National Yang Ming Chiao Tung University

Neural signal degradation poses a significant challenge in maintaining stable performance when decoding motor tasks using multiunit activity (MUA) and local field potential (LFP) signals in the implantable brain machine interface (iBMI) applications. Effective methods for imputing degraded or missing signals are essential to restore neural signal integrity, thereby improving decoding accuracy and system robustness over long-term recordings with fluctuating signal quality. This study introduces a confidence-weighted Bayesian linear regression (CW-BLR) approach to impute neural signals affected by degradation, enhancing the robustness and consistency of decoding. The performance of CW-BLR was compared to traditional methods—mean imputation (Mean-imp) and Gaussian-mixture-model-based expectation–maximization (GMM-EM)—using a kernel-sliced inverse regression (kSIR) decoder to evaluate decoding outcomes. Four Wistar rats were trained to perform a forelimb-reaching task while neural activity (MUA and LFPs) was recorded over 27 days. CW-BLR imputed signals degraded during days 8–27. Decoding performance was evaluated using kSIR and compared with Mean-imp and GMM-EM. CW-BLR demonstrated superior performance by effectively preserving both temporal and spatial dependencies within the neural signals. CW-BLR-imputed data significantly improved decoding accuracy over traditional imputation methods, with the kSIR decoder showing consistently higher performance, particularly in maintaining signal quality from the degraded period. CW-BLR offers a robust and effective imputation framework for iBMI applications, addressing signal degradation challenges and maintaining accurate decoding over prolonged recordings. By utilizing confidence-based quality metrics, CW-BLR surpasses traditional methods, providing stable neural decoding across fluctuating signal quality scenarios.

We employed a highly accurate transfer printing technique based on mechanically guided alignment to achieve side-coupled hybrid integration structures between different types of photonic crystal (PhC) nanobeam (NB) resonators and silicon waveguides. Both the nanocavity and band-edge resonators theoretically exhibit unidirectional in-plane optical leakages due to an asymmetric PhC lattice design, with nearly 90% theoretical unidirectional coupling efficiency when integrated with silicon waveguides in the side-coupling structure using additional tapered beams. In our measurements, we confirmed significant planar radiation resulting from the unidirectional coupling between both types of NB lasers and silicon waveguides. Furthermore, we investigated the wavelength-dependent coupling characteristics of NB cavity lasers with varying parameters within this integrated framework, as well as their planar lasing emission over long propagation distances when integrated with a U-bend waveguide. These experimental results demonstrate the applicability and feasibility of this side-coupling architecture for integrating nanoscale light sources into silicon-based integrated photonic circuits.

Background The diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is challenging due to its varied clinical manifestations and imaging findings. While it typically presents with a sudden, severe thunderclap headache and multifocal constriction of the cerebral arteries, the wide spectrum of radiological presentations may complicate the diagnosis. Main Body This review presents a series of cases that show both typical and atypical presentations of RCVS. Typical cases show the characteristic “string of beads” pattern on angiography, which usually resolves within 3–6 months. However, diagnostic challenges arise when angiography appears normal in the early stages or when imaging artifacts obscure the findings. In addition, the variability in vasoconstriction patterns and the need for a differential diagnosis further complicate the accurate identification. These cases highlight the importance of considering RCVS in patients with recurrent thunderclap headaches, even when the initial imaging is inconclusive. Recognizing these challenges and the variability in presentation, along with the use of high-resolution vessel wall MRI and blood-brain barrier imaging, can improve diagnostic accuracy and improve patient outcomes. Conclusion The diagnosis of RCVS requires careful integration of clinical evaluation and advanced imaging techniques, with particular attention to radiological findings that can guide accurate diagnosis and management. Despite challenges, such as normal early stage angiography and imaging variability, maintaining a high suspicion of RCVS is essential, especially in patients with recurrent thunderclap headaches.

