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This study presents a hybrid microfiltration technology designed for high-performance lead (Pb(II)) remediation, especially from aqueous solutions with high Pb(II) concentrations, by utilizing two-dimensional (2D) Ti 3 C 2 T x -MXene layers deposited on dry mycelium membranes. The hybrid Ti 3 C 2 T x -MXene/mycelium (MyMX) membranes were fabricated via a single-step electrochemical deposition (ECD) technique, which enabled a uniform coating of 2D Ti 3 C 2 T x -MXene onto individual hyphal fibers of a prefabricated mycelium membrane. Optimized ECD parameters for high Pb(II) uptake were identified using scanning electron microscopy and energy-dispersive X-ray spectroscopy. In immersion-based (no-flow) Pb(II) remediation experiments, MyMX membranes demonstrated significantly high Pb(II) removal efficiency (>87-99%) and rapid sorption kinetics across an initial Pb(II) concentration range of 60-1500 ppm in both single-ion and co-ion solutions. The enhanced Pb(II) sorption was attributed to electrostatic interactions and surface complexation assisted by hyphal surface proteins and Ti 3 C 2 T x -MXene functional groups, as confirmed by infrared and X-ray photoelectron spectroscopies. In cross-flow studies, the MyMX membranes achieved a Pb(II) sorption capacity of ∼1347 mg/g while maintaining a high permeation rate of 51,800 L m -2 bar -1 h -1 at 1500 ppm Pb(II), surpassing the performance of various polymer-based and MXene-based microporous membranes for heavy metal remediation. The biomaterial-based hybrid MyMX membrane represents a significant advancement in water treatment technology, providing a cost-effective, sustainable solution for Pb(II) remediation in contaminated water sources.

Background: The Computerized Adaptive Test for Measuring Children's Self-care Performance (CAT-SC) was developed with an interview administration approach for a limited population., Aims: We developed a new CAT-SC (the CAT-SC-T) based on the original candidate item bank of the CAT-SC, using the caregiver-report approach and targeting children with and without disability., Methods and Procedures Design: In this cross-sectional study in the general community, 1289 caregivers of children with and without disability were assessed with the original candidate item bank of the CAT-SC., Outcomes and Results: The item bank of the CAT-SC-T contained 69 items with unidimensionality. The three stopping rules were (1) administering a minimum of 10 items and a maximum of 16 items, (2) observing the first 10 items receiving the lowest scores, and (3) ensuring a reliability of self-care performance estimate of 0.95. From the simulation analyses, only 10-16 items were needed for each assessment to achieve good reliability and validity. The person reliability for most children (83.9 %) exceeded 0.95. Of the 16.1 % not meeting the 0.95 reliability criterion, 19 % (n = 39) were extreme responders. The good concurrent validity of the CAT-SC-T was proven by its very high correlation coefficient (r = 0.99) between the scores using the entire item bank and the estimated scores of the CAT-SC-T. Significant score differences between children with and without disability indicated good discriminant validity., Conclusions and Implications: The CAT-SC-T appears to be an efficient, reliable, and valid assessment of children's self-care performance. The CAT-SC-T can be applied to children with and without disability., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Murine double minute 2 (MDM2) inhibitors have shown promising activity in TP53-wild type tumors and are under active investigation across a spectrum of malignancies. Herein, we report a 51-year-old female with MDM2-amplified, TP53-wild type adenoid cystic carcinoma who was treated with a MDM2 inhibitor and developed persistent pancytopenia despite drug discontinuation. Her pancytopenia was associated with 20 distinct pathogenic TP53 mutations in peripheral blood and bone marrow not present in drug-resistant tumor tissue. Plasma TP53 mutations were similarly detected among 4 other patients treated at our institution, with the number of mutations correlating strongly with duration of treatment. This case suggests that MDM2 inhibitors are associated with TP53 clonal hematopoiesis, which may confer a risk of subsequent myeloid malignancy. As multiple MDM2 inhibitor trials are ongoing, our findings underscore the need for further investigation into the potential long-term deleterious effects of these inhibitors in the hematopoietic stem and progenitor compartment., Competing Interests: Competing interests: C.C. has received research grants (to his institution) from the following: Cholangiocarcinoma Foundation, ADC Therapeutics, Oric Pharmaceuticals, Seattle Genetics, Rain Therapeutics, Kinnate, Gilead, Mersana Therapeutics, Riboscience, Takeda, Palleon, Merus, Revolution Medicines, Tango Therapeutics, and Genentech-Roche, and has received consulting fees from Boxer Capital and Guidepoint Global Advisors. The remaining authors report no competing interests., (© 2025. The Author(s).)

The nanoscale control of phase transition in correlated materials offers significant insight into phase transition dynamics for the advancement of future nanoelectronics devices. This study explores the phase transition phenomenon in vanadium dioxide (VO 2 ), focusing on the heterogeneous phases evolved after low-pressure plasma irradiation on VO 2 thin films, a strong electron-correlated material. The modulation in the Argon (Ar) plasma power reveals the formation of homogeneous and heterogeneous phases with variable resistive states at room temperature. High-resolution transmission electron microscopy (HRTEM) is observed with the change in interplanar spacing revealing monoclinic (M1) at 0W, monoclinic-tetragonal rutile (phase coexistence, M1-R) at 50W, and tetragonal rutile (R) at 90W. Dielectric force microscopy (DFM) shows distinct dielectric responses corresponding to different phases, characterized by potential differences of 3 mV (M1), 5 mV (M1-R), and 7.44 mV (R) phases. The coexistence of M1-R phase is stabilized and examined at room temperature, with variations in the charge carrier density observed relative to M1 and R phases individually. The phase change in VO 2 is found to be reversible, enabling stable resistive states even after the plasma is removed. The changes in plasma geometry help find and stabilize unstable phases, which can be useful in nanoelectronics., (© 2024 Wiley‐VCH GmbH.)

Background: Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows., Materials and Methods: Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9 mg/kg) or reduced (<0.9 mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6 h of acute ischemic stroke onset, while those beyond 6 h as the extended window (EW) cohort. 90 days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed., Results: A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90 days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199)., Conclusion: In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

