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Background and Aims: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material., Methods: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material., Results: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm 2 and 10.74 mm 2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] μg vs .70 [interquartile range, .27-1.24] μg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001)., Conclusions: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

At different observation intervals of 1, 5, and 10 days during a trial period of 30 days, the mortality rates of Hypothenemus hampei were 100, 95, and 55%, and the fecundity rates were 0.55, 8.45, and 19.35 eggs/female, respectively. At temperatures of 18, 21, 24, and 27 °C, the development time of the immature stage of H. hampei was significantly shortened with increasing temperature. Furthermore, the lower developmental threshold ( T 0 ) and thermal summation ( K ) of the immature stage were 8.91 °C and 485.44 degree-days, respectively. The greatest longevity of female and male adults reached 115.77 and 26.50 days, respectively, at 18 °C. The highest fecundity was 29.00 eggs/female at 24 °C. The population parameters of H. hampei were analyzed on the basis of the age-stage, two-sex life table theory. According to the data, the parameters were significantly affected by temperature. The highest net reproductive rate ( R 0 ) was 13.32 eggs/individual at 24 °C. The highest intrinsic rate of increase ( r ) and finite rate of increase ( λ ) were calculated as 0.0401 and 1.0409 day -1 , respectively, at a temperature of 27 °C. The shortest mean generation time ( T ) was 51.34 days at 27 °C. Overall, we provide a discussion on comprehensive biological information regarding H. hampei , thus providing basic knowledge for further research on this pest.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population-based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011-2018) were obtained from Taiwan's National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11-0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41-8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35-77.2 and IS: aHR, 290.2; 95% CI, 103.1-816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections., (© 2023. The Author(s).)

The concept of chronic kidney disease (CKD) originated in the 2000s, and an estimated 850 million patients are currently suffering from health threats from different degrees of CKD. However, it is unclear whether the existing CKD care systems are optimal for improving patient prognosis and outcomes, so this review summarizes the burden, existing care models, effectiveness, challenges, and developments of CKD care. Even under the general care principles, there are still significant gaps in our understanding of the causes of CKD, prevention or care resources, and care burdens between countries worldwide. Receiving care from multidisciplinary teams rather than only a nephrologist shows potential profits in comprehensive and preferable outcomes. In addition, we propose a novel CKD care structure that combines modern technologies, biosensors, longitudinal data visualization, machine learning algorithms, and mobile care. The novel care structure could simultaneously change the care process, significantly reduce human contact, and make the vulnerable population less likely to be exposed to infectious diseases such as COVID-19. The information offered should be beneficial, allowing us to rethink future CKD care models and applications to reach the goals of health equality and sustainability.

Lungs and kidneys are two vital and frequently injured organs among critically ill patients. In this study, we attempt to develop a weaning prediction model for patients with both respiratory and renal failure using an explainable machine learning (XML) approach. We used the eICU collaborative research database, which contained data from 335 ICUs across the United States. Four ML models, including XGBoost, GBM, AdaBoost, and RF, were used, with weaning prediction and feature windows, both at 48 h. The model's explanations were presented at the domain, feature, and individual levels by leveraging various techniques, including cumulative feature importance, the partial dependence plot (PDP), the Shapley additive explanations (SHAP) plot, and local explanation with the local interpretable model-agnostic explanations (LIME). We enrolled 1789 critically ill ventilated patients requiring hemodialysis, and 42.8% (765/1789) of them were weaned successfully from mechanical ventilation. The accuracies in XGBoost and GBM were better than those in the other models. The discriminative characteristics of six key features used to predict weaning were demonstrated through the application of the SHAP and PDP plots. By utilizing LIME, we were able to provide an explanation of the predicted probabilities and the associated reasoning for successful weaning on an individual level. In conclusion, we used an XML approach to establish a weaning prediction model in critically ill ventilated patients requiring hemodialysis.

