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Background: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies. Methods: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023. Results: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9–48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention. Conclusions: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.

Purpose: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. Methods: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. Results: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. Conclusion: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Abstract Objective The number of patients using emergency medical services (EMS) through ambulance dispatch has been increasing annually in Taiwan. Due to limited medical resource allocation, patients may not get on-time admission after they are sent to a hospital Emergency Department. This study aimed to construct a forecasting system to predict the availability of ED and ICU beds. Materials and methods A simulation-based forecasting system integrated with Google Maps is proposed to provide ED recommendations for ambulance dispatch. The web crawler technique continuously collects open data from the emergency information systems. An arrival transfer mechanism was proposed to convert the raw data into a simulation input. The results were then integrated with hospital assessment and routing distance in Google Maps to provide the most appropriate hospital ED to which a patient should be sent. Results The results provided forecast accuracy for bed availability for the next 20, 40, and 60 min in 10 selected hospitals in central Taiwan. In most hospitals, the forecasting accuracy is high. For example, the ED and ICU bed availability accuracies in the next 20, 40, and 60 min are [100%, 88.7%], [100%, 90.5%], and [100%, 92.1%]. The two scenarios also showed hospital recommendations based on the available beds, routing distance, and eight-dimensional assessments. Conclusion Previous EMS research usually did not consider future bed availability as the research target. This study predicted future bed availability and recommended the most appropriate hospitals for EMS dispatchers.

ABSTRACT Background and Aims This systematic review and meta‐analysis evaluate the efficacy of moist versus non‐moist dressings for split‐thickness skin graft (STSG) donor sites, focusing on time to healing, pain management, and adverse events to guide clinical practice. Methods A comprehensive literature search was conducted across databases including Ovid/MEDLINE, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and Scopus up to November 28, 2023. The study adhered to PRISMA guidelines. Eligible randomized controlled trials (RCTs) were assessed for quality using the Newcastle‐Ottawa Scale and Cochrane risk‐of‐bias tool, with meta‐analysis performed using the DerSimonian and Laird random‐effects model. Results Out of 464 identified studies, 16 RCTs involving 1129 patients were included. Moist dressings such as Tegaderm, Hydrocolloid, Alginate, polyurethane, and hydrofiber showed a faster mean time to healing compared to non‐moist dressings like Mepitel and paraffin‐impregnated gauze. Hydrocolloid dressings were particularly effective in accelerating wound healing. Additionally, moist dressings were associated with lower pain levels during dressing removal and had comparable rates of adverse events. Conclusion The evidence strongly supports the use of moist dressings, particularly Hydrocolloid, for STSG donor site coverage. These dressings promote faster healing and superior pain management. The study highlights the need for further research to address existing limitations and refine recommendations for optimal wound care interventions.

Background In direct oral anticoagulant (DOAC) users with stroke due to large artery occlusion, endovascular thrombectomy is an effective treatment when intravenous thrombolytic therapy is unsuitable. The purpose of this study is to investigate the association between emergent DOAC levels and endovascular thrombectomy outcomes. Methods Participants with atrial fibrillation, who had a premorbid modified Rankin Scale score of ≤3 and had undergone endovascular thrombectomy for acute stroke, were enrolled. Drug levels upon hospital arrival were measured in the prestroke DOAC users. Head noncontrast computed tomography and computed tomographic angiography images were used to quantify thrombus permeability. The primary outcome was functional independence at 3 months (modified Rankin Scale 0–2 or a return to premorbid status for patients with a premorbid modified Rankin Scale of 3). Results The study included 250 patients (antithrombotic agent nonusers, 42.0%; oral anticoagulant users, 34.0%; and antiplatelet users, 24.0%). The primary outcomes did not differ among the 3 groups. Among oral anticoagulant users, 78.8% were DOAC users. Of the 59 DOAC users with available drug level measurements, 62.7% had low levels (

Objectives: The FilmArray gastrointestinal panel (FAGIP) is widely used to detect infectious diarrhoea due to its outstanding sensitivity compared to conventional methods, but there is geographic variation, such as in the distribution of pathogens, among populations. Methods: This was a retrospective study that analysed patients with acute diarrhoea who underwent FAGIP tests from all age groups during 2022. We compared positive rates of FAGIP between paediatric (n = 245) and adult patients (n = 242) of different origins. The targeted therapy rate and antimicrobial agent use rate were also analysed. Results: Among the 487 stool samples evaluated, the overall, community-origin (CO), and nosocomial (NC) positivity rates of paediatric patients were significantly higher than those of adults (73.9 % vs. 43.0 %, p = 0.000; 76.2 % vs. 51.7 %, p = 0.000; 50.0 % vs. 19.7 %, p = 0.000). Salmonella was the most frequently detected pathogen (35.9 %) in children, while the predominant pathogen in adult patients was toxin A/B-genic Clostridioides difficile (13.2 %). There was a significantly lower antimicrobial agent use rate after FAGIP results were available (79.1 % vs. 64.5 %, p = 0.000) and a higher rate of targeted therapy towards C. difficile infection in adults than in children (84.4 % vs. 69.0 %, p = 0.011). Conclusion: Paediatric diarrhoea patients showed higher positivity rates than adult patients. Application of FAGIP for acute diarrhoea might lower unnecessary antimicrobial use.

