Analysis of the chain mediation effect between intergenerational support and mental health of older adults in urban China: a structural equation model.

BACKGROUND: This study aimed investigate the impact of intergenerational support on the mental health of older adults in urban China. It also sought to evaluate the chain mediation effect of attitudes toward younger people and willingness to interact with younger people within a non-familial context between intergenerational support and mental health. METHODS: Data were derived from a community survey that adopted quota sampling in mainland China in 2022 (N = 780). Structural equation modeling was used to analyze the data, and the bootstrap technique was used to test the mediation effect. RESULTS: A significant positive association was found between intergenerational support and the mental health of older adults in urban China (B = 0.852, 95% confidence interval CI [0.157,1.617]). Intergenerational support had a specific indirect effect on mental health through older adults' attitudes toward younger people within a non-familial context (B = 0.665, 95% CI [0.443,1.046]). There was a chain mediation effect (B = 0.126, 95% CI [0.069,0.224]) in relation to attitudes toward younger people and the willingness to interact with younger people between intergenerational support and mental health. Mediation accounted for 44.44% of the total effects in the model. CONCLUSION: These findings help identify modifiable factors that can improve the mental health of older adults. In line with the proposed serial multiple mediation model, this study provides theoretical and practical insights concerning the synergistic effect of intergenerational support at the family level and intergenerational interaction at the community level. Policy and social service implications are also discussed.

Intrinsic and Effective Severity of Coronavirus Disease 2019 Cases Infected With the Ancestral Strain and Omicron BA.2 Variant in Hong Kong.

BACKGROUND: Understanding severity of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is crucial to inform public health measures. Here we used coronavirus disease 2019 (COVID-19) patient data from Hong Kong to characterize the severity profile of COVID-19. METHODS: Time-varying and age-specific effective severity measured by case hospitalization risk and hospitalization fatality risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through 26 October 2022 over 6 epidemic waves. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections. RESULTS: With 32 222 COVID-19 hospitalizations and 9669 deaths confirmed over 6 epidemic waves, the time-varying hospitalization fatality risk dramatically increased from <10% before the largest fifth wave of Omicron BA.2 to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, fatality risk was highest among older unvaccinated patients. CONCLUSIONS: Omicron has comparable intrinsic severity to the ancestral Wuhan strain, although the effective severity is substantially lower in Omicron cases due to vaccination.

Effectiveness of social distancing measures and lockdowns for reducing transmission of COVID-19 in non-healthcare, community-based settings.

Social distancing measures (SDMs) are community-level interventions that aim to reduce person-to-person contacts in the community. SDMs were a major part of the responses first to contain, then to mitigate, the spread of SARS-CoV-2 in the community. Common SDMs included limiting the size of gatherings, closing schools and/or workplaces, implementing work-from-home arrangements, or more stringent restrictions such as lockdowns. This systematic review summarized the evidence for the effectiveness of nine SDMs. Almost all of the studies included were observational in nature, which meant that there were intrinsic risks of bias that could have been avoided were conditions randomly assigned to study participants. There were no instances where only one form of SDM had been in place in a particular setting during the study period, making it challenging to estimate the separate effect of each intervention. The more stringent SDMs such as stay-at-home orders, restrictions on mass gatherings and closures were estimated to be most effective at reducing SARS-CoV-2 transmission. Most studies included in this review suggested that combinations of SDMs successfully slowed or even stopped SARS-CoV-2 transmission in the community. However, individual effects and optimal combinations of interventions, as well as the optimal timing for particular measures, require further investigation. This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.

Epidemiology of Infections with SARS-CoV-2 Omicron BA.2 Variant, Hong Kong, January-March 2022.

Our analysis of data collected from multiple epidemics in Hong Kong indicated a shorter serial interval and generation time of infections with the SARS-CoV-2 Omicron variant. The age-specific case-fatality risk for Omicron BA.2.2 case-patients without complete primary vaccination was comparable to that of persons infected with ancestral strains in earlier waves.

Estimating excess septicaemia mortality and hospitalisation burden associated with influenza in Hong Kong, 1998 to 2019.

Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04-0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94-2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.

A Mutation in Hnrnph1 That Decreases Methamphetamine-Induced Reinforcement, Reward, and Dopamine Release and Increases Synaptosomal hnRNP H and Mitochondrial Proteins.

Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous mutation in the first coding exon of Hnrnph1 (H1+/-) showed reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference. Furthermore, H1+/- mice showed a robust decrease in methamphetamine-induced dopamine release in the NAc with no change in baseline extracellular dopamine, striatal whole-tissue dopamine, dopamine transporter protein, dopamine uptake, or striatal methamphetamine and amphetamine metabolite levels. Immunohistochemical and immunoblot staining of midbrain dopaminergic neurons and their forebrain projections for TH did not reveal any major changes in staining intensity, cell number, or forebrain puncta counts. Surprisingly, there was a twofold increase in hnRNP H protein in the striatal synaptosome of H1+/- mice with no change in whole-tissue levels. To gain insight into the mechanisms linking increased synaptic hnRNP H with decreased methamphetamine-induced dopamine release and behaviors, synaptosomal proteomic analysis identified an increased baseline abundance of several mitochondrial complex I and V proteins that rapidly decreased at 30 min after methamphetamine administration in H1+/- mice. In contrast, the much lower level of basal synaptosomal mitochondrial proteins in WT mice showed a rapid increase. We conclude that H1+/- decreases methamphetamine-induced dopamine release, reward, and reinforcement and induces dynamic changes in basal and methamphetamine-induced synaptic mitochondrial function.SIGNIFICANCE STATEMENT Methamphetamine dependence is a significant public health concern with no FDA-approved treatment. We discovered a role for the RNA binding protein hnRNP H in methamphetamine reward and reinforcement. Hnrnph1 mutation also blunted methamphetamine-induced dopamine release in the NAc, a key neurochemical event contributing to methamphetamine addiction liability. Finally, Hnrnph1 mutants showed a marked increase in basal level of synaptosomal hnRNP H and mitochondrial proteins that decreased in response to methamphetamine, whereas WT mice showed a methamphetamine-induced increase in synaptosomal mitochondrial proteins. Thus, we identified a potential role for hnRNP H in basal and dynamic mitochondrial function that informs methamphetamine-induced cellular adaptations associated with reduced addiction liability.

Nanoreporter of an Enzymatic Suicide Inactivation Pathway.

Enzymatic suicide inactivation, a route of permanent enzyme inhibition, is the mechanism of action for a wide array of pharmaceuticals. Here, we developed the first nanosensor that selectively reports the suicide inactivation pathway of an enzyme. The sensor is based on modulation of the near-infrared fluorescence of an enzyme-bound carbon nanotube. The nanosensor responded selectively to substrate-mediated suicide inactivation of the tyrosinase enzyme via bathochromic shifting of the nanotube emission wavelength. Mechanistic investigations revealed that singlet oxygen generated by the suicide inactivation pathway induced the response. We used the nanosensor to quantify the degree of enzymatic inactivation by measuring response rates to small molecule tyrosinase modulators. This work resulted in a new capability of interrogating a specific route of enzymatic death. Potential applications include drug screening and hit-validation for compounds that elicit or inhibit enzymatic inactivation and single-molecule measurements to assess population heterogeneity in enzyme activity.

Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI.

BACKGROUND: There is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP). PURPOSE: To apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD. STUDY TYPE: Prospective. SUBJECTS: Forty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years. FIELD STRENGTH/SEQUENCE: 3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm. ASSESSMENT: Using quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed. STATISTICAL TESTS: Mixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF. RESULTS: The relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ /T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13). DATA CONCLUSION: Our study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:1219-1226.

Structure-induced switching of interpolymer adhesion at a solid-polymer melt interface.

Here we report a link between the interfacial structure and adhesive property of homopolymer chains physically adsorbed (i.e., via physisorption) onto solids. Polyethylene oxide (PEO) was used as a model and two different chain conformations of the adsorbed polymer were created on silicon substrates via the well-established Guiselin's approach: "flattened chains" which lie flat on the solid and are densely packed, and "loosely adsorbed polymer chains" which form bridges jointing up nearby empty sites on the solid surface and cover the flattened chains. We investigated the adhesion properties of the two different adsorbed chains using a custom-built adhesion testing device. Bilayers of a thick PEO overlayer on top of the flattened chains or loosely adsorbed chains were subjected to the adhesion test. The results revealed that the flattened chains do not show any adhesion even with the chemically identical free polymer on top, while the loosely adsorbed chains exhibit adhesion. Neutron reflectivity experiments corroborated that the difference in the interfacial adhesion is not attributed to the interfacial brodening at the free polymer-adsorbed polymer interface. Instead, coarse-grained molecular dynamics simulation results suggest that the tail parts of the loosely adsorbed chains act as "connector molecules", bridging the free chains and substrate surface and improving the interfacial adhesion. These findings not only shed light on the structure-property relationship at the interface, but also provide a novel approach for developing sticking/anti-sticking technologies through precise control of the interfacial polymer nanostructures.

