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Aim: To evaluate the acceptability, feasibility and potential effectiveness of a group-based instrumental musical training programme in improving resilience, depressive symptoms, self-esteem and quality of life among school-aged children from low-income families., Design: Assessor-blinded pilot randomised waitlist controlled trial with process evaluation., Methods: This study was conducted in the community from January 2022 to July 2023. Sixty-four children from low-income families (aged 8-12 years) were randomised (1:1) to intervention and waitlist control groups. The intervention group (n = 32) received weekly 1-hour instrumental musical training for 6 months in groups of four to five from professionally qualified musicians at a music centre. The participants in the waitlist control group (n = 32) received the same intervention as the participants in the intervention group after the completion of all outcome assessments. The primary outcome was the children's levels of resilience, measured using the Resilience Scale for Children - 10. The secondary outcomes were depressive symptoms, self-esteem and quality of life. Assessments were conducted at baseline (T0) and immediately post-intervention (T1). An intention-to-treat analysis was performed., Results: The 64 participants had a mean (SD) age of 9.5 (1.44) years, and 37 (57.8%) were boys. Compared with the waitlist control group, participants in the intervention group showed significantly greater improvements in resilience levels from baseline to T0 (group-by-time interaction coefficient β = 4.41; 95% CI, 1.82-6.99; p = 0.001), depressive symptoms (β = -6.42; 95% CI, -11.12 to -1.71; p = 0.008), self-esteem (β = -2.60; 95% CI, 0.28-4.92; p = 0.028) and quality of life (β = 6.69; 95% CI, 0.18-13.2; p = 0.044)., Conclusion: The group-based instrumental musical training programme was feasible and acceptable for school-aged underprivileged children and showed the potential to improve the resilience and quality of life of this vulnerable population., (© 2024 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.

In Asia, a few countries have a long and established history of collaborative clinical trials successfully formed national children's cancer study groups, but many still do not have such groups. The process of forming national children's cancer groups is fraught with many hurdles, which varies among the countries. One of the basic requirements for running clinical trials is an affordable health care system in which most of the children with cancer can receive the proposed treatment. The health insurance coverage for children with cancer varies from <20% to as high as 100% among Asian countries, and the operation of clinical trials must also be adjusted accordingly. Shortage of research personnel is common, including medical, nursing, research coordinators, and data managers. The establishment of the Asian Pediatric Hematology and Oncology Group aims to provide a good platform for promotion of international clinical trials in the Asian countries.

Background: Acute graft-versus-host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplantation of immunosuppressive human mesenchymal stromal cells (hMSCs) can protect against aGvHD post-HSCT; however, their efficacy is limited by poor engraftment and survival. Moreover, infused MSCs can be damaged by activated complement, yet strategies to minimise complement injury of hMSCs and improve their survival are limited., Methods: Human MSCs were derived from bone marrow (BM), adipose tissue (AT) and umbilical cord (UC). In vitro immunomodulatory potential was determined by co-culture experiments between hMSCs and immune cells implicated in aGvHD disease progression. BM-, AT- and UC-hMSCs were tested for their abilities to protect aGvHD in a mouse model of this disease. Survival and clinical symptoms were monitored, and target tissues of aGvHD were examined by histopathology and qPCR. Transplanted cell survival was evaluated by cell tracing and by qPCR. The transcriptome of BM-, AT- and UC-hMSCs was profiled by RNA-sequencing. Focused experiments were performed to compare the expression of complement inhibitors and the abilities of hMSCs to resist complement lysis., Results: Human MSCs derived from three tissues divergently protected against aGvHD in vivo. AT-hMSCs preferentially suppressed complement in vitro and in vivo, resisted complement lysis and survived better after transplantation when compared to BM- and UC-hMSCs. AT-hMSCs also prolonged survival and improved the symptoms and pathological features of aGvHD. We found that complement-decay accelerating factor (CD55), an inhibitor of complement, is elevated in AT-hMSCs and contributed to reduced complement activation. We further report that atorvastatin and erlotinib could upregulate CD55 and suppress complement in all three types of hMSCs., Conclusion: CD55, by suppressing complement, contributes to the improved protection of AT-hMSCs against aGvHD. The use of AT-hMSCs or the upregulation of CD55 by small molecules thus represents promising new strategies to promote hMSC survival to improve the efficacy of transplantation therapy. As complement injury is a barrier to all types of hMSC therapy, our findings are of broad significance to enhance the use of hMSCs for the treatment of a wide range of disorders., (© 2023. The Author(s).)

