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Background: The clinical value of therapeutic drug monitoring (TDM) for newer anti-seizure medications (ASMs) remains uncertain. This study aimed to assess the impact of newer ASM TDM on clinical decision making in patients with epilepsy. Methods: We retrospectively identified all plasma requests for newer ASM level measurement as part of routine clinical management in the outpatient departments of seven medical institutes across Taiwan between September 2016 and May 2019. Data collected from reviewed medical records included clinical and medication details, indications for TDM requests, test results, interpretation, and impact on patient management. Results: A total of 682 visits with 1051 plasma samples were included. The most frequently analyzed ASMs were levetiracetam (36.1%), oxcarbazepine (18.4%), and lamotrigine (12.0%). Reasons for TDM included poorly controlled seizures (55.3%), concerns about drug-drug interactions (12.3%), and suspicion of drug overdose (10.6%). 68.8% of samples were within the orienting therapeutic range, even for patients with poorly controlled seizures. TDM for non-adherence concerns showed 54.3% below the orienting therapeutic range, while ASM-related adverse events assessment only 8.9% showed levels exceeding the orienting therapeutic range. Following TDM results, 64.2% of cases had medication adjustments, mainly dosage increases. Overall, 55.9% of newer ASM TDM visits showed improved outcomes, including reduced seizures (47.5%) and fewer ASM-related side effects (8.4%). Conclusions: These findings suggest that appropriate utilization of TDM for newer ASMs provides clinical benefits in adjunct to complement clinical decision making in the management of epilepsy patients in a real-world clinical setting.

Due to energy shortages and the greenhouse effect, the efficient use of energy through phase-change materials (PCMs) is gaining increased attention. In this study, magnetic phase-change microcapsules (Mag-mc) were prepared by suspension polymerization. The shell layer of the microcapsules was formed by copolymerizing methyl methacrylate and triethoxyethylene silane, with the latter enhancing the compatibility of the shell layer with the magnetic additive. Ferric ferrous oxide modified by oleic acid (Fe3O4(m)) was added as the magnetic additive. Differential scanning calorimetry (DSC) testing revealed that the content of phase-change materials in microcapsules without and with ferric ferrous oxide were 79.77% and 96.63%, respectively, demonstrating that the addition of Fe3O4(m) improved the encapsulation efficiency and enhanced the energy storage ability of the microcapsules. Laser particle size analysis showed that the overall average particle sizes for the microcapsules without and with ferric ferrous oxide were 3.48 μm and 2.09 μm, respectively, indicating that the incorporation of magnetic materials reduced the size and distribution of the microcapsules. Thermogravimetric analysis indicated that the thermal stability of the microcapsules was enhanced by the addition of Fe3O4(m). Moreover, the infrared emissivity of the microcapsule-containing film decreased from 0.77 to 0.72 with the addition of Fe3O4(m) to the shell of microcapsules.

The mass production of grapevines, an agricultural waste, has imposed burdens on farmers and the environment. This study aims to address this issue by utilizing biochar derived from grapevines (GVC) in combination with polybutylene succinate (PBS) to develop an environmentally friendly bio-composite. To enhance the compatibility between GVC and PBS, maleic anhydride grafted PBS (MAPBS) was synthesized and incorporated into the bio-composite. Moreover, surface modification of GVC was conducted using a silane coupling agent to enhance its adhesion to the PBS matrix. The effects of GVC size, MAPBS content, and surface modification on the mechanical and thermal properties of PBS were investigated. The findings indicate that GVC sieved through a 200 mesh screen exhibited a better reinforcing effect compared to GVC sieved through a 120 mesh screen. The tensile test results indicated that the incorporation of 20 wt% GVC led to a reduction in the tensile strength of PBS. However, the introduction of silane-modified GVC resulted in a substantial enhancement of tensile strength, elevating it from 33.40 MPa to 40.16 MPa. Furthermore, when the composites contained both MAPBS and a lubrication agent, the tensile strength increased even further to 41.04 MPa. The thermal analysis results of the bio-composites revealed that the addition of GVC contributed to an increase in the char yield and heat resistance of PBS. Therefore, these GVC/PBS green bio-composites not only enhance the mechanical and thermal properties of PBS but also reuse the waste grapevines, and produce the high value-added green composites with carbon-storing and biodegradability characteristics.

Abstract Background Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. Methods This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. Results The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. Conclusions The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