Summary:. Lipomas are the most prevalent type of benign soft tissue tumors, primarily composed of adipocytes, and typically remain asymptomatic unless they reach a significant size. Although giant lipomas are infrequent, their occurrence on the chest wall, particularly in the interpectoral region, is exceedingly rare. We present a unique case of a 48-year-old man with a massive interpectoral lipoma measuring 19.4 × 12.9 × 9.4 cm, which resulted in venous thoracic outlet syndrome by compressing the subclavian vein. This case highlights the clinical challenges in diagnosing deep-seated chest wall lipomas and underscores the necessity of considering thoracic outlet syndrome as a potential complication, even in the absence of direct neural or arterial compression. The presentation of thoracic outlet syndrome can vary, and a comprehensive evaluation is imperative for accurate diagnosis and management.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and leukoencephalopathy (CADASIL) is the most frequent genetic cerebrovascular disease. The clinical aspects of the disease in relation to the various types of lesions on Magnetic Resonance Imaging (MRI) vary widely within families but also between multiple cohorts reported worldwide. Many limitations prevent the comparison of imaging data obtained using different scanners and sequences, in different patients cohorts. We aimed to develop and validate a practical tool to inventory quickly the most important MRI features in CADASIL for comparing imaging data across different populations. Methods: The Inventory Tool (CADA-MRIT) was designed by consensus after repeated expert meetings. It consisted of eleven imaging items for evaluating periventricular, deep, and superficial white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), centrum semiovale and basal ganglia dilated perivascular spaces (PVS), superficial and deep atrophy, large infarcts, and macrobleeds. The reliability, clinical relevance and time-effectiveness of the CADA-MRIT were assessed using data from three independent cohorts of patients. Results: Imaging data from 671 CADASIL patients (440 from France, 119 from Germany and 112 from Taiwan) were analyzed. Their mean age was 53.4 ± 12.2 years, 54.5% were women, 56.2% had stroke, and 31.1% had migraine with aura. Any lacune was present in at least 70% of individuals, while CMB were present in 83% of patients from the Asian cohort and in only 35% European patients. The CADA-MRIT scores obtained for WMH, CMB and PVS were comparable regardless of the scanner or sequence used (weighted κ > 0.60). Intrarater and interrater agreements were good to very good (weighted κ > 0.60). Global WMH and atrophy scores strongly correlated with the exact volumetric quantification of WMH or brain parenchymal fraction (Pearson r > 0.60). Different imaging scores were significantly associated with the main clinical manifestations of the disease. The time for evaluating one patient was around 2-3 minutes. Discussion: The CADA-MRIT is an easy-to-use instrument for analyzing and comparing the most frequent MRI lesions of CADASIL across different populations. This tool is reliable. It can be used with different imaging sequences or scanners.

The characteristics, risk factors, microbial distributions and effective treatment regimens for Chronic suppurative otitis media (CSOM) patients intractable to empirical therapy were analyzed.Adult CSOM patients of China Medical University Hospital from 2018 to 2020 were included. Subjects of refractory and non-refractory groups were investigated for characteristics of age, sex, nation, comorbidities, otomycosis, and associated complications. Risk factors, microbiology distributions, and treatment regimens were analyzed.Twenty-six refractory patients (55.0 ± 17.7 years) and 66 non-refractory patients (54.1 ± 13.7 years) were studied. A significantly higher rate of otomycosis and CSOM complications was observed in refractory group than in non-refractory one (73.1% vs. 36.4%; p = 0.002; 57.7% vs. 10.6%, p

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small‐vessel disease. Phenotype variability in CADASIL suggests the possible role of genetic modifiers. We aimed to investigate the contributions of the APOE genotype and Neurogenic locus notch homolog protein 3 (NOTCH3) variant position to cognitive impairment associated with CADASIL. Methods and Results Patients with the cysteine‐altering NOTCH3 variant were enrolled in a cross‐sectional study, including the Mini‐Mental State Examination (MMSE), brain magnetic resonance imaging, and APOE genotyping. Cognitive impairment was defined as an MMSE score

Background Endovascular thrombectomy (EVT) is the standard therapy for patients with acute ischemic stroke secondary to large‐artery occlusion. In January 2019, the Taiwan Stroke Society established a nationwide TREAT‐AIS (Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke). Here, we provide the study design, current progress, and baseline data of TREAT‐AIS. Methods TREAT‐AIS is a multicenter prospective registration program in Taiwan. Patients aged ≥20 years who underwent EVT for acute ischemic stroke were recruited. The key items on the registration form were divided into general stroke demographics and EVT‐related sections. The main outcome of effectiveness was functional independence (modified Rankin Scale score, 0–2) at 3 months. The influence of sex on post‐EVT outcomes was also analyzed in the presented study. Results By the end of June 2022, there were 10 medical centers and 9 community hospitals participating in the TREAT‐AIS and a total of 1522 patients (mean±SD age, 71.2±13.6 years; men, 55.6%) being enrolled. The median National Institutes of Health Stroke Scale score on admission was 18 (interquartile range, 12–23). The major cause of stroke was cardioembolism (43.6%), followed by large‐artery atherosclerosis (36.8%) and an undetermined cause (15.4%). Functional independence at 3 months poststroke was achieved in 36.2% of the patients. Male patients were more likely to have functional independence at 3 months compared with female patients (40.4% versus 30.8%; P

Hereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibited coexisting phenotypes of both CCMs and PKD. The index case was a 55-year-old woman with known PKD who developed an intracerebral hemorrhage (ICH) in the right medulla. Neuroimaging revealed numerous microbleeds in the bilateral cerebrum and cerebellum. Radiological CCMs were suspected given the absence of other imaging markers of small vessel disease. A comprehensive panel of 183 cerebral vascular malformation genes were investigated through genome sequencing. A novel CCM2 frameshift variant (c.607_608delCT, p.Leu203Valfs∗53) causing a pathogenic premature stop codon, and a known PKD2 nonsense variant (c.2407C > T, p.Arg803∗), were found. Segregation analysis revealed that four siblings were affected by either isolated aforementioned PKD2 or CCM2 variant. Notably, radiological CCMs were exclusively found in siblings who had this CCM2 variant, and bilateral internal carotid artery aneurysms were restricted to one sibling who had the PKD2 variant but not the CCM2 variant. Our study expands the genetic spectrum of CCM2 and demonstrates unambiguous cosegregation of CCM2 and PKD2 variants with their respective phenotypes.

Nutrient starvation-induced autophagy is a conserved process in eukaryotes. Plants defective in autophagy show hypersensitivity to carbon and nitrogen limitation. However, the role of autophagy in plant phosphate (Pi) starvation response is relatively less explored. Among the core autophagy-related (ATG) genes, ATG8 encodes a ubiquitin-like protein involved in autophagosome formation and selective cargo recruitment. The Arabidopsis thaliana ATG8 genes, AtATG8f and AtATG8h, are notably induced in roots under low Pi. In this study, we show that such upregulation correlates with their promoter activities and can be suppressed in the phosphate response 1 (phr1) mutant. Yeast one-hybrid analysis failed to attest the binding of the AtPHR1 transcription factor to the promoter regions of AtATG8f and AtATG8h. Dual luciferase reporter assays in Arabidopsis mesophyll protoplasts also indicated that AtPHR1 could not transactivate the expression of both genes. Loss of AtATG8f and AtATG8h leads to decreased root microsomal-enriched ATG8 but increased ATG8 lipidation. Moreover, atg8f/atg8h mutants exhibit reduced autophagic flux estimated by the vacuolar degradation of ATG8 in the Pi-limited root but maintain normal cellular Pi homeostasis with reduced number of lateral roots. While the expression patterns of AtATG8f and AtATG8h overlap in the root stele, AtATG8f is more strongly expressed in the root apex and root hair and remarkably at sites where lateral root primordia develop. We hypothesize that Pi starvation-induction of AtATG8f and AtATG8h may not directly contribute to Pi recycling but rely on a second wave of transcriptional activation triggered by PHR1 that fine-tunes cell type-specific autophagic activity.