The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF-α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Gata3, and Foxp3 mRNA expression in renal and splenic tissues. Kidneys of these mice displayed less CD11b+ infiltration, had downregulated MCP-1, and increased infiltration of Foxp3-expressing cells. Splenic CD4+ T cells showed increased ST2-expressing CD4+Foxp3+ population and reduced IFN-γ+ population. There were no differences in serum anti-dsDNA antibodies and renal C3 and IgG2a deposit in these mice. Exogenous IL-33 was found to ameliorate disease activity in lupus-prone mice with induction of M2 polarisation, Th2 response, and expansion of regulatory T cells. IL-33 likely orchestrated autoregulation of these cells through upregulation of ST2 expression., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: All authors have disclosed no conflicts of interest.

There is a paucity of evidence about the associations of physical activity (PA) and handgrip strength (HGS) within different domains of quality of life (QoL) in Chinese pediatric cancer survivors. We, therefore, conducted this multicenter cross-sectional study aimed to investigate whether increased PA level and HGS are associated with higher scores in different QoL domains (i.e., physical, emotional, social, and school functioning) in pediatric cancer survivors. PA was assessed with a validated self-reported PA rating scale. In total, 191 Chinese pediatric cancer survivors aged 9 to 16 years were included in the analysis. Results showed that engaging in a higher level of PA was significantly associated with improved QoL in different domains, including physical (β = 0.543, p < 0.001), emotional (β = 0.449, p < 0.001), social (β = 0.434, p < 0.001), and school functioning (β = 0.407, p < 0.001). Greater HGS was also associated with better physical (β = 0.230, p ≤ 0.001) and emotional (β = 0.261, p ≤ 0.001) functioning. Findings from this study provide evidence of the significant beneficial impact of regular PA on pediatric cancer survivors’ QoL along their survivorship trajectory.

Much research on children in high-risk environments has focused on the biological consequences of maltreatment, adversity, and trauma. Whether other early-life stress sources such as family financial hardship are implicated in the cellular mechanism of disease development remains unclear. This study investigated the long-term effect of childhood exposure to family financial pressure on telomere length. It involved two waves of data collection occurring when participants reached Grade 3 (W1) and 7 (W2), respectively. In W1, parents reported family demographics and perceived financial stressors and pressure. In W2, participants provided buccal swab samples for measurement of their telomere length. Data from 92 participants (M age in W2 = 13.2 years; 56.5% male) were analyzed. The main type of stressors reported by parents who perceived high family financial pressure in W1 were child-level stressors including affordability of their medical and educational expenses. Participants exposed to high parent-perceived family financial pressure in W1 had shorter telomeres in W2 when compared to those exposed to low parent-perceived family financial pressure (β = -0.61, p = 0.042). Subgroup analyses revealed stronger associations in girls than boys. These findings reveal an important spillover effect between parental financial perceptions and stress and children's health at the cellular level.

Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.8% of the population) was a carrier for one or more recessive conditions, and 1 in 12 individuals (8.30% of the population) was a carrier for treatable inherited conditions. In alignment with current American College of Obstetricians and Gynecologists (ACOG) pan-ethnic carrier recommendations, 1 in 26 individuals were identified as carriers of cystic fibrosis, thalassemia, and spinal muscular atrophy in the Southern Chinese population. When the >1% expanded carrier screening rate recommendation by ACOG was used, 11 diseases were found to meet the criteria in the Southern Chinese population. Approximately 1 in 3 individuals (35.5% of the population) were carriers of these 11 conditions. If the 1 in 200 carrier frequency threshold is used, and additional seven genes would meet the criteria, and 2 in 5 individuals (38.7% of the population) would be detected as a carrier. This study provides a comprehensive catalogue of the carrier spectrum and frequency in the Southern Chinese population and can serve as a reference for careful evaluation of the conditions to be included in expanded carrier screening for Southern Chinese people., (© 2022. The Author(s).)