Background: Perampanel (PER) is a newly developed antiseizure medication (ASM). This study aimed to determine the utilization of therapeutic drug monitoring (TDM) for PER in a real-world clinical setting and investigate the influence of concomitant use of ASMs on the plasma concentration profile of PER. Method: We analyzed data from the Chang Gung Research Database, which is the largest multi-institutional electronic medical records database in Taiwan. The main outcomes were the comparisons of PER plasma concentration and the ratio of concentration to the weight-adjusted dose (C/D; [ng/mL]/[mg/kg/d]) among patients received TDM of different clinical indication and among different ASM co-medication subgroups. Results: Overall, 88 plasma samples were collected from 66 epilepsy patients treated with PER. The majority of patients (77.3 %) underwent PER TDM owing to poorly controlled seizures. There was a trend toward a higher plasma concentration and C/D ratio in those suspected of having PER toxicity owing to adverse events than of other indications. The PER concentration exhibited dose linearity. The mean PER plasma concentrations in patients co-medicated with enzyme-inducing ASMs were significantly lower than those in the patients who were not prescribed enzyme-inducing or enzyme-inhibiting ASMs, and co-medication with carbamazepine (CBZ) resulted in a significant reduction in the PER concentration. Conclusion: PER concentration exhibited a linear regression relationship with PER dose, and the plasma concentration of the drug was highly susceptible to the drug's interactions with enzyme-inducing ASMs. TDM with clear indication could help determine the influence of ASMs used concomitantly on PER concentrations and guide clinical adjustments.

Abrupt changes in system states and dynamical behaviors are often observed in natural systems; such phenomena, named regime shifts, are explained as transitions between alternative steady states (more generally, attractors). Various methods have been proposed to detect regime shifts from time series data, but a generic detection method with theoretical linkage to underlying dynamics is lacking. Here, we provide a novel method named Nested-Library Analysis (NLA) to retrospectively detect regime shifts using empirical dynamic modeling (EDM) rooted in theory of attractor reconstruction. Specifically, NLA determines the time of regime shift as the cutting point at which sequential reduction of the library set (i.e., the time series data used to reconstruct the attractor for forecasting) optimizes the forecast skill of EDM. We illustrate this method on a chaotic model of which changing parameters present a critical transition. Our analysis shows that NLA detects the change point in the model system and outperforms existing approaches based on statistical characteristics. In addition, NLA empirically detected a real-world regime shift event revealing an abrupt change of Pacific Decadal Oscillation index around the mid-1970s. Importantly, our method can be easily generalized to various systems because NLA is equation-free and requires only a single time series.

The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59–79) years. The risk of dependent functional status (modified Rankin Scale score≧3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p

Wood–plastic composites (WPCs), abbreviated as WPCs, are typically composite materials made by mixing wood flour and thermoplastic resins, and then shaped through processes such as extrusion or compression. They have emerged as a viable and advanced alternative to traditional wood and plastic materials, offering an amalgamation of the best properties of both. This study utilized discarded milk bottles as the polymer matrix (mainly composed of high-density polyethylene, HDPE) and added wood flour, recycled protective clothing (Tyvek®), and diatomite recycled from brewery waste as reinforcement. Additionally, pre-treated aluminum hydroxide powder from waste artificial marble was added. The results indicated that the optimal processing temperature for the WPCs was 175 °C. The mechanical properties of the material increased with the addition of recycled protective clothing and pre-treated aluminum hydroxide powder. The increase in tensile strength can reach up to 28%. The thermal conductivity of the WPCs also significantly increased with the addition of pre-treated aluminum hydroxide powder. Furthermore, sunlight analysis showed that the surface temperature of the WPCs decreased by approximately 8.5 °C, which corresponds to a reduction of 13% after adding pre-treated aluminum hydroxide powder. Therefore, they can be applied to outdoor cool WPCs to reduce the risk of foot burns or used as roof heat-insulating layers to reduce indoor air conditioning usage, achieving energy-saving and carbon reduction. This study demonstrates that high-performance and high-value green plastics made from various recycled materials can contribute to the goals of a circular economy and sustainable carbon reduction.

Background: Combination therapy with antiseizure medications (ASMs) is a rational strategy if monotherapy cannot effectively control seizures, thereby aiming to improve tolerance and treatment persistence. Objectives: To compare the efficacy of different ASM combinations among patients. Design: Patients with epilepsy on monotherapy who had a second ASM added as concomitant two-drug therapy from January 2009 to May 2019 in the Chang Gung Research Database, Taiwan, were included in the analysis. Methods: ASM combinations were compared based on their primary mechanism of action (MoA) which are as follows: gamma-aminobutyric acid receptor (G), sodium channel blocker (SC), synaptic vesicle protein 2A (SV2), calcium channel blocker (C), and multiple mechanisms (M). Treatment persistence was compared, and the predictors of persistence were analyzed. Results: In total, 3033 patients were enrolled in this study. Combined ASMs with different MoAs had significantly longer treatment persistence than ASMs with similar MoAs, specifically SC and M combinations. Patients receiving combined ASMs with different MoAs were less likely to discontinue treatment [adjusted hazards ratio: 0.83 (95% CI: 0.75–0.93), p

This paper presents a novel digital combining method to implement a multilevel pulse modulation polar transmitter (PMPT) for 5G NR base station applications. Using pulse-width modulation on switch mode power amplifiers (PAs) is a promising method for PA efficiency improvement. Whereas using the interleaved multilevel architecture can eliminate unwanted harmonics. Previous PMPT implementations used passive power combiners to combine multiple PA outputs, this paper proposes combining to be performed digitally prior to the PAs. It was shown the proposed method is no longer susceptible to PA mismatch and is highly suitable for Doherty power amplifiers (DPAs). A transmitter prototype was developed and evaluated with a 256-QAM 5G NR 20-MHz instantaneous bandwidth signal centered at 2140 MHz. The overall system achieved an output level of 39.4 dBm with a power-added efficiency of 39%. It passes the 5G NR adjacent channel leakage ratio (ACLR) downlink spectral requirement with only memoryless digital predistortion.