Background/Purpose: Several risk scores have been developed to predict symptomatic intracerebral hemorrhage (SICH) after acute reperfusion therapy for ischemic stroke. We compared the performance of established risk scores in predicting SICH after EVT under different SICH criteria. Methods: A total of 258 patients with anterior circulation large vessel occlusion who received EVT in two medical centers of Taiwan were recruited. Three definitions of SICH, the European Collaborative Acute Stroke Study II (ECASS II), ECASS III, and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), were used. The HAT, SITS-SICH, SEDAN, and TAG risk scores were applied. Logistic regression and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of each risk model. Results: In the 258 included patients (mean age, 71.9 ± 11.8 years; men, 48.1%), the observed rates of SICH according to ECASS II, ECASS III, and SITS-MOST criteria were 10.1%, 5.0%, and 4.7%, respectively. Higher glucose level (>160 mg/dL) and unsuccessful recanalization independently predicted SICH under all criteria. Among the different risk scores, only SEDAN and TAG consistently predicted SICH. SEDAN and TAG scores exhibited the highest AUC in predicting SICH for ECASS III (SEDAN 0.72, TAG 0.72) and SITS-MOST (SEDAN 0.73, TAG 0.70) criteria. Conclusion: Among various risk scores, the TAG and SEDAN scores best predict SICH after EVT. Higher glucose level and unsuccessful recanalization, which are included in the TAG and SEDAN scores, are independent risk factors of SICH in the present cohort, highlighting their detrimental effects.

Background/Purpose: To evaluate whether a shorter length (20 cm) of C-UCM has potential benefits, compared to immediate cord clamping (ICC), in very preterm babies. Methods: Inborn preterm infants less than 30 weeks of gestational age (GA) were randomly assigned to the 20-cm C-UMC and ICC groups. The primary outcome was the need for packed red blood cell (pRBC) transfusion before the 21st day of life. The secondary outcomes were short- and long-term outcomes related to premature birth. Results: Seventy-six neonates were randomized to the two groups. GA were 27.2 ± 1.8 and 27.5 ± 1.7 weeks (p = 0.389) and birth weights were 987 ± 269 and 1023 ± 313 g (p = 0.601) in the 20-cm C-UCM and ICC groups, respectively. There was no significant difference between the groups in terms of the need for pRBC transfusion before the 21st day of life (59.4% versus 71.8%, adjusted odds ratio [aOR] 0.311, 95% confidence interval [CI] 0.090–1.079). An increased prevalence of late-onset sepsis was observed in the 20-cm C-UCM group compared to the ICC group (21.6% versus 5.1%, aOR 5.434, 95% CI 1.033–23.580). The mortality rates were 13.5% and 2.6% in the 20-cm C-UCM and ICC groups, respectively (aOR 5.339, 95% CI 0.563–50.626). The neurodevelopmental outcomes at 2 years of corrected age between the groups were also not statistically significant. Conclusion: A 20-cm C-UCM showed no effect on reducing the incidence of pRBC transfusion in preterm babies with GA less than 30 weeks compared with ICC in this small-scale randomized controlled trial.

BackgroundPrevious reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer’s disease (AD). We investigated whether CAA is associated with subcortical atrophy.MethodsThe study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity.ResultsParticipants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, −0.024% of intracranial volume; 95% confidence intervals, −0.041% to −0.006%; p = 0.005) than the HCs but not AD participants (−0.003%; −0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups.ConclusionIn contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.

Keloid is a type of disfiguring pathological scarring unique to human skin. The disorder is characterized by excessive collagen deposition. Immune cell infiltration is a hallmark of both normal and pathological tissue repair. However, the immunopathological mechanisms of keloid remain unclear. Recent studies have uncovered the pivotal role of both innate and adaptive immunity in modulating the aberrant behavior of keloid fibroblasts. Several novel therapeutics attempting to restore regulation of the immune microenvironment have shown variable efficacy. We review the current understanding of keloid immunopathogenesis and highlight the potential roles of immune pathway-specific therapeutics.

Summary: Background: Post-caesarean section analgesia is important physiologically and psychologically for both mothers and infants. Patient-controlled analgesia is a well-established method of administering opioids for postoperative pain. However, to date, no study has systematically investigated the effects of opioids administered through intravenous patient-controlled analgesia (IVPCA) or patient-controlled epidural analgesia (PCEA) in parturients who have undergone caesarean section. Methods: This systematic review and network meta-analysis aimed to evaluate the analgesic and adverse effects of opioids administered via IVPCA or PCEA in parturients who have undergone a caesarean section. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through 02 10, 2022 for relevant records. Randomised controlled trials (RCTs) that compared opioids administered via IVPCA or PCEA and reported outcomes of interest were included. Studies were excluded if the solution for patient-controlled analgesia contained antiemetics and/or other analgesics in addition to opioids. The methodological quality of RCTs was assessed using the revised Cochrane Risk of Bias Tool. Summary data were extracted from each eligible study. The primary outcome was pain intensity, and the secondary outcomes were opioid-related adverse effects. Frequentist network meta-analyses were performed using a contrast-based random-effects model. This study is registered with PROSPERO, CRD42021254040. Findings: Twenty-three studies with 2589 parturients were included. Compared with IVPCA morphine as a reference treatment, PCEA fentanyl had better analgesic effects at 4 h (mean difference [MD] in the visual analogue scale score, −0.75; 95% confidence interval [CI] [-1.16, −0.34]) and 8 h (MD, −0.93; 95% CI [-1.57, −0.28]) and yielded lower odds of developing nausea/vomiting (odds ratio [OR], 0.27; 95% CI [0.09, 0.80]) and sedation/drowsiness (OR, 0.22; 95% CI [0.11, 0.45]). However, PCEA fentanyl may be more likely to cause pruritus than IVPCA treatments. Interpretation: Considering the analgesic efficacy; opioid-induced nausea, vomiting, and sedation; and the well-being of breastfed infants, PCEA fentanyl may be the treatment of choice for post-caesarean section analgesia. Funding: The Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-111-27)