Background: Influenza is one of the most common causes of acute respiratory tract infections around the world. Influenza viruses can cause seasonal epidemics. There remains limited information on the impact of both seasonal influenza A and influenza B related hospitalisations from neurological complications in paediatric populations in Asia., Objectives: To examine both the clinical spectrum and healthcare burden of influenza-associated neurological complications (IANCs) within the paediatric population of Hong Kong., Methods: We conducted a population-based retrospective study to identify all paediatric patients (<18 years) admitted to a public hospital in Hong Kong with a confirmed influenza A or B infection between 2014 and 2018 using the Clinical Data Analysis and Reporting System of the Hospital Authority. The clinical spectrum of the paediatric patients with IANCs was studied. The clinical burden of paediatric influenza patients with IANCs were compared to paediatric influenza patients without neurological complications., Results: A total of 28,016 children admitted to the paediatric wards diagnosed to have influenza A or B infection were identified, accounting for 5.7% (28,016/489,955) of total paediatric admissions. 67.3% had influenza A and 32.7% had influenza B, and 8.9% had IANCs. The mean annual incidence of IANCs in children was 57 per 100,000 population. The spectrum of IANCs in our paediatric patients included febrile seizures (80.6%), myositis (11.4%), seizures with fever (5.4%), influenza-associated encephalitis/encephalopathy (IAE) (2.6%) and rarely Guillain-Barré syndrome (0.04%). Most paediatric patients with IANCs (85.5%) presented at a young age of <6 years. Paediatric patients with IANCs had significant longer hospital stays ( p < 0.001), higher percentages of mechanical ventilation use ( p < 0.05) and PICU admissions ( p < 0.001), and higher mortality rates ( p < 0.001) compared to those without neurological complications. Amongst those with IANCs, IAE was the sole cause of all seven reported mortalities., Conclusions: Seasonal influenza A & B is a common cause of hospitalisation for paediatric patients in Hong Kong. We found neurological complications from influenza A and B caused a significantly higher clinical burden compared to those without neurological complications. Children in younger age groups (<6 years old) are at highest risk and thus increasing vaccination coverage to this age group is recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Leung, Wong, Ho, Chiu, Zhi, Chan and Chan.)

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tsang, Chua, To, Wong, Tu, Kwok, Wong, Wang, Zhang, Rosa Duque, Chan, Chu, Pang, Tam, Lau, Wong, Leung, Yuen, Kwan and Ip.)

Background: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking., Methods: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19., Findings: 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated ( r  = 0.315, p  = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log 10 NPS ( r  = -0.532, p  < 0.001) and saliva ( r  = -0.417, p  < 0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p  < 0.05), and were inversely correlated with total lymphocyte ( r  = -0.43), CD3 ( r  = -0.55), CD4 ( r  = -0.60), CD8 ( r  = -0.41), B ( r  = -0.482), and NK ( r  = -0.416) lymphocyte counts (all p  < 0.05)., Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS.

Objectives: Meningitis in neonates and young infants leads to significant morbidity and mortality worldwide. This study aimed to investigate pathogens, antibiotic resistance and secular change of incidence in Hong Kong., Methods: A retrospective search was performed on meningitis in neonates and infants aged <3 months in three Hong Kong public hospitals from 2004 to 2019. Medical charts were reviewed, with focus on the identification and antibiotic resistance of the pathogens., Results: A total of 200 cases of meningitis were identified (67% were bacterial). Group B Streptococcus (GBS) and Escherichia coli (E. coli) were the commonest bacterial pathogens. The annual rates of early-onset GBS meningitis decreased after the implementation of universal GBS screening and intrapartum antibiotic prophylaxis (IAP) in 2012, while that of late-onset GBS meningitis remained similar. A significant portion of E. coli isolates were resistant to ampicillin and/or gentamicin., Conclusion: GBS and E. coli were the most common bacteria for meningitis in this age group. The annual rate of bacterial meningitis in Hong Kong has declined in recent years, which has been attributed to the decline in early-onset GBS meningitis due to universal GBS screening and IAP. Antimicrobial-resistant bacterial strains that cause meningitis require further clinical and public health attention., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Sleep disruption is a prevalent symptom reported by survivors of childhood cancer. However, there is no validated instrument for assessing this symptom in this population group. To bridge the literature gap, this study translated and adapted the Pittsburgh Sleep Quality Index (PSQI) for Hong Kong Chinese cancer survivors and examined its psychometric properties and factor structure., Methods: A convenience sample of 402 Hong Kong Chinese childhood cancer survivors aged 6-18 years were asked to complete the Chinese version of the PSQI, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Fatigue Scale-Child (FS-C)/Fatigue Scale-Adolescent (FS-A), and Pediatric Quality of Life Inventory (PedsQL). To assess known-group validity, 50 pediatric cancer patients and 50 healthy counterparts were recruited. A sample of 40 children were invited to respond by phone to the PSQI 2 weeks later to assess test-retest reliability. A cutoff score for the translated PSQI used with the survivors was determined using receiver operating characteristic analysis., Results: The Chinese version of the PSQI had a Cronbach alpha of 0.71, with an intraclass correlation coefficient of 0.90. Childhood cancer survivors showed significantly lower mean PSQI scores than children with cancer, and significantly higher mean scores than healthy counterparts. This reflected that childhood cancer survivors had a better sleep quality than children with cancer, but a poorer sleep quality than healthy counterparts. We observed positive correlations between PSQI and CES-DC scores and between PSQI and FS-A/FS-C scores, but a negative correlation between PSQI and PedsQL scores. The results supported that the Chinese version of the PSQI showed convergent validity. Confirmatory factor analysis showed that the translated PSQI data best fit a three-factor model. The best cutoff score to detect insomnia was 5, with a sensitivity of 0.81 and specificity of 0.70., Conclusion: The Chinese version of the PSQI is a reliable and valid instrument to assess subjective sleep quality among Hong Kong Chinese childhood cancer survivors. The validated PSQI could be used in clinical settings to provide early assessments for sleep disruption. Appropriate interventions can therefore be provided to minimize its associated long-term healthcare cost. Trial registration This study was registered in ClinicalTrials.gov with the reference number NCT03858218.

