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Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS). DAD is independently correlated with higher mortality compared with the absence of DAD. Traction bronchiectasis in areas of ground-glass opacity or consolidation is associated with the late fibroproliferative or fibrotic phase of DAD. This study examined whether the 60-day mortality related to DAD could be predicted using high-resolution computed tomography (HRCT) findings and HRCT scores. A total of 34 patients with DAD who received HRCT within 7 days of ARDS diagnosis were enrolled; they were divided into a 60-day survival group and a nonsurvival group, with 17 patients in each group. Univariate and multivariate binary regression analyses and the receiver operating characteristic curve revealed that only the total percentage of the area with traction bronchiectasis or bronchiolectasis was an independent predictor of 60-day mortality (odds ratio, 1.067; 95% confidence interval (CI), 1.011–1.126) and had favorable predictive performance (area under the curve (AUC): 0.784; 95% CI, 0.621–0.946; cutoff, 21.7). Physiological variables, including age, days from ARDS to HRCT, the sequential organ failure assessment (SOFA) score, the PaO2/fraction of inspired oxygen (FiO2) ratio, dynamic driving pressure, and dynamic mechanical power, were not discriminative between 60-day survival and nonsurvival. In conclusion, the extent of fibroproliferation on HRCT in early ARDS, presented as the total percentage of area with bronchiectasis or bronchiolectasis, is an independent positive predictor with a favorable predictive ability for the 60-day mortality of DAD.

Background:Precisely predicting coronary artery aneurysms (CAAs) remains a clinical challenge. We aimed to investigate whether coronary dimensions adjusted for body surface area (Z scores) on baseline echocardiography and clinical variables before primary treatment could predict the presence of late CAAs.Methods:We conducted a retrospective study including children hospitalized for Kawasaki disease and received intravenous immunoglobulin within 10 days of illness. We defined late CAAs as a maximum Z score (Zmax) ≥2.5 of the left main, right, or left anterior descending coronary artery at 11–60 days of illness. Associations between late CAAs and clinical parameters and baseline maximum Z scores were analyzed.Results:Among the 314 included children, 31 (9.9%) had late CAAs. Male, higher C-reactive protein, and higher baseline Zmax were risk factors of late CAAs. Late CAAs were significantly associated with baseline Zmax ≥2.0 vs. P< 0.001). The odds ratio for late CAAs among the patients with baseline Zmax ≥2.0 vs. P< 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of baseline Zmax ≥2.0 for the presence of later CAAs were 80.6, 81.6, 32.5, and 97.5%, respectively.Conclusions:Findings from this study suggest that Zmax ≥2.0 of coronary arteries on baseline echocardiography may be used to predict children at a high risk of late CAAs and allow for targeted early intensification therapy.

This study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA).We reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0-18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs.A total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0-1 month (OR, 6.52; 95% CI 1.09-38.92; P = 0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004-6.08; P = 0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P 0.001).S. aureus is the leading pathogen of culture-proven SSTIs in hospitalized children with MRSA accounting for more than half. Determining the optimal empirical antibiotics in CA-SSTIs may rely on the patient's age, disease severity, and local epidemiologic data.

Purpose The vast majority of research on traditional leadership focuses on effective and positive leadership behavior. However, scholars have begun to pay attention to the impact of negative leadership behavior on employees and the organization. Hence, the main purpose is to examine the effects of abusive supervision. While the literature does not examine the time future orientation of the effects of abusive supervision, the purpose of this paper is to fill up this gap and examine the moderating role of future orientation. Design/methodology/approach A total of 584 valid questionnaires were collected from respondents aged between 21 and 30 years old and analyzed using the hierarchical regression and structural equation modeling method. Findings The main results show that abusive supervision positively affects counterproductive work behavior and future orientation positively moderates both the relationship between abusive supervision and originality behavior and the relationship between abusive supervision and organizational citizenship behavior (OCB). Originality/value This study demonstrates the moderating roles of future orientation in the effects of abusive supervision, and thus deepens the understanding of the moderating effect. It departs from the prior works and presents a more detailed examination examines the distinct dimensions of personality traits. It makes three main theoretical contributions. First, it introduces uncertainty management theory as a means to interpret the effects of abusive supervision. Second, it contributes to the literature on abusive supervision. Third, it does not lead to discovery as an OCB and originality, conclusions which differ from the results suggested in past literature.

To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis.We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, laboratory, treatment, and outcome data were compared according to site(s) of infection.Involvement of a long bone of the lower extremity was present in 36.6% of the children, followed by foot bone (23.9%), rib or sternum (15.5%), upper extremity long bone (9.9%), hand bone (7%), multiple bones (4.2%), and vertebrae (2.8%). Children with lower extremity long bone involvement had a longer interval from receipt of BCG vaccine to presentation (median, 16.0 months; P = .02), and those with foot bone infection had higher rates of swelling (94.1%; P = .02) and local tenderness (76.5%; P = .004). Surgical intervention was performed in 70 children, with no significant difference in the number of procedures by site (median, 1.0 procedure per patient). Among the 70 children who received antimicrobial therapy, those with vertebral and multifocal infections had a longer duration of treatment (P .001) and/or second-line antituberculosis medications (P = .002). Three children with vertebral and multifocal infections had major sequelae with kyphosis or leg length discrepancy. Outcomes were good for children with involvement of the ribs, sternum, and peripheral bones without multifocal involvement. The average time for functional recovery was 6.2 ± 3.9 months.Children with BCG osteitis/osteomyelitis in different bones had distinct presentations and outcomes. Pediatricians should consider BCG bone infection in young vaccinated children with insidious onset of signs and symptoms, and consider affected site(s) in the management plan.