Background/aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses., Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed., Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568)., Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Background: Oral cancer is one of the leading causes of cancer-related deaths worldwide. Chemotherapy is widely used in the treatment of oral cancer, but its clinical efficacy is limited by drug resistance. Hence, novel compounds capable of overcoming drug-resistance are urgently needed., Purpose: Plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, has been used to treat various cancers. In this study, we investigated the anticancer effects of PG on drug-resistant oral cancer (CR-SAS) cells, as well as the underlying mechanism., Methods: MTT assays were used to evaluate the effect of PG on the viability of CR-SAS cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined using flow cytometry. Protein expression levels were detected by western blotting., Results: The results show that PG reduces the viability and causes the apoptosis of CR-SAS cells. PG is able to induce intracellular and mitochondrial ROS generation that leads to mitochondrial dysfunction. Furthermore, endoplasmic reticulum (ER) stress was triggered in PG-treated CR-SAS cells. The inhibition of ROS using N-acetylcysteine (NAC) abrogated the PG-induced ER stress and apoptosis, as well as the reduction in cell viability. Meanwhile, similar results were observed both in zebrafish and in murine models of drug-resistant oral cancer., Conclusion: Our results indicate that PG induces the apoptosis of CR-SAS cells via the ROS-mediated ER stress pathway and mitochondrial dysfunction. It will be interesting to develop the natural compound PG for the treatment of drug-resistant oral cancer., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The development of endocrine therapy resistance in the luminal A subtype of breast cancer is related to the appearance of protective autophagy. The bioactive component from the root of licorice, 18β-glycyrrhetinic acid (18β-GA), has many antitumor properties. Whether 18β-GA can modulate autophagy to inhibit proliferation of the luminal A subtype is still unclear. The proportion of apoptosis caused by 18β-GA in MCF-7 and T-47D cells was determined using flow cytometry. The autophagy marker, LC3-II conversion, was investigated using Western blotting, and a Premo TM Tandem Autophagy Sensor Kit. We found that the concentration (150-μM) of 18β-GA caused caspase-dependent apoptosis and LC3-II accumulation or blocked autophagic flux. Moreover, 18β-GA-mediated apoptosis was improved using rapamycin but reversed by 3-methyladenine (3-MA) addition. The phosphorylation level of Jun-amino-terminal kinase (JNK) was increased significantly in the 18β-GA treatment and combined incubation using rapamycin. A JNK inhibitor (SP600125) significantly inhibited 18β-GA-mediated apoptosis, LC3-II accumulation and rescued the numbers of MCF-7 and T-47D colony formation. Especially, 18β-GA can inhibit xenograft tumor growth in BALB/c nude mice. These data indicate the combination of 18β-GA with rapamycin or 3-MA can sensitize or decrease MCF-7 and T-47D cells to 18β-GA-induced apoptosis, respectively. 18β-GA modulated autophagy is cytotoxic to luminal A subtype breast cancer cells through apoptosis promotion and JNK activation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Patterns of shedding replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe or critical COVID-19 are not well characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical coronavirus disease 2019 (COVID-19)., Methods: We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using viral culture and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical and epidemiologic metadata were reviewed., Results: We collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset and in 1 of 67 (1.5%) immunocompetent patients 10 days after symptom onset (P = .001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6-45) for ICU patients and 58.5 days (range, 34-139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients., Conclusions: Immunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease., Competing Interests: Potential conflicts of interest. M. K. H. is a member of a clinical adjudication panel for a SARS-CoV-2 vaccine under development by Sanofi; reports support unrelated to this work from the CDC; and is 2021 President of the SHEA Board of Directors, Chair of IDSA Rapid Guidelines Committee for COVID-19 Diagnosis, and Chair of IDSA Diagnostics Committee. N. M. M. reports a research contract unrelated to this work and paid to his institution from Cepheid, Inc; honoraria for a continuing education lecture from South Central Association for Clinical Microbiology, honoraria for book chapters from Elsevier, honoraria for a continuing education lecture from the American Society for Clinical Laboratory Science; and a position as President-Elect of the Illinois Society for Microbiology. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to determine the impact on hearing prognosis of the coherent frequency with high magnitude-squared wavelet coherence (MSWC) in video head impulse test (vHIT) among patients with sudden sensorineural hearing loss with vertigo (SSNHLV) undergoing high-dose steroid treatment. This study was a retrospective cohort study. SSNHLV patients treated at our referral center from December 2016 to December 2020 were examined. The cohort comprised 64 patients with SSNHLV undergoing high-dose steroid treatment. MSWC was measured by calculating the wavelet coherence analysis (WCA) at various frequencies from a vHIT. The hearing prognosis were analyzed using a multivariable Cox regression model and convolution neural network (CNN) of WCA. There were 64 patients with a male-to-female ratio of 1:1.67. The greater highest coherent frequency of the posterior semicircular canal (SCC) was associated with the complete recovery (CR) of hearing. After adjustment for other factors, the result remained robust (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.86-2.35). In the feature extraction with Resnet-50 and proceeding SVM in the horizontal image cropping style, the classification accuracy [STD] for (CR vs. partial + no recovery [PR + NR]), (over-sampling of CR vs. PR + NR), (extensive data extraction of CR vs. PR + NR), and (interpolation of time series of CR vs. PR + NR) were 83.6% [7.4], 92.1% [6.8], 88.9% [7.5], and 91.6% [6.4], respectively. The high coherent frequency of the posterior SCC was a significantly independent factor that was associated with good hearing prognosis in the patients who have SSNHLV. WCA may be provided with comprehensive ability in vestibulo-ocular reflex (VOR) evaluation. CNN could be utilized to classify WCA, predict treatment outcomes, and facilitate vHIT interpretation. Feature extraction in CNN with proceeding SVM and horizontal cropping style of wavelet coherence plot performed better accuracy and offered more stable model for hearing outcomes in patients with SSNHLV than pure CNN classification. Clinical and Translational Impact Statement-High coherent frequency in vHIT results in good hearing outcomes in SSNHLV and facilitates AI classification.

Introduction: The FIGO 2018 staging of cervix cancer recognizes a total of 11 categories of loco-regionally advanced cervix cancer (LRACC). Whilst incorporating imaging is an improvement over clinical staging (FIGO 2009), this had led to more categories of disease which are not prognostically discrete groups. We aimed to analyze survival according to 2018 FIGO stages of cervix cancer and identify isoprognostic groups of patients based on primary tumor volume and nodal status., Methods: Patients referred for radiotherapy with curative intent between 1996 and 2014 were eligible. Baseline clinico-pathological and follow up information was retrieved from an ethics-approved institutional prospective database. Patients were classified according to FIGO 2018 staging based on histo-pathology, MRI (tumor volume and local compartmental spread assessment) and PET results (nodal spread). Kaplan-Meier method was used to estimate survival at five years. Following survival analysis using recognized prognostic factors, isoprognostic categories were identified and merged to form 5 isoprognostic groups., Results: Seven hundred and forty-four LRACC patients were included. The median (IQR) follow-up was 5.1 (2.6-8.4) yrs. Stage migration occurred in most patients, showing heterogeneous 5 years survival according to 2018 FIGO stages. In contrast progressively worsening prognosis could be demonstrated in the 5 observed isoprognostic clusters (p < 0.002)., Conclusion/implications: Prognosis in LRACC depends on the interplay between primary tumor characteristics, type of local spread and nodal disease. A prospective study of survival and patterns of failure according to isoprognostic clusters would be useful to determine the most appropriate treatment modality and estimate survival as well as better patient selection for clinical trials., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the relative progress of safety-net hospitals (SNHs) under Medicare's Comprehensive Care for Joint Replacement (CJR) mandatory bundled payment model over 2016-2020 and to identify the contributors to SNHs' realization of success under the program., Data Sources/study Setting: Secondary data on all CJR hospitals were collected from the Centers for Medicare and Medicaid Services (CMS) public use files and from the American Hospital Association., Study Design: We addressed whether SNHs can achieve progress in financial performance under CJR by focusing on the relative change in reconciliation payments or the difference between episode spending and target prices. We applied the method of dominance analysis to ordinary least squares regression to determine the relative importance of predictors of change in reconciliation payments over time., Principal Findings: Compared to CJR hospitals overall, SNHs were less successful in meeting episode spending targets. Hospital factors dominated socioeconomic factors in explaining progress among SNHs, but not among non-SNHs. The contribution of nurse staffing was negligible across all CJR hospitals., Conclusions: The formula used by CMS to determine spending targets may not be sufficient to address disparities in SNH financial performance under mandatory bundled payment., (© 2022 Health Research and Educational Trust.)

A new species Clyzomedus pani sp. nov. is described from Beijing, Shaanxi, Henan and Anhui, China. Quercus acutissima Carruth (Fagaceae) is the possible host plant. Images of habitus, external morphology and genitalia are provided. It is one of the currently discovered new species from Capital of China, since for the Biodiversity Survey and Assessment Project of Beijing.

