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The psychological effects of staged nasal reconstruction with a forehead flap were prospectively investigated. Thirty-three patients underwent nasal reconstruction with forehead flaps between March 2017 and July 2020. Three questionnaires were used to assess psychosocial functioning before surgery (time 1), 1 week after forehead flap transfer (time 2), 1 week after forehead flap division (time 3), and after refinement procedures (time 4). The patients were categorized into three groups according to the severity of nasal defects. Between- and within-group comparisons were conducted. All patients reported increased satisfaction with their appearance during nasal reconstruction. For most patients, levels of distress and social avoidance were highest before reconstruction (time 1). Both levels decreased as reconstruction advanced, and were significantly improved by times 3 and 4. The stage of reconstruction had a greater effect on these levels than did severity of nasal defect. Nasal reconstruction with forehead flap is beneficial physically and psychologically. Psychological evaluation before and after surgery facilitates patient-surgeon interactions and further enhances outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: This meta-analysis aimed to evaluate the impact of ketamine/esketamine on postoperative subjective quality of recovery (QoR)., Methods: MEDLINE, Embase, Cochrane library, and Google Scholar were searched for randomised controlled trials (RCTs) that examined the impacts of perioperative ketamine/esketamine use and postoperative QoR. The primary outcome was subjective QoR (QoR-9, QoR-15, QoR-40) on postoperative day (POD) 1-3, whereas the secondary outcomes included pain severity, anxiety scores, depression scores, risk of adverse events (i.e. nausea, vomiting, dizziness, drowsiness), and length of stay., Results: The analysis included 18 RCTs (1554 participants; ketamine: seven trials, esketamine: 11 trials), of which 15 were conducted in China. Ketamine/esketamine improved the QoR scores on PODs 1 and 2 compared with the control (standardised mean difference [SMD]: 0.63, P<0.0001 for POD 1; SMD: 0.56, P=0.04 for POD 2), without beneficial effect on POD 3. Subgroup analyses revealed significant differences in QoR scores on POD 1 by regimen (SMD: esketamine 1.14, ketamine 0.01) and country (SMD: China 0.82, other countries -0.21). The emotional domain of QoR was improved from PODs 1 to 3, whereas the other domains were only improved on POD 1. Lower postoperative anxiety (SMD: -0.48, P=0.003) and depression (SMD: -0.72, P=0.001) scores were also observed with ketamine/esketamine use. Furthermore, pain severity was reduced on PODs 1 and 2, with no difference in the risk of adverse events or length of stay., Conclusions: This meta-analysis demonstrated that ketamine/esketamine use in the perioperative period is associated with improved early subjective QoR, pain severity, and psychological symptoms without an increase in the likelihood of adverse events., Systematic Review Protocol: PROSPERO (CRD42023477580)., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Interleukin (IL)-33, a cytokine involved in immune responses, can activate its receptor, suppression of tumorigenicity 2 (ST2), is elevated during atrial fibrillation (AF). However, the role of IL-33/ST2 signaling in atrial arrhythmia is unclear. This study explored the pathological effects of the IL-33/ST2 axis on atrial remodeling and arrhythmogenesis. Patch clamping, confocal microscopy, and Western blotting were used to analyze the electrical characteristics of and protein activity in atrial myocytes (HL-1) treated with recombinant IL-33 protein and/or ST2-neutralizing antibodies for 48 hrs. Telemetric electrocardiographic recordings, Masson's trichrome staining, and immunohistochemistry staining of the atrium were performed in mice receiving tail vein injections with nonspecific immunoglobulin (control), IL-33, and IL-33 combined with anti-ST2 antibody for 2 weeks. IL-33-treated HL-1 cells had a reduced action potential duration, lower L-type Ca 2+ current, greater sarcoplasmic reticulum (SR) Ca 2+ content, increased Na + /Ca 2+ exchanger (NCX) current, elevation of K + currents, and increased intracellular calcium transient. IL-33-treated HL-1 myocytes had greater activation of the calcium-calmodulin-dependent protein kinase II (CaMKII)/ryanodine receptor 2 (RyR2) axis and nuclear factor kappa B (NF-κB) / NLR family pyrin domain containing 3 (NLRP3) signaling than did control cells. IL-33 treated cells also had greater expression of Nav1.5, Kv1.5, NCX, and NLRP3 than did control cells. Pretreatment with neutralizing anti-ST2 antibody attenuated IL-33-mediated activation of CaMKII/RyR2 and NF-κB/NLRP3 signaling. IL-33-injected mice had more atrial ectopic beats and increased AF episodes, greater atrial fibrosis, and elevation of NF-κB/NLRP3 signaling than did controls or mice treated with IL-33 combined with anti-ST2 antibody. Thus, IL-33 recombinant protein treatment promotes atrial remodeling through ST2 signaling. Blocking the IL-33/ST2 axis might be an innovative therapeutic approach for patients with atrial arrhythmia and elevated serum IL-33., (Copyright © 2024. Published by Elsevier Inc.)

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Background: The aim of palatoplasty is to create a functional palate to achieve normal speech, while minimizing post-operative complications. This study aimed to compare the long-term outcomes of modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ) and conventional Furlow palatoplasty (conventional-DOZ) performed in a single center., Methods: A retrospective review of consecutive patients who underwent Furlow palatoplasty between May 2007 and March 2014 was executed. Non-syndromic patients subjected to palatoplasty prior to 24 months of age and followed-up until at least 9 years of age were included., Results: A total of 196 small-DOZ and 280 conventional-DOZ palatoplasty patients were included in this study. Overall, 14 patients (2.9%) developed oronasal fistula, and 40 patients (8.4%) received velopharyngeal insufficiency (VPI) surgery. In comparisons, oronasal fistula rate was significantly higher in conventional-DOZ (0.5% vs. 4.6%, p = 0.01), and the VPI prevalence was not significantly different (9.2% vs. 7.9%, p = 0.62). Patients who developed fistula had a significantly higher likelihood of developing VPI than patients without oronasal fistula (50.0% vs. 7.1%, respectively; p < 0.01), with an odds ratio of 13.0., Conclusion: Both modalities of palatoplasty yielded commendable velopharyngeal function in the long-term follow-up. The small-DOZ with reduced tension lowered the risk of oronasal fistula., Competing Interests: Conflicts of interest statement No conflicting relationship exists for all authors., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein-ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC 50 values of 8.8 μM, 6.7 μM, and 7.6 μM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC 50 = 5.9 μM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC 50 of 9.3 μM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection.

Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes., (© 2024. The Author(s).)

