The Development of Epitope-Based Recombinant Protein Vaccines against SARS-CoV-2.

The COVID-19 pandemic continues to cause infections and deaths, which are attributable to the SARS-CoV-2 Omicron variant of concern (VOC). Moderna's response to the declining protective efficacies of current SARS-CoV-2 vaccines against Omicron was to develop a bivalent booster vaccine based on the Spike (S) protein from the Wuhan and Omicron BA.4/BA.5 strains. This approach, while commendable, is unfeasible in light of rapidly emerging mutated viral strains. PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2024. Articles included focused on specific themes such as the clinical history of recombinant protein vaccine development against different diseases, including COVID-19, the production of recombinant protein vaccines using different host expression systems, aspects to consider in recombinant protein vaccine development, and overcoming problems associated with large-scale recombinant protein vaccine production. In silico approaches to identify conserved and immunogenic epitopes could provide broad protection against SARS-CoV-2 VOCs but require validation in animal models. The recombinant protein vaccine development platform has shown a successful history in clinical development. Recombinant protein vaccines incorporating conserved epitopes may utilize a number of expression systems, such as yeast (Saccharomyces cerevisiae), baculovirus-insect cells (Sf9 cells), and Escherichia coli (E. coli). Current multi-epitope subunit vaccines against SARS-CoV-2 utilizing synthetic peptides are unfeasible for large-scale immunizations. Recombinant protein vaccines based on conserved and immunogenic proteins produced using E. coli offer high production yields, convenient purification, and cost-effective production of large-scale vaccine quantities capable of protecting against the SARS-CoV-2 D614G strain and its VOCs.

Enhanced-nitrogen removal through Fe(III)-triggered partial dissimilatory nitrate reduction to ammonium coupling with anammox in anammox bioreactor.

Anammox is recognized as a prospective alternative for future biological nitrogen removal technologies. However, the nitrate by-products produced by anammox bacteria limit its overall nitrogen removal efficiency below 88 %. This study introduced Fe(III) into the anammox bioreactor to enhance the nitrogen removal efficiency to approximately 95 %, surpassing the biochemical limit of 88 % imposed by anammox stoichiometry. Anammox sludge was demonstrated to utilize extracellular polymeric substances to reduce Fe(III) into Fe(II), and this process promoted the dominance of Ca. Brocadia. The iron addition improved the abundance of narGHI genes and facilitated the partial dissimilatory nitrate reduction to ammonium, with nitrite as the end product. The accumulated nitrite was then eliminated through the anammox pathway, along with the excess ammonium (30 mg/L) in the influent. Overall, this study deepens our understanding of the enhanced nitrogen removal triggered by Fe(III) in anammox sludge and offers an effective approach to boost anammox process.

Immunogenicity of trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against EV-A71 and CV-A16.

Aim: To develop a trivalent DNA vaccine candidate encapsulated in Chitosan-TPP nanoparticles against hand foot and mouth disease (HFMD) and assess its immunogenicity in mice.Materials & methods: Trivalent plasmid carrying the VP1 and VP2 genes of EV-A71, VP1 gene of CV-A16 was encapsulated in Chitosan-TPP nanoparticles through ionic gelation. In vitro characterization and in vivo immunization studies of the CS-TPP-NPs (pIRES-VP121) were performed.Results: Mice administered with CS-TPP NPs (pIRES-VP121) intramuscularly were observed to have the highest IFN-γ response. Sera from mice immunized with the naked pDNA and CS-TPP-NPs (pIRES-VP121) demonstrated good viral clearance against wild-type EV-A71 and CV-A16 in RD cells.Conclusion: CS-TPP-NPs (pIRES-VP121) could serve as a prototype for future development of multivalent HFMD DNA vaccine candidates.

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Identification and Validation of Peptides Specifying SARS-CoV-2 B-Cell Epitopes Eliciting Neutralizing Antibodies.