Nanoscale adsorbed structures as a robust approach for tailoring polymer film stability.

The stability or wettability of thin polymer films on solids is of vital interest in traditional technologies as well as in new emerging nanotechnologies. We report here that nanoscale structures of polymer chains adsorbed onto a solid surface play a crucial role in the thermal stability of the film. In this study, polystyrene (PS) spin-cast films (20 nm in thickness) with eight different molecular weights prepared on silicon (Si) substrates were used as a model. When low molecular weight (Mw≤ 50 kDa) PS films were subjected to thermal annealing at temperatures far above the bulk glass transition temperature, dewetting occurred promptly, while high molecular weight (Mw≥ 123 kDa) PS films were stable for at least 6 weeks at 150 °C. We reveal a strong correlation between the film stability and the two different interfacial structures of the adsorbed polymer chains: their opposing wettability against chemically identical free polymer chains results in a wetting-dewetting transition at the adsorbed polymer-free polymer interface. This is a unique aspect of the stability of polymer thin films and may be generalizable to other polymer systems regardless of the magnitude of solid-polymer attractive interactions.

Solution-grown 3D Cu2O networks for efficient solar water splitting.

We report a facile and large-scale solution fabrication of cuprous oxide (Cu2O) nanowires/nanorods and 3D porous Cu2O networks and their application as photocathodes for efficient solar water splitting. The growth mechanism and structural characterization of 3D porous Cu2O networks are studied in detail. The photocathodic performance of Cu2O electrodes prepared under different growth conditions is investigated in a pH-neutral medium. The porous Cu2O network photocathodes exhibit large photocurrent, high spectral photoresponse, and incident photon-to-current efficiency compared with Cu2O nanowire/nanorod photoelectrodes. The photoelectrochemical stability of the 3D Cu2O network is significantly improved by applying multi-layer metal oxide protection.

Si photoanode protected by a metal modified ITO layer with ultrathin NiO(x) for solar water oxidation.

We report an ultrathin NiOx catalyzed Si np(+) junction photoanode for a stable and efficient solar driven oxygen evolution reaction (OER) in water. A stable semi-transparent ITO/Au/ITO hole conducting oxide layer, sandwiched between the OER catalyst and the Si photoanode, is used to protect the Si from corrosion in an alkaline working environment, enhance the hole transportation, and provide a pre-activation contact to the NiOx catalyst. The NiOx catalyzed Si photoanode generates a photocurrent of 1.98 mA cm(-2) at the equilibrium water oxidation potential (EOER = 0.415 V vs. NHE in 1 M NaOH solution). A thermodynamic solar-to-oxygen conversion efficiency (SOCE) of 0.07% under 0.51-sun illumination is observed. The successful development of a low cost, highly efficient, and stable photoelectrochemical electrode based on earth abundant elements is essential for the realization of a large-scale practical solar fuel conversion.

Metal oxide composite enabled nanotextured Si photoanode for efficient solar driven water oxidation.

We present a study of a transition metal oxide composite modified n-Si photoanode for efficient and stable water oxidation. This sputter-coated composite functions as a protective coating to prevent Si from photodecomposition, a Schottky heterojunction, a hole conducting layer for efficient charge separation and transportation, and an electrocatalyst to reduce the reaction overpotential. The formation of mixed-valence oxides composed of Ni and Ru effectively modifies the optical, electrical, and catalytic properties of the coating material, as well as the interfaces with Si. The successful application of this oxide composite on nanotextured Si demonstrates improved conversion efficiency due to enhanced catalytic activity, minimized reflection, and increased surface reaction sites. Although the coated nanotextured Si shows a noticeable degradation from 500 cycles of operation, the oxide composite provides a simple method to enable unstable photoanode materials for solar fuel conversion.

Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib.

Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts. Methods: Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8-10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4-9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5-31.2) and CNS disease control rate was 92.0% (95% CI: 74.0-99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4-8.3) and median CNS TTP of 7.1 months (95% CI: 4.4-9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events. Conclusions: Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.