Bamboo fiber-reinforced polymers have been widely studied as natural fiber composites. This study fabricated a continuous bamboo-textile-reinforced polymer (BTRP) composite by using woven bamboo strips and epoxy through vacuum-assisted resin transfer molding (VA-RTM). The physical properties, including bulk density and equilibrium moisture content, of various BTRP specimens with different textile architectures, stacking sequences, loading axes, and numbers of layers were preliminarily evaluated. The specimens’ flexural properties, including strength, modulus, integral load – deflection relationship, damage parameters, and fractography characteristics, were also examined. As the number of layers increased, the flexural strength decreased but modulus values increased. When the number of layers was constant, the plain-woven BTRP specimens had slightly higher strength and modulus values than did the twill-woven specimens. The BTRP specimens exhibited remarkable mechanical properties and staged failure behaviors unique to laminated materials. Moreover, the stiffness of the specimens was attenuated before reaching the ultimate load, which was attributed to microscopic interphase damage, and the various architectures affected the specimens’ fracture modes. The gradual multistage failure modes of the specimens imply that the fabricated composite is relatively safe for use. According to these results, the fabricated composite incorporates the advantages of VA-RTM and continuous nontwisted bamboo strips, indicating that it has substantial commercial potential.

Although bamboo fiber-reinforced polymer has been extensively studied, its utilization has been limited by its unfavorable performance. This study developed a non twisting bamboo textile-reinforced polymer (BTRP) through vacuum resin transfer molding and then used two weaving methods, different layers, different edge treatments, two stacking sequences, and two sizes as factors to investigate the effect of woven structures on the hygroscopic behavior of BTRP, such as water absorption, diffusion, dimensional stability, and moisture transportation. The differences in the results of long-term immersion and the swelling at different locations of BTRP were also examined. The results of this study indicate that the weaving method directly affected the water absorption from the fiber area and that the size of the specimens affected the saturation rate. The swelling behavior differed with the weaving method and number of layers, which indicates that rate of water ingress and transverse fiber swelling were the reasons that cause the different swelling behavior. This study found that moisture may be transferred differently through different parts of BTRP due to variations in fiber saturation. Moreover, the analysis of the center and periphery of BTRP specimens indicated that textile structure significantly affected water uptake and indirectly caused two moisture transport mechanisms.

Abstract Background To study whether oral presentation (OP) assessment could reflect the novice learners’ interpretation skills and reading behaviour on brain computed tomography (CT) reading. Methods Eighty fifth-year medical students were recruited, received a 2-hour interactive workshop on how to read brain CT, and were assigned to read two brain CT images before and after instruction. We evaluated their image reading behaviour in terms of overall OP post-test rating, the lesion identification, and competency in systematic image reading after instruction. Students’ reading behaviour in searching for the target lesions were recorded by the eye-tracking technique and were used to validate the accuracy of lesion reports. Statistical analyses, including lag sequential analysis (LSA), linear mixed models, and transition entropy (TE) were conducted to reveal temporal relations and spatial complexity of systematic image reading from the eye movement perspective. Results The overall OP ratings [pre-test vs. post-test: 0 vs. 1 in case 1, 0 vs. 1 in case 2, p

Bamboo-fiber-reinforced polymers have gained popularity in numerous industries because of their mechanical properties, lightweight, and ecological benefits. In this study, to determine the effects of textile structure on the impact resistance performance of bamboo-textile-reinforced polymers (BTRPs), we evaluated three impact modes: simple support beam (SSB), drop weight, and Charpy impact. We then used 3D X-ray scanning to determine the effects of the textile structure and impact modes on the microscopic fracture and crack development. The results indicated that the woven structure allowed for energy transmission in all directions during the drop weight impact test. During the SSB impact test, the large quantity of bamboo tows parallel to the major axis of the specimen increased the absorbed energy. When additional layers were added in the loading direction, the deflection of the entire specimen decreased, thus leading to lower absorbed energy. According to 3D X-ray images and quasi-static bending fracture results, similar fracture patterns appeared on dynamic and static loaded specimens. Consequently, the energy required for internal fracture and the strain energy of deflection are the two significant reasons that enable the excellent impact resistance performance of BTRPs.

Disentangling causal interactions among biodiversity, ecosystem functioning and environmental factors is key to understanding how ecosystems respond to changing environment. This study presents a global scale analysis quantifying causal interactions and feedbacks among phytoplankton diversity, biomass and nutrients along environmental gradients of aquatic ecosystems.

