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The main goal of the study is to evaluate the three stone scoring systems (S.T.O.N.E nephrolithometry scoring system (STONE), Guy's stone score (GSS) and Seoul National University Renal Stone Complexity (S-ReSC)) for the stone-free rate (SFR) of mini-PCNL. We retrospectively analyzed 72 patients who received mini-PCNL from February 2018 to October 2020. The SFR, complication rates, hospitalization days and recurrence rates were analyzed using three stone scoring systems. The result showed statistical significance in the association between scoring system and stone-free (STONE: OR 95%CI 0.409 (0.221–0.759), p = 0.0045; S-ReSC OR 95%CI 0.633 (0.401–0.999), p = 0.0497), but not GSS (OR 95%CI 0.776 (0.397–1.516), p = 0.4581). After adjusting the potential confounding factors, the area under curve (AUC) of STONE, GSS, and S-ReSC was 0.86, 0.78, and 0.81, respectively, and Akaike information criterion (AIC) of STONE, GSS, and S-ReSC was 64.65, 74.89, and 69.92, respectively. The accuracy rate of STONE, GSS, and S-ReSC was 0.81, 0.75, and 0.79, respectively. There was no statistically difference of predicting stone recurrence (p = 0.46, 0.53, 0.86), complications (p = 0.74, 0.51, 0.16) and hospitalization days (p = 0.77, 0.86, 0.87) in STONE, GSS, and S-ReSC, respectively. In conclusion, both the STONE and S-ReSC stone scoring systems are viable for predicting the SFR following mini-PCNL, especially after variable adjustment with the STONE system demonstrating superiority over S-ReSC. [ABSTRACT FROM AUTHOR]

Background: Footbaths can be used to manage digital dermatitis (DD), a common cause of lameness in dairy cattle. Copper sulfate and chelated copper–zinc (CZS) solutions in footbaths are potentially harmful to the environment. Hypothesis/Objectives: To determine if a quaternary ammonium salt‐based disinfectant (QASD) footbath is as effective as a chelated CZS solution in controlling DD in dairy cows. Animals: Fifty‐one lactating Holstein cows were randomly assigned to one of two treatment groups, with DD status based on the M‐stage scoring system and locomotion score balanced between treatment groups. Materials and Methods: The groups were treated with a 1% QASD or a 2.5% chelated CZS. Footbaths were performed once per week for 15 weeks. Logistic regression was used to analyse clinical improvement. All cows received appropriate medical treatment for DD and other hoof diseases. Results: Clinical improvement rates were 67% in the QASD group and 38% in the CZS group (p = 0.03). Logistic regression analysis showed that the odds (95% confidence interval) for clinical improvement rate in the CZS group were 0.30 (0.095–0.948) times that of the QASD group (p = 0.04). The M0 score in the QASD and CZS groups increased significantly (p < 0.05) at the end of the 15 week study period. In the QASD group, the proportion of M2, M3 and M4 scores were significantly decreased (p < 0.05). Conclusion and Clinical Relevance: Over a 15 week period, QASD for footbathing was associated with a lower prevalence of active DD lesions than when using CZS. [ABSTRACT FROM AUTHOR]

Because longwave (LW) absorption by greenhouse gases and clouds is more significant than the LW scattering effect by clouds, most climate models neglect cloud LW scattering to save computational costs. Ignoring cloud LW scattering directly overestimates outgoing longwave radiation (OLR). This study included ice‐cloud LW scattering treatment in the Exascale Energy Earth System Model (E3SM) version 2 and ran fully‐coupled simulations, prescribed sea surface temperature simulations, and offline radiative transfer calculations to comprehensively assess the impact of ice‐cloud LW scattering on global climate simulation. The instantaneous effect due to ice‐cloud LW scattering reduces the OLR by ∼1 W/m2 on the global average and 2 W/m2 on the tropical average. Tropospheric warming and high cloud amount reduction act to partially compensate for such instantaneous OLR reduction caused by the inclusion of LW scattering. When the simulation reaches the equilibrium, the surface warms by 0.66 K on average with respect to the simulation without LW scattering, with the Arctic surface temperature differences more than twice as large as that of the global mean. The impact of including LW scattering on the simulated climate change in response to 4 × CO2 is also assessed. While including the cloud LW scattering does not significantly modify radiative forcing and total radiative feedback under such a scenario, it results in a 10% more positive cloud feedback. Plain Language Summary: Clouds are an essential mediator in the climate system because they can reflect solar radiation back to space and block longwave radiation emitted below reaching the top of the atmosphere by either absorbing it or scattering it elsewhere. Such longwave scattering physics is deemed less important and thus neglected in most climate models to save computational time. We incorporated this mechanism into a climate model and ran pairs of simulations, with or without cloud scattering, to see how it would affect the simulated global climate. We found that cloud longwave scattering reduces the longwave radiation that goes to space. Such reduction of outgoing longwave radiation is strongest in the tropics. Compared to the simulation without longwave scattering, the mean‐state surface temperature change is larger in the Arctic than in the tropics, which is primarily caused by the slow response to the inclusion of scattering. We also assessed to what extent the inclusion of cloud longwave scattering can affect the simulated response to abrupt 4 × CO2 increase. We concluded that it can increase the cloud feedback strength by ∼10%, but overall, the impact is not statistically significant. Key Points: Ice‐cloud longwave (LW) scattering leads to warming with a pattern similar to the response to quadrupled CO2 in Exascale Energy Earth System Model version 2Strong Arctic warming is part of the global response to radiative perturbation rather than a local impact of LW scatteringIncluding ice‐cloud LW scattering does not significantly affect the simulated responses to abrupt 4 × CO2 increases [ABSTRACT FROM AUTHOR]

To go beyond polyethylene oxide in lithium metal batteries, a hybrid polymer/oligomer cell design is presented, where an ester oligomer provides high ionic conductivity of 0.2 mS cm−1 at 40 °C within thicker composite cathodes with active mass loadings of up to 11 mg cm−2 (LiNbO3‐coated) LiNi0.6Mn0.2Co0.2 (NMC622), while a 30 µm thin scaffold‐supported polymer electrolyte affords mechanical stability. Corresponding discharge capacities of the hybrid cells exceed 170 mAh g−1 (11 mg cm−2) or 160 mAh g−1 (6 mg cm−2) at rates of either 0.1 or 0.25 C. Multilayer pouch cells are projected to enable energy densities of 235 Wh L−1 (6 mg cm−2) and even up to 356 Wh L−1 (11 mg cm−2), clearly superior to other reported polymer‐based cell designs. Polyester electrolytes are environmentally benign and safer compared to common liquid electrolytes, while the straightforward synthesis and affordability of precursors render hybrid polyester electrolytes suitable candidates for future application in solid‐state lithium metal batteries. [ABSTRACT FROM AUTHOR]

Background: Tobacco use and secondhand smoke (SHS) are risk factors of kidney stone disease (KSD). The hypothesis is that tobacco produces chemicals that increase oxidative stress and vasopressin, which leads to decreased urine output, and contributes to stone formation. The aim of this study was to examine the effects of smoking and SHS on the development of KSD. Materials and methods: We analyzed a total of 25,256 volunteers with no history of KSD participated in the Taiwan Biobank. The presence of underlying and follow-up KSD was surveyed by a self-administrated questionnaire. They were classified into three groups on the basis of smoking and SHS exposure, accessed with survey questionnaires; never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups. Results: KSD was noted in 352 (2.0%), 50 (3.3%) and 240 (4.1%) subjects in the never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups, respectively, with a mean follow-up of 4 years. The odds ratio (OR) of KSD was higher in the never-smokers with SHS exposure (OR, 1.622; 95% confidence interval [95% CI], 1.225 to 2.255) and ever-smokers groups (OR, 1.282; 95% CI, 1.044 to 1.574) than in the never-smokers with no SHS exposure group after adjustment of confounders. In addition, never-smokers with SHS exposure had similar effects on the development of KSD than ever-smokers (OR, 1.223; 95% CI, 0.852 to 1.756). Conclusion: Our study suggests that both smoking and SHS are a risk factor for developing KSD and that the impact of SHS is not inferior to that of smoking. Trial registration: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20,210,058). [ABSTRACT FROM AUTHOR]

Progressive massive pulmonary fibrosis among coal miners has unexpectedly increased. It would likely due to the greater generation of smaller rock and coal particles produced by powerful equipment used in modern mines. There is limited understanding of the relationship between micro- or nanoparticles with pulmonary toxicity. This study aims to determine whether the size and chemical characteristics of typical coal-mining dust contribute to cellular toxicity. Size range, surface features, morphology, and elemental composition of coal and rock dust from modern mines were characterized. Human macrophages and bronchial tracheal epithelial cells were exposed to mining dust of three sub- micrometer and micrometer size ranges at varying concentrations, then assessed for cell viability and inflammatory cytokine expression. Coal had smaller hydrodynamic size (180–3000 nm) compared to rock (495–2160 nm) in their separated size fractions, more hydrophobicity, less surface charge, and consisted of more known toxic trace elements (Si, Pt, Fe, Al, Co). Larger particle size had a negative association with in-vitro toxicity in macrophages (p < 0.05). Fine particle fraction, approximately 200 nm for coal and 500 nm for rock particles, explicitly induced stronger inflammatory reactions than their coarser counterparts. Future work will study additional toxicity endpoints to further elucidate the molecular mechanism causing pulmonary toxicity and determine a dose–response curve. [ABSTRACT FROM AUTHOR]

Background: Emphysematous cystitis (EC) is a complicated urinary tract infection (UTI) characterized by gas formation within the bladder wall and lumen. Immunocompetent people are less likely to suffer from complicated UTIs, but EC usually occurs in women with poorly controlled diabetes mellitus (DM). Other risk factors of EC include recurrent UTI, neurogenic bladder disorder, blood supply disorders, and prolonged catheterization, but DM is still the most important of all aspects. Our study investigated clinical scores in predicting clinical outcomes of patients with EC. Our analysis is unique in predicting EC clinical outcomes by using scoring system performance. Materials and Methods: We retrospectively collected EC patient data from the electronic clinical database of Taichung Veterans General Hospital between January 2007 and December 2020. Urinary cultures and computerized tomography confirmed EC. In addition, we investigated the demographics, clinical characteristics, and laboratory data for analysis. Finally, we used a variety of clinical scoring systems as a predictor of clinical outcomes. Results: A total of 35 patients had confirmed EC, including 11 males (31.4%) and 24 females (68.6%), with a mean age of 69.1 ± 11.4 years. Their hospital stay averaged 19.9 ± 15.5 days. The in-hospital mortality rate was 22.9%. The Mortality in Emergency Department Sepsis (MEDS) score was 5.4 ± 4.7 for survivors and 11.8 ± 5.3 for non-survivors (p = 0.005). For mortality risk prediction, the AUC of ROC was 0.819 for MEDS and 0.685 for Rapid Emergency Medicine Score (REMS). The hazard ratio of univariate and multivariate logistic regression analyses of REMS for EC patients was1.457 (p = 0.011) and 1.374 (p = 0.025), respectively. Conclusion: Physicians must pay attention to high-risk patients according to clinical clues and arrange imaging studies as soon as possible to confirm the diagnosis of EC. MEDS and REMS are helpful for clinical staff in predicting the clinical outcome of EC patients. If EC patients feature higher scores of MEDS (≥12) and REMS (≥10), they will have higher mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy delivers more precise treatment compared with conventional radiotherapy. While this innovation entails investment costs, the information about the treatment costs per patient is limited. This information gap might prevent policymakers from making informed decisions. This study aims to calculate the costs of Proton therapy at a single center during the start-up phase and to provide essential information for the health technology assessment of proton therapy. The total cost of proton therapy varied between EUR 12,062 for eye melanoma and EUR 89,716 for head and neck cancer. Overall, indirect costs were the most significant cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Nevertheless, to have an estimation that reflects the matured cost of proton therapy which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. However, this study provided insights into the financial situation of a new proton therapy center during its ramp-up period and laid the first stone for future costing studies. Background: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. Methods: The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. Results: The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. Conclusion: This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended. [ABSTRACT FROM AUTHOR]

Solid polymer electrolytes (SPEs) have attracted considerable attention for high energy solid‐state lithium metal batteries (LMBs). In this work, potentially ecofriendly, solid‐state poly(ε‐caprolactone) (PCL)‐based star polymer electrolytes with cross‐linked structures (xBt‐PCL) are introduced that robustly cycle against LiNi0.6Mn0.2Co0.2O2 (NMC622) composite cathodes, affording long‐term stability even at higher current densities. Their superior features allow for sufficient suppression of dendritic lithium deposits, as monitored by 7Li solid‐state NMR. Advantageous electrolyte|electrode interfacial properties derived from cathode impregnation with 1.5 wt% PCL enable decent cell performance until up to 500 cycles at rates of 1C (60 °C), illustrating the high potential of PCL‐based SPEs for application in high‐voltage LMBs. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients who receive radiotherapy often suffer from adverse effects that require healthcare resources to manage. This study summarized evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects and provided recommendations for including this evidence in economic evaluations. Our findings revealed unignorable differences for the same adverse effects, which implied that the potential for the economic burden of adverse effects was overestimated or underestimated. Background: Despite the need for a proper economic evaluation of new radiotherapies, the economic burden of radiotherapy-induced adverse effects remains unclear. A systematic review has been conducted to identify the existing evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects and also to provide recommendations for including this evidence in economic evaluations. Methods: This systematic review of healthcare resource use and/or medical costs related to radiotherapy-induced adverse effects was performed up until 2020, focusing on patients with head and neck cancer, brain cancer, prostate cancer, eye cancer and breast cancer. Results: Resource use for treating the same adverse effects varied considerably across studies; for instance, the cost for mucositis ranged from USD 2949 to USD 17,244. This broad range could be related to differences in (1) severity of adverse effects in the study population, (2) study design, (3) cost estimation approach and (4) country and clinical practice. Conclusions: Our findings revealed unignorable differences for the same adverse effects, which implied that the potential for the economic burden of adverse effects was being overestimated or underestimated in economic evaluation for radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a strong association between animal abuse and interpersonal violence; therefore, veterinarians may encounter both. Dealing with animal abuse cases is beneficial for advancing animal welfare and the overall public health. Veterinarians play an important professional role in identifying and responding to this relationship. This is the first study in Taiwan to investigate the current situation of animal abuse from the perspective of veterinarians. Our results established that the incidence of suspected physical animal abuse encountered by veterinarians in Taiwan was 0.16 cases per 100 patients, and 63.9% of our respondents had seen suspected of animal physical abuse in the past five years. Approximately 10% of animal abuse cases were likely concurrent with human abuse. Most respondents (about 80%) agreed that animal abuse and human abuse frequently co-occur. However, it did not affect their willingness to assist or report abuse. In total, 88.7% of respondents supported mandatory reporting of animal abuse. The results of this study underscore the urgent advancement of education and the importance of the crucial veterinary role in both animal and interpersonal abuse cases. There is a strong association between animal abuse and interpersonal violence; therefore, veterinarians may encounter both. Dealing with animal abuse cases is beneficial for advancing animal welfare and the overall public health. Veterinarians play an important role in identifying and responding to this relationship. This study estimated the incidence of animal abuse encountered by veterinarians, examined veterinarians' awareness of the relationship between animal abuse and human abuse, examined veterinarians' attitudes towards how they deal with abuse cases, and related demographic characteristics to their attitudes of intervention and the frequency of encountering abuse cases. An anonymous self-administered questionnaire was designed and distributed through social media. Our results show that respondents' motivation to interfere for animal abuse cases was positively related to their moral or legal responsibility, willingness to assist, and agreement of mandatory reporting. Our results indicated that respondents who believed they had been provided with adequate training were more willing to deal with animal abuse, more capable of distinguishing abuse cases, and did not believe that dealing with abuse cases was beyond their ability. However, more than 60% of our respondents self-evaluated that the animal cruelty awareness training courses were insufficient. Hence, in addition to the traditional role of veterinarians, identifying and responding to animal cruelty should be enhanced through education. [ABSTRACT FROM AUTHOR]

Oncogene activation, massive proliferation, and increased nutrient demands often result in nutrient and oxygen deprivation in solid tumors including breast cancer (BC), leading to the induction of oxidative stress and endoplasmic reticulum (ER) stress, and subsequently triggering integrated stress response (ISR). To elucidate the role of long non‐coding RNAs (lncRNAs) in the ISR of BC, we performed transcriptome analyses and identified a lncRNA, UBA6‐AS1, which was upregulated upon amino acid deprivation and ER stress. UBA6‐AS1 was preferentially induced in triple‐negative BC (TNBC) cells deprived of arginine or glutamine, two critical amino acids required for cancer cell growth, or treated with ER stress inducers. Mechanistically, UBA6‐AS1 was regulated through the GCN2/eIF2α/ATF4 pathway, one of the major routes mediating ISR in amino acid sensing. In addition, both in vitro and in vivo assays indicated that UBA6‐AS1 promoted TNBC cell survival when cells encountered metabolic stress, implicating a regulatory role of UBA6‐AS1 in response to intratumoral metabolic stress during tumor progression. Moreover, PARP1 expression and activity were positively regulated by the GCN2/UBA6‐AS1 axis upon amino acid deprivation. In conclusion, our data suggest that UBA6‐AS1 is a novel lncRNA regulating ISR upon metabolic stress induction to promote TNBC cell survival. Furthermore, the GCN2‐ATF4 axis is important for UBA6‐AS1 induction to enhance PARP1 activity and could serve as a marker for the susceptibility of PARP inhibitors in TNBC. [ABSTRACT FROM AUTHOR]

Introduction: Routine HIV testing is expected to facilitate early diagnosis and treatment. Nevertheless, to date, limited data are available on the presumed benefit of early detection with improved outcomes through routine HIV testing.Methods: This study was based on the Taiwan national HIV/AIDS registry, with follow-up data validated through December 31, 2014. Outcomes of people diagnosed with HIV infection through the routine (routinely offered in specific settings, opt-out) versus through nonroutine (individual risk-based) testing were compared. The main outcomes of the study were late diagnosis, HIV-related mortality, and all-cause mortality. Individuals were matched by year of HIV diagnosis and adjusted for age, sex, transmission routes, and SES. Analyses were conducted in 2019-2020.Results: This study included all 28,674 people diagnosed with HIV infection during 1986-2014 (8,431 [29%] by routine testing, 18,305 [64%] by individual risk-based testing) with a mean follow-up time of 6.2 years. Routine testing was associated with an 80% lower likelihood of late HIV diagnosis (AOR=0.20, 95% CI=0.18, 0.23, p<0.001), a 37% lower HIV-related mortality (adjusted hazard ratio=0.63, 95% CI=0.53, 0.75, p<0.001), and a 27% lower all-cause mortality (adjusted hazard ratio=0.73, 95% CI=0.67, 0.79, p<0.001).Conclusions: Routine HIV testing was associated with highly favorable outcomes, including decreased late diagnosis, lower HIV-related mortality, and lower all-cause mortality, among people diagnosed with HIV infection. Under universal health coverage, expanding routine HIV testing in well-targeted settings may improve both HIV epidemic control for society and clinical outcomes for people living with HIV. [ABSTRACT FROM AUTHOR]

• In early 2020, the first large COVID-19 outbreak outside China occurred in Daegu • The SARS-CoV-2 strain involved in Daegu outbreak has an R0 of 3.6 (range: 2.3 to 5.6) • The Daegu outbreak was successfully controlled without restricting movement. • A combination of social distancing and testing-contact tracing is highly effective. • Both interventions must be enacted for successful control of an COVID-19 outbreak In Spring 2020, South Korea applied non-lockdown social distancing (avoiding mass gathering and non-essential social engagement, without restricting the movement of people who were not patients or contacts), testing-and-isolation (testing), and tracing-and-quarantine the contacts (contact tracing) to successfully control the first large-scale COVID-19 outbreak outside China. However, the relative contributions of these two interventions remain uncertain. We constructed an SEIR model of SARS-CoV-2 transmission (disproportionately through superspreading events) and fit the model to outbreak data in Daegu, South Korea, from February to April 2020. We assessed the effect of non-lockdown social distancing (population-wide control measures) and/or testing-contact tracing (individual-specific control measures), alone or combined, in terms of the basic reproductive number (R0) and the trajectory of the epidemic. The point estimate for baseline R0 is 3.6 (sensitivity analyses range: 2.3 to 5.6). Combined interventions of non-lockdown social distancing and testing-contact tracing can suppress R0 to less than one and rapidly contain the epidemic, even under the worst scenario with a high baseline R0 of 5.6. In contrast, either intervention alone will fail to suppress R0. Non-lockdown social distancing alone just postpones the peak of the epidemic, while testing-contact tracing alone only flattens the curve but does not contain the outbreak. To successfully control a large-scale COVID-19 outbreak, both non-lockdown social distancing and testing-contact tracing must be implemented. The two interventions are synergistic. [ABSTRACT FROM AUTHOR]

Objectives: Patients with cleft lip–cleft palate (CLP) often require orthodontic treatment, with or without orthognathic surgery. Patient satisfaction is the most important outcome parameter in orthodontic treatment. This study aimed to (1) determine patient satisfaction and quality of life (QoL) after orthodontic treatment and (2) identify associated factors. Material and methods: This prospective cross-sectional study recruited patients with CLP who had completed orthodontic treatment at a craniofacial center in Taiwan. Participants (N=213) had received treatment for unilateral CLP (n=99), bilateral CLP (n=50), cleft lip and alveolus (n=39), and isolated cleft palate (n=25). Self-report questionnaires evaluated satisfaction with appearance and QoL; multiple regression analysis examined associated factors. Participants' expectations of treatment results were also reported. Results: Participants reported moderate satisfaction with facial appearance and QoL. Satisfaction with treatment was lower or much lower than expected for 13% of participants. Treatment for bilateral CLP was associated with the lowest satisfaction with overall appearance (r = −8.123, P < 0.05); participants who had received orthognathic surgery had the highest satisfaction (r = 5.534, P < 0.05). Treatment for unilateral and bilateral CLP was associated with low QoL for smile (both P < 0.05). Conclusions: Orthodontic treatment had a positive effect on facial appearance and quality of life in patients with CLP. Type of cleft and orthognathic surgery significantly influenced satisfaction with facial appearance. Clinical relevance: Efforts must be taken to modify treatment strategies for patients with bilateral CLP in order to improve satisfaction with appearance following treatment. [ABSTRACT FROM AUTHOR]

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD. [ABSTRACT FROM AUTHOR]

Background: Malignant obstruction and associated hydronephrosis is a common complication of advanced cervical cancer. Percutaneous nephrostomy (PCN) followed by antegrade stenting is often required to relieve obstruction as retrograde access fails in considerable proportion of such patients. Reno-pleural fistula is a rare complication of PCN which creates a patent connection between the renal collecting system and the thoracic cavity, and urine accumulation in the pleural space can cause pleural effusion (i.e., urinothorax). Upward or downward migration is a complication of indwelling ureteric stents. Further migration with extrusion outside of the urinary tract is uncommon. Herein we present an unprecedented case in adult of ureteric stent upward migration through a reno-pleural fistula into the thoracic cavity managed by thoracoscopy.Case Presentation: A 66-year-old female was diagnosed of advanced stage cervical cancer with suspicious bladder invasion. Given her bilateral hydronephrosis with impaired renal function, she underwent bilateral PCN and subsequent antegrade ureteric stenting. However, she presented with dyspnea, right back pain, and oliguria four days after bilateral PCN catheter removal. Computed tomography reported massive right pleural effusion and an intrathoracic ureteric stent within reno-pleural fistula. Thoracoscopy with thoracostomy was performed to remove the ureteric stent and urine in right pleural space. A week later, urinothorax had resolved and right PCN was performed again. She was discharged after regaining normal renal function with right PCN and a left ureteric stent in place.Conclusions: A reno-pleural fistula can serve as a route for ureteric stent migration and that continuous drainage of urine can cause urinothorax once the stent reaches the thoracic cavity. Anytime a supracostal approach is used for PCN, even when using small caliber catheters, clinicians should pay special attention given the risk of pleural injury and subsequent complications. [ABSTRACT FROM AUTHOR]

Most climate models neglect cloud longwave (LW) scattering because scattering is considered negligible compared to strong LW absorption by clouds and greenhouse gases. While this rationale is valid for simulating extrapolar regions, it is questionable for the polar regions, where the atmosphere is dry and hence has weak absorption, and ice clouds that have strong scattering capability frequently occur. Using the slab‐ocean Community Earth System Model, we show that ice cloud LW scattering can warm winter surface air temperature by 0.8–1.8 K in the Arctic and 1.3–1.9 K in the Antarctic, while this warming becomes much weaker in polar summer. Such scattering effect cannot be correctly assessed when sea surface temperature and sea ice are prescribed as this effect is manifested through a surface‐atmosphere coupling. Cloud LW scattering is a necessity for the correct simulation of polar climate and surface radiation budget, especially in the winter. Plain Language Summary: Cloud longwave scattering has never been deemed as a necessity in climate models. Out of all climate models in the IPCC fifth and sixth assessments, only three modeling centers have longwave scattering included in their models. Our study explained why the traditional wisdom of neglecting longwave scattering breaks down for the simulation of high‐latitude climate in the fully coupled models. We showed the critical importance of atmosphere‐surface radiative coupling for correctly assessing the role of cloud longwave scattering in the model simulation of climate mean state as well as climate changes, an issue overlooked by all previous studies. We argued that the cloud longwave scattering is a necessity in climate models, not an option. Key Points: Cloud longwave scattering is more important in the polar regions than the extrapolar regionsBy surface‐atmosphere radiative coupling, cloud longwave scattering can warm the polar surface, more in the winter than in the summerCloud longwave scattering is a necessity instead of an option for correctly simulating polar climate and surface energy budget [ABSTRACT FROM AUTHOR]

Introduction: Policies to adequately respond to the rise in multimorbidity have top-priority. To understand the actual burden of multimorbidity, this study aimed to: 1) estimate the trend in prevalence of multimorbidity in the Netherlands, 2) study the association between multimorbidity and physical and mental health outcomes and healthcare cost, and 3) investigate how the association between multimorbidity and health outcomes interacts with socio-economic status (SES). Methods: Prevalence estimates were obtained from a nationally representative pharmacy database over 2007–2016. Impact on costs was estimated in a fixed effect regression model on claims data over 2009–2015. Data on physical and mental health and SES were obtained from the National Health Survey in 2017, in which the Katz-10 was used to measure limitations in activities of daily living (ADL) and the Mental Health Inventory (MHI) to measure mental health. SES was approximated by the level of education. Generalized linear models (2-part models for ADL) were used to analyze the health data. In all models an indicator variable for the presence or absence of multimorbidity was included or a categorical variable for the number of chronic conditions. Interactions terms of multimorbidity and educational level were added into the previously mentioned models. Results: Over the past ten years, there was an increase of 1.6%-point in the percentage of people with multimorbidity. The percentage of people with three or more conditions increased with +2.1%-point. People with multimorbidity had considerably worse physical and mental health outcomes than people without multimorbidity. For the ADL, the impact of multimorbidity was three times greater in the lowest educational level than in the highest educational level. For the MHI, the impact of multimorbidity was two times greater in the lowest than in the highest educational level. Each additional chronic condition was associated with a greater worsening in health outcomes. Similarly, for costs, where there was no evidence of a diminishing impact of additional conditions either. In patients with multimorbidity total healthcare costs were on average €874 higher than in patients with a single morbidity. Conclusion: The impact of multimorbidity on health and costs seems to be greater in the sicker and lower educated population. [ABSTRACT FROM AUTHOR]

This article reports that the enhanced forward gate bias time-dependent dielectric breakdown (TDDB) reliability and interface quality are achieved in 5-nm ferroelectric Hf0.5Zr0.5O2 (HZO) technologies by using the NH3 plasma interfacial layer (IL) treatment and microwave annealing (MWA). An orthorhombic crystalline phase is observed in the annealed HZO film with NH3 plasma IL treatment and MWA, and NH3 plasma IL treatment can suppress Hf/Zr interdiffusion. Metal-oxide-semiconductor capacitors (MOSCAPs) subjected to NH3 plasma IL treatment and 2100-W MWA also have a higher extrapolated operating voltage for a ten-year lifetime at 0.01% failure and lower interface state density (Dit) compared to the devices subjected to only rapid thermal annealing (RTA) at 600 °C. Therefore, NH3 plasma treatment and MWA are effective for improving the TDDB reliability and interface quality of the ultrathin ferroelectric HZO. [ABSTRACT FROM AUTHOR]

This study quantifies the impact of the inclusion of realistic surface spectral emissivity in the Sahara and Sahel on the simulated local climate and beyond. The surface emissivity in these regions can be as low as 0.6–0.7 over the infrared window band while close to unity in other spectral bands, but such spectral dependence has been ignored in current climate models. Realistic surface spectral emissivities over the Sahara and Sahel are incorporated into the Community Earth System Model (CESM) version 1.1.1, while treatments of surface emissivity for the rest of the globe remain unchanged. Both the modified and standard CESM are then forced with prescribed climatological SSTs and fixed present-day forcings for 35-yr simulations. The outputs from the last 30 years are analyzed. Compared to the standard CESM, the modified CESM has warmer surface air temperature, as well as a warmer and wetter planetary boundary layer over the Sahara and Sahel. The modified CESM thus favors more convection in these regions and has more convective rainfall, especially in the Sahara. The moisture convergence induced by such inclusion of surface spectral emissivity also contributes to the differences in simulated precipitation in the Sahel and the region south to it. Compared to observations, inclusion of surface spectral emissivity reduces surface temperature biases in the Sahara and precipitation biases in the Gulf of Guinea but exacerbates the wet biases in the Sahara. Such realistic representation of surface spectral emissivity can help unmask other factors contributing to regional biases in the original CESM. [ABSTRACT FROM AUTHOR]

Objectives: To assess the surgical accuracy of 3D virtually planned orthognathic surgery among patients with and without cleft. Materials and methods: This retrospective cohort study included cleft and non-cleft patients with class III malocclusion who underwent bimaxillary surgery. CBCT scans were acquired before and immediately after surgery. 3D virtual surgical planning (VSP) was performed using CBCT and digitalized dentition data. All orthognathic surgeries were performed by the same surgeons using interocclusal splints. The primary outcome variable was surgical accuracy, defined as the difference between the planned and surgically achieved maxillary movements, quantified in six degrees of freedom. Analysis of covariance was used to test for intergroup differences in surgical accuracy after correcting for differences in the magnitude of planned surgical maxillary movements. Results: Twenty-eight cleft and 33 non-cleft patients were enrolled, with mean ages of 18.5 and 25.4 years, respectively (P=0.01). No significant gender difference was present between the groups (P=0.10). After adjustment for small differences in surgical movements, no significant differences in surgical accuracy were observed between cleft and non-cleft patients. Conclusion: The present study demonstrates that high surgical accuracy in maxillary movements can be achieved in both cleft and non-cleft patients using VSP and interocclusal splints. Clinical relevance: Orthognathic cases with cleft can be performed with 3D VSP to obtain a satisfactory surgical accuracy. [ABSTRACT FROM AUTHOR]

This paper considers an M/M/1 queue with second optional service, in which the server is subject to working breakdowns and repairs. All arriving customers require the first essential service, whereas only a portion of them require a second optional service. In case where the server may break down while providing the first (essential) or second (optional) service, the server continues operation at a reduced level rather than ceasing service entirely. The stability condition for this queue is derived in explicit form. The matrix-geometric method is used to compute the stationary probability distribution of the system size and various system performance measures. The genetic algorithm is applied to a cost optimization problem with the aim of optimizing service rates by minimizing the expected cost per unit time. Finally, a numerical example is presented for illustrative purposes. [ABSTRACT FROM AUTHOR]

In this paper, low-temperature polycrystalline silicon (poly-Si) tunnel thin-film transistors (tunnel-TFTs) are demonstrated to show excellent short-channel effects immunity due to their special current transport mechanism: inter-band tunneling. The ammonia (NH 3 ) plasma surface treatment before the deposition of gate dielectric can significantly reduce the grain boundary trap state densities (N GB ) of poly-Si channel film and the interface trap state densities (N it ) at the gate-oxide/poly-Si interface. About 27% reduction of N GB by NH 3 plasma surface treatment can reduce the minimum drain current ~ 0.51 × and improve the subthreshold slope due to the suppression of trap-assisted tunneling, which dominates the current transport in the subthreshold operation region. In addition, about 37% reduction of N it by NH 3 plasma surface treatment can significantly enhance the on-state current ~ 2.86 × due to the increase of band bending of poly-Si channel potential, which can decrease the tunneling distance to increase the electron tunneling probability. Consequently, the performance improvement of poly-Si tunnel-TFTs by the NH 3 plasma surface treatment would be helpful for the development of system-on-panel and three-dimension integrated circuits. [ABSTRACT FROM AUTHOR]

Fucoidans, sulfated and fucosylated polysaccharides extracted from brown seaweed, were found to inhibit radiotherapy-induced cell damage and fibrosis through the TGF-β1 pathway. However, the comprehensive molecular response during irradiation-induced fibrosis and fucoidan-assisted recovery still remain unclear. Rat hind limbs were irradiated and smeared with low molecular weight fucoidan (LMF). Protein profiles were examined by a mass spectrometry-based proteomics analysis. Out of a total of 4625 proteins, 233 were found to be significantly up-regulated after irradiation and down-regulated after LMF treatment. Pathway and protein-protein interaction network analyses further indicated that four proteins including Actb, Ezr, Msn and Cdc42 were clustered into the tight junction and regulation of actin cytoskeleton pathways. These four proteins may serve as biomarkers for the detection of skin fibrosis induced by irradiation or TGF-β1, and for the recovery following LMF treatment. [Display omitted] • Actb, Ezr, Msn and Cdc42, served as multiple biomarkers of skin fibrosis. • Fucoidan inhibits Actb, Ezr, Msn and Cdc42 expression induced by TGF-β1. [ABSTRACT FROM AUTHOR]

In this brief, the tunnel FETs (TFETs) with a polycrystalline-Si (poly-Si) channel have been demonstrated, and the performance of the poly-Si TFET shows a significant improvement by the reduction of interface trap states ( N\mathrm {{it}} ) near the conduction band edge. The ON-state current ( I\mathrm{\scriptscriptstyle ON} ) conduction mechanism, band-to-band tunneling, of poly-Si TFETs is strongly affected by the band bending of poly-Si channel. The N2 plasma surface treatment before the gate dielectric deposition can produce a plasma-induced interfacial layer to reduce N\mathrm {it} obviously, which greatly enhances the surface potential modulation by the gate and improves the I\mathrm{\scriptscriptstyle ON} value of poly-Si TFETs \sim 3.7\times . The OFF-state current ( I_{\mathrm { {min}}} ) attributed to the trap-assisted tunneling (TAT) can also be reduced by a factor of \sim 40 %, because of the passivation of grain boundary trap ( N\mathrm {trap} ) of the poly-Si channel film. Consequently, the ON/OFF current ratio is enhanced from 9.42\times 10^{5} to 6.13\times 10^6 . In addition, the subthreshold swing, $I_{{\mathrm{\scriptscriptstyle ON}}}$ , and I_{\mathrm { {min}}} of poly-Si TFET exhibit superior short-channel effect immunity, which shows good feasibility for implementing high packing density of poly-Si thin-film transistors, such as 3-D nonvolatile memory and pixel driving device. [ABSTRACT FROM AUTHOR]

In the logistics industry, unmanned aerial vehicles (UAVs) are mostly used for last-mile delivery, in combination with other types of vehicles. There is currently no operator in Taiwan that is completely reliant upon the usage of UAVs for cargo delivery services. Therefore, this study proposes a routing and scheduling model for UAVs by utilizing the network flow technique and mathematical programming methods. All advance requests must be satisfied, and the related operating constraints ensured in the model. The model aims to minimize the total operating cost. To effectively solve large problems that may occur in practice, this study develops a relax-and-fix heuristic. Numerical tests are conducted to preliminarily examine whether the model, coupled with the heuristic algorithm, could be applied in practice. The test results indicate that the proposed model and solution algorithm are effective and thus could be useful for UAV operators to perform delivery routing and scheduling. [ABSTRACT FROM AUTHOR]

(1) Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for predicting cardiovascular diseases. Metabolic syndrome is characterized by a state of chronic inflammation that is related to an increased risk of cardiovascular events and death. In the present study, we aimed to analyze the correlation between cardiometabolic risk factors and Lp-PLA2 levels. (2) We collected the related retrospective medical data of Chinese adults, of which 3983 were men and 2836 were women (aged ≥ 18 years), who underwent health check-ups, and discussed the sex and age-related differences. (3) Data analysis showed that Lp-PLA2 was significantly related to lipoproteins and glutamic pyruvic transaminase (GPT), and that a linear trend was observed with increasing Lp-PLA2 levels for all ages and sexes. However, fasting glucose was significantly related to Lp-PLA2 only in the younger population. The two obesity-related parameters (waist-to-height ratio and waist circumference) also had a greater correlation with Lp-PLA2 levels in the younger groups; however, the correlation weakened in the elderly population. Meanwhile, the correlation between mean arterial pressure and creatinine level and Lp-PLA2 was significant only in younger men. (4) The results show that the expression patterns of Lp-PLA2 differ between sexes and across age groups. [ABSTRACT FROM AUTHOR]

Key message: Apocynin is a natural organic compound structurally related to vanillin. We demonstrated that hydrogen peroxide and heme oxygenase participated in apocynin-induced lateral root formation in rice. Abstract: Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. Information concerning the effect of apocynin on plants is limited. In this study, we examined the effect of apocynin on lateral root (LR) formation in rice. Treatment with apocynin induced LR formation and increased HO production, but had no effect on nitric oxide production. Diphenyleneiodonium chloride, an inhibitor of HO generating NADPH oxidase, was effective in reducing apocynin-induced HO production and LR formation. Apocynin treatment also increased superoxide dismutase activity and decreased catalase activity. HO application was able to increase the number of LRs. Moreover, HO production caused by HO and apocynin was localized in the root area corresponding to the LR emergence. Treatment with HO and apocynin also increased heme oxygenase (HO) activity and induced OsHO1 mRNA expression. Lateral root formation and HO activity induced by HO and apocynin were reduced by Zn protoporphyrin IX (the specific inhibitor of HO). Our data suggest that both HO and HO are required for apocynin-induced LR formation in rice. [ABSTRACT FROM AUTHOR]

Lateral root (LR) development performs the essential tasks of providing water, nutrients, and physical support to plants. Therefore, understanding the regulation of LR development is of agronomic importance. In this study, we examined the effect of nitric oxide (NO), auxin, and hemin (Hm) on LR formation in rice. Treatment with Hm [a highly effective heme oxygenase (HO) inducer], sodium nitroprusside (SNP, an NO donor), or indole-3-butyric acid (IBA, a naturally occurring auxin) induced LR formation and HO activity. LR formation and HO activity induced by SNP and IBA but not Hm was reduced by the specific NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. As well, Hm, SNP, and IBA could induce OsHO1 mRNA expression. Zn protoporphyrin IX (the specific inhibitor of HO) and hemoglobin (the carbon monoxide/NO scavenger) reduced LR number and HO activity induced by Hm, SNP, and IBA. Our data suggest that HO is required for Hm-, auxin-, and NO-induced LR formation in rice. [ABSTRACT FROM AUTHOR]

