Chromatin lysine acylation: On the path to chromatin homeostasis and genome integrity.

The fundamental role of cells in safeguarding the genome's integrity against DNA double-strand breaks (DSBs) is crucial for maintaining chromatin homeostasis and the overall genomic stability. Aberrant responses to DNA damage, known as DNA damage responses (DDRs), can result in genomic instability and contribute significantly to tumorigenesis. Unraveling the intricate mechanisms underlying DDRs following severe damage holds the key to identify therapeutic targets for cancer. Chromatin lysine acylation, encompassing diverse modifications such as acetylation, lactylation, crotonylation, succinylation, malonylation, glutarylation, propionylation, and butyrylation, has been extensively studied in the context of DDRs and chromatin homeostasis. Here, we delve into the modifying enzymes and the pivotal roles of lysine acylation and their crosstalk in maintaining chromatin homeostasis and genome integrity in response to DDRs. Moreover, we offer a comprehensive perspective and overview of the latest insights, driven primarily by chromatin acylation modification and associated regulators.

Ring-Embedded Finger Over Proximal Interphalangeal Joint with Preserved Neurovascularization: A Case Report and Literature Review.

CASE: We present a unique case of a 45-year-old man with his right middle finger embedded with rings. Limited finger flexion was noted because of flexor tendon injury caused by the dorsal migration of the embedded ring through joint. The rings were removed under anesthesia, resulting in the resolution of swelling and recover of osseous structure. Follow-up examinations revealed no residual edema or numbness, indicating preserved neurovascularization, despite the dorsal migration of the ring. CONCLUSION: Our unique case reveals continuous finger ring migration without compromising neurovascular bundles, with review of 30 cases emphasizing the importance of psychiatric consultation. Timely intervention yielded nearly half of patients achieving full recovery.

Ultralow-Energy-Consumption Photosynaptic Transistor Utilizing Conjugated Polymers/Perovskite Quantum Dots Nanocomposites With Ligand Density Optimization.

The photosynaptic transistor stands as a promising contender for overcoming the von Neumann bottleneck in the realm of photo-communication. In this context, photonic synaptic transistors is developed through a straightforward solution process, employing an organic semiconducting polymer with pendant-naphthalene-containing side chains (PDPPNA) in combination with ligand-density-engineered CsPbBr3 perovskite quantum dots (PQDs). This fabrication approach allows the devices to emulate fundamental synaptic behaviors, encompassing excitatory postsynaptic current, paired-pulse facilitation, the transition from short-to-long-term memory, and the concept of "learning experience." Notably, the phototransistor, incorporating the blend of the PDPPNA and CsPbBr3 PQDs washed with ethyl acetate, achieved an exceptional memory ratio of 104. Simultaneously, the same device exhibited an impressive paired-pulse facilitation ratio of 223% at a moderate operating voltage of -4 V and an extraordinarily low energy consumption of 0.215 aJ at an ultralow operating voltage of -0.1 mV. Consequently, these low-voltage synaptic devices, constructed with a pendant side-chain engineering of organic semiconductors and a ligand density engineering of PQDs through a simple fabrication process, exhibit substantial potential for replicating the visual memory capabilities of the human brain.

Reduced mortality with antimicrobial stewardship guided by BioFire FilmArray Blood Culture Identification 2 panel in critically ill patients with bloodstream infection: a retrospective propensity score-matched study.

OBJECTIVES: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs). METHODS: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analyzed in both models. RESULTS: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analyzed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, p < 0.001 in Model 1; 23.5% vs. 58.6%, p = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2). CONCLUSION: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.

Association of copy number variation in X chromosome-linked PNPLA4 with heterotaxy and congenital heart disease.

BACKGROUND: Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD. METHODS: Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4 -overexpressing human induced pluripotent stem cell lines as well as pnpla4 -overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. RESULTS: Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. CONCLUSIONS: Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Rate of graft retear is higher in over-the-top superior capsular reconstruction for massive posterosuperior rotator cuff tears with subscapularis tear.