The use of exome and genome sequencing has increased rapidly nowadays. After primary analysis, further analysis can be performed to identify secondary findings that offer medical benefit for patient care. Multiple studies have been performed to evaluate secondary findings in different ethnicities. However, relevant data are limited in Chinese. Here, with the use of a cohort consisted of 1116 Hong Kong Chinese exome sequencing data, we evaluated the secondary findings in the 59 genes recommended by the American College of Medical Genetics and Genomics. Fifteen unique pathogenic or likely pathogenic variants in 17 individuals were identified, representing a frequency of 1.52% in our cohort. Although 20 individuals harboured pathogenic or likely pathogenic variants in recessive conditions, none carried bi-allelic mutations in the same gene. Our finding was in accordance with the estimation from the American College of Medical Genetics and Genomics that about 1% individuals harbour secondary findings.

Atopic diseases can impose a significant burden on children and adolescents. Telomere length is a cellular marker of aging reflecting the impact of cumulative stress exposure on individual health. Since elevated oxidative stress and inflammation burden induced by chronic atopy and snoring may impact telomere length, this study aimed to investigate whether snoring would moderate the relationship between atopic diseases and telomere length in early adolescence. We surveyed 354 adolescents and their parents. Parents reported the adolescents' history of atopic diseases, recent snoring history as well as other family sociodemographic characteristics. Buccal swab samples were also collected from the adolescents for telomere length determination. Independent and combined effects of atopic diseases and snoring on telomere length were examined. Among the surveyed adolescents, 174 were reported by parents to have atopic diseases (20 had asthma, 145 had allergic rhinitis, 53 had eczema, and 25 had food allergy). Shorter TL was found in participants with a history of snoring and atopic diseases (β = -0.34, p = 0.002) particularly for asthma (β = -0.21, p = 0.007) and allergic rhinitis (β = -0.22, p = 0.023). Our findings suggest that snoring in atopic patients has important implications for accelerated telomere shortening. Proper management of atopic symptoms at an early age is important for the alleviation of long-term health consequences at the cellular level.

Importance: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths., Objective: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020., Design, Setting, and Participants: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021., Main Outcomes and Measures: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections., Results: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post-COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts., Conclusions and Relevance: This cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small.

Regulatory B (Breg) cells are endowed with immune suppressive functions. Various human and murine Breg subtypes have been reported. While interleukin (IL)-10 intracellular staining remains the most reliable way to identify Breg cells, this technique hinders further essential functional studies. Recent findings suggest that CD9 is an effective surface marker of murine IL-10 competent Breg cells. However, the stability of CD9 and its relevance as a unique marker for human Breg cells, which have been widely characterized as CD24 hi CD38 hi , have not been investigated. Here, we demonstrate that CD9 expression is sensitive to in vitro B cell stimulations. CD9 expression could either be re-expressed or downregulated in purified CD9-negative B cells and CD9-positive B cells, respectively. We found no significant differences in the Breg differentiation capacity of the CD9-negative and CD9-positive B cells. Furthermore, CD9-positive B cells co-express CD40 and CD86, suggesting their nature as B cell activation or co-stimulatory molecules, rather than regulatory ones. Therefore, we report the relatively unstable CD9 as a distinct surface molecule, indicating the need for further research for a more reliable marker to purify human Breg cells.

