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Background: Inflammation, an important mechanism in the pathogenesis of atrial fibrillation (AF), can be regulated by CD36 in monocytes.Objective: The purpose of this study was to test the hypothesis that CD36 in monocytes contributes to the pathogenesis of AF.Methods: A prospective study that enrolled 87 patients with AF and 70 without AF was conducted.Results: Compared to patients without AF, patients with AF had monocytes with a lower level of CD36 protein, which correlated with left atrial diameter, left atrial emptying fraction, and left atrial mean voltage. In AF patients after catheter ablation, Kaplan-Meier analysis showed that the sinus rhythm maintenance rate was higher in patients with high CD36 levels. Low CD36 level was an independent predictor of recurrence. After successful ablation, the CD36 level increased by 57%, reaching that of control patients. CD36 level was not correlated with the level of high-sensitivity C-reactive protein. Analysis of mRNA levels from a buffy coat revealed that AF patients had lower CD36 and interleukin-10 levels and higher peroxisome proliferator-activated receptor-γ and tumor necrosis factor-α levels, with CD36 level positively correlated with interleukin-10 level but inversely correlated with peroxisome proliferator-activated receptor-γ and tumor necrosis factor-α levels.Conclusion: Low CD36 levels in circulating monocytes were associated with AF occurrence and predicted recurrence after catheter ablation. The link between CD36 and AF identified a novel AF-related inflammatory pathway. [ABSTRACT FROM AUTHOR]

Aims: A second procedure for recurrent atrial fibrillation (AF) may be associated with the need for a different positioning of the puncture site and may increase the difficulty and complications. This study investigated whether the transseptal puncture site changed and whether the difficult punctures increased in the patients who received a repeat ablation procedure for recurrent AF. Methods and Results: Twenty-nine AF patients (52 +/- 12 years old, 20 males) underwent catheter ablation for a recurrence of AF. Compared with the first procedure, the height between the transseptal puncture site and coronary sinus ostium was higher in the second procedure during both the atrial end-systolic phase (38.0 +/- 4.7 vs. 34.8 +/- 5.3 mm, P = 0.036), and end-diastolic phase (43.0 +/- 4.8 vs. 39.1 +/- 5.4 mm, P = 0.004) in the 30 degrees right anterior oblique view. No significant change in the vertical atrial diameter was noted between the first and second procedures. A higher incidence of a difficult puncture was noted during the second procedure than in the first procedure (28 vs. 7%, P = 0.014). All those difficult punctures were overcome by using a large-curved transseptal needle. No differences of age, gender, AF duration, interval between first and second procedures, procedure time of the first procedure, and left atrial anteroposterior diameter were noted between easy and difficult transseptal punctures during the second procedure. Conclusion: The incidence of a difficult puncture was higher in the second procedure compared with the first procedure. The transseptal puncture site moved higher in the second procedure. Chronic scarring over the previous transseptal site is a reasonable hypothesis to explain the observations. The difficult punctures experienced during the second procedure might be overcome by changing the needle curve from a small curve to a large curve design. [ABSTRACT FROM AUTHOR]

Background: Electrical isolation of pulmonary veins (PVs) is an effective therapy for atrial fibrillation (AF). Both segmental ostial PV ablation and circumferential ablation with PV-left atrial (LA) block have been implicated to eliminate AF. However, the mechanism of the recurrent AF after undergoing either strategy remains unclear. Methods and Results: Of the 73 consecutive patients with symptomatic AF that underwent PV isolation and had recurrences of AF, Group 1 consisted of 46 patients (age 56 +/- 13 years old, 35 males) who underwent PV isolation by segmental ostial PV ablation and Group 2 consisted of 27 patients (age 51 +/- 11 years old, 24 males) who underwent circumferential ablation with PV-LA block. In Group 1, the earliest ectopic beat or ostial PV potentials were targeted. In Group 2, circumferential ablation with PV-LA block was performed by encircling the extraostial regions around the left and right PVs. During the first procedure, all patients had PV-AF. There was no difference in the non-PV ectopy between Group 1 and Group 2. During the second procedure, the incidence of an LA posterior wall ectopy initiating AF was significantly lower (20% vs. 0%, P = 0.01) in Group 2. There was no difference in the PV ectopy initiating AF during the second procedure. Conclusion: Circumferential ablation of AF with PV-LA block may eliminate the LA posterior wall ectopy and decrease the incidence of LA posterior wall ectopy initiating AF during the second procedure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Atrial substrate properties have been demonstrated to be related to atrial arrhythmias. This study investigated whether the atrial substrate exhibits progressive remodeling in patients with recurrence of atrial fibrillation (AF) after catheter ablation. METHODS AND RESULTS: Fifteen consecutive AF patients (52 +/- 12 years old, 12 males) underwent the same mapping technique (NavX, St. Jude Medical, Minnetonka, MN, USA) and same ablation technique for primary AF and recurrence of AF (170 +/- 66 days after the first procedure). The bipolar mean peak-to-peak voltage (PPV) of the global left atrium during sinus rhythm significantly decreased in the second procedure (2.25 +/- 0.62 vs. 1.79 +/- 0.60 mV, P = 0.008). Also, the percentage of the surface area of the low voltage zone (LVZ; less than 0.5 mV) in the left atrium increased from 6 +/- 4% to 13 +/- 6% (P = 0.001) in the second procedure. There was no significant change in the right atrial bipolar mean PPV or surface area of the LVZ in the second procedure. CONCLUSION: Atrial substrate remodeling with a progressive decrease in the left atrial voltage was demonstrated in patients with recurrent AF. [ABSTRACT FROM AUTHOR]