PURPOSE: To compare side-to-side superior capsular reconstruction (SCR) with over-the-top SCR in terms of functional outcomes, pain relief and allograft survival rates. METHODS: Patients who had undergone arthroscopic dermal allograft SCR for massive irreparable rotator cuff tears and clinical follow-up for ≥2 years were recruited. All patients underwent postoperative assessment with routine radiographic analysis for acromiohumeral distances, ultrasound imaging 1 and 3 months after SCR and magnetic resonance imaging (MRI) at least 12 months after SCR. The outcome measures were visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES), Constant and Single Assessment Numeric Evaluation (SANE) scores. RESULTS: SCR was performed in 56 patients including side-to-side SCR in 32 and over-the-top SCR in 24. Postoperative MRI showed that the grafts were intact in 46 patients (82.1%; 26 who underwent side-to-side SCR and 20 who underwent over-the-top SCR). The proportion of nonhealing grafts in the over-the-top group was significantly higher with concomitant subscapularis tears (60% vs. 5.3%; p = 0.02). VAS scores and functional outcomes improved postoperatively in both groups and postoperative VAS (1.4 vs. 1.7; n.s.), Constant (74.8 vs. 76.0; n.s.), mean ASES (87.4 vs. 89.1; n.s.) and mean SANE (81.7 vs. 84.3; n.s.) scores did not differ significantly. CONCLUSION: For massive rotator cuff tears, over-the-top and side-to-side SCR achieve similar pain relief and functional improvement, and the rate of healing allografts is high. However, over-the-top SCR is not recommended for massive posterosuperior rotator cuff tears with repairable subscapularis tendon tears due to a higher nonhealing rate. LEVEL OF EVIDENCE: Level III.

Symbiotic defect-reinforced bimetallic MOF-derived fiber components for solar-assisted atmospheric water collection.

Conversion of atmospheric water to sustainable and clean freshwater resources through MOF-based adsorbent has great potential for the renewable environmental industry. However, its daily water production is hampered by susceptibility to agglomeration, slow water evaporation efficiency, and limited water-harvesting capacity. Herein, a solar-assisted bimetallic MOF (BMOF)-derived fiber component that surmounts these limitations and exhibits both optimized water-collect capacity and short adsorption-desorption period is proposed. The proposed strategy involves utilizing bottom-up interface-induced assembly between carboxylated multi-walled carbon nanotube and hygroscopic BMOF on a multi-ply glass fiber support. The designed BMOF (MIL-100(Fe,Al)-3) skeleton constructed using bimetallic-node defect engineering exhibits a high specific surface area (1,535.28 m2/g) and pore volume (0.76 cm3/g), thereby surpassing the parent MOFs and other reported MOFs in capturing moisture. Benefiting from the hierarchical structure of fiber rods and the solar-driven self-heating interface of photothermal layer, the customized BMOF crystals realize efficient loading and optimized water adsorption-desorption kinetics. As a result, the resultant fiber components achieve six adsorption-desorption cycles per day and an impressive water collection of 1.45 g/g/day under medium-high humidity outdoor conditions. Therefore, this work will provide new ideas for optimizing the daily yield of atmospheric water harvesting techniques.

Genome-wide association study identifies novel susceptible loci and evaluation of polygenic risk score for chronic obstructive pulmonary disease in a Taiwanese population.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) describes a group of progressive lung diseases causing breathing difficulties. While COPD development typically involves a complex interplay between genetic and environmental factors, genetics play a role in disease susceptibility. This study used genome-wide association studies (GWAS) and polygenic risk score (PRS) to elucidate the genetic basis for COPD in Taiwanese patients. RESULTS: GWAS was performed on a Taiwanese COPD case-control cohort with a sample size of 5,442 cases and 17,681 controls. Additionally, the PRS was calculated and assessed in our target groups. GWAS results indicate that although there were no single nucleotide polymorphisms (SNPs) of genome-wide significance, prominent COPD susceptibility loci on or nearby genes such as WWTR1, EXT1, INTU, MAP3K7CL, MAMDC2, BZW1/CLK1, LINC01197, LINC01894, and CFAP95 (C9orf135) were identified, which had not been reported in previous studies. Thirteen susceptibility loci, such as CHRNA4, AFAP1, and DTWD1, previously reported in other populations were replicated and confirmed to be associated with COPD in Taiwanese populations. The PRS was determined in the target groups using the summary statistics from our base group, yielding an effective association with COPD (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.17, p = 0.011). Furthermore, replication a previous lung function trait PRS model in our target group, showed a significant association of COPD susceptibility with PRS of Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FCV) (OR 0.89, 95% CI 0.83-0.95, p = 0.001). CONCLUSIONS: Novel COPD-related genes were identified in the studied Taiwanese population. The PRS model, based on COPD or lung function traits, enables disease risk estimation and enhances prediction before suffering. These results offer new perspectives on the genetics of COPD and serve as a basis for future research.

