SMARCA4 mutation induces tumor cell-intrinsic defects in enhancer landscape and resistance to immunotherapy.

Cancer genomic studies have identified frequent alterations in components of the SWI/SNF (SWItch/Sucrose Non- Fermenting) chromatin remodeling complex including SMARCA4 and ARID1A . Importantly, clinical reports indicate that SMARCA4 -mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. However, the mechanistic basis of immunotherapy resistance is unknown. Here, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, we show that SMARCA4 loss caused decreased response to anti-PD1 immunotherapy associated with significantly reduced infiltration of dendritic cells (DCs) and CD4+ T cells into the tumor microenvironment (TME). Mechanistically, we show that SMARCA4 loss in tumor cells led to profound downregulation of STING, IL1ß and other components of the innate immune system as well as inflammatory cytokines that are required for efficient recruitment and activity of immune cells. We establish that this deregulation of gene expression is caused by cancer cell-intrinsic reprogramming of the enhancer landscape with marked loss of chromatin accessibility at enhancers of genes involved in innate immune response such as STING, IL1ß, type I IFN and inflammatory cytokines. Interestingly, we observed that transcription factor NF-κB binding motif was highly enriched in enhancers that lose accessibility upon SMARCA4 deficiency. Finally, we confirmed that SMARCA4 and NF-κB co-occupy the same genomic loci on enhancers associated with STING and IL1ß, indicating a functional interplay between SMARCA4 and NF-κB. Taken together, our findings provide the mechanistic basis for the poor response of SMARCA4 -mutant tumors to anti-PD1 immunotherapy and establish a functional link between SMARCA4 and NF-κB on innate immune and inflammatory gene expression regulation.

The second Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of Helicobacter pylori infection in adult patients in Ireland.

BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Robust PWM control scheme for switched-capacitor MLI with leakage current suppression in grid-connected renewable energy application.

Typically, parasitic capacitances exist between the ground and the solar panel terminals in grid-connected PV systems. These parasitic capacitances provide a path for a leakage current, which leads to significant safety concerns, observable and seriously hazardous harmonic orders aligned with the injected grid current, and significant safety difficulties. In this research, a robust PWM controlling method that used competently in reducing the level of the leakage current and improving the power quality of a switched-capacitor Multilevel Inverter. This technique creates developed reference signals from the main signal to generate the switching scheme for the converter circuit. Additionally, the suggested control strategy only works with a small number of carrier signals, resulting in a quick system response and a simpler controller algorithm. Likewise, this controlling approach offers a stable way to maintain a constant output voltage in the suggested converter by adjusting the switching capacitors' voltages, which is not possible with traditional control techniques. MATLAB/Simulink is used to simulate the outcomes for both the suggested control approach and the traditional Phase Disposition (PD) PWM control method whereas the leakage current component reduces to 25 % compared to the captured component with the PDPWM. The simulation and the practical results based on the dSPACE-1103 hardware are quite similar.

AI analysis of super-resolution microscopy: Biological discovery in the absence of ground truth.

Super-resolution microscopy, or nanoscopy, enables the use of fluorescent-based molecular localization tools to study molecular structure at the nanoscale level in the intact cell, bridging the mesoscale gap to classical structural biology methodologies. Analysis of super-resolution data by artificial intelligence (AI), such as machine learning, offers tremendous potential for the discovery of new biology, that, by definition, is not known and lacks ground truth. Herein, we describe the application of weakly supervised paradigms to super-resolution microscopy and its potential to enable the accelerated exploration of the nanoscale architecture of subcellular macromolecules and organelles.

Improved dehydrogenation performance of LiAlH4 doped with BaMnO3.