Nitrogen-doped carbon dots (NCDs) featuring primary pyrrolic N and pyridinic N dominated configurations were prepared using hydrothermal (H-NCDs) and microwave (M-NCDs) methods, respectively. These H-NCDs and M-NCDs were subsequently applied to decorate CsPbBr 3 nanocrystals (CPB NCs) individually, using a ligand-assisted reprecipitation process. Both CPB/M-NCDs and CPB/H-NCDs nanoheterostructures (NHSs) exhibited S-scheme charge transfer behavior, which enhanced their performance in photocatalytic CO 2 reduction and selectivity of CO 2 -to-CH 4 conversion, compared to pristine CPB NCs. The presence of pyrrolic N configuration at the heterojunction of CPB/H-NCDs facilitated efficient S-scheme charge transfer, leading to a remarkable 43-fold increase in photoactivity. In contrast, CPB/M-NCDs showed only a modest 3-fold enhancement in photoactivity, which was attributed to electron trapping by pyridinic N at the heterojunction. The study offers crucial insights into charge carrier dynamics within perovskite/carbon NHSs at the molecular level to advance the understanding of solar fuel generation.

This study developed a DC-free technique that used dark-mode scanning capacitance microscopy (DM-SCM) with a small-area contact electrode to evaluate and image equivalent oxide thicknesses (EOTs). In contrast to the conventional capacitance-voltage (C-V) method, which requires a large-area contact electrode and DC voltage sweeping to provide reliable C-V curves from which the EOT can be determined, the proposed method enabled the evaluation of the EOT to a few nanometers for thermal and high-k oxides. The signal intensity equation defining the voltage modulation efficiency in scanning capacitance microscopy (SCM) indicates that thermal oxide films on silicon can serve as calibration references for the establishment of a linear relationship between the SCM signal ratio and the EOT ratio; the EOT is then determined from this relationship. Experimental results for thermal oxide films demonstrated that the EOT obtained using the DM-SCM approach closely matched the value obtained using the typical C-V method for frequencies ranging from 90 kHz to 1 MHz. The percentage differences in EOT values between the C-V and SCM measurements were smaller than 0.5%. For high-k oxide films, DM-SCM with a DC-free operation may mitigate the effect of DC voltages on evaluations of EOTs. In addition, image operations were performed to obtain EOT images showing the EOT variation induced by DC-stress-induced charge trapping. Compared with the typical C-V method, the proposed DM-SCM approach not only provides a DC-free approach for EOT evaluation, but also offers a valuable opportunity to visualize the EOT distribution before and after the application of DC stress.

The mutated SCN5A gene encoding defective Nav1.5 protein causes arrhythmic ailments and is associated with enhanced cardiac fibrosis. This study investigated whether SCN5A mutation directly affects cardiac fibroblasts and explored how defective SCN5A relates to cardiac fibrosis. SCN5A knockdown (SCN5AKD) human cardiac fibroblasts (HCF) had higher collagen, α-SMA, and fibronectin expressions. Micro-RNA deep sequencing and qPCR analysis revealed the downregulation of miR-452-5p and bioinformatic analysis divulged maladaptive upregulation of transforming growth factor β (TGF-β) signaling in SCN5AKD HCF. Luciferase reporter assays validated miR-452-5p targets SMAD4 in SCN5AKD HCF. Moreover, miR-452-5p mimic transfection in SCN5AKD HCF or AAV9-mediated miR-452-5p delivery in isoproterenol-induced heart failure (HF) rats, resulted in the attenuation of TGF-β signaling and fibrogenesis. The exogenous miR-452-5p significantly improved the poor cardiac function in HF rats. In conclusion, miR-452-5p regulates cardiac fibrosis progression by targeting the TGF-β/SMAD4 axis under the loss of the SCN5A gene., Competing Interests: Authors declare no conflict of interest., (© 2024 The Author(s).)

Background: Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer., Methods: We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity., Results: Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I 2  = 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I 2  = 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I 2  = 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I 2  = 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I 2  = 0%)., Conclusions: SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens., (© 2024. The Author(s).)

Objectives: Patients with chronic conditions enrolled in high-deductible health plans (HDHPs) face cost-related access barriers and high out-of-pocket spending. Our objectives were to develop a novel behavioural intervention to help HDHP enrollees with chronic conditions use cost-conscious strategies and evaluate the intervention's preliminary effectiveness, acceptability and feasibility., Design: Prospective., Setting: Online (USA)., Participants: 36 US adults enrolled in an HDHP through their employer or an exchange with diabetes, hypertension, asthma, coronary artery disease and/or chronic obstructive pulmonary disease. 31/36 participants completed the study., Intervention: We developed a 5-week intervention consisting of a website with educational modules on discussing costs with clinicians, saving for future healthcare costs, comparing healthcare prices and quality, preparing for appointments, following up after appointments and planning for future healthcare needs; and emails encouraging participants to access each module., Outcomes: We conducted a single-arm proof-of-concept pilot study of the intervention. Baseline and postintervention surveys measured primary outcomes of health insurance literacy and confidence in using cost-conscious strategies. 10 participants completed postintervention interviews., Results: 31 (86%) participants completed a baseline and postintervention survey. Mean health insurance literacy scores (20-80 scale) improved from 56.5 to 67.1 (p < 0.001). Mean confidence scores (0-10 scale) improved for talking to a healthcare provider about cost (6.1-7.6, p=0.0094), saving for healthcare (5.8-6.6, p = 0.068), comparing prices (5.4-6.9, p=0.005) and comparing quality (6.1 to 7.6, p=0.0034). Participants found the website easy to use and helpful for learning about cost-conscious strategies on postintervention interviews., Conclusions: Our novel behavioural intervention was acceptable to HDHP enrollees with chronic conditions, feasible to deliver and associated with increased health insurance literacy and confidence in using cost-conscious strategies. This intervention should be tested in a definitive randomised controlled trial that is fully powered to evaluate its effects on cost-related access barriers, out-of-pocket spending and health outcomes in this growing patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ammonia (NH 3 ) is attracting attention as a carbon-free energy source and a significant precursor to inorganic PM 2.5 (hereafter PM 2.5 ), aside from NO x and SO x . Since the emission of NH 3 has often been overlooked compared to NO x and SO x, this study aims to reveal the role of NH 3 and its emission control on PM 2.5 in Kanto, Japan. With the aid of gas ratio (GR) quantitatively defining the stoichiometry between the three precursors to PM 2.5 , and the aid of atmospheric modeling software ADMER-PRO, coupled with thermodynamics calculations, the spatiotemporal distribution along with PM 2.5 reduction under different NH 3 emission cutoff strategies in Kanto had been revealed for the first time. The cutoff of NH 3 emission could effectively reduce the PM 2.5 concentration, with sources originated from agriculture, human/pet activities, and vehicle sources, overall giving a 93.32% PM 2.5 reduction. Different cutoff strategies lead to distinct reduction efficiencies of the overall and local PM 2.5 concentrations, with GR as a crucial factor. The regions with GR ∼1, are sensitive to the NH 3 concentration for forming PM 2.5 , at which the NH 3 reduction strategies should be applied with high priority. On the other hand, installing a new NH 3 emission source should be avoided in the region with GR < 1, suppressing the so-yielded PM 2.5 pollution. The future PM 2.5 pollution control related to the NH 3 emission control strategies based on GR, which is stoichiometry-based and applicable to regions other than Kanto, has been discussed., 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.)

