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Background: This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug., Methods and Results: Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P =0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P =0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding., Conclusions: Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

A flexible approach is described for incorporating a weight-of-evidence (WoE) methodology into a tiered ecological risk assessment (ERA)/management framework for chemicals. The approach is oriented toward informing decisions about chemicals. Communication is regarded as a critical component of the risk assessment process. The paper resulted from insights gained from seven ERA workshops held by SETAC (Society of Environmental Toxicology and Chemistry, www.setac.org) in the Asia-Pacific, African, and Latin American regions. Formal ERA methods are not fully developed or applied in many of these countries and assessments often begin with tables of risk values and test methods from countries where ERA is already implemented. While appropriate and sometimes necessary, workshop participants had questions about the reliability and relevance of using this information for regionally specific ecosystems with different receptors, fate processes, and exposure characteristics. The idea that an assessment of reliability and relevance of available information and the need for additional information was necessary at an early stage of the assessment process was considered. The judgment of reliability and relevance is central to WoE approaches along with the identification of information needs and the integration of such information. The need to engage in WoE considerations early and throughout the assessment process indicates that a tiered approach is appropriate for unifying the evaluation process in a consistent way from early screening-level steps to later more involved evaluations. The approach outlined in this article is complementary to WoE guidance developed by the Organization for Economic Co-operation and Development and many national guidance documents. To link assessments of risk to management decisions, emphasis is given to communications at each tier between the risk assessor (technical side) and the decision-makers (policy and regulatory side). Tools and information sources are suggested for each tier and suggestions are meant to be illustrative and not prescriptive. Integr Environ Assess Manag 2024;20:2312-2325. © 2024 SETAC., (© 2024 SETAC.)

Heat-health warning systems and services are important preventive actions for extreme heat, however, global evidence differs on which temperature indicator is more informative for heat-health outcomes. We comprehensively assessed temperature predictors on their summer associations with adverse health impacts in a high-density subtropical city. Maximum, mean, and minimum temperatures were examined on their associations with non-cancer mortality and hospital admissions in Hong Kong during summer seasons 2010-2019 using Generalized Additive Models and Distributed Lag Non-linear Models. In summary, mean and minimum temperatures were identified as strong indicators for mortality, with a relative risk(RR) and 95% confidence interval(CI) of 1.037 (1.006-1.069) and 1.055 (1.019-1.092), respectively, at 95th percentile vs. optimal temperature. Additionally, minimum temperatures captured the effects of hospital admissions, RR1.009 (95%CI: 1.000- 1.018). In stratified analyses, significant associations were found for older adults, female sex, and respiratory-related outcomes. For comparison, there was no association between maximum temperature and health outcomes. With climate change and projected increase of night-time warming, the findings from this comprehensive assessment method are useful to strengthen heat prevention strategies and enhance heat-health warning systems. Other locations could refer to this comprehensive method to evaluate their heat risk, especially in highly urbanized environments and subtropical cities., (© 2024. The Author(s).)

A solid-state synthesis of blue-emitting lead halide nanoclusters has been demonstrated for the first time. The solid-state grinding synthesis provides a facile method to produce highly confined lead bromide clusters under ambient conditions. Both CH 3 NH 3 PbBr 3 perovskite magic-sized clusters and lead halide molecular clusters have been produced, as confirmed by comparison to those synthesized using a ligand-assisted reprecipitation method in terms of electronic absorption, photoluminescence, and solid state characterization.

We proposed a more realistic albeit slightly complicated multilayer Ti 3 C 2 T x model and performed a comprehensive theoretical study of its structural and electronic properties. In this work, we constructed various multilayer Ti 3 C 2 T x structures considering different concentrations of hydrofluoric acid (HF; 5, 10, and 48 wt%) as the etchant. The validity of our ternary mixed O/OH/F-terminated Ti 3 C 2 T x multilayer models is confirmed by the consistency of the calculated d -spacing (9.60 ± 0.07 Å), simulated X-ray diffraction (XRD) spectra and the predicted adhesion energy (0.77 ± 0.15 J m -2 ) with the reported experimental measurements. The uniform terminated and mixed terminated multilayer Ti 3 C 2 T x exhibit metallic characteristics, similar to those of monolayer Ti 3 C 2 T x . We found a stronger interaction between the interlayers with OH-rich ternary mixed terminated Ti 3 C 2 T x surfaces, due to the formation of hydrogen bonds between the hydroxyl groups and adjacent layers of F/O terminal groups as supported by the crystal orbital Hamilton population (COHP) calculation. From this finding, we propose that multilayer Ti 3 C 2 T x etched with a strong HF acid could be easily exfoliated into monolayer sheets due to smaller adhesion energy. Based on this work, we believe that the current findings will offer a fundamental understanding and a useful baseline multilayer model for the future investigation of the hydrogen and ion storage and diffusion properties in the MXene multilayer application.

Background: The COVID-19 pandemic has led to decreased measles vaccination rates globally, exacerbating vaccine hesitancy. This study examines the relationship between COVID-19 vaccine acceptance and childhood measles vaccination among parents in Hong Kong., Methods: A cross-sectional online survey was conducted in Hong Kong from March to September 2022. Parents were recruited via the Qualtrics panel, and a total of 588 parents were invited via email or social media account to participate in the survey. We used the adjusted Measles-containing Vaccine Hesitancy Scale for the assessment of parental vaccine hesitancy for children. A multiple linear regression analysis was conducted to examine the association between parental acceptance of the COVID-19 vaccine and their attitudes towards childhood measles vaccination., Results: Of the 588 participants, parents who have been vaccinated against COVID-19 exhibited significantly less measles-containing vaccine hesitancy comparing to those unvaccinated (β = -2.96, 95% confidence interval [CI]: -5.10 to -0.83, p = 0.007). Mothers exhibited more hesitancy compared to fathers (β = 1.64, 95% CI: 0.60 to 2.68, p = 0.002). Parents with a higher self-rated health (β = -2.20, 95% CI: -3.21 to -1.20, p < 0.001), or who have received advice from health professionals to offer measles, influenza, or COVID-19 vaccines for kids (β = -2.41, 95% CI: -3.49 to -1.32, p < 0.001) had lower levels of hesitancy., Conclusion: COVID-19 vaccine status of parents was associated with reduced hesitancy towards measles vaccines for their children. Addressing vaccine hesitancy effectively requires targeted communication strategies, particularly focusing on those unvaccinated and leveraging the influence of healthcare professionals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: As the SARS-CoV-2 virus evolves more rapidly than vaccines are updated, T cell immunity potentially confers protection against disease progression and death from new variants. In this study, we aimed to assess whether the current boosting vaccination schemes offer sufficient T cell protection against new SARS-CoV-2 variants., Methods: . 292 adults who had received the second booster of either monovalent wild type vaccines (inactivated virus or mRNA) (cohort 1) or the second/third booster of bivalent WT/BA.4-5 mRNA vaccine (cohort 2) were recruited in Hong Kong. All participants showed no serological evidence of recent infection of SARS-CoV-2. Blood samples of each participant were collected before and one-month after receiving the booster. T cell and antibody responses were determined by flow cytometry and neutralization test respectively., Results: . Among all vaccination strategies, only the adults who had received the bivalent vaccine as the third booster dose significantly elicited T cell responses to the XBB variant. Either monovalent or bivalent mRNA but not inactivated virus vaccine as the second/third booster induced antibody against different XBB variants., Conclusions: . Receiving bivalent mRNA vaccine as the third booster is preferrable to induce both T cell and antibody responses against XBB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Triple-negative breast cancer (TNBC), the most aggressive subtype, presents a critical challenge due to the absence of approved targeted therapies. Hence, there is an urgent need to identify effective therapeutic targets for this condition. While epidermal growth factor receptor (EGFR) is prominently expressed in TNBC and recognized as a therapeutic target, anti-EGFR therapies have yet to gain approval for breast cancer treatment due to their associated side effects and limited efficacy. Here, we discovered that intercellular adhesion molecule-1 (ICAM-1) exhibits elevated expression levels in metastatic breast cancer and serves as a pivotal binding adaptor for EGFR activation, playing a crucial role in malignant progression. The activation of EGFR by tumor-expressed ICAM-1 initiates biased signaling within the JAK1/STAT3 pathway, consequently driving epithelial-to-mesenchymal transition and facilitating heightened metastasis without influencing tumor growth. Remarkably, ICAM-1-neutralizing antibody treatment significantly suppressed cancer metastasis in a breast cancer orthotopic xenograft mouse model. In conclusion, our identification of ICAM-1 as a novel tumor intrinsic regulator of EGFR activation offers valuable insights for the development of TNBC-specific anti-EGFR therapies., (© 2024. The Author(s).)