Vaccination is an effective means of inducing immune protection to prevent transmissible diseases. During the Covid-19 pandemic, immunizations using traditional and novel vaccine platforms such as the inactivated SARSCo-V-2 vaccine, adenoviral-vectored, and nucleic acid-based mRNA vaccines have been relatively successful in controlling the rates of infection and hospitalizations. Nevertheless, the danger posed by the emergence of SARS-CoV-2 variants would set the stage for the design of next generation vaccines. To overcome the lack of efficacy of current vaccines against emerging SARS-CoV-2 variants, new vaccines must be able to overcome the reduced effectiveness of the current vaccines. Since the current Covid-19 vaccines are dependent on the whole S-protein of Wuhan strain as the antigen, mutations have rendered the current Covid-19 vaccines less effective against variants of concern (VoCs). Instead of using the whole S-protein, peptide-based epitopes could be predicted using immunoinformatic approaches, simulation of the 3D structures, overlapping peptides covering the whole length of the S-protein or peptide arrays based on synthetic peptide combinatorial libraries comprising peptides recognizable by monoclonal antibodies. B-cell epitopes were predicted, and immunogenicity of peptides was validated in mice by immunizing mice with peptides conjugated to keyhole limpet hemocyanin (KLH) mixed with Montanide 51 as an adjuvant. The immunogenicity of epitopes that could elicit peptide specific IgGs was determined by peptide-based ELISA. Neutralizing activities were determined by cPass and pseudovirus-based neutralization assays.

Caries trajectories from childhood to adolescence: Analysis of data from a nationwide school dental service.

OBJECTIVES: The aim of the study was to assess patterns of longitudinal changes in caries status among school-going children in Singapore. METHODS: Dental records for a single cohort of students who received dental examinations in six standard examination years between 2009 and 2017 were analysed (n = 24 699). Group-based trajectory modelling with a zero-inflated Poisson distribution was carried out to determine dental caries trajectories in the permanent dentition. Associations between sociodemographic factors and trajectory group membership were assessed using multinomial logistic regression. RESULTS: The predicted population distribution across the four caries trajectory groups identified was 65.0% ('none'), 16.8% ('low'), 14.8% ('medium') and 3.4% ('high'). The 'none' trajectory group had a decayed, missing and filled teeth (DMFT) score of 0 throughout the 8 years. Higher baseline DMFT counts and nonlinear increases in DMFT scores were noted for the 'low', 'medium' and 'high' trajectory groups. The correlation coefficient between DMFT counts in years 6 and 8 was 0.91, as compared to 0.77 between baseline and year 1. Factors associated with the 'high' caries trajectory include lower socio-economic status, female gender, Chinese race (compared to the Indian race), enrolment in primary schools in the Eastern and Western regions of Singapore, and enrolment in public secondary schools. CONCLUSIONS: Under a nationwide school dental service, four trajectory patterns of caries counts in the permanent dentition were identified over 8 years. Among students in the 'low', 'medium' and 'high' trajectory groups, greater caries increment was noted during the transition from primary to secondary school. The correlation between DMFT counts in successive examinations was stronger in older than younger ages.

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

OBJECTIVE: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test. METHODS: Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48 months; 19 demonstrated typical development, mean age: 61.16 ± 8.11 months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval. RESULTS: The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors. CONCLUSIONS: This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis.

Identification and Genomic Characterization of Two Novel Hepatoviruses in Shrews from Yunnan Province, China.

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV.

Cost-Effectiveness of a Home Telemonitoring System for Asian Adults with Type 2 Diabetes Mellitus.

Background: Telemonitoring programs have been found to be effective in improving diabetic control by promoting patients' self-management of diabetes through medication adherence, dietary modifications, and exercise. Nonetheless, few studies have assessed the cost-effectiveness of telemonitoring for the self-management of diabetes based on real-world data. Methods: A randomized controlled trial entitled Optimizing care of Patients via Telehealth In Monitoring and Augmenting their control of Diabetes Mellitus was conducted among adults with Type 2 Diabetes Mellitus in Singapore. Individuals in the intervention group (n = 159) underwent a telemonitoring program comprising of remote patient monitoring, education, individualized health coaching, and teleconsultations, whereas individuals in the control group (n = 160) received regular care. Economic evaluation was conducted from health care system and societal perspectives in 2020 in Singapore dollars, using health outcomes and costs documented at baseline and at 6 month follow-up. One-way sensitivity analyses and bootstrapping to generate scatter plot on cost-effectiveness planes were done. Results: The adjusted reduction in HbA1c scores was greater in the intervention group by -0.41 (95% confidence interval [CI], -0.65 to -0.17), while the change in utility scores was higher in the intervention group by 0.011 (95% CI, -0.016 to 0.0378). From a health care perspective, the incremental cost-effectiveness ratio (ICER) of the telemonitoring program per unit improvement in HbA1c, per additional case of well-controlled diabetes, and per unit improvement in quality adjusted life years was SGD 580.44, SGD 9100.15, and SGD 21,476.36, respectively. From a societal perspective, the ICERs were SGD 817.20, SGD 12,812.02, and SGD 30,236.36, respectively. Conclusions: The Optimizing care of Patients via Telehealth In Monitoring and Augmenting their control of Diabetes Mellitus telemonitoring program was effective and potentially cost-effective for the management and control of diabetes among patients in primary care.