Hidden Flaws Behind Expert-Level Accuracy of Multimodal GPT-4 Vision in Medicine.

Recent studies indicate that Generative Pre-trained Transformer 4 with Vision (GPT-4V) outperforms human physicians in medical challenge tasks. However, these evaluations primarily focused on the accuracy of multi-choice questions alone. Our study extends the current scope by conducting a comprehensive analysis of GPT-4V's rationales of image comprehension, recall of medical knowledge, and step-by-step multimodal reasoning when solving New England Journal of Medicine (NEJM) Image Challenges - an imaging quiz designed to test the knowledge and diagnostic capabilities of medical professionals. Evaluation results confirmed that GPT-4V performs comparatively to human physicians regarding multi-choice accuracy (81.6% vs. 77.8%). GPT-4V also performs well in cases where physicians incorrectly answer, with over 78% accuracy. However, we discovered that GPT-4V frequently presents flawed rationales in cases where it makes the correct final choices (35.5%), most prominent in image comprehension (27.2%). Regardless of GPT-4V's high accuracy in multi-choice questions, our findings emphasize the necessity for further in-depth evaluations of its rationales before integrating such multimodal AI models into clinical workflows.

Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study.

Background: Hong Kong contained COVID-19 for two years but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. We reflected on pandemic preparedness and responses by assessing COVID-19 transmission and associated disease burden in the context of implementation of various public health and social measures (PHSMs). Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing the temporal changes non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults ≥65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic. Funding: Health and Medical Research Fund.

Hospitalizations and mortality during the first year of the COVID-19 pandemic in Hong Kong, China: An observational study.

Background: Hong Kong followed a strict COVID-19 elimination strategy in 2020. We estimated the impact of the COVID-19 pandemic responses on all-cause and cause-specific hospitalizations and deaths in 2020. Methods: Interrupted time-series analysis using negative binomial regression accounting for seasonality and long-term trend was used on weekly 2010-2020 data to estimate the change in hospitalization risk and excess mortality occurring both within and out of hospitals. Findings: In 2020, as compared to a 2010-2019 baseline, we observed an overall reduction in all-cause hospitalizations, and a concurrent increase in deaths. The overall hospitalization reduction (per 100,000 population) was 4809 (95% CI: 4692, 4926) in 2020, with respiratory diseases (632, 95% CI: 607, 658) and cardiovascular diseases (275, 95% CI: 264, 286) contributing most. The overall excess mortality (per 100,000 population) was 25 (95% CI: 23, 27) in 2020, mostly among individuals with pre-existing cardiovascular diseases (12, 95% CI: 11, 13). A reduction in excess in-hospital mortality (-10 per 100,000, 95% CI: -12, -8) was accompanied by an increase in excess out-of-hospital mortality (32, 95% CI: 29, 34). Interpretation: The COVID-19 pandemic might have caused indirect impact on population morbidity and mortality likely through changed healthcare seeking particularly in youngest and oldest individuals and those with cardiovascular diseases. Better healthcare planning is needed during public health emergencies with disruptions in healthcare services. Funding: Health and Medical Research Fund, Collaborative Research Fund, AIR@InnoHK and RGC Senior Research Fellow Scheme, Hong Kong.

Extended gene set analysis of human neuro-psychiatric traits shows enrichment in brain-expressed human accelerated regions across development.

Human neuropsychiatric disorders are associated with genetic and environmental factors affecting the brain, which has been subjected to strong evolutionary pressures resulting in an enlarged cerebral cortex and improved cognitive performance. Thus, genes involved in human brain evolution may also play a role in neuropsychiatric disorders. We test whether genes associated with 7 neuropsychiatric phenotypes are enriched in genomic regions that have experienced rapid changes in human evolution (HARs) and importantly, whether HAR status interacts with developmental brain expression to predict associated genes. We used the most recent publicly available GWAS and gene expression data to test for enrichment of HARs, brain expression, and their interaction. These revealed significant interactions between HAR status and whole-brain expression across developmental stages, indicating that the relationship between brain expression and association with schizophrenia and intelligence is stronger among HAR than non-HAR genes. Follow-up regional analyses indicated that predicted HAR-expression interaction effects may vary substantially across regions and developmental stages. Although depression indicated significant enrichment of HAR genes, little support was found for HAR enrichment among bipolar, autism, ADHD, or Alzheimer's associated genes. Our results indicate that intelligence, schizophrenia, and depression-associated genes are enriched for those involved in the evolution of the human brain. These findings highlight promising candidates for follow-up study and considerations for novel drug development, but also caution careful assessment of the translational ability of animal models for studying neuropsychiatric traits in the context of HARs, and the importance of using humanized animal models or human-derived tissues when researching these traits.