Loss-of-function mutations in the human KCND3 gene encoding KV4.3 K⁺ channels are linked to the autosomal dominant neurodegenerative disease spinocerebellar ataxia type 19/22 (SCA19/22). Previous biophysical and biochemical analyses in vitro support the notion that the autosomal dominant inheritance pattern of SCA19/22 is associated with the dominant-negative effects of disease-causing KV4.3 mutants on proteostasis of their wild-type (WT) counterpart. Herein we aimed to explore whether the disease-causing mutants might perturb protein expression of endogenous KV4.3 channel in human cells, as well as contributing to in vivo pathomechanisms underlying motor impairments and neurodegeneration in an animal model of SCA19/22. Substantial reduction in human KV4.3 protein level was validated in skin fibroblasts derived from heterozygous SCA19/22 patients. Genetic knockdown of endogenous Shal, the fly ortholog of human KV4.3, in Drosophila led to locomotor impairment, ommatidia degeneration, and reduced brain cortex thickness, all of which was effectively ameliorated by transgenic expression of human KV4.3, but not KV1.1 K⁺ channel. Transgenic expression of SCA19/22-causing human KV4.3 mutants resulted in notable disruption of endogenous Shal proteostasis, locomotor function, and ommatidia morphology in Drosophila. Enhanced expression of the Drosophila molecular chaperones HSC70 and HSP83 in our fly model of SCA19/22 corrected Shal protein deficit, locomotor dysfunction, and neurodegeneration. Overexpression of Hsp90β also upregulated endogenous human KV4.3 protein level in patient-derived skin fibroblasts. Our findings highlight Drosophila as a suitable animal model for studying KV4.3 channelopathy in vivo, and accentuate a critical role of defective KV4.3 proteostasis in the pathogenesis of motor dysfunction and neurodegeneration in SCA19/22.

Despite the appeal of flawless order, semiconductor technology has demonstrated that implanting inhomogeneities into single-crystalline materials is pivotal for modern electronics. However, the influence of the local arrangement of chemical inhomogeneities on the material’s functionalities is underexplored. In this work, we control the distribution of chemical inhomogeneities in La³⁺-substituted ferroelectric BiFeO3 thin films. By means of a stress- and composition-driven phase transition, we trigger the formation of a lattice of La³⁺-rich and La³⁺-poor layers. This ordering correlates with the emergence of an antipolar phase. An electric field restores the original ferroelectric phase and re-randomizes the distribution of the La³⁺ inhomogeneities. Leveraging these insights, we tune the polar/antipolar phase coexistence to set the net polarization of La0.15Bi0.85FeO3 to any desired value between its saturation limits. Finally, we control the net polarization response in device-compliant capacitor heterostructures to show that inhomogeneity-distribution control is a valuable tool in the design of functional oxide electronics.

Background While problematic smartphone use screening tools are widely used and increasingly evaluated in student populations, their applicability and clinical stability across diverse groups—particularly those with comorbid substance use—remain unclear. Moreover, the overlap between problematic smartphone use and internet gaming disorder has not been well established in clinical contexts. This study explores the behavioral and psychological characteristics associated with problematic smartphone use, focusing on its relationship with online gaming behaviors among ketamine users referred for court-ordered addiction treatment. Methods The study involved 233 participants diagnosed with ketamine use disorder. Participants reported their daily smartphone use and primary usage purposes. Ketamine dependence was assessed using the Chinese version of the Severity of Dependence Scale. Emotional distress was evaluated using the Brief Symptom Rating Scale and Generalized Anxiety Disorder 7-Item Scale. Attention-deficit/hyperactivity disorder (ADHD) symptoms were assessed using the Adult ADHD Self-Report Scale (ASRS-V1.1). Problematic smartphone use risk was evaluated using the Short Form of the Problematic smartphone use Inventory (SPAI-SF). Logistic regression was used to analyze factors related to problematic smartphone use risk. Results The problematic smartphone use risk group reported significantly longer daily smartphone usage (odds ratio [OR]: 1.64; 95% confidence interval [CI]: 1.29–2.08), higher ASRS-V1.1 scores (OR: 1.14; 95% CI: 1.05–1.23), and a greater likelihood of using smartphones for online gaming (OR: 2.26; 95% CI: 1.19–4.29). Conclusions Excessive smartphone use in ketamine users is closely linked to online gaming, and ADHD symptoms may increase the risk of problematic smartphone use in this population.