Background Mutations in PKD1 or PKD2 gene lead to autosomal dominant polycystic kidney disease (ADPKD). The mechanism of ADPKD progression and its link to increased cardiovascular mortality is still elusive. Methods We differentiated ADPKD patient induced pluripotent stem cells (iPSCs) to cardiomyocytes (CMs). The electrophysiological properties at the cellular level were analyzed by calcium imaging and whole cell patch clamping. Findings The ADPKD patient iPSC-CMs had decreased sarcoplasmic reticulum calcium content compared with Control-CMs. Spontaneous action potential of the PKD2 mutation line-derived CMs demonstrated slower beating rate and longer action potential duration. The PKD1 mutation line-derived CMs showed a comparable dose-dependent shortening of phase II repolarization with the Control-CMs, but a significant increase in beating frequency in response to L-type calcium channel blocker. The PKD1-mutant iPSC-CMs also showed a relatively unstable baseline as a greater percentage of cells exhibited delayed afterdepolarizations (DADs). Both the ADPKD patient iPSC-CMs showed more β-adrenergic agonist-elicited DADs compared with Control-CMs. Interpretation Characterization of ADPKD patient iPSC-CMs provides new insights into the increased clinical risk of arrhythmias, and the results enable disease modeling and drug screening for cardiac manifestations of ADPKD. Fund Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Technology Supporting Platform Axis Scheme, Thematic Research Program and Summit Research Program, and Kaohsiung Medical University Hospital, Taiwan.

Background: Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM. Methods: Middle ear fluid samples from children

Background: Mutations in PKD1 or PKD2 gene lead to autosomal dominant polycystic kidney disease (ADPKD). The mechanism of ADPKD progression and its link to increased cardiovascular mortality is still elusive. Methods: We differentiated ADPKD patient induced pluripotent stem cells (iPSCs) to cardiomyocytes (CMs). The electrophysiological properties at the cellular level were analyzed by calcium imaging and whole cell patch clamping. Findings: The ADPKD patient iPSC-CMs had decreased sarcoplasmic reticulum calcium content compared with Control-CMs. Spontaneous action potential of the PKD2 mutation line-derived CMs demonstrated slower beating rate and longer action potential duration. The PKD1 mutation line-derived CMs showed a comparable dose-dependent shortening of phase II repolarization with the Control-CMs, but a significant increase in beating frequency in response to L-type calcium channel blocker. The PKD1-mutant iPSC-CMs also showed a relatively unstable baseline as a greater percentage of cells exhibited delayed afterdepolarizations (DADs). Both the ADPKD patient iPSC-CMs showed more β-adrenergic agonist-elicited DADs compared with Control-CMs. Interpretation: Characterization of ADPKD patient iPSC-CMs provides new insights into the increased clinical risk of arrhythmias, and the results enable disease modeling and drug screening for cardiac manifestations of ADPKD. Fund: Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Technology Supporting Platform Axis Scheme, Thematic Research Program and Summit Research Program, and Kaohsiung Medical University Hospital, Taiwan. Keywords: Human iPS cell, Autosomal dominant polycystic kidney disease, Cardiomyocyte, Arrhythmia

To develop a zebrafish cataract model for screening potential anti-cataract compounds.Living zebrafish were anesthetized and exposed to ultraviolet-C (UV-C) irradiation at a dosage of 3250 mJ/cm2/d until they developed severe cataracts. These cataracts were graded based on photographs analyzed with ImageQuant TL version 7.0. Fish with severe cataracts were used to evaluate a range of compounds for cataract treatment, including the previously demonstrated hit compound lanosterol. For the initial evaluation, fish were divided into four groups: no treatment, balanced salt solution, β-cyclodextrin (β-CD), and lanosterol dissolved in β-CD. The treatments were performed for 10 days, and the clarity of lenses was evaluated. To assess the persistence of treatment, fish were treated with β-CD and lanosterol dissolved in β-CD for seven consecutive days followed by monitoring for three days without treatment.The average time for zebrafish to develop severe cataracts using the present UV-C irradiation protocol was 7.8 days (range 4-15 days). Both study designs required only another 10 days to determine the effect of hit compounds. The total experimental period could be completed within one month, and the entire experiment was economical.We could assay a large number of hit compounds at a reasonable cost and within a short time using this newly developed zebrafish cataract model. These assays may allow development of an efficient platform for screening potential anti-cataract compounds.The results may facilitate the development of ani-cataract medication for humans after further experiments and investigations.