Temporal changes in factors associated with COVID-19 vaccine hesitancy and uptake among adults in Hong Kong: Serial cross-sectional surveys.

Background: COVID-19 vaccine hesitancy can lead to reduced vaccine uptake and hinder the safe relaxation of other public health measures. This study aims to explore the factors associated with vaccine hesitancy and uptake among adults before and after the implementation of the COVID-19 vaccination program in Hong Kong. Methods: Cross-sectional telephone surveys were conducted every four weeks over a nine-month period from November 2020 through July 2021. Target respondents were Hong Kong resident aged 18 or above and recruited by random-digit dialling. In each survey, responses on COVID-19 vaccine hesitancy and COVID-19 vaccine uptake were collected as primary and secondary outcomes, respectively. Data of potentially associated factors, including socio-demographics, chronic medical conditions, perceived risk of COVID-19, perceived personal efficacy in self-protection, confidence in the government's ability to control the pandemic, compliance with social distancing measures, and confidence in COVID-19 vaccines, were also collected. Multivariable logistic regression models were used to examine the factors associated with COVID-19 vaccine hesitancy at different time points. Findings: Ten cross-sectional surveys were conducted, including 7411 respondents. The levels of vaccine hesitancy fluctuated over time. From December 2020 to May 2021, the age group with the highest vaccine hesitancy was young adults 18-34y, while the vaccine hesitancy was highest among adults ≥ 65y in June-July 2021 (Fig. 2C). Our regression analyses (Fig. 3) showed that before and at the beginning of the rollout of the mass vaccination program, there was no statistically significant association between chronic medical conditions and vaccine hesitancy. However, two-five months after the program implementation respondents with chronic medical conditions were more likely to be hesitant. From January to June 2021, higher confidence in the government was associated with lower vaccine hesitancy (Fig. 3). Confidence in COVID-19 vaccines was consistently associated with lower vaccine hesitancy at different stages of the program. Interpretation: The factors associated with COVID-19 vaccine hesitancy changed over time. This study highlighted the importance to monitor temporal changes in COVID-19 vaccine hesitancy and associated factors, and adjust promotion strategies correspondingly to boost vaccination uptake. Funding: Health and Medical Research Fund, Hong Kong.

More than a duologue: In-depth insights into epitranscriptomics and ferroptosis.

Beyond transcription, RNA molecules are enzymatically modified to influence the biological functions of living organisms. The term "epitranscriptomics" describes the changes in RNA strands aside from altering the innate sequences. Modifications on adenosine (A) are the most widely characterized epitranscriptomic modification, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), polyadenylation, and adenosine-to-inosine (A-to-I) RNA editing, and modifications on other nucleotides seem to be fewer, such as N7-methylguanosine (m7G), 5-methylcytosine (m5C), and pseudouridine (Ψ). These changes on the RNA strand surface, exclusively by their RNA-modifying proteins (RMPs), are reported in various biological phenomena, including programmed cell death (PCD). One necro-biological phenomenon that has been observed for long but has started to gain heed in recent years is "ferroptosis." The phospholipid peroxidation by polyunsaturated-fatty-acid-containing-phospholipid hydroperoxyl (PLOOH) radicals destroys membrane integrity due to a series of mechanisms. The Fenton reaction, constituting the final Haber-Weiss reaction that is less recognized, collaboratively leading to the conversion of polyunsaturated fatty acid (PUFA) to PLOOH, is the etymological origin of ferroptosis. However, it is with increasing evidence that ferroptotic signaling is also intervened by epitranscriptomic modifications, although the truth is still ambiguous. We attempted to delineate some up-to-date discoveries on both epitranscriptomics and ferroptosis, bringing up the fundamentals to address any potential connection between the two. Next, we discussed whether a duologal relationship, or more, exists between the two, taking the ROS level and iron status into consideration. Lastly, we surveyed future perspectives that would favor the understanding of these topics.