National Yang Ming Chiao Tung University

An efficient pre-strained layer structure is proposed, which combines a pre-layer with a pre-well, to prepare a 2 × 3 InGaN green micro-light-emitting-diode (μ-LED) device array with a diameter of 20 μm. The addition of the pre-layer increases the lateral lattice constant of the bottom layer of the structure. This alleviates the strain accumulation of lattice mismatch, reduces the quantum-confined Stark effect (QCSE) of the green μ-LEDs, improves the crystal quality, and produces better optoelectronic properties. Under stress modulation, the external quantum efficiency and −3 dB modulation of the green μ-LED array reach 16.6% and 411 MHz, respectively, which are 14.8 and 91.2% higher than those of the traditional structure.

Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction. Mechanistically, we show that excess BCAA-induced mitochondrial reactive oxygen species (ROS) triggered the binding of protein phosphatase 2 A catalytic subunit (PP2Ac) to AMPK, suppressing AMPK activity. This initiated a dysregulated feedback loop of AMPK-mitochondrial interactions, exacerbating mitochondrial dysfunction and oxidative neuronal damage. Our study identifies BCAA imbalance as a critical driver of neuronal damage through AMPK suppression and autophagy dysfunction, offering insights into metabolic-neuronal interactions in neurological diseases and potential therapeutic targets for BCAA-related neurological conditions.

Background Polypharmacy (i.e., treatment with ≥ 5 drugs) is common in patients with atrial fibrillation (AF) and has been associated with suboptimal management and worse outcomes. Little is known about how prescribed drug patterns affect management and prognosis in patients with AF. Methods Based on data from the prospective global GLORIA-AF Registry Phase III (recruiting patients with AF and CHA2DS2-VASc score ≥ 1), we performed a latent class analysis to identify treatment patterns based on 14 drug classes including cardiovascular (CV) and non-CV drugs. We analysed associations with oral anticoagulant (OAC) use and risk of a composite primary outcome (all-cause death and major adverse cardiovascular events (MACE)) and secondary outcomes. Results Among 21,245 patients (mean age 70.2 ± 10.3 years, 44.9% females), we identified 6 patterns: i) Low Medicated pattern (18.3%); ii) Hypertension pattern (21.1%); iii) Heart Failure pattern (20.0%); iv) CV Prevention pattern (21.0%); v) Mixed Morbidity pattern (4.5%); and vi) High Medicated pattern (15.0%). All groups had higher odds of OAC use vs the Low Medicated pattern, with highest prevalences in the Heart Failure pattern (OR [95%CI]: 2.17 [1.90–2.48]) and the High Medicated pattern (OR [95%CI]: 2.08 [1.77–2.44]). Over 3-year follow-up, Heart Failure, Mixed Morbidity and High Medicated patterns were associated with higher risk of the primary composite outcome (aHR [95%CI]: 1.32 [1.14–1.53]; 1.45 [1.17–1.80] and 1.35 [1.14–1.60], respectively). Similar results were observed for all-cause mortality. Conclusions In patients with AF, different treatment patterns can be identified. Each pattern was associated with unique OAC use and long-term clinical outcomes.

Adult human hearts exhibit limited regenerative capacity. Post-injury cardiomyocyte (CM) loss can lead to myocardial dysfunction and failure. Although neonatal mammalian hearts can regenerate, the underlying molecular mechanisms remain elusive. Herein, comparative transcriptome analyses identify adherens junction protein N-Cadherin as a crucial regulator of CM proliferation/renewal. Its expression correlates positively with mitotic genes and shows an age-dependent reduction. N-Cadherin is upregulated in the neonatal mouse heart following injury, coinciding with increased CM mitotic activities. N-Cadherin knockdown reduces, whereas overexpression increases, the proliferation activity of neonatal mouse CMs and human induced pluripotent stem cell-derived CMs. Mechanistically, N-Cadherin binds and stabilizes pro-mitotic transcription regulator β-Catenin, driving CM self-renewal. Targeted N-Cadherin deletion in CMs impedes cardiac regeneration in neonatal mice, leading to excessive scarring. N-Cadherin overexpression, by contrast, promotes regeneration in adult mouse hearts following ischemic injury. N-Cadherin targeting presents a promising avenue for promoting cardiac regeneration and restoring function in injured adult human hearts.

