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Yi-Chia Wei,1– 4 Li-Yuan Huang,1,2,5 Chemin Lin,1,2,6 Yu-Chiau Shyu,1,7 Chih-Ken Chen1,2,6 1Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Keelung, Taiwan; 4Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan; 5Department of Nursing, Chang Gung Memorial Hospital, Keelung, Taiwan; 6Department of Psychiatry, Chang Gung Memorial Hospital, Keelung, Taiwan; 7Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, TaiwanCorrespondence: Chih-Ken ChenDepartment of Psychiatry, Chang Gung Memorial Hospital at Keelung, No. 200 Lane 208, Jijin 1st Road, Anle District, Keelung City, 204, TaiwanTel +886-2-24329292-2725Fax +886-2-24315931Email kenchen@cgmh.org.twBackground: Major depressive disorder (MDD) presents with emotional and somatic symptoms and sometimes subjective cognitive complaints (SCCs). This study developed a collaborative method to integrate SCC assessment for evaluating late-life MDD.Methods: Residents aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital in Taiwan during 2017– 2018 were prospectively recruited in this study. The participants were asked to report their depressive tendency and SCCs using the Taiwanese Depression Questionnaire (TDQ) and the AD8, respectively, and were administered psychiatric evaluation through the Mini–International Neuropsychiatric Interview (MINI). The participants were divided into elderly (age≥ 65 years) and older adult (age 50– 65) groups. The MDD predictive powers were assessed using logistic regression and receiver operating characteristic (ROC) curve analyses.Results: Of the 118 enrolled participants (mean age: 64.81± 4.99, female-to-male ratio: 1.62), 9, 21, and 88 were categorized as those with current MDD, past MDD, and non-MDD on the basis of the MINI results, respectively. After adjustments for age, sex, and sleep quality, the TDQ score (odds ratio: 1.152, p=0.003) and AD8 score (odds ratio: 1.710, p=0.020) were used individually to predict current MDD. Overall, the TDQ individually predicted current MDD well with area under the ROC curve (AUC) of 0.835 (p=0.001). However, in the elderly group (N=63), the TDQ score did not identify current MDD well (AUC: 0.780, p=0.063). After co-considering SCCs, the linear combination of the sum of the TDQ score and four folds of the AD8 score could effectively distinguished elderly people with current MDD from those without it (AUC: 0.875, p=0.013)—with the cutoff of the aforementioned combined score being ≥ 32.Conclusion: The self-reported response to the TDQ is a feasible approach of identifying MDD in community-dwelling people. Combining TDQ and AD8 scores further improved depression detection in elderly people.Keywords: geriatric depression, major depressive disorder, Taiwanese Depression Questionnaires, subjective cognitive complaint, AD8

Xingsi Liang,1,2,* Bin Zhang,3,* Quan Chen,4,* Jing Zhang,1,5 Biao Lei,1,5 Bo Li,5 Yangchao Wei,1,5 Run Zhai,1,5 Zhiqing Liang,2 Songqing He,1,5 Bo Tang1,5 1Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, 2Department of Infectious Diseases, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, 3Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 4Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, 5Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Characterized by its acute onset, critical condition, poor prognosis, and high mortality rate, severe acute pancreatitis (SAP) can cause multiple organ failure at its early stage, particularly acute lung injury (ALI). The pathogenesis of ALI is diffuse alveolar damage, including an increase in pulmonary microvascular permeability, a decrease in compliance, and invasion of many inflammatory cells. Corticosteroids are the main treatment method for ALI; however, the associated high toxicity and side effects induce pain in patients. Recent studies show that the effective components in many traditional Chinese medicines can effectively inhibit inflammation with few side effects, which can decrease the complications caused by steroid consumption. Based on these observations, the main objective of the current study is to investigate the effect of alpinetin, which is a flavonoid extracted from Alpinia katsumadai Hayata, on treating lung injury induced by SAP and to explore the mechanism underlying the alpinetin-mediated decrease in the extent of ALI. In this study, we have shown through in vitro experiments that a therapeutic dose of alpinetin can promote human pulmonary microvascular endothelial cell proliferation. We have also shown via in vitro and in vivo experiments that alpinetin upregulates aquaporin-1 and, thereby, inhibits tumor necrosis factor-α expression as well as reduces the degree of lung injury. Overall, our study shows that alpinetin alleviates SAP-induced ALI. The likely molecular mechanism includes upregulated aquaporin expression, which inhibits tumor necrosis factor-α and, thus, alleviates SAP-induced ALI. Keywords: alpinetin, aquaporin-1, severe acute pancreatitis, acute lung injury, HPMVEC, tumor necrosis factor-α

Schwannoma arising from the tympanic membrane is a rare neoplasm. This report describes an external ear canal mass obscuring the tympanic membrane. A transcanal approach identified a tumour adhered to the tympanic membrane. The tumour was excised without myringoplasty. Pathology confirmed the diagnosis of schwannoma. Clinical examination revealed no evidence of recurrence during a follow-up period of one year. The possible origins of schwannoma of the tympanic membrane and lesion management are also discussed. [ABSTRACT FROM AUTHOR]

Rust disease, an important plant pathogen, can lead to reduced crop or fruit production. Trifluoromethyloxadiazole (TFMO) is a class of histone deacetylase inhibitors (HDACs). Herein, a series of 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO)-based pyrimidin-4-ether derivatives were designed and synthesized. Antirust bioassay results of TFMOs showed that some of them possessed excellent activities against plant rust pathogens, such as Puccinia sorghi , Phakopsora pachyrhizi , and Puccinia rubigo . The most active compound, 3-(5-(((6-(difluoromethyl)pyrimidin-4-yl)oxy)methyl)thiophen-2-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole ( XII6 ), exhibited 50% control against P. pachyrhizi at 0.780 mg/L, which was significantly better than the commercial fungicide azoxystrobin (0%) at the same concentration. The field trial results indicated that the compound exhibited an excellent control effect against P. rubigo at 116 g a.i./ha. The acute toxic results indicated that compound XII6 has low toxicity. Furthermore, the enzyme activity results showed that compound XII6 is a strong, nonselective HDAC inhibitor. Finally, the structure-activity relationship was established, and the compound XII6 -HDAC binding mode was carried out based on the crystal structure of h HDAC1, h HDAC4, and h HDAC6. This work provided an excellent fungicide against rust for further optimization.