An 8-week regimen of glecaprevir/pibrentasvir is recommended for treatment-naïve patients with chronic hepatitis C (CHC). In alignment with the Taiwanese government's objective to eliminate hepatitis C by 2025, this study aimed to provide real-world evidence on the use of this regimen in treatment-naïve patients with chronic kidney disease (CKD) by using data from the Taiwan Association for the Study of the Liver HCV Registry (TACR). CKD was defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 or higher with proteinuria persisting for over 3 months. Patients were categorized as having early CKD (eGFR ≥45 mL/min/1.73 m 2 ) or pre-end-stage renal disease (pre-ESRD) (eGFR <45 mL/min/1.73 m 2 ). Among 1072 patients who received at least one dose of the regimen, 1054 had available data for assessing sustained virologic response at 12 weeks posttreatment (SVR12). The overall SVR12 rate was 99.6%, with rates of 99.7% for pre-ESRD patients and 99.6% for early CKD patients. Subgroup analysis showed 100% efficacy for genotype 3 and dyslipidemia, 99.5% for diabetes, 99.4% for cardiovascular disease, 96.9% for a history of cerebral vascular accident, and 95.5% for patients with a history of drug injection or HIV co-infection. Adverse events were reported in 16.8% of patients, with 0.8% experiencing serious events, and only two cases were treatment-related. Renal function significantly improved, with overall eGFR increasing from 39.2 to 41.9 mL/min/1.73 m 2 . Early CKD patients showed an eGFR rise from 53.5 to 57.1, while pre-ESRD patients improved from 27.1 to 29.2 at SVR12. The study concluded that the 8-week regimen is highly effective, well-tolerated, and associated with significant renal function improvement in treatment-naïve CHC patients with both early CKD and pre-ESRD., (© 2025 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Tetrahedral, pyramidal, and octahedral metal-oxygen coordinated ligands are fundamental components in all metal-oxide structures. Understanding the impacts of their spatiotemporal behaviors during electrochemical oxidation is crucial for diverse applications, yet remains unsolved due to challenges in designing model oxides and conducting operando characterizations. Herein, combining a suite of advanced operando characterizations and systematic computations, a link between oxygen-evolving performance and operational structural properties is established on model oxides. Compared with tetrahedral and octahedral structures, pyramidal structure is more susceptible to OH - attack due to its pristine unsaturated and asymmetric features and constant single-electron occupancy on the active z 2 orbital during reaction, leading to surface-to-bulk restructuration into active amorphous high-valence CoOOH x with edge-sharing configurations. This is accompanied by ion leaching to create nanoscale space, following a leaching tendency of Sr 2+ > Ba 2+ > La 3+ > Y 3+ . Operando soft X-ray absorption spectroscopy demonstrates a harder non-uniform dehydrogenation process over time (Co 3+ OOH → Co 3+/4+ OOH x → Co 4+ OO) because of the enhanced CoO covalency with higher energy barriers. Lattice oxygen participates in active CoOOH x formation but sacrifices stability. To address this activity-stability trade-off, an ion-tuning strategy is proposed to simultaneously enhance both activity and stability in electrode and device., (© 2024 Wiley‐VCH GmbH.)

Objectives: This study aimed to compare various frailty screening and assessment tools with the Frailty Phenotype (FP), Frailty Index (FI), and Comprehensive Geriatric Assessment (CGA), which are considered the current gold standards, among the Asia-Pacific population in community settings., Design: Systematic review and meta-analysis., Setting and Participants: This review included studies evaluating frailty identification tools based on the criteria of population, index and reference tests, and diagnosis of interest., Methods: A diagnostic test accuracy review was conducted to assess frailty instruments recommended by the Asia-Pacific Clinical Practice Guidelines. Comprehensive electronic database searches and manual searches were conducted up to August 20, 2024. Study quality, including risks of bias and applicability, was assessed using the QUADAS-2 tool. Hierarchical analysis and Youden's index were employed to identify the optimal tool and cutoff points, and pooled frailty prevalence was calculated., Results: Fourteen studies were included: 10 for the FRAIL scale, 3 for TUG, and 2 for the SOF index (screening tools), and 2 each for the CFS and KCL, and 1 for the REFS (assessment tools). All studies demonstrated a high risk of bias. The pooled sensitivity and specificity for screening tools were 0.63 and 0.89, respectively, whereas for assessment tools, they were 0.79 and 0.85. The pooled prevalence of frailty and pre-frailty was 19.7% and 31.7%, respectively. The pooled diagnostic odds ratios were highest for the FRAIL scale (15.72) and CFS (35.03) among the screening and assessment tools. The subgroup analysis revealed that the setting had no significant impact on screening tool performance (p = 0.58), but a borderline significant effect was observed for assessment tools (p = 0.06), although this result is limited by the small number of studies, with only one conducted in a community setting. The FRAIL scale, with a cutoff of 2, had a Youden's index of 0.60, signifying optimal screening performance., Conclusion: Among the frailty instruments recommended by the Asia-Pacific Clinical Practice Guidelines, this meta-analysis identifies the FRAIL scale as the most robust tool for distinguishing frailty, with a cutoff of 2 significantly enhancing diagnostic accuracy. Furthermore, the estimated prevalence of frailty in the Asia-Pacific region is 19.7% across various community settings, underscoring the need for further research and the development of validated assessment tools tailored to this population., Competing Interests: Declaration of competing interest The authors declare that there have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.All authors discussed the results and contributed to the final manuscript and there is no conflicts of interest., (Copyright © 2025. Published by Elsevier Masson SAS.)

The measurement efficiency of a grid multidimensional computerized classification test (grid MCCT), which makes a classification decision per dimension, can be improved by taking the correlations between the dimensions into account in the termination criterion. The higher the correlations, the better the improvement in measurement efficiency. However, a termination criterion utilizing inter-dimensional information (i.e., SPRT-C; Liu et al., 2022) was found to yield lower levels of correct classification rates than not utilizing it (i.e., SPRT-SF; Seitz & Frey, 2013) under the between-item grid MCCT when the cutoff was set at the mean of the latent trait distribution. This study proposes a pre-rule to determine whether the SPRT-SF or SPRT-C should be used during the process of classification test administration. Through a series of simulation studies, the results showed that our proposed method (called P-SPRT) can substantially improve upon the SPRT-C in terms of correct classification rates, while maintaining its high measurement efficiency in terms of test length. This paper concludes with a discussion of the findings and further applications., Competing Interests: Declarations. Conflicts of interest: The authors declare no competing financial interests. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2025. The Author(s).)

Insular species are usually endemic and prone to long-term population reduction, low genetic diversity, and inbreeding depression, which results in difficulties in species conservation. The situation is even more challenging for the glacial relict species whose habitats are usually fragmented in the mountainous regions. Amentotaxus formosana is an endangered and endemic relict tree species in Taiwan. It is typically found scattered across different mountain regions, leading to fragmented and discontinuous populations in various habitats. Consequently, reproductive isolation may lead to deep and cryptic population structures between and within populations. To test this hypothesis and assess the most effective conservation units for the species, comprehensive genetic analyses were conducted using multiple microsatellite loci to uncover fine-scale population structures in three mountainous regions. In this study, a substantial sample of over 600 individuals, predominantly middle-aged, was collected, representing a majority of the existing individuals in the Chachayalaishan and Dawu habitats. Population genetic structure analyses were conducted using three complementary Bayesian clustering approaches (STRUCTURE, InStruct, and GENELAND) to ensure robust identification of distinct genetic clusters in three key habitats (CHA, DAWU, and DL). Results indicated low genetic diversity, distinct genetic differentiation, and severe inbreeding within fragmented populations. Additionally, demographic analysis suggested a substantial downfall in effective population sizes and limited gene flow within and between populations. Based on these findings, we recommend several management strategies to ensure the effective preservation of A. formosana : (1) establishing genetic conservation units corresponding to distinct genetic clusters in the CHA (CG-8-1 to CG-8-8), DAWU (DG-15-1 to DG-15-15), and DL (LG-6-1 to LG-6-6) populations; (2) implementing interpopulation cross-breeding programs to enhance genetic diversity; (3) promoting habitat restoration efforts to establish connectivity among fragmented populations; and (4) implementing vegetative propagation of selected trees for ex-situ conservation, along with establishing conservation nurseries and seed production areas. These localized conservation approaches, combined with the comprehensive genetic insights provided by this study, serve as crucial directives for the genetic monitoring, policy formulation, and sustainable conservation of A. formosana ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Ko, Shih, Ho, Chen, Hsu, Shiao and Chiang.)