A base‐mediated one‐pot, two‐step, four‐component reaction has been developed to synthesize imidazole‐4(2H)‐ones, utilizing commercially available amino acid esters, aldehydes, alkynes, and amino alcohols. Control experiments and isolation of the intermediate revealed the mechanistic details. This four‐component reaction proceeds via imine formation, followed by the nucleophilic addition of alkyne to form a propargylamine precursor. Subsequently, the propargylamine precursor undergoes base‐mediated conversion into 1‐azadiene, followed by in situ ketene formation to generate (allyl‐dene‐amino)prop‐1‐en‐1‐one. The nucleophilic addition of amino alcohol and subsequent intramolecular cyclization provides imidazole‐4 (2H)‐ones exclusively.

The Hele-Shaw–Cahn–Hilliard model, coupled with phase separation, is numerically simulated to demonstrate the formation of anomalous fingering patterns in a radial displacement of a partially miscible binary-fluid system. The composition of injected fluid is set to be less viscous than the displaced fluid and within the spinodal or metastable phase-separated region, in which the second derivative of the free energy is negative or positive, respectively. Because of phase separation, concentration evolves non-monotonically between the injected and displaced fluids. The simulations reveal four areas of the concentration distribution between the fluids: the inner core; the low-concentration grooves/high-concentration ridges; the isolated fluid fragments or droplets; the mixing zone. The grooves/ridges and the fragments/droplets, which are the unique features of phase separation, form in the spinodal and metastable regions. Four typical types of patterns are categorized: core separation (CS); fingering separation (FS); separation fingering (SF); lollipop fingering, in the order of the dominance of phase separation, respectively. For the patterns of CS and FS, isolated fluid fragments or droplets around the inner core are the main features. Fingering formation is better maintained with droplets in the SF pattern if the phase separation is relatively weaker than viscous fingering (VF). Even continuous fingers are well preserved in the case of dominant VF; phase separation results in lollipop-shaped fingers. The evolving trend of the patterns is in line with the experiments. These patterns are summarized in a pattern diagram, mainly by the magnitude of the second derivative of the free energy profile.

For a connected graph G, an instance I is a set of pairs of vertices and a corresponding routing R is a set of paths specified for all vertex-pairs in I. Let $\mathfrak {R}_I$ be the collection of all routings with respect to I. The undirected optical index of G with respect to I refers to the minimum integer k to guarantee the existence of a mapping $\phi :R\rightarrow \{1,2,\ldots ,k\}$, such that $\phi (P)\ne \phi (P')$ if P and $P'$ have common edge(s), over all routings $R\in \mathfrak {R}_I$. A natural lower bound of the undirected optical index is the edge-forwarding index, which is defined to be the minimum of the maximum edge-load over all possible routings. Let w(G, I) and $\pi (G,I)$ denote the undirected optical index and edge-forwarding index with respect to I, respectively. In this paper, we derive the inequality $w(T,I_A)<\frac{3}{2}\pi (T,I_A)$ for any tree T, where $I_A:=\{\{x,y\}:\,x,y\in V(T)\}$ is the all-to-all instance.