Background: The relative risk of ischemic stroke (IS) in head and neck cancer (HNC) patients developing carotid artery stenosis (CAS) or vertebral artery stenosis (VAS) after radiation therapy (RT) remains uncertain due to limited studies, complicating vascular follow-ups and preventive strategies., Methods: We included HNC patients who received RT between 2010 and 2023. The patients were divided into nasopharyngeal carcinoma (NPC) and non-NPC groups. The primary outcome was the occurrence of IS after RT, and the secondary outcomes included the development of > 50% CAS or > 50% VAS after RT., Results: Of the 1,423 HNC patients, there were 19% of patients developed > 50% CAS, 6.8% of patients developed > 50% VAS, and 2.3% of patients developed IS. In patients with HNC, > 50% CAS (adjusted hazard ratio [HR] = 3.21, 95% confidence interval [CI] = 1.53-6.71), and > 50% VAS (adjusted HR = 2.89, 95% CI = 1.28-6.53) were both the independent predictors of IS. In the patients with NPC, > 50% CAS was an independent predictor of anterior circulation IS (adjusted HR = 4.39, 95% CI = 1.17-16.47). By contrast, > 50% VAS emerged as a predictor of posterior circulation IS in both the NPC (adjusted HR = 15.02, 95% CI = 3.76-60.06) and non-NPC groups (adjusted HR = 13.59, 95% CI = 2.21-83.46)., Conclusion: HNC patients with > 50% CAS or > 50% VAS after RT had an increased risk of IS within their corresponding vascular territory. CAS could be an important predictor of IS in NPC patients, whereas VAS might also be a significant predictor of IS in both NPC and non-NPC patients. Evaluation both the carotid and vertebral arteries after RT might be necessary., Trial Registration: ClinicalTrials.gov identifier No.: NCT06111430., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Institutional Review Board of Chang Gung Memorial Hospital (202101981B0, 202200464B0, and 202400107B0). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To observe the characteristics of ocular biological parameters in children with transfusion-dependent β-thalassemia (TDT) and the effect of iron chelator treatment on them. Methods: This was a cross-sectional study. Thirty-two children with TDT (TDT group) and 64 healthy children (control group) who were treated in the Affiliated Hospital of Guangdong Medical University from October 2022 to June 2023 were included. There were 17 males and 15 females in the TDT group, with an age of (10.32±3.58) years; and 34 males and 30 females in the control group, with an age of (10.70±3.23) years. The children with TDT were divided into TDT1 group (using a single iron chelator) and TDT2 group (using two iron chelators in combination) according to the treatment situation of blood transfusion combined with iron chelator. The growth and development indicators such as height, weight and BMI of the children were recorded; the axial length (AL), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), corneal horizontal diameter (WTW), and the mean corneal curvature (Km) was calculated; the average size (AVG) of corneal endothelial cells and corneal endothelial cell density (CD) were measured using the corneal endothelium cytometer SP-3000P. to integer values; the blood transfusion time, serum ferritin before and after blood transfusion, the Results: The height, weight and BMI of the TDT group were all smaller than those of the control group (all P <0.001). The AL of the TDT group was (23.21±0.98) mm, shorter than that of the control group (24.01±1.16) mm; the ACD was (3.49±0.24) mm, shallower than that of the control group (3.63±0.25) mm; the LT was (3.52±0.18) mm, thicker than that of the control group (3.39±0.16) mm; The Km value (44.12±1.59) D is higher than that of the control group (42.93±1.34) D; the CD was (3 035.71±312.59) cells/mm², smaller than that of the control group (3 260.46±248.11) cells/mm² (all P <0.05). In the TDT group, AL and ACD were positively correlated with height ( r =0.497,0.454;both P <0.05), and LT was negatively correlated with height ( r =-0.400, P <0.05). The age of the TDT2 group was greater than that of the TDT1 group, the LT was smaller than that of the TDT1 group ( P >0.05), and the CD was smaller than that of the TDT1 group ( P <0.05). Conclusions: The growth and development of children with TDT are retarded, manifested as short axial length, shallow anterior chamber, thickened lens, higher mean corneal curvature and decreased corneal endothelial cell density. The use of iron chelators may cause corneal changes such as decreased corneal endothelial cell density.