In this study, we establish a population-based human induced pluripotent stem cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 1,000 healthy donors and screening for high-frequency human leukocyte antigen (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the population. These "super donors" are also expected to represent at least 477,611,135 of the global population. By differentiating these representative hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput toxicity screen. To validate hit compounds, we demonstrate dose-dependent toxicity of the hit compounds and assess functional modulation. We also show reproducible in vivo drug toxicity results using mouse models with select hit compounds. This study shows the feasibility of using a population-based hiPSC drug screening platform to assess cytotoxicity, which can be used as an innovative tool to study inter-population differences in drug toxicity and adverse drug reactions in drug discovery applications.

ALDH2 gene is coded for the aldehyde dehydrogenase (ALDH), which is an enzyme involved in alcohol metabolism. Compared to normal aldehyde dehydrogenases, a homozygous point mutation on exon 12 from G to A significantly reduces its efficiency. In this study, we have reported the generation of IBMS-iPSC-021-04, IBMS-iPSC-022-01, and IBMS-iPSC-023-03 as induced pluripotent stem cell (iPSC) lines carrying the homozygous form of ALDH2 with the rs671 genetic polymorphism (E487K mutation). These cell lines were characterized in terms of pluripotency and differentiation potential. They serve as useful platforms to study alcohol metabolism and other chronic diseases associated with alcohol consumption.

Atrial fibrillation is the most common heart disease in the world, with around 35 million patients in 2020. Here we reported the generation of IBMS-iPSC-015-06, IBMS-iPSC-016-06, and IBMS-iPSC-017-02 as human induced pluripotent stem cell (iPSC) lines from patients' peripheral blood mononuclear cells (PBMCs) with atrial fibrillation. The cell lines expressed properties of pluripotent stem cells, including pluripotent markers and the ability to differentiate into three germ layers. These cell lines served as suitable models for studying alternative therapies of atrial fibrillation.

The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was suggested to be unreliable in low tidal volume (VT) ventilation. However, high PEEP can cause ARDS patients relatively hypovolemic and more fluid responsive. We hypothesized that high PEEP 15 cmH2O can offset the disadvantage of low VT and improve the predictive performance of PPV. We prospectively enrolled 27 hypovolemic ARDS patients ventilated with low VT 6 ml/kg and three levels of PEEP (5, 10, 15 cmH2O) randomly. Each stage lasted for at least 5 min to allow for equilibration of hemodynamics and pulmonary mechanics. Then, fluid expansion was given with 500 ml hydroxyethyl starch (Voluven 130/70). The hemodynamics and PPV were automatically measured with a PiCCO2 monitor. The PPV values were significantly higher during PEEP15 than those during PEEP5 and PEEP10. PPV during PEEP15 precisely predicts fluid responsiveness with a cutoff value 8.8% and AUC (area under the ROC curve) of ROC (receiver operating characteristic curve) 0.847, higher than the AUC during PEEP5 (0.81) and PEEP10 (0.668). Normalizing PPV with driving pressure (PPV/Driving-P) increased the AUC of PPV to 0.875 during PEEP15. In conclusions, high PEEP 15 cmH2O can counteract the drawback of low VT and preserve the predicting accuracy of PPV in ARDS patients.

A green synthesis method is proposed for the preparation of nitrogen-doped multiporous carbons (denoted as N-MPCs) from water-caltrop shell (WCS) using eggshell waste as both a nitrogen-dopant and an activating agent. It is shown that the surface area, porosity, yield and nitrogen content of the as-prepared N-MPCs can be easily controlled by adjusting the activation temperature. Moreover, in oxygen reduction reaction (ORR) tests performed in O2-saturated 0.1 M KOH(aq) electrolyte containing 1.0 M methanol, the N-MPC catalysts show a high ORR stability and good resistance to methanol corrosion. In addition, as a cathode material in Al–air battery tests, the N-MPCs achieve a power density of 16 mW g−1 in a saturated NaCl(aq) electrolyte. Overall, the results show that the N-MPCs have a promising potential as a green and sustainable material for ORR catalysis applications.

The anti-inflammatory effect of hispolon has identified it as one of the most important compounds from Sanghuangporus sanghuang. The research objectives were to study this compound using an animal model by lipopolysaccharide (LPS)-induced acute lung injury. Hispolon treatment reduced the production of the pro-inflammatory mediator NO, TNF-&alpha, IL-1&beta, and IL-6 induced by LPS challenge in the lung tissues, as well as decreasing their histological alterations and protein content. Total cell number was also reduced in the bronchoalveolar lavage fluid (BALF). Moreover, hispolon inhibited iNOS, COX-2 and I&kappa, B-&alpha, and phosphorylated IKK and MAPK, while increasing catalase, SOD, GPx, TLR4, AKT, HO-1, Nrf-2, Keap1 and PPAR&gamma, expression, after LPS challenge. It also regulated apoptosis, ER stress and the autophagy signal transduction pathway. The results of this study show that hispolon regulates LPS-induced ER stress (increasing CHOP, PERK, IRE1, ATF6 and GRP78 protein expression), apoptosis (decreasing caspase-3 and Bax and increasing Bcl-2 expression) and autophagy (reducing LC3 I/II and Beclin-1 expression). This in vivo experimental study suggests that hispolon suppresses the LPS-induced activation of inflammatory pathways, oxidative injury, ER stress, apoptosis and autophagy and has the potential to be used therapeutically in major anterior segment lung diseases.

