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Kuo-Cheng Wu,1,2 I-Cheng Lee,1,3 Chien-An Liu,4,5 Nai-Chi Chiu,3,5 Shao-Jung Hsu,1,3 Pei-Chang Lee,1,3 Chi-Jung Wu,1,3,4 Chen-Ta Chi,1,3,4 Jiing-Chyuan Luo,1,3 Ming-Chih Hou,1,3 Yi-Hsiang Huang1,3,4,6 1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Keelung Hospital, Ministry of Health and Welfare, Keelung, Taiwan; 3School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; 6Healthcare and Service Center, Taipei Veterans General Hospital, Taipei, TaiwanCorrespondence: I-Cheng Lee, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, 201 Shih-Pai Road, Sec. 2, Taipei, 112, Taiwan, Tel +886-2-28712121 ext. 7506, Fax +886-2-28739318, Email iclee@vghtpe.gov.twPurpose: Diabetes mellitus (DM) negatively impacts chronic hepatitis B patients, but its role in those with HBV-related hepatocellular carcinoma (HCC) undergoing ablation remains unclear. This study aims to evaluate the influence of DM on recurrence patterns and overall survival (OS) among patients with HBV-related HCC undergoing ablation.Patients and Methods: We retrospectively enrolled 372 patients receiving thermal ablation for HBV-related HCC, including 96 (25.8%) patients with DM. Factors associated with local tumor progression (LTP), distant recurrence, and OS were analyzed. The prognostic value of DM in IMbrave050-defined high-risk population was validated.Results: DM did not correlate with LTP, whereas patients with DM had significantly higher risk of distant recurrence (median time to recurrence 23.7 versus 46.2 months, p=0.032), poorer OS (median OS 75.6 versus 106 months, p=0.011), and poorer post-recurrence survival (70.7 versus 106 months, p=0.009). In multivariate analysis, DM (hazard ratio (HR)=1.466, p=0.012), FIB-4 score, multiple tumors, and AFP level were independent predictors of distant recurrence, while DM (HR=1.424, p=0.028), ALBI score, tumor size, AFP and creatinine levels were significantly associated with OS. A DM-based risk score effectively discriminated the risk of distant recurrence. The IMbrave050 criteria could stratify the risk of LTP but not distant recurrence. DM status further discriminated the risk of distant recurrence and mortality in the IMbrave050-defined high-risk population.Conclusion: Patients with DM had an increased risk of distant recurrence and mortality after thermal ablation for HBV-related HCC, highlighting the importance of increasing awareness of DM and implementing rigorous post-ablation monitoring for diabetic HCC patients.Keywords: hepatitis B virus, hepatocellular carcinoma, diabetes mellitus, ablation, recurrence, survival

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

There is emerging evidence to suggest that diet and dietary interventions can have an impact on heart failure (HF) outcomes. Currently, the restriction of salt intake is the only dietary advice that is consistently guideline-recommended for the management of HF despite conflicting evidence for its efficacy. Dietary components that have been investigated in people with HF include middle-chain triglyceride (MCT) oil, beta-hydroxybutyrate (BHB) salts, ketone esters and coenzyme Q10 (CoQ10). Supplementation with these components is thought to be cardioprotective possibly due to an increase in myocardial energy production. There have been research studies on the effectiveness of The Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean Diet (MedDiet) in the treatment of HF, but with conflicting results. The ketogenic diet (KD) has come to the forefront of interest due to evidence indicating its effectiveness in addressing the metabolic shift that occurs in HF. However, there is a lack of randomised controlled trials (RCT) centred around the KD. In any dietary intervention, factors such as adherence and compliance affect the validity of the results. Malnutrition, sarcopenia and/or cardiac cachexia can be present in the more advanced stages of heart failure. Nutritional screening, assessment and support/intervention are important aspects of treatment in the advanced stages of heart failure. Furthermore, HF management through dietary intervention is further complicated by the presence of comorbidities, such as diabetes mellitus (DM) and coronary artery disease (CAD). Long-term studies on the use of dietary modifications in people with HF are warranted to ascertain their efficacy, safety and side effects.