BackgroundAngiotensin receptor blockers (ARBs) are considered an alternative to angiotensin-converting enzyme inhibitors (ACEIs) in patients with acute myocardial infarction (AMI), but in the era of extensive use of preventive therapies and percutaneous coronary intervention, this has not been adequately evaluated in Asians.MethodsThis retrospective cohort study used data from the Taiwan National Health Insurance Research Database. In total, 52,620 patients initially hospitalized due to AMI between 2002 and 2015 were assessed.ResultsAfter propensity score matching, 14,993 patients each were assigned to ACEI and ARB groups. Patients who received ARBs had significantly lower all-cause mortality (adjusted hazard ratio [aHR]: 0.82; 95% confidence interval [CI]: 0.75-0.90) and hospitalization for heart failure (aHR: 0.92; 95% CI: 0.85-0.99) compared with those who received ACEIs at 18 month follow-up. No significant difference was observed between the two groups in terms of major adverse cardiovascular events (aHR: 098; 95% CI: 0.90-1.07), cardiovascular death (aHR: 0.82; 95% CI: 0.68-1.00), ischemia stroke (aHR: 0.93; 95% CI: 0.77-1.11), and nonfatal myocardial infarction (aHR: 1.04; 95% CI: 0.93-1.17). ARBs showed benefits in many subgroups in terms of all-cause mortality and cardiovascular death.ConclusionsReal-world data demonstrate that ARBs might be associated with lower all-cause mortality and hospitalization for heart failure compared with ACEIs among patients with AMI.

BackgroundDe novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy.MethodsWe investigated the association between 11C-acetate/18F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice.ResultsDual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with 11C-acetate uptake and negatively associated with 18F-FDG uptake. This finding represents the negative association between 11C-acetate and 18F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high 11C-acetate but low 18F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low 11C-acetate but high 18F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat.ConclusionThe proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy.

IntroductionAxial muscles are involved earlier and to a greater extent in late-onset Pompe disease (LOPD) than in myotonic muscular dystrophy type 1 (DM1). We aimed to evaluate abdominal muscles in LOPD compared in DM1 using muscle ultrasonography.MethodsPatients with LOPD (n = 3), DM1 (n = 10), and age- and gender-matched healthy subjects (n = 34) were enrolled for muscle ultrasonography. Patients with LOPD and DM1 were 20 to 59 years of age with a disease duration ranging between 7 and 30 years. A multifrequency linear transducer was used to evaluate quality and thickness in the abdominal muscles and extremities.ResultsThe quantitative muscle echo score revealed a higher Z score in abdominal muscles in Patients with LOPD (scores were relatively normal for the biceps and flexor digitorum groups). Patients with LOPD had significantly lower abdominal muscle thickness than patients with DM1. Abdominal muscle strength was significantly correlated with the muscle echogenicity, trunk impairment scale, and trunk control test. The extremities' sum score was correlated with the total Medical Research Council score.DiscussionThe increased quantitative muscle score in abdominal muscles, sparing the biceps and flexor digitorum groups, may offer differential diagnosis between LOPD and DM1. Ultrasound can easily access abdominal muscles and investigate muscle echogenicity and thickness. A quantitative approach using muscle echogenicity rather than muscle thickness may provide a greater correlation with trunk muscle function.

Abstract Background The incidence of cerebral stroke, including ischemic infarction and intracranial hemorrhage (ICH), increases in patients with nephrotic syndrome (NS). However, the clinical characteristics of patients with NS and stroke remain elusive. We aimed to investigate the clinical presentation and prognosis among patients with NS and ischemic stroke (IS) or ICH. Methods We conducted a population-based retrospective cohort study of patients with NS and acute stroke using the Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. The participants were recruited from the 7 branches of Chang Gung Memorial Hospital. Results A total of 233 patients with IS and 57 patients with ICH were enrolled. The median age was 60 (52–70) years. The prevalence rates of hyperlipidemia, hyperuricemia, and smoking were higher in IS than in ICH. IS demonstrated lower white blood cell count (7.80 vs. 8.92 × 109/L) and high-sensitivity C-reactive protein level (33.42 vs. 144.10 nmol/L) and higher cholesterol (5.74 vs. 4.84 mmol/L), triglyceride (1.60 vs. 1.28 mmol/L), and albumin (24 vs. 18 g/L) levels compared with ICH. The dependent functional status and 30-day mortality were higher in ICH than in IS. The risk factors for 30-day mortality for patients with NS and stroke were coronary artery disease (CAD), ICH, and total anterior circulation syndrome. The multivariate Cox regression analysis revealed that CAD was positively associated with 30-day mortality in patients with IS (hazard ratio 24.58, 95 % CI 1.48 to 408.90). In patients with ICH, CAD and subarachnoid hemorrhage were positively associated with 30-day mortality (hazard ratio 5.49, 95 % CI 1.54 to 19.56; hazard ratio 6.32, 95 % CI 1.57 to 25.53, respectively). Conclusions ICH demonstrated a higher risk of dependence and 30-day mortality compared with IS in patients with NS. Intensive monitoring and treatment should be applied particularly in patients with NS and ICH.

