Rare but elevated incidence of hematological malignancy after clozapine use in schizophrenia: A population cohort study.

Background: Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies.

Risk of mortality and complications in people with depressive disorder and diabetes mellitus: A 20-year population-based propensity score-matched cohort study.

People with depression have increased premature mortality and elevated prevalence of diabetes-mellitus compared to general population. However, risk of mortality and diabetes-related complications among patients with depression and co-occurring diabetes is under-studied. This population-based propensity score-matched (1:10) cohort study identified 12,175 patients with pre-existing depression and incident-diabetes (depression-diabetes group) and 117,958 patients with incident-diabetes only (diabetes-only group) between 2002 and 2021 in Hong-Kong, using territory-wide medical-record database of public-healthcare services, to investigate whether depression increased the risk of overall mortality, complications and post-complication mortality in people with diabetes.

Risk of mortality and complications in patients with severe mental illness and co-occurring diabetes mellitus: A systematic review and meta-analysis.

People with severe-mental-illness (SMI), often defined as "schizophrenia-spectrum disorders and bipolar disorder", have increased premature mortality and elevated prevalence of diabetes compared with general population. Evidence indicated that one-third of their premature death was from cardiovascular diseases (CVD), with risk conferred by diabetes. Although earlier studies have examined SMI-associated diabetes-related outcomes, findings were inconsistent and not systematically evaluated.

Cognitive functioning in people with psychotic experiences: a systematic review and meta-analysis study.

Earlier research suggested that psychotic experiences (PEs), the extended-psychosis phenotype, are associated with cognitive impairment. Recent studies, however, revealed more mixed findings, and patterns and magnitude of cognitive deficits in PEs remain uncertain. We aimed to systematically review and quantitatively synthesize estimates of cognitive functioning covering a wide array of domains in individuals with versus without PEs.

Excess mortality and life-years lost in people diagnosed with depression: A 20-year population-based cohort study of 126,573 depressed individuals followed for 1,139,073 persons-years.

Depression is associated with premature mortality, but evidence is mainly derived from Western countries. Very limited research has evaluated shortened lifespan in depression using life-years-lost (LYLs), a recently developed mortality metric taking into account the illness onset for life expectancy estimation. Temporal trends of differential mortality gap are understudied.

Adverse obstetric and neonatal outcomes associated with maternal schizophrenia-spectrum disorders and prenatal antipsychotic use: a meta-analysis of 37,214,330 pregnancy deliveries and propensity-score weighted population-based cohort study assessing confounder dependency of risk estimates.

Studies demonstrated increased obstetric and neonatal complications in women with schizophrenia-spectrum disorder (SSD), but most inadequately addressed confounders and rarely considered antipsychotic effects. We conducted a meta-analysis and a population-based cohort study evaluating associations of adverse obstetric/neonatal outcomes with SSD and prenatal antipsychotic use. In the meta-analysis, we searched four databases from inception to October-31-2023 and generated pooled risk estimates using random-effect models.

Risk of adverse pregnancy, delivery and neonatal outcomes associated with bipolar disorder and prenatal use of mood stabilizers: A population-based cohort study.

Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated effect between disorder and mood-stabilizers. This population-based study identified women age 15-50 years who delivered first/singleton child in 2003-2018 in Hong Kong, utilizing territory-wide medical-record database of public healthcare services. Propensity-score weighted logistic-regression analyses adjusted for confounders were employed to examine risk of adverse pregnancy, delivery and neonatal outcomes associated with BD and mood-stabilizers (lithium, anticonvulsants and antipsychotics).

Prenatal antidepressant use and risk of congenital malformations: A population-based cohort study.

Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15-50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.

Risk of congenital malformations associated with first-trimester exposure to antipsychotics: A propensity score-weighted population-based cohort study.

Background: There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong.

Single-Cell Omics for Transcriptome CHaracterization (SCOTCH): isoform-level characterization of gene expression through long-read single-cell RNA sequencing.

Recent development involving long-read single-cell transcriptome sequencing (lr-scRNA-Seq) represents a significant leap forward in single-cell genomics. With the recent introduction of R10 flowcells by Oxford Nanopore, we propose that previous computational methods designed to handle high sequencing error rates are less relevant, and that the traditional approach using short reads to compile "barcode space" (candidate barcode list) to de-multiplex long reads are no longer necessary. Instead, computational methods should now shift focus on harnessing the unique benefits of long reads to analyze transcriptome complexity.

Network analysis on psychopathological symptoms, psychological measures, quality of life and COVID-19 related factors in Chinese psychiatric patients in Hong Kong.

Background: Psychiatric patients are susceptible to adverse mental health impacts during COVID-19, but complex interplays between psychopathology and pandemic-related variables remain elusive. This study aimed to investigate concomitant associations between psychopathological symptoms, psychological measures and COVID-19 related variables in Chinese psychiatric patients during the peak of fifth pandemic wave in Hong Kong.