Introduction: Elimination of the initiating focus within the pulmonary vein (PV) using radiofrequency (RF) catheter ablation is a new treatment modality for treatment of drug-refractory atrial fibrillation. However, information on the long-term safety of RF ablation within the PV is limited. Methods and Results: In 102 patients with drug-refractory atrial fibrillation and at least one initiating focus from the PV, series transesophageal echocardiography was performed to monitor the effect of RF ablation on the PV. There were 66 foci in the right upper PV and 65 foci in the left upper PV. Within 3 days of ablation, 26 of the ablated right upper PVs (39%) had increased peak Doppler flow velocity (mean 130 ± 28 cm/sec, range 106 to 220), and 15 of the ablated left upper PVs (23%) had increased peak Doppler flow velocity (mean 140 ± 39 cm/sec, range 105 to 219). Seven patients had increased peak Doppler flow velocity in both upper PVs, No factor (including age, sex, site of ablation, number of RF pulses, pulse duration, and temperature) could predict PV stenosis after RF ablation. Three patients with stenosis of both upper PVs experienced mild dyspnea on exertion, but only one bad mild increase of pulmonary pressure. There was no significant change of peak and mean flow velocity and of PV diameter in sequential follow-up studies up to 16 (209 ± 94 days) months. Conclusion: Focal PV stenosis is observed frequently after RF catheter ablation applied within the vein, but usually is without clinical significance. However, ablation within multiple PVs might cause pulmonary hypertension and should be considered a limiting factor in this procedure. [ABSTRACT FROM AUTHOR]

Introduction: The characteristics of atrial tachycardia (AT) have varied widely among different reports. The anatomic locations of ATs may bias the results. We propose that septal ATs and free-wall ATs have different characteristics. Methods and Results: One hundred forty-one patients with AT underwent electropharmacologic study, endocardial mapping, and radiofrequency ablation. Forty-nine (34.7%) patients had septal AT originating from the anteroseptal, midseptal, and posteroseptal areas. Tachycardia cycle length was similar between septal AT and freewaIl AT(367 ± 46 msec vs 366 ± 58 msec, P> 0.05). More patients with septal AT required isoproterenol to facilitate induction (44.9% vs 31.5%, P < 0.05). Septal AT was more sensitive to adenosine than free-wall AT (84.4% vs 67.8%, p < 0.05). Only posteroseptal AT showed a positive P wave in lead V1 and negative P wave in all the inferior leads (II, III, aVF). Radiofrequency catheter ablation had a comparable success rate for septal AT and free-wall AT (96% vs 95%) without impairment of AV conduction. During follow-up of 49 ± 13 months (range 17 to 85), the recurrence rate was similar for septal AT and free-wall AT (3.2% vs 4.6%, P = 0.08). Conclusion: Septal AT has electrophysiologic characteristics that are distinct from those of free-wall AT. Catheter ablation of the septal AT is sale and effective. [ABSTRACT FROM AUTHOR]

Several atrial pacing modes have been reported to be effective in the prevention of atrial fibrillation (AF); they included biatrial pacing, dual site right atria! pacing. Bachmann 's bundle (BB) pacing, and coronary sinus pacing. However, the relative efficacy and electrophysioiogical mechanisms of these pacing modes in the prevention of AF are not clear. In 15 patients (age 54 :!: 14 years) with paroxysmal AF, P wave duration, effective refractory period, and atrial conduction time were determined with six different atria! drive pacings, that were right atrial appendage (BAA), BB, right posterior interatrial septum (EPS), distal coronary sinus (DCS), RAA plus BPS simultaneously (DSA), and BAA plus DCS simultaneously (BiA). All these patients consistently had AF induced with early BAA extrastimulation coupling to RAA drive pacing. No patient had AF induced with BAA extrastimulation coupled to BB. BPS. or DCS drive pacing, but seven and eight patients had AF induced with RAA extrastimulation coupled to DSA and BiA drive pacing, respectively. The P wave duration was longest during RAA pacing, and became shorter during other atrial pacing modes. Analysis of electrophysioiogical change showed that early RAA extrastimulation coupled to BAA drive pacing caused the longest atrial conduction delay among these atria! pacing modes; RR, HPS. and DCS drive pacing caused a greater reduction of this conduction delay than DSA and BiA drive pacing. In addition, the effective refractory periods of BAA determined with BB. RPS. and DCS drive pacing were similar and longer than that determined with DSA and BiA drive pacing. In patients with paroxysmal AF. this arrhythmia was readily induced with BAA extrastimuli coupled to BAA drive pacing. RB. BPS. and DCS pacing were similar and more effective than DSA and BiA pacing in preventing AF. [ABSTRACT FROM AUTHOR]

Ectopic beats from the pulmonary veins (PVs) have been demonstrated to initiate atrial fibrillation (AF). This article describes the conceptual approach to mapping, interpretation of different electrograms, and ablation of AF initiated by PV ectopic heats. [ABSTRACT FROM AUTHOR]

Introduction: Reports about the clinical and electrophysiologic characteristics of focal atrial tachycardia vary widely. Furthermore, the impact of age, gender, associated cardiac diseases, mechanism, location of atrial tachycardia, and the prediction of results of radiofrequency catheter ablation was not clear. The purpose of this study was to further understand the clinical and electrophyslologic characteristics of focal atrial tachycardia and the prediction of results of radiofrequency ablation. Methods and Results: We searched the literature published between January 1969 and July 1997 using the key word 'atrial tachycardia' from the MEDLINE and National Library of Medicine systems. The items analyzed were age, sex, cardiac disease, mechanism, attack pattern, cycle length, location, number of atrial tachycardias, results of ablation, and recurrence after ablation. Multivarlate analysis showed that age and paroxysmal type of tachycardia were independent predictors of nonautomatic mechanism; age and presence of other cardiac diseases were independent predictors of multiple atrial tachycardias, and age also was the independent predictor of right-sided atrial tachycardia. Atrial tachycardia located in the right atrium was the only significant predictor of successful radiofrequency catheter ablation. Other cardiac diseases and multiple atrial tachycardias were the significant predictors of recurrence after initial successful radiofrequency catheter ablation. Conclusion: Patient age is closely related to the clinical and electrophysiologic characteristics of atrial tachycardia based on our reanalysis, which found that patient age is an iidependent predictor of nonautomatic mechanism, right atrial location, existence of multiple atrial tachycardias, and recurrence of atrial tachycardia after initial successful ablation. [ABSTRACT FROM AUTHOR]