Backgrounds: Epilepsy surgery is the most efficacious therapeutic modality for patients with medical refractory epilepsy, especially resective surgery. However, the variable etiologies and multiple epileptic foci are usually associated with the outcomes. The aim of this study was to demonstrate that combination of different intervention procedures might be an alternative option for patients of refractory epilepsy. Methods: We retrospectively analyzed pre-operative and post-surgical outcomes in 30 patients who received epilepsy surgery between January 1, 2010 and December 31, 2014 at Chang Gung Memorial Hospital (CGMH), Linkou, according to Engel's classification. Results: Twenty-six of the 30 patients (86.7%) had good outcomes, sum of class I and class II after epilepsy surgery. The good outcome rate of our complicated group was 80.0% (12/15), compared to 93.3% (14/15) in the simple group, but no significant differences between the two groups (p = 0.569). Four patients whose epileptic foci involved eloquent area and received multiple subpial cortical transection, and good outcome rate was 75% (3/4). At last, six patients had previously failed epilepsy surgery and received a reoperation, with a good outcome rate of 83.3% (5/6). Conclusion: After complete pre-surgical evaluation and combined interventional procedures, the patients with refractory epilepsy had satisfactory outcomes and few neurological complications. Moreover, re-operation can improve the outcome in some patients who previously failed epilepsy surgery.

Abstract “Real-world” data on the nationwide epidemiology and treatment patterns of multiple sclerosis (MS) is very scarce in Asia. This study is aim to evaluate the 10-years trends in epidemiology and treatment patterns of MS with Taiwan’s National Health Insurance Database (NHIRD). Patients aged 20 years or older and were newly diagnosed with MS between 2007 and 2016 were identified. The crude incidences of MS were presented annually and stratified by sex and age. Baseline characteristics and treatment patterns, particularly disease-modifying drugs (DMDs), were also analyzed. This study included 555 MS patients (mean age was 36.9 and 74.4% were female). The crude incidence rate of MS decreased slightly from 0.43 per 100,000 persons in 2007 to 0.24 per 100,000 persons in 2015. The female to male ratios remained mainly between 2 to 3. Approximately 80% of MS patients received initial DMDs, with interferon β-1a as the dominant one. Furthermore, 37.5% of MS patients received subsequent DMDs, with fingolimod being the most frequently used. The median times from diagnosis to initial and to subsequent DMDs were 77 and 1239 days, respectively. This nationwide study provides up-to-date and sophisticated estimates of MS epidemiology and treatment pattern in “real-world” setting in Taiwan.

Patients with juvenile myoclonic epilepsy (JME) may not achieve seizure freedom despite optimal treatment with antiseizure medications (ASMs). The aim of this study was to investigate the clinical and social features of patients with JME, and to determine the factors associated with outcomes. We retrospectively identified 49 patients with JME (25 females, mean age 27.6 ± 8.9 years) who were assessed at the Epilepsy Centre of Linkou Chang Gung Memorial Hospital in Taiwan. The patients were divided into two groups, those who were seizure-free and those with ongoing seizures according to their seizure outcome at the last follow-up for one year. Clinical features and social status were compared between these two groups. Twenty-four (49%) of the JME patients were seizure-free for at least one year, while 51% continued to experience seizures despite being treated with multiple ASMs. The presence of epileptiform discharges in the last electroencephalogram and seizures during sleep were significantly associated with worse seizure outcomes (p < 0.05). The patients who were seizure-free had a higher employment rate compared to those who continued to experience seizures (75% vs. 32%, p = 0.004). Despite receiving ASM treatment, a considerable proportion of the patients with JME continued to have seizures. Moreover, poor seizure control was associated with a lower employment rate, which may lead to negative socioeconomic consequences related to JME.

Increased oxidative stress and neuroinflammation play a crucial role in the pathogenesis of Parkinson’s disease (PD). In this study, the expression levels of 52 genes related to oxidative stress and inflammation were measured in peripheral blood mononuclear cells of the discovery cohort including 48 PD patients and 25 healthy controls. Four genes, including ALDH1A, APAF1, CR1, and CSF1R, were found to be upregulated in PD patients. The expression patterns of these genes were validated in a second cohort of 101 PD patients and 61 healthy controls. The results confirmed the upregulation of APAF1 (PD: 0.34 ± 0.18, control: 0.26 ± 0.11, p < 0.001) and CSF1R (PD: 0.38 ± 0.12, control: 0.33 ± 0.10, p = 0.005) in PD patients. The expression level of APAF1 was correlated with the scores of the Unified Parkinson’s Disease Rating Scale (UPDRS, r = 0.235, p = 0.018) and 39-item PD questionnaire (PDQ-39, r = 0.250, p = 0.012). The expression level of CSF1R was negatively correlated with the scores of the mini-mental status examination (MMSE, r = −0.200, p = 0.047) and Montréal Cognitive Assessment (MoCA, r = −0.226, p = 0.023). These results highly suggest that oxidative stress biomarkers in peripheral blood may be useful in monitoring the progression of motor disabilities and cognitive decline in PD patients.

Abstract Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40–59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.