Due to its high gravimetric capacity of hydrogen (10.5 wt%), LiAlH4 has been regarded as a promising material for solid-state hydrogen storage material for onboard usage. However, high decomposition temperature, poor kinetics and irreversibility retard its application. To counter this problem, various weight percentages of BaMnO3 are introduced into the LiAlH4 system as an additive in this work. As a result, the starting hydrogen release of LiAlH4 was reduced to 109-115 °C and the second desorption temperature occurred at around 134-158 °C, much lower than pure LiAlH4. The isothermal desorption kinetics also proved that faster desorption kinetics can be observed at 90 °C for 80 min. About 2.00-2.60 wt% of H2 could be desorbed by the composite, whereas only <1.00 wt% of H2 was desorbed by undoped LiAlH4. Additionally, adding BaMnO3 reduced the activation energies by 30 kJ/mol for the first stages and 34 kJ/mol for the second stages. Based on the X-ray diffraction result, the active species formed of MnO2 and Ba or Ba-containing materials are believed to be responsible for the noticeable enhancement in the desorption properties of LiAlH4.

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.

The roles of angiotensin-converting enzyme 2 inhibitor, melatonin and its agonist on angiotensin II reactivity in intact and denuded rat aortic rings.

BACKGROUND: The pineal product melatonin (MEL) modulates blood vessels through G protein-coupled receptors (GPCRs) called melatonin type 1 receptor (MT1R) and melatonin type 2 receptor (MT2R), in that order. The renin-angiotensin system (RAS), which breaks down angiotensin II (Ang II) to create Ang 1-7, is thought to be mostly controlled by angiotensin-converting enzyme-2 (ACE2). AIM: The current work examines the involvement of ACE2 inhibitor, MEL, and ramelteon (RAM) in the vascular response to Ang II activities in the endothelial denuded (E-) and intact (E+) rat isolated thoracic aortic rings. METHOD: The isometric tension was measured to evaluate the vascular Ang II contractility using dose response curve (DRC). RESULTS: MEL and RAM caused a rightward shift of Ang II in endothelium E + and endothelium E- aorta. CONCLUSION: According to the current study, the distribution of MEL receptors and the endothelium's condition are related to the vasomodulatory effect of MEL and ACE2 on Ang II attenuation. These physiological interactions can control vascular tone and increase Ang II reactivity denude endothelial layaer.

Comparison between using inlet circular jet and elliptic jet in combustion chamber by using twin jet flow propane and methanol.

The current work aimed to improve the combustion behavior of a non-premixed twin-jet inlet. The effect of fuel and air inlet shape under different velocities was studied using ANSYS as the process takes place in species transport and finite rate/eddy dissipation, and the flow is considered to be turbulent. Two different shapes (circular-circular and circular-elliptic inlet jets) were investigated, and the results show that the behavior and intensity of the fire are affected by variations in the speed and, geometry of the inlet which affects temperature, heat release rate, combustion efficiency, and equivalent ratios. The optimum air/fuel velocities were found to be 2.5/1.5 with circular-circular inlet jets.

Influence of oxyhydrogen gas retrofit into two-stroke engine on emissions and exhaust gas temperature variations.

The generation of power and fuel sustainability that contributes to a cleaner output of exhaust gases is one of the most important objectives the world seeks. In this paper, oxyhydrogen gas is used to retrofit into a two-stroke engine. The water was electrolysed and generated a mixture of oxygen (O2) and hydrogen (H2) or known as oxyhydrogen (HHO) gas via an electrolytic dry cell generator. The HHO was retrofitted experimentally to investigate the engine emissions and exhaust gas temperature from a 1.5 kW gasoline engine. The engine was tested with different power ratings (84-720 W) to investigate the performance and emissions of the engine using gasoline followed by the addition of HHO. The emissions of CO and NOx were measured with different amounts of HHO added. The exhaust temperature was calculated as one of the variables to be considered in relation to pollution. The air-fuel ratios are varied from 12 to 20% in the experiment. The most appropriate air-fuel ratio needed to start the generator with the most environmentally friendly gas emission was analysed. The results showed that the addition of HHO to the engine is successful in reducing fuel consumption up to 8.9%. A higher percentage of HHO added also has improved the emissions and reduced exhaust gas temperature. In this study, the highest quantity of HHO added at 0.15% of the volume fraction reduced CO gas emission by up to 9.41%, NOx gas up to 4.31%, and exhaust gas temperature by up to 2.02%. Generally, adding oxyhydrogen gas has significantly reduced the emissions, and exhaust temperature and provided an eco-friendly environment.