Objectives: This study aimed to identify key factors affecting Healthcare workers (HCWs) perceived stress and risk of contracting COVID-19 among themselves and their family members during the pandemic. Methods: A cross-sectional online questionnaire study was conducted between 19 March and April 5, 2020 in Hong Kong. HCWs from public hospitals and private dentists, and their family members participated. Results: A total of 747 HCWs and 245 family members participated. Higher perceived stress in HCWs was associated with more negative changes in family relationship ( p = 0.025). The HCWs' perceived stress, however, was positively associated with family cohesion ( p = 0.033) and stress levels of family members ( p < 0.001). The level of HCWs' satisfaction toward the hospital policies in response to the COVID-19 outbreak was associated with lower levels of perceived stress and risk of themselves or their family members contracting COVID-19. HCWs' previous frontline experience of SARS was significantly associated with less perceived risk of themselves or their family members contracting COVID-19. Conclusion: Hospital policies addressing HCWs' needs, frontline experience of SARS, and family relationship influenced psychological wellbeing of HCWs during the COVID-19 outbreak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chua, Tung, Kwan, Wong, Chui, Li, Wong, Tso, Fu, Chan, Wing, Chen, Chun Lee, Rao, Chan, Hon, Hung, Lau, Ho, Wong, Xiong, Chi, Tang, Tam, Wong and Ip.)

Preemptive pharmacogenetic testing has the potential to improve drug dosing by providing point-of-care patient genotype information. Nonetheless, its implementation in the Chinese population is limited by the lack of population-wide data. In this study, secondary analysis of exome sequencing data was conducted to study pharmacogenomics in 1116 Hong Kong Chinese. We aimed to identify the spectrum of actionable pharmacogenetic variants and rare, predicted deleterious variants that are potentially actionable in Hong Kong Chinese, and to estimate the proportion of dispensed drugs that may potentially benefit from genotype-guided prescription. The projected preemptive pharmacogenetic testing prescription impact was evaluated based on the patient prescription data of the public healthcare system in 2019, serving 7.5 million people. Twenty-nine actionable pharmacogenetic variants/ alleles were identified in our cohort. Nearly all (99.6%) subjects carried at least one actionable pharmacogenetic variant, whereas 93.5% of subjects harbored at least one rare deleterious pharmacogenetic variant. Based on the prescription data in 2019, 13.4% of the Hong Kong population was prescribed with drugs with pharmacogenetic clinical practice guideline recommendations. The total expenditure on actionable drugs was 33,520,000 USD, and it was estimated that 8,219,000 USD (24.5%) worth of drugs were prescribed to patients with an implicated actionable phenotype. Secondary use of exome sequencing data for pharmacogenetic analysis is feasible, and preemptive pharmacogenetic testing has the potential to support prescription decisions in the Hong Kong Chinese population., Competing Interests: The authors have declared that no competing interests exist.

ABSTRACT As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p  < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p  < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p  < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p  < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p =0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin ( p  = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age.

We derived an integration-free induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 23-year-old male patient. This patient carries a 5' splice site point mutation in intron 1 (c.31+1G>A) of the dystrophin gene, a mutation associated with X-linked dilated cardiomyopathy (XLDCM). Sendai virus was used to reprogram the PBMCs and deliver OCT3/4, SOX2, c-MYC, and KLF4 factors. The iPSC line (HKUi002-A) generated preserved the mutation, expressed common pluripotency markers, differentiated into three germ layers in vivo, and exhibited a normal karyotype. Further differentiation into cardiomyocytes enables the study of the disease mechanisms of XLDCM., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are nanosized particles that have emerged as mediators for intercellular communication in physiologic and pathologic conditions. EVs carry signaling information on their bilipid membrane as well as cargo within, allowing them to perform a wide range of biologic processes and contribute to pathophysiologic roles in a wide range of diseases, including cancer, autoimmune diseases and coagulopathy. This review will specifically address the function of surface molecules on EVs under normal and diseased conditions, as well as their potential to emerge as therapeutic targets in clinical settings, and the importance of further research on the surface topography of EVs., (©2020 Society for Leukocyte Biology.)