Background Tunnel enlargement (TE) might jeopardize knee function and ligament stability after revision surgery of anterior cruciate ligament reconstruction. To date, only few studies concern TE following posterior cruciate ligament reconstruction (PCLR). This study aims to determine TE after isolated PCLR and its relationship with patient-reported outcomes. Methods Patients who received primary isolated PCLR were screened. Femoral and tibial tunnel size was measured using an anteroposterior and lateral view of radiographs at least 6 months after surgery. TE is considered significant if the width of the bone tunnel increases by 25% over the drilled size. Patient-reported outcomes were determined using the subjective International Knee Documentation Committee (IKDC) score and the Lysholm score. The association between patient baseline characteristics, patient-reported scores, and the severity of TE was investigated. Results Fifty-four patients were enrolled. TE was observed in 15 femoral tunnels and in 14 tibial tunnels. The average TE rate is 17.9% for femur and 7.9% for tibia. No correlation between the level of TE and patient-reported outcomes is noted. However, when patients are classified into TE and non-TE group on the basis of 25% of enlargement, those who exhibit femoral TE have a lower postoperative Lysholm score (81.1 ± 13.0 vs. 90.5 ± 12.3, P = 0.031) and those with tibial TE have a lower postoperative IKDC score (76.0 ± 17.4 vs. 87.1 ± 12.1, P = 0.031). Conclusions The overall incidence of femoral and tibial TE after isolated PCLR is low. However, femoral and tibial TE are correlated with worse patient-reported outcomes in terms of the lower postoperative Lysholm and IKDC scores.

Silicon nanowires (Si NWs) have attracted considerable interest owing to their distinctive properties, which render them promising candidates for a wide range of advanced applications in electronics, photonics, energy storage, and sensing. However, challenges in achieving large‐scale production, high uniformity, and shape control limit their practical use. This study presents a novel fabrication approach combining nanoimprint lithography, nanotransfer printing, and metal‐assisted chemical etching to produce highly uniform and shape‐controlled Si NW arrays. By optimizing the process parameters, Si NWs with various diameters (100, 200, and 400 nm) are successfully fabricated on 6‐inch wafers, achieving high uniformity confirmed through statistical and surface reflection analyses. Furthermore, a conformal coating of titanium nitride on the uniform Si NWs enables broadband absorption with average absorption of 75% in the wavelength range from 250 to 2500 nm, demonstrating their potential for next‐generation optoelectronic devices. These findings provide valuable insights for the scalable production of Si NWs and their integration into high‐performance electronic systems.

Aims/Purpose: To evaluate the efficacy and safety of intravitreal lenadogene nolparvovec gene therapy (LNGT) in patients with Leber hereditary optic neuropathy due to the m.11778G > A MT‐ND4 mutation for up to 5 years after administration. Methods: REFLECT is a randomized, double‐masked, placebo‐controlled phase 3 study. The first‐affected eye received LNGT; the other eye was randomly injected with LNGT or placebo. RESTORE is the 5‐year follow‐up study of the two phase 3 studies RESCUE and REVERSE, in which patients received an injection of LNGT in one eye and a sham injection in the other eye. REFLECT interim data at 4 years after LNGT and RESTORE final data at 5 years are presented. Results: In REFLECT, 48 patients were treated bilaterally and 50 unilaterally. The mean (standard deviation [SD ]) improvement in best‐corrected visual acuity (BCVA) from nadir to 4 years was ‐0.40 (0.32) (+20 ETDRS letters) and ‐0.34 (0.31) (+17 letters) LogMAR in the first and second‐affected eyes of bilaterally treated patients, and ‐0.38 (0.41) (+19 letters) and ‐0.27 (0.32) (+14 letters) LogMAR in the first and second‐affected eyes of unilaterally treated patients. Better BCVA improvement and higher responder rates were observed in patients treated bilaterally. In RESTORE, 62 unilaterally treated patients completed the study. At 5 years, mean (SD) change in BCVA from nadir was ‐0.44 (0.46) LogMAR (+22 ETDRS letters) for LNGT‐treated eyes and ‐0.39 (0.36) LogMAR (+20 ETDRS letters) for sham‐treated eyes. Overall, LNGT safety was favorable in REFLECT and RESTORE. Conclusions: The persistence of the LNGT effect and the favorable safety profile were confirmed 4 years after a unilateral or bilateral injection in REFLECT and 5 years after a unilateral injection in RESTORE. Bilateral LNGT provided additional benefit compared to unilateral LNGT.