CaCu 3 Fe 2 Re 2 O 12 and LaCu 3 Fe 2 Re 2 O 12 quadruple perovskite oxides are well known for their high ferrimagnetic Curie temperatures and half-metallic electronic structures. By A-site chemical substitution with lower valence state Na + , an isostructural compound NaCu 3 Fe 2 Re 2 O 12 with both A- and B-site ordered quadruple perovskite structures in Pn -3 symmetry was prepared using high-pressure and high-temperature techniques. The X-ray absorption study demonstrates the valence states to be Cu 2+ , Fe 3+ , and Re 5.5+ . A ferrimagnetic phase transition is found to take place at the Curie temperature T C ≈ 240 K, which is much less than that observed in A = Ca (560 K) and La (710 K) analogues. NaCu 3 Fe 2 Re 2 O 12 possesses a larger saturated magnetic moment up to 9.4 μ B /f.u. as well as a remarkably reduced coercive field less than 10 Oe at 2 K. Theoretical calculations suggest that NaCu 3 Fe 2 Re 2 O 12 displays a half-metallic electronic band structure with complete spin polarization of conduction electrons in the minority-spin bands. The magnetic properties and electronic structures of the ACu 3 Fe 2 Re 2 O 12 family are compared and discussed.

Partial oxidation of ethylene over silver catalysts produces more than 30 million metric tons of ethylene oxide (EO) annually. However, the form of active silver surfaces, reactive oxygen species, and dominant pathways of this chemical reaction remains controversial despite decades of research. Here, we use operando Raman spectroscopy and transient kinetic measurements to demonstrate that higher coverages of peroxide species, present only upon Ag oxide surfaces that form in situ , correlate with greater selectivities to EO. Ab initio calculations reveal that the reconstructed Ag oxides preferentially stabilize diatomic oxygen species (peroxide and superoxide) under relevant conditions, and these species contribute to the selective formation of EO. The dominant reaction pathways change with surface coverages; however, bound O 2 consistently activates by reaction with C 2 H 4 , and products form subsequently through peroxo- and oxometallacycle surface complexes. Taken together, density functional theory calculations and kinetic and transient experimental measurements show that the formation of peroxide intermediates requires oxidation of the Ag surface (via subsurface oxygen), and an increase in surface peroxides coincides with the highest EO selectivity for the unpromoted Ag catalyst. These findings suggest that the promoters ubiquitous for ethylene epoxidation (e.g., chlorine, transition metals, and alkali metals) may succeed by oxidation of Ag and increasing coverages of peroxides at industrial conditions., Competing Interests: The authors declare no competing financial interest., (© 2025 The Authors. Published by American Chemical Society.)

Background: Dry eye syndrome (DES) significantly affects quality of life. Meibomian Gland Dysfunction (MGD) is a primary contributor to DES and may be drug-induced., Research Design and Methods: This study analyzed data from the FDA Adverse Event Reporting System (FAERS) between January 2004 and September 2023 using the Ratio of Odds Ratios (ROR) and Proportional Reporting Ratio (PRR) to detect potential drug-induced MGD signals. Drugs were categorized by therapeutic class., Results: Among 289 MGD cases, the average patient age was 51.69 years, with 65.44% female. MGD reports have increased over time, peaking in 2023, primarily from the United States and Europe. Of 148 drugs, nine showed significant associations with MGD, including those in ophthalmology, oncology, immunomodulation, dermatology, and the urogenital system., Conclusion: This real-world study identifies drugs potentially linked to MGD, offering valuable insights for drug safety surveillance. These findings support the development of pharmacovigilance strategies and optimized clinical practice to mitigate ocular risks.

The electrical resistivity of conventional metals such as copper is known to increase in thin films as a result of electron-surface scattering, thus limiting the performance of metals in nanoscale electronics. Here, we find an unusual reduction of resistivity with decreasing film thickness in niobium phosphide (NbP) semimetal deposited at relatively low temperatures of 400°C. In films thinner than 5 nanometers, the room temperature resistivity (~34 microhm centimeters for 1.5-nanometer-thick NbP) is up to six times lower than the resistivity of our bulk NbP films, and lower than conventional metals at similar thickness (typically about 100 microhm centimeters). The NbP films are not crystalline but display local nanocrystalline, short-range order within an amorphous matrix. Our analysis suggests that the lower effective resistivity is caused by conduction through surface channels, together with high surface carrier density and sufficiently good mobility as the film thickness is reduced. These results and the fundamental insights obtained here could enable ultrathin, low-resistivity wires for nanoelectronics beyond the limitations of conventional metals.

Topological phases are robust against weak perturbations, but break down when disorder becomes sufficiently strong. However, moderate disorder can also induce topologically nontrivial phases. Thouless pumping, as a (1+1)D counterpart of the integer quantum Hall effect, is one of the simplest manifestations of topology. Here, we report experimental observations of the competition and interplay between Thouless pumping and disorder on a 41-qubit superconducting quantum processor. We improve a Floquet engineering technique to realize cycles of adiabatic pumping by simultaneously varying the on-site potentials and the hopping couplings. We demonstrate Thouless pumping in the presence of disorder and show its breakdown as the strength of disorder increases. Moreover, we observe two types of topological pumping that are induced by on-site potential disorder and hopping disorder, respectively. In particular, an intrinsic topological pump that is induced by quasi-periodic hopping disorder has never been experimentally realized before. Our highly controllable system provides a valuable quantum simulating platform for studying various aspects of topological physics in the presence of disorder., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The development of efficient platforms for the evaluation of anti-angiogenic agents is critical in advancing cancer therapeutics. In this study, we exploited an ultrabright semiconducting polymer dots (Pdots) integrating with a three-dimensional (3D) near-infrared-II (NIR-II) fluorescence imaging system designed to assess the efficacy of potent anti-angiogenic agents PX-478 and BPR0C261 in an oral squamous cell carcinoma (OSCC) tumour model, which depends on angiogenesis for dissemination. PX-478, a hypoxia-inducible factor-1α (HIF-1α) inhibitor, and BPR0C261, a microtubule-disrupting agent, were administrated into tumour-bearing mice established using murine MTCQ1 tongue cancer cells through intraperitoneal injection and oral gavage, respectively. Our findings showed that PX-478 and BPR0C261 significantly inhibited tumour growth and extended the life span of tumour-bearing mice without decreasing the body weights. The Pdots-based NIR-II vascular imaging demonstrated that the tumour vascularity was suppressed by PX-478 and BPRC0261. Accordingly, the excised tumours treated with anti-angiogenic agents showed less blood vessels than that treated with vehicles. The expression of endothelial markers CD31 was also found to be reduced in tumours treated with PX-478 and BPRC0261 using immunohistochemical (IHC) staining and Western blot analysis. Furthermore, PX-478 could suppress the expression of HIF-1α and vascular endothelial growth factor-A (VEGF-A), but BPRC0261 only suppressed VEGF-A. Taken together, this innovative 3D NIR-II imaging system combining the biocompatible Pdots with unique optical specificity enables non-invasive, real-time monitoring the efficacy of anti-angiogenic compounds., (© 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear., Methods: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded., Results: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS., Conclusion: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS., Competing Interests: Declaration of competing interest The authors declare no competing interests in this manuscript., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

An AI-assisted algorithm has been developed to improve the detection of significant coronary artery disease (CAD) in high-risk individuals who have normal electrocardiograms (ECGs). This retrospective study analyzed ECGs from patients aged ≥ 18 years who were undergoing coronary angiography to obtain a clinical diagnosis at Chang Gung Memorial Hospital in Taiwan. Utilizing 12-lead ECG datasets, the algorithm integrated features like time intervals, amplitudes, and slope between peaks, a total of 561 features, with the XGBoost model yielding the best performance. The AI-enhanced ECG algorithm demonstrated high sensitivity (0.82-0.84) when detecting CAD in patients with normal ECGs and gave remarkably high prediction rates among those with abnormal ECGs, both with and without ischemia (92 %-95 % and 80 %-83 %, respectively). Notably, the algorithm's top features, mostly related to slope and amplitude differences, are challenging for clinicians to discern manually. Additionally, the study highlights significant sex differences regarding feature prediction and ranking. Comparatively, the AI-enhanced ECG's detection capability matched that of myocardial perfusion scintigraphy, which is a costly nuclear medicine test, and offers a more accessible alternative for identifying significant CAD, especially among patients with atypical ECG readings., Competing Interests: YJC, CTM, TPS, NIY, CCL, CTC, HKS, and SFT do not have competing interests to disclose. CHY, THT, CHC, and TFT are inventors on the Taiwan patent I768624., (© 2025 The Authors.)