Esophageal cancer is a common malignancy worldwide with a poor prognosis without radical resection. Neoadjuvant concurrent chemoradiotherapy (NACRT) followed by esophagectomy is widely used for treating locally advanced esophageal cancer in the thorax. The study aimed to assess mutation profiles and their correlation with therapeutic outcomes in patients diagnosed with locally advanced thoracic esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted on 62 patients with ESCC who underwent NACRT. All patients received concurrent chemoradiotherapy (CCRT) utilizing intensity-modulated radiation therapy alongside concurrent chemotherapy with a cisplatin-based regimen. A 35-gene next-generation sequencing (NGS) panel detecting 402 genetic variants was used, which has been proven predictive in ESCC patients who received definitive chemoradiation. The 35-gene mutation profiles were analyzed in pre-treatment biopsies. The results reveled there were variants correlated with pathological complete remission or partial response, overall survival, and progression-free survival. A combination of p.Pro1319Ser and p.Arg2159Gly mutations in the MUC17 gene demonstrated an adverse impact on pathological response (OR [95% CI] = 7.00 (3.07-15.94), P < 0.001). Additionally, the variants located in the MUC17, MUC4 , and MYH4 genes exhibited notably effects on tumor recurrence or mortality. Patients harboring either the MUC17 p.Thr2702Val or MUC4 p.Thr3355Ser mutation displayed a more than four-fold increased risk for disease recurrence or mortality. We concluded that specific mutations correlated to the pathological complete response in ESCC receiving neoadjuvant chemoradiation can be identified through the utilization of 35-gene expression profiles. Further investigation into the pathophysiological roles of MUC17 and MUC4 mutations in ESCC is warranted., Competing Interests: None., (AJCR Copyright © 2024.)

Introduction: Corneal endothelial dysfunction results in cornea opacity, damaging sightedness, and affecting quality of life. A corneal transplant is the current effective intervention. Due to the scarcity of donated cornea, such an unmet medical need requires a novel therapeutic modality., Objectives: Customizing patients' corneal endothelial progenitor cells with proliferative activity and lineage restriction properties shall offer sufficient therapeutic cells for corneal endothelial dystrophy., Methods: The customized induced human corneal endothelial progenitor-like cell (iHCEPLC) was obtained through cell fate conversions starting from PBMC (peripheral blood mononuclear cell), hiPSC (human induced pluripotent stem cell), and hNCC (human neural crest cell), while it finally reached the iHCEPLC state via a series of induction. Several molecular diagnoses were applied to depict its progenitor state, including RNAseq, FlowCytometer, immunostainings, and rtPCR. Significantly, it can be induced to gain differentiation maturity through contact inhibition. In addition, a BAK-mediated rabbit model of corneal endothelial dystrophy was established in the present study to test the therapeutic effectiveness of the iHCEPLC., Results: After inducing cell fate conversion, the specific HCEC markers were detected by rtPCR and immunostaining in iHCEPLC. Further, RNAseq was applied to distinguish its progenitor-like cell fate from primary human corneal endothelial cells (HECE). FlowCytometry profiled the heterogeneity subpopulation, consistently displaying a subtle difference from primary HCEC. A terminal differentiation can be induced in iHCEPLC, addressing its progenitor-like fate. iHCEPLC can restore the BAK-based rabbit model of corneal endothelial dystrophy. Immunohistochemistry verified that such acuity restoration of the BAK-treated cornea is due to the introduced iHCEPLC, and such therapeutic effectiveness is observed in the long term., Conclusion: Here, we demonstrated that customized iHCEPLC has long-term therapeutic efficacy. As a progenitor cell, our iHCEPLC has a restricted cell lineage nature and can proliferate in vitro, supporting sufficient therapeutic candidate cells. Due to the immune-privileged nature of the cornea, our iHCEPLC proves the principle of therapeutical feasibility in both autogenic and allogeneic modalities., 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. Production and hosting by Elsevier B.V.)

The indirect chloride-mediated ammonia oxidation encounters challenges in maintaining the effectiveness of metal oxide anodes when treating wastewaters with complex compositions. This study aims to develop a highly stable anode with RuO 2 -SnO 2 coatings for treating an etching effluent from semiconductor manufacturing, which majorly contains NH 3 and organic compounds. The RuSnO x /Ti electrode was synthesized using wet impregnation and calcination processes. The metal oxide configuration on Ti plate substrate was tuned by varying the step-dipping process in RuCl 3 and SnCl 4 baths. A 10-day continuous-flow electrolysis was conducted for studying the ammonia removal and chlorine yield under variable conditions, including detention, pH, current density, and initial ammonia and chloride concentrations. In the RuSnO x coatings, the configuration comprising RuO 2 nanorods as the surface layer and an intermediate layer of SnO 2 crystallites (by plating Ru 3+ for three times to cover one Sn 4+ layer, denoted as the Ru 3 Sn/Ti electrode) exhibited the best durability for acid washing, along with relatively high Faradaic efficiency and low energy consumption. To further improve the treatability of real wastewater (NH 3 -N = 634 mg L -1 , chemical oxygen demand (COD) = 6700 mg L -1 , Cl - = 2000 mg L -1 , pH 11), the duel-cell electrolyzers were constructed in series under a current density of 30 mA cm -2 and 45 min detention. Ultimately, removals of NH 3 and COD reached 95.8% and 76.3%, respectively, with successful limitation of chloramine formation., 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.)

Background: The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown., Methods and Results: This study showed that sdc4 expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, sdc4 expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of sdc4 led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of tgfb1a and col1a1a, as well as the protein expression of Fibronectin, were all down-regulated under sdc4 knockdown. In addition, we verified that sdc4 expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of sdc4 expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients., Conclusions: Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration., (© 2024. The Author(s).)

Background: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks., Methods: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015., Results: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001)., Conclusion: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu 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.)

