Search

This comprehensive case study aimed to highlight the condition of pulmonary embolism (PE), which despite its relative obscurity, may be more common than initially assumed. PE frequently occurs in the Emergency Department. PE along with deep vein thrombosis are the two most prevalent forms of venous thromboembolism (VTE). VTE ranks as the third most common cardiovascular condition encountered in the Emergency Department, following heart attacks and strokes. Acknowledging the symptoms of VTE and acting on them early are important to prevent chronic manifestations and heart failure in some cases owing to persisting pulmonary hypertension. One of the most frequent causes of VTE is surgery, which often occurs owing to immobilization. However, in some cases, VTE is due to the procedure itself or due to what is used in the procedure or injected in the patient. We report the case of a patient who complained of dyspnea for some time before diagnostic steps were taken, such as computed tomography and echocardiography. This case report describes the complication of PE due to vertebroplasty, which is well described but underdiagnosed because it may not be considered. More focus on this complication during follow-up could help diagnose and treat patients more rapidly.

Objectives Ageing populations present substantial challenges for healthcare systems. Community-based health worker (CHW) interventions for promoting healthy ageing and preventing/managing non-communicable diseases have gained considerable attention in recent years. This study aimed to assess the impacts of a multidomain preventive health initiative delivered by CHWs, specifically the ‘My Health Map (MHM)’ programme, on participants’ health service utilisation using a propensity score matching methodology.Design, setting and participants The multidomain MHM programme, which was implemented in Bukit Batok township, encompassed screenings, vaccinations, chronic disease management, counselling and socio-environmental interventions. Individuals, aged ≥40 years old, who received care at Ng Teng Fong General Hospital and were enrolled in the MHM programme constituted the intervention group. Outcomes of the intervention group were compared with a 1:1 propensity-matched comparison group at enrolment and 1-year follow-up. The outcome measures were emergency department (ED) utilisation and hospital admissions. Statistical evaluations were performed using χ2/non-parametric tests and difference-in-difference (DiD) estimation with a bias-adjusted generalised estimating equation (α=0.05).Results A comparable comparison group was formed with no significant differences in baseline characteristics between groups. Data from a total of 299 MHM participants (mean age 70.7 (SD 9.6); 62.5% women) and 299 matched comparisons (mean age 72.1 (SD 16.6); 61.5% women) were appraised. DiD analysis indicated a significant reduction in ED attendance (−16.7%, p

Most universities in Indonesia have organized entrepreneurship courses through study programs according to their respective characteristics. However, many entrepreneurial product outputs from these courses remain irrelevant to the field of expertise in the study program, including the Educational Technology study program. A course's output or achievement can be conditioned through the curriculum or the context of the course, known as the micro curriculum. Based on this, this study aims to produce a micro curriculum design for entrepreneurship courses oriented towards educational technology products. The method used is Design-Based Research (DBR), which involves needs analysis, curriculum design, construction, evaluation, and reflection. The results showed that the curriculum design developed met the needs of entrepreneurial competencies relevant to the educational technology industry. In addition, this study also provides recommendations related to learning content, learning strategies, and assessment models that can be used to support the effectiveness of the designed curriculum. Hopefully, this curriculum can help students understand entrepreneurial theory and apply it to make innovative educational technology products. Abstrak Mayorititas perguruan tinggi di seluruh Indonesia pada dasarnya telah menyelenggarakan mata kuliah kewirausahaan melalui program studi sesuai dengan ciri khas masing-masing. Namun, masih banyak ditemui luaran produk kewirausahaan dari mata kuliah tersebut tidak relevan dengan bidang keahlian yang terdapat pada program studi, tidak terkecuali pada program studi Teknologi Pendidikan. Luaran atau capaian dari sebuah mata kuliah pada dasarnya dapat dikondisikan melalui kurikulum atau dalam konteks mata kuliah dikenal dengan kurikulum mikro. Berdasarkan hal tersebut, penelitian ini bertujuan untuk menghasilkan desain kurikulum mikro mata kuliah kewirausahaan yang berorientasi pada produk teknologi pendidikan. Metode yang digunakan adalah Design Based Research (DBR), yang melibatkan analisis kebutuhan, desain dan konstruksi kurikulum, serta evaluasi dan refleksi. Hasil penelitian menunjukkan bahwa desain kurikulum yang dikembangkan mampu memenuhi kebutuhan kompetensi kewirausahaan yang relevan dengan industri teknologi pendidikan. Selain itu, penelitian ini juga memberikan rekomendasi terkait konten pembelajaran, strategi pembelajaran, dan model penilaian yang dapat digunakan untuk mendukung efektivitas kurikulum yang dirancang. Diharapkan, kurikulum ini dapat membantu mahasiswa tidak hanya memahami teori kewirausahaan, tetapi juga menerapkannya dalam pembuatan produk teknologi pendidikan yang inovatif. Kata Kunci: kewirausahaan; mikro kurikulum; teknologi pendidikan

Background Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.Methods Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform’s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.Ethics and dissemination Approved by each trial’s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.Prospero registration CRD42022330532.