DYNC1H1 variants are associated with peripheral neuronal dysfunction and brain morphology abnormalities resulting in neurodevelopmental delay. However, few studies have focused on the association between DYNC1H1 variants and epilepsy. Herein, we report a case of drug-resistant focal epilepsy associated with a pathogenic variant of DYNC1H1. We further summarized the clinical, genetic, and neuroimaging characteristics of patients with DYNC1H1 variant–associated epilepsy from the relevant literature. This report expands the phenotypic spectrum of DYNC1H1-related disorder to include early-onset epilepsy, which is frequently associated with neurodevelopmental delay and intellectual disability, malformations of cortical development, and neuromuscular, ophthalmic, and orthopedic involvement.

In this study, we synthesize a hyaluronic acid-g-poly(N-isopropylacrylamide) (HPN) copolymer by grafting the amine-terminated poly(N-isopropylacrylamide) (PNIPAM-NH2) to hyaluronic acid (HA). The 5% PNIPAM-NH2 and HPN polymer solution is responsive to temperature changes with sol-to-gel phase transition temperatures around 32 °C. Compared with the PNIPAM-NH2 hydrogel, the HPN hydrogel shows higher water content and mechanical strength, as well as lower volume contraction, making it a better choice as a scaffold for chondrocyte delivery. From an in vitro cell culture, we see that cells can proliferate in an HPN hydrogel with full retention of cell viability and show the phenotypic morphology of chondrocytes. In the HPN hydrogel, chondrocytes demonstrate a differentiated phenotype with the upregulated expression of cartilage-specific genes and the enhanced secretion of extracellular matrix components, when compared with the monolayer culture on tissue culture polystyrene. In vivo studies confirm the ectopic cartilage formation when HPN was used as a cell delivery vehicle after implanting chondrocyte/HPN in nude mice subcutaneously, which is shown from a histological and gene expression analysis. Taken together, the HPN thermosensitive hydrogel will be a promising injectable scaffold with which to deliver chondrocytes in cartilage-tissue-engineering applications.

Abstract Background Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT. Methods We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3–6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage). Results Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (P interaction = 0.005) and UCHL1 (P interaction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03–4.08), T2 (OR, 2.08; 95% CI, 1.05–4.01), and T3 (OR, 3.94; 95% CI, 1.44–10.79) were independent predictors of death or disability at 90 days. Conclusion Among patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.

BackgroundDespite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19.MethodsHospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables.ResultsFour out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34–126.75) to 227.50 (185.25–237.50) and then 349.56 (293.03–367.92) within 7 days after hUC-MSC infusion (P < 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50–237.61]; day 3: 100.00 [72.00–232.68]; day 7: 250.00 [71.00–251.43], P = 0.923).ConclusionTransplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.

Abstract This pilot, randomized, open-label controlled study compared the basal–bolus regimens of insulin glargine (IG) and neutral protamine Hagedorn (NPH) insulin in stroke patients with hyperglycemia receiving intensive care. The study recruited acute stroke patients requiring intensive care within 72 h (h) of onset and had blood glucose > 200 mg/dL. 50 patients received IG (n = 26) or NPH (n = 24) with added short-acting prandial regular insulin over a 72-h period. The primary end point was the percentage of glucose within 80–180 mg/dL assessed through continuous glucose monitoring. The baseline characteristics were comparable, except the IG had higher glucose pre-randomization than the NPH (290.69 ± 82.31 vs. 246.04 ± 41.76 mg/dL, P = 0.021). The percentage of time with glucose between 80 and 180 mg/dL was 45.88 ± 27.04% in the IG and 53.56 ± 22.89% in the NPH (P = 0.341) and the percentage of glucose reduction was 31.47 ± 17.52% in the IG and 27.28 ± 14.56% in the NPH (P = 0.374). The percentage of time with glucose

An effective therapeutic strategy to treat tendon or ligament injury continues to be a clinical challenge due to the limited natural healing capacity of these tissues. Furthermore, the repaired tendons or ligaments usually possess inferior mechanical properties and impaired functions. Tissue engineering can restore the physiological functions of tissues using biomaterials, cells, and suitable biochemical signals. It has produced encouraging clinical outcomes, forming tendon or ligament-like tissues with similar compositional, structural, and functional attributes to the native tissues. This paper starts by reviewing tendon/ligament structure and healing mechanisms, followed by describing the bioactive nanostructured scaffolds used in tendon and ligament tissue engineering, with emphasis on electrospun fibrous scaffolds. The natural and synthetic polymers for scaffold preparation, as well as the biological and physical cues offered by incorporating growth factors in the scaffolds or by dynamic cyclic stretching of the scaffolds, are also covered. It is expected to present a comprehensive clinical, biological, and biomaterial insight into advanced tissue engineering-based therapeutics for tendon and ligament repair.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Abstract Objective To develop an easily applicable screening score to guide NOTCH3 p.R544C genetic testing for patients who presented with acute ischemic cerebrovascular events in Taiwan. Methods 1734 patients who presented with ischemic cerebrovascular events were enrolled from the Formosa Stroke Genetic Consortium stroke registry and were screened for the NOTCH3 p.R544C mutation. Clinical and MRI characteristics of NOTCH3 p.R544C mutation carriers (n = 36) and a subset of noncarriers (n = 673) were tested in a logistic regression model to identify key features associated with the NOTCH3 p.R544C carrier status. Variables and their odds ratios in the regression model were used to develop the R544C screening score to predict positive NOTCH3 p.R544C test results. Results We constructed the R544C screening score using five clinical and imaging characteristics, including stroke onset before 50 years of age, the small vessel occlusion subtype, a family history of stroke/TIA in siblings, external capsule involvement, and advanced deep white matter hyperintensity. The area under the ROC curve of the screening score was 0.867 (95% CI = 0.810‐0.924). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 0.75, 0.88, 0.13, 0.99, and 0.88, respectively, for a cutoff score of 5 points. In addition, the R544C screening score was validated in another cohort composed of 235 stroke patients with comparable performance (area under the ROC curve = 0.957, 95% CI = 0.916‐0.997). Interpretations For Taiwanese patients presenting with acute ischemic cerebrovascular events, the R544C screening score is easily applicable and can efficiently select high‐risk patients for NOTCH3 p.R544C mutation test.