Background: Telehealth programs and wearable sensors that enable patients to monitor their vital signs have expanded due to the COVID-19 pandemic. The electronic National Early Warning Score (e-NEWS) system helps identify and respond to acute illness., Objective: This study aimed to implement and evaluate a comprehensive telehealth system to monitor vital signs using e-NEWS for patients receiving integrated home-based medical care (iHBMC). The goal was to improve the early detection of patient deterioration and enhance care delivery in home settings. The system was deployed to optimize remote monitoring in iHBMC and reduce emergency visits and hospitalizations., Methods: The study was conducted at a medical center and its affiliated home health agency in central Taiwan from November 1, 2022, to October 31, 2023. Patients eligible for iHBMC were enrolled, and sensor data from devices such as blood pressure monitors, thermometers, and pulse oximeters were transmitted to a cloud-based server for e-NEWS calculations at least twice per day over a 2-week period. Patients with e-NEWSs up to 4 received nursing or physician recommendations and interventions based on abnormal physiological data, with reassessment occurring after 2 hours., Unlabelled: A total of 28 participants were enrolled, with a median age of 84.5 (IQR 79.3-90.8) years, and 32% (n=9) were male. All participants had caregivers, with only 5 out of 28 (18%) able to make decisions independently. The system was implemented across one medical center and its affiliated home health agency. Of the 28 participants, 27 completed the study, while 1 exited early due to low blood pressure and shortness of breath. The median e-NEWS value was 4 (IQR 3-6), with 397 abnormal readings recorded. Of the remaining 27 participants, 8 participants had earlier home visits due to abnormal readings, 6 required hypertension medication adjustments, and 9 received advice on oxygen supplementation. Overall, 24 out of 28 (86%) participants reported being satisfied with the system., Conclusions: This study demonstrated the feasibility of implementing a telehealth system integrated with e-NEWS in iHBMC settings, potentially aiding in the early detection of clinical deterioration. Although caregivers receive training and resources for their tasks, the system may increase their workload, which could lead to higher stress levels. The small sample size, short monitoring duration, and regional focus in central Taiwan may further limit the applicability of the findings to areas with differing countries, regions, and health care infrastructures. Further research is required to confirm its impact., (©Cheng-Fu Lin, Pei‐Jung Chang, Hui-Min Chang, Ching-Tsung Chen, Pi-Shan Hsu, Chieh-Liang Wu, Shih-Yi Lin. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

