A tabular data generation framework guided by downstream tasks optimization.

Recently, generative models have been gradually emerging into the extended dataset field, showcasing their advantages. However, when it comes to generating tabular data, these models often fail to satisfy the constraints of numerical columns, which cannot generate high-quality datasets that accurately represent real-world data and are suitable for the intended downstream applications. Responding to the challenge, we propose a tabular data generation framework guided by downstream task optimization (TDGGD). It incorporates three indicators into each time step of diffusion generation, using gradient optimization to align the generated fake data. Unlike the traditional strategy of separating the downstream task model from the upstream data synthesis model, TDGGD ensures that the generated data has highly focused columns feasibility in upstream real tabular data. For downstream task, TDGGD strikes the utility of tabular data over solely pursuing statistical fidelity. Through extensive experiments conducted on real-world tables with explicit column constraints and tables without explicit column constraints, we have demonstrated that TDGGD ensures increasing data volume while enhancing prediction accuracy. To the best of our knowledge, this is the first instance of deploying downstream information into a diffusion model framework.

Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.

Lynch syndrome (LS) is defined by inherited mutations in DNA mismatch repair genes, including MSH2, and carries 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, specific mechanisms for LS-associated endometrial carcinogenesis are not well understood. Here, we assessed the effects of MSH2 loss on EC pathogenesis using a novel mouse model (PR-Cre Msh2 flox/flox , abbreviated Msh2KO), primary cell lines established from this model, human tissues, and human EC cell lines with isogenic MSH2 knockdown. Beginning at eight months of age, 30% of Msh2KO mice exhibited endometrial atypical hyperplasia (AH), a precancerous lesion. At 12 to 16 months of age, 47% of Msh2KO mice exhibited either AH or ECs with histologic features similar to human LS-related ECs. Transcriptomic profiling of EC from Msh2KO mice revealed a transcriptomic signature for mitochondrial dysfunction. Studies in vitro and in vivo revealed mitochondrial dysfunction based upon two mechanisms: marked mitochondrial content reduction, along with pronounced disruptions to the integrity of retained mitochondria. Human LS-related ECs also exhibited mitochondrial content reduction compared with non-LS-related ECs. Functional studies revealed metabolic reprogramming of MSH2-deficient EC cells in vitro , including reduced oxidative phosphorylation and increased susceptibility to glycolysis suppression. We are the first to identify mitochondrial dysfunction and metabolic disruption as a consequence of MSH2 deficiency-related EC. Mitochondrial and metabolic aberrations should be evaluated as novel biomarkers for endometrial carcinogenesis or risk stratification and could serve as targets for cancer interception in women with LS. Significance: This is the first study to report mitochondrial dysfunction contributing to MSH2-deficient endometrial cancer development, identifying a noncanonical pathway for MSH2 deficient carcinogenesis, which also imparts vulnerability to metabolic targeting.

Visualizing nanoscale heterogeneity in perylene thin films via tip-enhanced photoluminescence with unsupervised machine learning.

We investigate the properties of ultrathin 3,4,9,10-perylenetetracarboxylic diimide (PTCDI) films using a combination of tip-enhanced photoluminescence and unsupervised machine learning. We expose nanoscale spectral heterogeneities that can be understood on the basis of the interplay between vibronic effects, intermolecular excitons, and intramolecular excitons in PTDCI films.

CWF19L2 is Essential for Male Fertility and Spermatogenesis by Regulating Alternative Splicing.

The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre-mRNA alternative splicing (AS) at the post-transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA-seq and LACE-seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre-mRNA splicing during the early steps of spermatogenesis.

Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity: a territory-wide target trial emulation.