Background: Stromal fibrosis is highly associated with therapeutic resistance and poor survival in esophageal squamous cell carcinoma (ESCC) patients. Low expression of plasma gelsolin (pGSN), a serum abundant protein, has been found to correlate with inflammation and fibrosis. Here, we evaluated pGSN expression in patients with different stages of cancer and therapeutic responses, and delineated the molecular mechanisms involved to gain insight into therapeutic strategies for ESCC., Methods: Circulating pGSN level in ESCC patients was determined by enzyme-linked immunosorbent assay analysis, and the tissue microarray of tumors was analyzed by immunohistochemistry staining. Cell-based studies were performed to investigate cancer behaviors and molecular mechanisms, and mouse models were used to examine the pGSN-induced tumor suppressive effects in vivo., Results: Circulating pGSN expression is distinctively decreased during ESCC progression, and low pGSN expression correlates with poor therapeutic responses and poor survival. Methylation-specific PCR analysis confirmed that decreased pGSN expression is partly attributed to the hypermethylation of the GSN promoter, the gene encoding pGSN. Importantly, cell-based immunoprecipitation and protein stability assays demonstrated that pGSN competes with oncogenic tenascin-C (TNC) for the binding and degradation of integrin αvβ3, revealing that decreased pGSN expression leads to the promotion of oncogenic signaling transduction in cancer cells and fibroblasts. Furthermore, overexpression of pGSN caused the attenuation of TNC expression and inactivation of cancer-associated fibroblast (CAF), thereby leading to tumor growth inhibition in mice., Conclusions: Our results demonstrated that GSN methylation causes decreased secretion of pGSN, leading to integrin dysregulation, oncogenic TNC activation, and CAF formation. These findings highlight the role of pGSN in therapeutic resistance and the fibrotic tumor microenvironment of ESCC., (© 2024. The Author(s).)

Lead halide perovskites have attracted significant attention for their wide-ranging applications in optoelectronic devices. A ubiquitous element in these applications is that charging of the perovskite is involved, which can trigger electrochemical degradation reactions. Understanding the underlying factors governing these degradation processes is crucial for improving the stability of perovskite-based devices. For bulk semiconductors, the electrochemical decomposition potentials depend on the stabilization of atoms in the lattice-a parameter linked to the material's solubility. For perovskite nanocrystals (NCs), electrochemical surface reactions are strongly influenced by the binding equilibrium of passivating ligands. Here, we report a spectro-electrochemical study on CsPbBr 3 NCs and bulk thin films in contact with various electrolytes, aimed at understanding the factors that control cathodic degradation. These measurements reveal that the cathodic decomposition of NCs is primarily determined by the solubility of surface ligands, with diminished cathodic degradation for NCs in high-polarity electrolyte solvents where ligand solubilities are lower. However, the solubility of the surface ligands and bulk lattice of NCs are orthogonal, such that no electrolyte could be identified where both the surface and bulk are stabilized against cathodic decomposition. This poses inherent challenges for electrochemical applications: (i) The electrochemical stability window of CsPbBr 3 NCs is constrained by the reduction potential of dissolved Pb 2+ complexes, and (ii) cathodic decomposition occurs well before the conduction band can be populated with electrons. Our findings provide insights to enhance the electrochemical stability of perovskite thin films and NCs, emphasizing the importance of a combined selection of surface passivation and electrolyte.

Endometriosis is characterised by endometrial tissue outside the confines of the endometrium in the uterus. Whilst commonly occurring in regions such as the ovaries or fallopian tubes, it is exceedingly uncommon for endometriosis to appear in the umbilical region. This condition may produce a painful and aesthetically unfavourable presentation for sufferers, and can be amendable to surgical excision of the lesion. This case outlines a very rare case of umbilical endometriosis that was managed by an Australian general surgical team., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes., (© 2024. The Author(s).)

The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 μM for Y25A, 15.2 μM for T44A, and 25 μM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 μM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug., 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 adaptive T cell response is accompanied by continuous rewiring of the T cell's electric and metabolic state. Ion channels and nutrient transporters integrate bioelectric and biochemical signals from the environment, setting cellular electric and metabolic states. Divergent electric and metabolic states contribute to T cell immunity or tolerance. Here, we report that neuritin (Nrn1) contributes to tolerance development by modulating regulatory and effector T cell function. Nrn1 expression in regulatory T cells promotes its expansion and suppression function, while expression in the T effector cell dampens its inflammatory response. Nrn1 deficiency causes dysregulation of ion channel and nutrient transporter expression in Treg and effector T cells, resulting in divergent metabolic outcomes and impacting autoimmune disease progression and recovery. These findings identify a novel immune function of the neurotrophic factor Nrn1 in regulating the T cell metabolic state in a cell context-dependent manner and modulating the outcome of an immune response., Competing Interests: Competing interests: C.D. is a co-inventor on patents licensed from JHU to BMS and Janssen and is currently an employee of Janssen Research. D.M.P. is a consultant for Compugen, Shattuck Labs, WindMIL, Tempest, Immunai, Bristol-Myers Squibb, Amgen, Janssen, Astellas, Rockspring Capital, Immunomic, and Dracen; owns founders equity in ManaT Bio Inc., WindMIL, Trex, Jounce, Enara, Tizona, Tieza, and RAPT; and receives research funding from Compugen, Bristol-Myers Squibb, and Enara. All other authors do not have conflicting financial interests.