Aims/Purpose: To evaluate the efficacy and safety of intravitreal lenadogene nolparvovec gene therapy (LNGT) in patients with Leber hereditary optic neuropathy due to the m.11778G > A MT‐ND4 mutation for up to 5 years after administration. Methods: REFLECT is a randomized, double‐masked, placebo‐controlled phase 3 study. The first‐affected eye received LNGT; the other eye was randomly injected with LNGT or placebo. RESTORE is the 5‐year follow‐up study of the two phase 3 studies RESCUE and REVERSE, in which patients received an injection of LNGT in one eye and a sham injection in the other eye. REFLECT interim data at 4 years after LNGT and RESTORE final data at 5 years are presented. Results: In REFLECT, 48 patients were treated bilaterally and 50 unilaterally. The mean (standard deviation [SD ]) improvement in best‐corrected visual acuity (BCVA) from nadir to 4 years was ‐0.40 (0.32) (+20 ETDRS letters) and ‐0.34 (0.31) (+17 letters) LogMAR in the first and second‐affected eyes of bilaterally treated patients, and ‐0.38 (0.41) (+19 letters) and ‐0.27 (0.32) (+14 letters) LogMAR in the first and second‐affected eyes of unilaterally treated patients. Better BCVA improvement and higher responder rates were observed in patients treated bilaterally. In RESTORE, 62 unilaterally treated patients completed the study. At 5 years, mean (SD) change in BCVA from nadir was ‐0.44 (0.46) LogMAR (+22 ETDRS letters) for LNGT‐treated eyes and ‐0.39 (0.36) LogMAR (+20 ETDRS letters) for sham‐treated eyes. Overall, LNGT safety was favorable in REFLECT and RESTORE. Conclusions: The persistence of the LNGT effect and the favorable safety profile were confirmed 4 years after a unilateral or bilateral injection in REFLECT and 5 years after a unilateral injection in RESTORE. Bilateral LNGT provided additional benefit compared to unilateral LNGT.

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 m² or higher with proteinuria persisting for over 3 months. Patients were categorized as having early CKD (eGFR ≥45 mL/min/1.73 m²) or pre‐end‐stage renal disease (pre‐ESRD) (eGFR <45 mL/min/1.73 m²). 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 m². 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.

Objectives To assess hotspot micro‐vessel flow velocity waveforms in human papillomavirus (HPV) cervical infections using transvaginal power Doppler ultrasound (TV‐PDU) and explore associations with high‐grade squamous intraepithelial lesions (HSIL, cervical intraepithelial neoplasia [CIN] II and III). Methods In all, 62 patients with confirmed HPV‐HSIL (14 CIN II, 48 CIN III) and 65 age‐ and parity‐matched women with neither HPV infection nor CIN were compared. Seven parameters by TV‐PDU were used to assess vascular classification and micro‐vessel flow velocity, including vascular grading (class I, II, III), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end‐diastolic velocity (ED), time average maximum velocity (TAMV), and the vascular index (VI = PS/ED). Results HSIL was primarily associated with vascular class I (75.8%), followed by class II (14.5%) and class III (9.7%). PI, RI, and VI in HSIL were significantly lower than the control group (P < 0.0001). Mean PI, RI, and VI values decreased progressively from the normal cervix to CIN II–III. At a PI cutoff of 1.03, sensitivity was 88.7%, specificity was 83.8%, and area under the curve (AUC) was 95.0. At an RI cutoff of 0.68, sensitivity was 96.8%, specificity 61.5%, and AUC 84.0. At a VI cutoff of 2.84, sensitivity was 85.5%, specificity 78.5%, and AUC 85.0. Conclusion Based on different patterns of hotspot vascular classification and micro‐vessel flow velocity waveforms, particularly PI between HSIL and the normal cervix, TV‐PDU may offer a potential role for aiding the planning for patients with suspicious HSIL. Further studies are needed to validate the findings.