Background: Data from previous studies of the MVC-COV1901 vaccine, a subunit vaccine against SARS-CoV-2 based on the stable prefusion spike protein (S-2P) adjuvanted with CpG 1018 adjuvant and aluminum hydroxide, suggest that the vaccine is generally safe and elicits a good immune response in healthy adults and adolescents. By comparing with AZD1222, this study adds to the findings from previous trials and further evaluates the breadth of protection offered by MVC-COV1901., Methods: In this phase 3, parallel group, randomized, double-blind, active-controlled trial conducted in 2 sites in Paraguay, we assigned adults aged 18-91 years in a 1:1 ratio to receive intramuscular doses of MVC-COV1901 or AZD1222 administered as scheduled in the clinical trial. Serum samples were collected on the day of vaccination and 14 days after the second dose. Primary and secondary safety and immunogenicity endpoints were assessed. In addition, other outcomes investigated were cross-reactive immunity against the Omicron strain and the induction of IgG subclasses., Results: A total of 1,030 participants underwent randomization. Safety data was derived from this set while primary immunogenicity data involved a per-protocol immunogenicity (PPI) subset including 225 participants. Among the participants, 58% are seropositive at baseline. When compared against AZD1222, MVC-COV1901 exhibited superiority in terms of neutralizing antibody titers and non-inferiority in terms of seroconversion rates. Reactogenicity was generally mild and no serious adverse event was attributable to MVC-COV1901. Both vaccines have a Th1-biased response predominated by the production of IgG1 and IgG3 subclasses. Omicron-neutralizing titers were 44.5 times lower compared to wildtype-neutralizing titers among seronegative individuals at baseline. This fold-reduction was 3.0 times among the seropositive., Conclusion: Safety and immunogenicity data of MVC-COV1901 from the study in Paraguay confirm previous results. The previous infection coupled with vaccination of this vaccine may offer protection against the Omicron strain though its durability is still unknown., Competing Interests: Declaration of Competing Interest M.-Y. L., C. E. L., J.A.E., L.E., H.-Y.C., and C.C. are employees of Medigen Vaccine Biologics Corporation. R.J. is an employee of Dynavax Technologies Corporation. J.T., O.C.T., 385 L.B., L.A.G., G.E., and G.S. declared no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors have reviewed and approved of the final version of the manuscript., (Copyright © 2022. Published by Elsevier Ltd.)

To date, few studies have been conducted on the relationship between postbiotics and air pollution, and there is limited knowledge if postbiotic and probiotic have synergistic effects. Therefore, we created a PM-induced lung inflammation mice model and demonstrated the effect of probiotic, postbiotic, and their combination treatment on attenuation of PM2.5-induced lung damage and allergic response. The mice were intratracheally given PM2.5 triggering conditions of acute lung damage and allergic response. Our results showed that individual treatment of probiotic and postbiotic reduced body weight loss by 47.1% and 48.9%, but the results did not show any effect on polarizing IFN-γ/IL-4 ratio. In addition, PM2.5-induced overactive expression of IgE treated by probiotic and postbiotic was reduced by 33.2% and 30.4%, respectively. While combination treatment of probiotic and postbiotic exerted a synergistic effect, especially considerably on improving IgE reduction by 57.1%, body weight loss by 78.3%, and IFN-γ/IL-4 ratio boost by 87.5%. To sum up the above functionality, these research findings may help establish a novel platform for postbiotic application, formulation, and mechanistic selection with regard to PM2.5-induced lung injury. PRACTICAL APPLICATION: Allergic inflammation caused by PM2.5 is not like common allergens (ex. Pollens, ovalbumin, dust mites), which simply skewing Th1/Th2 polarization to Th2. Thus using probiotics screened by Th1-skewing criteria might not be the best choice to treat on PM2.5-induced symptoms. This research proposed a combination of probiotics and postbiotics on modulating immunity homeostasis, and consequently attenuating complications of PM2.5-induced lung damage. These research findings may help establish a novel platform for postbiotic application, formulation and mechanistic selection with regard to PM2.5-induced lung injury., (© 2022 Institute of Food Technologists.)

Objective: With the increasing incidence of stage IA lung cancer ≤1 cm in size, the optimal primary treatment remains to be controversial, and thus, we compared the survival of these patients treated with radiotherapy, wedge resection, segmentectomy, or lobectomy in a large population., Methods: We identified patients with stage IA lung cancer ≤1 cm in size between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival (OS) via Kaplan-Meier analysis and conducted Cox regression analysis via propensity score matching (PSM) method to identify the relative hazard ratio (HR) and difference of OS among these treatments in the subgroup stratified by four variables (age, total number of tumors, pathological grade, and histology)., Results: A total of 5435 patients were included with a median age of 68 years (range, 6-94 years), of which 2131 (39.2%) were male, and 3510 (64.6%) were adenocarcinoma. The 5-year OS rate was 67.1%, 34.5%, 61.6%, 72.1%, and 75.0% for the entire study population, radiotherapy, wedge resection, segmentectomy, and lobectomy, respectively. In PSM analysis, wedge resection and segmentectomy were all superior to radiotherapy (P < 0.001), and segmentectomy was superior to wedge resection (P = 0.043), while segmentectomy was comparable with lobectomy (P = 0.058). In patients with multiple tumors, radiotherapy brought similar survival to surgery (wedge resection versus radiotherapy, P = 0.323; segmentectomy versus radiotherapy, P = 0.170; lobectomy versus radiotherapy, P = 0.796)., Conclusions: Among stage IA lung cancer with ≤1 cm, segmentectomy and lobectomy were identified as the potential effective treatments, with segmentectomy more preferred, while radiotherapy would be recommended in those with multiple tumors, which requires further verification., Competing Interests: Declaration of competing interest A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. ASJSUR Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The oncogenic fusion protein EWS::FLI1 is an attractive therapeutic target in Ewing sarcoma (ES). Mithramycin A (MithA) is a potent and specific inhibitor of EWS::FLI1 that can selectively radiosensitize ES cells through transcriptional inhibition of DNA double-strand break (DSB) repair. Here, we evaluate temporal changes in cell cycle progression and apoptosis in ES cells treated with MithA and/or ionizing radiation (RTx), testing the hypothesis that combining MithA with ionizing radiation would synergistically impair cell cycle progression and enhance apoptotic elimination to a greater extent than either agent alone., Materials and Methods: Four EWS::FLI1 + ES cell lines TC-71, RD-ES, SK-ES-1, and A673, and one EWS::ERG cell line (CHLA-25) were exposed to 10nM MithA or vehicle and followed 24 h later by exposure to 2 Gy x-radiation or sham irradiation. Reactive oxygen species (ROS) activity was evaluated by cytometric assay, and assay of antioxidant gene expression by RT-qPCR. Cell cycle changes were evaluated by flow cytometry of nuclei stained with propidium iodide. Apoptosis was assessed by cytometric assessment of Caspase-3/7 activity and by immunoblotting of PARP-1 cleavage. Radiosensitization was evaluated by clonogenic survival assay. Proliferation (EdU) and apoptosis (TUNEL) were evaluated in SK-ES-1 xenograft tumors following pretreatment with 1 mg/kg MithA, followed 24 h later by a single 4 Gy fraction of x-radiation., Results: MithA-treated cells showed reduced levels of ROS, and were associated with increased expression of antioxidant genes SOD1 , SOD2, and CAT . It nonetheless induced persistent G 0 /G 1 arrest and a progressive increase of the sub-G 1 fraction, suggesting apoptotic degeneration. In vitro assays of Caspase-3/7 activity and immunoblotting of Caspase-3/7 dependent cleavage of PARP-1 indicated that apoptosis began as early as 24 h after MithA exposure, reducing clonogenic survival. Tumors from xenograft mice treated with either radiation alone, or in combination with MithA showed a significant reduction of tumor cell proliferation, while apoptosis was significantly increased in the group receiving the combination of MithA and RTx., Conclusions: Taken together, our data show that the anti-proliferative and cytotoxic effects of MithA are the prominent components of radiosensitization of EWS::FLI1 + ES, rather than the result of acutely enhanced ROS levels.

