weights of evaluation indicators at all levels can be set independently and flexible. The experimental test data obtained through the example shows that: among the four chemicals selected to participate in the experiment, the comprehensive dust suppression performance score of Triton X-100 solution is in the poor-grade category. The comprehensive dust suppression performances of calcium chloride solution, water, and polyacrylamide solution scored high in the average-grade category. The comprehensive evaluation process is logically correct, and the results are consistent with the phenomena observed in the experiment, consistent with conventional understanding, and have strong credibility. This method can provide a standardized evaluation technique and test process for the comprehensive performance evaluation and comparison of chemical materials and dust suppressants.

PAM-less conditional DNA substrates leverage trans-cleavage of CRISPR-Cas12a for versatile live-cell biosensing.

The CRISPR-Cas system has been repurposed as a powerful live-cell imaging tool, but its utility is limited to genomic loci and mRNA imaging in living cells. Here, we demonstrated the potential of the CRISPR-Cas system as a generalizable live-cell biosensing tool by extending its applicability to monitor diverse intracellular biomolecules. In this work, we engineered a CRISPR-Cas12a system with a generalized stimulus-responsive switch mechanism based on PAM-less conditional DNA substrates (pcDNAs). The pcDNAs with stimulus-responsiveness toward a trigger were constructed from the DNA substrates featuring no requirement of a protospacer-adjacent motif (PAM) and a bubble structure. With further leveraging the trans-cleavage activity of CRISPR-Cas12a for signal reporting, we established a versatile CRISPR-based live-cell biosensing system. This system enabled the sensitive sensing of various intracellular biomolecules, such as telomerase, ATP, and microRNA-21, making it a helpful tool for basic biochemical research and disease diagnostics.

Expectation and Reality: International Students' Motivations and Motivational Adjustments to Sustain Academic Journey in Chinese Universities.

Considering the increasing influx of international students to Chinese universities in recent decades, it is surprising to find that few empirical research, especially longitudinal ones, have been conducted in exploring the motivation of international students in China. To fill up the existing gap, this study explored and tracked international students' motivations dynamically. Mixed research design, such as surveys, reflective journals, and interviews, was employed in this study. Data were collected from 671 international students and three teachers in three Chinese universities in Zhejiang province, mainland China on a longitudinal basis. The present study found that international students' motivation could be discussed with considerations to the following two different phases: preliminary phase before they come to China and follow-up phase when they are in China. This study found that the integrative understanding of the external pulling force and the self-motivated pushing force plays a vital role in answering international students' motivations to China. International students were driven more by the self-motivated pushing force than the external pulling force in selecting China as their study destinations. Moreover, international students experienced motivational changes when their expectations conflict with reality and their positive motivational adjustments and social interaction were important to the sustainability of their academic journey. Moreover, this study provides implications for the government, universities and international students in the aspects of policymaking, education and application.

Familial co-aggregation and shared heritability between depression, anxiety, obesity and substance use.

Depression, anxiety, obesity and substance use are heritable and often co-occur. However, the mechanisms underlying this co-occurrence are not fully understood. We estimated their familial aggregation and co-aggregation as well as heritabilities and genetic correlations to improve etiological understanding. Data came from the multi-generational population-based Lifelines Cohort Study (n = 162,439). Current depression and anxiety were determined using the MINI International Neuropsychiatric Interview. Smoking, alcohol and drug use were assessed by self-report questionnaires. Body mass index (BMI) and obesity were calculated by measured height and weight. Modified Cox proportional hazards models estimated recurrence risk ratios (λR), and restricted maximum likelihood variance decomposition methods estimated heritabilities (h2) and genetic correlations (rG). All analyses were adjusted for age, age2, and sex. Depression, anxiety, obesity and substance use aggregated within families (λR first-degree relative = 1.08-2.74) as well as between spouses (λR = 1.11-6.60). All phenotypes were moderately heritable (from h2depression = 0.25 to h2BMI = 0.53). Depression, anxiety, obesity and smoking showed positive familial co-aggregation. That is, each of these traits confers increased risk on the other ones within families, consistent with the positive genetic correlations between these phenotypes (rG = 0.16-0.94). The exception was obesity, which showed a negative co-aggregation with alcohol and drug use and vice versa, consistent with the negative genetic correlations of BMI with alcohol (rG = -0.14) and soft drug use (rG = -0.10). Patterns of cross-phenotype recurrence risk highlight the co-occurrence among depression, anxiety, obesity and substance use within families. Patterns of genetic overlap between these phenotypes provide clues to uncovering the mechanisms underlying familial co-aggregation.

Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

OBJECTIVES: In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). METHODS: A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. RESULTS: Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P < 0.01) and anti-Jo1 (64.9%, P < 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P < 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P < 0.05). CONCLUSIONS: Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

Progressive lymphocytosis in familial hemophagocytic lymphohistiocytosis with lymphocytic interstitial pneumonia: a case report.

Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder which is less typical in adults than pediatric patients. In this study, we reported a rare case of adult-onset FHL3 with progressive lymphocytosis and lymphocytic interstitial pneumonia (LIP). A 20-year old female was admitted to our institution for persistent cough with fever. A chest high-resolution computed tomography (HRCT) scan showed diffuse bilateral ground glass opacities (GGO). A lung biopsy revealed infiltration of lymphocyte in the pulmonary interstitium. The patient was treated with corticosteroids and immunosuppressants, followed by significant clinical improvement although lymphocytosis still persisted. The definitive diagnosis of FHL was based on whole genome sequencing by which heterozygous mutations in UNC13D gene were identified. Lymphocytosis may be a remarkable feature of some patients with FHL. Performing gene sequencing is important to improve the recognition of FHL to avoid misdiagnosis.