INTRODUCTION
Existing blood‐based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies on blood‐based biomarkers associated with other biological ...processes for a comprehensive evaluation of AD status are limited.
METHODS
We developed a blood‐based, multiplex biomarker assay for AD that measures the levels of 21 proteins involved in multiple biological pathways. We evaluated the assay's performance for classifying AD and indicating AD‐related endophenotypes in three independent cohorts from Chinese or European‐descent populations.
RESULTS
The 21‐protein assay accurately classified AD (area under the receiver operating characteristic curve AUC = 0.9407 to 0.9867) and mild cognitive impairment (MCI; AUC = 0.8434 to 0.8945) while also indicating brain amyloid pathology. Moreover, the assay simultaneously evaluated the changes of five biological processes in individuals and revealed the ethnic‐specific dysregulations of biological processes upon AD progression.
DISCUSSION
This study demonstrated the utility of a blood‐based, multi‐pathway biomarker assay for early screening and staging of AD, providing insights for patient stratification and precision medicine.
Highlights
The authors developed a blood‐based biomarker assay for Alzheimer's disease.
The 21‐protein assay classifies AD/MCI and indicates brain amyloid pathology.
The 21‐protein assay can simultaneously assess activities of five biological processes.
Ethnic‐specific dysregulations of biological processes in AD were revealed.
Background
We compared school participation patterns of students ages 5–17 with and without disabilities and examined whether features of the school environment were perceived to help or hinder their ...participation.
Methods
Parents (n = 576) residing in the USA and Canada completed the Participation and Environment Measure for Children and Youth (PEM‐CY) via the internet.
Results
Parents of students with disabilities reported that their children participated less frequently in school clubs and organizations and getting together with peers outside the classroom and that they were less involved in all school activities. Parents of students with disabilities also were significantly more likely to report that features of the environment hindered school participation and that resources needed to support their child's participation were not adequate.
Conclusions
Parents of students with disabilities report that their children are participating less in important school‐related activities. Barriers limiting school participation include features of the physical and social environment as well as limited resources.
Adult tissue repair and regeneration require stem-progenitor cells that can self-renew and generate differentiated progeny. Skeletal muscle regenerative capacity relies on muscle satellite cells ...(MuSCs) and their interplay with different cell types within the niche. However, our understanding of skeletal muscle tissue cellular composition is limited. Here, using a combined approach of single-cell RNA sequencing and mass cytometry, we precisely mapped 10 different mononuclear cell types in adult mouse muscle. We also characterized gene signatures and determined key discriminating markers of each cell type. We identified two previously understudied cell populations in the interstitial compartment. One expresses the transcription factor scleraxis and generated tenocytes in vitro. The second expresses markers of smooth muscle and mesenchymal cells (SMMCs) and, while distinct from MuSCs, exhibited myogenic potential and promoted MuSC engraftment following transplantation. The blueprint presented here yields crucial insights into muscle-resident cell-type identities and can be exploited to study muscle diseases.
Display omitted
•Combination of single-cell RNA sequencing and mass cytometry•Construction of a cell atlas of adult skeletal muscle•Skeletal muscle is composed of 10 mononucleated cell types and myofibers•Skeletal muscle contains interstitial tenocytes and smooth muscle-mesenchymal cells
A strong characterization of cell types present in adult skeletal muscle is needed. Giordani et al. use both single-cell transcriptomics and mass cytometry to build a single-cell survey of adult skeletal muscle tissue and reveal understudied cell populations.
Background
The strengths and difficulties questionnaire (SDQ) is now one of the most commonly used instruments for screening child psychiatric morbidities. Psychometric studies in the West affirm its ...reliability and validity, but similar studies are scarce among non-Western populations. This is an important gap because cultural differences can influence how children’s behaviours are perceived and rated. This study explores the psychometric properties of the Chinese version of the SDQ among children in Hong Kong.