BACKGROUND: Older adults with multimorbidity are at high risk of mortality following COVID-19 hospitalisation. However, the potential benefit of timely primary care follow-up on severe outcomes post-COVID-19 has not been well established. AIM: To examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged ≥85 years, with multimorbidity. METHOD: We emulated a target trial using a comprehensive public healthcare database in Hong Kong. The cloning-censoring-weighting technique was used to minimise immortal time bias and confounding bias by adjusting for demographics, hospitalisation duration and ICU admission, baseline chronic conditions, and medication history. The outcome included all-cause and cause-specific mortality. RESULTS: Of 6183 eligible COVID-19 survivors, the all-cause mortality rate following COVID-19 hospitalisation was lower in general out-patient clinics (GOPC) group compared to non-GOPC group (17.1 versus 42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI = 8.1% to 14.4%). We also observed better survival from respiratory diseases in the GOPC group. In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a GOPC visit after COVID-19 discharge, the better the survival. CONCLUSION: Timely primary care consultations after discharge may improve survival following COVID-19 hospitalisation among older adults aged ≥85 years, with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Optimising Transitional Care Following a Heart Failure Hospitalisation in Australia.

Hospitalisations for heart failure (HF) are associated with high rates of readmission and death, the most vulnerable period being within the first few weeks post-hospital discharge. Effective transition of care from hospital to community settings for patients with HF can help reduce readmission and mortality over the vulnerable period, and improve long-term outcomes for patients, their family or carers, and the healthcare system. Planning and communication underpin a seamless transition of care, by ensuring that the changes to patients' management initiated in hospital continue to be implemented following discharge and in the long term. This evidence-based guide, developed by a multidisciplinary group of Australian experts in HF, discusses best practice for achieving appropriate and effective transition of patients hospitalised with HF to community care in the Australian setting. It provides guidance on key factors to address before and after hospital discharge, as well as practical tools that can be used to facilitate a smooth transition of care.

Prevalence and correlates of depression, anxiety and trauma-like symptoms in Chinese psychiatric patients during the fifth wave of COVID-19 pandemic: a cross-sectional study in Hong Kong.

BACKGROUND: Psychiatric patients are susceptible to adverse mental health outcome during COVID-19 pandemic, but its associated factors are understudied. This observational cross-sectional study aimed to comprehensively examine prevalence and correlates of psychological distress, in terms of depression, anxiety and post-traumatic-stress-disorder (PTSD)-like symptoms, among Chinese adult psychiatric outpatients amidst the peak of fifth COVID-19 wave in Hong-Kong. METHODS: A total of 415 patients (comprising 246 patients with common-mental-disorders [CMD] and 169 with severe-mental-disorders [SMD]) and 399 demographically-matched controls without mental disorders were assessed with self-rated questionnaires between 28-March and 8-April-2022, encompassing illness profile, mental health symptoms, psychosocial measures (loneliness, resilience, coping styles) and COVID-19 related factors. Univariate and multivariable logistic regression analyses were conducted to determine variables associated with moderate-to-severe depressive, anxiety and PTSD-like symptoms among psychiatric patients. RESULTS: Our results showed that CMD patients had the greatest psychological distress relative to SMD patients and controls. Approximately 40-55% CMD patients and 25% SMD patients exhibited moderate-to-severe depression, anxiety and PTSD-like symptoms. Multivariable regression analyses revealed that female gender, lower educational attainment, single marital status, being housewife, more severe insomnia, psychotic-like symptoms and cognitive complaints, self-harm behavior, lower resilience, avoidance coping, never contracting COVID-19 infection, greater fear of contagion, and longer exposure to pandemic-related information were independently associated with depression, anxiety and/or PTSD-like symptoms in psychiatric patients. CONCLUSIONS: Our results affirm increased vulnerability of psychiatric patients toward psychological distress during pandemic. An array of identified correlates facilitates early detection of high-risk psychiatric patients for targeted strategies to minimize pandemic-related negative psychological impact.

Individual and Interactive Effects of Housing and Neighborhood Quality on Mental Health in Hong Kong: A Retrospective Cohort Study.