Design and Implementation of an Intensive Care Unit Command Center for Medical Data Fusion.

The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting.

The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens.

BACKGROUND: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. METHODS: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. RESULTS: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results. CONCLUSIONS: In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.

Heterointerfaces: Unlocking Superior Capacity and Rapid Mass Transfer Dynamics in Energy Storage Electrodes.

Heterogeneous electrode materials possess abundant heterointerfaces with a localized "space charge effect", which enhances capacity output and accelerates mass/charge transfer dynamics in energy storage devices (ESDs). These promising features open new possibilities for demanding applications such as electric vehicles, grid energy storage, and portable electronics. However, the fundamental principles and working mechanisms that govern heterointerfaces are not yet fully understood, impeding the rational design of electrode materials. In this study, the heterointerface evolution during charging and discharging process as well as the intricate interaction between heterointerfaces and charge/mass transport phenomena, is systematically discussed. Guidelines along with feasible strategies for engineering structural heterointerfaces to address specific challenges encountered in various application scenarios, are also provided. This review offers innovative solutions for the development of heterogeneous electrode materials, enabling more efficient energy storage beyond conventional electrochemistry. Furthermore, it provides fresh insights into the advancement of clean energy conversion and storage technologies. This review contributes to the knowledge and understanding of heterointerfaces, paving the way for the design and optimization of next-generation energy storage materials for a sustainable future.

Impact of unplanned second debridement, antibiotics and implant retention on long-term outcomes in knee exchange arthroplasty: Elevated risk of failure and reinfection.

Purpose: This study investigates the outcomes of two-stage exchange arthroplasty (EA) for periprosthetic joint infection (PJI) following initial or unplanned repeat debridement antibiotics, and implant retention (DAIR). Methods: We retrospectively reviewed cases of knee arthroplasty infection treated with two-stage EA after DAIR, spanning from January 1994 to December 2010. A total of 138 patients were included, comprising 112 with initial DAIR and 26 with an unplanned second DAIR. Data on demographics, comorbidities, infection characteristics and causative organisms were analyzed. The primary outcome was implant failure or reinfection, observed over a minimum follow-up of 10 years. Results: The overall success rate for two-stage EA was 87% (119/138 patients). Factors identified for treatment failure included reinfection with the same pathogen for unplanned second DAIR (hazard ratio [HR] = 3.41; 95% confidence interval [CI] = 1.35-4.38; p = 0.004), higher reinfection rates in patients undergoing EA after an unplanned second DAIR, especially with a prior history of PJI within 2 years (HR = 4.23; 95% CI = 2.39-5.31; p = 0.002), pre-first DAIR C-reactive protein (CRP) levels over 100 mg/dL (HR = 2.52; 95% CI = 1.98-3.42; p = 0.003) and recurrence with the same pathogen (HR = 2.35; 95% CI = 1.32-4.24; p = 0.007). Additional factors such as male gender (HR = 3.92; 95% CI = 1.21-5.25; p = 0.007) and osteoporosis (T score < -2.5; HR = 3.27; 95% CI = 1.23-5.28; p = 0.005) were identified as risk factors for implant failure in all EA cases. Conclusions: This study identifies key risk factors for worse knee EA outcomes following DAIR, including a pre-first DAIR CRP level over 100 mg/L, same pathogen recurrence, and PJI history within 2 years. It shows implant failure rates remain constant across EA cases, regardless of DAIR sequence, particularly with risk factors like male gender and severe osteoporosis (T score < -2.5). These results underscore the need for careful evaluation before an unplanned second DAIR, given its significant impact on EA success. Level of Evidence: Level III.

Assessing mortality risk in Type 2 Diabetes patients with prolonged ASCVD risk factors: the inclusive Poh-Ai predictive scoring system with CAC Score integration.