Phellinus linteus is a famous medicinal mushroom which exhibits various biological activities. This study aimed to investigate the effects of solid-state fermentation by Ph. linteus on the yield of bioactive compounds and antioxidant activities of beans. Four bean substrates were prepared and inoculated with inoculum of three strains of Ph. linteus, respectively. During the cultivation, the harvested samples were dried, grounded, extracted, and determined the contents of bioactive compounds and antioxidant activities. The results indicated that the mung bean fermented by Ph. linteus 04 had the highest polysaccharide content (98.8 mg/g). The highest total phenolic and flavonoid contents were in fermented soybeans by Ph. linteus 03 (15.03 mg gallic acid equivalents/g and 63.24 mg rutin equivalents/g, respectively). The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities of hot water extracts were higher than those of ethanolic extracts for fermented beans by three Ph. linteus strains. However, the superoxide anion radical scavenging ability of ethanolic extracts was higher than those of hot water extracts in the fermented beans of the three strains. The ferrous ion (Fe2+)-chelating abilities of hot water extracts were higher than those of ethanolic extracts in fermented beans by Ph. linteus 03 and 04. In contrast, ethanolic extracts were higher than hot water extracts in fermented beans by Ph. linteus 06. Overall, these results indicate that the fermentation by Ph. linteus strains increased the bioactive compounds and antioxidant activities of four beans.

Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from the age of 12-17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups, with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic.ClinicalTrials.gov registration: NCT04951388., (© 2022. The Author(s).)

The family Disteniidae is a moderately large and widely distributed lineage. Distenia punctulatoides belongs to the family Disteniidae from the cerambycoid assemblage. Here, we report the complete mitogenome of D. punctulatoides, which is 15,675 bp in length. It contains 37 genes and a noncoding control region, which are arranged in the same order as that of the putative ancestor of beetles. The total base composition of the new mitogenome is 40.2% for A, 17.1% for C, 10.0% for G, and 32.7% for T. The new mitogenomic organization, nucleotide composition, and codon usage do not differ significantly from other beetles. Using available complete mitogenomes, the high-level phylogeny of the family Disteniidae was explored. The phylogenetic analyses showed that Disteniidae were monophyletic, and the genus Distenia grouped with the genus Clytomelegena as sister groups. Combining the morphological and molecular data, Typodryas Thomson, 1864 is suggested to be a junior synonym of Distenia Lepeletier and Audinet-Serville, 1828., (© 2022 Wiley Periodicals LLC.)

Objectives: We quantified hospital-acquired coronavirus disease 2019 (COVID-19) during the early phases of the pandemic, and we evaluated solely temporal determinations of hospital acquisition., Design: Retrospective observational study during early phases of the COVID-19 pandemic, March 1-November 30, 2020. We identified laboratory-detected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) from 30 days before admission through discharge. All cases detected after hospital day 5 were categorized by chart review as community or unlikely hospital-acquired cases, or possible or probable hospital-acquired cases., Setting: The study was conducted in 2 acute-care hospitals in Chicago, Illinois., Patients: The study included all hospitalized patients including an inpatient rehabilitation unit., Interventions: Each hospital implemented infection-control precautions soon after identifying COVID-19 cases, including patient and staff cohort protocols, universal masking, and restricted visitation policies., Results: Among 2,667 patients with SARS-CoV-2, detection before hospital day 6 was most common (n = 2,612; 98%); detection during hospital days 6-14 was uncommon (n = 43; 1.6%); and detection after hospital day 14 was rare (n = 16; 0.6%). By chart review, most cases after day 5 were categorized as community acquired, usually because SARS-CoV-2 had been detected at a prior healthcare facility (68% of cases on days 6-14 and 53% of cases after day 14). The incidence rates of possible and probable hospital-acquired cases per 10,000 patient days were similar for ICU- and non-ICU patients at hospital A (1.2 vs 1.3 difference, 0.1; 95% CI, -2.8 to 3.0) and hospital B (2.8 vs 1.2 difference, 1.6; 95% CI, -0.1 to 4.0)., Conclusions: Most patients were protected by early and sustained application of infection-control precautions modified to reduce SARS-CoV-2 transmission. Using solely temporal criteria to discriminate hospital versus community acquisition would have misclassified many "late onset" SARS-CoV-2-positive cases.

The objective of this study was to estimate the genetic parameters of litter size and piglet weight from farrowing to weaning in KHAPS Black sows. The genetic parameters investigated were the direct (h 2 d ), maternal (h 2 m ), realized (h 2 r ), and total (h 2 T ) heritability, as well as correlations (r d , r m , and r dm ) within and between traits. The analyses were performed using single- and three-trait animal models with and without maternal genetic effects. In the three-trait model with maternal genetic effect, all estimates of h 2 d and h 2 m were significantly different from zero except the h 2 d of mean birth weight. Positive values of r d and r m between traits were observed as expected in the range of 0.322-1.000. Negative values of r dm were found within and between traits and were less associated with mean piglet weight traits than litter size traits. Estimates of h 2 T were consistently larger than those of h 2 r in both the single- and three-trait model analyses. In addition, the three-trait model can take into account the association between the traits, so the estimates are more accurate with smaller SEs. In conclusion, maternal genetic effects were not negligible in this study, and thus, a multiple-trait animal model with maternal genetic effects and full pedigree is recommended to assist future pig breeding decisions in this new breed.

Objectives: To investigate the level of 25 hydroxyvitamin D [25(OH)D] in late preterm infants and the effect of vitamin D 3 supplementation on the neurobehavioral development of infants and young children., Methods: In this prospective study, 161 late preterm infants who were admitted from June 2017 to June 2020 were enrolled. According to the level of 25(OH)D in umbilical cord blood, they were divided into three groups: sufficiency group ( n =52), insufficiency group ( n =53), and deficiency group ( n =56). Each group was further divided into subgroup A (vitamin D 3 800 IU/d) and subgroup B (individualized vitamin D 3 supplementation) using a random number table. The levels of 25(OH)D were measured at 3 months after birth and at the corrected ages of 10 months and 18 months. The neurobehavioral development levels were determined by the Gesell Developmental Scale at the corrected ages of 10 months and 18 months., Results: Within 24 hours and 3 months after birth, the insufficiency group and the deficiency group had a significantly lower level of 25(OH)D than the sufficiency group ( P <0.05), and the insufficiency group had a significantly higher level of 25(OH)D than the deficiency group ( P <0.05). In the deficiency group, subgroup B had a significantly higher level of 25(OH)D than subgroup A ( P <0.05) at 3 months after birth. At the corrected ages of 10 months and 18 months, the insufficiency and deficiency groups had significantly lower scores of five functional areas of the Gesell Development Scale than the sufficiency group ( P <0.05). Compared with the insufficiency group, the deficiency group had a significantly lower score of language at the corrected age of 10 months and a significantly lower score of gross motor at the corrected age of 18 months ( P <0.05). Compared with subgroup A of the deficiency group, subgroup B had a significantly higher score of adaptive ability at the corrected age of 10 months and significantly higher scores of adaptive ability and response ability at the corrected age of 18 months ( P <0.05)., Conclusions: There is a significant difference in the level of 25(OH)D in umbilical cord blood in late preterm infants. Individualized vitamin D supplementation appears to be more effective for the treatment of vitamin D deficiency. Vitamin D level at birth and in early infancy has certain influence on neurobehavioral development.

With the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need., Competing Interests: SG, HA, CB, KO, KT and VB are full time employees at BlueWillow Biologics. C.C. and C.-E. L. are employees of Medigen Vaccine Biologics (Taipei, Taiwan) and they report receiving grants from Taiwan Centres for Disease Control, Ministry of Health and Welfare, during the conduct of the study. CC also has a patent pending relating to the MVC-COV1901 vaccine against SARS-CoV-2 (US17/351,363). All other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6‑aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC 50 values in the micromolar range of 5.98-12.58 μM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G 2 /M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to develop and validate the psychometric properties of a novel instrument that measures Indoor Air Pollution Health Literacy (IAPHL). The qualitative phase was conducted to design questions based on the conceptual model of the European Health Literacy Survey Questionnaire. We developed a 38-item instrument covering 12 constructs, that is, four information competencies within three health domains to assess IAPHL. A cross-sectional online video survey of 647 adults aged 20 years and above in Taiwan was conducted. Various measures of validity and reliability coefficients were assessed to indicate the psychometric properties of the IAPHL instrument. The content validity indices for relevance, importance, and clarity of the 38 questions were 0.97, 0.96, and 0.89, respectively. The model fit indices obtained from the confirmatory factor analysis supported the acceptable structures of the theoretically hypothetical 12-factor model (standardized root mean square residual = 0.055; root mean square error of approximation = 0.065). Internal consistency for the instrument showed a Cronbach's alpha of 0.96. The IAPHL instrument developed in this study showed satisfactory validity and reliability and can be used in future fieldwork., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the delta variant after 2- or 3-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and beta (B) variants. Compared to 3 doses of W S-2P, 2 doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 virus and enhanced neutralization of omicron variant pseudovirus. Reduced lung live virus titer and pathology suggested that all vaccination regimens protect hamsters from SARS-CoV-2 delta variant challenge., Competing Interests: Potential conflicts of interest. C. C., T.-Y. K., C.-C. W., W.-.H. T, C.-E. L., Y.-J. L., and M.-Y. L. are coinventors for US provisional patent applications 63/240,408, 63/240,080, 63/248,189. and 63/251,741. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Identifying the source of healthcare personnel (HCP) coronavirus disease 2019 (COVID-19) is important to guide occupational safety efforts. We used a combined whole genome sequencing (WGS) and epidemiologic approach to investigate the source of HCP COVID-19 at a tertiary-care center early in the COVID-19 pandemic., Methods: Remnant nasopharyngeal swab samples from HCP and patients with polymerase chain reaction-proven COVID-19 from a period with complete sample retention (14 March 2020 to 10 April 2020) at Rush University Medical Center in Chicago, Illinois, underwent viral RNA extraction and WGS. Genomes with >90% coverage underwent cluster detection using a 2 single-nucleotide variant genetic distance cutoff. Genomic clusters were evaluated for epidemiologic linkages, with strong linkages defined by evidence of time/location overlap., Results: We analyzed 1031 sequences, identifying 49 clusters that included ≥1 HCP (265 patients, 115 HCP). Most HCP infections were not healthcare associated (88/115 [76.5%]). We did not identify any strong epidemiologic linkages for patient-to-HCP transmission. Thirteen HCP cases (11.3%) were attributed to a potential patient source (weak evidence involving nonclinical staff that lacked location data to prove or disprove contact with patients in same cluster). Fourteen HCP cases (12.2%) were attributed to HCP source (11 with strong evidence)., Conclusions: Using genomic and epidemiologic data, we found that most HCP severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were not healthcare associated. We did not find strong evidence of patient-to-HCP transmission of SARS-CoV-2., Competing Interests: Potential conflicts of interest. The authors: No potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Precision is crucial in determining the appropriate procedure for implementing further trials. We conducted a study to explore the reliability of a novel measuring system for human skin color., Methods: The novel skin color measuring system was used to capture the skin color of four volunteers (2 males and 2 females) from the same location on each subject by the same operator. The measurement was repeated for different poses and instrument factors (camera and shooting protocol) in the red, green, and blue (RGB) system. The average color depth in each image was calculated and converted from 0 to 255. The spread of measures and the Bland-Altman plot was displayed to determine each variance source's random error, with the interclass correlation coefficients applied to reflect the reliability., Result: The RGB color depth in the experiment ranged from 190, 152, and 122 to 208, 170, and 142. The 95% confidential interval of the differences from the means in RGB colors for the different protocols were ±2.8, ±2.6, and ±2.1, respectively. The largest variation in the replicate trials was observed when subjects were in a supine position (standard deviation: 2). The interclass correlation coefficients were greater than 90%, suggesting that the developed system is highly precise., Conclusion: This study demonstrated that the developed device could stably and reliably detect human skin color across different common sources of variation, and thus could be applied clinically to explore relationships between health/disease and skin color changes., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© 2022 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP + ) group, anti-HMGCR antibody positive (HMGCR + ) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP + , 8 (25.0%) with HMGCR + , and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP + group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb ( P <0.01). The axial muscle score was lower than the distal limb score ( P <0.05).(3) Extramuscular manifestations of HMGCR + group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P <0.017). Rash (60.0% vs.14.3%, P <0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P <0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P <0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups ( P <0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP + group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P <0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P <0.017) were common in HMGCR + group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP + group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR + group were more prone to myotonia potential and CRDs.