To explore the venom diversity and systematics of pit vipers under the genus Protobothrops, the venom phospholipases A2 (PLA2s) of P. mangshanensis, P. elegans and P. tokarensis were purified and characterized for the first time. The results were compared with the corresponding venom data of other co-generic species including P. mucrosquamatus, P. flavoviridis and P. jerdonii. Based on sequence features at the N-terminal regions, we identified five PLA2 subtypes, i.e., the Asp49-PLA2s with N6, E6 or R6 substitution and the Lys49-PLA2. However, not all subtypes were expressed in each of the species. Venom N6-PLA2s from P. mangshanensis and P. tokarensis venom were weakly neurotoxic toward chick biventer cervicis tissue preparations. The venoms of P. tokarensis and P. flavoviridis contained identical PLA2 isoforms. In most Protobothrop disintegrins, sequences flanking the RGD-motif are conserved. Phylogenetic analyses based on amino acid sequences of both families of the acidic PLA2s and the disintegrins clarify that these species could belong to a monophyletic group. [Copyright &y& Elsevier]

The tumor microenvironment plays a critical role in the control of metastasis. The epithelial–mesenchymal transition (EMT) is strongly associated with tumor metastasis, and consists of several protein markers, including E-cadherin and vimentin. We discovered that chrysophanol causes oral cancer cell apoptosis and the inhibition of migration/invasion and EMT. However, the detailed mechanisms of chrysophanol and its role in oral cancer with respect to the tumor microenvironment remain unknown. In the clinic, proinflammatory cytokines, such as IL-6 and IL-8, exhibit a higher expression in patients with oral cancer. However, the effect of chrysophanol on the production of IL-6 and IL-8 is unknown. We evaluated the expression of IL-6 and IL-8 in human SAS and FaDu oral cancer cell lines in the presence or absence of chrysophanol. The migration and invasion abilities were also determined using a Boyden chamber assay. Our results showed that treatment with chrysophanol significantly decreased the expression of IL-6 and IL-8, as well as the invasion ability of oral cancer cells. Moreover, chrysophanol also attenuated the EMT by increasing the expression of E-cadherin and reducing the expression of vimentin. Mechanistically, chrysophanol inhibited IL-6- and IL-8-induced invasion and STAT3 phosphorylation. IL-6 and IL-8 promote EMT and cell invasion, which is potentially related to the STAT3 signaling pathway in oral cancer. These findings provide insight into new aspects of chrysophanol activity and may contribute to the development of new therapeutic strategies for oral cancer. [ABSTRACT FROM AUTHOR]

Objectives: Surgery-first orthognathic surgery is rarely used in class III asymmetry due to concerns of reduced skeletal stability from unstable surgical occlusion. This study aimed to evaluate if skeletal stability after surgery-first orthognathic surgery is related to virtual surgical occlusal contact or surgical change. Materials and methods: We studied 58 adults with class III asymmetry, consecutively corrected by Le Fort I osteotomy and bilateral sagittal split osteotomy using a surgery-first approach. Dental casts were manually set to measure virtual surgical occlusal contact including contact distribution, contact number, and contact area. Cone-beam computed tomography taken before treatment, 1-week post-surgery, and after treatment was used to measure surgical change and post-surgical stability of the maxilla and mandible in translation (left/right, posterior/anterior, superior/inferior) and rotation (pitch, roll, yaw). The relationship between skeletal stability and surgical occlusal contact or surgical change was evaluated with correlation analysis. Results: Significant instability was found in the mandible but not in the maxilla. No correlation was found between the maxillary or mandibular stability and surgical occlusal contact (all p > 0.01). However, a significant correlation was found between the maxillary (roll and yaw) or mandibular (shift, roll and pitch) stability and its surgical change (all p < 0.001). Conclusions: In correction of class III asymmetry with surgery-first bimaxillary surgery, the skeletal stability is not related to the virtual surgical occlusal contact, but surgical skeletal change. Clinical relevance: Planned over-correction is a reasonable option for correction of severe shift or roll mandibular asymmetry in bimaxillary surgery for class III deformity. [ABSTRACT FROM AUTHOR]

Fetal loss (FL) from the 45th day of gestation until calving can impose a significant economic burden on dairy farmers, resulting in lost profits and increased production costs. Pregnancy-associated glycoprotein (PAG) is commonly used for detecting pregnancy in cows. PAG is secreted by binucleated trophoblast cells of the placenta and regulated by more than 24 genes. The purpose of this study was to determine the PAG threshold for FL and a probability of pregnancy maintenance until calving based on milk PAG levels. Our results reveal that primiparous and multiparous cows that maintained pregnancy until the 40th week exhibited higher PAG sample-negative (SN) values in their milk in the 6th week of gestation than did those that experienced FL later in gestation. Pregnant cows with higher PAG SN values in the 6th week of gestation were more likely to maintain their pregnancies. The area under the receiver operating characteristic curve for predicting the probability of pregnancy maintenance was 0.722 for our prediction model. On the other hand, a milk PAG SN value of <0.192 indicated 95 % confidence that FL would occur between the 7th and 40th weeks of gestation. Milk PAG testing is a noninvasive sampling technique that does not induce additional stress in lactating cows. The study reveals that PAG SN values increase significantly in Holstein cows during the 6th week of gestation. The predictive model developed was effective in forecasting pregnancy outcomes up to the 40th week of gestation or calving. The model's performance is moderately good for field application and could be a useful tool for dairy producers. • PAG levels in milk predict fetus gestational health in cows. • Effective prediction model of pregnancy maintenance to 40 weeks. • Model with 72.2 % accuracy aids in cow pregnancy management. [ABSTRACT FROM AUTHOR]

Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell lines and human glioma tissues. In addition, we used small interfering RNA (SiPLP2) and short hairpin RNA (shPLP2) to knockdown PLP2 expression in GBM8401 and LN229 glioma cell lines. After then, the alteration of PLP2 suppressed glioma cells behavior were examined by cell proliferation, wound healing, cell invasion, and colonies formation assays. Finally, the possible mechanism of PLP2 was analyzed by detecting the expression of the proteins related to cell-cycle checkpoints, cell-proliferative signaling factors, and cell-matrix interaction. Compared with normal brain cell lysates and mRNA, all glioma cell lines displayed PLP2 protein and mRNA overexpression. Besides, higher PLP2 IHC staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. Both siPLP2 transfected gliomas showed a clear inhibition of glioma cell proliferation, migration, and invasion as well as down-regulating p-p38, p-ERK, MMP-2, and MMP-9 expression. In conclusion, we successfully demonstrated that PLP2 overexpression played an oncogenic role in glioma development and aggressive tumor behavior. [ABSTRACT FROM AUTHOR]

Background Beginning from 2015–2016, unprecedented large outbreaks of acute hepatitis A that predominantly affected men who have sex with men (MSM) reemerged across the continents. We assessed the impact of an early initiated hepatitis A virus (HAV) vaccination campaign that targeted MSM living with human immunodeficiency virus (HIV) during the 2015–2017 hepatitis A outbreak in Taiwan. Methods First, we ascertained the effectiveness of HAV vaccination for MSM living with HIV using a nested case-control study of 1470 persons living with HIV who were initially HAV-seronegative. We then fitted a model of HAV transmission among MSM, risk-structured by HIV status, to the actual epidemic curve of reported acute hepatitis A cases in Taiwan during 2015–2017. Results Fifty-five cases of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided protection rates of 96.1% and 97.8% among recipient MSM living with HIV, respectively. Model fitting yielded basic reproductive number estimates of 7.26 (MSM living with HIV) and 3.04 (MSM not living with HIV). In a counterfactual scenario without an HAV vaccination campaign, the outbreak would have involved 7153 hepatitis A cases during 2015–2017 in contrast to the 1352 that were observed. We therefore estimated that the HAV vaccination campaign averted 80.7% (sensitivity analysis, 48.8%–92.7%) of acute hepatitis A cases that would otherwise have occurred by the end of 2017. Conclusions The early initiated HAV vaccination campaign, which targeted MSM living with HIV, very effectively curtailed the 2015–2017 hepatitis A outbreak in Taiwan. [ABSTRACT FROM AUTHOR]