Background and Purpose Neuronal inhibition is largely mediated by type‐A GABA receptors (GABAARs), a family of ligand‐gated chloride‐permeable channels, which can be sub‐classified by their subunit composition. Unravelling the function and distribution of each GABAAR subtype is essential for a holistic understanding of GABAergic inhibition in health and diseases. Photopharmacology, a technique that utilises light‐sensitive compounds to precisely manipulate endogenous proteins, is powerful for this purpose. To resolve the molecular complexity of neuronal inhibition, we aimed to develop subtype‐selective photoswitchable agonists for GABAARs. Experimental Approach Inspired by THIP (gaboxadol), an agonist selective for δ subunit‐containing GABAARs (δ‐GABAARs), we merged a photoswitch moiety (azobenzene) with an analogue of THIP (isoguvacine) to construct Az‐IGU. Using whole‐cell voltage‐clamp recording, Az‐IGU was tested on 13 GABAAR subtypes expressed in human embryonic kidney (HEK) cells. Optical activation of endogenous GABAARs was examined via electrophysiology in cultured cortical neurons. Key Results In HEK cells, Az‐IGU exerted reversible photo‐agonism selectively for α4β3δ and α6β3δ GABAARs, two major mediators of tonic inhibition. Pharmacological and mutagenesis studies suggested that activation of the α4β3δ GABAAR involves interaction between Az‐IGU and the GABA‐binding pocket and is strongly correlated with the spontaneous activity of the receptor. In cultured cortical neurons, photoisomerisation of Az‐IGU triggered responses that enabled reversible control of action potential firing. Conclusions and Implications GABAARs are potential therapeutic targets for many disorders. However, their physiological and pathophysiological roles remain largely unexplored. Az‐IGU may enable photopharmacological studies of α4/6β3δ GABAARs, providing new opportunities for biomedical and neurobiological applications.

Aims Clinical trials have shown an increased risk of death in patients with recent myocardial infarction who received antiarrhythmic drugs such as flecainide, encainide or moricizine, especially in the presence of associated structural heart disease such as cardiac dysfunction. This study aimed to evaluate the safety outcomes of propafenone use in atrial fibrillation patients with heart failure when compared to those of amiodarone use. Methods This population‐based cohort study used the National Health Insurance Research Database in Taiwan. Eligible patients were those who had atrial fibrillation or atrial flutter diagnosis, had heart failure diagnosis, and first received propafenone or amiodarone between 2002 and 2018. The primary endpoints were death due to arrhythmia and the composite proarrhythmic outcome, which consisted of sudden cardiac arrest, arrhythmic death, ventricular arrhythmia and implantation of defibrillator. Results After propensity score matching, the study cohort consisted of 7235 propafenone and 14 470 amiodarone users. Compared to amiodarone, propafenone was associated with significantly lower risk of the composite proarrhythmic outcome (adjusted hazard ratio: 0.52; 95% confidence interval: 0.42–0.64; P < .001). Propafenone users also had lower risk of death owing to arrhythmia compared to amiodarone users (adjusted hazard ratio: 0.22; 95% confidence interval: 0.08–0.65; P = .006). Subgroup analysis and sensitivity analysis showed similar trends, favouring propafenone. Conclusion Propafenone was not significantly associated with increased risk of proarrhythmia and mortality when compared to amiodarone in atrial fibrillation patients with heart failure in contemporary real‐world settings. Prospective studies are needed to determine whether propafenone should definitely be avoided in these patients.

Small cell lung cancer (SCLC) is associated with high mortality and limited therapeutic options. There is increasing recognition that SCLC harbors molecular heterogeneity. Using a new liquid biopsy assay, it is demonstrated that SCLC subtypes, as determined by patient tumor tissue staining and cell lines, can be accurately identified by measuring the mRNA expression of subtype transcription factors (ASCL1, POU2F3, and NEUROD1) in circulating exosome‐rich extracellular vesicles (Exo). Additionally, upregulation of Delta‐like ligand 3 (DLL3) mRNA in Exo and its membrane protein (mProtein) in extracellular vesicles associated with tumor (tEV) may distinguish both limited‐ and extensive‐stage SCLC patients from high‐risk smokers, with AUC/ROC values of 0.836 and 0.839, respectively. By incorporating Exo‐ASCL1 and Exo‐POU2F3 mRNA expression with DLL3 Exo‐mRNA/tEV‐mProtein expression, the classifier enhances the AUC/ROC to 0.912 and 0.963 for limited‐ and extensive‐stage SCLC patients, respectively.