Palmoplantar keratoderma-congenital alopecia syndrome type 2 is an autosomal recessive disorder with an unknown genetic basis. In this study, we identified biallelic variants in the LSS gene in two unrelated palmoplantar keratoderma-congenital alopecia syndrome type 2 cases (c.3G>A, p.Met1? and c.1025T>G, p.Ile342Ser in patient 1; c.1522G>T, p.Gly508Trp and c.428+42T>A in patient 2) presenting with additional clinical features, including early-onset cataracts, pseudoainhum, and agenesis of the corpus callosum. LSS encodes lanosterol synthase (LSS), which functions in the cholesterol biosynthesis pathway by converting (S)-2,3-oxidosqualene to lanosterol. The c.3G>A variant resulted in an alternative translation initiation at residue Met81, producing an N-terminal truncated protein (LSS-ΔN80), as shown by immunoblotting. The c.428+42T>A variant introduced a potential splicing site, leading to a premature stop codon. Ex vivo studies revealed downregulation of LSS in both patients. Remarkably decreased lanosterol levels were found in vitro in three LSS variants, LSS-ΔN80, p.Ile342Ser, and p.Gly508Trp, suggesting a loss of enzymatic activity. Transmission electron microscopy and immunofluorescence showed abnormal cornified envelope formation in the stratum corneum of the patients. Taken together, our findings indicate LSS as a causative gene for palmoplantar keratoderma-congenital alopecia syndrome type 2, which emphasizes the importance of the cholesterol synthesis pathway in human skin cornification., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract., Methods: We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)- α to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays., Results: HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF- α treatment increased the expression of certain cytokines, including IL-1 β , IL-8, M-CSF, and TGF- β 2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF- β 2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus , forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions . We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Mei-Yi Lin et al.)

Background: Understanding renal function state transition risk and associated factors in community residences is vital for appropriate preventive and care actions. We aim to investigate factors affecting renal function state transitions through 10-year longitudinal community screening surveys., Methods: The prospective cohort study included participants who attended the screening program ≥2 times from 2001 to 2009 and were divided into two cohorts: those with baseline estimated glomerular filtration rate (eGFR) ≥60 ( n = 46,278) and those with eGFR 59-30 mL/min/1.73 m 2 ( n = 4,656). We applied the illness-death model to identify associated factors with eGFR <60 and death for the cohort with baseline eGFR ≥60 and eGFR <30 and death for that with baseline eGFR ≥59-30., Results: Among the followed-up participants, 3,018 (6.5%) in the cohort of baseline eGFR ≥60 mL/min/1.73 m 2 and 322 (6.9%) in the cohort of eGFR 59-30 mL/min/1.73 m 2 experienced renal function state transition during a median over 7-year follow-up. Besides eGFR and grade of proteinuria, diabetes mellitus (adding nearly 50% hazard rate) is the main factor associated with both state transitions. Other early-phase eGFR state transition risk factors were metabolic syndrome score, triglyceride, uric acid, fasting blood sugar, and high-density lipoprotein cholesterol. Males, poor hemoglobin, high triglyceride, and high low-density lipoprotein cholesterol were all linked with the late-phase eGFR state transition hazard rate., Conclusion: The study developed the state transition functions for community participants with varying renal function levels. Further actions to develop precision screening plans and services that incorporate personal risk factors and state transition risks are necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsai, Lin, Hsu, Yen, Chen, Chiu and Hwang.)

Trichodermin (TCD), a trichothecene first isolated from marine Trichoderma viride, is an inhibitor of eukaryotic protein synthesis. However, the potential effects of TCD on human oral squamous cell carcinoma (OSCC) cells and the underlying molecular mechanisms remain unknown. In this study, the exposure of OSCC cells (Ca922 and HSC-3 cells) to TCD suppressed cell proliferation assessed using MTT assays and colony formation assays. TCD inhibited the migration and invasion of OSCC cells (Ca922 and HSC-3 cells) through the downregulation of matrix metalloproteinase 9. After treatment of OSCC cells with TCD, the G2/M phase was arrested, caspase-related apoptosis (cleaved caspase-3 and PARP expression) was induced, and the protein level of x-linked inhibitor of apoptosis was reduced. Meanwhile, the TCD-induced cell death was reversed by the pan-caspase inhibitor Z-VAD-FMK. Furthermore, TCD diminished mitochondrial membrane potential, mitochondrial oxidative phosphorylation and glycolytic function in OSCC cells. In addition, TCD decreased the levels of histone deacetylase 2 (HDAC-2) and downstream signaling proteins, including phosphorylated STAT3 and NF-κB. Finally, TCD significantly suppressed tumor growth in a zebrafish OSCC xenotransplantation model. Overall, this evidence demonstrates that TCD is a novel promising strategy for the treatment of OSCCs., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this study, researchers reviewed electronic health record data to assess whether the coronavirus disease 2019 pandemic was associated with disruptions in diabetes care processes of A1C testing, retinal screening, and nephropathy evaluation among patients receiving care with Wake Forest Baptist Health in North Carolina. Compared with the pre-pandemic period, they found an increase of 13-21 percentage points in the proportion of patients delaying diabetes care for each measure during the pandemic. Alarmingly, delays in A1C testing were greatest for individuals with the most severe disease and may portend an increase in diabetes complications., (© 2022 by the American Diabetes Association.)