The purpose of this study is to evaluate the influence of phospholipid-polymer nanoparticles (PNPs) on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling of dopaminergic neurons in degenerated brain. Resveratrol (RES)- and ceftriaxone (CEF)-entrapped PNPs with surface leptin (Lep) and transferrin (Tf) were fabricated to rescue both 1-methyl-4-phenylpyridinium (MPP + )-insulted SH-SY5Y cells and Wistar rats. Based on PNPs, anti-apoptosis of RES and CEF, and targeting of Lep and Tf were investigated. Experimental results revealed that 20-30 % alginic acid (Alg) yielded the maximal particle size, physical stability and entrapment efficiency of CEF, and the minimal release percentage of CEF. Increasing Alg content in PNPs decreased the entrapment efficiency of RES, and facilitated the release of RES. Optimized PNP composition was about 40 % Alg, 15 % phosphatidylserine and 45 % poly-ε-caprolactone. Lep-Tf-PNPs ameliorated brain permeability of RES and CEF without jeopardizing the blood-brain barrier, and promoted the viability of MPP + -insulted SH-SY5Y cells. Immunofluorescence images and western blots of MPP + -insulted SH-SY5Y cells showed that Lep-Tf-RES-CEF-PNPs upregulated dopamine transporter, tyrosine hydroxylase, B-cell lymphoma 2 (Bcl-2), cyclic AMP response element-binding protein and ERK5 expressions, and downregulated Bcl-2-associated X protein (Bax), α-synuclein (α-syn), phosphorylated tau protein (p-tau), c-Jun N-terminal kinase and ERK1/2 expressions. Lep-Tf-RES-CEF-PNPs unveiled a strong capacity to recover Bcl-2, Bax, α-syn and p-tau levels from MPP + injury in the substantia nigra of rats. Hence, Lep-Tf-RES-CEF-PNPs can retard α-syn fibril formation, prevent tau protein from phosphorylation, and moderate MAPK/ERK and phosphatidylinositol 3-kinase/protein kinase B, and are promising for brain- and neuron-targeted pharmacotherapy to manage Parkinson's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Surface electromyography (sEMG) is a widely employed bio-signal that captures human muscle activity via electrodes placed on the skin. Several studies have proposed methods to remove sEMG contaminants, as non-invasive measurements render sEMG susceptible to various contaminants. However, these approaches often rely on heuristic-based optimization and are sensitive to the contaminant type. A more potent, robust, and generalized sEMG denoising approach should be developed for various healthcare and human-computer interaction applications. This paper proposes a novel neural network (NN)-based sEMG denoising method called TrustEMG-Net. It leverages the potent nonlinear mapping capability and data-driven nature of NNs. TrustEMG-Net adopts a denoising autoencoder structure by combining U-Net with a Transformer encoder using a representation-masking approach. The proposed approach is evaluated using the Ninapro sEMG database with five common contamination types and signal-to-noise ratio (SNR) conditions. Compared with existing sEMG denoising methods, TrustEMG-Net achieves exceptional performance across the five evaluation metrics, exhibiting a minimum improvement of 20%. Its superiority is consistent under various conditions, including SNRs ranging from -14 to 2 dB and five contaminant types. An ablation study further proves that the design of TrustEMG-Net contributes to its optimality, providing high-quality sEMG and serving as an effective, robust, and generalized denoising solution for sEMG applications.

Background: Dental caries remains a significant global health problem. One of the fundamental mechanisms underlying the development and progression of dental caries is the dynamic process of demineralisation/remineralisation. In vitro models have played a critical role in advancing our understanding of this process and identifying potential interventions to prevent or arrest dental caries. This literature review aims to provide a structured oversight of in vitro mineralisation models which have been used to study the tooth demineralisation/remineralisation process., Methods: Publications from 2019 to 2023 were screened to identify articles reporting the use of in vitro models to study the demineralisation/remineralisation of tooth caries. The included studies were methodologically assessed for their information on (i) substrate, (ii) lesion formation, and (iii) mineralisation models., Results: The most reported substrates used in the studies were human teeth along with bovine incisors. Acetic/lactic buffers were the most common solutions to induce caries lesions. pH cycling was the most frequently used mineralisation model for simulating the daily change within the oral environment. This review discussed the advantages and limitations of various approaches., Conclusions: Standardisation of in vitro mineralisation models is crucial for enabling effective comparison between studies and advancing caries research.

Background: Multiple studies have reported the profound influence of various climate factors on dengue fever infection, while the effects of joint exposure to warm and wet environment, a condition favouring dengue vectors, on disease transmission were less evaluated. This study aims to investigate the impact of various compound temperature, rainfall, and relative humidity exposures on dengue fever infection in the South and Southeast Asia regions., Methods: Weekly dengue fever surveillance data from 2012 to 2020 were collected from 48 locations in four countries named Singapore (1 location), Sri Lanka (15 locations), Malaysia (9 locations), and Thailand (23 locations, with 11 locations having different study periods). The distributed lag non-linear models were built to assess the impacts of compound temperature, rainfall, and relative humidity exposures on dengue fever infection risks., Results: A total of 1,359,993 dengue fever cases were reported with 9.33%, 24.02%, 48.73%, and 17.91% cases contributed by Singapore, Sri Lanka, Malaysia, and Thailand, respectively. Compared to non-warm-non-wet, compound warm-wet was associated with an increased dengue risk (RR:1.32, 95% CI:1.21-1.44). Compared to moderate temperature-humidity, warm-wet environment was also associated with an increase in dengue risk (RR:1.37, 95% CI:1.22-1.55). In comparison to weeks with moderate temperature-rainfall, warm-wet weeks was linked to an elevated dengue risk (RR:1.39, 95% CI:1.27-1.52), whereas cold-dry weather would significantly reduce the infection risk (RR:0.70, 95% CI:0.62-0.80). Modification effects showed that the hot effect on dengue infection was more pronounced under higher humidity, while the impact of rainfall increased with warmer temperature., Conclusion: Warm-wet events were associated with an increased dengue fever risk, while the infection risk would decline in cold-dry environment, and modification effects exist among exposures. Findings from this study highlight the importance of considering joint temperature, humidity, and rainfall dependency of dengue fever infection in disease prevention and control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, represents one of the most significant global health crises in recent history. Despite extensive research into the immune mechanisms and therapeutic options for COVID-19, there remains a paucity of studies focusing on plasma cells. In this study, we utilized the DESeq2 package to identify differentially expressed genes (DEGs) between COVID-19 patients and controls using datasets GSE157103 and GSE152641. We employed the xCell algorithm to perform immune infiltration analyses, revealing notably elevated levels of plasma cells in COVID-19 patients compared to healthy individuals. Subsequently, we applied the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm to identify COVID-19 related plasma cell module genes. Further, positive cluster biomarker genes for plasma cells were extracted from single-cell RNA sequencing data (GSE171524), leading to the identification of 122 shared genes implicated in critical biological processes such as cell cycle regulation and viral infection pathways. We constructed a robust protein-protein interaction (PPI) network comprising 89 genes using Cytoscape, and identified 20 hub genes through cytoHubba. These genes were validated in external datasets (GSE152418 and GSE179627). Additionally, we identified three potential small molecules (GSK-1070916, BRD-K89997465, and idarubicin) that target key hub genes in the network, suggesting a novel therapeutic approach. These compounds were characterized by their ability to down-regulate AURKB, KIF11, and TOP2A effectively, as evidenced by their low free binding energies determined through computational analyses using cMAP and AutoDock. This study marks the first comprehensive exploration of plasma cells' role in COVID-19, offering new insights and potential therapeutic targets. It underscores the importance of a systematic approach to understanding and treating COVID-19, expanding the current body of knowledge and providing a foundation for future research., (© 2024. The Author(s).)