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children’s subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children’s psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood.

Abstract A 28-year-old man diagnosed with triple positive antiphospholipid syndrome (APS) and undergoing warfarin experienced three separate admissions to the cardiac ward within a one-month period due to escalating chest pain. While the initial two admissions revealed normal results in cardiological investigations, such as blood tests, electrocardiogram, and echocardiography, the third admission unveiled signs of ST-elevation myocardial infarction (STEMI), despite the patient maintaining an INR (International Normalized Ratio) of 4. Subsequent percutaneous coronary intervention (PCI) exposed spontaneous coronary artery dissection (SCAD) of type 3. Faced with hemodynamic instability and worsening symptoms, the patient underwent stenting and was prescribed dual antiplatelet therapy in addition to warfarin. A follow-up evaluation one month later indicated a normalization of his condition.

Abstract Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays a crucial role in remodeling the tumor microenvironment (TME). Here, through the integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups of CAFs and described their spatial distribution characteristics. Additionally, the analysis of single-cell RNA sequencing (scRNA-seq) data from three additional common cancer types and two newly generated scRNA-seq datasets of rare cancer types, namely epithelial-myoepithelial carcinoma (EMC) and mucoepidermoid carcinoma (MEC), expanded our understanding of CAF heterogeneity. Cell–cell interaction analysis conducted within the spatial context highlighted the pivotal roles of matrix CAFs (mCAFs) in tumor angiogenesis and inflammatory CAFs (iCAFs) in shaping the immunosuppressive microenvironment. In patients with breast cancer (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity in facilitating cancer cell proliferation, promoting epithelial-mesenchymal transition (EMT), and contributing to the establishment of an immunosuppressive microenvironment. Furthermore, a scoring system based on iCAFs showed a significant correlation with immune therapy response in melanoma patients. Lastly, we provided a web interface ( https://chenxisd.shinyapps.io/pancaf/ ) for the research community to investigate CAFs in the context of pan-cancer.

This study describes a pars plana incision surgical technique combined with 23 or 25-gauge vitrectomy in the management of intraocular foreign bodies (IOFBs) and to assess its anatomical and functional results. Sixteen patients with ocular trauma complicated with IOFB were enrolled in our study. The mean preoperative visual acuity was 2.01 ± 0.55 LogMAR, and the mean postoperative visual acuity at the final visit was improved to 0.91 ± 0.58 LogMAR (p

AbstractBackground Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 μg, 2.5 μg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 μg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 μg and placebo group was 8.81 mm (p = .110). Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5μg, 38.6% in 2.5 μg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Summary: As a prominent feature of gout, monosodium urate (MSU) crystal deposition induces gout flares, but its impact on immune inflammation in gout remission remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterize the transcription profiling of peripheral blood mononuclear cells (PBMCs) among intercritical remission gout, advanced remission gout, and normal controls. We find systemic inflammation in gout remission with MSU crystal deposition at the intercritical and advanced stages, evidenced by activated inflammatory pathways, strengthened inflammatory cell-cell interactions, and elevated arachidonic acid metabolic activity. We also find increased HLA-DQA1high classic monocytes and PTGS2high monocytes in advanced gout and overactivated CD8+ T cell subtypes in intercritical and advanced gout. Additionally, the osteoclast differentiation pathway is significantly enriched in monocytes, T cells, and B cells from advanced gout. Overall, we demonstrate systemic inflammation and distinctive immune responses in gout remission with MSU crystal deposition, allowing further exploration of the underlying mechanism and clinical significance in conversion from intercritical to advanced stage.