Abstract Background Women are well known to be susceptible to developing affective disorders, yet little attention has been given to effects of ovariectomy-reduced hormones and links with depression. This population-based cross-sectional study aimed to investigate possible associations between ovariectomy-reduced hormones and depression symptom scores of the Patient Health Questionnaire-9 (PHQ-9) in ovariectomized women. Methods Data of PHQ-9 scores, demographics and comorbidities of ovariectomized women were extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) database (2013–2016) and were analyzed retrospectively. Results Among ovariectomized women in the NHANES database, serum estradiol levels were significantly positively associated with PHQ-9 scores (ß = 0.014, 95% CI: 0.001, 0.028, P = 0.040), whereas serum testosterone was negatively associated with PHQ-9 scores (ß = -0.033, 95% CI: − 0.048, − 0.018, P

Abstract Objectives Blood–brain barrier (BBB) disruption is a critical pathological process involved in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterized the profile of five cell adhesion molecules in patients with NMOSD. Methods We measured levels of cell adhesion molecules, including ICAM‐1, ICAM‐2, VCAM‐1, PECAM‐1, and NCAM‐1, in the serum of 28 patients with NMOSD, 24 patients with multiple sclerosis (MS), and 25 healthy controls (HCs). Results ICAM‐2 levels (median: 394.8 ng/mL) were increased in patients with NMOSD compared with MS (267.1 ng/mL, P = 0.005) and HCs (257.4 ng/mL, P = 0.007), and VCAM‐1 and ICAM‐1 levels were higher in patients with NMOSD (641.9 ng/mL and 212.7 ng/mL, respectively) compared with HCs (465 ng/mL [P = 0.013] and 141.8 ng/mL [P = 0.002], respectively). However, serum PECAM‐1 levels were lower in patients with NMOSD (89.62 ng/mL) compared with MS (106.9 ng/mL, P = 0.015) and HCs (107.2 ng/mL, P = 0.007). Receiver operating characteristic curve analysis revealed that PECAM‐1 (area under the curve (AUC): 0.729) and ICAM‐2 (AUC: 0.747) had adequate abilities to distinguish NMOSD from MS, and VCAM‐1 (AUC: 0.719), PECAM‐1 (area under the curve: 0.743), ICAM‐1 (AUC: 0.778), and ICAM‐2 (AUC: 0.749) exhibited potential to differentiate NMOSD and HCs. Serum levels of PECAM‐1 also demonstrated a negative correlation with Kurtzke Expanded Disability Status Scale scores in patients with NMOSD. Interpretation Our results reveal possible BBB breakdown signals specifically observed in NMOSD and highlight the potential role of cell adhesion molecules as biomarkers of this disease.

Background/purpose: Early diagnosis of vertical root fracture (VRF) has been a great challenge. Since there is no single specific etiology identified, prevention of VRFs in endodontically treated teeth is quite difficult. The study aimed to evaluate the clinical associated factors of VRFs. Materials and methods: A retrospective observational study of medical charts was conducted in the Department of Endodontics of Taipei Medical University Hospital in Taiwan from January 2012 to July 2018. Logistic regression model was performed to determine the association between VRF and its clinical associated factors, inclusive of the tooth characteristics (age, gender and tooth type) and iatrogenic risk factors (history of root canal treatment, restoration and post). Results: A total of 359 teeth were included in the study. The prevalence of VRF on a tooth basis was 18.7%. The result showed that age of more than 50 years (adjusted OR = 3.20, 95% CI: 1.81–5.64, p

This study found that biochar made from grapevines (GVC), an agricultural waste product, can be used as a nucleating agent to promote the crystallization of polylactic acid (PLA). Differential scanning calorimetry (DSC) analysis of GVC/PLA composites showed that different particle sizes (200 and 100 mesh size) and amounts (1 wt%, 10 wt%) of biochar affect the re-crystallization of PLA, with 200 mesh GVC in the amount of 10 wt% being the most significant. In addition, it was found that there were two peaks related to imperfect and perfect crystals in the Tm part for GVC/PLA composites. TGA analysis showed that adding GVC tends to lower the maximum decomposition temperature of PLA, revealing that GVC may accelerate the degradation reaction of PLA. This research also studied the effects of GVC in various particle sizes and amounts on the mechanical properties and degradation of PLA. The results revealed that the tensile and impact strengths of GVC/PLA composite could reach 79.79 MPa and 22.67 J/m, respectively, and the increments were 41.4% and 32.1%, greater than those of pristine PLA. Moreover, the molecular weight of PLA decreased as the amount of GVC increased. Therefore, GVC particles can be used as reinforcing fillers for PLA to improve its mechanical properties and adjust its molecular weight. These agricultural-waste-reinforced biocomposites can reduce both greenhouse gas (GHG) emissions and the cost of biodegradable polymers and achieve the goals of a circular economy.