Background: Patients with head and neck squamous cell carcinoma (HNSCC) frequently develop synchronous esophageal cancer (ESCC), but there is a lack of clinical predictors. The neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR), and lymphocyte to monocyte ratios (LMRs), reflect the balance between pro-cancer inflammation and anti-cancer immune responses, but their role in HNSCC and synchronous cancer remain uncertain., Method: The study consecutively enrolled a total of 717 patients with newly diagnosed HNSCC who received pre-treatment esophageal endoscopic screening. The pretreatment NLR, LMR and PLRs were calculated and analyzed in comparison with the clinical factors., Results: A total of 103 patients (14.4%) were found to have synchronous ESCCs, and were associated with a significantly lower absolute lymphocyte count (p < 0.001), higher NLRs (p = 0.044) and lower LMRs (p = 0.001), but not PLRs (p = 0.49). The ROC curve for the presence of synchronous ESCC verified the optimal cutoff value as 2.5 for NLRs and 4.0 for LMRs. Multivariable logistic regression revealed that a LMR <4 (OR 2.22; 95% CI 1.27-3.88, p = 0.005), alcohol consumption (OR 4.19; 95% CI 1.47-11.91, p = 0.007), tumor location over the pharynx (OR 1.68; 95% CI 1.07-2.64, p = 0.025), and low body mass index (OR 0.94; 95% CI 0.88-0.99, p = 0.039) were risk factors for developing synchronous ESCC. A low-LMR was significantly associated with decreases in overall survival (p < 0.0001), in both synchronous and non-synchronous groups. Multivariate analysis demonstrated that LMR <4 (HR 1.97; 95% CI 1.38-2.81, p < 0.001), a low-BMI (HR 0.96; 95% CI 0.93-0.99, p = 0.044) and presence of synchronous ESCC (HR 1.56; 95% CI 1.10-2.22, p = 0.013) were independent prognostic factors for HNSCC patients., Conclusion: Incorporation of LMR into other identified risk factors, such as alcohol consumption, tumor location over pharynx, and low-BMI, may establish a more efficient screening program for esophageal exploration in HNSCC patients. The significances of LMR also suggest that anti-cancer immunity may play a role in the filed cancerization to initiate multiple cancers, and the immunotherapy may have potentials for prevention or as an adjuvant treatment for synchronous SCC in the future., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Endoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating ultralong-segment ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture., Methods: We prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area of >10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared with an historical control group of 25 patients who received RFA without oral steroids. The primary endpoint was the frequency of post-RFA stricture. Secondary endpoints were the number of balloon dilation sessions and adverse event rate., Results: No significant differences were found in the worst pathology grade at baseline and length of unstained lesions between the 2 groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared with the control group, the oral prednisolone group had a significantly lower stricture rate (4% [2/48 patients] vs 44% [11/25 patients]; P < .0001) and a lower number of balloon dilation sessions (median, 0 [range, 0-4] vs 6 [range, 0-10]). Two cases of asymptomatic candida esophagitis occurred in the study group, but no severe adverse effects., Conclusions: Oral prednisolone may offer a useful and safe preventive option for post-RFA stricture in ultralong ESCNs. (Clinical trial registration number: NCT05768282.)., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided to Wen-Lun Wang, Ching-Tai Lee, Ying-Nan Tsai, and Ming-Hung Hsu by grants from the Ministry of Health and Welfare (MOHW111-TDU-B-221-114006), the Ministry of Science and Technology, Taiwan (MOST-110-2314-B-650-003), and E-Da Hospital (EDAHP110008, EDPJ105060, EDPJ106069, EDAHS111016, EDAHS111018, and EDAHS111019)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Cancer immunotherapy enhances the body's natural immune system to combat cancer, offering the advantage of lowered side effects compared to traditional treatments because of its high selectivity and efficacy. Utilizing computational methods to identify tumor T cell antigens (TTCAs) is valuable in unraveling the biological mechanisms and enhancing the effectiveness of immunotherapy. In this study, we present ENCAP, a predictor for TTCA based on ensemble classifiers and diverse sequence features. Sequences were encoded as a feature vector of 4349 entries based on 57 different feature types, followed by feature engineering and hyperparameter optimization for machine learning models, respectively. The selected feature subsets of ENCAP are primarily composed of physicochemical properties, with several features specifically related to hydrophobicity and amphiphilicity. Two publicly available datasets were used for performance evaluation. ENCAP yields an AUC (Area Under the ROC Curve) of 0.768 and an MCC (Matthew's Correlation Coefficient) of 0.522 on the first independent test set. On the second test set, it achieves an AUC of 0.960 and an MCC of 0.789. Performance evaluations show that ENCAP generates 4.8% and 13.5% improvements in MCC over the state-of-the-art methods on two popular TTCA datasets, respectively. For the third test dataset of 71 experimentally validated TTCAs from the literature, ENCAP yields prediction accuracy of 0.873, achieving improvements ranging from 12% to 25.7% compared to three state-of-the-art methods. In general, the prediction accuracy is higher for sequences of fewer hydrophobic residues, and more hydrophilic and charged residues. The source code of ENCAP is freely available at https://github.com/YnnJ456/ENCAP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yu 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.)

Background and Aim: An early and accurate diagnosis of ampullary neoplasia is crucial; however, sampling bias is still a major concern. New-generation endocytoscopy enables real-time visualization of cellular structures and enables an accurate pathological prediction; however, its feasibility for small ampullary lesions has never been investigated., Methods: We developed a novel endocytoscopic (EC) classification system for ampullary lesions after an expert review and agreement from five experienced endoscopists and one pathologist. We then consecutively enrolled a total of 43 patients with an enlarged ampulla (< 3 cm), all of whom received an endocytoscopic examination. The feasibility of endocytoscopy was evaluated, and the performance of the EC classification system was then correlated with the final histopathology., Results: In five cases (11.6%), the endocytoscope could not approach the ampulla, and these cases were defined as technical failure. Among the remaining 38 patients, 8 had histopathology-confirmed adenocarcinoma, 15 had adenoma, and 15 had non-neoplastic lesions. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification system to diagnose ampullary neoplasias were 95.7%, 86.7%, 91.7%, 92.9%, and 92.1%, respectively. Moreover, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the EC classification to diagnose ampullary cancer were 62.5%, 100%, 100%, 90.9%, and 92.1%, respectively. One case with intra-ampullary papillary-tubular carcinoma was classified as having a non-neoplastic lesion by endocytoscopy., Conclusions: Endocytoscopy and the novel EC classification system demonstrated good feasibility to discriminate ampullary neoplasias from non-neoplastic lesions and may be useful for optical biopsies of clinically suspicious ampullary lesions., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