Abstract Background Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. Methods Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. Results Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19–3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21–6.53) predicted incident ICH. Conclusions In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.

Background Simultaneous multivessel occlusions (MVOs) are a rare condition, which may be encountered during endovascular thrombectomy (EVT) for acute ischemic stroke. This study aimed to investigate the prevalence, associated factors, and outcome of patients with acute ischemic stroke and MVO who underwent EVT. Methods Consecutive patients with acute ischemic stroke who received EVT between September 2014 and April 2021 were included. Acute MVO was defined as simultaneous occlusions of ≥2 intracranial or extracranial major vessels in either bilateral anterior circulation or anterior plus posterior circulation. Patients’ baseline characteristics and outcome of MVO were analyzed. Results Of 602 patients with acute ischemic stroke (mean age, 71±13 years; male, 53.1%) who received EVT, 11 patients (1.8%) had acute MVO. The involved vessels included bilateral internal carotid arteries in 3, bilateral middle cerebral arteries in 4, vertebral artery and distal middle cerebral artery in 1, and internal carotid artery and distal posterior cerebral artery in 3 patients. Preadmission dependence (modified Rankin scale score >2), higher initial stroke severity, and posterior cerebral artery occlusion were more frequently found in MVO. The cause of MVO included large vessel atherosclerosis in 4, cardioembolic in 4, cancer‐related hypercoagulability in 2, and postpartum in 1 patient. Several patients had received simultaneous multitargeted EVT, but only 4 of them achieved optimal reperfusion in both vessels. Compared with patients without MVO, those with MVO had higher mortality (adjusted odds ratio, 6.75; 95% CI, 1.93–23.6) and poor functional outcome (common odds ratio for 1‐point improvement at modified Rankin scale, 0.14, 95% CI, 0.05–0.45) at 90 days. Conclusion Acute simultaneous MVO in patients who underwent EVT is a rare yet devastating condition. Multitarget mechanical thrombectomy to achieve reperfusion is challenging but still possible.

Summary: Background: Hearing loss is a common morbidity that requires a hearing device to improve quality of life and prevent sequelae, such as dementia, depression falls, and cardiovascular disease. However, conventional hearing aids have some limitations, including poor accessibility and unaffordability. Consequently, personal sound amplification products (PSAPs) are considered a potential first-line alternative remedy for patients with hearing loss. The main objective of this study was to compare the efficacy of PSAPs and conventional hearing aids regarding hearing benefits in patients with hearing loss. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to January 12, 2022. Studies including randomised, controlled trials; nonrandomised, controlled trials; or observational studies comparing PSAPs and hearing aids with regard to hearing gain performance (e.g., speech intelligence) were considered eligible. The review was registered prospectively on PROSPERO (CRD42021267187). Findings: Of 599 records identified in the preliminary search, five studies were included in the review and meta-analysis. A total of 124 patients were divided into the PSAP group and the conventional hearing aid group. Five studies including seven groups compared differences for speech intelligence in the signal-noise ratio (SNR) on the hearing in noise test (HINT) between PSAPs and conventional hearing aids. The pooled results showed nonsignificant differences in speech intelligence (SMD, 0.14; 95% CI, -0.19 to 0.47; P = .41; I2=65%), sound quality (SMD, -0.37; 95% CI, -0.87 to 0.13; P = .15; I2=77%) and listening effort (SMD 0.02; 95% CI, -0.24 to 0.29; P = .86; I2=32%). Nonsignificant results were also observed in subsequent analyses after excluding patients with moderately severe hearing loss. Complete sensitivity analyses with all of the possible combinations suggested nonsignificant results in most of the comparisons between PSAPs and conventional hearing aids. Interpretation: PSAPs are potentially beneficial as conventional hearing aids are in patients with hearing loss. The different features among PSAPs should be considered for patients indicated for hearing devices. Funding: This work was supported by grants from Ministry of Science and Technology (MOST-10-2622-8-075-001) and Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST111-G6-11-2 and VGHUST111c-140).

Long patient waiting time is one of the major problems in the healthcare system and it would decrease patient satisfaction. Previous studies usually investigated how to improve the treatment flow in order to reduce patient waiting time or length of stay. The studies on blood collection counters have received less attention. Therefore, the objective of this study is to reduce the patient waiting time at outpatient clinics for metabolism and nephrology outpatients. A discrete-event simulation is used to analyze the four different strategies for blood collection counter resource allocation. Through analyzing four different strategic settings, the experimental results revealed that the maximum number of patients waiting before the outpatient clinics was reduced from 41 to 33 (20%); the maximum patient waiti-ng time at the outpatient clinics was decreased from 201.6 minutes to 83 minutes (59%). In this study, we found that adjusting the settings of blood collection counters would be beneficial. Assigning one exclusive blood collection counter from 8 to 10 am is the most suitable option with the least impact on the operational process for hospital staff. The results provide managerial insight regarding the cost-effective strategy selection for the hospital operational strategy.

BackgroundThe efficacy and safety of intravenous alteplase administered 3–4.5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown.Patients and MethodsThe current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 3–4.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion.ResultsOverall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27–1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80–1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21–2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase.ConclusionIn the 3–4.5 h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in NOTCH3, is the most common cause of hereditary cerebral small vessel disease. Whether it will involve systemic vasculopathy such as retinal vessel remains unknown. Optical coherence tomography angiography (OCT-A) is a noninvasive technique for visualising retinal blood flow. We analysed vessel density and retinal thickness in patients with CADASIL and investigated their correlations with disease severity.MethodsThis prospective study enrolled 35 patients with CADASIL (59 eyes) and 35 healthy controls (54 eyes). OCT-A was used to measure the vessel density of the macular region and the thickness of retinal layers. Patients with CADASIL were divided into stroke (n = 20) and nonstroke (n = 15) subgroups and underwent cognition and gait speed evaluation. Neuroimaging markers of cortical thickness, white matter hyperintensity, lacunae, and cerebral microbleeds were examined through brain magnetic resonance imaging.ResultsThe OCT-A parameters, including vessel density, were comparable between the patients with CADASIL and the controls. In patients with CADASIL, vessel density in the superficial retinal plexus in the macula as was inner retinal thickness was significantly lower in the stroke than the nonstroke subgroup. Macular vessel density and inner retinal thickness were positively correlated with gait speed, while negatively correlated with number of lacunae.ConclusionsOCT-A is potentially a useful tool for evaluating disease severity, ischaemic burden, and neurodegeneration in patients with advanced CADASIL.