We report the engendering an isogenic iPSC line from the IBMS-iPSC-014-05 with homozygous correction of the R803X, Chr4: 88989098C > T in PKD2, using CRISPR/Cas9 technology. The results from the isogenic control, IBMS-iPSC-014-05C, showed that mutation had been corrected, while maintaining normal morphology, pluripotency, and differentiation capacity into three germ layers.

This study developed an inheritance coding with Gagn&eacute, based learning hierarchy approach to building systems for assessing mathematics skills and diagnosing student learning problems. The proposed Gagn&eacute, based learning hierarchy approach combines Gagn&eacute, learning hierarchy theory with an inheritance coding approach. First, Gagn&eacute, learning hierarchy theory is used to generate test questions and learning path diagrams for a skills assessment system. To assess learning achievement, an inheritance coding approach is used to encode the test questions according to learning hierarchy paths. The analysis, design, development, implementation, and evaluation design model is used throughout the process of developing the assessment system. Statistical analyses of the test questions for assessing student learning achievement included expert validity, internal reliability, test&ndash, retest reliability, and parallel-form reliability. System performance questionnaires were also designed to survey the opinions of the students regarding the mathematics skills assessment system. The internal reliability of the overall questionnaire was also calculated. The experimental practical application of the assessment system, developed by the Gagn&eacute, based learning hierarchy approach, showed that it can accurately diagnose student learning barriers and provide learning suggestions for students and teachers.

Successful hospital brand management enables employees to understand the hospital’s brand value and to directly reflect upon their behaviour and job performance, which in turn positively influences...

University–industry collaboration (UIC) has been booming for several decades worldwide. Integrating knowledge and resources from universities and industries has become a common method to maintain the innovation capacities of the industries. UIC activities have been promoted in Taiwan through various incentive policies for more than 20 years. However, most university faculty members still obtain research resources from government-related organizations much more than from the industries. Thus, this study focuses on the mechanism between faculty inputs and UIC outputs and tries to answer how faculty characteristics, background, motivation, and the collaboration patterns between universities and industries affect the work outputs of university faculty members. The sample consisted of 2031 questionnaires, and 376 traceable questionnaires were deemed valid and were analyzed. The results showed that age, gender, universities, work experience, award records, seniority of the faculty member, and the strength of social ties between the collaborative teams indeed had significant effects on the UIC outputs. The results of this study may be informative for the industries when business organizations are interested in seeking academia partners to achieve their expected collaboration outputs.

Leucine rich repeat kinase (LRRK2) is the most prevalent genetic cause for Parkinson's disease. LRRK2 p.G2385R is an Asian specific genetic risk factor for sporadic Parkinson's disease. We generated two induced pluripotent stem cells (iPSCs), IBMS-iPSC-018-09 and IBMS-iPSC-020-01, from the peripheral blood mononuclear cells of two patients carrying LRRK2 p.G2385R variant by using the Sendai-virus delivery system. These iPSCs had a normal karyotype and exhibited pluripotency, such as an embryonic stem cell-like morphology, expression of pluripotent markers, and capacity to differentiate into three germ layers. This cellular model will provide a platform for pathophysiological studies of neurodegeneration in Parkinson's disease.

Mitochondrial defects are associated with clinical manifestations from common diseases to rare genetic disorders. Myoclonus epilepsy associated with ragged-red fibers (MERRF) syndrome results from an A to G transition at nucleotide position 8344 in the tRNALys gene of mitochondrial DNA (mtDNA) and is characterized by myoclonus, myopathy and severe neurological symptoms. In this study, Sendai reprogramming method was used to generate an iPS cell line carrying the A8344G mutation of mtDNA from a MERRF patient. This patient-specific iPSC line expressed pluripotent stem cell markers, possessed normal karyotype, and displayed the capability to differentiate into mature cells in three germ layers.

Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment. We reported the generation and characterization of an iPS cell line, IBMS-iPSC-063-06, from a patient carrying the BBS2 homologous c534 + 1G > T mutation. The generated iPS cell line retains the mutation and exhibits pluripotency and differentiation ability both in vivo and in vitro condition.

Sensorineural hearing loss (SNHL) is a prevalent form of deafness commonly arising from damage to the cochlear sensory hair cells and degeneration of the spiral ganglion neurons. In this study, Sendai virus was used to generate an induced pluripotent stem cell (iPSC) line from a 39-year-old female patient diagnosed with severe-to-profound, non-syndromic SNHL. The patient also carries a A1555G mutation in the mitochondrial 12S ribosome RNA gene (MTRNR1). This iPSC line was verified to express pluripotent markers, possess normal karyotype, harbor the specific mutation and demonstrated the capacity to differentiate into three germ layers.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers.

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by interactions between genetic and environmental factors. Leucine rich repeat kinase (LRRK2) is the most prevalent mutation in autosomal-dominant inheritance of PD. Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with p.I2012T mutation in LRRK2 gene by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the 3 germ layers in vivo. This cellular model will provide a useful platform for further pathophysiological studies of PD.