Existing literature has widely explored the individual roles of housing and neighborhood quality, and there is limited research examining their interactive effects on mental health. This 3-year cohort study utilized a longitudinal design to investigate the individual and interactive effects of housing and neighborhood quality on mental health among 962 community-dwelling adults in Hong Kong. Participants were asked to rate their residential qualities over the 3-year period. Mental health outcomes, including levels of psychological distress and common mental disorders (CMD), were assessed using the Revised Clinical Interview Schedule (CIS-R). Logistic regression and generalized linear models were used to examine the association between housing and neighborhood quality and CMD/psychological distress, adjusting for sociodemographic and residential characteristics and baseline mental disorders. Housing quality was associated with the 3-year CMD (adjusted OR 0.95; 95% CI 0.91 to 0.98). Likewise, neighborhood quality was associated with CMD over 3 years (adjusted OR 0.92; 95% CI 0.87 to 0.96). In a separate model including both quality measures, the effect of housing quality on CMD was attenuated, whereas the neighborhood impact remained significant (adjusted OR 0.92; 95% CI 0.87 to 0.98). Generalized linear models indicated that for participants residing in substandard housing, those with high neighborhood quality had lower CIS-R scores at follow-up compared to those with low neighborhood quality (p = 0.041). Better neighborhood quality alleviated the detrimental effects of poor housing quality on mental health. Planning for an enhanced neighborhood would improve population mental health in an urban environment.

Environmental stress and emotional reactivity: an exploratory experience sampling method study.

Background: Previous studies have shown a relationship between environments and mental health. However, limited studies have investigated the impact of environment stress (ES) on emotional reactivity. Our study aimed to fill this gap by examining how daily ES affects momentary emotional reactivity using experience sampling method (ESM). Methods: Participants were randomly recruited from a prospective cohort study in Hong Kong to participate in a 7-day ESM study. The participants received eight electronic signals daily assessing their ES, positive affect (PA) and negative affect (NA). Participants were categorized into depressed group or control group based on Revised Clinical Interview Schedule. Psychometric properties of the ESM assessment were evaluated. Multilevel linear regression analyzes were conducted to examine the association of ES with PA, NA and the group status of the participants (cases versus controls). Results: A total of 15 participants with depression and 15 healthy controls were recruited, and 1307 momentary assessments were completed with a compliance rate of 77.8%. The depressed group demonstrated a significant increase in NA in response to ES, while the control group showed a decrease in PA. In addition, the depressed group reported a lower perception of control and interaction with their environment compared to the control group. Conclusion: Using ESM, a valid, reliable, and easy-to-use self-reporting tool, our findings provided valuable insights on the potential mechanisms underlying emotional responses to stressful environments.

Endothermic Charge Separation Occurs Spontaneously in Non-Fullerene Acceptor/Polymer Bulk Heterojunction.

Organic photovoltaics (OPVs) based on non-fullerene acceptors (NFAs) have achieved a power conversion efficiency close to 20%. These NFA OPVs can generate free carriers efficiently despite a very small energy level offset at the donor/acceptor interface. Why these NFAs can enable efficient charge separation (CS) with low energy losses remains an open question. Here, the CS process in the PM6:Y6 bulk heterojunction is probed by time-resolved two-photon photoemission spectroscopy. It is found that the CS, the conversion from bound charge transfer (CT) excitons to free carriers, is an endothermic process with an enthalpy barrier of 0.15 eV. The CS can occur spontaneously despite being an endothermic process, which implies that it is driven by entropy. It is further argued that the morphology of the PM6:Y6 film and the anisotropic electron delocalization restrict the electron and hole wavefunctions within the CT exciton such that they can primarily contact each other through point-like junctions. This configuration can maximize the entropic driving force.

Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment.

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.

The modulation effect of cognition on mentalization in late-life depression: a study of gaze perception-a potential screening tool for high-risk group of late-life depression.