This research aimed to enhance the performance of surface-enhanced Raman scattering (SERS) substrates through the implementation of periodic nanostructures, effectively increasing surface area and uniformity. The approach involved a two-step process: initially, magnetron sputtering was employed to minimize the Raman background signal from the polymer substrate, and subsequently, the microplasma nanoparticle coating method was utilized to augment the presence of silver nanoparticles (AgNPs) for enhancing SERS efficacy. The outcome revealed several key findings: a coefficient of variation (CV) of approximately 8% for individual substrates (3 × 3 cm 2 ), a CV of 6% between different fabrication batches, and a sustained signal strength of 85% over a storage period exceeding two months in a moisture-proof enclosure, thus meeting commercial product standards. Moreover, the substrate demonstrated a limit of detection of 8.4 × 10 -7 M (306.5 ppb) for malachite green under non-resonance Raman excitation conditions along with an impressive enhancement factor of 2.69 × 10 6 , establishing it as a high-performance and stable SERS substrate.

Recent advances in scaffold-free three-dimensional (3D) culture methods have significantly enhanced the potential of stem cell-based therapies in regenerative medicine. This cutting-edge technology circumvents the use of exogenous biomaterial and prevents its associated complications. The 3D culture system preserves crucial intercellular interactions and extracellular matrix support, closely mimicking natural biological niches. Therefore, stem cells cultured in 3D formats exhibit distinct characteristics, showcasing their capabilities in promoting angiogenesis and immunomodulation. This review aims to elucidate foundational technologies and recent breakthroughs in 3D scaffold-free stem cell engineering, offering comprehensive guidance for researchers to advance this technology across various clinical applications. We first introduce the various sources of stem cells and provide a comparative analysis of two-dimensional (2D) and 3D culture systems. Given the advantages of 3D culture systems, we delve into the specific fabrication and harvesting techniques for cell sheets and spheroids. Furthermore, we explore their applications in pre-clinical studies, particularly in large animal models and clinical trials. We also discuss multidisciplinary strategies to overcome existing limitations such as insufficient efficacy, hostile microenvironments, and the need for scalability and standardization of stem cell-based products., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Background: Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong., Methods: This retrospective cohort study used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. Patients aged 18 years and older who tested positive for SARS-CoV-2 between March 11, 2022, and Oct 10, 2023, and who were admitted to hospital with COVID-19 were included. The treatment group included patients prescribed nirmatrelvir-ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir-ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. Standardised mortality ratio weights were applied to balance covariates, and Cox proportional hazards regression was used to investigate the relationship between nirmatrelvir-ritonavir and outcomes., Findings: 136 973 patients were screened for inclusion, among whom 50 055 were eligible and included in the analysis (24 873 [49·7%] were female and 25 182 [50·3%] were male). 15 242 patients were prescribed nirmatrelvir-ritonavir during acute COVID-19 and 23 756 patients were included in the control group; 11 057 patients did not meet our definition for the exposed and unexposed groups. Patients were followed up for a median of 393 days (IQR 317-489). In the nirmatrelvir-ritonavir group compared with the control group, there was a significantly lower hazard of post-acute inpatient death (hazard ratio 0·62 [95% CI 0·57-0·68]; p<0·0001), congestive heart failure (0·70 [0·58-0·85]; p=0·0002), atrial fibrillation (0·63 [0·52-0·76]; p<0·0001), coronary artery disease (0·71 [0·59-0·85]; p=0·0002), chronic pulmonary disease (0·68 [0·54-0·86]; p=0·0011), acute respiratory distress syndrome (0·71 [0·58-0·86]; p=0·0007), interstitial lung disease (0·17 [0·04-0·75]; p=0·020), and end-stage renal disease (0·37 [0·18-0·74]; p=0·0049). There was no evidence indicating difference between the groups in deep vein thrombosis, seizure, anxiety, post-traumatic stress disorder, acute kidney injury, and pancreatitis., Interpretation: This study showed extended benefits of nirmatrelvir-ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. Further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae., Funding: Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: As nucleos/tide analogue (NA) therapy (e.g. entecavir and tenofovir) for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. A systematic review to quantify resistance to these agents has not previously been undertaken., Methods: We performed a systematic review and random-effects meta-analysis to estimate the risk of HBV resistance to entecavir and tenofovir. We searched nine databases up to 29-Aug-23. We included studies of HBV infection featuring >10 individuals, written in English, reporting treatment ≥48 weeks, with assessment of HBV resistance based on viral sequence data. Data were analysed according to prior exposure history to NA, and choice of NA agent. Analyses were performed in R., Findings: 62 studies involving a total of 12,358 participants were included. For entecavir, in treatment-naive individuals (22 studies; 4326 individuals), resistance increased over time to 0.9 % at ≥5 years (95 %CI 0.1-2.3 %), and resistance was increased in NA-experienced individuals (18 studies; 1112 individuals), to 20.1 % (95 %CI 1.6-50.1 %) at ≥5 years. For tenofovir, pooled resistance risk was 0.0 % at all time points, whether previously NA naive (11 studies; 3778 individuals) or experienced (19 studies; 2059 individuals). There was a lack of consistent definitions, poor global representation and insufficient metadata to support subgroup analysis., Interpretation: We have generated the first pooled estimates of HBV entecavir and tenofovir resistance over time. HBV resistance to entecavir in treatment-experienced groups in particular may represent a clinical and public health challenge. To date, tenofovir appears to have an excellent resistance profile, but due to data gaps, we caution that existing studies under-estimate the true real-world risk of resistance. Robust prospective data collection is crucial to reduce health inequities and reduce blind-spots in surveillance as treatment is rolled out more widely., Competing Interests: Declaration of competing interest CC receives doctoral funding support from GSK for a PhD supervised by PCM. YS receives research grant from Gilead Sciences., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Diabetes and CRC share many overlapping lifestyle risk factors such as obesity, heavy alcohol use, and diet. This study aims to develop a risk scoring system for CRC prediction among diabetes patients using routine medical records., Methods: A retrospective cohort study was conducted using electronic health records of Hong Kong. Patients who received diabetes care in public general outpatient clinics between 2010 and 2019 and had no cancer history were identified, and followed up until December 2019. The outcome was diagnosis of CRC during follow-up. For model building, predictors were first selected using random survival forest, and weights were subsequently assigned to selected predictors using Cox regression., Results: Of the 386,325 patients identified, 4,199 patients developed CRC during a median follow-up of 6.2 years. The overall incidence rate of CRC was 1.93 per 1000 person-years. In the final scoring system, age, waist-to-hip ratio, and serum creatinine were included as predictors. The C-index on test set was 0.651 (95%CI: 0.631-0.669). Elevated serum creatinine (≥127 µmol/L) could be a potential important predictor of increased CRC risk., Conclusion: While obesity is a well-known risk factor for CRC, renal dysfunction could be potentially linked to an elevated risk of CRC among diabetes patients. Further studies are warranted to explore whether renal function could be a potential parameter to guide screening recommendation for diabetes patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yau, Hung, Leung, Chong, Lee and Yeoh.)