In the present study, a nanocrystalline Ni-Fe matrix with reinforced TiO2 nanoparticles as a functional nanocomposite material was fabricated by pulsed current electroforming in UV-LIGA (lithography, electroplating, and molding). The influences of TiO2 nanoparticles on the Ni-Fe nanocomposite deposition were also investigated using scanning electron microscopy, transmission electron microscopy, and in vitro cytotoxicity assay. It was found that the Ni-Fe nanocomposite with 5 wt.% TiO2 nanoparticles showed a smooth surface and better dispersion property. When the Ni-Fe nanocomposite is combined with 20 wt.% TiO2, it resulted in congeries of TiO2 nanoparticles. In addition, TiO2 nanoparticles possessed better dispersion properties as performed in pulse current electrodeposition. The microstructure of the electrodeposited Ni-Fe-TiO2 nanocomposite was a FeNi3 phase containing anatase nano-TiO2. Moreover, the electrodeposited Ni-Fe-5 wt.% TiO2 nanocomposite exhibited a smooth surface and structural integrity. Cytotoxicity assay results also proved that the Ni-Fe nanocomposite with different concentrations of TiO2 nanoparticles had good biocompatibility. Therefore, the optimization of pulse current electroforming parameters was successfully applied to fabricate the Ni-Fe-TiO2 nanocomposite, and thus could be used as an endodontic file material for dental applications.

Abstract Background Few systematic methods prioritize the image education in medical students (MS). We hope to develop a checklist of brain computerized tomography (CT) reading in patients with suspected acute ischemic stroke (AIS) for MS and primary care (PC) physicians. Methods Our pilot group generated the items indicating specific structures or signs for the checklist of brain CT reading in suspected AIS patients for MS and PC physicians. These items were used in a modified web-based Delphi process using the online software “SurveyMonkey”. In total 15 panelists including neurologists, neurosurgeons, neuroradiologists, and emergency department physicians participated in the modified Delphi process. Each panelist was encouraged to express feedback, agreement or disagreement on the inclusion of each item using a 9-point Likert scale. Items with median scores of 7–9 were included in our final checklist. Results Fifty-two items were initially provided for the first round of the Delphi process. Of these, 35 achieved general agreement of being an essential item for the MS and PC physicians. The other 17 of the 52 items in this round and another two added items suggested by the panelists were further rated in the next round. Finally, 38 items were included in the essential checklist items of brain CT reading in suspected AIS patients for MS and PC physicians. Conclusions We established a reference regarding the essential items of brain CT reading in suspected AIS patients. We hope this helps to minimize malpractice and a delayed diagnosis, and to improve competency-based medical education for MS and PC physicians.

Background/Purpose: Diagnosis of vertical root fractures (VRFs) can often be challenging due to the similarity of signs and symptoms with other common dental infectious diseases. This study was aimed at evaluating the potential relationship between VRFs and commonly used clinical diagnostic factors. Methods: 330 root-filled teeth with endodontic failures were subjected to endodontic microsurgery over a six-year period. VRFs were identified in 61 teeth. A randomly age- and sex-matched retrospective case-control study was conducted on a subset of 59 root-filled teeth with VRFs (cases) and 177 root-filled teeth without VRFs (controls). The strength of association between preoperative signs and radiographic findings and VRFs was evaluated using logistic regression model. Results: Sinus tract, periodontal pocket depth ≥5 mm, periodontal swelling or abscess, and radiological image of J-shaped or “halo” radiolucency were significantly more frequent in cases than in controls (p

The pulse-modulated polar transmitter (PMPT) uses radio-frequency (RF) phase modulated signal with pulse-width modulated envelope to drive a power amplifier (PA) as a switch to achieve high linearity and high efficiency. However, as the signal bandwidth increases, various non-idealities limit the performance of the PMPT architecture. In this paper, a Gibbs-phenomenon reduction filter is proposed with a partial Fourier series of digital pulse-width modulation (PWM) such that the pulsed signal is more immune to the distortion in nonlinear high-efficiency RF PAs. For validation, a prototype transmitter was tested with a 20-MHz bandwidth 256-QAM 5G new radio (NR) signal at 2.14 GHz. The proposed method achieved a drain efficiency of 28.3%, error vector magnitude (EVM) of 1.67%, and adjacent channel leakage ratio (ACLR) of -45.4 dBc at an output power of 18 dBm using the prototype transmitter. Linearity requirements for base stations were met without the use of any digital predistortion methods.

Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy which is closely related to the sleep-wake cycle. This study aimed to investigate whether sleep disturbance is more common among patients with JME and the impact this may have on their quality of life (QOL). Thirty-four patients with JME and age- and gender-matched controls were recruited into this case control study, and assessed using validated sleep questionnaires including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Stanford Sleepiness Scale (SSS). QOL was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-31). The patients had a significantly higher PSQI score and higher proportion of abnormal PSQI scores than the controls. They also had higher ESS and SSS scores, but without statistical significance. The patients with poor sleep quality had significantly lower overall QOL, emotional well-being, and energy/fatigue subscale scores. The use of a higher number of antiseizure medications, dosage of levetiracetam, and usage of antiseizure medication polytherapy were associated with sleep disorders. Our results showed that sleep disturbance is common in patients with JME, and also that it has an impact on their QOL.