Phenotypic and genotypic characterization of Escherichia coli isolated from the chicken liver in relation to slaughterhouse conditions.

Avian pathogenic Escherichia coli (APEC) has been identified as a sub-group of extraintestinal pathogenic E. coli (ExPEC). Recent studies indicate APEC as a potential foodborne zoonotic pathogen and a source or reservoir of human extraintestinal infections. The slaughtering and processing of poultry in low-income countries such as Jordan occurs in two distinct ways: in informal facilities known as Natafat and in formal slaughterhouses. This study compared E. coli phenotypes and genotypes according to slaughtering conditions (formal slaughterhouses vs. informal slaughter facilities). Therefore, liver samples (n = 242) were collected from formal (n = 121) and informal slaughter facilities (n = 121). Results revealed a high prevalence (94.2%) of E. coli among all isolates, with 59 (17 formal and 42 informal) isolates considered avian pathogenic E. coli (APEC) based on the virulence-associated genes. The prevalence of resistance among isolates was relatively high, reaching up to 99% against penicillin and 97% against nalidixic acid. However, the prevalence of resistance was the lowest (1.3%) against both meropenem and imipenem. Based on the MIC test findings, colistin resistance was 46.9% (107/228). The mcr -1 gene prevalence was 51.4% (55/107), of which 17.1 % were from formal plants (6/36) and 68.1% from informal facilities (49/72). Interestingly, only one isolate (0.9%) expressed mcr-10. Escherichia coli O157:H7 and associated virulence genes were found more in informal (n = 15 genes) than in formal slaughterhouses (n = 8). Phylogroups B1, C, and A were the most frequent in 228 E. coli isolates, while G, B2, and clade were the least frequent. In conclusion, these findings highlight the importance of implementing biosecurity measures in slaughterhouses to reduce antibiotic-resistant E. coli spread. Furthermore, this study provides valuable insights into the effects of wet market (Natafat) slaughter conditions on increasing bacterial resistance and virulence.

Basic Overview of Conventional Coronary Angiography for Planning Cardiac Surgery.

Coronary angiography is a common procedure performed by the cardiologist to evaluate coronary atherosclerotic disease (CAD) and the result is utilized by both cardiologists and cardiac surgeons to perform catheter and surgical interventions on the coronary artery. In addition to evaluating CAD, other useful investigative modalities such as left ventriculography and aortography can be performed at the time of coronary angiography. Despite its limitations and the emergence of newer investigative modalities like coronary computed tomography angiography, intravascular ultrasound scan, and magnetic resonance coronary angiography, conventional coronary angiography has remained the gold standard for the evaluation of coronary artery disease. Hence, it remains an investigative modality that every member of the cardiothoracic team performing coronary artery bypass grafting must learn how to interpret.

Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Dispersant-enhanced migration of radiocesium among soil size fractions: A novel strategy for volume reduction of radioactively contaminated soil.