A proposed contributor to Alzheimer's disease (AD) pathology is the induction of neuroinflammation due to tau and beta-amyloid protein accumulation causing neuronal injury and dysfunction. Dysregulation of lipid mediators derived from polyunsaturated fatty acids may contribute to this inflammatory response in the brain of patients with AD, yet the literature has not yet been systematically reviewed. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to April 22, 2024. Papers were included if they measured levels of lipid mediators and/or enzymes involved in their production in post-mortem brain samples from patients with AD and control without neurological disease. A total of 50 relevant studies were identified. Despite heterogeneity in the results, pro-inflammatory lipid mediators, including 5-, 11-, 12- and 15-hydroxyeicosatetraenoic acid oxylipins and prostaglandin D2, were significantly higher, while anti-inflammatory lipoxin A4 and DHA-derived docosanoids were significantly lower in brains of patients with AD compared to control (16 studies). Thirty-seven articles reported on enzymes, with 32 reporting values for enzyme level changes between AD and controls. Among the 32 articles, the majority reported on levels of cyclooxygenase (COX) (18/32), with fewer studies reporting on phospholipase (8/32), lipoxygenase (LOX) (4/32) and prostaglandin E synthase (4/32). Enzyme levels also exhibited variability in the literature, with a trend towards elevated expression of enzymes involved in the pro-inflammatory response, including COX and LOX enzymes. Overall, these results are consistent with the involvement of neuroinflammation in the pathogenesis of AD measured by lipid mediators. However, the specific contribution of each lipid metabolite and enzymes to either the progression or persistence of AD remains unclear, and more research is required., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Richard Bazinet reports financial support was provided by 10.13039/501100000024Canadian Institutes of Health Research. 10.13039/100001818RPB is supported by grant funding through the Canadian Institutes of Health Research and the 10.13039/501100000038Natural Sciences and Engineering Research Council of Canada and holds a Canada Research Chair in Brain Lipid Metabolism. RPB has received industrial grants, including those matched by the Canadian government, and/or travel support related to work on brain fatty acid uptake from Arctic Nutrition, Bunge Ltd., Capsoil Technologies, DSM, Fonterra, Mead Johnson, Natures Crops International, and Nestec Inc. Moreover, RPB is on the executive committee of the International Society for the Study of Fatty Acids and Lipids and held a meeting on behalf of fatty acids and cell signaling, both of which rely on corporate sponsorship. RPB has given expert testimony in relation to supplements and the brain. There was no role of funders in the conceptualization, design, data collection, analysis, decision to publish or preparation of the manuscript. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients. This study successfully uses the CRC PDX model to develop clinical indications for the new multi-target kinase inhibitor BPR1J481 and demonstrated the anti-cancer mechanism and competitive advantages of this drug candidate. The results demonstrate that BPR1J481 exhibits significant anticancer efficacy by inducing apoptosis in CRC PDX tumor tissues and corresponding PDX-derived CRC cells. Through kinase competitive binding and kinase activity assays, we discover that BPR1J481 effectively inhibits SRC kinase activity by directly binding to its active site. The reduction in SRC phosphorylation observed in CRC PDX tumor tissues and derived cells upon treatment with BPR1J481 further validates its inhibitory potential. Furthermore, the decrease in viable cells after SRC knockout and the poorer prognosis observed in patients with higher SRC expression, emphasizes the critical significance and clinical relevance of SRC in CRC. Additionally, BPR1J481 exhibits robust anti-angiogenic effects by suppressing VEGF- and PDGF-induced endothelial cell proliferation, migration, and capillary-like tube formation through inhibition of VEGFR2 and PDGFRβ phosphorylation. Remarkably, BPR1J481 appears to demonstrate greater efficacy against CRC compared to regorafenib. These findings highlight the therapeutic potential of BPR1J481 for patients with CRC., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Fibroblast growth factor receptor (FGFR) inhibitors have significantly improved outcomes for patients with FGFR-altered cholangiocarcinoma, leading to their regulatory approval in multiple countries. However, as with many targeted therapies, acquired resistance limits their efficacy. A comprehensive, multimodal approach is crucial to characterizing resistance patterns to FGFR inhibitors., Patients and Methods: This study integrated data from six investigative strategies: cell-free DNA, tissue biopsy, rapid autopsy, statistical genomics, in vitro and in vivo studies, and pharmacology. We characterized the diversity, clonality, frequency, and mechanisms of acquired resistance to FGFR inhibitors in patients with FGFR-altered cholangiocarcinoma. Clinical samples were analyzed longitudinally as part of routine care across 10 institutions., Results: Among 138 patients evaluated, 77 met eligibility, yielding a total of 486 clinical samples. Patients with clinical benefit exhibited a significantly higher rate of FGFR2 kinase domain mutations compared to those without clinical benefit (65% vs 10%, p<0.0001). We identified 26 distinct FGFR2 kinase domain mutations, with 63% of patients harboring multiple. While IC50 assessments indicated strong potency of pan-FGFR inhibitors against common resistance mutations, pharmacokinetic studies revealed that low clinically achievable drug concentrations may underly polyclonal resistance. Molecular brake and gatekeeper mutations predominated, with 94% of patients with FGFR2 mutations exhibiting one or both, whereas mutations at the cysteine residue targeted by covalent inhibitors were rare. Statistical genomics and functional studies demonstrated that mutation frequencies were driven by their combined effects on drug binding and kinase activity rather than intrinsic mutational processes., Conclusion: Our multimodal analysis led to a model characterizing the biology of acquired resistance, informing the rational design of next-generation FGFR inhibitors. FGFR inhibitors should be small, high-affinity, and selective for specific FGFR family members. Tinengotinib, a novel small molecule inhibitor with these characteristics, exhibited preclinical and clinical activity against key resistance mutations. This integrated approach offers a blueprint for advancing drug resistance research across cancer types., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Cryptococcosis is an opportunistic fungal infection in immunocompromised patients. The major species include Cryptococcus grubii, Cryptococcus neoformans, and rarely, Cryptococcus gattii. Here we present a disseminated Cryptococcus gattii infection in a patient with elevated granulocyte-macrophage colony-stimulating-factor autoantibody which was successfully treated with antifungal therapy., Case Presentation: A 61-year-old healthy man presented with a 3-week history of blurred vision, low-grade fever, headache, and a one-year history of low back pain following a fall on his farm. Physical examination revealed lower back tenderness and diplopia. He was tested negative for hepatitis B, C, and human immunodeficiency virus. Chest X-ray revealed a focal opacity in the right retrocardiac paraspinal region and pleural effusion. Magnetic resonance imaging showed a mass located at the L1 prevertebral region and multiple rim-enhancing lesions in bilateral cerebral hemispheres. Thoracoscopy demonstrated cystic lesions at the right costopleural angle. Pathology and microbiology studies confirmed the diagnosis of disseminated Cryptococcus gatti infection. Autoantibodies to granulocyte-macrophage colony-stimulating factor were detected and were considered to cause disseminated cryptococcosis. The patient was started on amphotericin B followed by fluconazole treatment. One month later, the symptoms ameliorated and repeated image studies after 1 year of follow-up showed the resolution of lesions., Conclusion: This report describes the first case of disseminated Cryptococcus gattii infection involving the musculoskeletal system, respiratory system, and central nervous system with granulocyte-macrophage colony-stimulating-factor autoantibody by evidence of histology and microbiology., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: The written consent for publication of identifying images and details was obtained from the patient. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Proton exchange membrane water electrolyzers powered by sustainable energy represent a cutting-edge technology for renewable hydrogen generation, while slow anodic oxygen evolution reaction (OER) kinetics still remains a formidable obstacle that necessitates basic comprehension for facilitating electrocatalysts' design. Here, we report a low-iridium complex oxide La 1.2 Sr 2.7 IrO 7.33 with a unique hexagonal structure consisting of isolated Ir(V)O 6 octahedra and true peroxide O 2 2- groups as a highly active and stable OER electrocatalyst under acidic conditions. Remarkably, La 1.2 Sr 2.7 IrO 7.33 , containing 59 wt % less iridium relative to the benchmark IrO 2 , shows about an order of magnitude higher mass activity, 6-folds higher intrinsic activity than the latter, and also surpasses the state-of-the-art Ir-based oxides ever reported. Combined electrochemical, spectroscopic, and density functional theory investigations reveal that La 1.2 Sr 2.7 IrO 7.33 follows the peroxide-ion participation mechanism under the OER condition, where the inherent peroxide ions with accessible nonbonded oxygen states are responsible for the high OER activity. This discovery offers an innovative strategy for designing advanced catalysts for various catalytic applications.

Studies in murine experimental models have made significant contributions to the understanding of asthma pathophysiology and the discovery of innovative therapeutic approaches. Nonetheless, there is a plethora of options available for selecting mouse strains, sensitization methods, challenge routes and doses, as well as approaches to evaluating host response in murine asthma model protocols. Due to the diversity of models employed, comparing results across different studies proves exceedingly challenging. The study conducted a search of pertinent PubMed articles from 2022 to April 15th, 2024. After relevant publications had been selected, the characteristics of each study were extracted, including animal strains, animal sex, sensitization methods, challenge methods, and reported outcome measures. The modeling parameters of Ovalbumin (OVA)-induced asthma model, and House Dust Mite-induced asthma model were analyzed. Additionally, we extracted data on the dose of OVA sensitization, alum administration, challenge OVA dose, and alum/sensitization OVA ratio from seven included studies. Subsequently, we conducted an analysis to determine the correlation between each of these factors and the lung resistance index (RI). This study presents an overview of the current mouse asthma models, offering valuable methodological guidance for researchers. Furthermore, this study highlights that certain parameters like sensitization dose, challenge dose, and so on, exert specific effects on the asthma lung resistance. However, there is a lack of standardized criteria and guidelines in this regard. The effects and underlying mechanisms of parameters on asthma responses remain unclear, necessitating further investigation into model parameters.

To enhance the efficiency of machine vision system, physical hardware capable of sensing and encoding is essential. However, sensing and encoding color information has been overlooked. Therefore, this work utilizes an indium-gallium-zinc oxide (IGZO) phototransistor to detect varying densities of red, green, and blue (RGB) light, converting them into corresponding drain current (I D ) states. By applying stochastic gate voltage (V G ) pulses to the IGZO phototransistor, the fluctuations are generated in these I D states. When the I D exceeds the threshold current (I TC ), a spike signal is generated. This approach enables the conversion of light densities into spike signals, achieving spike-rate encoding. Moreover, adjusting the standard deviation (σ) of the V G pulses controls the range of light densities converted into spike rates, while altering the mean (μ) of the V G pulses changes the baseline level of spike rates. Remarkably, separate RGB channels offer a tunable encoding process, which can emphasize individual colors and correct color bias. The encoded spike rates are also fed into a spiking neural network (SNN) for CIFAR-10 pattern recognition, achieving an accuracy of 86%. The method allows the operation of SNN and shows the tunability in the process of light-to-spike encoding, opening possibilities for color image processing., (© 2024 Wiley‐VCH GmbH.)

