The role of hope in college transition: Its cross-lagged relationships with psychosocial resources and emotional well-being in first-year college students.

INTRODUCTION: College transition is often regarded as the most stressful phase of life by college students. Hence, it is necessary to find ways to help them adjust more smoothly to this transition. Hope, as conceptualized by C. R. Snyder, has been widely studied as a predictor of optimal functioning and has been shown to be associated with better adjustment among college students. This study aimed to shed light on the role of hope in college transition by examining its unique reciprocal relationships with an array of important psychosocial resources and emotional well-being among first-year college students. METHODS: Data were collected from a sample of Hong Kong college freshmen (N = 433, Medianage = 18 years old, 63.7% female) at two time points. At each time point, participants completed self-reported measures tapping into their levels of hope, psychosocial resources, and emotional well-being. Psychological resources included general and academic self-efficacy, meaning in life, and optimism. Social resources included secure attachment, perceived school environment, and social support. Emotional well-being was operationalized as positive and negative emotions. Cross-lagged panel models were constructed and tested by path analyses. RESULTS: When autoregression and the effects of other variables were controlled, a greater sense of hope uniquely predicted higher levels of general and academic self-efficacy, greater presence of life meanings, more secure attachment, and more positive and fewer negative emotions. On the other hand, higher levels of meaning in life (both presence and search) and social support uniquely predicted greater hope. Academic hope and presence of life meanings reciprocally predicted one another, whereas other significant cross-lagged relationships were unidirectional. CONCLUSIONS: The findings suggest interventions that promote hope can be useful in helping college freshmen adjust to the new college environment by enhancing their psychosocial resources and emotional well-being. Such interventions would be more effective if they included elements that boost meaning in life and social support, which are expected to further enhance the perceptions of hope.

Online Learning Stress and Chinese College Students' Academic Coping during COVID-19: The Role of Academic Hope and Academic Self-Efficacy.

Colleges around the world have adopted emergency online learning to continue with teaching and learning activities during COVID-19. Existing research has indicated that this teaching mode is perceived negatively by many college students. The difficulty students encounter in emergency online learning can adversely affect their mental health and academic performance. To shed further light on how emergency online learning may have impeded college students' academic functioning and adjustment, this study examined the association between online learning stress and academic coping and the mediating roles of academic self-efficacy and academic hope. It was conducted in early 2021, a year after the outbreak of the pandemic. Ninety-nine Chinese college students in Hong Kong were recruited and they completed an online questionnaire for this study. Results showed that online learning stress was negatively associated with approach academic coping and social support seeking, and the associations were mediated by academic hope. On the other hand, online learning stress was positively associated with avoidance academic coping, which was not mediated by academic hope. The mediation effects of academic self-efficacy were all non-significant. In sum, college students used more passive and maladaptive coping to handle academic problems when they experienced more online learning stress, and this was partly explained by lower levels of academic hope.

Validation of a developmental screening checklist for Chinese preschoolers in Hong Kong.

There are concerns about the cultural validity of applying developmental screeners developed and normed in Western countries to other sociocultural contexts. Given the scarcity of culturally validated developmental checklists for use among Chinese children, the Hong Kong Society for the Protection of Children (HKSPC) has developed the HKSPC Developmental Checklist (HKSPC-DC) for preschool teachers to identify children at risk of developmental delays through daily observation of children's functioning at school. This study explored the psychometric properties of the HKSPC-DC among 1183 preschool children aged 2-6 recruited from 14 nursery schools in Hong Kong. The HKSPC-DC showed excellent internal consistency, good interrater and test-retest reliabilities, and acceptable concurrent validity when correlated with the Taipei City Developmental Checklist for Preschoolers (Taipei II), which is the only screening instrument developed in a Chinese society and validated across 4- to 72-month-olds. The HKSPC-DC also showed good discriminatory power in identifying preschoolers potentially at risk of developmental delays. This screening tool may help facilitate early identification of children with developmental vulnerabilities in Chinese preschool populations.

Generation of genomic-integration-free human induced pluripotent stem cells and the derived cardiomyocytes of X-linked dilated cardiomyopathy from DMD gene mutation.

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.

Genome-Wide DNA Methylation Analysis of Chinese Patients with Systemic Lupus Erythematosus Identified Hypomethylation in Genes Related to the Type I Interferon Pathway.