Rationale: Triple gallbladder is a rare congenital anatomical abnormality because of the incomplete regression of rudimentary bile ducts and is often not found until it is accidentally detected during imaging research., Patient Concerns: We report a rare case of triple gallbladder malformation and review the English literature on biliary tract variation caused by gallbladder malformation. The diagnosis, treatment, and postoperative situation of the patients were summarized and analyzed., Diagnoses: The patient was diagnosed with triple gallbladder malformation., Interventions: We conducted laparoscopic cholecystectomy for the patient., Outcomes: We successfully removed all 3 gallbladders by laparoscopic cholecystectomy, and the patient had no postoperative complications such as bleeding or bile leakage and recovered well., Lessons: At present, the best treatment for triple gallbladder malformation is to remove all 3 gallbladders by laparoscopic cholecystectomy, which can effectively prevent the occurrence of "postcholecystectomy syndrome" caused by individual gallbladder residue. However, the diagnosis of triple gallbladder is very challenging and often requires a combination of advanced imaging methods. However, sometimes preoperative imaging does not fully reveal biliary tract variation. Therefore, we need to rely on the guidance of evidence-based medicine before surgery and the accurate evaluation of surgical plans to complete the operation without risk., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Guillain-Barré syndrome (GBS), an acute inflammatory disorder of the peripheral nervous system, is characterized by muscle weakness and paralysis. Prompt identification of patients at a high risk of poor outcomes is crucial for timely intervention. In this study, we combined clinical data with nerve conduction study and electromyography data to identify the predictors of GBS outcomes., Methods: We retrospectively analyzed the data of patients with GBS who had received treatment at Chang Gung Memorial Hospital, Taiwan, between 1998 and 2022. Comprehensive clinical and electrophysiological data were collected. Statistical analyses were performed to identify the predictors of poor outcomes. The patients were stratified into two groups by their scores on the GBS Disability Scale: good (score ≤ 2) and poor (score > 2) outcome groups., Results: The study finally included 24 GBS patients (mean age: 53.0 ± 20.9 years; female-to-male ratio: 2.3; good outcome group: 13; poor outcome group: 11). Compared with the good outcome group, the poor outcome group was old (43.0 ± 20.4 vs. 64.0 ± 15.7, p = 0.011), had a short time-to-treatment period (12.9 ± 7.8 vs. 6.5 ± 5.4 days, p = 0.033), exhibited more prevalent mechanical ventilation use (0 vs. 36.4%, p = 0.017), and had a prolonged hospitalization duration (14.7 ± 10.2 vs. 53.1 ± 20.0 days, p < 0.001). Poor outcomes were associated with low compound muscle action potential (CMAP), slow motor nerve conduction velocity (MNCV), abnormal F-wave latency, and more conduction block and temporal dispersion. In the subgroup of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), there were 19 patients, out of which 10 had good outcomes, while nine had poor outcomes. The clinical features that differentiate between good and poor outcomes in the AIDP subgroup were similar to those observed in all GBS patients. Notably, the motor conduction features, including distal and proximal CMAP and MNCV of the median and tibial nerves (all p < 0.05), were particularly important electrodiagnostic features of outcome discrimination in the AIDP subgroup., Discussion: Combining clinical data with nerve conduction study and electromyography data can assist in predicting outcomes of both GBS patients and the AIDP subgroup. Poor outcomes are associated with older age, a more abrupt onset pattern, low CMAP, and slow nerve conduction, and abnormal tibial F responses can predict poor outcomes. Early identification of high-risk patients facilitates tailored interventions. This highlights the importance of combining clinical and electrophysiological data in GBS management., (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

This study aimed to establish and validate a multiparameter prediction model for Ki67 expression in hepatocellular carcinoma (HCC) patients while also exploring its potential to predict the one-year recurrence risk. The clinical, pathological, and imaging data of 83 patients with HCC confirmed by postoperative pathology were analyzed, and the patients were randomly divided into a training set (n = 58) and a validation set (n = 25) at a ratio of 7:3. All patients underwent a magnetic resonance imaging (MRI) scan that included multi-b value diffusion-weighted scanning before surgery, and quantitative parameters were obtained via intravoxel incoherent motion (IVIM) and diffusion kurtosis (DKI) models. Univariate and multivariate logistic regression analyses were conducted using the training set data to construct a model, which was internally validated. The area under the curve (AUC) of the receiver operating characteristics (ROC), a decision curve analysis (DCA), and a calibration analysis were used to evaluate the model's performance. Additionally, for patients with available follow-up data, the combined model was evaluated for its potential utility in predicting the one-year recurrence risk by analyzing the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.The combined model outperformed the clinicaland parametric models in predicting high Ki67 expression. The nomograms based on the combined model included the neutrophil-to-lymphocyte ratio (NLR), ADCslow&#95;Aver. The model showed strong discrimination in the training set, with an AUC of 0.836 (95% CI: 0.729-0.942) and acceptable calibration (Hosmer-Lemeshow p = 0.109). In the validation set, the model maintained moderate discrimination (AUC 0.806, 95% CI: 0.621-0.990) with good calibration (p = 0.663). DCA revealed that the combined model provided good clinical value and correction effects. Additionally, when used to predict the one-year recurrence risk, the combined model achieved moderate accuracy (AUC = 0.747), highlighting its potential utility in identifying patients at a higher risk of recurrence. A nomogram incorporating the NLR and quantitative MR diffusion parameters effectively predicts Ki67 expression in HCC patients before surgery. The model also shows promise in predicting recurrence risk, which may aid in postoperative risk stratification and patient management. Clinical Relevance Statement We established a model that incorporated the NLR and quantitative magnetic resonance diffusion parameters, which demonstrated robust performance in predicting both high Ki67 expression and the one-year recurrence risk in HCC patients. This model shows potential clinical value in guiding postoperative risk stratification and personalized treatment planning., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This research involved human participants. All data were obtained from routine clinical tests, and there was no clinical intervention for the participants in the study. This was a prospective study conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of the First Affiliated Hospital of Guangxi Medical (Approval Number: 2024-E432-01). Informed consent: All patients provided their written informed consent., (© 2024. The Author(s).)

We demonstrated that the aspect ratio (AR)-tunable CdSe/CdS dot-in-rod (DiR) nanostructures with quasi-type-II band structure were successively synthesized using the hot injection method. When the AR of CdSe/CdS DiR was tuned from 10 to 37, the exciton localization efficiency along the longitudinal CdS rod shell decreased from 57.9 to 15.1%, resulting in a 5-fold improvement in the efficiency of photocatalytic hydrogen (H 2 ) evolution. The optimal CdSe/CdS DiR exhibited the highest H 2 evolution rate of 2.11 mmol·g -1 ·h -1 at an AR of 29 without any cocatalyst assistance. In situ transient absorption spectroscopy was employed to investigate the interfacial charge carrier dynamics of CdSe/CdS DiR during practical photocatalytic H 2 evolution. The findings indicated that the half-life of delocalized electrons on the conduction band along the longitudinal CdS rod shell increases from 11.5 to 20.1 μs as the AR increased, demonstrating that the AR-dependent charge carrier dynamics significantly influences the photoactivity of CdSe/CdS DiR. This study provides valuable and novel insights into the tunability of charge carrier dynamics through AR manipulation in one-dimensional semiconductor nano-heterostructures for solar fuel generation.