Background: Behcet's disease (BD) is an inflammatory disorder known for various symptoms, including oral and genital ulcers and ocular inflammation. Panuveitis, a severe eye condition, is rare as the first sign of BD., Case Summary: We present an unusual case of a 30-year-old man who developed panuveitis after receiving the mRNA-based coronavirus disease 2019 (COVID-19) vaccine (Moderna). Laboratory tests ruled out infections, but he had a positive HLA-B51 result and a history of genital ulcer and oral ulcers, leading to a BD diagnosis. Treatment with corticosteroids improved his condition. Interestingly, he had another episode of panuveitis after the second mRNA vaccine dose, which also responded to corticosteroids., Conclusion: This case highlights the rare onset of BD following mRNA COVID-19 vaccination, suggesting a potential link between these vaccines and BD's eye symptoms, emphasizing the importance of quick treatment in similar cases., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest for this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hydroxyapatite (HA) forms an essential constituent of human teeth and bone. Its distinctive characteristic features, such as bioactivity and osteoconductivity, make it an ideal candidate to be used as an implant coating in restorative dentistry and maxillofacial surgery for bone regeneration. However, low fracture toughness and brittleness are a few of the inherent features of HA, which limit its application in load-bearing areas. The potential of HA to engage its lattice structure with either partial or complete substitution with external ions has become an increasing area of research as this phenomenon has the potential to enhance the biological and functional properties of the material. Consequently, this review aimed to highlight the role of various substituted ions in dental applications. Data indicate that the newly formed HA-substituted biomaterials demonstrate enhanced remineralization and antimicrobial activity along with improved hardness. Ion-substituted HA offers a promising strategy for future clinical research as these materials may be incorporated into various dental products for therapeutic treatments.

This study evaluated the antioxidant and anti-glycemic properties of black lemon Chenpi (BLC) ( Citrus limon (L.) Burm. f. cv. Eureka), processed using three thermal browning models-hot-air drying (HAL), high temperature and humidity, and steam-drying cycle (SCL)-and compared them to fresh lemon peel and commercial Chenpi. The moisture-assisted aging technology (MAAT) is an environmentally friendly process for inducing browning reactions in the lemon peel, enhancing its functional properties. Our results demonstrated significant increases in sucrose, total flavonoid content, and antioxidant capacities (2,2-diphenylpicrylhydrazyl: 12.86 Trolox/g dry weight; ferric reducing antioxidant power: 14.92 mg Trolox/g dry weight) with the MAAT-HAL model. The MAAT-SCL model significantly improved the browning degree, fructose, total polyphenol content, narirutin, and 5-hydroxymethylfurfural synthesis ( p < 0.05). Additionally, aged lemon peel exhibited potential α-glucosidase inhibitory activity (28.28%), suggesting its role in blood sugar regulation after meals. The multivariate analysis (principal component and heatmap analyses) indicated that BLC processed using the MAAT-SCL model exhibited similarities to commercial Chenpi, indicating its potential for functional food development. Our results indicate that MAAT-SCL can enhance the economic value of lemon by-products, offering a sustainable and functional alternative to traditional Chenpi.

Background and Aims: Virtual reality is an emerging technology in rehabilitation. This umbrella review aimed to identify, critically appraise, and summarize current systematic reviews on the effects of virtual reality on stroke rehabilitation., Methods: Five biomedical databases, PubMed, Embase, CINAHL, PsycINFO, and Scopus were searched from inception to December 30th, 2023, for systematic reviews with or without meta-analyses published in English. Two reviewers independently conducted abstract screening, full-text selection, and quality assessments. The methodological quality of included studies was evaluated by the Assessing the Methodological Quality of Systematic Reviews 2. Results were qualitatively synthesized according to domains of function to ascertain the effects of virtual reality intervention on functional improvement within stroke rehabilitation., Results: A total of 78 articles were included; 23 were systematic reviews, and 55 were systematic reviews with meta-analyses. Among them, 30 studies were evaluated as critically low quality, 32 as low, 15 as moderate, and one as good. Outcomes regarding upper extremity motor function, upper extremity activity, participation, functional independence, balance, functional mobility, walking speed, and cognitive function were summarized. While positive effects in favor of virtual reality were revealed by a majority of systematic reviews on these outcomes, evidence supporting the significantly different effects of virtual reality compared to conventional rehabilitation on participation and cognitive function was lacking., Conclusion: The umbrella review demonstrated promising clinical outcomes regarding the use of virtual reality as an advanced therapeutic approach in stroke rehabilitation to optimize patient care. Future systematic reviews and meta-analyses in this field should adhere to established guidelines to enhance the quality of evidence., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