Background Conventional prognostic scores usually require predefined clinical variables to predict outcome. The advancement of natural language processing has made it feasible to derive meaning from unstructured data. We aimed to test whether using unstructured text in electronic health records can improve the prediction of functional outcome after acute ischemic stroke. Methods and Results Patients hospitalized for acute ischemic stroke were identified from 2 hospital stroke registries (3847 and 2668 patients, respectively). Prediction models developed using the first cohort were externally validated using the second cohort, and vice versa. Free text in the history of present illness and computed tomography reports was used to build machine learning models using natural language processing to predict poor functional outcome at 90 days poststroke. Four conventional prognostic models were used as baseline models. The area under the receiver operating characteristic curves of the model using history of present illness in the internal and external validation sets were 0.820 and 0.792, respectively, which were comparable to the National Institutes of Health Stroke Scale score (0.811 and 0.807). The model using computed tomography reports achieved area under the receiver operating characteristic curves of 0.758 and 0.658. Adding information from clinical text significantly improved the predictive performance of each baseline model in terms of area under the receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement indices (all P

BackgroundHearing loss is one of the most common disabilities worldwide and affects both individual and public health. Pure tone audiometry (PTA) is the gold standard for hearing assessment, but it is often not available in many settings, given its high cost and demand for human resources. Smartphone-based audiometry may be equally effective and can improve access to adequate hearing evaluations. ObjectiveThe aim of this systematic review is to synthesize the current evidence of the role of smartphone-based audiometry in hearing assessments and further explore the factors that influence its diagnostic accuracy. MethodsFive databases—PubMed, Embase, Cochrane Library, Web of Science, and Scopus—were queried to identify original studies that examined the diagnostic accuracy of hearing loss measurement using smartphone-based devices with conventional PTA as a reference test. A bivariate random-effects meta-analysis was performed to estimate the pooled sensitivity and specificity. The factors associated with diagnostic accuracy were identified using a bivariate meta-regression model. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. ResultsIn all, 25 studies with a total of 4470 patients were included in the meta-analysis. The overall sensitivity, specificity, and area under the receiver operating characteristic curve for smartphone-based audiometry were 89% (95% CI 83%-93%), 93% (95% CI 87%-97%), and 0.96 (95% CI 0.93-0.97), respectively; the corresponding values for the smartphone-based speech recognition test were 91% (95% CI 86%-94%), 88% (95% CI 75%-94%), and 0.93 (95% CI 0.90-0.95), respectively. Meta-regression analysis revealed that patient age, equipment used, and the presence of soundproof booths were significantly related to diagnostic accuracy. ConclusionsWe have presented comprehensive evidence regarding the effectiveness of smartphone-based tests in diagnosing hearing loss. Smartphone-based audiometry may serve as an accurate and accessible approach to hearing evaluations, especially in settings where conventional PTA is unavailable.

Abstract Background Bone regeneration is a crucial and challenging issue in clinical practice. Bone tissue engineering (BTE) with an optimal cell source may provide an ideal strategy for the reconstruction of bone defects. This study examined whether induced pluripotent stem cells (iPSCs) derived from adipose-derived stem cells (ASCs) could act as an osteogenic substitute and whether these ASC-iPSCs yield more new bone formation than ASCs in hydrogel scaffolds. Methods ASC-iPSCs were reprogrammed from ASCs through a retroviral system. ASCs were harvested and isolated from adipose tissue of humans. An aliquot of cell suspension (1 × 106 cells/mL) was seeded directly onto the nHAP-gelatin cryogel scaffolds. Nude mice back implantation of cell-seeded scaffolds was designed for in vivo comparison of osteogenic potentials between ASCs and ASC-iPSCs. Samples were harvested 4 and 8 weeks after implantation for further analysis based on histology and RT-PCR. Results ASC-iPSCs were successfully obtained from human adipose-derived stem cells. PCR results also showed that specific genes of iPSCs with the ability to cause the differentiation of cells into the three germ layers were expressed. In our in vivo experiments, iPSCs were subcutaneously injected into nude mice to induce teratoma formation. The morphology of the three germ layers was confirmed by histological staining. ASC is an essential cell source for BTE with benefits of high volume and less-invasive acquisition. With additional transforming Yamanaka factors, ASC-iPSCs showed higher osteogenic differentiation and elevated expression of collagen type I (Col I), osteocalcin (OCN), alkaline phosphate (ALP), and runt-related transcription factor 2 (RunX-2). Conclusions This report suggests that ASC-iPSCs could be a superior cell source in BTE with better osteogenic differentiation efficacy for future clinical applications.

Hyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH) FMS to provide a milieu for 3D culture and delivery of ASCs. The prepared FMS shows adequate cytocompatibility and is suitable for attachment and growth of ASCs. Compared with PG, the PGH offers an enhanced proliferation rate of ASCs, shows higher cell viability, and better maintains an ASC-like phenotype during in vitro cell culture. The ASCs in PGH also show upregulated expression of genes associated with angiogenesis and wound healing. From a rat full-thickness wound healing model, a wound treated with PGH/ASCs can accelerate the wound closure rate compared with wounds treated with PGH, alginate wound dressing, and gauze. From H&E and Masson’s trichrome staining, the PGH/ASC treatment can promote wound healing by increasing the epithelialization rate and forming well-organized dermis. This is supported by immunohistochemical staining of macrophages and α-smooth muscle actin, where early recruitment of macrophages, macrophage polarization, and angiogenesis was found due to the delivered ASCs. The content of type III collagen is also higher than type I collagen within the newly formed skin tissue, implying scarless wound healing. Taken together, using PGH FMS as a topical wound dressing material for the therapeutic delivery of ASCs, a wound treated with PGH/ASCs was shown to accelerate wound healing significantly in rats, through modulating immunoreaction, promoting angiogenesis, and reducing scar formation at the wound sites.