Introduction: Impairment in mentalization is implicated in the development and maintenance of depression. Major depressive disorders showed significant impairment in social cognition and such impairment appears to be positively associated with the severity of depression. Self-referential gaze perception (SRGP), a measurement of mentalization, was predominantly measured in patients with psychosis but rarely examined in late-life depression (LLD). Methods: To assess the effect of cognition on the interpretation bias of mentalization, 29 LLD patients and 29 healthy controls were asked to judge if various gaze directions were directed to self in SRGP. Results: Patients with better cognition showed less unambiguous-SRGP bias than those with worse cognitive scores; this difference was not found in healthy controls. Global cognition and executive function contributed to the SRGP rate in patients. Conclusion: The current study is the first study to explore the relationship between cognition and SRGP in the LLD population. Our study findings suggested that the cognitive function of LLD patients may contribute to the modulation of interpretation bias, which in turn underlie the role of SRGP bias. Greater SRGP bias in patients may reflect social cognition deterioration, impairing the social interaction and functioning of LLD patients. This highlights the need for early intervention and cognitive decline identification to facilitate better prognosis and treatment effectiveness; thus, further studies could navigate the potential of SRGP task as a screening tool for high-risk group of LLD likely to develop dementia.

The single-cell chromatin landscape in gonadal cell lineage specification.

Gonad development includes sex determination and divergent maturation of the testes and ovaries. Recent advances in measuring gene expression in single cells are providing new insights into this complex process. However, the underlying epigenetic regulatory mechanisms remain unclear. Here, we profiled chromatin accessibility in mouse gonadal cells of both sexes from embryonic day 11.5 to 14.5 using single-cell assay for transposase accessible chromatin by sequencing (scATAC-seq). Our results showed that individual cell types can be inferred by the chromatin landscape, and that cells can be temporally ordered along developmental trajectories. Integrative analysis of transcriptomic and chromatin-accessibility maps identified multiple putative regulatory elements proximal to key gonadal genes Nr5a1, Sox9 and Wt1. We also uncover cell type-specific regulatory factors underlying cell type specification. Overall, our results provide a better understanding of the epigenetic landscape associated with the progressive restriction of cell fates in the gonad.

Automatic detection of cardiac conditions from photos of electrocardiogram captured by smartphones.

BACKGROUND: Researchers have developed machine learning-based ECG diagnostic algorithms that match or even surpass cardiologist level of performance. However, most of them cannot be used in real-world, as older generation ECG machines do not permit installation of new algorithms. OBJECTIVE: To develop a smartphone application that automatically extract ECG waveforms from photos and to convert them to voltage-time series for downstream analysis by a variety of diagnostic algorithms built by researchers. METHODS: A novel approach of using objective detection and image segmentation models to automatically extract ECG waveforms from photos taken by clinicians was devised. Modular machine learning models were developed to sequentially perform waveform identification, gridline removal, and scale calibration. The extracted data were then analysed using a machine learning-based cardiac rhythm classifier. RESULTS: Waveforms from 40 516 scanned and 444 photographed ECGs were automatically extracted. 12 828 of 13 258 (96.8%) scanned and 5399 of 5743 (94.0%) photographed waveforms were correctly cropped and labelled. 11 604 of 12 735 (91.1%) scanned and 5062 of 5752 (88.0%) photographed waveforms achieved successful voltage-time signal extraction after automatic gridline and background noise removal. In a proof-of-concept demonstration, an atrial fibrillation diagnostic algorithm achieved 91.3% sensitivity, 94.2% specificity, 95.6% positive predictive value, 88.6% negative predictive value and 93.4% F1 score, using photos of ECGs as input. CONCLUSION: Object detection and image segmentation models allow automatic extraction of ECG signals from photos for downstream diagnostics. This novel pipeline circumvents the need for costly ECG hardware upgrades, thereby paving the way for large-scale implementation of machine learning-based diagnostic algorithms.

A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

Characterization of the Tissue and Strain-Specific Microbiota of Anopheles funestus Giles (Diptera: Culicidae).