This study employs a chemically controlled strategy to construct a few‐atomic‐layer ZnO structure integrated with polyvinylpyrrolidone (PVP) and nanoscale metallic copper on active carbon. Hydrogen‐bond interactions from PVP's N‐vinylpyrrolidone allow ZnO to retain a specific proportion of metal atoms, confining electrons at the Cu/ZnO interface to form CuZn nanoalloy clusters. The nanoalloy's dual role in promoting CO adsorption and C─C coupling synergistically boosts C2H4 production during electrochemical CO2 reduction (ECR). Rapid Cu regeneration further increases adsorbed hydrogen (Hads) from water splitting, achieving a remarkable C2H4 selectivity of ≈50.2% with stable performance over 10 h. The Zn→Cu electron confinement and interfacial synergy at the organic‐oxide‐metal heterojunction underscore the catalyst's superior efficiency, offering a promising pathway for sustainable CO2‐to‐C2H4 conversion.

While environmental and lifestyle factors contribute to urothelial carcinoma (UC) development, their differential effects on bladder cancer (UB) versus upper tract urothelial carcinoma (UTUC) and the underlying epigenetic mechanisms remain unclear. This study investigated location-specific risk factors and the mediating role of LINE-1 DNA methylation in UC carcinogenesis. A hospital-based case–control study was conducted, comprising 478 UC cases (266 UB, 204 UTUC) and 569 controls. The risk factors, including smoking, Chinese herbal medicine use, comorbidities, and blood levels of arsenic, cadmium, and lead, were assessed through questionnaires and blood sample analysis. LINE-1 DNA methylation levels were measured by pyrosequencing. LASSO regression for variable selection and logistic regression for risk assessment. Mediation analysis was performed to evaluate the role of LINE-1 DNA methylation in the relationship between environmental exposures and UC risk. UB risk was associated with male sex, smoking, chronic kidney disease (CKD), elevated blood arsenic, and diabetes (all p < 0.0001), while UTUC risk was primarily linked to female sex (p = 0.0004) and CKD (p < 0.0001). LINE-1 hypermethylation was associated with both UB and UTUC risk (p < 0.0001). Notably, LINE-1 methylation significantly mediated the relationship between smoking and UC risk, particularly in males, while no significant mediation was observed for other exposures. This study demonstrates distinct risk profiles for UB and UTUC, and identifies LINE-1 methylation as a key mediator in smoking-related UC risk, especially in men. These findings suggest the need for location-specific prevention strategies and highlight the importance of epigenetic mechanisms in UC development.

Silicon photonic physical unclonable function (PUF) stands out as a promising hardware security primitive, offering the advantages of CMOS compatibility and a compact chip-scale footprint compared to other optical PUFs. It harnesses inherent fabrication variations arising during mass production to generate unique digital keys. In this paper, we experimentally demonstrate a silicon photonic PUF using an 8-channel waveguide array with embedded phase shifters, enabling the active generation of challenge-response pairs. Through testing six device copies fabricated on the same wafer, we achieve a false acceptance rate of 4.06 × 10⁻²¹. Both challenge generation and response detection can be performed on-chip, leading to a stand-alone PUF on the silicon photonic platform.