Background: The Asia Pacific Society for Immunodeficiencies (APSID) conducted nine primary immunodeficiency (PID) Schools in 5 years since inauguration to provide PID care training for early career physicians in Asia Pacific, a region with divergent needs in PID resources and training. Objective: To identify differences in PID patient care resource and training needs across Asia Pacific and propose a corresponding action plan. Methods: The Human Development Index (HDI) indicates the degree of socio-economic development in each country/region. Information related to investigations and learning issues were extracted from the abstracts and personal statements from all Schools and mapped onto resource and training needs. Correlations between HDI and country/region-specific parameters were tested by two-tailed Pearson correlation. Results: A total of 427 abstracts were received in nine Schools between 2015 and 2020, predominantly on immunodeficiencies affecting cellular and humoral immunity. Genetic confirmation was described in 61.8% of abstracts, and its absence negatively correlated with HDI ( r = -0.696, p = 0.004). Essential immunologic and genetic tests were not available in 25.4 and 29.5% of abstracts, respectively, and their absence negatively correlated with HDI ( r = -0.788, p < 0.001; r = -0.739, p = 0.002). HDI positively correlated with average testing level ( r = 0.742, p = 0.002). Cases from medium-HDI countries/regions focused on learning how to investigate a patient for PIDs in cases of severe or atypical infections, whereas those from very-high-HDI countries/regions, from which most faculty members originated, listed hematopoietic stem cell transplantation and gene therapy, newborn screening, and research as learning issues more frequently. Conclusion: There are unique HDI-related PID resource and training needs in each country/region. APSID proposes HDI group-specific strategies to improve PID care and education in her member countries/regions. Further quantitative analysis of needs in PID care in Asia Pacific is needed for lobbying governments to increase their support for PID care and research., (Copyright © 2020 Leung, Chua, Mondragon, Zhong, Nguyen-Ngoc-Quynh, Imai, Vignesh, Suratannon, Mao, Lee, Kim, Chan, Liew, Huong, Kanegane, Muktiarti, Zhao, Santos-Ocampo, Latiff, Seger, Ochs, Singh, Lee and Lau.)

Background: Rapid whole-exome sequencing (rWES) offers the potential for early diagnosis-predicated precision medicine. Previous evidence focused predominantly on infants from the intensive care unit (ICU). This study sought to examine the diagnostic and clinical utility, and the economic impact on clinical management of rWES in patients beyond infancy and ICU setting., Methods: rWES was performed on a prospective cohort of patients with suspected monogenic disorder referred from territory-wide paediatric ICUs and non-ICUs in Hong Kong urging for rapid genetic diagnosis. All eligible families were invited. We aimed to achieve a rapid turnaround time (TAT) of 14 days. Clinical utility and costs associated with clinical management were assessed in diagnosed cases. Actual quantitative changes in healthcare utilisation were compared with a counterfactual diagnostic trajectory and/or with matched historical control whenever possible., Findings: rWES were offered to 102 families and 32/102 (31%) patients received a molecular diagnosis, with a median TAT of 11 days. Clinical management changed in 28 of 32 diagnosed patients (88%), including but not limited to modifications in treatment, avoidance of surgeries, and informing decisions on redirection of care. Cost analysis was performed in eight patients. rWES was estimated to reduce hospital length of stay by 566 days and decrease healthcare costs by HKD$8,044,250 (GBP£796,460) for these eight patients. The net cost-savings after inclusion of rWES costs were estimated to be HKD$5,325,187 (GBP£527,246)., Interpretation: This study replicates the diagnostic capacity and rapid TAT of rWES in predominantly Chinese patients, and demonstrates diagnosis-predicated precision medicine and net healthcare savings. Findings were corroborated by evidence from multinational cohorts, combined as part of a meta-analysis. rWES merits consideration as a first-tier diagnostic tool for patients with urgent needs in the clinical setting., Funding: Health and Medical Research Fund, HKU Seed Fund for Basic Research, The Society for the Relief of Disabled Children, and Edward and Yolanda Wong Fund., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors. Published by Elsevier Ltd.)

Haematological and immunological data of children with COVID-19 infection is lacking. Between 21st January and 20th March 2020, 244 children who were confirmed to have COVID-19 infection and admitted to the Wuhan Children's Hospital, China were retrospectively reviewed. 193 children were considered as symptomatic, which was defined as having either the presence of clinical symptoms or the presence of CT thorax abnormalities. Their haematological and immunological profiles, including complete blood counts, lymphocyte subsets (T, B and NK cell counts), immunoglobulin (Ig) profiles (IgG, IgA and IgM) and cytokine profiles were analysed and compared between the symptomatic and asymptomatic groups. The median values and the interquartile ranges were calculated. Comparison was made using the Mann-Whitney U test. Children with symptomatic COVID-19 infection had significantly lower haemoglobin levels, but higher absolute lymphocyte and monocyte counts, IgG and IgA levels, as well as interleukin 6 (IL-6), IL-10, tumour necrosis factor alpha and interferon gamma levels. The obtained data will be utilized for further studies in comparing children and adults with COVID-19 infections in other parts of the world and with different severity ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Authors.)