Background: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition that is known to recur and that leads to unfavorable clinical outcomes. Middle meningeal artery embolization (MMAE) has emerged as an alternative treatment to prevent recurrence. This study investigated the efficacy of combined 2 therapies in a hybrid operative suite for high-risk patients., Methods: This retrospective review provides evidence for the indications and benefits of one-stage combined therapy in a hybrid neurovascular operative suite. The procedures include burr hole craniostomy, irrigation, and drainage followed by adjuvant MMAE at the lesion site. Subsequently, routine cone beam computed tomography is conducted after the whole process., Results: Five patients with symptomatic CSDH and mass effect were enrolled in this study. Among them, 3 patients had undergone burr hole surgery previously but experienced hematoma recurrence. Two patients presented with a history of recent cardiac stent placement due to coronary artery disease, precluding the cessation of antiplatelet or anticoagulant therapy. All patients experienced symptom resolution and demonstrated no evidence of CSDH recurrence during the follow-up period., Conclusions: In our initial case experiences, one-stage burr hole surgery and adjuvant MMAE for treating chronic subdural hematoma in a hybrid operative angiography suite could be a feasible and effective treatment modality., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the safety, efficacy, and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM)., Methods: The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety, efficacy, and prognosis of this treatment approach were evaluated., Results: Of the 17 patients, 10 were male and 7 were female, with a median age of 56 (45-64) years. The stem cell engraftment rate was 100%, with a median neutrophil engraftment time of +10 (9-12) days and a median platelet engraftment time of +12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100%, with 2 cases of pulmonary infection, 1 case of urinary tract infection, 1 case of skin infection, and 11 cases of transient elevation of serum amylase. After transplantation, 13 patients achieved a complete response (CR) or better, and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17; P =0.078). The median follow-up time was 18 (6-36) months, and 15 patients survived without progression, 1 patient experienced disease progression, and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0% and 83.9%, respectively., Conclusion: High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response, further improve therapeutic efficacy, and the transplant-related complications are controllable, making it a viable option worth promoting in clinical practice.

Background: Traumatic optic neuropathy (TON) is a rare complication of facial trauma that results in vision loss. Clinical diagnosis of TON is based on a history of head trauma and an ophthalmic examination; however, the risk factors for TON and the ideal treatment strategy remain undetermined. This study aimed to identify predictive risk factors for TON and evaluate the effectiveness of current treatments with respect to visual outcomes in patients with TON., Methods: This study retrospectively enrolled patients with periorbital facial bone fracture between 2008 and 2019. Initial facial bone computed tomography, ophthalmic exam results, initial Glasgow Coma Scale, and Injury Severity Score were recorded. This study classified patients into 4 intervention groups (i.e., medication, surgery, combination therapy, and observation) to compare the outcome of visual acuity., Results: This study enrolled 1168 patients with facial bone fractures, 93 (7.96%) of whom were diagnosed as having TON. Independent risk factors for TON included optic canal fracture, medial orbital wall fracture, retrobulbar hematoma, and head Abbreviated Injury Scale ≥4. Patients with TON who initially presented with no light perception tended to have poor final visual acuity (VA) outcomes. The results indicated no significant difference in VA improvement among patients receiving observation, megadose corticosteroid therapy, surgical decompression, or combined steroid therapy and decompression., Conclusion: Clinicians can achieve early prediction of TON in patients with an initial unconscious state and the identified risk factors. The results indicated that the conservative observation yielded noninferior VA outcomes in patients with TON compared with those receiving medication or surgical treatment., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to determine the most effective non-pharmacological intervention for pain relief following chest tube removal in adult patients., Methods: We performed a systematic review with network meta-analysis, searching electronic databases for randomized controlled trials up to January 20, 2024. Compared to control or placebo groups, the trials included adult patients receiving non-pharmacological interventions, such as cold therapy, relaxation exercises, music therapy, transcutaneous electrical nerve stimulation, or aromatherapy. Data analysis utilized a random-effects model, reporting standardized mean differences (SMD) with 95% confidence intervals (CI), and treatment ranking was determined through surface under the cumulative ranking analysis and forest plots., Results: Sixteen studies enrolling 1,342 patients were included, with moderate to high heterogeneity. Cold therapy and relaxation exercises effectively reduced pain after chest tube removal, with SMD of -1.84 (95 % CI: -2.81 to -0.87) and -2.04 (95 % CI: -3.43 to -0.65), respectively, from baseline to immediately post-removal. From baseline to ten to twenty minutes after removal, both therapies continued to show significant pain reduction, with SMD of -1.96 (95 % CI: -3.14 to -0.77) for cold therapy and -2.01 (95 % CI: -3.75 to -0.28) for relaxation exercises. Sensitivity analysis supported these findings, and cold therapy's efficacy appeared unaffected by obesity. However, publication bias, possibly due to small study samples, was noted., Conclusions: Cold therapy and relaxation exercises proved most effective for reducing pain immediately and up to ten to twenty minutes after chest tube removal. Given their cost-effectiveness, lack of side effects, and ease of use, we recommend relaxation exercises as a practical alternative to cold therapy. Nonetheless, further studies are needed to comprehensively assess non-pharmacological options for managing chest tube removal pain., Implications for Clinical Practice: Incorporate cold therapy and relaxation exercises into post-chest tube removal pain management to improve patient comfort and minimize reliance on pharmacological interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nickel-based electrocatalysts are promising for industrial water electrolysis, but the dense hydroxyl oxide layer formed during the oxygen evolution reaction (OER) limits active sites accessibility and presents challenges in balancing structural stability with effective charge transfer. Based on this, an efficient in situ leaching strategy is proposed to construct grain boundary-rich catalyst structure with high charge transfer ability and a deep catalytic active layer reached >200-nm. Under OER conditions, stable sub-nano Ni 3 Al particles are embedded in Ni(Fe)OOH, originating from leaching out the unstable Ni 2 Al 3 phase of the initial Ni 2 Al 3 /Ni 3 Al alloy doped with Fe. The structural evolutions are characterized using in situ Raman spectroscopy, transmission electron microscopy, and X-ray absorption spectroscopy. The catalyst exhibits exemplary performance, evidenced by a low overpotential of 212 mV at 10 mA cm -2 , a minimal Tafel slope of 25.0 mV dec -1 . The catalyst maintains stable for >500 h at 500 mA cm -2 under industrial conditions. Furthermore, its performance in seawater electrolysis is notably superior, exhibiting an overpotential of 223 mV at 10 mA cm -2 and a Tafel slope of 37.5 mV dec -1 . The in situ high activity in the deep porous phase by leaching out unstable phases provides a new method for engineering high-performance industrial catalysts., (© 2024 Wiley‐VCH GmbH.)

Parkinson's disease (PD) is a neurodegenerative disorder and always results in balance loss. Although studies in lower-extremity exoskeleton robots are ample, applications with a lower-extremity exoskeleton robot for PD patients are still challenging. This paper aims to develop an effective assistive control for PD patients with a lower-extremity exoskeleton robot to maintain standing balance while being subjected to external disturbances. When an external force is applied to participants to force them to lose balance, the hip strategy for balance recovery based on the zero moment point (ZMP) metrics is used to generate a reference trajectory of the hip joint, and then, a model-free linear extended state observer (LESO)-based fuzzy sliding mode control (FSMC) is synthesized to regulate the human body to recover balance. Balance recovery trials for healthy individuals and PD patients with and without exoskeleton assistance were conducted to evaluate the performance of the proposed exoskeleton robot and balance recovery strategy. Our experiments demonstrated the potential effectiveness of the proposed exoskeleton robot and controller for standing balance recovery control in PD patients.