It is often difficult to obtain adequate tissue for genomic study from distant metastases for assessment of targeted therapy in colorectal carcinomas. The study aims to explore the genomic differences between matched distant metastatic colorectal carcinomas (mCRC) and primary carcinoma using surgical specimens of both with adequate tissue. Thirty-four paired primary and distant metastatic colorectal carcinoma samples (liver, ovary, and lung) were obtained from surgical excisions (not small biopsies) and are microsatellite stable. They were subjected to DNA sequencing using comprehensive next-generation sequencing. This included mutation concordance analysis and mutational signature analysis. The mutation concordance analysis showed 49.6% shared mutations between primary and metastatic tumours, with 23.0% mutations exclusive to primary tumours and 27.4% mutations exclusive to distant metastases. While many patients with KRAS/BRAF mutations had shared mutations, two cases had unique KRAS mutations in the primary tumours only. Additionally, TMB (tumour mutational burden) analysis revealed that half of the TMB-high (≥7.5 mutations/Mb) metastatic colorectal carcinomas had a low TMB (<7.5 mutations/Mb) in the primary tumours. The mutational signature analysis identified de novo signatures consistent with known single base substitution patterns such as SBS11 (alkylation agents) and SBS30 (base excision repair deficiency) post-chemotherapy. To conclude, this study demonstrates significant genomic variations in resected distant metastasis when compared to primary colorectal carcinomas when adequate tissue is available. This finding underscores the importance of considering these differences and selecting tissue for mutation analysis in planning targeted and effective treatment strategies for mCRC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite current guidelines for tuberculosis (TB) control in health care settings, which focused on smear-positive cases, prevention of nosocomial TB transmission continues to be a challenge. Here, we report the results of the first hospital-wide prospective study applying interferon-gamma release assay to investigate the role of smear-negative, culture-positive index cases in nosocomial TB transmission., Methods: We prospectively identified cases of culture-confirmed smear-negative pulmonary TB receiving aerosol-generating procedures (AGPs) and cases of culture-confirmed smear-positive pulmonary TB admitted at a medical center. Nosocomial transmission was evaluated by screening their close contacts for latent TB infection (LTBI) using an interferon-gamma release assay., Results: A total of 93 smear-negative index receiving AGP and 122 smear-positive index were enrolled. Among them, 13 (14.0%) and 43 (35.2%) index cases, respectively, had secondary cases of LTBI (P < .001). Sputum smear negativity (adjusted odds ratio: 0.20 [0.08-0.48]) and AGP (sputum suction; adjusted odds ratio: 3.48 [1.34-9.05]) are independent factors of transmission. A similar proportion in the close contacts of the 2 index groups had LTBI (17 [15.3%] and 63 [16.0%], respectively), and the former index group contributed to 21.3% of the nosocomial transmission., Conclusions: Smear-negative, culture-positive index cases receiving AGPs could be as infectious as smear-positive index cases. Hospital TB control policy should also focus on the former group., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The "double tongue sign" is a characteristic finding in patients with Ludwig's angina, a potentially life-threatening infection due to airway compromise. Management primarily focuses on early airway protection and antibiotic administration. Submandibular sialolithiasis, on the other hand, could present with the double tongue sign without symptoms suggestive of airway involvement. Unlike Ludwig's angina, conservative treatment is usually the first-line approach for sialolithiasis. The importance of rapidly recognizing and distinguishing between the 2 conditions is emphasized through effective triage and risk stratification, particularly in rural areas where physicians are not readily available., (Copyright © 2024 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Objective: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored., Methods: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups., Results: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3 + CD28 + cells, CD4 + CD28 + cells and significant increases in the percentage of CD8 + cells, CD8 + CD28 - cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4 + cells, CD3 + CD28 + cells, CD4 + CD28 + cells, and negative correlation with proportions of CD8 + cells, CD8 + CD28 - cells., Conclusions: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males.

Background: Haemodialysis (HD) patients are predisposed to physical ailments, and their occurrence of coronavirus disease 2019 (COVID-19) could potentially lead to a more unfavourable prognosis. However, the impact of SARS-CoV-2 (Omicron variant) infection on the prognosis of HD patients remains unclear. This study aimed to explore the impact of Omicron variant infection on the prognosis of HD patients., Methods: Eligible participants were patients undergoing maintenance HD treatment during a large-scale outbreak of COVID-19 (Omicron variant) in Shanghai, China, from April 7 to May 30, 2022. According to SARS-CoV-2 infection status of participants, the HD patients were divided into two groups: a COVID-19 group and a non-COVID-19 group. The primary outcome assessed was in-hospital mortality, and secondary outcomes encompassed the incidence of severe cases, admission to intensive care, length of hospital stay, and blood indices. Statistical analysis was conducted by comparative analysis and multiple logistic regression., Results: This study recruited 588 HD patients, including 199 cases in the COVID-19 group and 389 in the non-COVID-19 group. In the COVID-19 group, the mortality rate was 8.45% (17/199), whereas in the non-COVID-19 group, the rate was 3.34% (13/389) ( p  < 0.05). Compared with the non-COVID-19 group, the COVID-19 group had a risk ratio (RR) with 95% confidence interval (CI) of 2.56 (1.27-5.15) for mortality, and the absolute risk difference (ARD) with 95% CI of 5.20% (1.34%-9.06%). Multiple logistic regression confirmed Omicron variant as a risk factor for mortality among HD patients. Additionally, the COVID-19 group had a higher proportion of severe cases, intensive care admission, hypocalcaemia and hyperphosphatemia and longer hospitalization duration, compared to the non-COVID-19 group ( p  < 0.05)., Conclusions: Omicron variant infection was associated with increased mortality risk in HD patients, and Omicron infection worsen the prognosis of HD patients. Enhancing immune protection against SARS-CoV-2 is crucial for HD patients during the ongoing COVID-19 pandemic.

We present a novel photon-acid diffusion method to integrate polymer microlenses (MLs) on a four-channel, high-speed photo-receiver consisting of normal-incidence germanium (Ge) p-i-n photodiodes (PDs) fabricated on a 200 mm Si substrate. For a 29 µm diameter PD capped with a 54 µm diameter ML, its dark current, responsivity, 3 dB bandwidth (BW), and effective aperture size at -3 V bias and 850 nm wavelength are measured to be 138 nA, 0.6 A/W, 21.4 GHz, and 54 µm, respectively. The enlarged aperture size significantly decouples the tradeoff between aperture size and BW and enhances the optical fiber misalignment tolerance from ±5 µm to ±15 µm to ease the module packaging precision. The sensitivity of the photo-receiver is measured to be -9.2 dBm at 25.78 Gb/s with a bit error rate of 10 -12 using non-return-to-zero (NRZ) transmission. Reliability tests are performed, and the results show that the fabricated Ge PDs integrated with polymer MLs pass the GR-468 reliability assurance standard. The demonstrated photo-receiver, a first of its kind to the best of our knowledge, features decent performance, high yield, high throughput, low cost, and compatibility with complementary metal-oxide-semiconductor (CMOS) fabrication processes, and may be further applied to 400 Gb/s pulse-amplitude modulation four-level (PAM4) communication.