The regulation of virulence in plant-pathogenic fungi has emerged as a key area of importance underlying host infections. Recent work has highlighted individual transcription factors (TFs) that serve important roles. A prominent example is PnPf2, a member of the Zn2Cys6 family of fungal TFs, which controls the expression of effectors and other virulence-associated genes in Parastagonospora nodorum during infection of wheat. PnPf2 orthologues are similarly important for other major fungal pathogens during infection of their respective host plants, and have also been shown to control polysaccharide metabolism in model saprophytes. In each case, the direct genomic targets and associated regulatory mechanisms were unknown. Significant insight was made here by investigating PnPf2 through chromatin-immunoprecipitation (ChIP) and mutagenesis approaches in P. nodorum. Two distinct binding motifs were characterised as positive regulatory elements and direct PnPf2 targets identified. These encompass known effectors and other components associated with the P. nodorum pathogenic lifestyle, such as carbohydrate-active enzymes and nutrient assimilators. The results support a direct involvement of PnPf2 in coordinating virulence on wheat. Other prominent PnPf2 targets included TF-encoding genes. While novel functions were observed for the TFs PnPro1, PnAda1, PnEbr1 and the carbon-catabolite repressor PnCreA, our investigation upheld PnPf2 as the predominant transcriptional regulator characterised in terms of direct and specific coordination of virulence on wheat, and provides important mechanistic insights that may be conserved for homologous TFs in other fungi., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 John et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We have synthesized L-cysteine and oleylamine stabilized CsPbBr3 perovskite quantum dots (PQDs) and coupled them with gold nanoparticles (AuNPs). The PQDs and AuNPs, as well as their hybrid nanostructures (HNS), were characterized using UV-visible (UV-vis) and photoluminescence (PL) spectroscopy. The UV-vis spectra show absorption bands of the HNS at 503 and 520 nm, attributed mainly to PQDs and AuNPs, respectively. The PQDs show a strong excitonic PL band peaked at 513 nm from PQDs. The HR-TEM results show the formation of hybrid structures between PQDs and AuNPs, which is also supported by the PL quenching of the PQDs by the coupled AuNPs. Ultrafast dynamics of the exciton and charge carriers in the HNS and pristine PQD were studied using femtosecond transient absorption. Multiexponential fitting of the dynamic data revealed the existence of shallow and deep trap states in pristine PQDs and ultrafast electron transfer from PQDs to AuNPs in the HNS. A kinetic model was proposed to account for the key dynamic processes involved and to extract the time for electron transfer from PQDs to AuNPs in the HNS, found to be ∼2 ps. Dynamic processes in pristine PQDs are largely unchanged by HNS formation with AuNPs., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Two-photon high-speed fluorescence calcium imaging stands as a mainstream technique in neuroscience for capturing neural activities with high spatiotemporal resolution. However, challenges arise from the inherent tradeoff between acquisition speed and image quality, grappling with a low signal-to-noise ratio (SNR) due to limited signal photon flux. Here, a contrast-enhanced video-rate volumetric system, integrating a tunable acoustic gradient (TAG) lens-based high-speed microscopy with a TAG-SPARK denoising algorithm is demonstrated. The former facilitates high-speed dense z-sampling at sub-micrometer-scale intervals, allowing the latter to exploit the spatial redundancy of z-slices for self-supervised model training. This spatial redundancy-based approach, tailored for 4D (xyzt) dataset, not only achieves >700% SNR enhancement but also retains fast-spiking functional profiles of neuronal activities. High-speed plus high-quality images are exemplified by in vivo Purkinje cells calcium observation, revealing intriguing dendritic-to-somatic signal convolution, i.e., similar dendritic signals lead to reverse somatic responses. This tailored technique allows for capturing neuronal activities with high SNR, thus advancing the fundamental comprehension of neuronal transduction pathways within 3D neuronal architecture., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Neuronal connections provide the scaffolding for neuronal function. Revealing the connectivity of functionally identified individual neurons is necessary to understand how activity patterns emerge and support behavior. Yet, the brain-wide presynaptic wiring rules that lay the foundation for the functional selectivity of individual neurons remain largely unexplored. Cortical neurons, even in primary sensory cortex, are heterogeneous in their selectivity, not only to sensory stimuli but also to multiple aspects of behavior. Here, to investigate presynaptic connectivity rules underlying the selectivity of pyramidal neurons to behavioral state 1-12 in primary somatosensory cortex (S1), we used two-photon calcium imaging, neuropharmacology, single-cell based monosynaptic input tracing, and optogenetics. We show that behavioral state-dependent neuronal activity patterns are stable over time. These are minimally affected by neuromodulatory inputs and are instead driven by glutamatergic inputs. Analysis of brain-wide presynaptic networks of individual neurons with distinct behavioral state-dependent activity profiles revealed characteristic patterns of anatomical input. While both behavioral state-related and unrelated neurons had a similar pattern of local inputs within S1, their long-range glutamatergic inputs differed. Individual cortical neurons, irrespective of their functional properties, received converging inputs from the main S1-projecting areas. Yet, neurons that tracked behavioral state received a smaller proportion of motor cortical inputs and a larger proportion of thalamic inputs. Optogenetic suppression of thalamic inputs reduced behavioral state-dependent activity in S1, but this activity was not externally driven. Our results revealed distinct long-range glutamatergic inputs as a substrate for preconfigured network dynamics associated with behavioral state.

Rationale: Approximately one-fifth ischemic stroke are attributed to cardioembolism. Patients with cardioembolic stroke often develop a more severe disability and a higher risk of stroke recurrence. Cardiac myxoma, although uncommon, can serve as a potentially curable cause of acute embolic strokes., Patient Concerns: A 55-year-old male patient presented to the emergency department with acute vertigo and unsteady gait, accompanied by left upper limb numbness. Concurrently, purple-like lesions on the left hand were noticed., Diagnoses: Brain magnetic resonance imaging showed multiple infarctions in the posterior circulation. Additionally, skin examination showed Janeway lesions, Osler nodes and splinter hemorrhages. There was no evidence of systemic infection. Subsequently, transthoracic echocardiogram revealed a left atrial myxoma., Intervention: Early surgical resection of cardiac myxoma was performed., Outcomes: The patient recovered well from the surgery. No recurrent embolic event was reported at 3-month postoperatively., Lessons: Clinicians should be vigilant for skin manifestations of cardiac embolism. In patients with acute ischemic strokes, the presence of cutaneous embolic phenomena could serve as a warning sign of cardioembolism., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study presents a comprehensive investigation into a 3D simulation of magnetorheological (MR) conical bearings, focusing on considering viscous dissipation using the conjugated heat transfer approach. The behavior of MR fluids is expressed through the utilization of the Bingham-Papanastasiou constitutive equation. Notably, this study considers variations in viscosity and yield stress as functions of both magnetic field intensity and temperature. The study utilizes a multidisciplinary approach, encompassing fluid dynamics, magnetism, and heat transfer, to model and analyze the behavior of MR fluids within conical bearing geometries. The governing equations containing Cauchy momentum, energy, and Maxwell equations are solved using the finite element method. This research delves into the impacts of viscous dissipation on the functional and characteristic attributes of conical bearings. The energy equations in solid and fluid domains and extended considerations to the plug region within viscous dissipation are specifically addressed. Extensive validation is performed through a comparative analysis involving experimental, numerical, and analytical studies to ensure the validity of results. The results reveal the substantial impact of temperature on both the characteristics and functionality of magnetorheological conical bearings., (© 2024. The Author(s).)

BACKGROUND Cardiac calcified amorphous tumor (CCAT), a peculiar and uncommon non-neoplastic cardiac lesion, was initially characterized by Reynolds and colleagues in the medical literature in 1997. This distinctive entity is hallmarked by its unique feature of pedunculated and diffused calcifications, primarily infiltrating the cardiac structures, with a predilection for the mitral valve annulus initially, followed in sequence by the right atrium, right ventricle, left atrium, left ventricle, and tricuspid valve annulus. The nature of CCATs, despite being benign, poses diagnostic dilemmas, as they frequently masquerade as malignant tumors due to their clinical presentations, which resemble those caused by potential complications such as obstructive masses and thromboembolic events. CASE REPORT A 50-year-old man presented to our hospital with shortness of breath. He had been short of breath for more than 5 years after repeated activities. Transthoracic echocardiography showed a mobile high echogenic mass from the middle of the right ventricular wall and pericardial effusion and right heart insufficiency. The electrocardiogram (ECG) results demonstrated a sinus rhythm, complete right bundle branch block, and T-wave alterations. Additionally, the chest computed tomography (CT) scan revealed a slightly enlarged heart with a lack of density and calcification in the right ventricle. He had an uneventful postoperative recovery after the resection of the cardiac tumor. The mass had not continued to grow when we compared it with preoperative cardiac color doppler echocardiography, after 3 months follow-up. CONCLUSIONS CCAT is a rare non-neoplastic cardiac entity. Diagnosis of CCAT poses a challenge due to the absence of distinct clinical features and its frequent misidentification as a malignant tumor mimic. Surgical resection serves as the sole treatment for symptom relief.