Objectives: To investigate the prevalence and association with mortality of inability to perform sit-to-stand independently in critically ill survivors 3 months following medical ICU (MICU) discharge., Design: Prospective cohort study., Setting: Six MICUs at a tertiary care hospital., Patients: MICU survivors who could sit-to-stand independently before the index hospitalization., Interventions: None., Measurements and Main Results: Inability to sit-to-stand (yes/no) was measured at four points following MICU discharge: upon ICU discharge, 1, 2, and 3 months afterward. Mortality was evaluated at 6- and 12-month post-MICU discharge. Among 194 participants, 128 (66%) had inability to sit-to-stand upon MICU discharge. Recovery occurred, with rates decreasing to 50% at 1 month, 38% at 2 months, and 36% at 3 months post-MICU discharge, plateauing at 2 months. Inability to sit-to-stand at 3 months was significantly associated with 21% mortality at 12 months and a 4.2-fold increased risk of mortality (adjusted hazard ratio, 4.2; 95% CI, 1.61-10.99), independent of age, Sequential Organ Failure Assessment score, and ICU-acquired weakness. Notably, improvement in sit-to-stand ability, even from "totally unable" to "able with assistance," correlates with reduced mortality risk., Conclusions: Inability to sit-to-stand affects about 36% of MICU survivors even at 3 months post-ICU discharge, highlighting rehabilitation challenges. Revisiting sit-to-stand ability post-ICU discharge is warranted. Additionally, using sit-to-stand as a screening tool for interventions to improve return of its function and mortality is suggested., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

A series of green phosphors, Ca 1-y% MoO 4 :y%Tb 3+ (where y = 0.1, 0.5, 1, 2, 3, 4, and 5) were successfully prepared via hydrothermal synthesis. The pH levels were used to modulate the luminescent of CMO:Tb. To confirm the potential application of proposed phosphors, Blueberry anthocyanin (BBA) was loading onto CMO:Tb surface to form a luminescence probe. The synthesized phosphors and probes were characterized using X-ray diffraction (XRD), FT-IR spectra, transmission electron microscopy (TEM), and high-resolution TEM (HRTEM). As a proof-of-concept, the constructed probes were adopted to evaluate the acidity of solution. The results showed that luminescence emission intensity at 546 nm increased with pH value increasing in the range of 2-12. Meanwhile, the color of the sensor solution changed from bright red to pink, then to purple, and finally to yellow as the pH varies between 2 and 12. The above results indicated that the proposed probe could evaluate the acidity of solution via the dual-mode luminescence detecting and naked eye to obtain accurate results. This proposed strategy gives an insight to design the efficient probes to precisely and sensitively evaluate the acidity in complex samples., (© 2024 John Wiley & Sons Ltd.)

Vibrational strong coupling can modify chemical reaction pathways in unconventional ways. Thus far, Fabry-Perot cavities formed by pairs of facing mirrors have been mostly utilized to achieve vibrational strong coupling. In this study, we demonstrate the application of non-local metasurfaces that can sustain surface lattice resonances, enabling chemical reactions under vibrational strong coupling. We show that the solvolysis kinetics of para-nitrophenyl acetate can be accelerated by a factor of 2.7 by strong coupling to the carbonyl bond of the solvent and the solute with a surface lattice resonance. Our work introduces a new platform to investigate polaritonic chemical reactions. In contrast to Fabry-Perot cavities, metasurfaces define open optical cavities with single surfaces, which removes alignment hurdles, facilitating polaritonic chemistry across large areas., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

We investigate the vibrational ultrastrong coupling between molecular vibrations of water molecules and surface lattice resonances (SLRs) sustained by extended arrays of plasmonic microparticles. We design and fabricate an array of gold bowties, which sustain a very high field enhancement, with its SLR resonated with the OH stretching modes of water. We measure a Rabi splitting of 567 cm-1 in the strongly coupled system, whose coupling strength is 8% of the OH vibrational energy, at the onset of the ultrastrong coupling regime (10%). These results introduce metallic microparticle arrays as a platform for the investigation of ultrastrong coupling, which could be used in polaritonic chemistry to modify the dynamics of chemical reactions that require high coupling strengths., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND) license (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aims: To compare the individual and combined effects on 90-day mortality among four critically ill survivor groups: normal (without ICU-acquired delirium or ICU-acquired weakness), delirium-only (with ICU-acquired delirium only), weakness-only (with ICU-acquired weakness only) and delirium-weakness (combined ICU-acquired delirium and weakness)., Methods: A prospective cohort study consecutively recruited delirium-free critically ill patients admitted to six medical ICUs at a university hospital. Delirium was assessed once daily for 14 days (or until death or ICU discharge) using the Confusion Assessment Method for the ICU. Participants who were discharged from the ICUs were assessed for weakness using the Medical Research Council scale. A summed score below 48 defines ICU-acquired weakness. These survivors were evaluated again for 90-day mortality. The study is reported using the STROBE checklist., Results: Delirium developed in 107 (43.2%) participants during their first 14 days of ICU stay; 55 (22.2%) met criteria for weakness by ICU discharge. Participants with delirium were at increased risk for also developing ICU-acquired weakness, and the 90-day mortality was 18.2%. Independent of age and Acute Physiology and Chronic Health Evaluation II score at ICU admission, delirium-only and weakness-only were not associated with higher 90-day mortality, while participants in the delirium-weakness group had a 3.69-fold higher risk of death, compared to those who were normal during the ICU stay. A non-significant interaction was found, suggesting the joint effect of delirium and weakness on mortality is not higher than the sum of both effects individually., Conclusions: Mortality is substantially high among critically ill survivors who experience both delirium and weakness, although no additive effect on mortality was observed when these conditions occur together. Our findings highlight the urgent need to optimise ICU care by prioritising the prevention, early identification and management of these two common ICU-acquired conditions., Patient Contribution: Study participation and completion of all assessments., Trial Registration: ClinicalTrials.gov identifier: NCT04206306., (© 2024 John Wiley & Sons Ltd.)