(1) Background: Pediatric intracranial aneurysms (PIA) are rare and clinicopathologically distinct neurovascular entities. The aims of this study are to evaluate our institution’s experience and corroborate our results with updated literature. (2) Methods: This is a single-institution, retrospective study. Patients with a confirmed diagnosis of PIA are included. Variables of interest include patient demographics, clinical presentation, treatment outcomes and features specific to each patient’s PIA. A literature review on PIA-centric clinical studies was conducted. (3) Results: A total of 14 PIAs in 11 patients were treated from 2000 to 2022. The mean age was 5.8 years old, and most were males (90.1%). Anterior circulation PIAs constituted 78.6% of the cohort. Half of the PIAs were of the dissecting type, and 14.3% were giant aneurysms. Of interest, 14.3% of patients had subsequent de novo aneurysms after treatment of their index aneurysm. For treatment, 57.1% underwent surgery, 35.7% had endovascular intervention and the remaining 7.1% were managed conservatively. Based on the literature review, this study had congruent findings to other existing publications. (4) Conclusions: PIAs are unique neurovascular lesions that have good outcomes if managed in a timely fashion by an experienced multidisciplinary team. We recommend longer surveillance periods due to the risk of developing de novo aneurysms.

Summary: Background: Aotearoa New Zealand does not provide publicly-funded intensive autism support. While parent-mediated supports are promising, children and families may also benefit from direct clinician support. We tested the efficacy of a low-intensity programme involving parent- and clinician-delivered support for autistic children. Methods: This single-blind, two-arm randomised controlled trial assessed outcomes of a six-month low-intensity parent- and clinician-delivered support (2–3 h per week) based on the Early Start Denver Model compared to a control group who received monthly support calls and assistance with referrals. Children aged 1–4.5 years who were autistic or showing signs of autism and their parents were randomised to the low-intensity or control group by a blinded statistician using the Urn minimisation method. Assessments were conducted at baseline and immediately following the support period (24-weeks post-baseline). The primary outcome was child engagement during an interaction with their parent. The trial was pre-registered with ANZCTR: U1111-1260-2529. Findings: From March 2021 to May 2023, 56 families were randomised to either the low-intensity or control group. Following drop-outs, 21 families in the low-intensity group and 24 in the control group were included in analysis. There was large and significantly greater improvement in children's engagement in the low-intensity group compared to the control group (F (1, 43) = 21.47, p

Meihui Li,1,2 Haiyan Zheng,3 Jae Chul Koh,4 Ghee Young Choe,5,6 Eun Joo Choi,1,2 Francis Sahngun Nahm,1,2 Pyung Bok Lee1,2 1Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Korea; 2Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 3Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Anesthesiology and Pain Medicine, Korea University College of Medicine, Seoul, Korea; 5Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea; 6Department of Pathology, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Pyung Bok Lee, Email painfree@snu.ac.krObjective: To create a deep learning (DL) model that can accurately detect and classify three distinct types of rat dorsal root ganglion neurons: normal, segmental chromatolysis, and central chromatolysis. The DL model has the potential to improve the efficiency and precision of neuron classification in research related to spinal injuries and diseases.Methods: H&E slide images were divided into an internal training set (80%) and a test set (20%). The training dataset was labeled by two pathologists using pre-defined grades. Using this dataset, a two-component DL model was developed with the first component being a convolutional neural network (CNN) that was trained to detect the region of interest (ROI) and the second component being another CNN used for classification.Results: A total of 240 lumbar dorsal root ganglion (DRG) pathology slide images from rats were analyzed. The internal testing results showed an accuracy of 93.13%, and the external dataset testing demonstrated an accuracy of 93.44%.Conclusion: The DL model demonstrated a level of agreement comparable to that of pathologists in detecting and classifying normal and segmental chromatolysis neurons, although its agreement was slightly lower for central chromatolysis neurons. Significance: DL in improving the accuracy and efficiency of pathological analysis suggests that it may have a role in enhancing medical decision-making.Keywords: deep learning, dorsal root ganglion, chromatolysis, automated detection and spinal stenosis

Abstract Background Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo. Results The attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creER T2 Apc flx/flx and BlgCreBrca2 flx/fl p53 flx/flx orthotopic immunocompetent mouse models of colorectal and breast cancer, respectively. In vitro co-cultures of breast and colorectal cancer cell lines with modified SL7207 demonstrated a significant 50–95% (P