Methods: We employed network analysis to investigate inter-relationships among psychopathological symptoms (including depression, anxiety, post-traumatic stress disorder-like [PTSD-like] symptoms, insomnia, psychotic symptoms), cognitive complaints, health-related quality of life, loneliness, resilience and selected pandemic-related factors in 415 psychiatric outpatients between 28 March and 8 April, 2022.

A signal processing and deep learning framework for methylation detection using Oxford Nanopore sequencing.

Oxford Nanopore sequencing can detect DNA methylations from ionic current signal of single molecules, offering a unique advantage over conventional methods. Additionally, adaptive sampling, a software-controlled enrichment method for targeted sequencing, allows reduced representation methylation sequencing that can be applied to CpG islands or imprinted regions. Here we present DeepMod2, a comprehensive deep-learning framework for methylation detection using ionic current signal from Nanopore sequencing.

The risk of stroke and post-stroke mortality in people with schizophrenia: A systematic review and meta-analysis study.

Sources of heterogeneity in risk of stroke and mortality risk following acute-stroke in schizophrenia are understudied. We systematically searched four electronic-databases until 1-November-2022, and conducted meta-analysis to synthesize estimates of stroke-risk and post-stroke mortality for schizophrenia patients relative to non-schizophrenia counterparts. Subgroup-analyses and meta-regression models stratified by sex, nature of sample (incident/prevalent), geographical region, study-period and time-frame following stroke were conducted when applicable.

Life expectancy and years of potential life lost in people with mental disorders: a systematic review and meta-analysis.

Background: Mental disorders are associated with premature mortality. There is increasing research examining life expectancy and years-of-potential-life-lost (YPLL) to quantify the disease impact on survival in people with mental disorders. We aimed to systematically synthesize studies to estimate life expectancy and YPLL in people with any and specific mental disorders across a broad spectrum of diagnoses.

Temporal trends of antidepressant utilization patterns in children and adolescents in Hong Kong: A 14-year population-based study with joinpoint regression analysis.

Background: There is limited research on real-world antidepressant utilization patterns in children and adolescents, particularly in non-western countries. We aimed to examine temporal trends of antidepressant prescribing practice among Chinese children and adolescents in Hong Kong over 14-year period.

Methods: This population-based study identified 9566 patients aged 5-17 years who had redeemed at least one antidepressant prescription within 2005-2018, using data from health-record database of Hong Kong public healthcare services.

Prevalence and correlates of subjective cognitive impairment in Chinese psychiatric patients during the fifth wave of COVID-19 in Hong Kong.

Introduction: The extent of cognitive impairment and its association with psychological distress among people with pre-existing mental illness during COVID-19 is understudied. This study aimed to investigate prevalence and correlates of subjective cognitive impairment (SCI) in Chinese psychiatric patients during fifth-wave of COVID-19 in Hong Kong (HK).

Methods: Four-hundred-eight psychiatric outpatients aged 18-64 years were assessed with questionnaires between 28 March and 8 April 2022, encompassing illness profile, psychopathological symptoms, coping-styles, resilience, and COVID-19 related factors.

Validation of a High-Sensitivity Assay for Detection of Chimeric Antigen Receptor T-Cell Vectors Using Low-Partition Digital PCR Technology.

Although in vivo engraftment, expansion, and persistence of chimeric antigen receptor (CAR) T cells are pivotal components of treatment efficacy, quantitative monitoring has not been implemented in routine clinical practice. We describe the development and analytical validation of a digital PCR assay for ultrasensitive detection of CAR constructs after treatment, circumventing known technical limitations of low-partitioning platforms. Primers and probes, designed for detection of axicabtagene, brexucabtagene, and Memorial Sloan Kettering CAR constructs, were employed to validate testing on the Bio-Rad digital PCR low-partitioning platform; results were compared with Raindrop, a high-partitioning system, as reference method.

COVID-19 perseverative cognition and depressive symptoms in Hong Kong: The moderating role of resilience, loneliness and coping strategies.

Background: The COVID-19 pandemic significantly increased depression prevalence in general population. However, the relationship between persistent dysfunctional thinking associated with COVID-19 (perseverative-cognition) and depression, and its potential moderators are understudied. We aimed to examine the association between COVID-19 perseverative-cognition and depression, and the moderating effect of potential risk and protective factors on this association in general public during the peak of fifth COVID-19 wave in Hong Kong.

Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: A Randomized Clinical Trial.

Rationale & Objective: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.

Study Design: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.

DNA polymerase θ protects leukemia cells from metabolically induced DNA damage.

Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/1-carbon cycle metabolism contributed to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases (OTKs: FLT3(internal tandem duplication [ITD]), JAK2(V617F), BCR-ABL1). To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) via ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation.