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Background: This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration., Methods: Specialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson-Goldner's trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig)., Result: Rabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson-Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while - 8% in the 2:1 ratio group., Conclusion: This study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth., (© 2024. The Author(s).)

This systematic review aims to investigate and determine the effectiveness of interventions on improving mental health (anxiety, depression, stress or mental well-being) and/or reducing burnout of nurses working in hospitals during the COVID-19 pandemic. A search was conducted on studies from conception to December 2022 in databases: PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, Scopus and Web of Science and in ProQuest Thesis & Dissertations Global Database, Google Scholar and ClinicalTrials.gov. A total of 17 randomised controlled trials that evaluated different interventions were included. The outcomes were anxiety (n = 11), depression (n = 5), stress (n = 13) mental well-being (n = 7) and burnout (n = 7). Not all interventions led to positive outcomes. Grading of Recommendations Assessment, Development and Evaluation (GRADE) appraisal and risk of bias assessment using the Cochrane tool for randomised controlled trials (RoB 2.0) revealed poor quality of currently available literature, with low to very low certainty. Meta-analysis showed high heterogeneity among the five different outcomes, with subgroup analysis showing greater success in interventions conducted on nurses involved in the care of COVID-19 patients. More well-designed trials are necessary to reinforce current evidence to improve the mental health of nurses, to not only protect their quality of life but also to ensure the quality of patient care., (© 2023 John Wiley & Sons Australia, Ltd.)

Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively. Drug screening of NPC268 together with six other NPC cell lines using 339 compounds, representing the largest high-throughput drug testing in NPC, revealed biomarkers associated with specific drug classes. NPC268 represents the first and only available EBV-positive non-keratinizing differentiated NPC model, and extensive genomic, methylomic, transcriptomic, and drug response data should facilitate research in EBV and NPC, where current models are limited., Significance: NPC268 is the first and only EBV-positive cell line derived from a primary non-keratinizing, differentiated nasopharyngeal carcinoma, an understudied but important subtype in Southeast Asian countries. This model adds to the limited number of authentic EBV-positive lines globally that will facilitate mechanistic studies and drug development for NPC., (© 2024 The Authors; Published by the American Association for Cancer Research.)

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Objective To investigate the impact of Pseudomonas aeruginosa (PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P <0.05),down-regulated mRNA level of CDH5( P =0.023),disrupted continuity and down-regulated protein level of VE-cadherin( P <0.001),and elevated lactate level( P =0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5( P =0.043),lowered lactate level( P =0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3( P =0.013 and P =0.003),elevated lactate level( P =0.015),and down-regulated mRNA level of CDH5( P =0.020) and protein level of VE-cadherin( P =0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.

Background: COVID-19 is continuing to ravage globally and has resulted in a huge health and financial burden. Chinese proprietary medicines, such as Lianhua Qingwen (LHQW) and Huoxiang Zhengqi (HXZQ) capsules, have been recommended for non-high-risk patients with COVID-19 in China. Based on this, we described the baseline information, using status of LHQW and HXZQ capsules and inoculation history of quarantined patients in the second half of 2022 in Macao. Additionally, we analyzed the underlying association among medicines administration, vaccination and COVID-19 indices, in order to explore novel clues for the regular control and prevention of local epidemic situation in the future., Methods: A total of 976 patients in Macao quarantine hotels from June to August 2022 were included in the present study, of which, 857 subjects were followed-up for prognosis evaluation. During quarantine, the baseline demographic information, including sex, age, BMI, occupation and personal habits were collected. Additionally, the inoculation history, medicine employment status and cycle threshold (Ct) values were also reported. We interviewed the patients for collection of their symptoms at the beginning and end of quarantine, as well as prognostic ones. Basic statistical description of baseline information, vaccination history and medication were displayed. Chi-squared test or with continuous correction test was employed for comparison of dichotomous data between two or multiple groups. Binary logistic regression was applied to reveal the correlation between potential risk factors and Ct values or prognosis symptoms. We also used Cox regression model to identify the effect of different types of vaccine products on Ct value altering rate., Results: Patients who were female (52.0%), engaged in service industry (31.8%), from Macao native (65.8%), never took physical exercises (33.6%) and preferred irritated diet (59.5%) enjoyed more dominant proportions. Over 80% of participants were inoculated and 74.6% of them chose inactivated COVID-19 vaccine produced by China National Biotech Group (CNBG). Participants used LHQW capsules accounted for 92.1% and the duration of medicating lasted for one to two weeks. All of the reported symptoms were significantly ameliorated after quarantine and the duration of quarantine was concentrated on 21 days. People with different age, sex, occupation and region had different choices of HXZQ administration and vaccination. Additionally, middle dose (4-5 boxes) of LHQW capsules exhibited evidently negative association with positive Ct values (adjusted, - 0.037 ± 0.19, p = 0.04). Two doses of CNBG and one dose of mRNA vaccine had obvious protective effect on reducing Ct positive rate (p = 0.041). Meanwhile, symptoms after quarantine were significantly positive correlated with those in prognosis (adjusted, 1.38 ± 0.18, p < 0.0001)., Conclusion: Our study found that the administration of LHQW capsules was beneficial for Ct value turning negative, meanwhile, certain mixed inoculation may be the promoting factor to reduce the positive rate of Ct value. These findings provide data basis for the Chinese proprietary medicine treatment and mixed vaccination applying for prevention and control of local COVID-19 epidemic in the future., (© 2024. The Author(s).)

Introduction: Acquired hemophilia A (AHA) is a rare bleeding disorder with destruction of factor VIII by autoantibodies. Comprehensive data for Chinese patients are lacking. Predictors of hospital stay have not been investigated., Methods: A territory-wide review of patients diagnosed with AHA from January 1, 2012, to December 31, 2021 was performed by retrieving patients' information from an electronic database system in Hong Kong., Results: Overall, 165 patients were included in this 10-year study, and the estimated incidence was 2.4 per million/year, which was higher than those reported from Caucasian cohorts. The median age of diagnosis was 80 years old. Patients had a long hospital stay (median: 25 days) and high mortality (55.2 %). The majority of deaths were caused by immunosuppression-related sepsis (49.5 %). Age was an independent predictor of overall survival (Hazard ratio: 1.065, 95 % CI: 1.037-1.093, p < 0.001), complete remission (CR) status (odd ratios (OR): 0.948, 95 % CI: 0.921-0.976, p < 0.001) and time to achieve CR (OR: 1.043, 95 % CI: 1.019-1.067, p < 0.001). Higher hemoglobin level on presentation was associated with shorter time to achieve CR (OR: 0.888, 95 % CI: 0.795-0.993, p = 0.037). Factor VIII level < 1 % normal, high inhibitor titer and intensive immunosuppressive regimen predicted long hospital stay., Conclusion: We presented comprehensive data of Chinese patients with AHA which comprised predominantly frail elderly who required long hospital stay and had high sepsis-related mortality. This posed challenges in managing AHA in such patients. Individualized immunosuppressive therapy is needed to balance the benefits and risk of septic complications., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Since diagnostic laboratories handle large COVID-19 samples, researchers have established laboratory-based assays and developed biosensor prototypes. Both share the same purpose; to ascertain the occurrence of air and surface contaminations by the SARS-CoV-2 virus. However, the biosensors further utilize internet-of-things (IoT) technology to monitor COVID-19 virus contamination, specifically in the diagnostic laboratory setting. The IoT-capable biosensors have great potential to monitor for possible virus contamination. Numerous studies have been done on COVID-19 virus air and surface contamination in the hospital setting. Through reviews, there are abundant reports on the viral transmission of SARS-CoV-2 through droplet infections, person-to-person close contact and fecal-oral transmission. However, studies on environmental conditions need to be better reported. Therefore, this review covers the detection of SARS-CoV-2 in airborne and wastewater samples using biosensors with comprehensive studies in methods and techniques of sampling and sensing (2020 until 2023). Furthermore, the review exposes sensing cases in public health settings. Then, the integration of data management together with biosensors is well explained. Last, the review ended with challenges to having a practical COVID-19 biosensor applied for environmental surveillance samples.