Conceptualising TMD symptom burden in youths: Symptom duration, frequency, intensity and interference.

OBJECTIVE: This study aimed to conceptualise Temporomandibular disorder (TMD) symptom burden and severity and explored their interrelationships with somatic symptoms and psychological distress. METHODS: Participants were recruited from a local polytechnic. The quintessential five TMD symptoms (5Ts) of the Diagnostic Criteria for TMDs (DC/TMD) were appraised and extended to evaluate the duration, frequency, intensity and interference of discrete TMD symptoms. Global TMD severity (GS) was computed by totaling the points for all TMD symptoms and dimensions. TMD (TS) and somatic symptom (SS) burden were assessed based on the Somatic Symptoms Scale-8, while psychological distress was measured with the Depression, Anxiety and Stress Scales-21. Statistical analyses were performed using Kruskal-Wallis/Dunn tests and Spearman's correlation (α = .05). RESULT: Of the 366 eligible participants (mean age 19.1 ± 2.3 years), 51.4% were 5Ts-negative and 48.6% were 5Ts-positive. Among the 5Ts-positive individuals, 25.3%/64.0% were 'bothered a little' whereas 4.5%/10.7% were 'bothered a lot' by TMD pain/headache. Correspondingly, 32.6%/12.4%/5.1% were 'bothered a little' while 2.8%/2.8%/1.1% were 'bothered a lot' by TMJ sounds/closed/open locking. TS burden was moderate-to-strongly correlated to aggregate symptom duration, frequency, intensity, interference, GS and SS burden (rs = .50-.88). While TS burden and GS were weakly associated with psychological distress (rs = .18-.36), SS burden was moderately related to depression, anxiety and stress (rs = .47-.53). CONCLUSIONS: TS burden can serve as a proxy for global TMD severity and may be more meaningful than the mere presence of TMD symptoms in clinical and research settings.

Impact of income and financial subsidies on oral health care utilization among persons with disabilities in Singapore.

BACKGROUND/AIM(S): Globally, studies have shown that the dental disease burden among persons with intellectual and/or developmental disabilities (IDD) is high and can be attributed to lower utilization levels of dental services. The aim of the study was to assess the influence of income and financial subsidies on the utilization of dental care services among persons with IDD in Singapore. METHODS: Between August 2020 and August 2021, a cross-sectional study was conducted via centres offering Early Intervention Programme for Infants and Children, special education schools and adult associations in Singapore serving persons with IDD. A sample of 591 caregivers of children and adults with IDD completed the survey. Data on sociodemographic information, oral health behaviours and dental utilization were collected. Financial subsidy status was assessed by the uptake of a government-funded, opt-in Community Health Assist Scheme (CHAS) for low-income families that provided a fixed subsidy amount for dental services in the primary care setting. Statistical analysis was carried out using univariable, multiple logistic regression and modified Poisson regression. Propensity score matching was carried out in R version 4.0.2 to assess the impact of financial subsidies on oral health care utilization among persons with IDD. RESULTS: Compared to those with lower gross monthly household incomes, the adjusted prevalence ratios of having at least one dental visit in the past year, having at least one preventive dental visit in the past year, and visiting the dentist at least once a year for persons with IDD with gross monthly household incomes of above SGD$4000 were 1.28 (95% CI 1.08-1.52), 1.48 (95% CI 1.14-1.92) and 1.36 (95% CI 1.09-1.70), respectively. Among those who were eligible for CHAS Blue subsidies (247 participants), 160 (62.0%) took up the CHAS Blue scheme and 96 (35.4%) visited the dentist at least yearly. There was no statistically significant difference in the utilization of dental services among individuals enrolled in the CHAS Blue subsidy scheme among those eligible for CHAS Blue subsidies. CONCLUSION: Higher household income was associated with a higher prevalence of dental visits in the past year, preventive dental visits in the past year, and at least yearly dental visits. CHAS Blue subsidies alone had limited impact on dental utilization among persons with IDD who were eligible for subsidies.

Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice.

The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.

Safety and efficacy of sequential treatments for postmenopausal osteoporosis: a network meta-analysis of randomised controlled trials.

Background: The sequential anti-osteoporotic treatment for women with postmenopausal osteoporosis (PMO) is important, but the order in which different types of drugs are used is confusing and controversial. Therefore, we performed a network meta-analysis to compare the efficacy and safety of available sequential treatments to explore the most efficacious strategy for long-term management of osteoporosis. Methods: In this network meta-analysis, we searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov from inception to September 19, 2023 to identify randomised controlled trials comparing sequential treatments for women with PMO. The identified trials were screened by reading the title and abstract, and only randomised clinical trials involving sequential anti-osteoporotic treatments and reported relevant outcomes for PMO were included. The main outcomes included vertebral fracture risk, the percentage change in bone mineral density (BMD) in different body parts, and all safety indicators in the stage after switching treatment. A frequentist network meta-analysis was performed using the multivariate random effects method and evaluated using the surface under the cumulative ranking curve (SUCRA). Certainty of evidence was assessed using the Confidence in the Network Meta-Analysis (CINeMA) framework. This study is registered with PROSPERO: CRD42022360236. Findings: A total of 19 trials comprising 18,416 participants were included in the study. Five different sequential treatments were investigated as the main interventions and compared to the corresponding control groups. The intervention groups in this study comprised the following treatment switch protocols: switching from an anabolic agent (AB) to an anti-resorptive agent (AR) (ABtAR), transitioning from one AR to another AR (ARtAAR), shifting from an AR to an AB (ARtAB), switching from an AB to a combined treatment of AB and AR (ABtC), and transitioning from an AR to a combined treatment (ARtC). A significant reduction in the incidence of vertebral fractures was observed in ARtC, ABtAR and ARtAB in the second stage, and ARtC had the lowest incidence with 81.5% SUCRA. ARtAAR and ABtAR were two effective strategies for preventing fractures and improving BMD in other body parts. Especially, ARtAAR could improve total hip BMD with the highest 96.1% SUCRA, and ABtAR could decrease the risk of total fractures with the highest 94.3% SUCRA. Almost no difference was observed in safety outcomes in other comparisons. Interpretation: Our findings suggested that the ARtAAR and ABtAR strategy are the effective and safe sequential treatment for preventing fracture and improving BMD for PMO. ARtC is more effective in preventing vertebral fractures. Funding: The National Natural Science Foundation of China (82170900, 81970762), the Hunan Administration of Traditional Chinese Medicine, and the Hunan Province High-level Health Talents "225" Project.

Hsa_circ_0005397 promotes hepatocellular carcinoma progression through EIF4A3.

PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.

The Chinese translation and cross-cultural adaptation of PRISMA-7 questionnaire: an observational study to establish the accuracy, reliability and validity.

BACKGROUND: Frailty is a health condition linked to adverse health outcomes and lower life quality. The PRISMA-7, a 7-item questionnaire from the Program on Research for Integrating Services for the Maintenance of Autonomy (PRISMA), is a validated case-finding tool for frailty with good sensitivity and specificity. This study aimed to translate, culturally adapt, and validate the PRISMA-7 questionnaire for Chinese use. METHODS: A prospective observational study with convenience sampling recruited bilingual adults aged 65 and over living in the community. The Functional Autonomy Measurement System (SMAF) was the gold standard benchmark. The English PRISMA-7 questionnaire was culturally adapted to Chinese using forward and backward translation. Intra- and inter-rater reliability were determined using the intraclass correlation coefficient (ICC). Face, content and criterion validity were determined. The Receiver Operator characteristic (ROC) curve determined the optimal cut-off score. RESULTS: One-hundred-twenty participants (55 females and 65 males) were recruited. The Chinese PRISMA-7 questionnaire had excellent intra-rater and inter-rater reliability (ICC = 1.000). The rigorous forward and backward translation established the face and content validity. The moderately high correlations between the English PRISMA-7 with SMAF (r = - 0.655, p <  0.001) and Chinese PRISMA-7 with SMAF (r = - 0.653, p <  0.001) pairs established the criterion validity. An optimal cut-off score of three "Yes" responses was reported with 100% sensitivity and 85.3% specificity. CONCLUSION: This translation, cross-cultural adaptation, and validation study established the Chinese PRISMA-7 questionnaire. The preliminary results suggest adequate diagnostic test accuracy for frailty screening among the Chinese-literate community.