Purpose: Femtosecond laser arcuate keratotomy (FS-AK) and toric intraocular lens (IOL) implantation are effective for the correction of eyes with corneal astigmatism. In this study, the postoperative refractive outcomes of patients receiving femtosecond laser-assisted cataract surgery (FLACS) with FS-AK and patients receiving standard phacoemulsification with toric IOL implantation were evaluated., Methods: This retrospective study reviewed the postoperative outcomes of patients undergoing FLACS with FS-AK (the FS-AK group) and patients undergoing standard phacoemulsification with toric IOL implantation (the toric IOL group). The main outcome measures were uncorrected and corrected visual acuities, keratometric and refractive astigmatism, and vector analysis., Results: The FS-AK group included 41 eyes with preoperative keratometric astigmatism of - 1.64 ± 0.42 diopters (D), and the toric IOL group included 53 eyes with preoperative keratometric astigmatism of - 2.29 ± 0.91 D (P < 0.001). Postoperative refractive astigmatism was comparable between the two groups. Compared with the FS-AK group, postoperative uncorrected visual acuity was significantly better (P = 0.005) and corrected visual acuity was marginally better in the toric IOL group (P = 0.051). The absolute angles of error were 9.95° ± 9.57° and 5.08° ± 4.94° (P = 0.02) in the FS-AK and the toric IOL groups, respectively., Conclusion: Both FLACS with FS-AK and standard phacoemulsification with toric IOL implantation are safe and effective methods for astigmatism correction during cataract surgery. Standard phacoemulsification with toric IOL implantation achieves better visual acuity than FLACS with FS-AK at the 6-month follow-up., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Competing Interests: Conflicts of interest None disclosed.

Background: A crucial barrier to the routine application of whole-genome sequencing (WGS) for infection prevention is the insufficient criteria for determining whether a genomic linkage is consistent with transmission within the facility. We evaluated the use of single-nucleotide variant (SNV) thresholds, as well as a novel threshold-free approach, for inferring transmission linkages in a high-transmission setting., Methods: We did a retrospective genomic epidemiology analysis of samples previously collected in the context of an intervention study at a long-term acute care hospital in the USA. We performed WGS on 435 isolates of Klebsiella pneumoniae harbouring the bla KPC carbapenemase (KPC-Kp) collected from 256 patients through admission and surveillance culturing (once every 2 weeks) of almost every patient who was admitted to hospital over a 1-year period., Findings: Our analysis showed that the standard approach of using an SNV threshold to define transmission would lead to false-positive and false-negative inferences. False-positive inferences were driven by the frequent importation of closely related strains, which were presumably linked via transmission at connected health-care facilities. False-negative inferences stemmed from the diversity of colonising populations that were spread among patients, with multiple examples of hypermutator strain emergence within patients and, as a result, putative transmission links separated by large genetic distances. Motivated by limitations of an SNV threshold, we implemented a novel threshold-free transmission cluster inference approach, in which each of the acquired KPC-Kp isolates were linked back to the imported KPC-Kp isolate with which it shared the most variants. This approach yielded clusters that varied in levels of genetic diversity but where 105 (81%) of 129 unique strain acquisition events were associated with epidemiological links in the hospital. Of 100 patients who acquired KPC-Kp isolates that were included in a cluster, 47 could be linked to a single patient who was positive for KPC-Kp at admission, compared with 31 and 25 using 10 SNV and 20 SNV thresholds, respectively. Holistic examination of clusters highlighted extensive variation in the magnitude of onward transmission stemming from more than 100 importation events and revealed patterns in cluster propagation that could inform improvements to infection prevention strategies., Interpretation: Our results show how the integration of culture surveillance data into genomic analyses can overcome limitations of cluster detection based on SNV-thresholds and improve the ability to track pathways of pathogen transmission in health-care settings., Funding: US Center for Disease Control and Prevention and University of Michigan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Hypertension is a common chronic cardiovascular disease reported among both men and women. Hypertension in males affects the testis and reproduction function; however, the pathogenesis is poorly understood. Rapamycin has been reported to have a variety of beneficial pharmacological effects; however, high-doses rapamycin does have side effects such as immunosuppression. The present study investigates whether low-dose rapamycin can reduce the damage caused by hypertension to the testis of spontaneously hypertensive rats (SHRs) and further examines molecular mechanism of low-dose rapamycin in preventing testicular toxicity induced by angiotensin II (Ang II). Low rapamycin dose restores the testicle size, histological alterations, 3β-hydroxysteroid dehydrogenase (3β-HSD) expression, and prevents apoptosis in SHR rats. Ang II downregulates angiotensin-converting enzyme-2 (ACE2) expression through AT1R, p-ERK, and MAS receptor in LC-540 Leydig cells in a dose-dependent manner. Low doses of rapamycin effectively upregulate steroidogenic enzymes, steroidogenic acute regulatory protein and 3β-HSD expression in Leydig cells. Rapamycin upregulates ACE2 expression through p-PKAc and p-PI3k in Ang II-treated cells. Further, rapamycin curbs mitochondrial superoxide generation and depleted mitochondrial membrane potential induced by Ang II through activation of Nrf2-mediated Gpx4 and superoxide dismutase 2 expression. Our results revealed the involvement of ACE2, AT1R, AT2R, PKAc, and oxidative stress in Ang-II-induced testicular toxicity, suggesting low-dose rapamycin could be a potential therapeutic candidate to attenuate testicular toxicity., (© 2022 Wiley Periodicals LLC.)

The emergence and spread of multidrug-resistant bacteria highlight the need for new antibacterial interventions. A screening of 24 newly synthesized dibenzoxazepines identified a small molecule compound, SW14, with potent inhibitory activity against intracellular multidrug-resistant and fluoroquinolone-resistant strains of S. typhimurium in macrophages and epithelial cells. Moreover, intra-macrophagic Salmonella typhi , Yersinia enterocolitica , and Listeria monocytogenes and methicillin-resistant Staphylococcus aureus are also susceptible to SW14. Overall, our findings suggest that SW14 has a broad-spectrum activity against intracellular bacteria., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Ventilator-capable skilled nursing facilities (vSNFs) are critical to the epidemiology and control of antibiotic-resistant organisms. During an infection prevention intervention to control carbapenem-resistant Enterobacterales (CRE), we conducted a qualitative study to characterize vSNF healthcare personnel beliefs and experiences regarding infection control measures., Design: A qualitative study involving semistructured interviews., Setting: One vSNF in the Chicago, Illinois, metropolitan region., Participants: The study included 17 healthcare personnel representing management, nursing, and nursing assistants., Methods: We used face-to-face, semistructured interviews to measure healthcare personnel experiences with infection control measures at the midpoint of a 2-year quality improvement project., Results: Healthcare personnel characterized their facility as a home-like environment, yet they recognized that it is a setting where germs were 'invisible' and potentially 'threatening.' Healthcare personnel described elaborate self-protection measures to avoid acquisition or transfer of germs to their own household. Healthcare personnel were motivated to implement infection control measures to protect residents, but many identified structural barriers such as understaffing and time constraints, and some reported persistent preference for soap and water., Conclusions: Healthcare personnel in vSNFs, from management to frontline staff, understood germ theory and the significance of multidrug-resistant organism transmission. However, their ability to implement infection control measures was hampered by resource limitations and mixed beliefs regarding the effectiveness of infection control measures. Self-protection from acquiring multidrug-resistant organisms was a strong motivator for healthcare personnel both outside and inside the workplace, and it could explain variation in adherence to infection control measures such as a higher hand hygiene adherence after resident care than before resident care.