Pantetheinase is a key biomarker for the diagnosis of acute kidney injury and the monitoring of malaria progression. Currently, existing methods for sensing pantetheinase, also known as Vanin-1, show considerable potential but come with certain limitations, including their inability to directly sense analytes in turbid biofluid samples without tedious sample pretreatment. Here, we describe the first activity-based electrochemical probe, termed VaninLP, for convenient and specific direct targeting of pantetheinase activity in turbid liquid biopsy samples. The probe was designed such that cleavage of the pantetheinase amide linkage, triggered by a self-immolative reaction, simultaneously ejects an amino ferrocene reporter. Among the distinctive properties of the VaninLP probe for sensing pantetheinase are its high selectivity, sensitivity, and enzyme affinity, a wide linear concentration range (8-300 ng/mL), and low limit of detection (2.47 ng/mL). The designed probe precisely targeted pantetheinase and was free of interference by other electroactive biological species. We further successfully applied the VaninLP probe to monitor and quantify the activity of pantetheinase on the surfaces of HepG2 tumor cells, blood, and urine samples. Collectively, our findings indicate that VaninLP holds significant promise as a point-of-care tool for diagnosing early-stage kidney injury, as well as monitoring the progression of malaria.

The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R 2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis.

Hot springs are known to harbor potentially unique microorganisms due to the extreme temperatures in which they thrive and their biotechnologically important enzymes that are active at high temperature, which are beneficial for various industries. Sabah, Malaysia, houses several hot springs, yet knowledge of their microbiological diversity remains limited. Here, the raw sequence data of bacterial communities in a hot spring through metagenomic analysis are revealed. The data were obtained by collecting water and sediment samples from Poring Hot Spring (PHS) in Ranau, Sabah, and their bacterial diversity was analyzed using 16S rRNA amplicon sequencing targeting the V3-V4 regions. The analysis identified bacterial diversity in both water and sediment samples, with 35 phyla, 76 families, and 90 genera in water, and 38 phyla, 114 families, and 128 genera in sediment. Proteobacteria dominated the water samples (87 %), while Cyanobacteria were most abundant in sediment samples (51 %). The most abundant genera in water were Tepidimonas, Hydrogenophilus and Methylothermus, whereas Geitlerinema, Calothrix and Nitrospira dominated the sediment. Sediment samples exhibited higher bacterial richness and diversity compared to water samples, as indicated by α-diversity analysis. Sequences and sample data are deposited in the NCBI Sequence Read Archive under Bioproject ID PRJNA982554 (Accession number: SRX20671661 to SRX20671666) at https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA982554&o=acc&#95;s%3Aa)., (© 2024 The Authors.)

Characterization of T-cell receptors (TCRs) repertoire was revolutionized by next-generation sequencing technologies; however, standardization using biological controls to facilitate precision of current alignment and assembly tools remains a challenge. Additionally, availability of TCR libraries for off-the-shelf cloning and engineering TCR-specific T cells is a valuable resource for TCR-based immunotherapies. We established nine human TCR α and β clones that were evaluated using the 5'-rapid amplification of cDNA ends-like RNA-based TCR sequencing on the Illumina platform. TCR sequences were extracted and aligned using MiXCR, TRUST4, and CATT to validate their sensitivity and specificity and to validate library preparation methods. The correlation between actual and expected TCR ratios within libraries confirmed accuracy of the approach. Our findings established the development of biological standards and library of TCR clones to be leveraged in TCR sequencing and engineering. The remaining human TCR clones' libraries for a more diverse biological control will be generated., (© The Author(s) 2024. Published by Oxford University Press.)

MT-1207 (MT) as a new antihypertensive drug is under clinical trial. However, its hypotensive mechanism has not been experimentally explored, and it is unknown whether MT can be used for bilateral renal artery stenosis hypertension. Using two-kidney two-clip (2K2C) to mimic bilateral renal artery stenosis in rats, a stroke-prone renovascular hypertension model, the present study further verified its antihypertensive effect, cardiovascular and renal protection, mortality reduction and lifespan prolongation, as well as demonstrated its two novel pharmacological effects for uric acid-lowering and cognition-improving. Notably, MT did not aggravate renal dysfunction; instead, it had beneficial effects on reducing serum uric acid level and maintaining serum K + at a relatively stable level in 2K2C rats. In contrast, angiotensin receptor blocker losartan aggravated renal dysfunction in 2K2C rats. Mechanistically, MT hypotensive effect was dependent on its blockade of α 1 and 5-HT 2 receptors, since MT pretreatment abolished these receptor agonists-induced blood pressure elevations in vivo. Further evidence showed MT bound to and interacted with these receptor subtypes including α 1A , α 1B , α 1D , 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors known for control of blood pressure. In conclusion, MT may be used for treatment of bilateral renal artery stenosis hypertension, different from losartan that is prohibited for treatment of bilateral renal artery stenosis hypertension. Targets validation of MT hypotensive mechanism and beneficial effects of MT on uric acid and cognitive function provide new insights for this novel multitarget drug, deserving clinical trial attention., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Older adults with major depressive disorder (MDD) or early cognitive decline during the subjective cognitive decline (SCD) stage may exhibit neuropsychiatric symptoms such as anxiety, depression, and subtle cognitive impairment. The clinicopathological features and biological mechanisms of MDD differ from those of SCD among older adults; these conditions thus require different treatment strategies. This study enrolled 82 participants above 50 years old with normal cognitive levels from the communities to examine biomarker-behavior correlations between MDD (n = 23) and SCD (n = 23) relative to a normal control (NC) group (n = 36). Multidomain assessments were performed for all participants, including immunomagnetic reduction tests to detect plasma beta-amyloid (Aβ), total tau (Tau), phosphorylated tau-181 (p-Tau181), neurofilament light chain, and glial fibrillary acidic protein (GFAP). This study observed that depressive symptoms in MDD were associated with amyloid pathology (plasma Aβ40 vs. HADS-D: R = 0.45, p = 0.031; Aβ42/Aβ40 vs. HADS-D: R = -0.47, p = 0.024), which was not observed in the NC (group difference p < 0.05). Moreover, cognitive decline in MDD was distinguished by a mixed neurodegenerative process involving amyloid (plasma Aβ42 vs. facial memory test: R = 0.48, p = 0.025), tau (Tau/Aβ42 vs. digit symbol substitution test (DSST): R = -0.53, p = 0.01), and astrocytic injury (plasma GFAP vs. Montreal cognitive assessment score: R = -0.44, p = 0.038; plasma GFAP vs. DSST: R = -0.52, p = 0.014), findings that did not apply to the NC (group difference p < 0.05). Moreover, this study revealed different biomarker-behavior correlations between individuals with SCD and the NC. Compared with the NC, cognitive decline in the SCD group might be unrelated to amyloid pathology and instead might be early manifestations of tau pathology. This study underscores the difference in clinicopathological features between MDD and SCD among older adults, which differ from those of the NC. These findings enhance our understanding of the mechanisms underlying MDD and SCD in older individuals., (© 2024. The Author(s).)