PURPOSE: To enhance the predictive risk model for all-cause mortality in individuals with Type 2 Diabetes (T2DM) and prolonged Atherosclerotic Cardiovascular Disease (ASCVD) risk factors. Despite the utility of the Coronary Artery Calcium (CAC) score in assessing cardiovascular risk, its capacity to predict all-cause mortality remains limited. METHODS: A retrospective cohort study included 1929 asymptomatic T2DM patients with ASCVD risk factors, aged 40-80. Variables encompassed demographic attributes, clinical parameters, CAC scores, comorbidities, and medication usage. Factors predicting all-cause mortality were selected to create a predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. RESULTS: In our analysis of all-cause mortality in T2DM patients with extended ASCVD risk factors over 5 years, we identified significant risk factors, their adjusted hazard ratios (aHR), and scores: e.g., CAC score > 1000 (aHR: 1.57, score: 2), CAC score 401-1000 (aHR: 2.05, score: 2), and more. These factors strongly predict all-cause mortality, with varying risk groups (e.g., very low-risk: 2.0%, very high-risk: 24.0%). Significant differences in 5-year overall survival rates were observed among these groups (log-rank test < 0.001). CONCLUSION: The Poh-Ai Predictive Scoring System excels in forecasting mortality and cardiovascular events in individuals with Type 2 Diabetes Mellitus and extended ASCVD risk factors.

Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Next-Generation Sequencing-Based Copy Number Variation Analysis in Chinese Patients with Primary Ciliary Dyskinesia Revealed Novel DNAH5 Copy Number Variations.

Primary ciliary dyskinesia (PCD) is a rare disorder characterized by extensive genetic heterogeneity. However, in the genetic pathogenesis of PCD, copy number variation (CNV) has not received sufficient attention and has rarely been reported, especially in China. Next-generation sequencing (NGS) followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing (WES) analysis. Quantitative real-time polymerase chain reaction (qPCR) and Sanger sequencing were used to confirm these CNVs. To further characterize the ciliary phenotypes, high-speed video microscopy analysis (HSVA), transmission electron microscopy (TEM), and immunofluorescence (IF) analysis were used. Patient 1 (F1: II-1), a 0.6-year-old girl, came from a nonconsanguineous family-I. She presented with situs inversus totalis, neonatal respiratory distress, and sinusitis. The nasal nitric oxide level was markedly reduced. The respiratory cilia beat with reduced amplitude. TEM revealed shortened outer dynein arms (ODA) of cilia. chr5:13717907-13722661del spanning exons 71-72 was identified by NGS-based CNV analysis. Patient 2 (F2: IV-4), a 37-year-old man, and his eldest brother Patient 3 (F2: IV-2) came from a consanguineous family-II. Both had sinusitis, bronchiectasis and situs inversus totalis. The respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile, with ODA defects. Two novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_1 3707643del, spanning exons 69-71 and exons 77-79 were identified by NGS-based CNV analysis. Abnormalities in DNA copy number were confirmed by qPCR amplification. IF showed that the respiratory cilia of Patient 1 and Patient 2 were deficient in dynein axonemal heavy chain 5 (DNAH5) protein expression. This report identified three novel DNAH5 disease-associated variants by WES-based CNV analysis. Our study expands the genetic spectrum of PCD with DNAH5 in the Chinese population. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00130-0.

5.1 µm Ion-Regulated Rigid Quasi-Solid Electrolyte Constructed by Bridging Fast Li-Ion Transfer Channels for Lithium Metal Batteries.

An ultra-thin quasi-solid electrolyte (QSE) with dendrite-inhibiting properties is a requirement for achieving high energy density quasi-solid lithium metal batteries (LMBs). Here, a 5.1 µm rigid QSE layer is directly designed on the cathode, in which Kevlar (poly(p-phenylene terephthalate)) nanofibers (KANFs) with negatively charged groups bridging metal-organic framework (MOF) particles are served as a rigid skeleton, and non-flammable deep eutectic solvent is selected to be encapsulated into the MOF channels, combined with in situ polymerization to complete safe electrolyte system with high rigidness and stability. The QSE with constructed topological network demonstrates high rigidity (5.4 GPa), high ionic conductivity (0.73 mS cm-1 at room temperature), good ion-regulated properties, and improved structural stability, contributing to homogenized Li-ion flux, excellent dendrite suppression, and prolonged cyclic performance for LMB. Additionally, ion regulation influences the Li deposition behavior, exhibiting a uniform morphology on the Li-metal surface after cycling. According to density-functional theory, KANFs bridging MOFs as hosts play a vital function in the free-state and fast diffusion dynamics of Li-ions. This work provides an effective strategy for constructing ultrathin robust electrolytes with a novel ionic conduction mode.

Comparison of continuous 24-hour and 14-day ECG monitoring for the detection of cardiac arrhythmias in patients with ischemic stroke or syncope.