The mosquito microbiota is a critical determinant of mosquito life history. It is therefore a target for novel vector control strategies like paratransgenesis. However, the microbiota in Anopheles funestus, a major African malaria vector, is poorly characterized. Thus, the study aimed to investigate the overall bacterial landscape in the salivary glands, ovaries and midguts of three laboratory strains of An. funestus differing in insecticide-resistant phenotype by sequencing the V3-V4 hypervariable region of bacterial 16S rRNA genes. When examining alpha diversity, the salivary glands harbored significantly more bacteria in terms of species richness and evenness compared to ovaries and midguts. On the strain level, the insecticide-susceptible FANG strain had significantly lower bacterial diversity than the insecticide-resistant FUMOZ and FUMOZ-R strains. When looking at beta diversity, the compositions of microbiota between the three tissues as well as between the strains were statistically different. While there were common bacteria across all three tissues and strains of interest, each tissue and strain did exhibit differentially abundant bacterial genera. However, overall, the top five most abundant genera across all tissues and strains were Elizabethkingia, Acinetobacter, Aeromonas, Cedecea and Yersinia. The presence of shared microbiota suggests a core microbiota that could be exploited for paratransgenesis efforts.

An outbreak of Burkholderia cepacia complex exit site infection among peritoneal dialysis patients caused by contaminated spray dressing.

Background: Wound dressing is intended to provide a physical barrier from microorganisms. Spray dressing is convenient and can be applied to wounds of various contours. In July 2020, a cluster of four Burkholderia cepacia complex (BCC) exit site infections was identified among peritoneal dialysis patients in a regional hospital in Hong Kong. In response, our hospital infection control team conducted an epidemiologic investigation. Methods: We conducted a retrospective cohort study of peritoneal dialysis patients with culture-confirmed BCC exit site infections from January 2011 to July 2020. Outbreak investigations, including case finding, molecular typing and post-outbreak surveillance, were performed. Discussion: A substantial increase in BCC exit site infections has been observed since 2013, rising from 0.23 in 2012 to 1.09 episodes per 100 patient-year in 2015, with the number of cases in the first half of 2020 already surpassing the total from 2019. The potential source had been traced to a spray dressing introduced to exit site care in December 2012. Burkholderia cepacia complex was isolated from both the unopened and in-use sprays from the same lot. Multilocus sequence typing analysis confirmed their genetic relatedness. The spray dressing was subsequently removed from exit site care. Post-outbreak surveillance over two years showed a marked and sustained decrease in BCC exit site infection. Conclusion: Water-based spray dressing can be a source of BCC causing wound infections. The use of contaminated spray dressing, especially in chronic wounds with proximity to indwelling catheters, may pose an inherent risk to patients.

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

BACKGROUND: Psychiatric patients are susceptible to adverse mental health impacts during COVID-19, but complex interplays between psychopathology and pandemic-related variables remain elusive. This study aimed to investigate concomitant associations between psychopathological symptoms, psychological measures and COVID-19 related variables in Chinese psychiatric patients during the peak of fifth pandemic wave in Hong Kong. METHODS: We employed network analysis to investigate inter-relationships among psychopathological symptoms (including depression, anxiety, post-traumatic stress disorder-like [PTSD-like] symptoms, insomnia, psychotic symptoms), cognitive complaints, health-related quality of life, loneliness, resilience and selected pandemic-related factors in 415 psychiatric outpatients between 28 March and 8 April, 2022. Network comparisons between genders, diagnosis (common mental disorders [CMD] vs. severe mental disorders [SMD]), and history of contracting COVID-19 at fifth wave were performed as exploratory analyses. RESULTS: Our results showed that anxiety represented the most central node in the network, as indicated by its highest node strength and expected influence, followed by depression and quality of life. Three comparatively strong connections between COVID-19 and psychopathological variables were observed including: fear of contagion and PTSD-like symptoms, COVID-19 stressor burden and PTSD-like symptoms, and COVID-19 stressor burden and insomnia. Network comparison tests revealed significant network structural difference between participants with history of contracting COVID-19 and those without, but showed no significant difference between genders as well as between CMD and SMD patients. CONCLUSIONS: Our findings suggest the pivotal role of anxiety in psychopathology network of psychiatric patients amidst COVID-19. Pandemic-related variables are critically associated with trauma/stress and insomnia symptoms. Future research is required to elucidate potential network structural changes between pandemic and post-COVID periods.