Studies in model microorganisms showed that cell division is highly vulnerable to high hydrostatic pressure (HHP). Disassembly of FtsZ filaments induced by HHP results in the failure of cell division and formation of filamentous cells in E. coli . The specific characteristics of FtsZ that allow for functional cell division in the deep-sea environments, especially in obligate piezophiles that grow exclusively under HHP condition, remain enigmatic. In this study, by using a self-developed HHP in-situ fixation apparatus, we investigated the effect of HHP on FtsZ by examining the subcellular localization of GFP-tagged FtsZ in vivo and the stability of FtsZ filament in vitro . We compared the pressure tolerance of FtsZ proteins from pressure-sensitive strain Shewanella oneidensis MR-1 (FtsZ So ) and obligately piezophilic strain Shewanella benthica DB21MT-2 (FtsZ Sb ). Our findings showed that, unlike FtsZ So , HHP hardly affected the Z-ring formation of FtsZ Sb , and filaments composed of FtsZ Sb were more stable after incubation under 50 MPa. By constructing chimeric and single amino acid mutated FtsZ proteins, we identified five residues in the N-terminal GTPase domain of FtsZ Sb whose mutation would impair the Z-ring formation under HHP conditions. Overall, these results demonstrate that FtsZ from the obligately piezophilic strain exhibits superior pressure tolerance than its homologue from shallow water species, both in vivo and in vitro . Differences in pressure tolerance of FtsZ are largely attributed to the N-terminal GTPase domain. This represents the first in-depth study of the adaptation of microbial cytoskeleton protein FtsZ to high hydrostatic pressure, which may provide insights into understanding the complex bioprocess of cell division under extreme environments., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cui, Wei, Li, Qi, Wu and Zhang.)

A 63-year-old female patient presented with "flashes of light in both eyes accompanied by decreased visual acuity for one year." Visual field examination revealed partial defects in the central 30° of the visual field in both eyes. Scanning laser ophthalmoscopy showed extensive atrophic lesions across the entire posterior pole of the retina in both eyes. Optical coherence tomography revealed atrophy and thinning of the retina in the macular regions, with significant atrophy of the photoreceptor inner segment and outer segment layer in the areas corresponding to the visual field defects. Fluorescein fundus angiography demonstrated thinning of the retinal arterioles. Early-phase imaging showed large window-like defects in the posterior retina with background fluorescence from choroidal macrovessels. In the late phase, patchy fluorescence staining with a circumferential hyperfluorescent area was observed. Pattern visual evoked potential and pattern electroretinography tests revealed a significant decrease in the P100 amplitude in both eyes. The patient was diagnosed with acute regional occult outer layer retinopathy in both eyes.

Catalyzing reactions effectively by vacuum fluctuations of electromagnetic fields is a significant challenge within the realm of chemistry. As opposed to most studies based on vibrational strong coupling, we introduce an innovative catalytic mechanism driven by weakly coupled polaritonic fields. Through the amalgamation of macroscopic quantum electrodynamics (QED) principles with Marcus electron transfer (ET) theory, we predict that ET reaction rates can be precisely modulated across a wide dynamic range by controlling the size and structure of nanocavities. Compared to QED-driven radiative ET rates in free space, plasmonic cavities induce substantial rate enhancements spanning the range from 10 3 - to 10-fold. By contrast, Fabry-Perot cavities engender rate suppression spanning the range from 10 -2 - to 10 -1 -fold. This work overcomes the necessity of using strong light-matter interactions in QED chemistry, opening up a new era of manipulating QED-based chemical reactions in a wide dynamic range.

Background: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood., Methods: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire., Results: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively., Conclusion: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Natural Language Processing (NLP) is a subfield of artificial intelligence that focuses on the interaction between computers and human language, enabling computers to understand, generate, and derive meaning from human language. NLP's potential applications in the medical field are extensive and vary from extracting data from Electronic Health Records -one of its most well-known and frequently exploited uses- to investigating relationships among genetics, biomarkers, drugs, and diseases for the proposal of new medications. NLP can be useful for clinical decision support, patient monitoring, or medical image analysis. Despite its vast potential, the real-world application of NLP is still limited due to various challenges and constraints, meaning that its evolution predominantly continues within the research domain. However, with the increasingly widespread use of NLP, particularly with the availability of large language models, such as ChatGPT, it is crucial for medical professionals to be aware of the status, uses, and limitations of these technologies., (Copyright © 2024. Published by Elsevier Inc.)

Background: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers., Methods: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk., Results: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10 -7 ) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10 -6 ). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field., Conclusion: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers., (© 2024. The Author(s).)