BACKGROUND: Epigenetic variants have been shown in recent studies to be important contributors to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report a 2-step study of discovery followed by replication to identify DNA methylation alterations associated with SLE in a Chinese population. Using a genome-wide DNA methylation microarray, the Illumina Infinium HumanMethylation450 BeadChip, we compared the methylation levels of CpG sites in DNA extracted from white blood cells from 12 female Chinese SLE patients and 10 healthy female controls. RESULTS: We identified 36 CpG sites with differential loss of DNA methylation and 8 CpG sites with differential gain of DNA methylation, representing 25 genes and 7 genes, respectively. Surprisingly, 42% of the hypomethylated CpG sites were located in CpG shores, which indicated the functional importance of the loss of DNA methylation. Microarray results were replicated in another cohort of 100 SLE patients and 100 healthy controls by performing bisulfite pyrosequencing of four hypomethylated genes, MX1, IFI44L, NLRC5 and PLSCR1. In addition, loss of DNA methylation in these genes was associated with an increase in mRNA expression. Gene ontology analysis revealed that the hypomethylated genes identified in the microarray study were overrepresented in the type I interferon pathway, which has long been implicated in the pathogenesis of SLE. CONCLUSION: Our epigenetic findings further support the importance of the type I interferon pathway in SLE pathogenesis. Moreover, we showed that the DNA methylation signatures of SLE can be defined in unfractionated white blood cells.

CFTR founder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a rare condition in Asians. Since 1985, only about 30 Chinese patients have been reported with molecular confirmation. METHOD: Using our in-house next-generation sequencing (NGS) pipeline for childhood bronchiectasis, we identified disease-causing CFTR mutations in CF patients in Hong Kong. After identifying p.I1023R in multiple patients, haplotype analysis was performed with genome-wide microarray to ascertain the likelihood of this being a founder mutation. We also assessed the processing and gating activity of the mutant protein by Western hybridization and patch-clamp test. RESULTS: Molecular diagnoses were confirmed in four patients, three of whom shared a missense mutation: CFTR:c.3068T>G:p.I1023R. The results suggested that p.I1023R is a founder mutation in southern Han Chinese. In addition, the processing and gating activity of the mutant protein was assessed by gel electrophoresis and a patch-clamp test. The mutant protein exhibited trafficking defects, suggesting that the dysfunction is caused by reduced cell surface expression of the fully glycosylated proteins. CONCLUSION: Together with other previously reported mutations, the specific founder mutation presented herein suggests a unique CFTR mutation spectrum in the southern Chinese populations, and this finding has vital implications for improving molecular testing and mutation-specific treatments for Chinese patients with CF.

Prenatal Tobacco Exposure Shortens Telomere Length in Children.

INTRODUCTION: Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association. METHODS: This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling. RESULTS: Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose-response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child's telomere length. The association between the child's telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood. CONCLUSIONS: Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy. IMPLICATIONS: As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children's biological programming.

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV.

Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients.

Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report the phase I trial of a recombinant vaccinia virus, MVA-EL, which encodes an EBNA1/LMP2 fusion protein designed to boost T-cell immunity to these antigens. The vaccine was delivered to Hong Kong patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-γ ELIspot assays using complete EBNA1 and LMP2 15-mer peptide mixes and known epitope peptides relevant to patient MHC type. Eighteen patients were treated, three per dose level one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 18 patients and, in many cases, were mapped to known CD4 and CD8 epitopes in EBNA1 and/or LMP2. The range of these responses suggested a direct relationship with vaccine dose, with all six patients at the highest dose level giving strong EBNA1/LMP2 responses. We concluded that MVA-EL is both safe and immunogenic, allowing the highest dose to be forwarded to phase II studies examining clinical benefit.

CXCR6 and CCR5 localize T lymphocyte subsets in nasopharyngeal carcinoma.

The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8(+), CD4(+), and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8(+) and (nonregulatory) CD4(+) T cells also were more frequently CCR5(+) in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumor.

TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance.

Genomic gain represents an important mechanism in the activation of proto-oncogenes. In many instances, induced oncogenes hold clinical implications both as prognostic markers and targets for therapeutic design. In hepatocellular carcinoma (HCC), although chromosomal gains are common, information on underlying oncogenes induced remains minimal. Here, we examined 7 causal sites of HCC for overexpressed genes by array-based transcriptional mapping. In 22 HCC cell lines and early passages of cultures studied, clusters of up-regulated genes were indicated, where TOP2A expression ranked the highest. Distinct TOP2A transcriptions were confirmed in an independent series of HCC tumors relative to adjacent non-tumoral liver (p=0.0018). By tissue microarray analysis of 172 HCC, we found TOP2A expressions correlated with advance histological grading (p<0.001), microvascular invasion (p=0.004) and an early age onset of the malignancy (

Plasma osteopontin, hypoxia, and response to radiotherapy in nasopharyngeal cancer.