Abstract Background Rare disease is a general term for a disease that affects a small number of people but recognized as a global public health priority. Governments worldwide are paying more and more attention to the academical research and drug investment of rare diseases. The conduct of rare disease clinical trials is still difficult, despite the promotion of government policies and the awakening of social consciousness. In this article, we outlined the characteristics and obstacles of clinical trials of rare diseases in China and expected to provide reference for subsequent clinical trials in this field. Results In recent years, China has made some progress in clinical trials of rare diseases in the past 10 years. There were 481 clinical trials on rare diseases in total, covering more than 10 rare diseases with high incidence. Clinical trial applications on rare diseases for a total of 481 were submitted and with an average annual growth rate of 28.2% from 2013 to 2022. The number of clinical trial application for rare diseases in 2016 dramatically increased by 80% compared to 2015 due to the policy document issued by China for clinical research in rare diseases in 2015. Besides, about 70% of applications registering for clinical trials could recruit subjects as expected. Despite this, the number of clinical trials of rare diseases in China was less compared with the United States, Europe and Japan, and the types of infant drugs were limited to biological products and chemical drugs lacking other new treatments. Conclusions Efforts have been made in recent years to develop clinical research on rare diseases in China. The number of clinical trials for rare diseases in China was growing steadily every year, which was inseparable from the support of the country, society and rare disease patients. Still, there was a large gap between China and other developed countries in this field and this merit further investigation.

Along with reducing traffic congestion, electric car-sharing (ECS) can also solve travel demand, utilize idle resources, and enhance forms of transportation. Accordingly, university students are identified in Guangzhou, China as a promising customer group for ECS companies. Although university students in Guangzhou, China are unique in the context of ECS, few researchers have studied the factors that influence their willingness to use such services. Hence, this paper investigates the key determinants that affect university students’ behavioral intention (BI) to use ECS in Guangzhou, China. Based on an extension of the unified theory of acceptance and use of technology (UTAUT), this paper examines the effects of the constructs on BI to use ECS and the moderating role of trust in ECS. Based on results from a questionnaire of 486 university students in Guangzhou, China, conditional value (CV) was the most critical driver of BI, followed by personal attitude (PA) and sustainability (SUST). The moderating analysis showed that taking gender, education, and driving experience of university students as control variables, trust was found to have a significant positive moderating impact on the relationship between PA and BI to use ECS, and a significant negative moderating effect of trust on the relationship between CV and BI to use ECS. The implications of these findings are discussed.

Introduction: Researchers have investigated the causal effect between serum uric acid (SUA) concentrations and kidney function for decades, but studies produced inconsistent results. This study aimed to clarify the bidirectional causal effects between SUA concentrations and kidney function and to explore the potential ethnic disparities by conducting a trans-ethnic Mendelian randomization study in European, African, and Asian ancestries. Materials and methods: The summary-level data for this study were obtained from the Global Urate Genetics Consortium, CKDGen Consortium, UK Biobank, and Japan Biobank for different outcomes and exposures, respectively. The traits of kidney function were estimated glomerular filtration rate from serum creatinine (eGFRcr), estimated glomerular filtration rate from cystatin C (eGFRcys), and blood urea nitrogen (BUN). Using the multiplicative random-effects inverse variance weighting mode, our primary analysis produced robust results despite heterogeneity. Additionally, we performed the Mendelian randomization pleiotropy residual sum and outlier test to eliminate the horizontal pleiotropy and obtain accurate results. Results: Our findings revealed that elevated SUA concentrations had causal effects on declined eGFRcys, BUN, and a diagnosis of chronic kidney disease in European ancestries and eGFRcr in Asian ancestries. Additionally, the causal effects of declined eGFRcr and elevated BUN concentrations on elevated SUA concentrations were observed in both European and Asian ancestries. However, no bidirectional causal effect was found between SUA concentrations and eGFRcr among African ancestries. Conclusions: This trans-ethnic Mendelian randomization study confirmed the bidirectional causal effects between SUA concentrations and kidney function and highlighted the importance of considering ethnic disparities in clinical treatments.

Background: Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures. Methods: A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores. Results: FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores. Conclusions: We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years.

Abstract Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.