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP)., Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups., Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis., Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Purpose: Brachytherapy is a critical component of the standard-of-care curative radiotherapy regimen for women with locally advanced cervical cancer (LACC). However, existing literature suggests that many patients will not receive the brachytherapy boost. We used machine learning (ML) and explainable artificial intelligence to characterize this disparity., Materials and Methods: Patients with LACC diagnosed from 2004 to 2020 who received definitive radiation were identified in the National Cancer Database. Five ML models were trained to predict if a patient received a brachytherapy boost. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To identify trends that may be attributable to the coronavirus disease 2019 (COVID-19) pandemic, the previous analysis was repeated and limited to 2019 to 2020., Results: A total of 37,564 patients with LACC were identified; 5799 were diagnosed from 2019 to 2020 (COVID cohort). Of these patients, 59.3% received a brachytherapy boost, with 76.4% of patients diagnosed in 2019 to 2020 receiving a boost. The random forest model achieved the best performance for both the overall and COVID cohorts. In the overall cohort, the most important predictive features were the year of diagnosis, stage, age, and insurance status. In the COVID cohort, the most important predictive features were FIGO stage, age, insurance status, and hospital type. Of the 26 patients who tested positive for COVID-19 during their course of radiotherapy, 19 (73.1%) received a brachytherapy boost., Conclusions: A gradual increase in brachytherapy boost utilization has been noted, which did not seem to be significantly impacted by the onset of the COVID-19 pandemic. ML could be considered to identify patient populations where brachytherapy is underutilized, which can provide actionable feedback for improving access., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Melanoma predominantly occurs in White individuals, which is associated with factors such as exposure to UV radiation and skin pigmentation. Despite its low incidence, melanoma is the primary cause of skin cancer-related death in Asia, typically in areas with low sun exposure. In our previous whole-exome sequencing study, we identified mutational signature 12 as the most prevalent variant in Asian patients, differing from the common UV-associated mutational signature 7 observed in White individuals. We also observed major differences between acral melanoma (AM) and nonacral melanoma (NAM) in terms of signatures 7, 21, and 22. Notably, few studies have investigated the genomic differences between AM and NAM in Asian individuals. Therefore, in this study, we conducted transcriptomic sequencing to examine the disparities in RNA expression between AM and NAM. Ribosomal RNA depletion was performed to enhance the detection of functionally relevant coding and noncoding transcripts. Ingenuity pathway analysis revealed significant differences in gene expression and regulatory pathways between AM and NAM. The results also indicate that the genes involved in cell cycle signaling or immune modulation and programmed cell death protein 1/programmed cell death 1 ligand 1 signaling were differentially expressed in NAM and AM. In addition, high CDK4 expression and cell cycle variability were observed in AM, with high immunogenicity in NAM. Overall, these findings provide further insights into the pathogenesis of melanoma and serve as a reference for future research on this major malignant disease., (© 2024 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.

Background: Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear., Methods: Rats with myosin peptide-induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat's RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca 2+ transients, and Ca 2+ -modulated protein expression in individual myocytes isolated from the RVOTs., Results: The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca 2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca 2+ transients, lower L-type Ca 2+ currents, larger late Na + currents , larger Na + -Ca 2+ exchanger currents, higher reactive oxygen species levels, and higher Ca 2+ /calmodulin-dependent protein kinase II levels than did those of the control and treatment groups., Conclusion: Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling., (© 2024. The Author(s).)

Aim: To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses (IOLs)., Methods: This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June 2020. All patients underwent comprehensive preoperative and postoperative ophthalmologic examination, and data were collected including age, sex, surgical indications, best-corrected visual acuity, refractive error, intraocular pressure. Presence of intraoperative and postoperative surgical complications was documented., Results: A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±5.3mo. Visual acuity improved from a mean of 0.35 (0.46±0.32 logMAR) preoperatively to 0.61 (0.21±0.18 logMAR) at the 3-month follow-up ( P =0.002). The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was -1.24±0.80 diopters (D) and -1.42±0.97 D, respectively. There was no statistically significant difference between preoperative and postoperative astigmatism ( P =0.156). The mean IOL-induced astigmatism was -0.23±0.53 D. The mean spherical equivalent at the 3-month follow-up was -0.1±0.94 D. No major complications were noted during the follow-up period., Conclusion: Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications., Competing Interests: Conflicts of Interest: Huang WY, None; Chen YJ, None., (International Journal of Ophthalmology Press.)

Objectives: To describe a population health-based program to support employee and dependent mental health and learn from engagement trends., Methods: Retrospective analysis of a program utilizing an assessment of mental health risk. For scoring "at risk," a Care Concierge is offered to connect users with resources., Results: Participation was offered to 56,442 employees and dependents. Eight thousand seven hundred thirty-one completed the assessment (15%). Of those, 4,644 (53%) scored moderate or higher. A total of 418 (9%) engaged the Care Concierge. Factors that negatively influenced the decision to engage care included bodily pain, financial concerns. Positive influences were younger age, high stress, anxiety, PTSD and low social support., Conclusion: Proactive assessment plus access to a Care Concierge facilitates mental healthcare utilization. Several factors influence likelihood to engage in care. A better understanding of these factors may allow for more targeted outreach and improved engagement., Competing Interests: MF was employed by Quest Diagnostics. JoH was employed by BHS. JeH was employed by emVitals. SC was employed by Johns Hopkins Healthcare. The remaining 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 Woodard, Bailey, Esagoff, Fragala, Hayward, Hunter, Hsu, Kim, Peters and Carr.)

Background: This study aimed to develop an automated method to measure the gray-white matter ratio (GWR) from brain computed tomography (CT) scans of patients with out-of-hospital cardiac arrest (OHCA) and assess its significance in predicting early-stage neurological outcomes., Methods: Patients with OHCA who underwent brain CT imaging within 12 h of return of spontaneous circulation were enrolled in this retrospective study. The primary outcome endpoint measure was a favorable neurological outcome, defined as cerebral performance category 1 or 2 at hospital discharge. We proposed an automated method comprising image registration, K-means segmentation, segmentation refinement, and GWR calculation to measure the GWR for each CT scan. The K-means segmentation and segmentation refinement was employed to refine the segmentations within regions of interest (ROIs), consequently enhancing GWR calculation accuracy through more precise segmentations., Results: Overall, 443 patients were divided into derivation N=265, 60% and validation N=178, 40% sets, based on age and sex. The ROI Hounsfield unit values derived from the automated method showed a strong correlation with those obtained from the manual method. Regarding outcome prediction, the automated method significantly outperformed the manual method in GWR calculation (AUC 0.79 vs. 0.70) across the entire dataset. The automated method also demonstrated superior performance across sensitivity, specificity, and positive and negative predictive values using the cutoff value determined from the derivation set. Moreover, GWR was an independent predictor of outcomes in logistic regression analysis. Incorporating the GWR with other clinical and resuscitation variables significantly enhanced the performance of prediction models compared to those without the GWR., Conclusions: Automated measurement of the GWR from non-contrast brain CT images offers valuable insights for predicting neurological outcomes during the early post-cardiac arrest period., (© 2024. The Author(s).)