BACKGROUND: Previous studies show that using 12-lead electrocardiogram (ECG) or 24-h ECG monitor for the detection of cardiac arrhythmia events in patients with stroke or syncope is ineffective. HYPOTHESIS: The 14-day continuous ECG patch has higher detection rates of arrhythmias compared with conventional 24-h ECG monitoring in patients with ischemic stroke or syncope. METHODS: This cross-sectional study of patients with newly diagnosed ischemic stroke or syncope received a 24-h ECG monitoring and 14-day continuous cardiac monitoring patch and the arrhythmia events were measured. RESULTS: This study enrolled 83 patients with ischemic stroke or syncope. The detection rate of composite cardiac arrhythmias was significantly higher for the 14-day ECG patch than 24-h Holter monitor (69.9% vs. 21.7%, p = .006). In patients with ischemic stroke, the detection rates of cardiac arrhythmias were 63.4% for supraventricular tachycardia (SVT), 7% for ventricular tachycardia (VT), 5.6% for atrial fibrillation (AF), 4.2% for atrioventricular block (AVB), and 1.4% for pause by 14-day ECG patch, respectively. The significant difference in arrhythmic detection rates were found for SVT (45.8%), AF (6%), pause (1.2%), AVB (2.4%), and VT (9.6%) by 14-day ECG patch but not by 24-h Holter monitor in patients with ischemic stroke or syncope. CONCLUSIONS: A 14-day ECG patch can be used on patients with ischemic stroke or syncope for the early detection of AF or other cardiac arrhythmia events. The patch can be helpful for physicians in planning medical or mechanical interventions of patients with ischemic stroke and occult AF.

TRIM59-mediated ferroptosis enhances neuroblastoma development and chemosensitivity through p53 ubiquitination and degradation.

Neuroblastoma, predominantly afflicting young individuals, is characterized as an embryonal tumor, with poor prognosis primarily attributed to chemoresistance. This study delved into the impact of tripartite motif (TRIM) 59, an E3 ligase, on neuroblastoma development and chemosensitivity through mediating ferroptosis and the involvement of the tumor suppressor p53. Clinical samples were assessed for TRIM59 and p53 levels to explore their correlation with neuroblastoma differentiation. In neuroblastoma cells, modulation of TRIM59 expression, either through overexpression or knockdown, was coupled with doxorubicin hydrochloride (DOX) or ferrostatin-1 (Fer-1) therapy. In vivo assessments examined the influence of TRIM59 knockdown on neuroblastoma chemosensitivity to DOX. Co-immunoprecipitation and ubiquitination assays investigated the association between TRIM59 and p53. Proliferation was gauged with Cell Counting Kit-8, lipid reactive oxygen species (ROS) were assessed via flow cytometry, and protein levels were determined by Western blotting. TRIM59 expression was inversely correlated with neuroblastoma differentiation and positively linked to cell proliferation in response to DOX. Moreover, TRIM59 impeded lipid ROS generation and ferroptosis by directly interacting with p53, promoting its ubiquitination and degradation in DOX-exposed neuroblastoma cells. Fer-1 countered the impact of TRIM59 knockdown on neuroblastoma, while TRIM59 knockdown enhanced the therapeutic efficacy of DOX in xenograph mice. This study underscores TRIM59 as an oncogene in neuroblastoma, fostering growth and chemoresistance by suppressing ferroptosis through p53 ubiquitination and degradation. TRIM59 emerges as a potential strategy for neuroblastoma therapy.

Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units.

BACKGROUND: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.

Clinical characteristics and treatment outcomes among the hospitalized elderly patients with COVID-19 during the late pandemic phase in central Taiwan.

BACKGROUND: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents. METHODS: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: 'old' (65-79 years) and 'oldest-old' (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality. RESULTS: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p < 0.001), dexamethasone (49.3 % versus 36.7 %, p < 0.001), and tocilizumab (10.0 % versus 6.8 %, p < 0.001) than old patients. The mortality rate was comparable between the two age subgroups (14 % versus 15.2 %). Independent predictors of in-hospital mortality included disease severity and comorbidities such as end-stage renal disease (ESRD), cirrhosis, solid tumours, and haematologic malignancies. Ageing was not correlated with increased in-hospital mortality across all comorbidity subgroups. CONCLUSIONS: In the later stages of the pandemic, with widespread vaccination and advancements in COVID-19 treatments, outcomes for hospitalized elderly and oldest-old patients with COVID-19 have improved. The influence of age on in-hospital mortality has diminished, while comorbidities such as ESRD, cirrhosis, solid tumours, and hematologic malignancies have been associated with mortality.