Risk of incident chronic kidney disease in metabolically healthy obesity and metabolically unhealthy normal weight: A systematic review and meta-analysis.

Studies have reported inconsistent results about the risk of incident chronic kidney disease (CKD) in people with metabolically healthy obesity (MHO). We designed this systematic review and meta-analysis to evaluate the risk of developing CKD in people with MHO and metabolically unhealthy normal weight (MUNW). We used a predefined search strategy to retrieve eligible studies from multiple databases up to June 20, 2022. Random-effects model meta-analyses were implied to estimate the overall hazard ratio (HR) of incident CKD in obesity phenotypes. Eight prospective cohort studies, including approximately 5 million participants with a median follow-up ranging between 3 and 14 years, were included in this meta-analysis. Compared to the metabolically healthy normal weight (MHNW), the mean differences in cardiometabolic and renal risk factors in MHO, MUNW, and metabolically unhealthy obesity (MUO) were evaluated with overall HR of 1.42, 1.49, and 1.84, respectively. Compared to MHNW, the mean estimated glomerular filtration rate (eGFR) and high-density lipoprotein (HDL) were significantly lower, and low-density lipoprotein (LDL), blood pressure, blood glucose, and triglycerides were higher in MHO and MUNW. In conclusion, MHO and MUNW are not benign conditions and pose a higher risk for incident CKD. Obesity, whether in the presence or absence of metabolic health, is a risk factor for CKD.

Clinical study of standard residual liver volume and transient elastography in predicting poor prognosis of patients after hemihepatectomy.

BACKGROUND: Liver cancer resection, especially in patients with hemihepatectomy or extended hemihepatectomy, often leads to poor prognosis, such as liver insufficiency and even liver failure and death, because the standard residual liver volume (SRLV) cannot be fully compensated after surgery. AIM: To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches. METHODS: The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed. The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy. It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation. RESULTS: The liver stiffness measure (LSM) value and SRLV were associated with liver dysfunction after hemihepatectomy. Logistic regression analysis showed that an LSM value ≥ 25 kPa [odds ratio (OR) = 6.254, P < 0.05] and SRLV ≤ 0.290 L/m2 (OR = 5.686, P < 0.05) were independent risk factors for postoperative liver dysfunction. The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score (P < 0.05). CONCLUSION: SRLV and LSM values can be used to evaluate the safety of hemihepatectomy. The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.

Cancer patients' experience of receiving variant of uncertain significance results: An Asian perspective.

Due to a lack of ancestry-matched, functional, and segregation data, Asians have a higher rate of receiving a variant of uncertain significance (VUS) result following panel testing. Managing VUS results presents challenges, as it often leads to increased anxiety and distress among cancer patients undergoing genetic testing. This exploratory study aims to investigate the experience of Asian cancer patients upon receiving a VUS result. A qualitative, semi-structured interview study was conducted, involving cancer patients who had received a VUS result through the Cancer Genetics Service of the National Cancer Centre Singapore. Twenty participants were interviewed, and their responses were transcribed and analyzed using thematic analysis to identify key themes. Thematic analysis revealed five major themes: (1) VUS results are interpreted as uncertain outcomes; (2) a VUS result provides relief and prompts positive behavioral adjustments; (3) patients employ fatalism and religion as coping mechanisms to navigate uncertainty; (4) genetic counselors, family, and the community offer reassurance and support; (5) patients value updates on variant classifications for future management. While this novel study provides unique insights into the perspectives of Asian patients who receive VUS results, it also highlights patients' effective management of VUS results and uncertainty, which has implications for improving counseling practices in Asia. Emphasis must be placed on accurate interpretation and clear communication of VUS results to dispel the possibility of misconceptions, misdiagnosis, and mismanagement in cancer care.

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

DLAT is a promising prognostic marker and therapeutic target for hepatocellular carcinoma: a comprehensive study based on public databases.

Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.