Abstract Polystyrene (PS) nanotubes prepared using the solvent‐vapor‐induced wetting method with anodic aluminum oxide templates are for the first time applied to study the thermal stabilities of polymer nanotubes confined in cylindrical geometries. The morphologies of the PS nanotubes and the corresponding transformed PS nanostructures driven by the Rayleigh instabilities after thermal annealing treatments are characterized by scanning electron microscopy. Morphology diagrams of the Rayleigh‐instability‐induced nanostructures for PS nanotubes prepared via the solvent‐vapor‐induced wetting method and the solution wetting method are constructed to study the differences in kinetics for samples using different wetting methods. Slower transformation kinetics for the PS samples prepared by the solvent‐vapor‐induced wetting method than those prepared by the solution wetting method are observed, indicating the better thermal stabilities and the relatively denser packings of the polymer chains in the nanopores for the PS samples prepared using the solvent‐vapor‐induced wetting method.

This study emphasizes the warpage phenomenon of thin-walled parts using acrylonitrile-butadiene styrene (ABS) plus polycarbonate (PC) plastics for optimal processing by thin-wall injection molding. The authors first employed the Moldflow software to analyze the runner’s balance on multicavities for thin-walled parts and to simulate the warpage of thin-walled parts with thin-wall injection molding. Then, this study used those data to fabricate a real mold by computer numerical control machining. For this study, the authors fabricated thin-walled parts and measured their warpage using various process parameters (injection speed, injection pressure, mold temperature, packing time, and melt temperature) with thin-walled injection molding. Finally, the authors found that the most important processing parameter was the packing time for warpage phenomenon of thin-walled parts by thin-wall injection molding.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and α-synuclein plays a critical role in the pathogenesis of PD. Studies have revealed controversial results regarding the correlation between motor severity and α-synuclein levels in peripheral blood from patients with PD.Objective: We examined α-synuclein levels in plasma or serum in patients with PD and investigated the relationship between plasma or serum α-synuclein level and motor symptom severity.Methods: We recruited 88 participants (48 patients with PD and 40 healthy controls). Clinical information was collected, and venous blood was drawn from each participant to be processed to obtain plasma or serum. The plasma or serum α-synuclein level was detected using monoclonal antibodies with magnetic nanoparticles, and was measured through immunomagnetic reduction. Plasma or serum α-synuclein levels were quantitatively detected.Results: In patients with PD, the means of plasma and serum α-synuclein level were 3.60 ± 2.53 and 0.03 ± 0.04 pg/mL, respectively. The areas under the receiver operating characteristic curve of plasma and serum α-synuclein for distinguishing patients with PD from healthy controls were 0.992 and 0.917, respectively. The serum α-synuclein level also showed a significant correlation with patients in H-Y stages 1–3 (r = 0.40, p = 0.025), implying that the serum α-synuclein level may be a potential marker of motor symptom severity in patients with early PD.Conclusions: Our data suggest that the α-synuclein level in serum or plasma can differentiate between healthy controls and patients with PD. Serum α-synuclein levels moderately correlate with motor severity in patients with early PD.

In a previous study, we reported the alterations of primary antioxidant enzymes and decreased citrate synthase (CS) activities in different grades of human astrocytoma tissues. Here, we further investigated coenzyme Q10 (CoQ10) levels and protein levels of polyprenyl diphosphate synthase subunit (PDSS2) and several COQ proteins required for CoQ10 biosynthesis in these tissues. We found that the level of endogenous CoQ10, but not of exogenous α-tocopherol, was higher in nontumor controls than in all grades of astrocytoma tissues. The levels of COQ3, COQ5, COQ6, COQ7, COQ8A, and COQ9, but not of COQ4, were lower in Grade IV astrocytoma tissues than in controls or low-grade (Grades I and II) astrocytomas, but PDSS2 levels were higher in astrocytoma tissues than in controls. Correlation analysis revealed that the levels of CoQ10 and COQ proteins were negatively correlated with malignancy degree and positively correlated with CS activity, whereas PDSS2 level was positively correlated with malignancy. Moreover, lower level of mitochondrial DNA-encoded cytochrome c oxidase subunit 2 was not only associated with a higher malignancy degree but also with lower level of all COQ proteins detected. The results revealed that mitochondrial abnormalities are associated with impaired CoQ10 maintenance in human astrocytoma progression.

Background: To analyze the efficacy and safety of perampanel over a 3-month period in a sample of Asian people with epilepsy. Methods: The efficacy and safety of perampanel as an adjunctive therapy for patients with epilepsy were retrospectively reviewed and analyzed. Patients were categorized according to seizure type, concomitant antiepileptic drug usage, and perampanel dosage. Results: A total of 210 patients were included in the study and 131 patients completed 3 months of perampanel treatment. The average dosage of perampanel was 5.31 mg/day, and the 50% responder rate (≥50% seizure frequency reduction) in all patients was 45.8%, with a 27.5% seizure-free rate. For focal seizures, focal to bilateral tonic-clonic seizures, and primary generalized seizures, the 50% responder rates were respectively 29.4%, 49.5%, and 36.4%. In total, 39.5% of patients experienced adverse events within 3 months of observation period, and the rate of drug withdrawal due to adverse events was 8.6%. Dizziness, ataxia, irritability/aggression were the most common adverse events. Conclusions: The efficacy and safety of perampanel in a real-world setting with Asian patients is comparable to that in clinical trials that have included fewer Asian patients.