Method
The SDQ was translated into Chinese. A community sample of 3,722 students between 6 and 12 years were recruited by stratified random sampling from across the whole of Hong Kong. Comparison group consisted of 494 consecutive children attending a general child psychiatric clinic. SDQ and basic socio-demographic data were collected from parents and teachers. Reliability was determined by internal consistency and test–retest stability. Validity was assessed by the questionnaire’s ability to discriminate between community and clinic samples, and ROC curves. Cutoff scores and their sensitivity, specificity, positive predictive value and negative predictive value were calculated.
Results
Our results confirm the questionnaire’s reliability and validity. The total difficulties scale and hyperactivity subscale are potentially the most useful in discriminating between community and clinic children. The emotional subscale was relatively weaker, especially with respect to teachers’ ratings. Of note also is that our normative scores are significantly higher than those reported in the West, highlighting once again the importance of examining a questionnaire’s cultural applicability.
Conclusion
Our data support the use of the Chinese version of the SDQ, especially the total difficulties scale, as a screening instrument for psychiatric morbidities among children in Hong Kong.
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins ...and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, leading to autophagy induction through the activation of the Ca(2+)/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.
PTF10ops is a Type Ia supernova (SN Ia), whose light curve and spectral properties place it outside the current SN Ia subtype classifications. Its spectra display the characteristic lines of ...subluminous SNe Ia, but it has a normal-width light curve with a long rise time, typical of normal-luminosity SNe Ia. The early-time optical spectra of PTF10ops were modelled using a spectral fitting code and found to have all the lines typically seen in subluminous SNe Ia, without the need to invoke more uncommon elements. The host galaxy environment of PTF10ops is also unusual with no galaxy detected at the position of the SN down to an absolute limiting magnitude of r≥−12.0 mag, but a very massive galaxy is present at a separation of ∼148 kpc and at the same redshift as suggested by the SN spectral features. The progenitor of PTF10ops is most likely a very old star, possibly in a low-metallicity environment, which affects its explosion mechanism and observational characteristics. PTF10ops does not easily fit into any of the current models of either subluminous or normal SN Ia progenitor channels.
Cycling is associated with a greater risk of traumatic brain injury (TBI) than other recreational activities. This study aimed to investigate the epidemiology of sports-related TBI in Hong Kong and ...to examine predictors for recreational cycling-induced intracranial haemorrhage.
This retrospective multicentre study included patients diagnosed with sports-related TBI in public hospitals in Hong Kong from 2015 to 2019. Computed tomography scans were reviewed by an independent assessor. The primary endpoint was traumatic intracranial haemorrhage. The secondary endpoint was an unfavourable Glasgow Outcome Scale (GOS) score at discharge from hospital.
In total, 720 patients were hospitalised with sports-related TBI. The most common sport was cycling (59.2%). The crude incidence of cycling-related TBI was 1.1 per 100 000 population. Cyclists were more likely to exhibit intracranial haemorrhage and an unfavourable GOS score, compared with patients who had TBI because of other sports. Although 47% of cyclists had intracranial haemorrhage, only 15% wore a helmet. In multivariate analysis, significant predictors for intracranial haemorrhage were age ≥60 years, antiplatelet medication, moderate or severe TBI, and skull fracture. Among 426 cyclists, 375 (88%) had mild TBI, and helmet wearing was protective against intracranial haemorrhage, regardless of age, antiplatelet medication intake, and mechanism of injury. Of 426 cyclists, 31 (7.3%) had unfavourable outcomes on discharge from hospital.
The incidence of sports-related TBI is low in Hong Kong. Although cycling-related head injuries carried greater risks of intracranial haemorrhage and unfavourable outcomes compared with other sports, most cyclists experienced good recovery. Helmet wearing among recreational cyclists with mild TBI was protective against intracranial haemorrhage and skull fracture.
Objective
To perform a systematic review and meta‐analysis to evaluate the impact of body mass index (BMI) on oncological (primary) and surgical (secondary) outcomes of patients who underwent ...nephrectomy, as obesity or high BMI is a known risk factor for renal cell carcinoma (RCC) and predictor of poorer outcomes.
Methods
Studies were identified from four electronic databases from database inception to 2 June 2021, according to the Preferred Reporting Items for Systematic Review and Meta‐analysis statement. The review protocol was registered in the International Prospective Register of Systematic Reviews with the identification number: CRD42021275124.