PURPOSE: Recent studies have suggested that osteopontin is induced by hypoxia in head and neck cancer cell lines and its plasma level may serve as a surrogate marker for tumor hypoxia and treatment outcome in head and neck cancer. We investigated the response of osteopontin to in vitro hypoxia in nasopharyngeal carcinoma cell lines, and determined plasma osteopontin levels in nasopharyngeal carcinoma patients, nonnasopharyngeal carcinoma head and neck cancer patients, and healthy controls. We explored the relationship of plasma osteopontin and response to radiotherapy in nasopharyngeal carcinoma. EXPERIMENTAL DESIGN: Nasopharyngeal carcinoma cell lines HK1, HONE-1, C666-1, and CNE-2 were treated with 0 to 48 hours of hypoxia or normoxia, +/- reoxygenation. Osteopontin secretion in the supernatant was measured by ELISA assay. Cellular osteopontin protein and mRNA were detected by Western blotting and reverse transcription-PCR, respectively. Plasma osteopontin levels in patients (n=66; 44 nasopharyngeal carcinoma, 22 head and neck cancer) and controls (n=29) were measured by ELISA. RESULTS: Hypoxia has no effect on osteopontin protein and mRNA level in nasopharyngeal carcinoma cells. Only CNE-2 secreted osteopontin, and there was no significant induction by hypoxia. Plasma osteopontin levels in patients of metastatic nasopharyngeal carcinoma and head and neck cancer, but not in locoregional nasopharyngeal carcinoma, were significantly higher than in controls. In patients with locoregional nasopharyngeal carcinoma receiving curative radiotherapy (n=31), a high (>median) pretreatment plasma osteopontin level was a significant predictor of poor response to radiotherapy (complete response rate, 40% versus 88%; P=0.009), which remained significant in multivariate analysis. CONCLUSION: Our results suggested that the pretreatment plasma osteopontin level may be a useful biomarker of response to radiotherapy in nasopharyngeal carcinoma.

Differential effects of glial cell line-derived neurotrophic factor and neurturin in RET/GFRalpha1-expressing cells.

The c-ret protooncogene, RET, encodes a receptor tyrosine kinase. RET is activated by members of the glial cell line-derived neurotrophic factor (GDNF) family of ligands, which include GDNF, neurturin, artemin, and persephin. The ligands bind RET through GDNF family receptor alpha, termed GFRalpha1-4. Despite the importance of RET signaling in the development of the enteric nervous system and the kidney, the differential signaling mechanisms between RET ligands are poorly established. It has been suggested that signal specificity is achieved through binding of the ligand to its preferred GFRalpha. To compare the signaling profiles of GDNF and neurturin, we have identified a cell line, NG108-15, which endogenously expresses RET and GFRalpha1 but not GFRalpha2-4. Immunoblot data showed that GDNF caused a transient activation, whereas neurturin caused a sustained activation, of both p44/p42 MAP kinases and PLCgamma. Under serum starvation, NG108-15 cells differentiate and form neurites. Neurturin but not GDNF stimulated neurite outgrowth, which could be blocked by the selective PLC inhibitor U73122. On the other hand, GDNF but not neurturin promoted cell survival, and this could be blocked by the p44/p42 MAP kinase inhibitor PD98059. Our findings not only show the differential signaling of GDNF and neurturin but also suggest that this can be achieved through binding to the same GFRalpha subtype, leading to distinct biological responses.

High frequency of promoter hypermethylation of RASSF1A in tumorous and non-tumourous tissue of breast cancer.

AIM: To determine the presence of RASSF1A promoter methylation in tumorous and non-tumorous tissues of breast cancer. METHODS: Methylation-specific PCR was used to detect RASSF1A methylation in DNA extracted from tumorous and paired non-tumorous tissues of 40 breast cancer patients. The associations of RASSF1A hypermethylation with clinicopathological characteristics in tumorous and non-tumorous breast tissues were analysed. RESULTS: RASSF1A promoter hypermethylation was detected in 38 of the 40 breast cancer tissues (95%) and 37 of the paired non-tumorous tissues (92.5%). When compared with the non-tumorous tissues, aberrant methylation was detected to be higher in 24 of the tumorous tissues (60%). The latter was found to be associated with lower histological grade tumours (p=0.048). CONCLUSION: RASSF1A promoter hypermethylation occurred at a high frequency in breast cancer tumorous and non-tumorous tissues; the majority of tumours have a higher level of methylation status when compared with non-tumorous tissues. This supports the notion that RASSF1A methylation is an early and premalignant alteration.

High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma.

PURPOSE: To determine the presence of ras association domain family 1A (RASSF1A) promoter methylation in the tumor tissues and plasma of patients with hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Methylation-specific polymerase chain reaction was used to detect RASSF1A methylation in DNA extracted from HCC tumors and paired plasma samples of 40 patients. The association of RASSF1A hypermethylation in tumor and plasma DNA of HCC patients with clinicopathological characteristics was also analyzed. RESULTS: RASSF1A promoter hypermethylation was detected in 37 of the 40 HCC tissues (92.5%). Of the paired plasma from the 40 HCC patients, aberrant methylation was detected in 17 (42.5%). No RASSF1A methylation was detected in the plasma in the absence of methylation in the corresponding tumor. The presence of RASSF1A promoter hypermethylation in plasma DNA was found to associate with HCC size of > or =4 cm (P = 0.035). CONCLUSION: RASSF1A promoter hypermethylation occurred at a high frequency in HCC. The aberrant methylation was also detectable in over 40% of matched plasma. The latter should be evaluated as a screening tool and/or prognosticator of HCC patients.