Chlorella has a variety of biological activities, and it is worth further exploring its pharmacological effects. In this study, we investigated the antioxidant and anti-ageing activities of Chlorella polysaccharide extract (CPE). Further studies revealed that CPE exhibited anti-ageing, and antioxidant activities in vivo , including an extended Caenorhabditis elegans stress resistance, decreased deposition of lipofuscin, and reduced effects of amyloid β protein on mobility, decreased levels of reactive oxygen species and increased activity of antioxidant enzymes. Moreover, it dramatically increased the expression of anti-stress and longevity genes and reduced the expression of ageing-related genes; therefore, it was hypothesised that the mechanism of the age-delaying effect of CPE was related to the insulin signalling pathway. In summary, CPE could delay ageing and provide a new avenue for the application and development of CPE.

Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting angiogenesis, are promising candidates in cancer treatment. We propose AAPL, a sequence-based predictor to identify AAPs with machine learning models of improved prediction accuracy. Each peptide sequence was transformed to a vector of 4335 numeric values according to 58 different feature types, followed by a heuristic algorithm for feature selection. Next, the hyperparameters of six machine learning models were optimized with respect to the feature subset. We considered two datasets, one with entire peptide sequences and the other with 15 amino acids from peptide N-termini. AAPL achieved Matthew's correlation coefficients of 0.671 and 0.756 for independent tests based on the two datasets, respectively, outperforming existing predictors by a range of 5.3% to 24.6%. Further analyses show that AAPL yields higher prediction accuracy for peptides with more hydrophobic residues, and fewer hydrophilic and charged residues. The source code of AAPL is available at https://github.com/yunzheng2002/Anti-angiogenic ., (© 2024. The Author(s).)

Objectives: The impact of the Standard Protocol Items: Recommendations for Interventional Trials of Traditional Chinese Medicine (SPIRIT-TCM) Extension 2018 statement on the reporting quality of randomized controlled trial (RCT) protocols in traditional Chinese medicine (TCM) is not clear. This review aimed to assess the reporting characteristics and quality of RCT protocols involving interventions such as Chinese herbal medicine formulas (CHMF), acupuncture, and moxibustion published in the last 3 years., Methods: We conducted an extensive search among multiple databases, including All EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid MEDLINE(R), PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for publications in English from 1 January 2020 to 10 August 2023. Two reviewers independently assessed the eligibility of the publications, extracted predetermined information, and evaluated the reporting based on the SPIRIT-TCM Extension 2018 checklist., Results: Of the 420 eligible protocols (comprising 163 studies on CHMF, 239 on acupuncture, and 18 on moxibustion), the average reporting compliance rate was only 35.4%. Approximately half of the assessed items fell into the category of poorly reported, demonstrating a compliance rate below 65%. Notably, reporting compliance in acupuncture and moxibustion interventional studies exhibited higher scores than compliance in CHMF studies., Conclusion: Continued, concerted, and coordinated efforts are required by journals, editors, reviewers, and investigators to improve the application and promotion of the SPIRIT-TCM Extension 2018 reporting guideline., 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 Zhang, Li, Hu, Ou, Tan, Zhang, Lau, Lyu, Bian and Zhang.)

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes., Competing Interests: D.S.R. is the paid consultant and shareholder of Dovetail Genomics. The other authors have declared that no competing interests exist., (Copyright: © 2024 Lin 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.)

The single-atom Fe-N-C is a prominent material with exceptional reactivity in areas of sustainable energy and catalysis research. It is challenging to obtain the dense Fe-N 4 site without the Fe nanoparticles (NPs) sintering during the Fe-N-C synthesis via high-temperature pyrolysis. Thus, a novel approach is devised for the Fe-N-C synthesis at low temperatures. Taking FeCl 2 as Fe source, a hydrogen environment can facilitate oxygen removal and dichlorination processes in the synthesis, efficiently favouring Fe-N 4 site formation without Fe NPs clustering at as low as 360 °C. We shed light on the reaction mechanism about hydrogen promoting Fe-N 4 formation in the synthesis. By adjusting the temperature and duration, the Fe-N 4 structural evolution and site density can be precisely tuned to directly influence the catalytic behaviour of the Fe-N-C material. The FeNC-H 2 -360 catalyst demonstrates a remarkable Fe dispersion (8.3 wt %) and superior acid ORR activity with a half-wave potential of 0.85 V and a peak power density of 1.21 W cm -2 in fuel cell. This method also generally facilitates the synthesis of various high-performance M-N-C materials (M=Fe, Co, Mn, Ni, Zn, Ru) with elevated single-atom loadings., (© 2024 Wiley-VCH GmbH.)

Introduction: Parkinson disease (PD) caused substantially disability. The impairment of fine motor skills (FMSs) is correlated with the severity of functional disability (FD) cross-sectionally in people with PD (PwP). The present study investigated the decline in FMSs and the predictive value of baseline FMSs for the progression of FD., Methods: People with moderate-to-advanced PD who received two evaluations within 1-5 years were identified from the Taiwan Data Bank of Persons with Disability database. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to evaluate FD, and FMSs including pen-holding, buttoning, and knotting were assessed., Results: Our study included 2,271 people with moderate-to-advanced PD. We observed annual progression of FD in each domain of the WHODAS 2.0, with no difference between the sexes. The most significant correlation between FD and FMSs was that of decline in buttoning ability and deterioration of summary WHODAS 2.0 scores. Deterioration in FD across all domains of WHODAS 2.0 was associated with at least one FMS. The extent of disability in all three types of FMS at baseline was also correlated with deterioration of motility. Additionally, baseline disability in buttoning was significantly correlated with cognitive decline, and disability in knotting was significantly associated with the progression of FD., Conclusion: FMSs may be reliable markers for further FD, particularly in the areas of cognition, motility, and life activity. Because of the significant FD observed in people with moderate-to-advanced PD, the availability of predictors is essential for applying precautionary measures and providing appropriate treatment., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain., Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days., Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98)., Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19., (Copyright © 2024. Published by Elsevier B.V.)