The objectives of this study is to figure out the appropriate initial treatment and criteria for clinical decision for early-stage small-sized non-small cell lung cancer (NSCLC) among octogenarians. Elderly patients (≥80 years) with stage I NSCLC (<3 cm) were identified between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database. Patients were divided into four cohorts regarding treatment modalities, and overall survival and cancer-specific survival were evaluated via Kaplan-Meier analysis and Cox proportional hazard model. The propensity score matching method was introduced in the subgroup analysis stratified by four clinical characteristics to identify the preferable treatment. A total of 7861 patients were included with a median overall survival of 43 months (range 1-155 months). In younger patients (80-85 years), lobectomy was superior in improving the survival (versus segmentectomy, HR = 0.68, 95%CI 0.55-0.84; versus wedge resection, HR = 0.77; 95%CI 0.67-0.88). While in those over 85 years, lobectomy was superior to wedge resection (HR = 0.72; 95%CI 0.53-0.98), and all other treatments were comparable. As stratified by T stage in those over 85 years, lobectomy was superior to wedge resection (P = 0.023) for T1 disease, and the four treatments were all comparable in overall survival for T2 disease. In conclusions, the favored treatment of early stage NSCLC for octogenarians may be evaluated by age and T stage. Lobectomy might be preferred in patients between 80 and 85 years whenever possible. Among those over 85 years, radiotherapy might lead to a comparable prognosis and could be recommended as the prior treatment, while should surgery be recommended, lobectomy might be preferred for T1 disease and wedge resection for T2 disease., (© 2022. Italian Society of Surgery (SIC).)

Background: Reintubation is a severe complication during foreign body (FB) removal that uses flexible bronchoscopy., Objective: To investigate the incidence and risk factors for reintubations in children undergoing FB extraction by flexible bronchoscopy in a single center., Design: A retrospective cross-sectional study., Setting: All children with foreign body aspiration at Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University from January 2015 to December 2020., Patients: Children with FB removal using a flexible bronchoscopy were enrolled in the trial according to the inclusion criteria., Measurements: Both multivariable and logistic regression analyses were used to analyze the association between characteristic data and reintubations. The results were presented as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: In total, 244 patients met with the inclusion criteria and were included in the analysis. Among those participants, 28 children (11.5%) underwent reintubations after FB removal by flexible bronchoscopy. Independent factors associated with reintubations were identified as operative time ≥ 60 min [OR: 3.68, 95% CI (1.64-8.82)] and ASA ≥ III [OR: 5.7, 95% CI (1.23-26.4)]., Conclusions: Children undergoing FB removal by a flexible bronchoscopy may encounter with a high incidence of postoperative reintubations. Both long operative duration and a severe physical status cause a growing risk of reintubations., (© 2022. The Author(s).)

Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS-CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC-COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics., (© 2022. The Author(s).)

Objectives: To evaluate temporal changes in pediatric emergency department (ED) visits for mental health problems in Massachusetts based on diagnoses and patient characteristics and to assess trends in all-cause pediatric ED visits., Study Design: This statewide population-based retrospective cohort study used the Massachusetts All-Payer Claims Database, which includes almost all Massachusetts residents. The study sample consisted of residents aged <21 years who were enrolled in a health plan between 2013 and 2017. Using multivariate regression, we examined temporal trends in mental health-related and all-cause ED visits in 2013-2017, with person-quarter as the unit of analysis; we also estimated differential trends by sociodemographic and diagnostic subgroups. The outcomes were number of mental health-related (any diagnosis, plus 14 individual diagnoses) and all-cause ED visits/1000 patients/quarter., Results: Of the 967 590 Massachusetts residents in our study (representing 14.8 million person-quarters), the mean age was 8.1 years, 48% were female, and 57% had Medicaid coverage. For this population, mental health-related (any) and all-cause ED visits decreased from 2013 to 2017 (P < .001). Persons aged 18-21 years experienced the largest declines in mental health-related (63.0% decrease) and all-cause (60.9% decrease) ED visits. Although mental health-related ED visits declined across most diagnostic subgroups, ED visits related to autism spectrum disorder-related and suicide-related diagnoses increased by 108% and 44%, respectively., Conclusions: Overall rates of pediatric ED visits with mental health diagnoses in Massachusetts declined from 2013 to 2017, although ED visits with autism- and suicide-related diagnoses increased. Massachusetts' policies and care delivery models aimed at pediatric mental health may hold promise, although there are important opportunities for improvement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Autosomal Dominant polycystic kidney disease (ADPKD) is the most common inherited adult kidney disease. Although ADPKD is primarily caused by PKD1 and PKD2, the identification of several novel causative genes in recent years has revealed more complex genetic heterogeneity than previously thought. To study the disease-causing mutations of ADPKD, a total of 920 families were collected and their diagnoses were established via clinical and image studies by Taiwan PKD Consortium investigators. Amplicon-based library preparation with next-generation sequencing, variant calling, and bioinformatic analysis was used to identify disease-causing mutations in the cohort. Microsatellite analysis along with genotyping and haplotype analysis was performed in the PKD2 p.Arg803* family members. The age of mutation was calculated to estimate the time at which the mutation occurred or the founder arrived in Taiwan. Disease-causing mutations were identified in 634 families (68.9%) by detection of 364 PKD1, 239 PKD2, 18 PKHD1, 7 GANAB, and 6 ALG8 pathogenic variants. 162 families (17.6%) had likely causative but non-diagnostic variants of unknown significance (VUS). A single PKD2 p.Arg803* mutation was found in 17.8% (164/920) of the cohort in Taiwan. Microsatellite and array analysis showed that 80% of the PKD2 p.Arg803* families shared the same haplotype in a 250 kb region, indicating those families may originate from a common ancestor 300 years ago. Our findings provide a mutation landscape as well as evidence that a founder effect exists and has contributed to a major percentage of the ADPKD population in Taiwan., (© 2022. The Author(s).)

A new species, Cylindroeme yunnanensis sp. nov., is described and illustrated from Yunnan Province of China. Cylindroeme vietnamica Vives, 2019 is recorded from China for the first time. A key to the species of Cylindroeme is provided.