Iodine-123 metaiodobenzylguanidine (I-123 MIBG) is a crucial radiopharmaceutical widely used in nuclear medicine for its diagnostic capabilities in both cardiology and oncology. This review aims to present a comprehensive evaluation of the clinical applications of I-123 MIBG, focusing on its use in diagnosing and managing various diseases. In cardiology, I-123 MIBG has proven invaluable in assessing cardiac sympathetic innervation, particularly in patients with heart failure, where it provides prognostic information that guides treatment strategies. In oncology, I-123 MIBG is primarily utilized for imaging neuroendocrine tumors, such as neuroblastoma and pheochromocytoma, where it offers high specificity and sensitivity in the detection of adrenergic tissue. Additionally, its role in neurology, specifically in differentiating between Parkinson's disease, dementia, and Lewy body dementia, has become increasingly significant due to its ability to identify postganglionic sympathetic dysfunction. Despite its established clinical utility, the use of I-123 MIBG is not without limitations, including variability in imaging protocols and interpretation challenges. This review will explore these issues and discuss emerging alternatives, while also highlighting areas where I-123 MIBG continues to be a gold standard. By synthesizing the current research, this article aims to provide a clear understanding of the strengths, limitations, and prospects of I-123 MIBG in clinical practice.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation., Competing Interests: Declaration of interests S.-H.U., S.-H.Y., S.-Y.L., H.H.L., and C.S. have a granted patent (no. US10544113 B2) covering BPRMU191., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Blunt cerebrovascular injury (BCVI) accounts for 1-3 % of patients with blunt trauma, which should be promptly diagnosed and managed due to risk of cerebral infarction and death. Antithrombotic therapy had been proven to reduce risk of stroke and mortality. However, due to concern of hematoma progression, treatment suggestion is still inconclusive for patients with concurrent traumatic intracranial hemorrhage., Materials and Methods: We performed a retrospective, observational study from 2002 to 2020 at a Level I trauma center, all patients with BCVI and concurrent traumatic intracranial hemorrhage were recruited. Patients' demographics, initial CT findings, severity of BCVI, treatment and outcomes were documented and analyzed to define possible risk factors of death and stroke., Results: Among all 57 patients, 49 (86.0 %) patients had injury at ICA, 6 (10.5 %) had VA injury, and 2 (3.5 %) suffered from both. Targeted treatments for BCVI were provided to 33 (57.9 %) patient, mostly endovascular intervention (78.8 %), antithrombotic treatment was given to 11 (19.3 %) patients. At 3-month follow-up, 17 (29.8 %) patients expired, and 18 (31.6 %) patients had cerebral infarction due to BCVI. We identified more severe initial CT findings (p = 0.016), higher head Abbreviated Injury Scale (p = 0.049) and initial life-threatening events (p = 0.047) as risk factors of death, and traumatic basal cistern subarachnoid hemorrhage(SAH) (p = 0.040) as single risk factor of cerebral infarction., Conclusions: Around one-thirds of patients with concurrent BCVI and traumatic intracranial hemorrhage were death or suffered from cerebral infarction within 3 months, with severity of initial head injury and SAH at basal cistern as risk factors, respectively., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of opioid analgesics with reduced adverse effects is an unmet need. In a previous study, we discovered a unique combination of BPRMU191 and morphinan antagonists that produced potent antinociception with reduced adverse effects after central administration (intrathecal or intracerebroventricular). BPRMU191/naltrexone exhibits notable in vitro and in vivo pharmacological properties. However, the poor blood-brain barrier penetrative ability of BPRMU191 restricts its clinical application. In this study, we utilized a prodrug strategy to deliver sufficient brain concentrations of BPRMU191 and selected compound 2 (DBPR116) with the best physicochemical and pharmacological properties among other in vivo active prodrugs. The in vivo pharmacological studies of compound 2 /naltrexone, including thermally stimulated pain, cancer pain, constipation, sedation, psychological dependence, heart rate, and respiratory frequency measurements, demonstrated that it was a safer opioid analgesic than morphine in pain control.

Objective: This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods., Methods: FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms., Results: Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs., Conclusion: The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

Probiotics, as defined by the World Health Organization, are live microorganisms that, when consumed in sufficient quantities, provide health benefits to the host. Although some countries have approved specific probiotic species for use in food, safety concerns may still arise with individual strains. Lacticaseibacillus paracasei subsp. paracasei NTU 101 (NTU 101), isolated from the gut of healthy infants, has demonstrated various probiotic effects and shown safety in a prior 28-day animal feeding study. To further verify its safety and mitigate potential risks, we performed a comprehensive genotypic and phenotypic safety evaluation in accordance with the European Food Safety Authority guidelines for safety assessment through whole genome sequencing and related literature. In this research, minimum inhibitory concentration testing identified NTU 101's resistance to chloramphenicol; however, subsequent gene analysis confirmed no associated risk of resistance. Assessments of safety, including biogenic amine content, hemolytic activity, mucin degradation, and D-lactic acid production, indicated a low level of risk. Additionally, a repeated-dose 90-day oral toxicity study in Sprague-Dawley rats revealed no toxicity at a dose of 2000 mg/kg body weight, further supporting the strain's safety for consumption. Based on these comprehensive analyses, NTU 101 is considered safe for regular consumption as a health supplement.

The discovery of "mismatch repair deficient (MMRd)-crypt foci" in non-neoplastic intestinal mucosa in Lynch syndrome (LS) has significantly enhanced our understanding of how tumors and tumor immunity form and evolve in LS. In this study, we report the frequent presence of "mismatch repair proficient (MMRp)-crypt foci" in both non-neoplastic and neoplastic intestinal mucosa in a patient with constitutional MMR deficiency (CMMRD), who carried a germline MSH6 pathogenic variant (c.3261dupC) in trans with an MSH6 likely pathogenic variant (c.3724&#95;3726del) and whose tissues were otherwise deficient in MMR globally. The MMRp-crypts occurred at a rate of 1.1/100 crypts in non-neoplastic intestinal mucosa and were readily discernible in adenomas > 1 cm. Sequencing analysis revealed normalization of the MSH6c.3261dupC variant in MMRp-adenoma crypts, indicating reverse frameshifting of the exon 5 C8 microsatellite. Interestingly but not surprisingly, the MMRp-adenoma crypts remained microsatellite-instability-high (MSI-H), and shared oncogenic APC mutations with the background MMRd-adenoma. Contrasting with MSH6-CMMRD, no PMS2-CMMRD individuals (0/5) harbored MMRp-crypts. In conclusion, our study documents distinct MMRp-crypts in MSH6-CMMRD, a phenomenon in keeping with MSH6 being a frequent target of MSI-H due to its coding microsatellite and suggesting that MSH6-CMMRD can potentially serve as a unique model system to further our understanding of MSH6's role in MSI-H tumor formation and evolution. Our findings also bear diagnostic implications; when using MMR immunohistochemistry as an ancillary tool in detecting CMMRD, awareness of these MMRp crypts can help avoid diagnostic pitfalls., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Anionic redox chemistry can surpass theoretical limits of conventional layered oxide cathodes in energy density. A recent model system of sodium-ion batteries, O3-NaLi 1/3 Mn 2/3 O 2 , demonstrated full anionic redox capacity but is limited in reversibility and kinetics due to irreversible structural rearrangement and oxygen loss. Solutions to these issues are missing due to the challenging synthesis. Here, we harness the unique structural richness of sodium layered oxides and realize a controlled ratio of P2 structural intergrowth in this model compound with the overall composition maintained. The resulted O3 with 27 % P2 intergrowth structure delivers an excellent initial Coulombic efficiency of 87 %, comparable to the state-of-the-art Li-rich NMCs. This improvement is attributed to the effective suppression of irreversible oxygen release and structural changes, evidenced by operando Differential Electrochemical Mass Spectroscopy and X-ray Diffraction. The as-prepared intergrowth material, based on the environmentally benign Mn, exhibits a reversible capacity of 226 mAh g -1 at C/20 rate with excellent cycling stability stemming from the redox reactions of oxygen and manganese. Our work isolates the role of P2 structural intergrowth and thereby introduces a novel strategy to enhance the reversibility and kinetics of anionic redox reactions in sodium layered cathodes without compromising capacity., (© 2024 Wiley-VCH GmbH.)