In the aftermath of the Fukushima Daiichi Nuclear Power Plant accident, a pioneering large-scale decontamination project was initiated, aiming to enable the return of evacuees. This project, the first of its kind in human history, involved the transportation of soils collected during decontamination to interim storage facilities. Before recycling or disposal, these soils undergo processes like volume reduction. However, there's a need for innovative methods to reduce volume effectively and treat secondary wastes more efficiently. The current study explores the impact of a dispersant, sodium hexametaphosphate (SHMP), on the behavior of radiocesium (r-Cs: 137Cs) dynamics in different size fractions of radioactively contaminated soils from Fukushima. The solid-phase speciation analysis of Fukushima soils validated that at least 50% of the 137Cs or other minerals are associated with difficult-to-extract soil phases. Nonetheless, the low 137Cs/133Cs ratio in corresponding soil phases implies a slower r-Cs fixation mechanism. The wet-sieving of r-Cs contaminated soil fraction, < 2 mm, with SHMP, resulted in different soil subfractions (2000-212, 212-53, and < 53 µm). Following SHMP treatment, dispersion of > 92% of 137Cs associated with < 212 µm soil size fractions was observed. The migration of 137Cs towards smaller soil size fractions can be attributed to either SHMP-induced cation exchange or the formation of polyvalent complexes involving SHMP and soil minerals. The condensation of 137Cs in < 212 µm, as induced by SHMP, enabled the subsequent reuse of the larger soil fraction (> 212 µm), which was less contaminated. This study provides a new perspective on the effects of dispersants and contributes to a better understanding of the complex interactions among organic carbon, 137Cs, monovalent and polyvalent cations, and soil functional groups concerning the volume reduction of soils contaminated with r-Cs.

Epidemiology of Clostridioides difficile infection at a tertiary care facility in Saudi Arabia: Results of prospective surveillance.

OBJECTIVES: To determine the incidence of Clostridioides difficile infection (CDI) and the frequency of known risk factors. METHODS: A prospective hospital-based surveillance for CDI, according to the Centers for Disease Control and Prevention criteria, was carried out from July 2019 to March 2022 for all inpatients aged more than one year in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. RESULTS: A total of 139 cases of CDI were identified during the survey among 130 patients admitted in the hospital. Most cases were incident (n=130; 93.5%), and almost three-quarters (n=102; 73.4%) were hospital-onset (HO) CDI, with an incidence rate of 1.62 per 10,000 patient days (PD). The highest rates were noted in intensive care units with an incidence rate of 3 per 10,000 PD and wards for immunocompromised patients with an incidence rate of 2.72 per 10,000 PD. The most prevalent risk factor for CDI was acid-reducing drugs (72.6%). Vancomycin (48%) and ciprofloxacin (25%) were the most frequently prescribed antibiotics for patients with CDI. Clostridioides difficile infection complications were identified in 5.7% of the cases, with a reported 28-day mortality rate of 3.8%. CONCLUSION: In our hospital, HO-CDI incidence rate is lower than that in high-income countries. National multicenter surveillance is needed to evaluate the actual burden of CDI in Saudi Arabia.

Efficiency of Electronic Nose in Detecting the Microbial Spoilage of Fresh Sardines (Sardinella longiceps).

The assessment of microbial spoilage in fresh fish is a major concern for the fish industry. This study aimed to evaluate the efficiency and reliability of an electronic nose (E-nose) to detect microbial spoilage of fresh sardines (Sardinella longiceps) by comparing its measurements with Total Bacterial Count (TBC), Hydrogen Sulfide (H2S) producing bacterial count and Trimethylamine Oxide (TMAO) reducing bacterial count after variable storage conditions. The samples were stored at 0 °C (0, 2, 4, 6, and 8 days) and 25 °C (0, 3, 6, and 9 h), while day 0 was used as a control. The E-nose measurements were analyzed by Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA) and Artificial Neural Network (ANN). Microbial counts increased significantly and simultaneously with the changes in E-nose measurements during storage. The LDA and ANN showed a good classification of E-nose data for different storage times at two storage temperatures (0 °C and 25 °C) compared to PCA. It is expected as PCA is based on linear relationships between the factors, while ANN is based on non-linear relationships. Correlation coefficients between E-nose and TBC, TMAO-reducing bacterial and H2S-producing bacterial counts at 0 °C were 0.919, 0.960 and 0.915, respectively, whereas at 25 °C, the correlation coefficients were 0.859, 0.945 and 0.849, respectively. These positive correlations qualify the E-nose as an efficient and reliable device for detecting microbial spoilage of fish during storage.

Study of the effect of implantation temperature on the migration behaviour of Xe implanted into glassy carbon.