This study aimed to determine the mediating role of training (perceived trainer performance, PTP; perceived usefulness of training, PUT and perceived efficiency of training, PET) between future orientation and context performance. Questionnaire was the tool of collecting data from a sample of (210) pharmacists. The results of the study indicated that there is a positive effect of future orientation on context performance. Also, there is partial effect of the three mediator variables (perceived trainer performance, PTP; perceived usefulness of training, PUT and perceived efficiency of training, PET) on the relationship between independent and dependent variables.

Autosomal dominant polycystic kidney disease is one of the most prevalent forms of inherited cystic kidney disease, and can be characterized by kidney cyst formation and enlargement. Here we report the generation of a Type 1 ADPKD disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such as ES-like morphology, expression of pluripotent markers and capacity to differentiate into all three germ layers. Our results show that we have successfully generated a patient-specific iPS cell line with a mutation in PKD1 for study of renal disease pathophysiology.

Purpose By integrating the diffusion of innovation (DOI) theory, technology acceptance model (TAM), and social capital theory, the purpose of this paper is to: develop a model of consumer behavior and trial willingness toward nano-foods from product, consumer, and social perspectives; examine the effects of innovative features, consumer characteristics, and trust in authority on subjective perceptions (perceived trustworthiness and perceived benefit) as well as the social influence on attitudes toward nano-foods and trial willingness; examine the moderating role of product uncertainty on the relationship between these characteristics and subjective perceptions; and examine the effect of perceived benefit on perceived trustworthiness. Design/methodology/approach The results of the structural equation model (SEM), with nano-food knowledge data collected from 431 respondents, supported the research model and revealed the main effects hypothesized in this study and the moderating effect of product uncertainty. Simple slope analysis was further adopted to test the significant moderating effects. Findings The SEM results indicated that innovative characteristics (relative advantage, lack of observability, and novelty), consumer characteristics (perceived technology application), and social characteristics (trust in authority) affect perceived trustworthiness or perceived benefit. Social influence also has a direct effect on attitude toward nano-foods and trial willingness. Product uncertainty significantly moderates the relationship between characteristics (relative advantage and perceived technology application) and subjective perceptions (perceived trustworthiness and perceived benefit). Research limitations/implications With increasing numbers and kinds of nanotechnology products now being developed and sold, it is important to go further to determine consumer perceptions and attitudes toward these. This study, thus, applied the DOI, TAM, and social capital theory to examine this issue. However, other theories might also be used to carry out research from other perspectives. This study should, thus, be seen as preliminary, and it is hoped that more works will discuss consumer attitudes toward nanotechnology products in the future. Practical implications When a new nano-food is introduced, the current study suggests that food manufacturers use the description on the package as a communicative tool. Detailing the advantages of nano-foods on food packages might be a useful way to enhance trial willingness and to reduce the fears and insecurities related to the use of nano-related products. In addition, if food manufacturers could cooperate with organizations or individuals seen as having some authority in this area (e.g. nanotechnology researchers) in order to disseminate accurate information about nanotechnology and related food products, this might be an effective way to increase sales and profits. Originality/value This is the first paper integrating the DOI, the social capital theory and the TAM to empirically investigate consumer willingness to try nano-food products.

Additional file 1. Figure S1. Characterization of iPSC cell line IBMS-iPSC-002-07. (A) Reverse transcription-polymerase chain reaction (RT-PCR) analyses of Sendai-virus (SEV) and human KLF4, KLF4- OCT3/4-SOX2 (KOS), c-MYC, and GAPDH . (B) RT-PCR analyses of ESC-marker expression in the iPSC line. (C) Immunofluorescence analyses of stemness marker expression. (D) In vitro differentiation of iPSCs into the three different germ-layers by embryonic formation assay. (E) Histological staining of teratoma derived from a normal iPSC line; N: neuronal structure, G: glandular structure; C: cartilage-like structure. (F) Representative G-banded chromosomes. Karyotypes of normal iPSCs. Figure S2 Karyotype analysis of the iPSC lines. (A) Karyotype of premature ovarian failure iPSC, NTUH-iPSC-004-06 (Turner disease). (B) Karyotype of parental cells of TVGH-iPSC-016, arrow indicates rearranged chromosome 16. (C) Karyotype of TVGH-iPSC-016 (monogenic diabetes iPSC), arrow indicates missing chromosome 16. Figure S3 In vitro and in vivo functional evaluation of iPSC derived cardiomyocytes. (A) Beating frequency (beats/min) of iPSC-derived cardiomyocytes under isoproterenol or propranolol treatment. (B) The dose-response relationship for doxorubicin (DOX) treatment of iPSC derived cardiomyocytes, as evaluated by TetraZ cell counting assay. (C) TUNEL assay showing cell death 24 h after doxorubicin treatment. (D) Workflow of iPSC-CM engraftment in the mouse heart. (E) Immunostaining of the mouse myocardium engrafted with derived from human iPSC, showing engrafted of human iPSC-CMs. h-Mito: anti-human mitochondria antibody. Data are represented as mean ± SEM.