Abstract Rural children are more at risk for childhood obesity but may have difficulty participating in pediatric weight management clinical trials if in-person visits are required. Remote assessment of height and weight observed via videoconferencing may provide a solution by improving the accuracy of self-reported data. This study aims to validate a low-cost, scalable video-assisted protocol for remote height and weight measurements in children and caregivers. Families were provided with low-cost digital scales and tape measures and a standardized protocol for remote measurements. Thirty-three caregiver and child (6–11 years old) dyads completed remote (at home) height and weight measurements while being observed by research staff via videoconferencing, as well as in-person measurements with research staff. We compared the overall and absolute mean differences in child and caregiver weight, height, body mass index (BMI), and child BMI adjusted Z-score (BMIaz) between remote and in-person measurements using paired samples t-tests and one sample t-tests, respectively. Bland–Altman plots were used to estimate the limits of agreement (LOA) and assess systematic bias. Simple regression models were used to examine associations between measurement discrepancies and sociodemographic factors and number of days between measurements. Overall mean differences in child and caregiver weight, height, BMI, and child BMIaz were not significantly different between remote and in-person measurements. LOAs were − 2.1 and 1.7 kg for child weight, − 5.2 and 4.0 cm for child height, − 1.5 and 1.7 kg/m2 for child BMI, − 0.4 and 0.5 SD for child BMIaz, − 3.0 and 2.8 kg for caregiver weight, − 2.9 and 3.9 cm for caregiver height, and − 2.1 and 1.6 kg/m2 for caregiver BMI. Absolute mean differences were significantly different between the two approaches for all measurements. Child and caregiver age were each significantly associated with differences between remote and in-person caregiver height measurements; there were no significant associations with other measurement discrepancies. Remotely observed weight and height measurements using non-research grade equipment may be a feasible and valid approach for pediatric clinical trials in rural communities. However, researchers should carefully evaluate their measurement precision requirements and intervention effect size to determine whether remote height and weight measurements suit their studies. Trial registration: ClinicalTrials.gov NCT04142034 (29/10/2019).

This data article presents details on the assessment of fracture parameters of laboratory asphalt mixtures produced using both natural and recycled concrete aggregates. The gap-graded stone matrix asphalt (SMA) is created by incorporating Trinidad Lake Asphalt (TLA) binder with carefully calibrated mixtures of recycled concrete aggregates (0 %, 10 %, 35 %, and 50 %) and natural aggregates (limestone and dust filler). The dataset variables were chosen based on the specifications of the single-edge notched beam (SENB) and semi-circular bending (SCB) tests, which are currently used for quality control and assurance (QC & QA) assessment of asphalt concrete mixtures. The data parameters provided include air void content, voids in mineral aggregates, voids filled with asphalt, density, Marshall Stability, Flow, test temperature, peak loads, RCA content, and notch depths. The fracture resistance of the mixes was studied by analysing the fracture energy, tensile strength, and fracture toughness for the collected dataset. The data shows that incorporating up to 10 % of RCA into SMA mixes, similar fracture properties can be achieved compared to traditional SMA mixtures. This presents a sustainable and environmentally advantageous option, however, it is important to exercise caution as the RCA content increases.