The effect of implantation temperature on the migration behaviour of xenon (Xe) implanted into glassy carbon and the effect of annealing on radiation damage retained by ion implantation were investigated. Glassy carbon substrates were implanted with 320 keV Xe+ to a fluence of 2 × 1016 cm-2. The implantation process was performed at room temperature (RT) and 100 °C Some of the as-implanted samples were isochronally annealed in vacuum at temperatures ranging from 300 °C to 700 °C in steps of 100 °C for 10 h. The as-implanted and annealed samples were characterized using Rutherford backscattering spectrometry (RBS) and Raman spectroscopy. The RT implanted depth profiles indicated that the migration of Xe towards the surface of glassy carbon was accompanied by a loss of Xe ions. The samples implanted at 100 °C indicated no diffusion or loss of Xe after annealing at 300 °C. However, annealing at temperatures ranging from 400 °C to 700 °C resulted in a slight shift in the Xe profile tail-end towards the bulk of glassy carbon. The diffusion coefficients (D) in the temperature range of 300 °C-700 °C for the RT and 100 °C implanted samples, activation energies (Ea), and pre-exponential factors (Do), were extracted. The values of D ranged from (9.72 ± 0.48) × 10-21 to (1.87 ± 0.09) × 10-20 m2/s with an activation energy of (6.25 ± 0.31) × 10-5 eV for RT implanted samples, and the samples implanted at 100 °C, D ranged from (3.85 ± 0.19) × 10-21 to (6.96 ± 0.34) × 10-20 m2/s with activation energy of (4.10 ± 0.02) × 10-5 eV. The Raman analysis revealed that implantation at the RT amorphised the glassy carbon structure while the samples implanted at 100 °C showed mild damage compared to RT implantation. Annealing of the RT-implanted sample resulted in some recovery of the damaged region as a function of increasing annealing temperature.

Optimisation of virtual monoenergetic reconstructions for the diagnosis of pulmonary embolism using photon-counting detector computed tomography angiography.

Purpose: Computed tomography (CT) pulmonary angiography is considered the gold standard for pulmonary embolism (PE) diagnosis, relying on the discrimination between contrast and embolus. Photon-counting detector CT (PCD-CT) generates monoenergetic reconstructions through energy-resolved detection. Virtual monoenergetic images (VMI) at low keV can be used to improve pulmonary artery opacification. While studies have assessed VMI for PE diagnosis on dual-energy CT (DECT), there is a lack of literature on optimal settings for PCD-CT-PE reconstructions, warranting further investigation. Material and methods: Twenty-five sequential patients who underwent PCD-CT pulmonary angiography for suspicion of acute PE were retrospectively included in this study. Quantitative metrics including signal-to-noise ratio (SNR) and contrast-to-noise (CNR) ratio were calculated for 4 VMI values (40, 60, 80, and 100 keV). Qualitative measures of diagnostic quality were obtained for proximal to distal pulmonary artery branches by 2 cardiothoracic radiologists using a 5-point modified Likert scale. Results: SNR and CNR were highest for the 40 keV VMI (49.3 ± 22.2 and 48.2 ± 22.1, respectively) and were inversely related to monoenergetic keV. Qualitatively, 40 and 60 keV both exhibited excellent diagnostic quality (mean main pulmonary artery: 5.0 ± 0 and 5.0 ± 0; subsegmental pulmonary arteries 4.9 ± 0.1 and 4.9 ± 0.1, respectively) while distal segments at high (80-100) keVs had worse quality. Conclusions: 40 keV was the best individual VMI for the detection of pulmonary embolism by quantitative metrics. Qualitatively, 40-60 keV reconstructions may be used without a significant decrease in subjective quality. VMIs at higher keV lead to reduced opacification of the distal pulmonary arteries, resulting in decreased image quality.

Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID).

BACKGROUND: Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. METHODS: A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the 'exposed cohorts' and 'reference cohort' was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. RESULTS: Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final 'matched' analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3-120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9-21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. CONCLUSIONS: Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.