Background: Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms., Methods: PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains., Results: A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p  = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores ( p  = 0.003, p  = 0.012, and p  = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p  < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis., Conclusion: Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms., 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 Chiu, Fang, Lei, Lin, Chang and Guo.)

Background/purpose: Newly developed temporary anchorage devices (TADs) serve a strong orthodontic anchorage to intrude molars for correction of anterior open bite (AOB). We measured cephalometric changes in skeletal open bite patients which developed subsequently to temporomandibular joint disorders with bilateral point contacts at terminal molars., Methods: We retrospectively recruited 32 patients who had been treated their TMD before orthodontic correction (overbite: -3.14 ± 1.86 mm). Partial orthodontic appliances were used to intrude posterior teeth using TADs until positive OB obtained (T1). Full fixed appliances were then used to achieve proper overjet and overbite (T2). We collected lateral cephalograms before (T0), during (T1) and after (T2) treatment, and at follow-ups (T3). Using ANOVA, we analyzed the differences among these time points to determine treatment changes and stability of orthodontic results., Results: In this group predominantly comprising young adult women, orthodontic treatment with TADs significantly reduced upper posterior dental heights (T2-T0:-1.84 ± 0.66 mm) and facilitated the retraction and uprighting upper incisors (T2-T0: -9.92 ± 1.72°), to achieve appropriate OJ (T2-T0: -3.21 ± 0.49 mm) and OB (T2-T0: 4.10 ± 0.28 mm) with p < 0.05. Except upper posterior dental height, most of cephalometric changes including OJ, OB, and upper incisal axis remained significant at follow-ups with retention time of 3.7 ± 2.6 years. Only three out of 30 patients experienced small amount of open bite at T3., Conclusion: Orthodontic correction of OJ remained relatively stable among 90 % of patients with TMJ degeneration by intrusion via TADs. This modern but conservative orthodontic approach can improve occlusal functions in skeletal open bites., (Copyright © 2023. Published by Elsevier B.V.)

Background: The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence., Methods: Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models., Results: The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors., Conclusion: This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes., Competing Interests: Conflicts of interest: Dr. Chien-Wei Su, Dr. Fa-Yauh Lee, Dr. Yi-Hsiang Huang, and Dr. Ming-Chih Hou, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y 12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Skilled home healthcare (HH) provided in-person care to older adults during the COVID-19 pandemic, yet little is known about the pandemic's impact on HH care transition patterns. We investigated pandemic impact on (1) HH service volume; (2) population characteristics; and (3) care transition patterns for older adults receiving HH services after hospital or skilled nursing facility (SNF) discharge., Methods: Retrospective, cohort, comparative study of recently hospitalized older adults (≥ 65 years) receiving HH services after hospital or SNF discharge at two large HH agencies in Baltimore and New York City (NYC) 1-year pre- and 1-year post-pandemic onset. We used the Outcome and Assessment Information Set (OASIS) and service use records to examine HH utilization, patient characteristics, visit timeliness, medication issues, and 30-day emergency department (ED) visit and rehospitalization., Results: Across sites, admissions to HH declined by 23% in the pandemic's first year. Compared to the year prior, older adults receiving HH services during the first year of the pandemic were more likely to be younger, have worse mental, respiratory, and functional status in some areas, and be assessed by HH providers as having higher risk of rehospitalization. Thirty-day rehospitalization rates were lower during the first year of the pandemic. COVID-positive HH patients had lower odds of 30-day ED visit or rehospitalization. At the NYC site, extended duration between discharge and first HH visit was associated with reduced 30-day ED visit or rehospitalization., Conclusions: HH patient characteristics and utilization were distinct in Baltimore versus NYC in the initial year of the COVID-19 pandemic. Study findings suggest some older adults who needed HH may not have received it, since the decrease in HH services occurred as SNF use decreased nationally. Findings demonstrate the importance of understanding HH agency responsiveness during public health emergencies to ensure older adults' access to care., (© 2024 The American Geriatrics Society.)

Background: Metabolic stress predisposes to ventricular arrhythmias and sudden cardiac death. Right ventricular outflow tract (RVOT) is the common origin of ventricular arrhythmias. Adenosine monophosphate-regulated protein kinase (AMPK) activation is an important compensatory mechanism for cardiac remodeling during metabolic stress., Objectives: The purpose of this study was to access whether AMPK inhibition would modulate RVOT electrophysiology, calcium (Ca 2+ ) regulation, and RVOT arrhythmogenesis or not., Methods: Conventional microelectrodes were used to record electrical activity before and after compound C (10 µM, an AMPK inhibitor) in isoproterenol (1 µM)-treated rabbit RVOT tissue preparations under electrical pacing. Whole-cell patch-clamp and confocal microscopic examinations were performed in baseline and compound C-treated rabbit RVOT cardiomyocytes to investigate ionic currents and intracellular Ca 2+ transients in isolated rabbit RVOT cardiomyocytes., Results: Compound C decreased RVOT contractility, and reversed isoproterenol increased RVOT contractility. Compound C decreased the incidence, rate, and duration of isoproterenol-induced RVOT burst firing under rapid pacing. Compared to baseline, compound C-treated RVOT cardiomyocytes had a longer action potential duration, smaller intracellular Ca 2+ transients, late sodium (Na + ), peak L-type Ca 2+ current density, Na + -Ca 2+ exchanger, transient outward potassium (K + ) current, and rapid and slow delayed rectifier K + currents., Conclusion: AMPK inhibition modulates RVOT electrophysiological characteristics and Ca 2+ homeostasis, contributing to lower RVOT arrhythmogenic activity. Accordingly, AMPK inhibition might potentially reduce ventricular tachyarrhythmias., (© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Background: New-onset diabetes after transplantation and increased insulin resistance have both been shown to affect graft performance and survival after kidney transplantation. Thus, we aimed to evaluate the predictive roles of different insulin resistance indices on early graft function in kidney transplant recipients., Materials and Methods: We conducted a retrospective analysis of non-diabetic patients who received kidney transplantation between January 1, 2018 and December 31, 2021. The primary outcome was the predictive role of different insulin resistance indices on early graft function of serum creatinine level and estimated glomerular filtration rate at 1, 3, 6, and 12 months. The secondary outcome analyzed was the possible clinical predictive factors for poor kidney graft function at 12 months., Results: Among 123 kidney transplantation patients, stratification with homeostatic model assessment for insulin resistance showed no significant difference in kidney graft function outcome at 1, 3, 6, and 12 months. However, patients with a higher insulin-to-glucose ratio exhibited a significantly higher serum creatinine level at 3 and 6 months and a significantly lower estimated glomerular filtration rate level at 3, 6, and 12 months. Using multivariate logistic regression analysis, patients with a higher insulin-to-glucose ratio were associated with a poorer kidney graft function 12 months after transplantation., Conclusion: Patients with a higher baseline insulin resistance with an insulin-to-glucose ratio ≥of 0.092 exhibited a significantly worse early kidney graft function. Thus, with the identification of patients with increased insulin resistance, early intervention, and preventive measures can be implemented to enhance graft performance further., Competing Interests: Declaration of competing interest All the authors declare 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.)