Purpose: Despite being the most common pediatric solid tumors, incidence and outcome of CNS tumors in Chinese children have not been systematically reported. We addressed this knowledge gap by comparing the epidemiology of pediatric CNS tumors in Hong Kong and the United States., Patients and Methods: Data between 1999 and 2016 from a population-based cancer registry in Hong Kong, China, on patients < 18 years old with CNS tumors (Hong Kong cohort) and from the US SEER Program (Asian/Pacific Islander and all ethnicities) were compared. Incidence and overall survival (OS) by histology were evaluated., Results: During the study period, 526 children were newly diagnosed with CNS tumors in Hong Kong (crude incidence rate, 2.47 per 100,000; 95% CI, 2.26 to 2.69). Adjusted incidences were significantly lower in the Hong Kong (2.51; 95% CI, 2.30 to 2.74) than in the SEER (Asian/Pacific Islander: 3.26; 95% CI, 2.97 to 3.57; P < .001; all ethnicities: 4.10 per 100,000; 95% CI, 3.99 to 4.22; P < .001) cohorts. Incidences of germ cell tumors (0.57 v 0.24; P < .001) were significantly higher, but those of glial and neuronal tumors (0.94 v 2.61; P < .001), ependymomas (0.18 v 0.31; P = .005), and choroid plexus tumors (0.08 v 0.16; P = .045) were significantly lower in Hong Kong compared with SEER (all ethnicities) cohorts. Compared with the SEER (Asian/Pacific Islander) cohort, histology-specific incidences were similar except for a lower incidence of glial and neuronal tumors in Hong Kong (0.94 v 1.74; P < .001). Among cohorts, OS differed only for patients with glial and neuronal tumors (5-year OS: Hong Kong, 52.5%; SEER [Asian/Pacific Islander], 73.6%; SEER [all ethnicities], 79.9%; P < .001)., Conclusion: We identified important ethnic differences in the epidemiology of CNS tumors in Chinese children. These results will inform the development of pediatric neuro-oncology services in China and aid further etiologic studies.

Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of many diseases, including myocardial ischemia/reperfusion injury. We hypothesized that human umbilical cord mesenchymal stromal cells derived extracellular vesicles (HuMSC-EVs) could protect cardiac cells against hyperactive ER stress induced by hypoxia/reoxygenation (H/R) injury. The H/R model was generated using the H9c2 cultured cardiac cell line. HuMSC-EVs were extracted using a commercially available exosome isolation reagent. Levels of apoptosis-related signaling molecules and the degree of ER stress were assessed by western blot. The role of the PI3K/Akt pathway was investigated using signaling inhibitors. Lactate dehydrogenase leakage and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) analysis were used for evaluating the therapeutic effects of HuMSC-EVs in vitro . The results showed that ER stress and the rate of apoptosis were increased in the context of H/R injury. Treatment with HuMSC-EVs inhibited ER stress and increased survival in H9c2 cells exposed to H/R. Mechanistically, the PI3K/Akt pathway was activated by treatment with HuMSC-EVs after H/R. Inhibition of the PI3K/Akt pathway by a specific inhibitor, LY294002, partially reduced the protective effect of HuMSC-EVs. Our findings suggest that HuMSC-EVs could alleviate ER stress-induced apoptosis during H/R via activation of the PI3K/Akt pathway.