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan-Meier analysis revealed no significant difference between the NPC and non-NPC groups ( p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3-7%) after both surgery and RT, 4% (95% CI = 2-6%) after surgery alone, and 5% (95% CI = 3-7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Backgrounds: Fatigability is prevalent in older adults. However, it is often associated with depressed mood. We aim to investigate these two psychobehavioral constructs by examining their underpinning of white matter structures in the brain and their associations with different medical conditions., Methods: Twenty-seven older adults with late-life depression (LLD) and 34 cognitively normal controls (CN) underwent multi-shell diffusion MRI. Fatigability was measured with the Pittsburgh Fatigability Scale. We examined white matter integrity by measuring the quantitative anisotropy (QA), a fiber tracking parameter with better accuracy than the traditional imaging technique., Results: We found those with LLD had lower QA in the 2nd branch of the left superior longitudinal fasciculus (SLF-II), and those with more physical fatigability had lower QA in more widespread brain regions. In tracts associated with more physical fatigability, the lower QA in left acoustic radiation and left superior thalamic radiation correlated with higher blood glucose (r = - 0.46 and - 0.49). In tracts associated with depression, lower QA in left SLF-II correlated with higher bilirubin level (r = - 0.58)., Discussion: Depression and fatigability were associated with various white matter integrity changes, which correlated with biochemistry biomarkers all related to inflammation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD., Methods: Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments., Results: The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aβ42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05)., Conclusion: Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aβ42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD., (© 2024. The Author(s).)

A key challenge in realizing practical quantum networks for long-distance quantum communication involves robust entanglement between quantum memory nodes connected by fibre optical infrastructure 1-3 . Here we demonstrate a two-node quantum network composed of multi-qubit registers based on silicon-vacancy (SiV) centres in nanophotonic diamond cavities integrated with a telecommunication fibre network. Remote entanglement is generated by the cavity-enhanced interactions between the electron spin qubits of the SiVs and optical photons. Serial, heralded spin-photon entangling gate operations with time-bin qubits are used for robust entanglement of separated nodes. Long-lived nuclear spin qubits are used to provide second-long entanglement storage and integrated error detection. By integrating efficient bidirectional quantum frequency conversion of photonic communication qubits to telecommunication frequencies (1,350 nm), we demonstrate the entanglement of two nuclear spin memories through 40 km spools of low-loss fibre and a 35-km long fibre loop deployed in the Boston area urban environment, representing an enabling step towards practical quantum repeaters and large-scale quantum networks., (© 2024. The Author(s).)

Background: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated., Patients and Methods: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS)., Results: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score., Conclusions: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP., Competing Interests: Conflicts of interest sources of funding: T.C.Y. owns equity in APRINOIA Therapeutics. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Singlet fission (SF) holds great promise for current photovoltaic technologies, where tetracenes, with their relatively high triplet energies, play a major role for application in silicon-based solar cells. However, the SF efficiencies in tetracene dimers are low due to the unfavorable energetics of their singlet and triplet energy levels. In the solid state, tetracene exhibits high yields of triplet formation through SF, raising great interest about the underlying mechanisms. To address this discrepancy, we designed and prepared a novel molecular system based on a hexaphenylbenzene core decorated with 2 to 6 tetracene chromophores. The spatial arrangement of tetracene units, induced by steric hindrance in the central part, dictates through-space coupling, making it a relevant model for solid-state chromophore organization. We then revealed a remarkable increase in SF quantum yield with the number of tetracenes, reaching quantitative (196 %) triplet pair formation in hexamer. We observed a short-lived correlated triplet pair and limited magnetic effects, indicating ineffective triplet dissociation in these through-space coupled systems. These findings emphasize the crucial role of the number of chromophores involved and the interchromophore arrangement for the SF efficiency. The insights gained from this study will aid designing more efficient and technology-compatible SF systems for applications in photovoltaics., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Pseudoachalasia is a rare disease that behaves similarly to achalasia (AC), making it sometimes difficult to differentiate., Case Presentation: We report a case of 49-year-old male with adenocarcinoma of the gastroesophageal junction misdiagnosed as achalasia. No obvious abnormalities were found in his initial examinations including upper digestive endoscopy, upper gastrointestinal imaging and chest computed tomography (CT). During the subsequent introduced-peroral endoscopic myotomy (POEM), it was found that the mucosal layer and the muscular layer had severe adhesion, which did not receive much attention, delayed the clear diagnosis and effect treatment, and ultimately led to a poor prognosis for the patient., Conclusions: This case suggests that when patients with AC found mucosal and muscular adhesions during POEM surgery, the possibility should be considered that the lesion may be caused by a malignant lesion., (© 2024. The Author(s).)

The typical presentation of multifocal motor neuropathy (MMN) is progressive asymmetric limb weakness. Cranial neuropathy is rare. We report a 28-year-old woman with cranial and bulbar palsies but with typical electrophysiological features of MMN by multifocal motor conduction blocks and serological markers of anti-ganglioside GM1 antibodies. The previous consensus on the treatment of MMN is intravenous immunoglobulins, but our patient responded to oral steroids and had clinical and electrophysiological improvement under continuous low-dose prednisolone treatment. In summary, MMN is a treatable chronic inflammatory disease of peripheral nerves. Cranial neuropathies can be its initial presentations. Electromyography studies are crucial for MMN diagnosis and helpful in monitoring disease activity and treatment responses. Although the previous guideline did not suggest using steroids for MMN, with careful patient selection, low-dose oral steroids can be an effective treatment in patients with relatively minor symptoms. Keywords: Multifocal motor neuropathy, conduction block, bulbar palsy, cranial nerve, cranial neuropathy.