A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) gene causes a heterogeneous neurodegenerative disorder that includes amyotrophic lateral sclerosis (ALS), frontotemporal degeneration (FTD), and parkinsonism. Here, we used the Sendai virus delivery system to generate induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a male patient with an increased hexanucleotide repeat expansion in C9orf72. The resulting iPSCs exhibited pluripotency, confirmed by immunofluorescent staining for pluripotency markers, and differentiated into three germ layers in vivo. This cellular model will provide a useful platform for further pathophysiological studies of C9orf72-related neurodegeneration.

We conducted a systemic search of several databases for randomized controlled trials (RCTs) that reported efficacy and safety outcomes of drugs for left-sided and right-sided metastatic colorectal cancer (mCRC), to identify the best available treatment. A network meta-analysis with mixed comparisons was created to interpret the best treatment option using the surface under the cumulative ranking curve. In the left-sided rat sarcoma (RAS) wild-type (WT) mCRC patients, bevacizumab, panitumumab, or cetuximab with chemotherapy groups showed a significantly better objective response rate than the chemotherapy alone group. The progression-free survival (PFS) and overall survival were better with panitumumab or cetuximab with chemotherapy than with chemotherapy alone. In the right-sided RAS WT mCRC patients, PFS for bevacizumab with chemotherapy was significantly better than that for cetuximab with chemotherapy. Cetuximab, closely followed by panitumumab, is the most effective treatment in left-sided RAS WT mCRC. Bevacizumab is more effective in right-sided mCRC.

With its low attenuation and high directivity, the 77 ~ 110 GHz (W-band) frequency range is suitable for long-distance broadband applications. Although only 77 GHz and 94 GHz have been used for vehicular radar and military surveillance so far, the W-band spectra is destined to play an even important role in the post-5G era. This manuscript describes our development on the 40 nm-CMOS W-band phase shifter design where 5 bits are used for phase shift of 11.25° while additional 4-bit logics are for fine-tuning purpose. The input signal is first be amplified by a wideband amplifier and then transformed through poly-phase circuit into I/Q signals, whose magnitude will then be altered by the following digital VGAs. By making the vector sum at the output, phase shifting in the range of 0° ~ 360° can be obtained and the resolution is 11.25°.

Learning science concepts can be challenging as these concepts are usually abstract and complex. Science visualization and analogies are applied in teaching practices for improving students' understanding of the concepts. This study seeks to promote students' learning performance and flow engagement by integrating visual representation as scaffoldings with game elements. An electric potential gamified teaching activity based on CSLS teaching model (Card-game, Slide, and Learning Sheet gamification teaching model) was proposed and evaluated [1]. The results indicate that the proposed teaching activity could improve students understanding. In the meantime, students generally possessed positive perception toward the game and were having positive flow experiences. Implication and suggestion for future study is discussed based on the findings.

Background Neonatal listeriosis is a major cause of mortality in newborn; however, there is limited information about this disease in Taiwan. The aim of our study was to identify the outcome determinants, clinical features, and incidence of pregnancy-associated listeriosis, which includes both neonatal and maternal listeriosis. Methods We retrospectively analyzed the medical records of neonatal and maternal patients with pregnancy-associated listeriosis at two hospitals in Taiwan from January 2000 to December 2018. Listeriosis was indicated by positive Listeria monocytogenes culture. Results Our study examined 18 neonates and 19 mothers. The neonatal and fetal death rate was 24%. All five cases of fetal losses or neonatal deaths occurred before 29 weeks of gestational age. The annual incidence of confirmed neonatal listeriosis increased significantly from 0.94/10,000 neonatal inpatients in 2000–2011 to 5.45/10,000 neonatal inpatients in 2012–2018 (p = 0.026). Clinical presentations of neonatal listeriosis included respiratory distress (85%), leukocytosis or leukopenia (77%), bandemia (69%), thrombocytopenia (77%), hypocalcemia (100%) and elevated C-reactive protein (CRP) levels (92%). Lower gestation correlated with a higher fatality rate (p = 0.002). Among the maternal cases investigated, 67% had a diagnosis of listeriosis, and 72% presented with fever. However, only 21% of the 19 mothers received complete antepartum ampicillin treatment. Conclusions The incidence of neonatal listeriosis is increasing, especially in preterm neonates. Maternal listeriosis should be adequately treated with appropriate empirical antibiotics.

Leucine rich repeat kinase 2 (LRRK2) is the causative gene for autosomal-dominant familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with LRRK2 c.4111A > G (p.I1371V) mutation by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the three germ layers in vivo. This cellular model will provide a platform for studying the role of LRRK2 in the disease process.

Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. Protection against I/R injury in sterile organs by hypoxic preconditioning (HPC) had been attributed to erythropoietic and angiogenic responses. Our previous study showed attenuation of intestinal I/R injury by HPC for 21 days in a neutrophil-dependent manner. To investigate the underlying mechanisms of neutrophil priming by HPC, and explore whether adoptive transfer of primed neutrophils is sufficient to ameliorate intestinal I/R injury. Rats raised in normoxia (NM) and HPC for 3 or 7 days were subjected to sham operation or superior mesenteric artery occlusion for I/R challenge. Neutrophils isolated from rats raised in NM or HPC for 21 days were intravenously injected into naive controls prior to I/R. Similar to the protective effect of HPC-21d, I/R-induced mucosal damage was attenuated by HPC-7d but not by HPC-3d. Naive rats reconstituted with neutrophils of HPC-21d rats showed increase in intestinal phagocytic infiltration and myeloperoxidase activity, and barrier protection against I/R insult. Elevated free radical production, and higher bactericidal and phagocytic activity were observed in HPC neutrophils compared to NM controls. Moreover, increased serum levels of tumor necrosis factor α (TNFα) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were seen in HPC rats. Naive neutrophils incubated with HPC serum or recombinant TNFα, but not CINC-1, exhibited heightened respiratory burst and bactericidal activity. Lastly, neutrophil priming effect was abolished by neutralization of TNFα in HPC serum. TNFα-primed neutrophils by HPC act as effectors cells for enhancing barrier integrity under gut ischemia.

Key points Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria-derived septic complications. Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive. A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes. Pyruvate suppressed epithelial cell death in an ATP-independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut. Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti-necroptotic role of glycolytic pyruvate under ischaemic stress. Abstract Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor-interacting protein kinase (RIP)-dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium-glucose transporter 1 ameliorated ischaemia/reperfusion-induced epithelial injury, partly via anti-apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1-dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell-permeable pyruvate suppressed epithelial cell death in an ATP-independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal-to-serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP.

Executive Summary: Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia. Keywords: Pneumonia, Guidelines, Treatment, Taiwan

This paper describes our progress in designing the K-band receiver in WIN 0.15μm GaAs pHEMT process. The LNA contains three stages of common-source transistors, and its noise performance has been optimized over the intended bandwidth; the following mixer is made of single-balanced transistors where the edge-coupled Marchand balun provides the required 18∼26GHz differential-mode LO while active balun is used for combining the 8GHz IF signals. The conversion gain measured on-wafer at room temperature is around 20dB and the noise temperature is close to 300K, with overall power consumption 140mW, and the chip area is 1000×2500μm2. A close inspection on the wide-IF-band noise measurement procedure is also provided where the impact of conversion gain on the measured Tn is explored. This receiver circuit will facilitate the construction of large focal plane arrays where compact cryogenic receiver module is in urgent demand.

This paper describes our progress in the design of cryogenic LNAs using OMMIC 70nm mHEMT for the Square-Kilometer-Array (SKA) project and the Shanghai 65-Meter radio-astronomical telescope. Different LNAs covering the aggregate 1∼40GHz frequency range are designed and measured on-wafer at room temperature, and Tn for the 1∼10, 5∼15, and 10∼40GHz LNAs are 80K, 90K, and 120K, respectively, with the gain all larger than 20dB. One 1∼10GHz LNA chip is then packaged and tested cryogenically, and the noise temperature improvement factor is 6∼8, which is smaller than what can be obtained from the WIN pHEMT. Performance repeatability among different chips has been carried out.

Rationale: Lapatinib (LAP) is a crucial alternative to trastuzumab upon the onset of drug resistance during treatment of metastatic human epidermal growth factor receptor 2-positive breast cancer. Like trastuzumab, LAP is commonly used alongside anthracyclines as a combination therapy, due to enhanced anti-cancer efficacy. However, this is notably associated with cardiotoxicity so it is imperative to understand the mechanisms driving this cardiotoxicity and develop cardioprotective strategies. To this end, here we utilize human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), which exhibit several characteristics representative of in vivo cardiomyocytes that make them breakthrough models to study drug toxicity. Methods: We investigated LAP- and doxorubicin (DOX)-induced toxicity in hPSC-CMs and evaluated the involvement of inducible nitric oxide (NO) synthase (iNOS). The significance of iNOS-mediated cardiotoxicity was furthermore evaluated in animal studies. Results: LAP synergistically increased DOX toxicity in hPSC-CMs in a dose- and time-dependent manner. At concentrations that were otherwise non-apoptotic when administered separately, LAP significantly potentiated DOX-induced hPSC-CM apoptosis. This was accompanied by increased iNOS expression and pronounced production of NO. iNOS inhibition significantly reduced hPSC-CM sensitivity to LAP and DOX co-treatment (LAP-plus-DOX), leading to reduced apoptosis. Consistent with our observations in vitro, delivery of an iNOS inhibitor in mice treated with LAP-plus-DOX attenuated myocardial apoptosis and systolic dysfunction. Moreover, inhibition of iNOS did not compromise the anti-cancer potency of LAP-plus-DOX in a murine breast cancer xenograft model. Conclusions: Our findings suggest that iNOS inhibition is a promising cardioprotective strategy to accompany HER2-inhibitor/anthracycline combination therapies. Furthermore, these results support the promise of hPSC-CMs as a platform for investigating cardiotoxicity and developing cardioprotectants as a whole.