Background REMIT is the first real-world study of mepolizumab effectiveness in patients with severe asthma (SA) in Taiwan. Objectives The primary objective evaluated changes in clinically significant exacerbations (CSEs; defined as use of oral corticosteroids (OCS) or emergency department (ED) visits and/or hospitalizations) in the 12 months pre- and post-mepolizumab treatment. Secondary objectives assessed changes in the number of CSEs requiring ED visits/hospitalizations and daily maintenance OCS (mOCS) dosage 12 months pre- and post-mepolizumab treatment. Three- and four-component clinical remissions were analyzed based on OCS-free, exacerbation-free, and asthma control (± stability in lung function). Design REMIT was a retrospective, observational, self-controlled study analyzing patients in Taiwan with SA who were newly prescribed subcutaneous mepolizumab 100 mg Q4W. Methods Data were extracted from records of 15 medical centers in Taiwan for patients indexed between November 1, 2018 and October 31, 2020. Results A total of 170 patients were included: mean age at index date, 58.7 years; 53.5% female; 100% Chinese; 7.1% with chronic rhinosinusitis with nasal polyps, 1.8% with eosinophilic granulomatosis with polyangiitis, 1.2% with hypereosinophilic syndrome; and 55.7% with blood eosinophil count >300/µL. Pre-treatment, 71.2% had ⩾2 exacerbations, and 28.7% were on mOCS; 75.3% had no prior biologic treatment, and 24.7% had switched from other biologics. Most patients (80.0%) completed ⩾10 mepolizumab doses. Following the first mepolizumab administration (index date), CSEs reduced by 46.0% (rate ratio (RR): 0.545, 95% confidence interval (CI): 0.418–0.710; p < 0.0001) in the 12 months post-index. Exacerbations requiring ED visits/hospitalization reduced by 46.9% (RR: 0.531, 95% CI: 0.349–0.808; p = 0.0031). Median mOCS dose reduced by 100% by end of study and 81.8% of patients discontinued mOCS post-treatment. After 1 year of mepolizumab treatment, 28% and 23% patients achieved three- and four-component clinical remission, respectively. Conclusion Mepolizumab use in a patient population in Taiwan with SA significantly reduced CSEs and mOCS use in routine clinical practice.

Background The standard treatment for periprosthetic joint infections (PJI) typically involves a two-stage resection arthroplasty using antibiotic-loaded bone cement (ALBC) spacers. This study hypothesizes that there is no significant correlation between antibiotic levels in blood and synovial fluid and the patient’s kidney function, and that the success rates of staged resection arthroplasty are comparable between groups, specifically targeting gram-positive bacterial infections. Methods This retrospective review included patients treated from 2017 to 2022 with two-stage arthroplasty using vancomycin-loaded ALBC spacers, selectively targeting gram-positive infections. Patients with non-gram-positive infections or those with allergies or treatments affecting serum antibiotic levels were excluded. The study assessed comorbidities, renal function, specifics of the spacers, and vancomycin concentrations in joint fluid and blood. Results Among 62 PJI cases analyzed (22 hips and 40 knees), 34 patients (54.8%) had renal insufficiency (RI), associated with significantly lower albumin (2.64 g/dL vs. 3.43 g/dL, p < 0.05) and estimated glomerular filtration rate (eGFR) (58.17 mL/min/1.73 m² vs. 121.74 mL/min/1.73 m², p < 0.05). No significant differences were found in comorbidities, antibiotic regimen, or the weight of the ALBC spacers between the groups (p > 0.05). Both groups exhibited high vancomycin levels in joint fluid, with peak blood vancomycin levels inversely correlated with eGFR (coefficient − 3.612, 95% CI -8.543 to -2.753, p < 0.001). RI patients displayed higher peak blood vancomycin levels (1.23–5.43 mg/L) but remained below toxicity thresholds. The infection-free interval, aseptic revision rates, and bacterial profiles specific to gram-positive species showed no significant differences between the groups. Conclusion Systemic absorption of vancomycin from ALBC spacers was evident in patients with RI and inversely correlated with eGFR, yet remained well below toxic thresholds across all patients. These findings suggest that the use of vancomycin-loaded ALBC spacers appears to be safe for managing gram-positive infections in patients with varying renal function. Additionally, renal insufficiency did not adversely affect the infection-free interval, aseptic revision rates, or bacterial diversity. Level of evidence III.