Abstract Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value

Abstract Background Chronic kidney disease (CKD) is a severe public health problem associated with a disordered gut microbiome. However, the functional alterations of microbiota and their cross talk with metabolism pathways based on disease severity remain unclear. Results We performed metagenomics and untargeted metabolomics in a cohort of 68 patients with CKD of differing severities and 20 healthy controls to characterize the complex interplay between the gut microbiome and fecal and serum metabolites during CKD progression. We identified 26 microbial species that significantly changed in patients with CKD; 18 species changed as the disease progressed, and eight species changed only in a specific CKD group. These distinct changes in gut microbiota were accompanied by functional alterations in arginine and proline, arachidonic acid, and glutathione metabolism and ubiquinone and other terpenoid-quinone biosynthesis pathways during CKD progression. Further metabolomic analyses revealed that the distributions of toxic and pro-oxidant metabolites from these four essential metabolic pathways varied in the feces and serum as CKD progressed. Furthermore, we observed a complex co-occurrence between CKD severity-related bacteria and the characterized metabolites from the four essential metabolic pathways. Notably, Ruminococcus bromii, fecal hydroquinone, and serum creatinine were identified as the main contributors to the integrated network, indicating their key roles in CKD progression. Moreover, a noninvasive model including R. bromii and fecal hydroquinone, L-cystine, and 12-keto-tetrahydro-LTB4 levels classified the CKD severity (area under the curve [AUC]: > 0.9) and had better performance than the serum creatinine level for mild CKD (AUC: 0.972 vs. 0.896). Conclusions Perturbed CKD severity-related gut microbiota may contribute to unbalanced toxic and pro-oxidant metabolism in the gut and host, accelerating CKD progression, which may be an early diagnostic and therapeutic target for CKD. Video Abstract

Gout is a metabolic disease that can result in the formation of gout stones. It is essential to promptly identify and confirm the type of gout stone to alleviate pain and inflammation in patients and prevent complications associated with gout stones. Traditional detection methods, such as X-ray, ultrasound, CT scanning, and blood uric acid measurement, have limitations in early diagnosis. Therefore, this article aims to explore the use of micro Raman spectroscopy, Fourier transform infrared spectroscopy, and Terahertz time-domain spectroscopy systems to detect gout stone samples. Through comparative analysis, Terahertz technology and Raman spectroscopy have been found to provide chemical composition and molecular structure information of different wavebands of samples. By combining these two technologies, faster and more comprehensive analysis and characterization of samples can be achieved. In the future, handheld portable integrated testing instruments will be developed to improve the efficiency and accuracy of testing. Furthermore, this article proposes establishing a spectral database of gout stones and urinary stones by combining Raman spectroscopy and Terahertz spectroscopy. This database would provide accurate and comprehensive technical support for the rapid diagnosis of gout in clinical practice.

Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations. However, the lack of homotopic correspondence between left and right Schaefer parcels has limited their use for brain lateralization studies. Here, we extend our previous model to derive homotopic areal-level parcellations. Using resting-fMRI and task-fMRI across diverse scanners, acquisition protocols, preprocessing and demographics, we show that the resulting homotopic parcellations are as homogeneous as the Schaefer parcellations, while being more homogeneous than five publicly available parcellations. Furthermore, weaker correlations between homotopic parcels are associated with greater lateralization in resting network organization, as well as lateralization in language and motor task activation. Finally, the homotopic parcellations agree with the boundaries of a number of cortical areas estimated from histology and visuotopic fMRI, while capturing sub-areal (e.g., somatotopic and visuotopic) features. Overall, these results suggest that the homotopic local-global parcellations represent neurobiologically meaningful subdivisions of the human cerebral cortex and will be a useful resource for future studies. Multi-resolution parcellations estimated from 1479 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Yan2023_homotopic).

Results 175 participants were included. Six months after initial AZ vaccination, 87.5%, 85.4% and 79.2% (p=0.756) in the withhold, continue and control groups remained seropositive compared with 91.4%, 100% and 100% (p=0.226), respectively, in the Pfizer group. Both vaccine groups developed robust humoral immune responses following a booster with seroconversion rates being 100% for all three intervention categories. The mean SARS-CoV-2 antibody levels were significantly lower in the targeted synthetic DMARD (tsDMARD) group that continued therapy compared with the control (2.2 vs 4.8 U/mL, p=0.010). The mean time interval until loss of protective antibodies in the IMID group was 61 days for the AZ and 137.5 days for the Pfizer vaccine. Within each DMARD class the interval until loss of protective antibody titres in the csDMARD, bDMARD and tsDMARD groups were 68.3, 71.8 and 64.0 days in the AZ group and 185.5, 137.5 and 116.0 days in the Pfizer group, respectively.Conclusion Antibody persistence was longer in the Pfizer group due to a higher peak antibody level following second vaccination with levels of protection in IMID on DMARD therapy similar to controls except in those on tsDMARDs where it was lower. A third mRNA vaccine booster can restore immunity in all groups.