Our experience of time is strikingly plastic: Depending on contextual factors, the same objective duration can seem to fly by or drag on. Perhaps the most direct demonstration of such subjective time dilation is the oddball effect: when seeing identical objects appear one after another, followed by an "oddball" (e.g., a disc that suddenly grows in size, in a sequence of otherwise static discs), observers experience this oddball as having lasted longer than its nonoddball counterparts. Despite extensive work on this phenomenon, a surprisingly foundational question remains unasked: What actually gets dilated? Beyond the oddball, are the objects just before (or just after) the oddball also dilated? As in previous studies, observers viewed sequences of colored discs, one of which could be the oddball-and subsequently reproduced the oddball's duration. Unlike previous studies, however, there were also critical trials in which observers instead reproduced the duration of the disc immediately before or after the oddball. A clear pattern emerged: oddball-induced time dilation extended to the post-oddball disc, but not the pre-oddball disc. Whence this temporal asymmetry? We suggest that an oddball's sudden appearance may induce uncertainty about what will happen next, heightening attention until after the uncertainty is resolved., (© 2023. The Psychonomic Society, Inc.)

Lung inflammation indicated by 18F-labeled fluorodeoxyglucose (FDG) in patients with tuberculosis is associated with disease severity and relapse risk upon treatment completion. We revealed the heterogeneity and intercellular crosstalk in lung tissues with 18F-FDG avidity and adjacent uninvolved tissues from 6 tuberculosis patients by single-cell RNA-sequencing. Tuberculous lungs had an influx of regulatory T cells (Treg), exhausted CD8 T cells, immunosuppressive myeloid cells, conventional DC, plasmacytoid DC, and neutrophils. Immune cells in inflamed lungs showed general up-regulation of ATP synthesis and interferon-mediated signaling. Immunosuppressive myeloid and Treg cells strongly displayed transcriptions of genes related to tuberculosis disease progression. Intensive crosstalk between IL4I1-expressing myeloid cells and Treg cells involving chemokines, costimulatory molecules, and immune checkpoints, some of which are specific in 18F-FDG-avid lungs, were found. Our analysis provides insights into the transcriptomic heterogeneity and cellular crosstalk in pulmonary tuberculosis and guides unveiling cellular and molecular targets for tuberculosis therapy., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pigmented epithelioid melanocytomas (PEM) are intermediate-grade melanocytic lesions with frequent lymph node involvement and rare metastases that tend to follow an indolent course with a favorable outcome. We report two unique cases of congenital PEM with PRKCA fusion transcripts: a multifocal PEM with an aggressive incompletely resectable scalp tumor and a solitary palmar PEM with newly reported ITGB5-PRKCA fusion. Through these case reports and a summary of previously reported cases, we outline the spectrum of disease of PEM and highlight the key clinical and histopathologic features associated with PEM with PRKCA fusion transcripts. We also discuss the treatment options and suggest that surgical excision without further adjuvant systemic treatment is reasonable first-line therapy given the favorable prognosis.

Background: There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia., Objectives: To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors., Methods: We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV., Results: The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV., Conclusions: Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition., Competing Interests: Conflicts of interest: S.E.C. declares paid activities as advisor, speaker or consultant for AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Sanofi and UCB. C.E.M.G. has received honoraria and/or research grants from AbbVie, Almirall, Amgen, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Evelo Bioscience, Galderma, GSK, Inmagene, LEO Pharma, Janssen, ONO Pharmaceuticals, Novartis, Pfizer, Sandoz and UCB Pharma. D.M.A. reports research grants from AbbVie, Almirall, Eli Lilly, Janssen, Novartis, UCB, and the LEO Foundation., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Objective: This scoping review aims to map and summarize the direct impact of contracting COVID-19, and the indirect consequences of the pandemic on the health of peri- and postmenopausal women., Methods: Searches for published studies were conducted in CINAHL, Cochrane, EMBASE, PubMed, Scopus, Web of Science, PsycINFO and ProQuest from inception to 26 Oct, 2022. Grey literature and reference lists of included studies were searched. Results are presented as a narrative synthesis and tables., Results: Thirty-eight studies were selected in this review. Overall, a majority of studies (n = 31) suggest that menopausal women were negatively impacted, while lesser studies (n = 21) concluded that they were not and some studies (n = 14) produced both negative and neutral results. Twenty-three studies presented on the direct health impact of COVID-19 infections on menopausal women. Eleven studies focused on the indirect impact of COVID-19 in terms of contact restriction measures on menopausal health during the pandemic compared to before the pandemic. Six studies described the different indirect impact of COVID-19 on health of menopausal women with various characteristics or lifestyles., Conclusion: The direct and indirect impacts of COVID-19 on menopausal women on physical, mental health and social wellbeing are largely negative., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

N 6 -methyladenosine (m 6 A) RNA modification plays important roles in the governance of gene expression and is temporally regulated in different cell states. In contrast to global m 6 A profiling in bulk sequencing, single-cell technologies for analyzing m 6 A heterogeneity are not extensively established. Here, we developed single-nucleus m6A-CUT&Tag (sn-m6A-CT) for simultaneous profiling of m 6 A methylomes and transcriptomes within a single nucleus using mouse embryonic stem cells (mESCs). m6A-CT is capable of enriching m 6 A-marked RNA molecules in situ, without isolating RNAs from cells. We adapted m6A-CT to the droplet-based single-cell omics platform and demonstrated high-throughput performance in analyzing nuclei isolated from thousands of cells from various cell types. We show that sn-m6A-CT profiling is sufficient to determine cell identity and allows the generation of cell-type-specific m 6 A methylome landscapes from heterogeneous populations. These indicate that sn-m6A-CT provides additional dimensions to multimodal datasets and insights into epitranscriptomic landscape in defining cell fate identity and states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteogenesis Imperfecta (OI) is a heritable collagen-related bone dysplasia characterized by bone fractures, growth deficiency and skeletal deformity. Type XIV OI is a recessive OI form caused by null mutations in TMEM38B, which encodes the ER membrane intracellular cation channel TRIC-B. Previously, we showed that absence of TMEM38B alters calcium flux in the ER of OI patient osteoblasts and fibroblasts, which further disrupts collagen synthesis and secretion. How the absence of TMEM38B affects osteoblast function is still poorly understood. Here we further investigated the role of TMEM38B in human osteoblast differentiation and mineralization. TMEM38B-null osteoblasts showed altered expression of osteoblast marker genes and decreased mineralization. RNA-Seq analysis revealed that cell-cell adhesion was one of the most downregulated pathways in TMEM38B-null osteoblasts, with further validation by real-time PCR and Western blot. Gap and tight junction proteins were also decreased by TRIC-B absence, both in patient osteoblasts and in calvarial osteoblasts of Tmem38b-null mice. Disrupted cell adhesion decreased mutant cell proliferation and cell cycle progression. An important novel finding was that TMEM38B-null osteoblasts had elongated mitochondria with altered fusion and fission markers, MFN2 and DRP1. In addition, TMEM38B-null osteoblasts exhibited a significant increase in superoxide production in mitochondria, further supporting mitochondrial dysfunction. Together these results emphasize the novel role of TMEM38B/TRIC-B in osteoblast differentiation, affecting cell-cell adhesion processes, gap and tight junction, proliferation, cell cycle, and mitochondrial function., Competing Interests: Declaration of Competing Interest No conflict of interest for all authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Generalized Pustular psoriasis (GPP), a rare and potentially life-threatening auto-inflammatory disease, is associated with IL36RN mutations. Here, we analyse the prevalence of IL36RN mutations in our multi-ethnic GPP cohort and assess differences in the clinical profile of patients with (IL36RN-positive) and without (IL36RN-negative) mutations. IL36RN mutations were present in 17.7% of 137 GPP patients (29.7% of Chinese cases, 17.3% of Malay cases, but 0% of Indian patients). 92% of these individuals carried the c.115 + 6 T > C mutation. Male: female ratio was 1:2.3. Females predominate in both groups with no significant difference between IL36RN-positive and IL36RN-negative individuals. The overall mean age (±SD) at disease onset for GPP was 37.6 ± 17.2 years, but disease onset was significantly earlier in IL36RN-positive vs IL36RN-negative cases (mean age:30.6 ± 18.92 vs. 39.2 ± 16.49 years, p = 0.027). IL36RN-positive patients were less likely to have associated plaque psoriasis (52.4% vs. 83.5%, p-value = 0.002). There was no difference in the common clinical and laboratory manifestations or triggers of GPP between IL36RN-positive and -negative patients, except for geographic tongue which was significantly more common in IL36RN-positive patients (41.7% vs. 11.9%, p-value = 0.002). Annual flare rate was significantly higher in IL36RN-positive compared to IL36RN-negative (mean ± SD of 1.92 ± 1.32 vs. 1.46 ± 0.90, p = 0.041) cases. However, no significant difference in the rate of hospitalization and length of hospital stay was observed between the two groups. These observations demonstrate that IL36RN disease alleles occur with varying frequencies among Asian populations and are associated with a severe, early-onset clinical phenotype., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Free-range eggs are ethically desirable but as with all high-value commercial products, the establishment of provenance can be problematic. Here, we compared a simple one-step isopropanol method to a two-step methyl-tert-butyl ether method for extracting lipid species in chicken egg yolks before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The isopropanol method extracted 937 lipid species from 20 major lipid subclasses with high reproducibility (CV < 30 %). Machine learning techniques could differentiate conventional cage, barn, and free-range eggs using an external test dataset with an accuracy of 0.94, 0.82, and 0.82, respectively. Lipid species that differentiated cage eggs were predominantly phosphocholines and phosphoethanolamines whilst the free-range egg lipidomes were dominated by acylglycerides with up to three fatty acids. The lipid profiles were found to be characteristic of the cage, barns, and free-range eggs. The lipidomic analysis together with the statistical modeling approach thus provides an efficient tool for verifying the provenance of conventional chicken eggs., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigated the spatiotemporal variation, chemical characteristics, and source resolution of PM 2.5 in an East Asian seaport adjacent to industrial complex and urban area. Three representative harbor sites were selected to simultaneously sample 24-h PM 2.5 once every 13 days in four seasons. A significant seasonal variation was observed with the highest and the lowest PM 2.5 concentration in February (winter) and May (summer), respectively. High contribution of secondary inorganic aerosols (SIAs) showed that SO 2 and NO x emitted from neighboring combustion sources burning coal and heavy fuel oil (HFO) were the major precursors forming secondary inorganic PM 2.5 . High ratios of V/Ni and V/Cu were observed in summer (June~August) since the prevailing west and southwest winds from outer port carried ship emissions to inter port. The correlation of chemical fingerprints (V, Ni, V/Ni, Zn, nss-SO 4 2- , OC) and the number of ships were high at the Zhung-He Site and moderate at the Qi-Ho Site. The Cl - , Na + , V, Ni, nss-SO 4 2- , OC, and V/Ni of PM 2.5 were co-influenced by ship missions and oceanic spray in the Kaohsiung Harbor. The influences were relatively higher for winds blown from the harbor areas than those blown from the industrial areas. Oppositely, the Fe, Mn, Cr, Cu, Ca, Zn, and Al in PM 2.5 were higher for winds blown from the industrial areas than those from the harbor areas. The CMB receptor modelling resolved that the major sources of PM 2.5 were industrial missions, secondary aerosols, mobile sources, ship emissions, oceanic spray, fugitive dust, biomass burning, and organic carbon. Similar to Busan (South Korea), Brindisi (Italy), Lampedusa (Italy), and Barcelona (Spain), the contributions of ship emissions in the Kaohsiung Harbor were in the range of 7.4-7.8 %. Meanwhile, Kaohsiung Harbor was highly influenced by emissions from industrial areas and urban areas., 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. Published by Elsevier B.V.)

African Swine Fever (ASF) has spread rapidly across different continents since 2007 and caused huge biosecurity threats and economic losses. Establishing an effective risk assessment model is of great importance for ASF prevention, especially for those ASF-free countries such as Australia. With a vast territory and an economy heavily relying on primary industry, Australia faces a threat from the spread of ASF. Although ordinary quarantine measures have been well-performed throughout Australia, there is still a need to develop an effective risk assessment model to understand the spread of ASF due to the strong transmission ability of ASF. In this paper, via a comprehensive literature review, and analyzing the transmission factors of ASF, we provide a fuzzy model to assess the epidemic risk of Australian states and territories, under the assumption that ASF has entered Australia. As demonstrated in this work, although the pandemic risk of ASF in Australia is relatively low, there is a risk of irregular and scattered outbreaks, with Victoria (VIC) and New South Wales (NSW) - Australia Capital Territory (NSW-ACT) showed the highest risk. The reliability of this model was also systematically tested by a conjoint analysis model. To our knowledge, this is the first study to comprehensively analyze the ASF epidemic risk in a country using fuzzy modeling. This work can provide an understanding of the risk ASF transmission within Australia based on the fuzzy modeling, the same methodology can also provide insights and useful information for the establishment of fuzzy models to perform the ASF risk assessment for other countries., Competing Interests: Conflict of interest No conflict of interest has been declared by the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: CLEFT-Q is a condition-specific patient-reported outcome measure (PROM) for patients with cleft lip and/or palate (CL/P). The aim of this study was to examine the cross-sectional construct validity of the CLEFT-Q scales., Design: Construct validity was assessed through a prospective study that tested hypotheses regarding correlations of scores with other PROMs that measure related constructs., Setting: Seven cleft centres in Canada, the USA, and UK were involved., Patients/participants: Patients were aged eight to 29 years with CL/P., Interventions: Before undergoing rhinoplasty, orthognathic, cleft lip scar revision, and alveolar bone graft, participants were asked to complete the following PROMs: CLEFT-Q (9 scales), Child Oral Health Impact Profile (socio-emotional subscale) and Cleft Hearing Appearance and Speech Questionnaire (features 1 subscale)., Main Outcome Measure(s): The correlation coefficients examining the relationship between the scales were the main outcome measures. Correlations (Spearman) were calculated and interpreted as follows: <0.3 weak, 0.30 to 0.50 moderate, ≥0.50 strong., Results: Participants ( n  = 177) were mostly male (61%) and aged between eight and 11 years (42%). Overall, 38 of 52 (73%) hypotheses tested were supported. More specifically, 20 of 26 (77%) hypotheses about correlations between the appearance scales were supported, two of three (67%) hypotheses about correlations between the health-related quality of life scales were supported, and 16 of 23 (70%) hypotheses about correlations between the appearance and health-related quality of life scales were supported., Conclusions: Cross-sectional construct validity of the CLEFT-Q scales adds further evidence of the psychometric properties of this instrument.