Background: Intraperitoneal pressure measurement offers therapeutic and prognostic benefits in predicting leak risks and gastrointestinal symptoms in Peritoneal Dialysis (PD) patients. This systematic review aims to evaluate the prognostic utility of intraperitoneal pressure measurements and different estimated intraperitoneal pressure equations in predicting the risk of non-infectious complications in PD patients., Methods: Databases including MEDLINE, EMBASE and Cochrane were searched up to July 2023. Randomised and non-randomised trials were included, focusing on End-Stage Kidney Disease (ESKD) patients undergoing PD. Primary outcomes were variables associated with intraperitoneal pressure, while secondary outcomes included PD-related non-infectious complications and gastrointestinal symptoms. Data synthesis combined meta-analysis with narrative synthesis. This review has been registered on PROSPERO (CRD42023475138)., Results: Out of 1828 identified studies, 12 were included for systematic review and 10 for meta-analysis. Body Mass Index (BMI) and Body Surface Area (BSA) showed a consistent positive correlation with intraperitoneal pressure (BMI: r = 0.49, 95% CI 0.35-0.61, I 2  = 67.39%, p = 0.003; BSA: r = 0.2, 95% CI 0.08-0.31, I 2  = 14.10%, p = 0.324). Conversely, the association between intraperitoneal pressure and age, intraperitoneal volume, and Charlson Comorbidity Index were less consistent. Subgroup analysis demonstrated an association between higher intraperitoneal pressure in patients with increased BMI and BSA. However, the relationship between intraperitoneal pressure and non-infectious mechanical complications remained inconclusive., Discussion: This review underscores a significant association between intraperitoneal pressure and anthropometric measures (BMI and BSA). The majority of the studies identified included a small sample and considerable bias. However, the association between intraperitoneal pressure and clinically relevant outcomes was not clear., Conclusions: While increasing body mass index and body surface areas are associated with increasing intraperitoneal pressure, the clinical relevance of measuring intraperitoneal pressure in an adult population remains unclear, particularly given the absence of an association with clinically relevant non-infectious outcomes., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Febrile seizures are convulsions predominately occurring in young children. The effects of various exposomes, including influenza infection and external environmental factors, on febrile seizures have not been well-studied. In this study, we elucidated the relationships between ambient temperature, air pollutants, influenza infection, and febrile seizures using 22-year territory-wide hospitalization data in Hong Kong. The aggregated data were matched with the meteorological records and air pollutant concentrations. All-type and type-specific influenza-like illness positive (ILI+) rates were used as proxies for influenza activity. Distributed lag non-linear model in conjunction with the quasi-poisson generalized additive model was used to examine the associations of interest. According to the results, all-type influenza infections were significantly associated with an increased risk of hospital admissions for febrile seizures (cumulative adjusted relative risk [ARR] = 1.59 at 95th percentile vs. 0; 95% CI, 1.51-1.68). The effect of ILI + A/H3N2 on febrile seizure was more pronounced than other type-specific ILI + rates. A low mean ambient temperature was identified as a significant risk factor for febrile seizures (cumulative ARR = 1.50 at 5th percentile vs. median; 95% CI, 1.35-1.66), while the redox-weighted oxidant capacity and sulfur dioxide were not associated with febrile seizures. In conclusion, our study underscores that influenza infections and exposure to cold conditions were related to an increased risk of febrile seizures in children. Thus, we advocate for influenza vaccination before the onset of the cold season for children to mitigate the burden of febrile seizures., (© 2024. The Author(s).)

Several studies have shown developmental changes in EEG oscillations during working memory tasks. Although the load-modulated theta and alpha activities in adults are well-documented, the findings are inconsistent if children possess the adult-like brain oscillations that are similarly modulated by memory load. The present study compares children's and adults' true theta and alpha EEG oscillations, separated from aperiodic components, in the maintenance stage of working memory. The EEG was recorded in 25 Chinese-speaking children (14 male, M age = 9.4 yrs) and 31 adults (19 male, M age = 20.8 yrs) in Hong Kong while they performed an n-back task that included four conditions differing in load (1- vs. 2-back) and stimulus type (Chinese character vs. visual pattern). The results show that aperiodic activities (i.e., broadband power and slope) during the maintenance stage in the n-back task were significantly higher in children than adults. The periodic theta and alpha oscillations also changed with age. More importantly, adults showed significant periodic theta increase with memory load, whereas such an effect was absent in children. Regardless of age, there was a significant alpha power decrease with load increase, and a significant theta power enhancement when maintaining visual patterns than Chinese characters. In adults, load-modulated alpha peak shift (towards higher frequency) was linked to higher behavioral efficiency in the n-back task. In children, higher load-modulated theta enhancement was linked to better behavioral efficiency. The findings suggest that the load-modulated theta power during working memory maintenance matures from childhood to adulthood., Competing Interests: Declaration of Competing Interest The authors declare that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate the prevalence of urinary incontinence (UI) and its associated risk factors among pregnant Korean women, as UI significantly impacts their quality of life., Methods: A cross-sectional study involving singleton pregnant women was conducted between April and December 2023. Data were collected using a questionnaire assessing demographic information and UI symptoms. The International Consultation on Incontinence Questionnaire-UI short form was used to diagnose UI., Results: A total of 824 pregnant women from three centers participated, with an overall prenatal UI prevalence of 40.2% (331/824). Stress UI was most common (77.1%), followed by mixed UI (16.9%), and urgency UI (6.0%). Risk factors for UI included prior delivery mode, specifically vaginal delivery (adjusted odds ratio [aOR], 5.61; 95% confidence interval [CI], 1.40-22.50; P=0.015) and combined vaginal and cesarean delivery (aOR, 23.14; 95% CI, 1.77-302.74; P=0.017). Additionally, second trimester (aOR, 1.99; 95% CI, 1.19-3.32; P=0.009) and third trimester (aOR, 4.44; 95% CI, 2.65-7.40; P<0.001) were associated with increased UI risk. Conversely, drinking alcohol before pregnancy was a protective factor (aOR, 0.72; 95% CI, 0.53-0.99; P=0.046)., Conclusion: Approximately 40% of Korean pregnant women experience prenatal UI. Prior delivery mode and advanced gastrointestinal age are significant risk factors. Further research with postpartum and long-term follow-ups is needed.

Accurate screening of cancer types is crucial for effective cancer detection and precise treatment selection. However, the association between gene expression profiles and tumors is often limited to a small number of biomarker genes. While computational methods using nature-inspired algorithms have shown promise in selecting predictive genes, existing techniques are limited by inefficient search and poor generalization across diverse datasets. This study presents a framework termed Evolutionary Optimized Diverse Ensemble Learning (EODE) to improve ensemble learning for cancer classification from gene expression data. The EODE methodology combines an intelligent grey wolf optimization algorithm for selective feature space reduction, guided random injection modeling for ensemble diversity enhancement, and subset model optimization for synergistic classifier combinations. Extensive experiments were conducted across 35 gene expression benchmark datasets encompassing varied cancer types. Results demonstrated that EODE obtained significantly improved screening accuracy over individual and conventionally aggregated models. The integrated optimization of advanced feature selection, directed specialized modeling, and cooperative classifier ensembles helps address key challenges in current nature-inspired approaches. This provides an effective framework for robust and generalized ensemble learning with gene expression biomarkers.

Tarso-metatarsal joints and naviculocuneiform joints comprising midfoot is the second most commonly involved joints following the first metatarsophalangeal joint in the foot. However, related factors of midfoot arthritis (MA) have been rarely reported. The bony structure and alignment can be more precisely assessed using Weight-Bearing Computed Tomography (WBCT) than conventional radiographs. Therefore, the aim of this study was to investigate risk factors for MA related to medical history and comorbid foot deformities using WBCT. WBCT data from September 2014 to April 2022 were extracted from a single referral hospital. All cases were divided into two groups by the presence of MA. Twenty-five potential related factors including demographics, etiology, and common co-occurring foot deformities were collected for comparison. Six hundred six cases (247 males and 359 females) among consecutive 1316 cases between September 2014 to April 2022 were selected. One hundred thirty-nine male cases (56.3%) and 210 female cases (58.5%) showed MA. In stepwise multiple logistic regression analysis, 5 factors remained statistically significant. The multivariate-adjusted odds ratios for age, laterality, body mass index (BMI), Progressive Collapsing Foot Deformity (PCFD), and lesser toe deformities (LTD) were 1.08, 1.54, 1.05, 6.62, and 3.03 respectively. Risk factors for MA associated with medical history and foot deformities included age, laterality, BMI, PCFD, and LDT., (Copyright © 2024 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