Background Proximal upper limb tremor is a common, functionally disabling condition. Medical therapy is often ineffective. IncobotulinumtoxinA can significantly improve tremor with minimal adverse effects. Objectives We aimed to compare clinical, functional, and quality of life measures in patients with proximal upper limb tremor following incobotulinumtoxinA treatment. Methods We undertook a double‐blind, randomized two‐sequence, two‐period, two‐treatment, placebo‐controlled cross‐over trial. Twenty adult patients with proximal upper limb tremor were recruited from a tertiary movement disorders clinic. Patients were randomized 1:1 to alternate electromyographically guided intramuscular injections of either incobotulinumtoxinA or saline to the dominant upper limb using computer‐generated randomization. Patients were injected at baseline, then 4 months after cross‐over. Primary outcome was change in Goal Attainment Rating Scale (GARS) at two‐months post intervention. Secondary outcomes were dominant upper limb The Essential Tremor Rating Assessment Scale (TETRAS), Fahn‐Tolosa‐Marin tremor rating scale (FTM‐TRS) and three patient‐related outcome measures. Outcomes were assessed at baseline and monthly intervals for 3‐months post each intervention. Results There was no significant improvement in the GARS at 2‐months post injection ( OR 1.83, 95% CI 0.14–24.32). Secondary outcomes showed a mean reduction in TETRAS score of −1.05 (95% CI −1.99 to −0.13) and FTM ‐ TRS of −6.84 (95% CI −12.37 to −1.31) in those receiving incobotulinumtoxinA . There was no significant change in patient‐rated outcome scores. Conclusion Single dose incobotulinumtoxinA injections are effective in reducing objective measures of proximal upper limb tremor and function. This did not translate into improved patient‐rated outcomes in this single therapeutic dose study.

Photocatalytic CO2 conversion with H2O to carbonaceous fuels is a desirable strategy for CO2 management and solar utilization, yet its efficiency remains suboptimal. Herein, efficient and durable CO2 photoreduction is realized over a RuNPs/Ru‐PHI catalyst assembled by anchoring Ru single atoms (SAs) and nanoparticles (NPs) onto poly(heptazine imide) (PHI) via the in‐plane Ru‐N4 coordination and interfacial Ru‐N bonds, respectively. This catalyst shows an unsurpassed CO production (32.8 μmol h‐1), a record‐high apparent quantum efficiency (0.26%) beyond 800 nm, and the formation of the valuable H2O2. Ru SAs tune PHI’s electronic structure to promote in‐plane charge transfer to Ru NPs, forming a built‐in electron field at the interface, which directs electron‐hole separation and rushes excited electron movement from Ru‐PHI to Ru NPs. Simultaneously, Ru SAs introduce an impurity level in PHI to endow long‐wavelength photoabsorption, while Ru NPs strengthen CO2 adsorption/activation and expedite CO desorption. These effects of Ru species together effectively ensure CO2‐to‐CO conversion. The CO2 reduction on the catalyst is revealed to follow the pathway CO2→ *CO2→ *COOH→ *CO→ CO, based on the intermediates identified by in situ diffuse reflectance infrared Fourier transform spectroscopy and further supported by density functional theory calculations.

Li4Ti5O12 (LTO) is a highly promising anode material for both Li‐ion and Na‐ion batteries due to its remarkable structural stability, minimal volumetric expansion, and high safety. Despite extensive research on LTO performance in conventional systems, little attention has been given to its behavior in mismatched electrolyte environments. This study explores the electrochemical behavior of LTO anodes in Na⁺‐containing electrolytes for Li⁺/Na⁺ intercalation, providing new insights into ion intercalation mechanisms and enhancing battery performance. Using different counter electrode and electrolyte configurations, it is revealed that LTO exhibits superior capacity and cycle stability in a mismatched Li/Na⁺ environment compared to the standard Li/Li⁺ system, delivering capacities of up to 219 mAh g⁻¹. Electrochemical and structural analyses indicate that enhanced performance stems from the unique interaction between Li⁺/Na⁺ and LTO structure, leading to improved charge–discharge performance. Additionally, the Na/Li⁺ configuration displays unique behavior, where a distinct plateau splitting emerges after the first cycle, indicating complex ion interactions that ultimately affect cycling stability. These findings not only highlight the potential of LTO anodes in mismatched electrolyte systems but also offer a pathway toward more cost‐effective and sustainable energy storage solutions by leveraging sodium–ion electrolytes in place of traditional lithium‐based systems.