Objective: To describe the clinical characteristics, management and quality of life of psoriasis patients with and without coexistent lupus erythematosus (LE)., Methods: This retrospective cross-sectional study uses data from the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018., Results: Of 21 735 psoriasis patients, 34 (0.16%) had coexistent LE. The male to female ratio among psoriasis patients with coexistent LE was 1:5.8 versus 1.3:1 in patients with psoriasis but without LE. Nearly 70% presented with LE preceding psoriasis. Psoriasis patients with LE had an earlier age of psoriasis onset (27.56 ± 11.51 versus 33.31 ± 16.94 years, P = 0.006), a higher rate of psoriatic arthropathy (26.5% versus 13.0%, P = 0.02), and a significantly greater impairment of quality of life (Dermatology Quality of Life Index >10; 57.6% versus 40.3%, P = 0.04) compared with psoriasis patients without LE. The majority (87.5%) had systemic LE. The incidences of lupus nephritis (72.7% versus 40%) and hematological abnormalities (50% versus 20%) were higher among patients with LE preceding psoriasis compared with those with psoriasis preceding LE. Antinuclear antibody and double-stranded DNA were positive in 59.4% and 28.1% of psoriasis patients with LE, respectively. Hydroxychloroquine triggered the onset of psoriasis in 7 (24.1%) patients. Patients with LE were more likely to receive systemic treatment for psoriasis compared with those without LE (30.3% versus 14.2%, P = 0.008)., Conclusions: Psoriasis patients with coexistent LE were uncommon, displayed a female preponderance, were more likely to have joint involvement, and had greater quality of life impairment than those without LE. LE preceded psoriasis in most of these patients, and systemic LE was the most common subtype., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

We typically think of intuitive physics in terms of high-level cognition, but might aspects of physics also be extracted during lower-level visual processing? Might we not only think about physics, but also see it? We explored this using multiple tasks in online adult samples with objects covered by soft materials-as when you see a chair with a blanket draped over it-where you must account for the physical interactions between cloth, gravity, and object. In multiple change-detection experiments ( n = 200), observers from an online testing marketplace were better at detecting image changes involving underlying object structure versus those involving only the superficial folds of cloths-even when the latter were more extreme along several dimensions. And in probe-comparison experiments ( n = 100), performance was worse when both probes (vs. only one) appeared on image regions reflective of underlying object structure (equating visual properties). This work collectively shows how vision uses intuitive physics to recover the deeper underlying structure of scenes.

Oxidative stress and its constant companion, inflammation, play a critical part in the pathogenesis of many acute and chronic illnesses. The discovery of new multi-targeted drug candidates with antioxidant and anti-inflammatory properties is deemed necessary. Thus, a series of novel xanthone derivatives with halogenated benzyl (4b-4d, 4f-4h) and methoxylated benzyl groups (4e) attached to the butoxy amine substituent were synthesized in this study. The synthesized xanthone derivatives exhibited stronger antioxidant activity against H 2 O 2 scavenging than the standard drug, α-tocopherol, but weaker towards DPPH scavenging and ferrous ion chelation. Besides that, 4b-4d, 4f-4h demonstrated good anti-inflammatory activities through NO production inhibition towards lipopolysaccharide (LPS)-induced RAW 264.7 cells and showed 2-4 times stronger effects than the standard drug, diclofenac sodium. Moreover, compound 4b with two brominated benzyl groups attached to the butoxy amine substituent suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1β, significantly. Structure-activity relationship elucidated that the halogenated benzylamine substituent plays an important role in contributing the antioxidant and anti-inflammatory activities of xanthones. In summary, xanthone 4b was identified as a potential lead compound to be further developed into antioxidant and anti-inflammatory drugs. Thus, further studies on the related mechanisms of action of 4b are recommended., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Background: Patient's acceptance and compliance to spinal orthosis could influence the outcome of orthotic treatment in adolescent idiopathic scoliosis. Two innovative undergarments (thin and thick designs) were designed to improve the patient's orthosis wearing experience and acceptance., Objective: This study aimed to evaluate the effects of patients' self-provided undergarment and 2 newly designed undergarments with respect to the orthosis wearing compliance and quality of life (QoL) measures., Methods: A prospective randomized-controlled study was conducted to compare the effect of three types of undergarments. Thirty-eight subjects with adolescent idiopathic scoliosis were randomly assigned to one of the three groups: self-provided, thin-design, or thick-design undergarment. Wearing compliance logbook, Scoliosis Research Society questionnaire, and Brace Questionnaire were used to document the orthosis wearing period and quantify the health-related and orthosis-related QoL measures. Kruskal-Wallis one-way analysis of variance (ANOVA) and Friedman two-way ANOVA by ranks tests were conducted for intergroup and intragroup comparisons, respectively., Results: The compliance and QoL domains of the subjects in the thin-design undergarment group were significantly higher than those of the other two undergarment groups (P < .05). The intragroup compliance and QoL scores varied significantly in the 4 visits throughout the study period (P < .05)., Conclusions: It was observed that an adaptation period toward the prescribed spinal orthosis is required to help patients gradually achieve a more stable acceptance. The thin-design undergarment was ranked higher than the other two tested undergarments in compliance and QoL measures., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Background: There are no population-based epidemiological data on psoriasis in Southeast Asia, including Malaysia., Objectives: To determine the incidence and prevalence of psoriasis over 11 years in multiethnic Johor Bahru, Malaysia., Methods: A population-based cohort study was made using the Teleprimary Care database between January 2010 and December 2020. Cases of psoriasis, identified by ICD-10 diagnostic codes, were validated by dermatologists. Annual prevalence and incidence were estimated and stratified by age, sex and ethnicity., Results: We identified 3932 people with dermatologist-confirmed psoriasis, including 1830 incident cases, among 1 164 724 Malaysians, yielding an 11-year prevalence of 0·34% [95% confidence interval (CI) 0·33-0·35] and incidence of 34·2 per 100 000 person-years (95% CI 32·6-35·8). Rates were higher in Indian patients; the prevalences were 0·54% (0·50-0·58) in Indian, 0·38% (0·36-0·40) in Chinese and 0·29% (0·28-0·30) in Malay patients, and the respective incidences per 100 000 person-years were 52·5 (47·3-57·7), 38·0 (34·1-41·8) and 30·0 (28·2-31·8). Rates were higher in males; the prevalence was 0·39% (0·37-0·41) in males and 0·29% (0·27-0·30) in females, and the respective incidences per 100 000 person-years were 40·7 (38·2-43·2) and 28·3 (26·4-30·3). Between 2010 and 2020, annual psoriasis prevalence and incidence increased steadily from 0·27% to 0·51% and from 27·8 to 60·9 per 100 000 person-years, respectively. Annual rates were consistently higher in male and Indian patients. Overall, psoriasis was significantly more common in males than females [odds ratio (OR) 1·37, 95% CI 1·29-1·46] and in Indian and Chinese patients vs. Malay (OR 1·85, 1·71-2·01 and OR 1·30, 1·20-1·41, respectively). Prevalence increased with age, with the highest rates in the groups aged 50-59 and 60-69 years at 0·67% and 0·66%, respectively. A modest bimodal trend in age of psoriasis onset was observed, with first and second peaks at 20-29 and 50-59 years. Disease onset was significantly earlier in females than males [mean (SD) 36·8 (17·3) vs. 42·0 (17·2) years, P < 0·001] and in Malay vs. Indian and Chinese patients [mean (SD): Malay 36·4 (17·5), Indian 40·8 (15·2), Chinese 47·4 (16·9) years, P < 0·001]., Conclusions: We found that psoriasis incidence and prevalence are increasing and varied by age, sex and ethnicity. Our findings should help inform healthcare planning and management for patients with psoriasis in Malaysia. What is already known about this topic? The incidence and prevalence of psoriasis are generally lower in Asian populations and children. There is a lack of agreement on sex-specific differences in psoriasis incidence and prevalence. There has been no population-based study on the incidence and prevalence of psoriasis in Southeast Asia, including Malaysia. There is no information on differences in psoriasis prevalence and incidence by sex, age and ethnicity in Malaysia. What does this study add? Psoriasis incidence and prevalence are increasing in the multiethnic population of Johor Bahru, Malaysia. Incidence and prevalence rates were higher in male than female patients and were consistently highest among Indian patients, followed by Chinese and Malay. A modest bimodality in the age of psoriasis onset was observed among the groups aged 20-29 and 50-59 years. Psoriasis onset was significantly later in male than female patients and in Chinese vs. Indian and Malay patients., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: Limited information exists regarding drug survival of biologics among psoriasis patients in Malaysia. This study aimed to determine the drug survival of biologics in Malaysian psoriasis patients, the reasons for drug discontinuation and to identify the predictor of drug survival., Materials and Methods: A retrospective review of case notes on adult psoriasis patients treated with biologics in Hospital Sultanah Aminah Johor Bahru Malaysia, between January 2006 and December 2020. Drug survival was analysed using the Kaplan-Meier method., Results: By December 2020, 100 patients with 154 treatment courses of biologics were included in the study. Male to female ratio was 1:1. The mean age at onset was 31.36 ± 11.72 years. Ustekinumab was the most frequently prescribed biologics (39%), followed by adalimumab (29.2%), secukinumab (14.9%), etanercept (13%), and infliximab (3.2%). Overall median drug survival for biologics was 25 months (interquartile range [IQR]= 12.0-.0). The median drug survival for ustekinumab was 35 months (IQR, 12-93); followed by 25 months (IQR, 12.0-), 18 months (IQR, 7-85), 17 months (IQR, 11-43), and 8 months (IQR, 1-10) for secukinumab, adalimumab, etanercept, and infliximab, respectively. The main reason for drug discontinuation was loss of efficacy (26%), inadequate funding (14.3%), loss to follow-up (10.4%), adverse events (4.5%), and patients' request (1.3%)., Conclusion: Our study shows ustekinumab has the best long-term drug survival among biologics in Malaysian patients with psoriasis in real-life setting. Further study is required to evaluate the long-term drug survival for newer biologics.

A novel calcium copper titanate (CaCu 3 Ti 4 O 12 )-polyvinylidene fluoride composite (CCTO@PVDF) with Cu-deficiency was successfully prepared through the molten salt-assisted method. The morphology and structure of polymer composites uniformly incorporated with CCTO nanocrystals were characterized. At the same volume fraction, the CCTOs with Cu-deficiency displayed higher dielectric constants than those without post-treatment. A relatively high dielectric constant of 939 was obtained at 64% vol% CCTO@PVDF content, 78 times that of pure PVDF. The high dielectric constants of these composites were attributed to the homogeneous dispersion and interfacial polarization of the CCTO into the PVDF matrix. These composites also have prospective applications in high-frequency regions (10 6 Hz). The enhancement of the dielectric constant was predicted in several theoretical models, among which the EMT and Yamada models agreed well with the experimental results, indicating the excellent distribution in the polymer matrix.

Introduction and Hypothesis: Women with missed obstetric anal sphincter injuries (OASIs) are at an increased risk of anal incontinence. Our aim was to assess the accuracy of three-dimensional (3D) transperineal ultrasound (TPUS) compared with clinical examination for detecting OASIs., Methods: A cross-sectional study of women undergoing their first vaginal delivery. Perineal trauma was initially assessed by the doctor or midwife performing the delivery (accoucheur) and women were then re-examined by the trained research fellow (KW). A 3D TPUS was performed immediately after delivery before suturing to identify OASIs. The research fellow's clinical diagnosis was used as the reference standard. A power calculation determined that 216 women would be required for the study., Results: Two hundred and sixty-four women participated and 226 (86%) delivered vaginally. Twenty-one (9%) sustained OASIs. Six (29%) of these tears were missed by the accoucheur but were identified by the research fellow. TPUS identified 19 of the 21 (90.5%) OASIs. One percent (n = 2) had sonographic appearances of an anal sphincter defect that was not seen clinically. The positive and negative predictive value of TPUS to detect OASIs was 91% and 99% respectively. TPUS identified 91% of OASIs compared with 71% detected by the accoucheur, which was not statistically significant., Conclusions: The detection rate of OASIs with TPUS and with the clinical findings of the accoucheur was similar. Given the training and financial implications needed for TPUS, attention needs to be focused on the training of midwives and doctors to identify anal sphincter injuries by clinical examination., (© 2022. Crown.)

Antibiotics are widely used for the treatment of bacterial infections. However, injudicious use of antibiotics based on an empirical method may lead to the emergence of resistant strains. Despite appropriate administration of antibiotics, their concentrations may remain subinhibitory in the body, due to individual variations in tissue distribution and metabolism rates. This may promote bacterial virulence and complicate the treatment strategies. To investigate whether the administration of certain classes of antibiotics will induce bacterial virulence and worsen the infection under in vivo conditions. Different classes of antibiotics were tested in vitro for their ability to induce virulence in a methicillin-resistant S. aureus strain Mu3 and clinical isolates. Antibiotic-induced pathogenicity was assessed in vivo using mouse peritonitis and bacteremia models. In vitro, β-lactam antibiotics and tetracyclines induced the expression of multiple surface-associated virulence factors as well as the secretion of toxins. In peritonitis and bacteremia models, mice infected with MRSA and treated with ampicillin, ceftazidime, or tetracycline showed enhanced bacterial pathogenicity. The release of induced virulence factors in vivo was confirmed in a histological examination. Subinhibitory concentrations of antibiotics belonging to β-lactam and tetracycline aggravated infection by inducing staphylococcal virulence in vivo . Thus, when antibiotics are required, it is preferable to employ combination therapy and to initiate the appropriate treatment plan, following diagnosis. Our findings emphasize the risks associated with antibiotic-based therapy and underline the need for alternative therapeutic options. IMPORTANCE Antibiotics are widely applied to treat infectious diseases. Empirically treatment with incorrect antibiotics, or even correct antibiotics always falls into subinhibitory concentrations, due to dosing, distribution, or secretion. In this study, we have systematically evaluated in vitro virulence induction effect of antibiotics and in vivo exacerbated infection. The major highlight of this work is to prove the β-lactam and tetracyclines antibiotics exacerbated disease is due to their induction effect on staphylococcal virulence. This phenomenon is common and suggests that if β-lactam antibiotics remain the first line of defense during empirical therapy, we either need to increase patient reliability or the treatment approach may improve in the future when paired with anti-virulence drugs.

Objective: We aimed to systematically determine the incidences of wound infection and dehiscence after primary obstetric anal sphincter injury repair., Data Sources: MEDLINE, Embase, CINAHL, EmCare, the Cochrane Library, and Trip Pro databases were searched from inception to February 2021., Study Eligibility Criteria: We included observational clinical studies reporting the incidences of wound infection and dehiscence after primary obstetric anal sphincter injury repair. Case series and reports were excluded. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data., Methods: Data were analyzed as incidence (percentage) with 95% confidence intervals. Moreover, the prediction intervals were calculated to provide a predicted range for the potential incidence of wound complications when applied to an individual study setting. Study quality and risk of bias were assessed using the relevant tool from the Joanna Briggs Institute., Results: Of 956 studies found, 39 were selected for full-text review. Moreover, 10 studies (n=4767 women) were eligible and included in the meta-analysis. All 10 studies were conducted in high-income countries (Denmark [n=1], the United Kingdom [n=3], and the United States [n=6]). The incidences of wound infection (n=4593 women) and wound dehiscence (n=3866 women) after primary obstetric anal sphincter injury repair ranged between 0.1% to 19.8% and 1.9% to 24.6%, respectively. The overall incidences were 4.4% (95% confidence interval, 0.4-8.4) for wound infection and 6.9% (95% confidence interval, 1.6-12.2) for wound dehiscence. The prediction intervals were wide and suggested that the true incidences of wound infection and dehiscence in future studies could lie between 0.0% to 11.7% and 0.0% to 16.4%, respectively. Overall, 8 studies had a high or unclear risk of bias across ≥1 assessed element. None of the studies used the same set of clinical parameters to define wound infection or dehiscence. Furthermore, microbiological confirmation with wound swabs was never used as a diagnostic measure., Conclusion: This was a systematic review and meta-analysis of wound infection and dehiscence incidences after primary obstetric anal sphincter injury repair. The incidence estimates from this review will be useful for clinicians when counseling women with obstetric anal sphincter injury and when consenting them for primary surgical repair., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Influx of eosinophils into the lungs is typically associated with type II responses during allergy and fungal and parasitic infections. However, we previously reported that eosinophils accumulate in lung lesions during type I inflammatory responses to Mycobacterium tuberculosis (Mtb) in humans, macaques, and mice, in which they support host resistance. Here we show eosinophils migrate into the lungs of macaques and mice as early as one week after Mtb exposure. In mice this influx is CCR3 independent and instead requires cell-intrinsic expression of the oxysterol receptor GPR183, which is highly expressed on human and macaque eosinophils. Murine eosinophils interact directly with bacilli-laden alveolar macrophages, which upregulate the oxysterol-synthesizing enzyme Ch25h, and eosinophil recruitment is impaired in Ch25h-deficient mice. Our findings show that eosinophils are among the earliest cells from circulation to sense and respond to Mtb infection of alveolar macrophages and reveal a role for GPR183 in the migration of eosinophils into lung tissue., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We present a novel approach to reconstruct three-dimensional (3D) electron temperature distributions of inertially confined fusion plasma hotspots at the National Ignition Facility. Using very limited number of two-dimensional (2D) x-ray imaging lines of sight, we perform 3D reconstructions of x-ray emission distributions from different x-ray energy channels ranging from 20 to 30 keV. 2D time-integrated x-ray images are processed using the algebraic reconstruction technique to reconstruct a 3D hotspot x-ray emission distribution that is self-consistent with the input images. 3D electron temperatures are computed using the energy channel ratios. We demonstrate the high accuracy and applicability of this method with different complex hotspot geometries in both synthetic and experimental results.

Introduction: To improve the nutritional care and resource allocation of critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), we described their characteristics, treatment modalities and clinical outcomes, and compared their nutrition interventions against the American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations., Methods: This was a retrospective observational study conducted in 5 tertiary hospitals in Singapore. Characteristics, treatment modalities, clinical outcomes and nutrition interventions of critically ill patients with SARS-CoV-2 who received enteral and parenteral nutrition were collected between January and May 2020., Results: Among the 83 critically ill patients with SARS-CoV-2, 22 (28%) were obese, 45 (54%) had hypertension, and 21 (25%) had diabetes. Neuromuscular blockade, prone therapy and dialysis were applied in 70% (58), 47% (39) and 35% (29) of the patients, respectively. Refeeding hypophosphataemia and hospital mortality occurred respectively in 6% (5) and 18% (15) of the critically ill patients with SARS-CoV-2. Late enteral nutrition and cardiovascular comorbidities were associated with higher hospital mortality (adjusted relative risk 9.00, 95% confidence interval [CI] 2.25-35.99; 6.30, 95% CI 1.15-34.40, respectively). Prone therapy was not associated with a higher incidence of high gastric residual volume (≥250mL). The minimum caloric (15kcal/kg) and protein (1.2g/kg) recommendations of ASPEN were achieved in 54% (39) and 0% of the patients, respectively., Conclusion: The high obesity prevalence and frequent usage of neuromuscular blockade, prone therapy, and dialysis had considerable implications for the nutritional care of critically ill patients with SARS-CoV-2. They also did not receive adequate calories and protein. More audits should be conducted to refine nutritional interventions and guidelines for this ever-evolving disease.

Introduction and Hypothesis: OASI complicates approximately 6% of vaginal deliveries. This risk is increased with operative vaginal deliveries (OVDs), particularly forceps. However, there is conflicting evidence supporting the use of mediolateral/lateral episiotomy (MLE/LE) with OVD. The aim of this study was to assess whether MLE/LE affects the incidence of OASI in OVD., Methods: Electronic searches were performed in OVID Medline, Embase and the Cochrane Library. Randomised and non-randomised observational studies investigating the risk of OASI in OVD with/without MLE/LE were eligible for inclusion. Pooled odds ratios (OR) were calculated using Revman 5.3. Risk of bias of was assessed using the Cochrane RoB2 and ROBINS-I tool. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE)., Results: A total of 703,977 patients from 31 studies were pooled for meta-analysis. MLE/LE significantly reduced the rate of OASI in OVD (OR 0.60 [95% CI 0.42-0.84]). On sub-group analysis, MLE/LE significantly reduced the rate in nulliparous ventouse (OR 0.51 [95% CI 0.42-0.84]) and forceps deliveries (OR 0.32 [95% CI 0.29-0.61]). In multiparous women, although the incidence of OASI was lower when a ventouse or forceps delivery was performed with an MLE/LE, this was not statistically significant. Heterogeneity remained significant across all studies (I 2 > 50). The quality of all evidence was downgraded to "very low" because of the critical risk of bias across many studies., Conclusions: MLE/LE may reduce the incidence of OASI in OVDs, particularly in nulliparous ventouse or forceps deliveries. This information will be useful in aiding clinical decision-making and counselling in the antenatal period and during labour., (© 2022. The Author(s).)

Porous carbon derived from grape marc (GM) was synthesized via carbonization and chemical activation processes. Extrinsic nitrogen (N)-dopant in GM, activated by KOH, could render its potential use in supercapacitors effective. The effects of chemical activators such as potassium hydroxide (KOH) and zinc chloride (ZnCl 2 ) were studied to compare their activating power toward the development of pore-forming mechanisms in a carbon electrode, making them beneficial for energy storage. GM carbon impregnated with KOH for activation (KAC), along with urea as the N-dopant (KAC urea ), exhibited better morphology, hierarchical pore structure, and larger surface area (1356 m 2 g -1 ) than the GM carbon activated by ZnCl 2 (ZnAC). Moreover, density functional theory (DFT) investigations showed that the presence of N-dopant on a graphite surface enhances the chemisorption of O adsorbates due to the enhanced charge-transfer mechanism. KAC urea was tested in three aqueous electrolytes with different ions (LiOH, NaOH, and NaClO 4 ), which delivered higher specific capacitance, with the NaOH electrolyte exhibiting 139 F g -1 at a 2 mA current rate. The NaOH with the alkaline cation Na + offered the best capacitance among the electrolytes studied. A multilayer perceptron (MLP) model was employed to describe the effects of synthesis conditions and physicochemical and electrochemical parameters to predict the capacitance and power outputs. The proposed MLP showed higher accuracy, with an R 2 of 0.98 for capacitance prediction.

The NOD-like receptors (NLRs) have been shown to be involved in infection and autoinflammatory disease. Previously, we identified a zebrafish NLR, nlrc3-like , required for macrophage homeostasis in the brain under physiological conditions. Here, we found that a deficiency of nlrc3-like leads to decreased bacterial burden at a very early stage of Mycobacterium marinum infection, along with increased production of pro-inflammatory cytokines, such as il-1β and tnf-α . Interestingly, myeloid-lineage specific overexpression of nlrc3-like achieved the opposite effects, suggesting that the impact of nlrc3-like on the host anti-mycobacterial response is mainly due to its expression in the innate immune system. Fluorescence-activated cell sorting (FACS) and subsequent gene expression analysis demonstrated that inflammasome activation-related genes were upregulated in the infected macrophages of nlrc3-like deficient embryos. By disrupting asc , encoding apoptosis-associated speck-like protein containing a CARD, a key component for inflammasome activation, the bacterial burden increased in asc and nlrc3-like double deficient embryos compared with nlrc3-like single deficient embryos, implying the involvement of inflammasome activation in infection control. We also found extensive neutrophil infiltration in the nlrc3-like deficient larvae during infection, which was associated with comparable bacterial burden but increased tissue damage and death at a later stage that could be alleviated by administration of dexamethasone. Our findings uncovered an important role of nlrc3-like in the negative regulation of macrophage inflammasome activation and neutrophil infiltration during mycobacterial infection. This highlights the importance of a balanced innate immune response during mycobacterial infection and provides a potential molecular basis to explain how anti-inflammatory drugs can improve treatment outcomes in TB patients whose infection is accompanied by a hyperinflammatory response., 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 Niu, Luo, Liang, Qiu, Yang, Xie, Zhang, Tian, Wang, Song, Takiff, Wong, Fan, Gao and Yan.)

Background: Tenckhoff catheter (TC) insertion for patients with previous intraperitoneal surgery (IPS) is challenging., Methods: This is a case series of 11 patients with history of previous IPS who underwent TC insertion under combined fluoroscopic and sonographic (CFS) guidance with preperitoneal tunneling at our center., Results: This is an interim result of our study. The mean age of the patients was 49.1 (±12.7). Seven were females, and four were males. Only two patients underwent more than one IPS prior to this procedure. The mean body mass index (BMI) of patients was 29.2 kg/m 2 (±6.2). All patients underwent the procedure successfully. One patient developed post-procedure exit site bleeding which resolved spontaneously. One patient had urgent-start peritoneal dialysis (PD) (less than 72 h), and two patients had early-start PD (less than 2 weeks). Median catheter survival is 8 months at the time of writing., Conclusion: CFS-assisted TC insertion with preperitoneal tunneling for patients with previous IPS is a safe and effective technique., (© 2021 Wiley Periodicals LLC.)

In this study, the pollution characteristics, spatiotemporal variation, and potential sources of atmospheric speciated mercury (ASM) in an industrial harbor area were explored. Gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and particle-bound mercury (PBM) were sampled by a self-designed manual system at three harbor sites in four seasons. The yearly average concentrations of GEM, GOM, and PBM were 6.7 ± 2.0 ng/m 3 , 244 ± 70 pg/m 3 , and 410 ± 105 pg/m 3 , respectively. The seasonal average ASM concentration was in the order of: winter > fall > spring > summer. In terms of species, GEM dominated ASM, while reactive mercury (RM = GOM + PBM) accounted for 6.0-15.7%of ASM, implying that ASM was governed by anthropogenic sources in the harbor area. The highest ASM concentrations were observed at Site Zhonghe (ZH), which is mainly influenced by both ship exhausts and industrial emissions, and positively correlated with CO, NO x , and SO 2 . In particular, GOM was positively correlated with O 3 , and negatively correlated with air temperature and relative humidity, showing high impact from atmospheric photochemical reactions. Air masses transporting westerly in spring were mainly from ship exhausts. In summer, air masses transporting from the south were from utility power plants and machinery exhausts. In fall and winter, air masses were transported mainly from the north, blowing by the long-range transport of polluted air masses originated from the north. Both principal component analysis and positive matrix factorization results indicate that coal burning, industrial emissions, and vehicular exhausts are the main contributors to ASM. Site Zhongdao (ZD) was close to the bulk carrier loading and unloading zones and was highly influenced by mobile sources, while Site ZH was mainly influenced by the neighboring industrial complex., 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 © 2021. Published by Elsevier B.V.)

Objective: When obstetric anal sphincter injuries are identified, it is crucial that the defects are repaired appropriately to achieve a better outcome. Although the presence of an intact anal sphincter is not the sole mechanism for maintaining continence, and not all women with an anal sphincter defect are symptomatic, there is an association between sphincter defects and anal incontinence. Our aim was to evaluate whether transperineal ultrasound (TPUS) is useful in assessing anal sphincter integrity immediately following primary repair of obstetric anal sphincter injuries (OASIs)., Study Design: This is a prospective observational study of women who sustained OASIs during their first vaginal delivery. Three dimensional (3D) TPUS was performed immediately after repair of OASIs to identify anal sphincter defects. A repeat TPUS was performed 12 weeks following repair., Results: 21 women sustained OASIs of whom 20 (95%) attended follow up. Eight (40%) had a grade 3a tear and 12 (60%) a 3b tear. 8/20 (40%) women had residual external anal sphincter (EAS) defects identified by TPUS immediately after repair. Of these eight defects, six (75%) persisted at 12 weeks postpartum. No new defects were seen at follow up among the twelve women in whom no defect was seen immediately following the repair. Six residual EAS defects were found at 12 weeks postpartum. An EAS defect at 12 weeks postpartum was associated with anal incontinence (p = 0.04). Women with 3b tears were more likely to have anal incontinence (AI) and residual sonographic EAS defects when compared with 3a tears but this was not statistically significant., Conclusions: Women who had no TPUS defect detected immediately following primary repair of OASIs, remained as such at 12 weeks postpartum. Of those in whom a defect was seen immediately after repair, it persisted in 75% of cases at 12 weeks. We believe that the value of TPUS immediately after repair appears to be limited and would need to be defined if it were to be considered for routine practice. Further research on its role immediately after repair of major tears (Grade 3C/4) is needed. In addition, performing ultrasound would require widespread training of obstetricians to develop expertise. This highlights the importance of adequate training of obstetricians in OASI repair., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chronic kidney disease (CKD), a common clinical problem in primary care, can be defined as any abnormality of the kidney structure and/or function that has been present for at least 3 months. Over the past 20 years, the incidence and prevalence of CKD have been increasing in Malaysia in line with the rising number of non-communicable diseases. At present, CKD has no cure. The treatment of CKD is very much dependent on early diagnosis and prevention of CKD progression. In this article, we aim to illustrate a practical approach to CKD in primary care, including diagnosis, evaluation, and management of CKD., (© Academy of Family Physicians of Malaysia.)

Deoxyribonucleic acid (DNA) sequencing has found wide applications in medicine including treatment of diseases, diagnosis and genetics studies. Rapid and cost-effective DNA sequencing has been achieved by measuring the transverse electronic conductance as a single-stranded DNA is driven through a nanojunction. With the aim of improving the accuracy and sensitivity of DNA sequencing, we investigate the electron transport properties of DNA nucleobases within gold nanogaps based on first-principles quantum transport simulations. Considering the fact that the DNA bases can rotate within the nanogap during measurements, different nucleobase orientations and their corresponding residence time within the nanogap are explicitly taken into account based on their energetics. This allows us to obtain an average current that can be compared directly to experimental measurements. Our results indicate that bare gold electrodes show low distinguishability among the four DNA nucleobases while the distinguishability can be substantially enhanced with sulfur atom decorated electrodes. We further optimized the size of the nanogap by maximizing the residence time of the desired orientation.