Background: This study aimed to evaluate the feasibility of using mHealth devices for monitoring postoperative ambulation among patients with colorectal cancer undergoing minimally invasive surgery (MIS)., Methods: Patients with colorectal cancer undergoing MIS were prospectively recruited to wear mHealth devices for recording postoperative ambulation between October 2018 and January 2021. The primary outcome was the compliance by evaluating the weekly submission rate of step counts. The secondary outcome was the association of weekly step counts and postoperative length of stay., Results: Of 107 eligible patients, 53 patients wore mHealth devices, whereas 54 patients did not. The average weekly submission rate was 72.6% for the first month after surgery. The total step counts <4000 or >10 000 in the postoperative week one were negatively associated with postoperative length of stay (β = -2.874, p = 0.038)., Conclusions: mHealth devices provide an objective assessment of postoperative ambulation among patients with colorectal cancer undergoing MIS., Clinical Trial Registration: NCT03277235., (© 2024 John Wiley & Sons Ltd.)

Purpose: We observed transient elevations in creatinine levels among kidney recipients after three traditional holidays in Taiwan. This retrospective cohort study aimed to compare the changes in eGFR levels after Chinese New Year, Dragon Boat Festival, and Mid-Autumn Festival, all of which are associated with high-calorie and high-fat diets., Materials and Methods: We conducted a retrospective analysis of 364 kidney recipients with stable graft function who were following at Chang Gung Memorial Hospital Linkou from 2018 to 2020. The graft function before and after the festival was determined by calculating the eGFR level using the serum creatinine measured during clinic visits prior to and following the festival. The patients were then categorized into subgroups based on their sex, BMI, and co-morbidities. The eGFR levels before and after the festival were evaluated and compared within these subgroups., Results: A total of 301 kidney recipients have been finally included in this retrospective cohort study. The analysis showed a significant decrease in overall eGFR levels after Chinese New Year (from 56.92 ± 29.70 to 55.14 ± 24.79, P = .006), Mid-Autumn Festival (from 54.03 ± 24.61 to 53.35 ± 24.33, P = .008), and Dragon Boat Festival only in 2020 (from 50.98 ± 24.35 to 49.99 ± 23.45, P = .018). The analysis of subgroups suggested a tendency of renal function decline after all 3 traditional holidays in patient groups with DM or hypertension or nonoverweight status., Conclusion: In this study, we observed a significant decline in renal function among kidney recipients following traditional holidays in Taiwan, particularly among recipients with hypertension or diabetes mellitus or those who were not overweight., 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.)

Introduction: Urothelial cancers were one of the most common malignancies in patients with kidney transplants. Although radical nephroureterectomy is still the standard of care in current guidelines, studies have shown that significantly improved perioperative outcomes can be achieved for patients who underwent bilateral nephroureterectomy. Our study provides evidence on the outcome of bilateral nephroureterectomy and unilateral nephroureterectomy in kidney recipients with upper tract urothelial carcinoma., Material and Methods: In the study, the data of patients from a single center, Chang Gung Memorial Hospital Linkou branch, were collected retrospectively from 1981 to 2023. The patient's detailed information was collected through the medical records in the hospital., Results: A total of 44 cases of kidney recipients with upper urinary tract urothelial carcinoma were collected in this study. Of the patients, 19 nephroureterectomies were performed before 2008 and 24 afterward. Incidental findings of contralateral tumors were noted in 3 out of 6 patients who underwent bilateral nephroureterectomy before 2008 and 3 out of 12 after 2008. Contralateral upper urinary tract urothelial carcinoma after unilateral nephroureterectomy was noted in 3 patients within a median of 8.1 years. The progression-free survival of bilateral nephroureterectomy was significantly better compared with a unilateral group (not reached, 15.8 years, respectively)., Discussion: Our study, along with previous studies, provides evidence that bilateral nephroureterectomy may be a better treatment option in kidney recipients with upper tract urothelial carcinoma. Our study has several limitations based on its retrospective nature., 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.)