Background: Real-time surveillance of COVID-19 in large-scale community outbreaks presents challenges. Simple counts of the daily confirmed cases can be misleading due to constraints from bottlenecks in access to care or laboratory testing. This study aimed to investigate the role of the SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) in addressing these challenges for real-time COVID-19 surveillance., Methods: This study included the results of 86,933 SARS-CoV-2 Ag-RDT and real-time reverse transcription polymerase chain reaction (RT-PCR) tests. These were conducted at four community testing stations within the Taipei metropolitan area during a community COVID-19 outbreak spanning from May 17, 2021, to August 9, 2021. We examined the correlation between the positive rates of Ag-RDT tests and the epidemic curve of laboratory-confirmed COVID-19 cases by onset date to examine its role in real-time surveillance., Results: During the 85-day study period, the trend of Ag-RDT test positive rates paralleled that of the epidemic curve. The correlation between the Ag-RDT positive rate and the number of cases (Pearson correlation coefficient: 0.968) is comparable to that of the RT-PCR positive rate (Pearson correlation coefficient: 0.964). The Ag-RDT positive rate exhibited a more advanced leading trend, with Ag-RDT leading by 3 days in comparison to the 2-day lead for RT-PCR., Conclusion: The positive rate of SARS-CoV-2 Ag-RDT tests at community testing stations serves as a good surrogate for assessing virus activity within the community and a useful tool for real-time COVID-19 surveillance. It is a robust indicator of the outbreak trend and near-term numbers of cases. This finding may facilitate the management of subsequent outbreaks of emerging infectious diseases., Competing Interests: Conflict of interest disclosure All authors have no competing interest to disclose., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups., Methods: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden., Results: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB., Conclusions: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power., (Copyright © 2024. Published by Elsevier B.V.)

Background: Attention-deficit/hyperactivity disorder (ADHD) is diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria by using subjective observations and information provided by parents and teachers. However, subjective analysis often leads to overdiagnosis or underdiagnosis. There are two types of motor abnormalities in patients with ADHD. First, hyperactivity with fidgeting and restlessness is the major diagnostic criterium for ADHD. Second, developmental coordination disorder characterized by deficits in the acquisition and execution of coordinated motor skills is not the major criterium for ADHD. In this study, a machine learning-based approach was proposed to evaluate and classify 96 patients into ADHD (48 patients, 26 males and 22 females, with mean age: 7y6m) and non-ADHD (48 patients, 26 males and 22 females, with mean age: 7y8m) objectively and automatically by quantifying their movements and evaluating the restlessness scales., Methods: This approach is mainly based on movement quantization through analysis of variance in patients' skeletons detected in outpatient videos. The patients' skeleton sequence in the video was detected using OpenPose and then characterized using 11 values of feature descriptors. A classification analysis based on six machine learning classifiers was performed to evaluate and compare the discriminating power of different feature combinations., Results: The results revealed that compared with the non-ADHD group, the ADHD group had significantly larger means in all cases of single feature descriptors. The single feature descriptor "thigh angle", with the values of 157.89 ± 32.81 and 15.37 ± 6.62 in ADHD and non-ADHD groups (p < 0.0001), achieved the best result (optimal cutoff, 42.39; accuracy, 91.03%; sensitivity, 90.25%; specificity, 91.86%; and AUC, 94.00%)., Conclusions: The proposed approach can be used to evaluate and classify patients into ADHD and non-ADHD objectively and automatically and can assist physicians in diagnosing ADHD., (© 2024. The Author(s).)

Head and neck squamous cell carcinoma (HNSCC) faces low response rates to anti-PD-1 immunotherapies, highlighting the need for enhanced treatment strategies. Auranofin, which inhibits thioredoxin reductase (TrxR) through its gold-based composition, has shown potential in cancer treatment. It targets the TrxR system, essential for safeguarding cells from oxidative stress. The overproduction of TrxR in cancerous cells supports their proliferation. However, auranofin's interference with this system can upset the cellular redox equilibrium, boost levels of reactive oxygen species, and trigger the death of cancer cells. This study is the first to highlight TXNRD1 as a crucial factor contributing to resistance to anti-PD-1 treatment in HNSCC. In this study, we identified targetable regulators of resistance to immunotherapy-induced ferroptosis in HNSCC. We observed a link of thioredoxin reductase 1 (TXNRD1) with tumoral PD-L1 expression and ferroptosis suppression in HNSCC. Moreover, HNSCC tumors with aberrant TXNRD1 expression exhibited a lack of PD-1 response, NRF2 overexpression, and PD-L1 upregulation. TXNRD1 inhibition promoted ferroptosis in HNSCC cells with NRF2 activation and in organoid tumors derived from patients lacking a PD-1 response. Mechanistically, TXNRD1 regulated PD-L1 transcription and maintained the redox balance by binding to ribonucleotide reductase regulatory subunit M2 (RRM2). TXNRD1 expression disruption sensitized HNSCC cells to anti-PD-1-mediated Jurkat T-cell activation, promoting tumor killing through ferroptosis. Moreover, TXNRD1 inhibition through auranofin cotreatment synergized with anti-PD-1 therapy to potentiate immunotherapy-mediated ferroptosis by mediating CD8 + T-cell infiltration and downregulating PD-L1 expression. Our findings indicate that targeting TXNRD1 is a promising therapeutic strategy for improving immunotherapy outcomes in patients with HNSCC., 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.)

Introduction: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions., Methods: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp., Results: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group., Discussion: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Vitamin B12 and folic acid could reduce blood homocysteine levels, which was thought to slow down the progression of Alzheimer's disease (AD), but previous studies regarding the effect of vitamin B12 and folic acid in treatment of AD have not reached conclusive results. We searched PubMed and Embase until January 12, 2023. Only randomized control trials involving participants clearly diagnosed with AD and who received vitamin B12 and folic acid were enrolled. Five studies that met the criteria were selected for inclusion in the meta-analysis. Changes in cognitive function were measured based on either the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Changes in daily life function and the level of blood homocysteine were also investigated. After a 6-month treatment, administration of vitamin B12 and folic acid improved the MMSE scores more than placebo did (SMD = 0.21, 95% CI = 0.01 to 0.32, p = 0.04) but did not significantly affect ADAS-Cog scores (SMD = 0.06, 95% CI = -0.22 to 0.33, p = 0.68) or measures of daily life function. Blood homocysteine levels were significantly decreased after vitamin B12 and folic acid treatment. Participants with AD who received 6 months of vitamin B12 and folic acid supplementation had better MMSE scores but had no difference in ADAS-Cog scores. Daily life function did not improve after treatment.