Human health risk and phytoremediation of potentially toxic metals (PTMs) in the edible vegetables have been widely discussed recently. This study aimed to determine the concentrations of four PTMs, namely Cd, Fe, Ni, and Zn) in Amaranthus viridis (leaves, stems, and roots) collected from 11 sampling sites in Peninsular Malaysia and to assess their human health risk (HHR). In general, the metal levels followed the order: roots > stems > leaves. The metal concentrations (µg/g) in the leaves of A. viridis ranged from 0.45 to 2.18 dry weight (dw) (0.05−0.26 wet weight (ww)), 74.8 to 535 dw (8.97−64.2 ww), 2.02 to 7.45 dw (0.24−0.89 ww), and 65.2 to 521 dw (7.83−62.6 ww), for Cd, Fe, Ni, and Zn, respectively. The positive relationships between the metals, the plant parts, and the geochemical factions of their habitat topsoils indicated the potential of A. viridis as a good biomonitor of Cd, Fe, and Ni pollution. With most of the values of the bioconcentration factor (BCF) > 1.0 and the transfer factor (TF) > 1.0, A. viridis was a very promising phytoextraction agent of Ni and Zn. Additionally, with most of the values of BCF > 1.0 and TF < 1.0, A. viridis was a very promising phytostabiliser of Cd and Fe. With respect to HHR, the target hazard quotients (THQ) for Cd, Fe, Pb, and Zn in the leaves of A. viridis were all below 1.00, indicating there were no non-carcinogenic risks of the four metals to consumers, including children and adults. Nevertheless, routine monitoring of PTMs in Amaranthus farms is much needed.

Human activities due to different land uses are being studied widely in many countries. This study aimed to determine the ecological risks and human health risk assessments (HHRA) of Cd, Pb, Ni, Cu, and Zn in the topsoils of six land uses in Peninsular Malaysia. The ranges of the potentially toxic metals (PTMs) in the soils (mg/kg, dry weight) of this study were 0.24-12.43 for Cd (mean: 1.94), 4.66-2363 for Cu (mean: 228), 2576-116,344 for Fe (mean: 32,618), 2.38-75.67 for Ni (mean: 16.04), 7.22-969 for Pb (mean: 115) and 11.03-3820 for Zn (mean: 512). For the ecological risk assessments, the potential ecological risk index (PERI) for single metals indicated that the severity of pollution of the five metals decreased in the following sequence: Cd > Cu > Pb > Zn > Ni. It was found that industry, landfill, rubbish heap, and mining areas were categorized as "very high ecological risk". For HHRA, the land uses of industry, landfill and rubbish heap were found to have higher hazard quotient (HQ) values for the three pathways (with the order: ingestion > dermal contact > inhalation ingestion) of the five metals for children and adults, when compared to the mining, plantation, and residential areas. The values for both the non-carcinogenic (Cd, Cu, Ni, and Zn), and carcinogenic risks (CR) for inhalation (Cd and Ni) obtained for children and adults in this study showed no serious adverse health impacts on their health. However, of public concern, the hazard index (HI), for Pb of children at the landfill (L-3) and the rubbish heap (RH-3) sites exceeded 1.0, indicating non-carcinogenic risk (NCR) for children. Therefore, these PERI and HHRA results provided fundamental data for PTMs pollution mitigation and environmental management in areas of different land uses in Peninsular Malaysia.

Background: The aerosol box and intubation tent are improvised barrier-enclosure devices developed during the novel coronavirus pandemic to protect health care workers from aerosol transmission., Objective: Using time to intubation as a crude proxy, we aimed to compare the efficiency and usability of the aerosol box and intubation tent in a simulated manikin., Methods: This was a single-center, randomized, crossover manikin study involving 28 participants (9 anesthetists, 16 emergency physicians, and 3 intensivists). Each participant performed rapid sequence intubations in a random sequence of three different scenarios: 1) no device use; 2) aerosol box; 3) intubation tent. We compared the time to intubation between different scenarios., Results: The median total intubation time with no device use, aerosol box, and intubation tent were 23.7 s (interquartile range [IQR] 19.4-28.4 s), 30.9 s (IQR 24.1-52.5 s), and 26.0 s (IQR 22.1-30.8 s), respectively. Post hoc analysis showed a significantly longer intubation time using the aerosol box compared with no device use (p < 0.001) and compared with the intubation tent (p < 0.001). The difference between the intubation tent and no device use was not significant. The first-pass intubation success rate did not differ between the groups. Only aerosol box use had resulted in breaches of personal protective equipment. Participants considered intubation with the intubation tent more favorable than the aerosol box., Conclusions: The intubation tent seems to have a better barrier-enclosure design than the aerosol box, with a reasonable balance between efficiency and usability. Further evaluation of its efficacy in preventing aerosol dispersal and in human studies are warranted prior to recommendation of widespread adoption., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lactating medical residents face unique barriers due to intense clinical work schedules, limited support in the clinic and hospital workspaces, and competing pressures between career development and childcare. The objective of this project was to explore the perceived culture of breastfeeding support among medical trainees and design an action plan to improve support for lactating residents in Hawai'i. Resident and faculty representatives from the Hawai'i Residency Programs and the University of Hawai'i John A Burns School of Medicine participated in an 8 month national learning collaborative to review the existing resident lactation policy and resident perception of lactation support. In a pre-survey, the majority of residents (88%) agreed that 20-30 minutes every 2-3 hours should be allowed to express milk but only 18% felt comfortable asking for a change in schedule to accommodate time to pump. An action plan was created with the following objectives: (1) revamping the existing policy to address protected pumping times, lactation spaces, and responsibilities of administration, faculty, and residents; (2) improving lactation space through uniform provision of educational material on available facilities and efficiency tips for new parents, and (3) improving awareness of the unique challenges lactating residents face and empowering faculty and trainees to advocate for lactating residents through department and educational presentations. Medical residents in Hawai'i recognize the importance of breastfeeding but perceive a lack of support in the workplace. A comprehensive action plan to revamp the resident lactation policy and improve faculty and resident education may foster an increased culture of lactation support and healthy development of the physician workforce., (©Copyright 2021 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Abstract: Diagnosing influenza in children aged 5 years and under can be challenging because of their difficulty in verbalizing symptoms. This study aimed to explore the value of the triage heart rate (HR), respiratory rate (RR), and temperature, either alone or when combined with individual symptoms and signs, in predicting influenza infection in this age group.This was a retrospective study covering 4 influenza seasons from 2017 to 2019 in an emergency department (ED) in Hong Kong. We recruited patients ≤5 years of age who had an reverse transcription polymerase chain reaction influenza test within 48 hours of ED presentation. The diagnostic performance of the triage HR, RR, and temperature was evaluated as dichotomized or categorized values with diagnostic odds ratios (DORs) calculated based on different age-appropriate thresholds. Linear discriminant analysis was performed to assess the combined discriminatory effect of age, HR, RR, and temperature as continuous variables.Of 322 patients (median age 26 months), 99 had influenza A and 13 had influenza B infection. For HR and RR dichotomized based on age-appropriate thresholds, the DORs ranged from 1.16 to 1.54 and 0.78 to 1.53, respectively. A triage temperature ≥39.0 °C had the highest DOR (3.32) among different degrees of elevation of temperature. The diagnostic criteria that were based on the presence of fever and cough and/or rhinitis symptoms had a higher DOR compared with the Centers for Disease Control and Prevention influenza-like illness criteria (4.42 vs 2.41). However, combining HR, RR, or temperature with such diagnostic criteria added very little to the diagnostic performance. The linear discriminant analysis model had a high specificity of 92.5%, but the sensitivity (18.3%) was too low for clinical use.Triage HR, RR, and temperature had limited value in the diagnosis of influenza in children ≤5 years of age in the ED. Fever and cough and/or rhinitis symptoms had a better diagnostic performance than the Centers for Disease Control and Prevention influenza-like illness criteria in predicting influenza in this age group., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. An influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, using complementary genetic models of eosinophil deficiency, we demonstrate that in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice., Competing Interests: Disclosures:   D.M. Lowe reported personal fees from Merck, non-financial support from CSL Behring, and non-financial support from Fujifilm Chemical Co. outside the submitted work. No other disclosures were reported., (© 2021 Bohrer et al.)