Dinitrosyl iron unit (DNIU), [Fe(NO) 2 ], is a natural metallocofactor for biological storage, delivery, and metabolism of nitric oxide (NO). In the attempt to gain a biomimetic insight into the natural DNIU under biological system, in this study, synthetic dinitrosyl iron complexes (DNICs) [(NO) 2 Fe(μ-SCH 2 CH 2 COOH) 2 Fe(NO) 2 ] ( DNIC-COOH ) and [(NO) 2 Fe(μ-SCH 2 CH 2 COOCH 3 ) 2 Fe(NO) 2 ] ( DNIC-COOMe ) were employed to investigate the structure-reactivity relationship of mechanism and kinetics for cellular uptake of DNICs, intracellular delivery of NO, and activation of cytoprotective heme oxygenase (HO)-1. After rapid cellular uptake of dinuclear DNIC-COOMe through a thiol-mediated pathway ( t max = 0.5 h), intracellular assembly of mononuclear DNIC [(NO) 2 Fe(SR)(S Cys )] n - /[(NO) 2 Fe(SR)(S Cys-protein )] n - occurred, followed by O 2 -induced release of free NO ( t max = 1-2 h) or direct transfer of NO to soluble guanylate cyclase, which triggered the downstream HO-1. In contrast, steady kinetics for cellular uptake of DNIC-COOH via endocytosis ( t max = 2-8 h) and for intracellular release of NO ( t max = 4-6 h) reflected on the elevated activation of cytoprotective HO-1 (∼50-150-fold change at t = 3-10 h) and on the improved survival of DNIC-COOH -primed mesenchymal stem cell (MSC)/human corneal endothelial cell (HCEC) under stressed conditions. Consequently, this study unravels the bridging thiolate ligands in dinuclear DNIC-COOH / DNIC-COOMe as a switch to control the mechanism, kinetics, and efficacy for cellular uptake of DNICs, intracellular delivery of NO, and activation of cytoprotective HO-1, which poses an implication on enhanced survival of postengrafted MSC for advancing the MSC-based regenerative medicine., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: To compare short-term cognitive outcomes among groups with and without neuropsychiatric symptoms (NPSs) or antipsychotic prescription and to determine which disease status or treatment modality is associated with relatively faster cognitive decline., Methods: We retrospectively analyzed a prospective cohort of patients diagnosed with dementia and mild cognitive impairment. All participants were evaluated using the Cognitive Abilities Screening Instrument (CASI) during their initial clinical assessments and at the annual follow-up. The dependent variable was annual delta CASI. Multivariate linear regression analysis was used to assess the degree of association between NPS, antipsychotic use, and cognitive decline after adjusting for confounding factors. Neuropsychiatric symptoms were examined individually to determine their predictive value for cognitive decline., Results: A total of 407 (N = 407) patients were included in the study. NPSs, rather than antipsychotic use, led to faster cognitive decline. A higher baseline NPI total score predicted a significantly faster decline in CASI scores (1-year delta CASI = -0.22, 95% CI = -0.38~ -0.05, p = 0.010). Specific items (delusions, agitation, depression, anxiety, euphoria, and apathy) in the NPS significantly increased cognitive decline., Conclusion: Certain neuropsychiatric symptoms, rather than antipsychotic use, lead to faster cognitive decline in a dementia collaborative care model. Checking for and providing appropriate interventions for NPS in people with dementia and their caregivers are highlighted., Competing Interests: Yen-Jen Chen, Ming-Che Chang, Kai-Ming Jhang and Wen-Fu Wang contributed equally to this work and share first authorship. The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 Chen et al.)

Objectives: The protective effects and related mechanisms of Jing-Si herbal tea (JSHT) were investigated in cellular damage mediated by pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, on normal human lung fibroblast by multiomic platform analysis., Materials and Methods: The in silico high-throughput target was analyzed using pharmacophore models by BIOVIA Discovery Studio 2022 with ingenuity pathway analysis software. To assess cell viability, the study utilized the MTT assay technique. In addition, the IncuCyte S3 ZOOM System was implemented for the continuous monitoring of cell confluence of JSHT-treated cytokine-injured HEL 299 cells. Cytokine concentrations were determined using a Quantibody Human Inflammation Array. Gene expression and signaling pathways were determined using next-generation sequencing., Results: In silico high-throughput target analysis of JSHT revealed ingenuity in canonical pathways and their networks. Glucocorticoid receptor signaling is a potential signaling of JSHT. The results revealed protective effects against the inflammatory cytokines on JSHT-treated HEL 299 cells. Transcriptome and network analyses revealed that induction of helper T lymphocytes, TNFSF12, NFKB1-mediated relaxin signaling, and G-protein coupled receptor signaling play important roles in immune regulatory on JSHT-treated cytokine-injured HEL 299 cells., Conclusion: The findings from our research indicate that JSHT holds promise as a therapeutic agent, potentially offering advantageous outcomes in treating virus infections through various mechanisms. Furthermore, the primary bioactive components in JSHT justify extended research in antiviral drug development, especially in the context of addressing coronavirus., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Histamine modulates immunity by binding to histamine receptor 2 (H2R). Cimetidine, an H2R antagonist that inhibits gastric acid secretion and treats gastrointestinal ulcers, interferes with histamine-mediated immunomodulation and may have anticancer activity. This study examined cimetidine's effect on the anticancer effect of anti-PD-L1 in colon cancer. The MTT assay, colony formation assay, and DNA histograms assessed cell viability, clonogenicity, and cell cycle distribution, respectively. Flow cytometry measured H2R and PD-L1 expression and estimated specific immune cell lineages. For the in vivo study, tumor cells were subcutaneously implanted into the right flank of BALB/c mice. Cimetidine had no significant effect on CT26 cell viability, clonogenicity, or cell cycle distribution. It also did not affect H2R and PD-L1 expression levels in CT26 cells. In vivo, anti-PD-1 and anti-PD-L1 suppressed CT26 tumor growth, whereas cimetidine showed mild antitumor activity. In the combined experiment, cimetidine significantly attenuated anti-PD-1 and anti-PD-L1' antitumor effects without major toxicity. In the tumor microenvironment, anti-PD-L1 increased CD3 + T, CD4 + T, and CD8 + T cells and M1 macrophages. Combined treatment with cimetidine reversed this. Cimetidine also reversed anti-PD-1 and anti-PD-L1's decrease in circulating and tumor-associated neutrophils. Cimetidine attenuated anti-PD-L1's antitumor effect and modulated the tumor microenvironment in colon cancer.

Background: This meta-analysis aimed to synthesize current evidence on the association between the Geriatric Nutritional Risk Index (GNRI) and long-term outcomes in patients undergoing hemodialysis., Methods: Electronic databases were systematically searched for relevant studies that investigated the association between GNRI and long-term outcomes in hemodialysis patients until November 2023. The primary outcome was the association between the GNRI (i.e., low versus high) and overall mortality risk, while the secondary outcome was the relationship between the GNRI and cardiovascular mortality risk., Results: Thirty cohort studies involving 55,864 patients were included. A low GNRI was found to be significantly associated with increased overall mortality (hazard ratio [HR]: 2.42, 95% confidence interval [CIs]: 2.10-2.79, p  < 0.00001, I 2  = 65%). Each unit increase in GNRI corresponded to a 5% reduction in mortality risk (HR: 0.95, 95% CI: 0.93-0.96, p  < 0.00001, I 2  = 79%). The association remained consistent across Asian (HR = 2.45, 95% CI: 2.08-2.88, p  < 0.00001, I 2  = 70%) and non-Asian subgroups (HR = 2.3, 95% CI: 1.72-3.06, p  < 0.00001, I 2  = 23%). Meta-regression analysis of patient age (coefficient: -0.002; p = 0.896), male proportion (coefficient: 0.002; p = 0.875), percentage of diabetes mellitus (coefficient: -0.003; p = 0.605), and follow-up duration (coefficient: -0.003; p = 0.431) revealed that these moderator variables did not significantly influence the association between GNRI and overall mortality risk. Cardiovascular mortality risk also increased with low GNRI (HR, 1.93; 95%CI: 1.51-2.45, p  < 0.00001; I 2 = 2%). Similarly, an inverse association was observed between the GNRI values and cardiovascular mortality risk (HR, 0.94; 95% CI: 0.91-0.97; p  < 0.0001; I 2  = 65%) (per unit increase)., Conclusion: The GNRI is a simple nutritional screening tool that can be used to effectively stratify patients undergoing hemodialysis globally. Further studies are warranted to determine whether nutrition optimization based on the GNRI improves long-term outcomes., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42023483729., 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 Hung, Kao, Hsu, Yu, Lin, Chen, Chang, Liao and Chen.)