The advancement of metabolic engineering and synthetic biology has promoted in-depth research on the nonmodel microbial metabolism, and the potential of nonmodel organisms in industrial biotechnology is becoming increasingly evident. The nonmodel organism Pseudomonas chlororaphis is a safe plant growth promoting bacterium for the production of phenazine compounds; however, its application is seriously hindered due to the lack of an effective gene expression precise regulation toolkit. In this study, we constructed a library of 108 promoter-5'-UTR (PUTR) and characterized them through fluorescent protein detection. Then, 6 PUTRs with stable low, intermediate, and high intensities were further characterized by report genes lacZ encoding β-galactosidase from Escherichia coli K12 and phzO encoding PCA monooxygenase from P. chlororaphis GP72 and thus developed as a static gene expression regulation system. Furthermore, the stable and high-intensity expressed P MOK&#95;RS0128085 UTR was fused with the LacO operator to construct an IPTG-induced plasmid, and a self-induced plasmid was constructed employing the high-intensity P MOK&#95;RS0116635 UTR regulated by cell density, resulting in a dynamic gene expression regulation system. In summary, this study established two sets of static and dynamic regulatory systems for P. chlororaphis , providing an effective toolkit for fine-tuning gene expression and reprograming the metabolism flux.

Urothelial carcinoma (UC) is common cancer worldwide with a high prevalence in Taiwan, especially in the upper urinary tract, including the renal pelvis and ureter, also classifying as upper urinary tract urothelial carcinoma. Here, we aim to find a representative prognostic marker that strongly correlates to this type of carcinoma. Transforming growth factor beta-1-induced transcript 1 (TGFB1I1) is a cofactor of cellular TGF-β1 and interacts with various nuclear receptors. The previous study showed that TGFB1I1 promotes focal adhesion formation, contributing to the epithelial-mesenchymal transition (EMT) with actin cytoskeleton and vimentin through TGFB1I1 regulation. We aim to reveal the role of TGFB1I1 in the tumorigenesis of UC. In silico and clinicopathological data of upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC) were accessed and analyzed for IHC staining regarding tumor characteristics, including survival outcome. Finally, an in vitro study was performed to demonstrate the biological changes of UC cells. In UTUC, overexpression of TGFB1I1 was significantly correlated with advanced tumor stage, papillary configuration, and frequent mitosis. Meanwhile, overexpression of TGFB1I1 was significantly correlated with advanced tumor stage and histological grade in UBUC. Moreover, the in vitro study shows that TGFB1I1 affects cell proliferation, viability, migration and wound healing. The EMT markers also decreased upon TGFB1I1 knockdown. In this study, we identified that TGFB1I1 regulates UC cell proliferation and viability and induces the EMT to facilitate cell migration in vitro, leading to its essential role in promoting tumor aggressiveness in both UTUC and UBUC., (© 2024 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Persons who have experienced traumatic brain injury (TBI) may encounter a range of changes in their physical, mental, and cognitive functions as well as high fatigue levels. To gain a comprehensive understanding of the challenges faced by persons after TBI, we conducted multi-domain assessments among community-dwelling persons with a history of TBI and compared them with age- and sex-matched controls from the Northeastern Taiwan Community Medicine Research Cohort between 2019 and 2021. A total of 168 persons with TBI and 672 non-TBI controls were not different in terms of demographics, comorbidities, and physiological features. However, compared with the non-TBI group, the TBI group had a distinct lifestyle that involved increased reliance on analgesics (6.9% vs. 15.0%, respectively; p  = 0.001) and sleep aids ( p  = 0.008), which negatively affected their quality of life. Moreover, they consumed more coffee ( p  < 0.001), tea ( p  < 0.001), cigarettes ( p  = 0.002), and betel nuts ( p  = 0.032) than did the non-TBI group. Notably, the use of coffee had a positive effect on the quality of life of the TBI group ( F  = 4.034; p  = 0.045). Further, compared with the non-TBI group, the TBI group had increased risks of sarcopenia ( p  = 0.003), malnutrition ( p  = 0.003), and anxiety ( p  = 0.029) and reduced blood levels of vitamin D (29.83 ± 10.39 vs. 24.20 ± 6.59 ng/mL, respectively; p  < 0.001). Overall, the TBI group had a reduced health-related quality of life, with significant challenges related to physical health, mental well-being, social interactions, pain management, and fatigue levels. Moreover, the TBI group experienced poorer sleep quality and efficiency than did the non-TBI group. In conclusion, persons who have sustained brain injuries that require comprehensive and holistic care that includes lifestyle modification, mental and physical healthcare plans, and increased long-term support from their communities. ClinicalTrials.gov (identifier: NCT04839796)., Competing Interests: No competing financial interests exist., (© Yi-Chia Wei et al., 2024; Published by Mary Ann Liebert, Inc.)

The prognosis for pathologically node-negative (pN0) esophageal squamous cell carcinoma (ESCC) with surgery alone remains poor. We aimed to develop a model for a more precise prediction of recurrence, which will allow personalized management for pN0 ESCC after upfront complete resection. Clinical and pathological records of patients with completely resected pT1-3N0M0 ESCC were retrospectively analyzed between January 2014 and December 2019. A nomogram for the prediction of recurrence was established based on the Cox regression analysis and evaluated by C-index, AUC, and calibration curves. The model was further validated using bootstrap resampling and k-fold cross-validation and compared with the 8th edition of the AJCC TNM staging system using Td-ROC, NRI, IDI, and DCA. Two-hundred-and seventy cases were included in this study. The median follow-up was 45 months. Distant and/or loco-regional recurrences were noted in 89 (33.0%) patients. The predictive model revealed pT-category, differentiation, perineural invasion, examined lymph nodes (ELN), and prognostic nutritional index (PNI) as independent risk factors for recurrence, with a c-index of 0.725 in the bootstrapping cohort. Td-ROC, NRI, and IDI showed a better predictive ability than the AJCC 8th TNM staging system. Based on this model, patients in the low-risk group had a significantly lower recurrence incidence than those in the high-risk group (p < .001). The predictive model developed in this study may facilitate the precise prediction of recurrences for pN0 ESCC after upfront surgery. Stratifying management of those patients might bring significantly better survival benefits., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.