A B-site ordered double perovskite oxide Cd 2 CrSbO 6 was synthesized under high-pressure and high-temperature conditions. The compound crystallizes to a monoclinic structure with a space group of P 2 1 / n . The charge configuration is confirmed to be that of Cd 2+ /Cr 3+ /Sb 5+ . The magnetic Cr 3+ ions form a tetrahedral structural frustrated lattice, while a long-range ferromagnetic phase transition is found to occur at T C = 16.5 K arising from the superexchange interaction via the Cr-O-Cd-O-Cr pathway. Electrical transport measurements indicate that Cd 2 CrSbO 6 is an insulator that can be described by the Mott 3D variable range hopping mechanism. First-principles calculations reproduce well the ferromagnetic and insulating ground state of Cd 2 CrSbO 6 with an energy band gap of 1.55 eV. The intrinsic ferromagnetic insulating nature qualifies Cd 2 CrSbO 6 as a promising candidate for possible spintronics applications.

Artificial intelligence has accelerated the application scenarios and business value of map applications. However, the sustained intention of map applications utilizing artificial intelligence technology has not received sufficient attention and scholarly investigation. Therefore, this study constructs a theoretical model of the continuance intention of map applications, based on their characteristics and combined with user satisfaction and trust, aiming to explore the influence mechanism of this continuance intention. The results of structural equation modeling show that not only user trust and satisfaction have a positive effect on continuance intention towards map applications, but also interactivity characteristics, reliability characteristics, richness characteristics, and personalized characteristics have a positive effect on user satisfaction and trust towards map applications. This study reveals the influence mechanism of map application continuance intention, which can effectively guide map application operators to optimize their services and then provide practical insights for users to use map applications consistently., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

High-order topological phases of matter refer to the systems of n-dimensional bulk with the topology of m-th order, exhibiting (n-m)-dimensional boundary modes and can be characterized by topological pumping. Here, we experimentally demonstrate two types of second-order topological pumps, forming four 0-dimensional corner localized states on a 4×4 square lattice array of 16 superconducting qubits. The initial ground state of the system at half-filling, as a product of four identical entangled 4-qubit states, is prepared using an adiabatic scheme. During the pumping procedure, we adiabatically modulate the superlattice Bose-Hubbard Hamiltonian by precisely controlling both the hopping strengths and on-site potentials. At the half pumping period, the system evolves to a corner-localized state in a quadrupole configuration. The robustness of the second-order topological pump is also investigated by introducing different on-site disorder. Our Letter studies the topological properties of high-order topological phases from the dynamical transport picture using superconducting qubits, which would inspire further research on high-order topological phases.

Anionic redox allows the direct formation of O─O bonds from lattice oxygens and provides higher catalytic in the oxygen evolution reaction (OER) than does the conventional metal ion mechanism. While previous theories have predicted and experiments have suggested the possible O─O bond, it has not yet been directly observed in the OER process. In this study, operando soft X-ray absorption spectroscopy (sXAS) at the O K-edge and the operando Raman spectra is performed on layered double CoFe hydroxides (LDHs) after intercalation with [Cr(C 2 O 4 ) 3 ] 3- , and revealed a three-step oxidation process, staring from Co 2+ to Co 3+ , further to Co 4+ (3d6L), and ultimately leading to the formation of O─O bonds and O 2 evolution above a threshold voltage (1.4 V). In contrast, a gradual oxidation of Fe is observed in CoFe LDHs. The OER activity exhibits a significant enhancement, with the overpotential decreasing from 300 to 248 mV at 10 mA cm -2 , following the intercalation of [Cr(C 2 O 4 ) 3 ] 3- into CoFe LDHs, underscoring a crucial role of anionic redox in facilitating water splitting., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Deep and extensive wounds usually cannot be closed directly by suturing or skin grafting. Flap transplantation is typically used to reconstruct large wounds clinically. The flap survival is based on a stable blood perfusion. It is established that estrogen promotes wound healing and angiogenesis, and regulates the inflammatory response, leading to enhanced flap survival after transplantation. However, estrogen concentrations administered in previous studies were significantly higher than physiological levels, potentially causing systemic side effects. Estrogen-sustained-release silastic capsules can maintain blood serum estrogen closer to physiological levels. This study aimed to investigate whether administering estrogen at a lower concentration, closer to physiological levels, could still enhance flap survival., Materials and Methods: This study was performed in a random skin flap model in ovariectomized (OVX) mice. Sustained-release estrogen silastic capsules were implanted into OVX mice to determine the functional role of estrogen in wound healing after flap transplantation. Flap blood perfusion was analysed using a colour laser Doppler scanner. Immunohistochemical staining of CD31, hypoxia-inducible factor 1 alpha (HIF-1α), alpha-smooth muscle actin (α-SMA), cleaved caspase 3 and apoptotic terminal dUTP nick end-labelling stain was used to investigate flap angiogenesis, tissue hypoxia, wound healing and cell death in the flap tissue, respectively., Results: We observed that administering estrogen at a lower concentration enhanced superficial blood perfusion while reducing the flap's ischemic area and tissue necrosis. HIF-1α expression was significantly decreased in the dermis layer but not in the fascia, whereas cleaved caspase 3 levels decreased in the fascia but remained unchanged in the dermis. Additionally, there was no significant difference in CD31and α-SMA expression between the groups., Conclusion: In summary, the study showed that an estrogen silastic capsule maintained physiological estrogen levels and improved superficial perfusion, thereby reducing dermal hypoxia, and cell death in a mouse random pattern skin flap model. Although no significant promotion of angiogenesis was observed, the study suggests that appropriate estrogen supplements could enhance flap wound recovery., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The recent past has witnessed remarkable progress in organic electronics, driven by the quest for flexible, lightweight, and cost-effective electronic devices. Semiconducting polymers (SCPs) have emerged as key materials in this field, offering unique electronic and optoelectronic properties along with mechanical flexibility. This study focuses on designing, synthesizing, and utilizing novel donor-acceptor (D-A) copolymer-based SCPs introducing a difluorothiophene moiety in the polymeric backbone. The importance of fluorine substitution for backbone planarity was verified by density functional theory calculations, comparing it with a nonfluorine substituted counterpart. Through the Unidirectional Floating Film Transfer Method (UFTM), we fabricated highly oriented thin films, resulting in increased optical anisotropy with dichroic ratios reaching 19.3 in PC20-FT thin films, one of the highest optical anisotropy observed for solution processable SCP thin films. X-ray diffraction and atomic force microscopy results validated the increase in the crystallinity and domain size with the increasing alkyl chain length. Finally, we elucidate these findings in the context of electrical applications by fabricating organic field-effect transistors revealing anisotropic charge transport achieving a promising mobility of 1.24 cm 2 V -1 s -1 and mobility anisotropy of 39.5. This study offers insights into the design principles and performance optimization of SCP-based devices, paving the way for advancements in plastic electronics.

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)