We use low-molecular-weight branched polyethylenimine (PEI) to produce cytocompatible reduced graphene oxide quantum dots (rGOQD) as a photothermal agent and covalently bind it with the photosensitizer IR-820. The rGOQD/IR820 shows high photothermal conversion efficiency and produces reactive oxygen species (ROS) after irradiation with near-infrared (NIR) light for photothermal/photodynamic therapy (PTT/PDT). To improve suspension stability, rGOQD/IR820 was PEGylated by anchoring with the DSPE hydrophobic tails in DSPE-PEG-Mal, leaving the maleimide (Mal) end group for covalent binding with manganese dioxide/bovine serum albumin (MnO 2 /BSA) and targeting ligand cell-penetrating peptide (CPP) to synthesize rGOQD/IR820/MnO 2 /CPP. As MnO 2 can react with intracellular hydrogen peroxide to produce oxygen for alleviating the hypoxia condition in the acidic tumor microenvironment, the efficacy of PDT could be enhanced by generating more cytotoxic ROS with NIR light. Furthermore, quercetin (Q) was loaded to rGOQD through π-π interaction, which can be released in the endosomes and act as an inhibitor of heat shock protein 70 (HSP70). This sensitizes tumor cells to thermal stress and increases the efficacy of mild-temperature PTT with NIR irradiation. By simultaneously incorporating the HSP70 inhibitor (Q) and the in situ hypoxia alleviating agent (MnO 2 ), the rGOQD/IR820/MnO 2 /Q/CPP can overcome the limitation of PTT/PDT and enhance the efficacy of targeted phototherapy in vitro. From in vivo study with an orthotopic brain tumor model, rGOQD/IR820/MnO 2 /Q/CPP administered through tail vein injection can cross the blood-brain barrier and accumulate in the intracranial tumor, after which NIR laser light irradiation can shrink the tumor and prolong the survival times of animals by simultaneously enhancing the efficacy of PTT/PDT to treat glioblastoma.

Di(2-ethylhexyl) phthalate (DEHP) is a worldwide common plasticizer. Nevertheless, DEHP is easily leached out to the environment due to the lack of covalent bonds with plastic. High dose of DEHP exposure is often observed in hemodialysis patients because of the continual usage of plastic medical devices. Although the liver is the major organ that catabolizes DEHP, the impact of long-term DEHP exposure on the sensitivity of liver cancer to chemotherapy remains unclear. In this study, we established long-term DEHP-exposed hepatocellular carcinoma (HCC) cells and two NOD/SCID mice models to investigate the effects and the underlying mechanisms of long-term DEHP exposure on chemosensitivity of HCC. The results showed long-term DEHP exposure potentially increased epithelial-mesenchymal transition (EMT) in HCC cells. Next generation sequencing showed that long-term DEHP exposure increased cell adhesion/migratory related genes expression and blunted sorafenib treatment induced genes alterations. Long-term exposure to DEHP reduced the sensitivity of HCC cells to sorafenib-induced anti-migratory effect by enhancing the EMT transcription factors (slug, twist, and ZEB1) and mesenchymal protein (vimentin) expression. In NOD/SCID mice model, we showed that long-term DEHP-exposed HCC cells exhibited higher growth rate. Regarding the anti-HCC effects of sorafenib, subcutaneous HuH7 tumor grew slowly in sorafenib-treated mice. Nonetheless, the anti-tumor growth effect of sorafenib was not observed in long-term DEHP-exposed mice. Higher mesenchymal markers and proliferating cell nuclear antigen (PCNA) expression were found in sorafenib-treated long-term DEHP-exposed mice. In conclusion, long-term DEHP exposure promoted migratory activity in HCC cells and decreased sorafenib sensitivity in tumor-bearing mice., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Total antioxidant capacity (TAC), representative of the capacity to combat oxidative stress, is closely linked to numerous diseases. Here, we present a protocol for measuring TAC using minimal samples that are stable across varying pH levels and at room temperature. We describe steps for preparing and loading samples and working solutions and conducting and analyzing the colorimetric reaction. Sample sources include aqueous humor, vitreous, tears, and plasma, which allow the protocol to be used in various clinical diagnostic settings. For complete details on the use and execution of this protocol, please refer to publications by Tsao et al. (2022). 1 , 2 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The emergence of SARS-CoV-2 variants has raised concerns about the sustainability of vaccine-induced immunity. Little is known about the long-term humoral responses and spike-specific T cell memory to Omicron variants, with specific attention to BA.4/5, BQ.1.1, and XBB.1., Methods: We assessed immune responses in 50 uninfected individuals who received varying three-dose vaccination combinations (2X AstraZeneca + 1X Moderna, 1X AstraZeneca + 2X Moderna, and 3X Moderna) against wild-type (WT) and Omicron variants at eight months post-vaccination. The serum antibody titers were analyzed by enzyme-linked immunosorbent assays (ELISA), and neutralizing activities were examined by pseudovirus and infectious SARS-CoV-2 neutralization assays. T cell reactivities and their memory phenotypes were determined by flow cytometry., Results: We found that RBD-specific antibody titers, neutralizing activities, and CD4+ T cell reactivities were reduced against Omicron variants compared to WT. In contrast, CD8+ T cell responses, central memory, effector memory, and CD45RA+ effector memory T cells remained unaffected upon stimulation with the Omicron peptide pool. Notably, CD4+ effector memory T cells even exhibited a higher proportion of reactivity against Omicron variants. Furthermore, participants who received three doses of the Moderna showed a more robust response regarding neutralization and CD8+ T cell reactions than other three-dose vaccination groups., Conclusion: Reduction of humoral and CD4+ T cell responses against Omicron variants in vaccinees suggested that vaccine effectiveness after eight months may not have sufficient protection against the new emerging variants, which provides valuable information for future vaccination strategies such as receiving BA.4/5 or XBB.1-based bivalent vaccines., 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 Ho, Yen, Huang, Lu, Hung, Liao, Hung and Chiu.)