Introduction: Endovascular therapy (EVT) is established as first-line treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. For basilar artery occlusion, recent randomized clinical trials demonstrated not only equipoise but also advantages for EVT under particular circumstances. It remains unclear whether EVT offers an advantage over best medical management (BMM) including thrombolysis (IVT) in isolated occlusion of the proximal posterior cerebral artery (PCAO).Methods: Patients with AIS due to PCAO proven by CT or MR angiography were retrospectively identified from local databases at four comprehensive stroke centers in Germany, USA, and Taiwan between 2012 and 2020. Demographic and clinical data were collected, and imaging characteristics including pretherapeutic, interventional, and follow-up imaging were reviewed locally at each center. Patients were grouped according to therapy, i.e., BMM including IVT alone vs. BMM and EVT. Efficacy endpoints were early neurological improvement (ENI) after 24 h or at discharge, good outcome (modified Rankin scale 0–2) after 3 months, as well as hemorrhagic complications and in-house deaths as safety endpoints.Results: We included 130 patients of whom 23 (17.7%) received EVT. EVT patients had more proximal occlusions (69.9 vs. 43%, p = 0.023) and had a better premorbid function [premorbid mRS, 0 (0–4) vs. 1 (0–3), p < 0.01] when compared to BMM patients. IVT showed a trend toward being less performed in the EVT group (21.7 vs. 41.1%, p = 0.1), while other baseline parameters were balanced. Successful reperfusion was achieved in 52% of EVT patients. ENI was more frequent in the EVT group (61 vs. 35.5%, p = 0.034). Good outcome at 90 days and safety endpoints did not differ. In a bivariate analysis, ENI was independently predicted by the use of EVT (OR, 2.76; CI, 1.055–7.04) and the baseline National Institutes of Health Stroke Scale (NIHSS) (OR, 1.082; CI, 1.027–1.141 per point increase).Discussion: EVT in isolated PCAO appears safe and feasible. Positive effects on clinical outcome are primarily on ENI but also depend on the initial stroke severity. Further prospective or randomized studies are needed to better describe the potential long-term clinical benefits of EVT for PCAO as compared with best medical management.

Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 μg kg−1) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, −3.64; confidence interval (CI), −5.47 to −1.81 and after endotracheal intubation (MD, −9.71; CI, −11.91 to −7.51). Remifentanil (1 μg kg−1) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 μg kg−1) should be considered the drug of choice in the circumstances where increased IOP is a great concern.

Acute low-tone hearing loss (ALHL) is a common clinical disease and was first proposed by Abe in 1981 as sensorineural hearing loss confined to low frequencies. The best strategy for initiating medication is still unclear, as the superiority of steroids and diuretics is still debated, and combination therapy might yield additional benefits. However, no study regarding combination therapy has been published. The objective of this study was to evaluate the efficacy of steroid therapy versus combination therapy of diuretics with steroids by conducting a systematic review with a meta-analysis and trial sequential analysis (TSA). Studies enrolling patients with a diagnosis of acute low-tone hearing loss were considered eligible. After searching the PubMed, Cochrane Library, Embase, Scopus and Web of Science databases from inception to 31 December 2021, five studies including 433 patients were enrolled. Overall, the comparison between combination therapy with steroids and diuretics and single-modality treatment with steroids (OR, 1.15; 95% CI, 0.51 to 2.59; p = 0.74; I2 = 34%) and the comparison between combination therapy and treatment with diuretics alone (OR, 1.73; 95% CI, 0.93 to 3.23; p = 0.09; I2 = 5%) showed that combination therapy did not confer significant benefits when compared to single-modality treatments. A trial sequential analysis (TSA) showed conclusive nonsignificant results of the comparison between the combination of steroids and diuretics and a single-modality treatment. In conclusion, we reported that the combination of steroids and diuretics did not yield significant benefits when compared to single-modality treatment with steroids or diuretics. We suggest that treatment should be initiated with steroids or diuretics alone to avoid potential adverse effects.

Electrooculography (EOG) is considered as the most stable physiological signal in the development of human-computer interface (HCI) for detecting eye-movement variations. EOG signal classification has gained more traction in recent years to overcome physical inconvenience in paralyzed patients. In this paper, a robust classification technique, such as eight directional movements is investigated by introducing a concept of buffer along with a variation of the slope to avoid misclassification effects in EOG signals. Blinking detection becomes complicated when the magnitude of the signals are considered. Hence, a correction technique is introduced to avoid misclassification for oblique eye movements. Meanwhile, a case study has been considered to apply these correction techniques to HCI baseball game to learn eye-movements.

Traditional otoscopy has some limitations, including poor visualization and inadequate time for evaluation in suboptimal environments. Smartphone-enabled otoscopy may improve examination quality and serve as a potential diagnostic tool for middle ear diseases using a telemedicine approach. The main objectives are to compare the correctness of smartphone-enabled otoscopy and traditional otoscopy and to evaluate the diagnostic confidence of the examiner via meta-analysis. From inception through 20 January 2022, the Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus databases were searched. Studies comparing smartphone-enabled otoscopy with traditional otoscopy regarding the outcome of interest were eligible. The relative risk (RR) for the rate of correctness in diagnosing ear conditions and the standardized mean difference (SMD) in diagnostic confidence were extracted. Sensitivity analysis and trial sequential analyses (TSAs) were conducted to further examine the pooled results. Study quality was evaluated by using the revised Cochrane risk of bias tool 2. Consequently, a total of 1840 examinees were divided into the smartphone-enabled otoscopy group and the traditional otoscopy group. Overall, the pooled result showed that smartphone-enabled otoscopy was associated with higher correctness than traditional otoscopy (RR, 1.26; 95% CI, 1.06 to 1.51; p = 0.01; I2 = 70.0%). Consistently significant associations were also observed in the analysis after excluding the simulation study (RR, 1.10; 95% CI, 1.00 to 1.21; p = 0.04; I2 = 0%) and normal ear conditions (RR, 1.18; 95% CI, 1.01 to 1.40; p = 0.04; I2 = 65.0%). For the confidence of examiners using both otoscopy methods, the pooled result was nonsignificant between the smartphone-enabled otoscopy and traditional otoscopy groups (SMD, 0.08; 95% CI, -0.24 to 0.40; p = 0.61; I2 = 16.3%). In conclusion, smartphone-enabled otoscopy was associated with a higher rate of correctness in the detection of middle ear diseases, and in patients with otologic complaints, the use of smartphone-enabled otoscopy may be considered. More large-scale studies should be performed to consolidate the results.

Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (111In/177Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 μm for TARE. The radiochemical yields of 111In/177Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the 111In/177Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administration. Except for liver accumulation, radioactivity in each normal organ was less than 1% of the injected radioactivity (%IA) at 72 h after injection. At 10 days after injection of 177Lu-DTPA-CMS (18.6 ± 1.3 MBq), the size of the hepatoma was significantly reduced by around 81%, while that of the rats in the control group continued to grow. This study demonstrated the effectiveness of 177Lu-DTPA-CMS in the treatment of N1-S1 hepatoma. 111In/177Lu-DTPA-CMS have the potential to be a superior theranostic pair for the treatment of clinical hepatoma.

Semiconductors are enabling technologies that drive today’s information economy by producing a broad spectrum of microelectronic consumer products including computers, flat-panel displays, sensors, storage devices, and lighting devices. Manufacturing of these semiconductor devices and products is capital and resources intensive and typically operates with either a vertically integrated manufacturing mode or with a cluster of supply-chain partnering companies in the vicinity of each other. Our research group has previously reported the water recycling and reuse efficiencies of “fabs” in the Science Parks in Taiwan (Lin et al., Res. Cons. Recycl. 2015), which exemplify this unique cluster of tech-manufacturing fabs demanding intensive supply of water and energy. We extend our discussion by summarizing the status of water consumption of major semiconductor and optomicroelectronic plants, and the industry’s collective and individual water reuse goals. Though the geographical location of fabs plays an important part of the water reuse efficiency, the industry generally displays a strong urgency to use water responsibly to maintain corporates’ competitiveness and to effectively manage the risks associated with water shortage. Additionally, the examination of water and energy expenditures of semiconductor fabs indicated a close water-energy relationship in the compartment of ultrapure water production process. The energy needed to treat, recycle and reuse spent water is secondary as compared to the energy demand for manufacturing processes. Using the industrial cluster in Taiwan as an example to illustrate the potential of improve water reuse through collaborative schemes, we conducted a survey-based study to assess how the industry perceived the proposed “inter-plants” and “inter-park” schemes designed to create a reclaimed water trading mechanism in place of the existing “in-plant” practice of water reclamation. Respondents showed an overall positive perception to such schemes on the basis of reducing water and energy demands in a cost-effective manner. The cost of water supply was a dominant factor in the perceived extent of benefits. Keywords: Water reuse, Water reclamation, Industrial water use, Semiconductors, Wafer fabrication, Fabs, Green manufacturing

Summary: Background: Zygoma fracture is of clinical importance because malar prominence plays an essential role in facial appearance. Traditionally, most maxillofacial surgeons perform osteosynthesis with titanium plates and screws for rigid fixation. However, this procedure has certain disadvantages that include the possibility of implant exposure, palpability or loosening of the screws, painful irritation, temperature sensitization, and radiographic artifacts. In this study, we compared the function and satisfaction outcome between Bonamates® bioabsorbable implant and Leibinger titanium implant. Method: Consecutively 53 patients with isolated unilateral zygomatic fracture that were treated with the Bonamates® bioabsorbable plate system, n = 53 were compared to patients with the titanium plate system, n = 55 in the period between 2009 and 2013. All patients were followed-up at least 6 months. Preoperative and postoperative facial computed tomography (CT) scans were performed and scored from 0 to 2 in the 5 areas of zygoma. A score of 2 indicated the most severely displaced fracture in one of the areas. A visual analogue scale ranging from 0 to 10 was used to assess the postoperative aesthetic and functional satisfactions. Result: The mean ages of the patients in the bioabsorbable and titanium plate groups were 33 years and 30 years, respectively. The male to female ratios were 1.2:1 (bioabsorbable plate group) and 1.1:1 (titanium plate group). The average preoperative CT scan scores of the bioabsorbable and titanium plate groups were 5.7 and 5.1, respectively. The postoperative CT scan scores of the bioabsorbable and titanium plate groups were 1.3 and 1.1, respectively. The implant cost of the bioabsorbable group was approximately 6-fold higher than that of the titanium plate group. The complication rate was similar in both groups and included complications such as palpable implant, skin irritation, and hypersensitive cheek. The patients in both groups attained similar mouth-opening function and a satisfactory score at 6 months after operation. Conclusion: This study revealed that the bioabsorbable plate outcome was similar to the titanium plate outcome for patients with isolated unilateral zygomatic fracture. The bioabsorbable implant system provides another option for internal fixation devices in the treatment of zygomatic fractures and avoids implant removal surgery; however, the implant cost of bioabsorbable plates is higher than that of titanium plates in Taiwan. Keywords: Bioabsorbable plate, Titanium plate, Comparison, Zygoma fracture

The risk of water shortage has been posing as a threat to water demanding industries in Taiwan, including the high-tech industries where ultrapure water is needed for the production of microchips. Such risks are especially unpredictable in the age of climate change, where more frequent extreme climate events such as prolonged droughts have sent these industries scrambling for securing water supply at a very high cost. The national policy also mandates strict water recycling standards for these high-tech plants, while the risk of water supply shortage also forces the industry to be water-conscious. However, most plants set their water recycling strategies based on experience or “rules of thumb” practices, without implementing optimization tools that can help making decisions in a more scientific approach. In this study we applied linear programming technique to optimize the water recovery path for a microchip assembly plant. A water balance diagram was formulated and completed to determine the existing water recycling performance, and the data was converted to a water flow network. The water flow network was then derived with a mathematical model to formulate a linear optimization problem. The proposed linear programming model is composed of mass balance constraints, unit specification constraints, capacity constraints as well as water quality constraints (discharge limits). The linear programming method was effectively appplied to improve the efficiency of water reuse. With the installation of the regeneration units, an increase of ∼40.1% in the volume of reused water was predicted. The results from water cost structure also indicated that, at higher water tariff, water reuses through reclaiming and generating spent effluents can alleviate the overall water consumption costs. Keywords: Water reclamation, Water regeneration, Water network, Semiconductor, Fabs, Water resource management