Background: Simulation-based training is effective for ultrasound (US)-guided procedures. However, commercially developed simulators are costly. This study aims to evaluate the feasibility of a hand-made phantom for US-guided paracentesis., Methods: We described the recipe to prepare an agar phantom. We collected the US performance data of 50 novices, including 22 postgraduate-year (PGY) residents and 28 undergraduate-year (UGY) students, who used the phantom for training, as well as 12 emergency residents with prior US-guided experience. We obtained the feedback after using the phantom with the Likert 5-point scale. The data were presented with medians and interquartile ranges (IQRs) and analyzed by the Wilcoxon rank sum test., Results: While emergency residents demonstrated superior performance compared to trainees, all trainees exhibited acceptable proficiency (global rating of ≥ 3, 50/50 vs. 12/12, p = 1.000) and comparable needle steadiness [5 (5) vs. 5 (5), p = 0.223]. No significant difference in performance was observed between PGYs [5 (4-5)] and UGYs [5 (4-5), p = 0.825]. No significant differences were observed in terms of image stimulation, puncture texture, needle visualization, drainage simulation, and endurance of the phantom between emergency residents and trainees. However, experienced residents rated puncture texture and draining fluid as "neutral" (3/5 on the Likert scale). The cost of the paracentesis phantom is US$16.00 for at least 30 simulations, reducing it to US$6.00 without a container., Conclusions: The paracentesis phantom proves to be a practical and cost-effective training tool. It enables novices to acquire paracentesis skills, enhances their US proficiency, and boosts their confidence. Nevertheless, further investigation is needed to assess its long-term impact on clinical performance in real patients., Trial Registration: NCT04792203 at the ClinicalTrials.gov., (© 2024. The Author(s).)

The global spread of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b virus since 2021 necessitates a re-evaluation of the role of vaccination in controlling HPAI outbreaks among poultry, which has been controversial because of the concern of silent spread with viral mutation and spillover to human. We systematically reviewed and meta-analyzed all existing data from experimental challenge trials to assess the efficacy of HPAI vaccines against mortality in specific pathogen free (SPF) chickens, with evaluation of the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Out of 223 screened publications, 46 trials met our eligibility criteria. Inactivated vaccines showed an efficacy of 95% (risk ratio [RR] = 5% [95% CI: 1% to 17%], I 2  = 0%, CoE high) against homologous strains and an efficacy of 78% (RR = 22% [95% CI: 14% to 37%], I 2  = 18%, CoE high) against heterologous strains (test for subgroup difference p  = 0.02). Live recombinant vaccines exhibited the highest efficacy at 97% (RR = 3% [95% CI: 1% to 13%], I 2  = 0%, CoE high). Inactivated recombinant vaccines had an overall efficacy of 90% (RR = 10% [95% CI: 6% to 16%], I 2  = 47%, CoE high). Commercial vaccines showed an overall efficacy of 91% (RR = 9% [95% CI: 5% to 17%], I 2  = 23%, CoE high), with 96% efficacy (RR = 4% [95% CI: 1% to 21%], I 2  = 0%, CoE high) against homologous strains and 90% efficacy (RR = 10% [95% CI: 5% to 20%], I 2  = 31%, CoE moderate) against heterologous strains. Our systematic review offers an updated and unbiased assessment of vaccine efficacy against HPAI-related mortality, providing timely and crucial information for re-evaluating the role of vaccination in poultry avian influenza control policy amist the global HPAI outbreak post-2021., Competing Interests: All authors declare that they have no conflicts of interest., (© 2024 The Authors.)

Synaptic dysfunction plays a key role in Parkinson's disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. Assessment of plasma EV synaptic proteins for their efficacy as biomarkers in PD and their relationship with disease progression was conducted. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs. In PwP, the changes in plasma EV synaptic protein levels were significantly associated with the changes in Unified Parkinson's Disease Rating Scale (UPDRS)-II and III scores. Moreover, PwP with elevated levels (first quartile) of any one plasma EV synaptic proteins (synaptosome-associated protein 25, growth-associated protein 43 or synaptotagmin-1) had significantly greater disease progression in UPDRS-II score and the postural instability and gait disturbance subscore in UPDRS-III than did the other PwP after adjustment for age, sex, and disease duration. The promising potential of plasma EV synaptic proteins as clinical biomarkers of disease progression in PD was suggested. However, a longer follow-up period is warranted to confirm their role as prognostic biomarkers., Competing Interests: CH, CC, RY, LC No competing interests declared, (© 2023, Hong et al.)

Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum , integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects., Methods: To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis., Results: Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups., Conclusions: This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis., Competing Interests: The authors assert that they have no financial or non-financial interests that could be influenced by the publication of this manuscript, either now or in the future., (© 2024 The Authors.)

Context: The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events., Objective: The relevant outcomes associated with the use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D) with/without concomitant AF remained unknown., Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, there were 344,392 and 31,351 patients with T2D without AF, and 11,462 and 816 T2D patients with AF treated with SGLT2i and GLP-1RA from May 1, 2016, to December 31, 2019. Patients were followed from the drug-index date until the occurrence of study events, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. We used propensity score stabilized weight to balance covariates across two medication groups., Results: The incidence rate of all study outcomes in patients with concomitant AF was much higher than in those without concomitant AF. For the AF cohort, SGLT2i vs. GLP-1RA was associated with a lower risk of hospitalization for heart failure (2.32 vs. 4.74 events per 100 person-years; hazard ratio (HR):0.48 [95% confidential interval (CI):0.36-0.66]), with no benefit seen for the non-AF cohort (P for homogeneity < 0.01). SGLT2i vs. GLP-1RA was associated with a lower risk of composite kidney outcomes both in the AF (0.38 vs. 0.79 events per 100 person-years; HR:0.47; [95%CI:0.23-0.96]) and non-AF cohorts (0.09 vs. 0.18 events per 100 person-years; HR:0.53; [95%CI:0.43-0.64]). There were no significant differences in the risk of major adverse cardiovascular events and all-cause mortality in those who received SGLT2i compared to GLP-1RA for the AF or non-AF cohorts., Conclusion: Considering the high risk of developing HF and/or high prevalence of concomitant HF in patients with diabetes, whether SGLT2i should be the preferred treatment to GLP-1RA for such a high-risk population requires further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. 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.)