Given the newly reformed recommendations calling for students' engagement in scientific practices, we developed a learning game, entitled Anter: Ant Research Institute, for students to experiene the practices of ant scientists. The development process involved three iterations. The 1st iteration included 23 in-service science teachers (15 junior high school and 8 senior high school) to validate the game content and provide feedback to improve the game design. The 2nd iteration consisted of 103 junior high school (7th-8th grade, aged 12–14) and 95 senior high school (10th-11th grade, aged 15–17) students to evaluate the effectiveness of the game and the experiential value in gameplay. The 3rd iteration included 368 7th graders to test the behavioural learning hierarchy ("do-learn-feel") model. The testing indicated that Anter is effective for students to acquire knowledge about ants and develop skills related to conducting ant investigations. It provided students with a positive experience of value in gameplay, supporting the theorisation of the "do-learn-feel" ordering of relationships. This successful articulation of developing Anter to reliably achieve instructional goals in systematic procedures is of benefit for game-based science learning. • The design of Anter through three iterations of testing is systematically reported. • Anter is effective for students to learn knowledge about ants. • Anter is effective for students to develop the skills related to investigating ants. • Anter provided students with a positive experience of value in gameplay. • The theorisation of the "do-learn-feel" ordering of relationships was supported. [ABSTRACT FROM AUTHOR]

• Type III necrotizing fasciitis (NF) is encountered predominantly in Asian countries. • Type III NF has a mortality risk two-fold higher than type I or type II NF. • Type III NF caused by extraintestinal pathogenic Escherichia coli (ExPEC) exhibits the highest mortality risk. • Type III NF caused by Klebsiella pneumoniae has the second highest mortality risk. The aim of this study was to investigate the prognostic value of reclassified new type III monomicrobial gram-negative necrotizing fasciitis (NF) and the microbial factors associated with an increased risk of mortality. This study included 235 NF cases treated at National Taiwan University Hospital. We compared the mortality risk of NF caused by different causal microorganisms and examined the bacterial virulence genes profile and antimicrobial susceptibility pattern associated with an increase in mortality risk. Type III NF (n = 68) had a mortality risk two-fold higher than type I (polymicrobial, n = 64) or type II (monomicrobial gram-positive, n = 79) NF (42.6% vs 23.4% or 19.0%, P = 0.019 and 0.002, respectively). Mortality differed by causal microorganism (Escherichia coli [61.5%], Klebsiella pneumoniae [40.0%], Aeromonas hydrophila [37.5%], Vibrio vulnificus [25.0%], polymicrobial [23.4%], group A streptococci [16.7%], and Staphylococcus aureus [16.2%], in decreasing rank, P <0.001). Type III NF caused by E. coli , identified as extraintestinal pathogenic E. coli (ExPEC) via virulence gene analyses, was associated with a particularly high mortality risk (adjusted odds ratio: 6.51, P = 0.003) after adjusting for age and comorbidities. Some (38.5%/7.7%) of the E. coli strains were non-susceptible to third/fourth-generation cephalosporins but remained susceptible to carbapenems. Type III NF, especially cases caused by E. coli or K. pneumoniae , are associated with a comparatively higher mortality risk than type I or type II NF. Wound gram stain-based rapid diagnosis of type III NF may inform empirical antimicrobial therapy to include a carbapenem. [ABSTRACT FROM AUTHOR]

Background: The birth rate in Taiwan has declined rapidly; thus, encouraging women to give birth is an important issue in the country. Pregnant women may experience psychological distress, which may negatively impact the health of children and mothers. Prenatal psychological distress is more common in multiparous women than in primiparous women. In addition, compared with that in the second and third trimesters, psychological distress in the first trimester is relatively high. Understanding psychological distress and the associated factors for multiparous women in the first trimester is important to providing early interventions and preventing subsequent maternal and child health problems. Purpose: This study was designed to examine the important predictive factors related to depression, anxiety, and stress among Taiwanese multiparous women in the first trimester. Methods: A cross-sectional design was used. In all, 216 multiparous women at 16 weeks of pregnancy were recruited from three hospitals in Taiwan. Self-reported questionnaires were used to gather data on demographic characteristics, the parenting stress of motherhood, spousal support, and psychological distress. A multiple logistic regression analysis was conducted to examine the factors associated with psychological distress. Results: The prevalence of depression, anxiety, and stress in multiparous women was found to be 31.9%, 42.6%, and 11.1%, respectively. The multiple logistic regression analysis indicated that the stress related to parent–child interaction was a significant predictor of depression and anxiety, the stress related to child-rearing was a significant predictor of anxiety, and low spousal instrumental support was a significant predictor of stress. The model respectively explained 30%, 27%, and 23% of the variance in depression, anxiety, and stress. Conclusions/Implications for Practice: Reducing the stress related to parent–child interaction and child-rearing and encouraging spousal instrumental support should be considered during prenatal care when designing interventions to reduce the psychological distress of multiparous women in their first trimester. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach. • Circulating tumour cells (CTCs) from patients with pancreatic ductal adenocarcinoma were collected and expanded ex vivo to form organoids. • CTC-derived organoids were tested for sensitivity to a panel of pancreatic ductal adenocarcinoma treatments. • Drug sensitivity results correlated with clinical outcomes in patients. • First study to correlate drug sensitivity results from CTCs with clinical outcomes. • This system can potentially facilitate treatment selection and monitor resistance. [ABSTRACT FROM AUTHOR]

Abstract: Neutrophils have a crucial role in the immune system and are the first line of defense against pathogenic invaders. Neutrophil activation is required for their defensive function and can be induced by diverse stimuli, through either binding to cell surface receptors or direct intracellular target molecule stimulation. In this study, we found that 4?a,5?,6?,7?,8?,8?a-hexahydro-5,3?,4?-trihydroxy-5?,5?,8?a-trimethyl-4H-chromeno [2?,3?:7,6]flavone (ugonin U), a flavonoid isolated from Helminthostachys zeylanica (L) Hook, significantly induced superoxide production and release in a time- and concentration-dependent manner. A series of experiments was performed to dissect the mechanism of ugonin U-induced respiratory burst in human neutrophils. Our results demonstrated that ugonin U induced a slow increase in intracellular Ca2+, which was necessary for ugonin U-stimulated superoxide release. Use of a formyl peptide receptor (FPR) blocker, G protein inhibitor, and protein tyrosine kinase (PTK) inhibitor proved that FPR, G proteins, and PTKs were not associated with ugonin U-induced respiratory burst. Additionally, immunoblotting results revealed that ugonin U did not affect the phosphorylation of mitogen-activated protein kinases and protein tyrosine. Nevertheless, a phospholipase C (PLC) inhibitor and an inositol triphosphate (IP3) receptor antagonist considerably suppressed ugonin U-stimulated Ca2+ mobilization and subsequent superoxide release. Ugonin U also induced an increase in intracellular IP3 formation, which could be blocked using a PLC inhibitor. In conclusion, our study reveals that ugonin U represents the first identified natural flavonoid compound to directly stimulate PLC. Moreover, ugonin U induces respiratory burst via the PLC/IP3/Ca2+ pathway in human neutrophils. [Copyright &y& Elsevier]