The physicochemical properties of grafting materials affect the quality of the osteointegration, resorption rate, and the new bone (NB) formation. This study assessed the physicochemical properties and integration of a low temperature deproteinized bovine bone xenograft (BBX), referred to as optimized MoaBone® (OMB). This novel BBX was physiochemically characterized both pre and post chemical bleaching and sterilization by gamma irradiation. OMB was compared to two commercial BBX; Bio-Oss® (BO) and MoaBone® (MB) using a rabbit cranial model. Residual graft and NB were quantified using histology and micro-computed tomography. Results showed that chemical treatment and gamma irradiation had limited effect on the surface texture. A significant decrease in the collagen content was detected post chemical treatment and in the carbonate content post gamma irradiation. There was no evidence of inflammatory infiltrate, necrosis, or connective tissue encapsulation, and a significant increase of NB in all grafted sites as compared to untreated defects could be observed. However, there was no statistically significant difference between the grafted sites. We conclude that chemical treatment and terminal sterilization strongly impact the final graft's properties. OMB graft showed equivalence with BO for in vivo bone formation and potentially results in lower levels of graft retention., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

While previous research examined coronavirus disease 2019 (COVID-19) antiviral-vaccine interactions through exploratory subgroup analysis, none specifically designed for examining this interaction or its impact on post-acute outcomes. This study examined the interaction between nirmatrelvir-ritonavir and complete COVID-19 vaccination on reducing the risk of post-acute outcomes among COVID-19 patients. We followed COVID-19 patients hospitalized between 11 March 2022 and 10 October 2023, until 31 October 2023 in Hong Kong. Exposure groups were based on nirmatrelvir-ritonavir usage and vaccination status (fully or not fully vaccinated). Post-acute death and all-cause rehospitalization were the study outcomes. Propensity score weighting was applied to balance covariates among exposure groups, including age, sex, Charlson Comorbidity Index, and concomitant treatments. Multiplicative and additive interactions between nirmatrelvir-ritonavir and vaccination status were assessed. A total of 50,438 COVID-19 patients were included in this study and arranged into four exposure groups. Significant additive interaction on post-acute rehospitalization was observed (relative excess risk, 0.10; 95% CI, 0.02-0.19; p -value, 0.018; attributable proportion, 0.07; 95% CI, 0.01-0.12; p -value, 0.017; synergy index, 1.26; 95% CI, 1.02-1.55; p -value, 0.032). The interaction on post-acute mortality was marginally significant. In the subgroup analysis, the interaction effect is more pronounced in older adults, female, and CoronaVac recipients. In conclusion, our study demonstrated an additive interaction between nirmatrelvir-ritonavir and complete vaccination on post-acute outcomes, suggesting greater long-term benefits of the antiviral for fully vaccinated individuals compared to not fully vaccinated patients.

Objective: To determine the correlation, precision, mean percentage difference and agreement between cardiac indices (stroke volume [SV], cardiac output [CO], SV index [SVI], and cardiac index [CI]) measured by noninvasive cardiac output monitor (NICOM ® , Cheetah Medical, Boston, MA, USA) and 2-dimensional transthoracic echocardiography (2D-TTE) across gestations in Chinese pregnant women., Methods: This was a prospective longitudinal study performed in women with singleton pregnancy at 11-14 +6 ( n  = 152), 19-24 +6 ( n  = 152), 30-34 +6 ( n  = 141), and 35-37 +6 ( n  = 103). Cardiac indices, including CO and SV, were obtained by NICOM ® , which uses thoracic bioreactance, and 2D-TTE. CI and SVI were calculated from CO and SV adjusted for body surface area. The measurements of cardiac indices obtained using NICOM ® were assessed relative to that of 2D-TTE by calculating correlation coefficient, bias, precision, mean percentage difference, and 95% limits of agreement, adjusted for repeated measurements., Results: Comparison of the SV and SVI measurements by the two approaches showed significant moderate correlation in the first trimester ( r  = 0.2-0.3; p  = .01). Overall, the SV and SVI measurements obtained using NICOM ® relative to that obtained by 2D-TTE revealed a bias of -12.1 mL and -6.1 mL/m 2 (95% confidence interval [CI]: -44.5 to 20.2 and -24.8 to 12.5), respectively. Comparison of the CO and CI measurements by the two approaches showed significant moderate correlation in the first trimester ( r ∼0.2; p  = .01). Overall, the CO and CI measurements obtained using NICOM ® relative to that obtained by 2D-TTE revealed a bias of -0.50 L/min and -0.18 L/min/m 2 (95% CI: 2.26-3.27 and -1.79 to 1.39), respectively. Mean percentage difference for all cardiac parameters in all three trimesters were more than 30%., Conclusions: In Chinese pregnant women, NICOM ® has underestimated cardiac indices (SV, CO, SVI, and CI) compared to that measured by 2D-TTE. The mean percentage differences for all cardiac indices are more than 30%, which are higher than the clinically acceptable limit. Future research is needed to determine whether adjustment factors should be applied to the proprietary algorithms used by the NICOM ® for the estimation of SV and CO in the Chinese pregnant population.

Purpose: General differences in surgeon ergonomics between laparoscopic and robotic-assisted inguinal hernia repairs (LIHR vs. RIHR) have been previously studied. However, specific differences in the ergonomics of mesh placement (MP) and mesh fixation (MF) are undetermined. Our aim was to determine if there are differences in the ergonomics of MP and MF between the surgical approaches. We hypothesize that we will identify differences, with the potential for worse ergonomics during LIHR., Methods: Data was collected from fifteen LIHR and fifteen RIHR. All cases were elective, primary inguinal hernias completed by a fellowship-trained minimally invasive surgeon. Surface electromyography (EMG) of four upper extremity muscle groups, including the upper trapezius (UT), anterior deltoid (AD), flexor carpi radialis (FCR) and extensor digitorum (ED), was recorded bilaterally during MP and MF. Muscle activation as a percent of maximum voluntary contraction (%MVC RMS ) and muscle fatigue denoted as the median frequency of muscle activations (Fmed) were calculated for each muscle., Results: EMG analysis showed increased %MVC RMS in LIHR compared to RIHR cases, with significant findings in the left UT, right UT, ED, and FCR for MP and MF and the left FCR during MP. Muscle fatigue was decreased in LIHR compared to RIHR cases, with significant differences in left FCR and right ED and AD., Conclusion: Despite greater muscle activations during LIHR, RIHR had greater muscle fatigue. It is possible that short periods of high muscle activation are ergonomically protective during minimally invasive inguinal hernia repair. Identifying these differences may aid in development of procedure-specific interventions to improve ergonomics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Infection is a major concern in surgery involving grafting and should be considered thoroughly when designing biomaterials. There is considerable renewed interest in silver nanoparticles (AgNPs) owing to their ability to potentiate antibacterial properties against multiple bacterial strains. This study aimed to develop two antibacterial bone regenerative scaffolds by integrating AgNPs in bovine bone particles (BBX) (Product 1), and a light cross-linked hydrogel GelMA (Product 2). The constructs were characterized using scanning electron microscopy. Metabolic activity of osteoblasts and osteoclasts on the constructs was investigated using PrestoBlue™. Disk diffusion assay was conducted to test the antibacterial properties. The regenerative capacity of the optimized AgNP functionalized BBX and GelMA were tested in a rabbit cranial 6 mm defect model. The presence of AgNPs appears to enhance proliferation of osteoblasts compared to AgNP free controls in vitro. We established that AgNPs can be used at a 100 μg dose that inhibits bacteria, with minimal adverse effects on the bone cells. Our rabbit model revealed that both the BBX and GelMA hydrogels loaded AgNPs were biocompatible with no signs of necrosis or inflammatory response. Grafts functionalized with AgNPs can provide antibacterial protection and simultaneously act as a scaffold for attachment of bone cells., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Objectives: To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation., Methods: Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies., Results: During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy., Conclusions: HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in highly heterogeneous systems. However, this technique often results in the analysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we developed PURE-seq (PIP-seq for Rare-cell Enrichment and Sequencing) for scalable sequencing of rare cells. PURE-seq allows direct cell loading from FACS into PIP-seq reactions, minimizing handling and reducing cell loss. PURE-seq reliably captures rare cells, with 60 minutes of sorting capturing tens of cells at a rarity of 1 in 1,000,000. Using PURE-seq, we investigated murine long-term hematopoietic stem cells and their transcriptomes in the context of hematopoietic aging, identifying Egr1 as a potential master regulator of hematopoiesis in the aging context. PURE-seq offers an accessible and reliable method for isolating and sequencing cells that are currently too rare to capture successfully with existing methods.

Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in highly heterogeneous systems. However, this technique often results in the analysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we developed PURE-seq (PIP-seq for Rare-cell Enrichment and Sequencing) for scalable sequencing of rare cells. PURE-seq allows direct cell loading from FACS into PIP-seq reactions, minimizing handling and reducing cell loss. PURE-seq reliably captures rare cells, with 60 minutes of sorting capturing tens of cells at a rarity of 1 in 1,000,000. Using PURE-seq, we investigated murine long-term hematopoietic stem cells and their transcriptomes in the context of hematopoietic aging, identifying Egr1 as a potential master regulator of hematopoiesis in the aging context. PURE-seq offers an accessible and reliable method for isolating and sequencing cells that are currently too rare to capture successfully with existing methods.

Background: Understanding the global burden of enteric infections is crucial for prioritizing control strategies for foodborne and waterborne diseases. This study aimed to assess the global burden of enteric infections in 2021 and identify risk factors from One Health aspects., Methods: Leveraging the Global Burden of Disease (GBD) 2021 database, the incidence, disability-adjusted life years (DALYs), and deaths of enteric infections and the subtypes were estimated, including diarrheal diseases, typhoid and paratyphoid fever, invasive non-typhoidal Salmonella (iNTS) infections, and other intestinal infectious diseases. The estimates were quantified by absolute number, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized DALY rate with 95% uncertainty intervals ( UI s). Thirteen pathogens and three risk factors associated with diarrheal diseases were analyzed., Results: In 2021, the global age-standardized DALY rate of enteric infections was 1020.15 per 100,000 popultion (95% UI : 822.70-1259.39 per 100,000 population) with an estimated annual percentage change (EAPC) of -4.11% (95% confidence interval: -4.31% to -3.90%) in 1990-2021. A larger burden was observed in regions with lower Socio-demographic index (SDI) levels. Diarrheal disease was the most serious subtype with Western Sub-Saharan Africa exhibiting the highest age-standardized DALY rate (2769.81 per 100,000 population, 95% UI : 1976.80-3674.41 per 100,000 population). Children under 5 and adults over 65 years suffered more from diarrheal diseases with the former experiencing the highest global age-standardized DALY rate (9382.46 per 100,000 population, 95% UI : 6771.76-13,075.12 per 100,000 population). Rotavirus remained the leading cause of diarrheal diseases despite a cross-year decline in the observed age-standardized DALY rate. Unsafe water, sanitation, and handwashing contributed most to the disease burden., Conclusion: The reduced burden of enteric infections suggested the effectiveness of previous control strategies; however, more efforts should be made in vulnerable regions and populations through a One Health approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

The fungus Parastagonospora nodorum causes septoria nodorum blotch on wheat. The role of the fungal Velvet-family transcription factor VeA in P. nodorum development and virulence was investigated here. Deletion of the P. nodorum VeA ortholog, PnVeA, resulted in growth abnormalities including pigmentation, abolished asexual sporulation and highly reduced virulence on wheat. Comparative RNA-Seq and RT-PCR analyses revealed that the deletion of PnVeA also decoupled the expression of major necrotrophic effector genes. In addition, the deletion of PnVeA resulted in an up-regulation of four predicted secondary metabolite (SM) gene clusters. Using liquid-chromatography mass-spectrometry, it was observed that one of the SM gene clusters led to an accumulation of the mycotoxin alternariol. PnVeA is essential for asexual sporulation, full virulence, secondary metabolism and necrotrophic effector regulation., (© 2024. The Author(s).)

Near-infrared (NIR) emitting phosphors draw much attention because they show great applicability and development prospects in many fields. Herein, a series of inverse spinel-type structured LiGa 5 O 8 phosphors with a high concentration of Cr 3+ activators is reported with a dual emission band covering NIR-I and II regions. Except for strong ionic exchange interactions such as Cr 3+ -Cr 3+ and Cr 3+ clusters, an intervalence charge transfer (IVCT) process between aggregated Cr ion pairs is proposed as the mechanism for the ~1210 nm NIR-II emission. Comprehensive structural and luminescence characterization points to IVCT between two Cr 3+ being induced by structural distortion and further enhanced by irradiation. Construction of the configurational energy level diagram enabled elucidation of this transition within the IVCT process. Therefore, this work provides insight into the emission mechanism within the high Cr 3+ concentration system, revealing a new design strategy for NIR-II emitting phosphors to promote its response., (© 2024 Wiley-VCH GmbH.)

Background: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) reduce the risk of hepatocellular carcinoma (HCC) in patients of hepatitis B. This study compared the difference between ETV and TDF on risk of HCC recurrence and mortality in patients with HBV-related HCC after curative intent treatment., Methods: Patients with HBV-related HCC who received HCC treatment (surgery or radiofrequency ablation [RFA]) and underwent long-term ETV or TDF therapy were retrospectively included. Baseline characteristics including age, sex, antiviral therapy, liver reserve, HCC stages, pathology reports and treatment modality were obtained. The risk of tumor recurrence, all-cause mortality, HCC-related mortality, and liver function were compared., Results: We identified 390 HBV-related HCC patients with curative intent treatment for HCC and treated with ETV (n = 328) or TDF (n = 62) between January 2011 and December 2020. The median age was 60 years, and 90.7% patients were males. After a median follow-up of 29 months, 186 patients developed recurrent HCC and 111 died. The baseline characteristics were comparable except more ALBI grade 3 patients in TDF group (76% vs. 48%, P < 0.001). Compared to ETV group, TDF users had lower all-cause mortality (adjusted hazard ratio [aHR]: 0.38, P = 0.003), and HCC-related mortality (aHR: 0.23, P = 0.005). Lower recurrence rate was noticed in TDF users after inverse probability of treatment weighting (IPTW). TDF users had improved ALBI grade and FIB-4 index compared with ETV groups., Conclusion: TDF therapy is associated with a reduced risk of HCC-related outcomes among patients with HBV-related HCC after curative intent treatment compared with ETV usage., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Neuroimaging techniques have been widely adopted to detect the neurological brain structures and functions of the nervous system. As an effective noninvasive neuroimaging technique, functional magnetic resonance imaging (fMRI) has been extensively used in computer-aided diagnosis (CAD) of mental disorders, e.g., autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). In this study, we propose a spatial-temporal co-attention learning (STCAL) model for diagnosing ASD and ADHD from fMRI data. In particular, a guided co-attention (GCA) module is developed to model the intermodal interactions of spatial and temporal signal patterns. A novel sliding cluster attention module is designed to address global feature dependency of self-attention mechanism in fMRI time series. Comprehensive experimental results demonstrate that our STCAL model can achieve competitive accuracies of 73.0 ± 4.5%, 72.0 ± 3.8%, and 72.5 ± 4.2% on the ABIDE I, ABIDE II, and ADHD-200 datasets, respectively. Moreover, the potential for feature pruning based on the co-attention scores is validated by the simulation experiment. The clinical interpretation analysis of STCAL can allow medical professionals to concentrate on the discriminative regions of interest and key time frames from fMRI data.