Introduction: Nausea and vomiting are two most common symptoms reported by children with cancer when they undergo active treatment. However, pharmacological treatment is not sufficient to manage these two symptoms, with over 40% of children still experience nausea and vomiting after receiving antiemetics. There has been an exponential growth of studies to demonstrate the effectiveness of different complementary complementary medicine (CAM) to control nausea and vomiting during cancer treatment. Appropriate application of CAM enhances the effectiveness of antiemetics, thus reducing the symptom burden on children as well as improving their general condition and quality of life during cancer treatment. Nevertheless, it remains unclear which CAM is the best approach to help children to prevent or reduce nausea and vomiting during and after cancer treatment. This paper describes a protocol for identifying, analysing and synthesising research evidence on the effectiveness of CAM on nausea and vomiting in children with cancer., Methods and Analysis: A total of 10 databases will be searched to identify appropriate literature: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, CINAHL, PsycINFO, LILACS, OpenSIGLE, the Chinese Biomedical Literature Database, the Chinese Medical Current Contents and the Chinese National Knowledge Infrastructure. All randomised controlled trials which meet the inclusion criteria will be included. The primary outcome is the changes in nausea and vomiting either assessed by self-reported and/or objective measures. Review Manager 5.3 will be used to synthesise the data, calculate the treatment effects, perform any subgroup analysis and assess the risk of bias., Ethical and Dissemination: The results will be presented at international conferences and published in peer-reviewed journals. As no individual data will be involved in this review, ethical approval is not required., Prospero Registration Number: CRD42019135404., Competing Interests: Competing interests: No, there are no competing interests for any author., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Regulatory B cells (Breg) are crucial immunoregulators that maintain peripheral tolerance and suppress inflammatory autoimmune responses. In recent years, our understanding on the nature and mechanism of action of Bregs has revealed the important role of cytokines in promoting the regulatory properties of this unique B cell subset, both in animal and human models. In this review, we compiled the cytokines that have been reported by multiple studies to induce the expansion of Breg. The Breg-inducing cytokines which are currently known include IL-21, IL-6, IL1β, IFNα, IL-33, IL-35, BAFF and APRIL. As cytokines are also known to play a pivotal role in the pathogenesis of autoimmune diseases, in parallel we reviewed the pattern of expression of the Breg-inducing cytokines in Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Inflammatory Bowel Diseases (IBD) and Multiple Sclerosis (MS). We show here that Breg-inducing cytokines are commonly implicated in these inflammatory diseases where they typically have a higher expression than in healthy individuals, suggesting their paradoxical nature. Interestingly, despite the general overexpression of Breg-inducing cytokines, it is known that Breg cells are often numerically or functionally impaired in various autoimmune conditions. Considering these alterations, we explored the possible parameters that may influence the function of Breg-inducing cytokines in exhibiting either their regulatory or pro-inflammatory properties in the context of autoimmune conditions., (© 2019 The Authors.)

Competing Interests: As an editor of the journal, KL Hon was not involved in the peer review process. Other authors have no conflicts of interest to disclose.

We report the first case of microabscesses detected by polymerase chain reaction (PCR) amplification of nucleic acid from ultrasound-guided aspirated fluid in a three-year old boy with acute lymphoblastic leukemia and febrile neutropenia during induction chemotherapy. Fever persisted despite effective antifungal treatment. The addition of corticosteroid therapy successfully controlled the suspected immune reconstitution inflammatory syndrome (IRIS). This case highlights the utility of PCR and adjunctive corticosteroid in the approach of Candida tropicalis renal microabscesses in leukemic patients undergoing chemotherapy., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cord blood (CB) is an alternative stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT). The unique advantages of using CB as a stem cell source are a degree of permissibility for HLA mismatch, rapid availability, and relatively risk-free cell collection. Because HLA is highly polymorphic and population-specific, optimal HLA-matched unrelated donors or cord blood units (CBUs) might not be available. In view of the possibility that matched CBUs that include noninherited maternal antigens (NIMAs) might contain acceptable HLA mismatches, we attempted to determine the degree of alloreactivity of CB mononuclear cells (MNCs) on stimulation by the maternal, paternal, and unrelated stimulator cells. Suppression of T cell proliferation, cytotoxicity, and a cytokine profile indicating suppressed Th1 and elevated IL-10 and TGF-β1 responses were observed in the mixed lymphocyte reaction in response to NIMAs. The increases in IL-10 and TGF-β1 production may be due to the Th2 response and/or regulatory T cells (Tregs). The reduced IL-10 and TGF-β1 production after CD25 depletion could have been due to removal of Tregs from the CB cells. Thus, Tregs appear to play an important role in the CB MNC response to NIMAs, possibly due to the induction of IL-10 and TGF-β1. We hope that our work can provide some evidence of the beneficial effect of NIMAs., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Apart from the spatial resolution enhancement, scaling of temporal resolution, equivalently the imaging throughput, of fluorescence microscopy is of equal importance in advancing cell biology and clinical diagnostics. Yet, this attribute has mostly been overlooked because of the inherent speed limitation of existing imaging strategies. To address the challenge, we employ an all-optical laser-scanning mechanism, enabled by an array of reconfigurable spatiotemporally-encoded virtual sources, to demonstrate ultrafast fluorescence microscopy at line-scan rate as high as 8 MHz. We show that this technique enables high-throughput single-cell microfluidic fluorescence imaging at 75,000 cells/second and high-speed cellular 2D dynamical imaging at 3,000 frames per second, outperforming the state-of-the-art high-speed cameras and the gold-standard laser scanning strategies. Together with its wide compatibility to the existing imaging modalities, this technology could empower new forms of high-throughput and high-speed biological fluorescence microscopy that was once challenged.

Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones. Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients. Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrow-derived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs. Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224-32. ©2017 AACR ., (©2017 American Association for Cancer Research.)