BACKGROUND: Neonicotinoids are widely used insecticides, and tea is a popular non‐alcoholic beverage in Taiwan. However, the levels of neonicotinoids in Taiwanese tea leaves remain unclear. Therefore, this study aims to understand the characteristics of neonicotinoid and metabolite residues in Taiwanese tea leaves. METHODS: In this study, 12 tea leaf samples were collected in Taiwan and extracted by solid‐phase extraction before analysis by liquid chromatography–tandem mass spectrometry. In addition, the levels of neonicotinoids were compared with the maximum residue level standards from other countries. RESULTS: In Taiwanese tea leaves, five neonicotinoids and seven metabolites were detected. Different tea species influenced the levels of neonicotinoids and their metabolites in the present study. Moreover, the levels of neonicotinoids and their metabolites in partially fermented leaves were higher than in completely fermented leaves. In Jin‐Xuan tea, the levels of neonicotinoids and their metabolites in most winter‐harvested teas were lower than in summer‐harvested teas. CONCLUSION: The residue levels of neonicotinoids and their metabolites were detectable in Taiwanese tea leaves. Moreover, different tea species, manufacturing processes, and harvest seasons might influence the levels of these pesticides. Therefore, the government should monitor the use of neonicotinoids. © 2021 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The paper proposed a Fuzzy Multiple Criteria Decision Making (FMCDM) approach for banking performance evaluation. Drawing on the four perspectives of a Balanced Scorecard (BSC), this research first summarized the evaluation indexes synthesized from the literature relating to banking performance. Then, for screening these indexes, 23 indexes fit for banking performance evaluation were selected through expert questionnaires. Furthermore, the relative weights of the chosen evaluation indexes were calculated by Fuzzy Analytic Hierarchy Process (FAHP). And the three MCDM analytical tools of SAW, TOPSIS, and VIKOR were respectively adopted to rank the banking performance and improve the gaps with three banks as an empirical example. The analysis results highlight the critical aspects of evaluation criteria as well as the gaps to improve banking performance for achieving aspired/desired level. It shows that the proposed FMCDM evaluation model of banking performance using the BSC framework can be a useful and effective assessment tool. [Copyright &y& Elsevier]

Geographic venom samples of Crotalus viridis viridis were obtained from South Dakota, Wyoming, Colorado, Oklahoma, Texas, New Mexico, and Arizona. From these samples, the phospholipases A2 (PLA2s) were purified and their N-terminal sequences, precise masses, and in vitro enzymatic activities were determined. We purified two to four distinct acidic PLA2s from each sample; some of them displayed different inhibition specificities toward mammalian platelets. One of the acidic PLA2s induced edema, but had no anti-platelet activity. There was also a common basic PLA2 myotoxin in all the samples. We have cloned five acidic PLA2s and several hybrid-like nonexpressing PLA2s. Molecular masses and N-terminal sequences of the purified PLA2s were matched with those deduced from the cDNA sequences, and the complete amino acid sequences of five novel acidic PLA2s were thus solved. They share 78% or greater sequence identity, and a cladogram based on the sequences of many venom acidic PLA2s of New World pit vipers revealed at least two subtypes. The results contribute to a better understanding of the ecogenetic adaptation of rattlesnakes and the structure–activity relationships and evolution of the acidic PLA2s in pit viper venom. [Copyright &y& Elsevier]

Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP‐13) expression are higher in prostate cancer patients than in healthy cancer‐free individuals. Mechanistic investigations revealed that melatonin inhibits MMP‐13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c‐Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP‐13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations. [ABSTRACT FROM AUTHOR]

Cloud macrophysics schemes are unique parameterizations for general circulation models. We propose an approach based on a probability density function (PDF) that utilizes cloud condensates and saturation ratios to replace the assumption of critical relative humidity (RH). We test this approach, called the Global Forecast System (GFS) – Taiwan Earth System Model (TaiESM) – Sundqvist (GTS) scheme, using the macrophysics scheme within the Community Atmosphere Model version 5.3 (CAM5.3) framework. Via single-column model results, the new approach simulates the cloud fraction (CF)–RH distributions closer to those of the observations when compared to those of the default CAM5.3 scheme. We also validate the impact of the GTS scheme on global climate simulations with satellite observations. The simulated CF is comparable to CloudSat/Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) data. Comparisons of the vertical distributions of CF and cloud water content (CWC), as functions of large-scale dynamic and thermodynamic parameters, with the CloudSat/CALIPSO data suggest that the GTS scheme can closely simulate observations. This is particularly noticeable for thermodynamic parameters, such as RH, upper-tropospheric temperature, and total precipitable water, implying that our scheme can simulate variation in CF associated with RH more reliably than the default scheme. Changes in CF and CWC would affect climatic fields and large-scale circulation via cloud–radiation interaction. Both climatological means and annual cycles of many of the GTS-simulated variables are improved compared with the default scheme, particularly with respect to water vapor and RH fields. Different PDF shapes in the GTS scheme also significantly affect global simulations. [ABSTRACT FROM AUTHOR]

Background Chlorhexidine (CHG) bathing decreases the incidence of bloodstream infections in intensive care units, but its effect has been understudied in patients with hematological malignancies in noncritical care units. Methods Adults with hematological malignancies hospitalized for cytotoxic chemotherapy in noncritical care units were offered daily 2% CHG bathing. We compared outcomes of patients who chose CHG bathing (CHG group) with outcomes of those who did not choose CHG bathing (usual-care group). The primary outcome was gram-positive cocci–related, skin flora–related, or central line–associated bloodstream infection. The negative control outcome was gut-origin bacteremia. Results The CHG group (n = 485) had a crude incidence rate of the primary outcome that was 60% lower than the rate for the usual-care group (n = 408; 3.4 vs 8.4 per 1000 patient-days, P =.02) but had a similar crude incidence rate of the negative control outcome (4.5 vs 3.2 per 1000 patient-days; P =.10). In multivariable analyses, CHG bathing was associated with a 60% decrease in the primary outcome (adjusted hazard ratio [HR], 0.4; P <.001). In contrast, CHG bathing had no effect on the negative control outcome (adjusted HR, 1.1; P =.781). CHG bathing was well tolerated by participants in the CHG group. Conclusions CHG bathing could be a highly effective approach for preventing gram-positive cocci–related, skin flora–related, or central line–associated bacteremia in patients with hematological malignancies who are hospitalized for cytotoxic chemotherapy in noncritical care units. [ABSTRACT FROM AUTHOR]

Fibromyalgia syndrome (FM) is a multifactorial disorder whose pathogenesis and diagnosis are poorly understood. This study investigated differential serum proteome profiles in patients with FM and healthy pain-free controls and explored the association between serum proteome and clinical profiles in patients with FM. Twenty patients with FM (according to the American College of Rheumatology criteria, 2010) and 20 healthy pain-free controls were recruited for optimized quantitative serum proteomics analysis. The levels of pain, pressure pain threshold, sleep, anxiety, depression, and functional status were evaluated for patients with FM. We identified 22 proteins differentially expressed in FM when compared with healthy pain-free controls and propose a panel of methyltransferase-like 18 (METTL18), immunoglobulin lambda variable 3–25 (IGLV3–25), interleukin-1 receptor accessory protein (IL1RAP), and IGHV1OR21-1 for differentiating FM from controls by using a decision tree model (accuracy: 0.97). In addition, we noted several proteins involved in coagulation and inflammation pathways with distinct expression patterns in patients with FM. Novel proteins were also observed to be correlated with the levels of pain, depression, and dysautonomia in patients with FM. We suggest that upregulated inflammation can play a major role in the pathomechanism of FM. The differentially expressed proteins identified may serve as useful biomarkers for diagnosis and evaluation of FM in the future. [ABSTRACT FROM AUTHOR]

Background. Oral cancer belongs to the class of head and neck cancers and can be life threatening if not diagnosed and treated early. Activation of cell death via apoptosis or reactive oxygen species (ROS) accumulation and inhibition of cell cycle progression, migration, and epithelial-to-mesenchymal transition (EMT) may be a good strategy to arrest the development of oral cancer. In this study, we analyzed the possible action of chrysophanol isolated from the rhizomes of Rheum palmatum on the oral cancer cell lines FaDu (human pharynx squamous cell carcinoma) and SAS (human tongue squamous carcinoma) by investigating whether chrysophanol could influence cell death. Method. Cell viability was measured by using the MTT assay. For the detection of apoptosis, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and subG1 population analysis were used. We also examined cell cycle progression and ROS levels by flow cytometry. Additionally, the expression of p53, p21, procaspase 3, cyclin D1, CDK4, cdc2, CDK2, E-cadherin, vimentin, and PCNA was evaluated by western blotting. Conclusion. Chrysophanol has an anticancer effect on FaDu and SAS cell lines. There is an increase in subG1 accumulation, ROS production, and cell cycle G1 arrest after treatment with chrysophanol. On the other hand, chrysophanol inhibited cell migration/metastasis and EMT. We proposed that chrysophanol may be a good candidate compound on oral cancer treatment in the further. [ABSTRACT FROM AUTHOR]