This study compared parenting across four non-Western cultures to test cross-cultural commonality and specificity principles in three aspects: measurement properties, parenting normativeness, and their associations with child outcomes. Both mothers and fathers (N = 1509 dyads) with preschool-aged children (M = 5.00 years; 48% girls) from urban areas of four countries (Malaysia, N = 372; China, N = 441; Turkey, N = 402; and Japan, N = 294) reported on four parenting constructs (authoritative, authoritarian, group harmony socialization, and intrusive control) and their sub-dimensions using modified culturally relevant measures. Teachers reported on children's internalizing, externalizing, and prosocial behaviors. The commonality principle was supported by two sets of findings: (1) full measurement invariance was established for most parenting constructs and sub-dimensions, except that intrusive control only reached partial scalar invariance, and (2) no variations were found in associations between parenting and any child outcomes across cultures or parent gender at the construct level for all four parenting constructs and at the sub-dimensional level for authoritarian and intrusive control sub-dimensions. The specificity principle was supported by the other two sets of findings: (1) cross-cultural differences in parenting normativeness did not follow the pattern of economic development but yielded culture-specific patterns, and (2) at the sub-dimensional level, the authoritative parenting and group harmony socialization sub-dimensions were differently associated with child outcomes across cultures and/or parent gender. The findings suggested that examining specific dimensions rather than broad parenting constructs is necessary to reflect cultural specificities and nuances. Our study provided a culturally-invariant instrument and a three-step guide for future parenting research to examine cross-cultural commonalities/specificities.

Background: Childhood depression is a highly distinct and prevalent condition with an unknown neurobiological basis. We wish to explore the resting state fMRI data in children for potential associations between neural connectivity and childhood depressive symptoms. Methods: A longitudinal birth cohort study with neuroimaging data obtained at 4.5, 6.0 and 7.5 years of age and the Children Depression Inventory 2 (CDI) administered between 8.5 and 10.5 years was used. The CDI score was used as the dependent variable and tested for correlation, both simple Pearson and network based statistic, with the functional connectivity values obtained from the resting state fMRI. Cross-validated permutation testing with a general linear model was used to validate that the identified functional connections were indeed implicated in childhood depression. Results: Ten functional connections and four brain regions (Somatomotor Area B, Temporoparietal Junction, Orbitofrontal Cortex and Insula) were identified as significantly associated with childhood depressive symptoms for girls at 6.0 and 7.5 years. No significant functional connections were found in girls at 4.5 years or for boys at any timepoint. Network based statistic and permutation testing confirmed these findings. Conclusions: This study revealed significant sex-dependent associations of neural connectivity and childhood depressive symptoms. The regions identified are implicated in speech/language, social cognition and information integration and suggest unique pathways to childhood depressive symptoms.

The performance evolution of subgrade soil under the coupling effect of drying?wetting cycle and dynamic load is essential for the safety and stability of the subgrade. In this study, a series of electrical resistivity tests was carried out on the compacted silty clay samples subjected to different drying?wetting cycles and dynamic loads using alternating current (AC) two-electrode method. The effect of drying?wetting cycles sequentially coupled with dynamic loads on the electrical resistivity of soil samples was investigated. Then, a mathematical relationship was established to quantitatively characterize the dynamic behaviors of soil samples based on electrical resistivity. Finally, the effectiveness of the electrical resistivity method in evaluating the state of compacted soil was discussed. Test results showed that under the action of drying?wetting cycles coupled with dynamic loads, the electrical resistivity of soil samples decreased greatly with the increases in the number and amplitude of drying?wetting cycles, but the reduction of the electrical resistivity of soil samples caused by dynamic load decreased gradually. The test results can provide a reference for the evaluation of the state of subgrade soil under drying?wetting cycles sequentially coupled with dynamic loads using electrical resistivity method.

Abstract Background Gout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls. Methods We established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8). Results Eleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process. Conclusions Histone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process. Trial registration This study is not a clinical trial.

Abstract Background The global reputation of coronavirus disease (COVID-19) has led universities in China to conduct online teaching. However, the actual feedback from medical teachers and students regarding online education remains unclear. Methods A prospective questionnaire survey examined the current opinions of online education from teachers and students at the Medical School of Tongji University. Results A total of 488 valid questionnaires were collected (223 males, 45.7%; 265 females, 54.3%), including 394 students (80.7%) and 94 teachers (19.3%). Most teachers and students were “in favor of online teaching,” had “positive views for online education,” were “satisfied with online teaching,” and “expected for regular online education,” although students thought that “too much learning tasks had been assigned” (90.4% teachers vs. 43.1% students, P