Results
A total of 18 studies containing 13 865 patients were identified for the final meta‐analysis. Regarding oncological outcomes, higher BMI predicted higher overall survival (BMI >25 vs BMI <25 kg/m2: hazard ratio HR 0.70, 95% confidence interval CI 0.58–0.85), cancer‐specific survival (BMI >25 vs BMI <25 kg/m2: HR 0.60, 95% CI 0.50–0.73; BMI 25–30 vs BMI <25 kg/m2: HR 0.46, 95% CI 0.23–0.95; BMI >30 vs BMI <25 kg/m2: HR 0.50, 95% CI 0.36–0.69), and recurrence‐free survival rates (BMI >25 vs BMI <25 kg/m2: HR 0.72, 95% CI 0.63–0.82; BMI 25–30 vs BMI <25 kg/m2: HR 0.59, 95% CI 0.42–0.82). Those with a lower BMI fared better in surgical outcomes, such as operation time and warm ischaemic time, although the absolute difference was minimal and unlikely to be clinically significant. There was no difference between groups for length of hospital stay, intraoperative or postoperative complications, blood transfusion requirements, and conversion to open surgery.
Conclusion
Our study suggests that a higher BMI is associated with improved long‐term oncological survival and similar perioperative outcomes as a lower BMI. More research into the underlying biological and physiological mechanisms will enable better understanding of the effect of BMI, beyond mere association, on post‐nephrectomy outcomes.
This study examined the early pragmatic language skills in typically developing (TD) preschool-age children, children with language impairment (LI) and children with autism spectrum disorder (ASD). ...Two hundred and sixty-two TD children, 73 children with LI, and 16 children with ASD were compared on early pragmatics through direct assessment (DA). Post hoc analysis revealed that children in two clinical groups displayed significant pragmatic language deficits. Children in the ASD group who were older exhibited comparable degree of impairments as their LI peers, suggesting a relatively stagnant development of pragmatic language skills in children with ASD. Findings also supported the use of DA in identifying pragmatic language deficits, which have implications for the adoption of this assessment approach in clinical settings.
Purpose
To evaluate the outcomes of pre-stented (PS) versus non-pre-stented (NPS) patients who have undergone retrograde intrarenal surgery (RIRS) for renal calculi with subgroup analysis of Asian ...and non-Asian cohorts.
Methods
Protocol is registered in PROSPERO, CRD42021261123. Eligible studies identified from four electronic databases. Meta-analysis was done to enumerate the outcomes of RIRS in between PS and NPS. Secondary sub-analysis was done to look for differences in outcomes in Asian and non-Asian cohorts.
Results
Fourteen studies involving 3831 patients (4 prospective, 10 retrospective studies) were included. PS patients experienced higher success rates of ureteral access sheath (UAS) insertion than NPS (RR 1.09, 95% CI 1.05–1.13,
p
< 0.00001). PS patients had lower risk of ureteral injuries from UAS placement (RR 0.69, 95% CI 0.50–0.96,
p
= 0.03). No significant differences in intra- and postoperative complications between two groups were found. Stone-free rate (SFR) outcomes for residual fragment (RF) cut-off of < 1 mm and < 4 mm favoured the PS patients (RR 1.10, 95% CI 1.04–1.17,
p
= 0.002 for < 4 mm, RR1.10, 95% CI 1.02–1.19,
p
= 0.02 for < 1 mm). In the subgroup analysis, PS Asian patients had similar SFR as NPS patients for SFR(< 4 mm) but non-Asian population showed better outcomes in the PS patients for SFR(< 4 mm) (RR 1.31, 95% CI 1.13–1.52,
p
= 0.0005).
Conclusions
This meta-analysis suggests that pre-stenting results in a higher success for UAS placement, minimising intraoperative ureteric injury, with higher overall SFR for any RF cut-off in PS cohorts. In non-Asian cohort, significant differences occurred at SFR < 4 mm but not for SFR < 1 mm. No difference was seen in our Asian cohort for any SFR cut-off in both PS and NPS patients.
PDF