This manuscript describes the Q-band 90nm-CMOS receiver design where the 33∼50GHz RF-LNA, actively-biased double-balanced mixer, 10GHz IF amplifier, wideband frequency tripler and power amplifier in the LO chain are all integrated into one single chip. With overall power consumption of 170mW under 1.2V bias, the measured conversion gain is 15dB, noise figure close to 8dB, input-referred P1dB around −30dBm, and the LO-IF port isolation is more than 60dB. Therefore, it can be easily driven by an external 11∼16GHz signal source and used in applications such as next-generation broadband mobile communications where several specific Q-band frequency points have been considered. However, contrary to most receiver designs where the optimization is carried out over a relatively narrow bandwidth, here the main challenge lies in how to effectively extend the RF, IF, and LO bandwidth simultaneously without rendering performance deterioration. By possessing such broadband RF, IF, and LO characteristics, this Q-band circuit is also eligible for use in radio-astronomical, atmospheric, and other scientific instrumentations.

This manuscript describes a 34–42GHz single-sideband 90nm-CMOS transmitter where PLL has been integrated into the LO chain and, with I/Q input and two-stage up-conversion, a 30dB image-rejection ratio is achieved within the intended bandwidth. This transmitter's wideband tuning range is made possible by the use of additional capacitor on the VCO, and the phase noise of the resulting RF output is in the range of −70 to −90dBc/Hz at 1MHz, and all below −100dBc/Hz at 10MHz. The circuit's IF-to-RF conversion gain is 30dB, with saturated output power around 5dBm, and the total power consumption is 260mW. Through the control of the power amplifier's drain bias, a 50dB power level difference can be obtained, thus allows signal modulation and further combination with the receiver. This 1100×650um2 transmitter can be used as a prototypical circuit to explore next-generation mobile communication and civilian radar array systems.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent monogenic kidney disorder leading to kidney failure. We generated induced pluripotent stem cells (iPSCs) from a 37-year-old man carrying a PKD1 Q533X mutation who suffered from kidney failure and a myocardial infarction. The iPSCs were reprogrammed from the patient's peripheral blood mononuclear cells using the Sendai virus system, and were confirmed to possess the specific PKD1 Q533X mutation and normal karyotype. Pluripotency was confirmed using in vitro and in vivo assays. This iPSC line will be useful for studying the mechanisms driving the complicated pathophysiology of ADPKD.

Background: Most cases of complicated pneumonia in children are caused by pneumococcal infections. Thomsen-Friedenreich antigen (TA) is present on erythrocytes, platelets and glomeruli, and it can be activated during pneumococcal infection. The aim of this study was to investigate the predictive value of TA activation for pneumococcal infection and association with the severity of complicated pneumonia. Materials and methods: Patients with lobar pneumonia were routinely tested for TA at the Department of Pediatrics, Mackay Memorial Hospital from January 2010 to December 2015. We retrospectively reviewed and analyzed their charts and data including age, sex, etiology of infection, chest tube insertion or video-assisted thoracoscopic surgery, length of hospital stay, TA activation, white blood cell count and level of C reactive protein. Results: A total of 142 children with lobar pneumonia were enrolled, including 35 with empyema, 31 with effusion, 11 with necrotizing pneumonia and four with lung abscess. Streptococcus pneumoniae was the most commonly identified pathogen. Twenty-two patients (15.4%) had activated TA, all of whom were infected with S. pneumoniae. TA activation had 100% specificity and 100% positive predictive value for pneumococcal infection. In the multivariate analysis in lobar pneumonia, TA activation (OR, 15.8; 95% CI, 3.0–83.5; p = 0.001), duration of fever before admission (OR, 1.2; 95% CI, 1.1–1.5; p = 0.013) and initial CRP level (OR, 1.1; 95% CI, 1.0–1.1; p = 0.004) were independent predictors of empyema. Conclusions: TA activation is a specific marker for pneumococcal pneumonia and might indicate higher risk for complicated pneumonia. Keywords: Empyema, Parapneumonic effusion, Pediatric, Streptococcus pneumoniae, Thomsen-Friedenreich antigen

Estrus detection in cattle is very important for breeding management. The detection results help determine the optimum time for artificial insemination. The success of estrus detection not only increases conception rates but also raises milk production for the herd. The proposed image processing method to detect cows in heat from video is passive and therefore does not require devices to be attached to the cow’s body. The observed scene is a commercial dairy farm, where Holstein cattle are reared in roofed cowsheds. The proposed method is based on the inherent behavior of cows in heat which is characterized by a cow following another cow before mounting it for a short period of a few seconds. A region of interest was first determined around image locations where high levels of motion occurred across the video frames. Foreground segmentation then follows to partition the moving target object from the region of interest in each image frame. The following and mounting behaviors are identified based on the changes of moving object lengths. When an estrus event is declared, the detected event is recorded into the computer to be verified later. The detection system observed 20 cows in a cowshed from the top view. Over the period of 800 h (80 days at 10 h each day), only 0.33% of video frames detected were false positive indicating the system was reliable at detecting mating and estrus behavior from the video frames. Using the method the farmer is required to view the recorded video frames for approximately 2 min per day to confirm that the detection results are true estrus events. The proposed method is capable of real-time detection of mating and estrus behavior speeds with a processing rate of 35 fps.