Antimicrobial resistance of pathogenic bacteria to currently used antibiotics killed an estimated 1.27 million people in 2019 and it is believed that this toll will increase to 10 million per year by 2050. This remains one of the most urgent threats to human health and the hunt for novel antimicrobial natural products (NPs) from microorganisms is essential in efforts to combat this threat, but recent efforts have been unsuccessful. The investigation of extreme ecological niches, such as hot springs, has gained recent interest due to their unique ecosystems, increasing the chance for novel antimicrobial NP discovery. The Roman Baths (Bath) is the UK’s only hot spring and it remains unexplored in terms of microbial diversity. In this study, samples of water, biofilm and sediment were taken from the King’s Spring and the Great Bath, and 16 S rRNA metagenomic sequencing was performed for bacterial and archaeal community exploration. Additionally, samples were used for culture-dependent isolation of antimicrobial NP producing isolates. At the phylum level, data from water samples revealed a shift from an archaeal dominant community in the King’s Spring (Crenarchaeota, Aenigmarchaeota and Nanoarchaeota) to bacteria in the Great Bath (Cyanobacteria and Proteobacteria). Archaea were still present in the biofilm and sediment of the hot spring but consistently the bacterial phyla Cyanobacteria, Bacteroidota, Proteobacteria and Nitrospirota were dominant at both sites. The antimicrobial NP producing candidate phyla Actinobacteria and Myxococcota were found in all samples. From initial isolation experiments, 297 isolates were purified, of which 15 showed broad spectrum activity against human pathogens, though interestingly these were not from target genera in the Actinobacteria. From these data, there is clear potential for novel NP discovery from the Roman Baths, as has been demonstrated from other thermal hot springs globally.

This paper describes an innovative method to provide a micro-electric tractor which has been developed as part of an initiative that aims to provide socially inclusive and affordable green energy solutions to smallholders in sub-Saharan Africa. It utilizes a 15.0-kW solar array and battery system to power micro-electric tractors for an agricultural practice called deep bed farming in Malawi. Deep bed farming increases smallholder crop yield by about two and half times, which increases revenue by up to 12 times. The extra revenue can then be used to perpetually purchase domestic energy from the solar array, creating a self-sustaining model for decentralized energy access. However, the requirement for land preparation is onerous, and mechanization is needed to help overcome barriers to entry. This paper describes the technical requirements of a solar base station and micro-tractor for use with the deep bed farming technique. The paper covers the 5.9 kWp modular solar design and a 10.0-kWh rated micro-tractor. Testing was undertaken at an isolated grid in Loughborough as a precursor for large-scale testing in Malawi.

This data article presents information on the measurement of Indirect Tensile Stiffness Modulus of laboratory and field asphalt mixtures. The asphalt mixes are composed of three distinct binders that were categorised by their penetration grade (40/55-TLA, 60/75-TLA, and 60/70-MB) and aggregates (limestone, sharp sand, and filler). The asphalt mixtures are called dense-graded hot mix asphalt (HMA) and gap-graded stone matrix asphalt (SMA). The variables in the dataset were selected in accordance with the specifications of the dynamic modulus models that are currently in use as well as the needs for the quality control and assurance (QC & QA) assessment of asphalt concrete mixes. The data parameters included are temperature, asphalt content, and binder viscosity, air void content, cumulative percent retained on 19, 12.5, and 4.75 mm sieves, maximum theoretical specific gravity, aggregate passing #200 sieve, effective asphalt content, density, flow, marshal stability, coarse-to-fine particle ratio and the Indirect Tensile Stiffness Modulus (ITSM). Utilising soft computing techniques, models were developed utilising the data thus eliminating the requirement for complex and time-consuming laboratory testing.

Abstract Background Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI. Methods This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5–20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint. Results Our findings showed significant effects for time (χ2 = 7.771, p = 0.005), treatment (χ2 = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ2 = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047). Conclusion Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo. Trial Registration NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

Pei-Chi Lee,1,* Cun-Zhao Li,2,* Chun-Te Lu,3,4,* Min-Han Zhao,2 Syu-Ming Lai,2 Man-Hua Liao,5 Cheng-Liang Peng,6 Hsin-Tung Liu,1 Ping-Shan Lai2 1xTrans Corporate Research and Innovation Center, Taipei City, Taiwan; 2Department of Chemistry, National Chung Hsing University, Taichung, Taiwan; 3Division of Plastic and Reconstructive Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; 4Institute of Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan; 6Isotope Application Division, National Atomic Research Institute, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: Ping-Shan Lai, Department of Chemistry, National Chung Hsing University, No. 145, Xingda Road, Taichung, 402, Taiwan, Tel +886-4-22840411 ext. 428, Fax +886-4-22862547, Email pslai@email.nchu.edu.twPurpose: Larger nanoparticles of bioactive compounds deposit high concentrations in follicular ducts after skin penetration. In this study, we investigated the effects of microcurrent cloth on the skin penetration and translocation of large nanoparticle applied for wound repair applications.Methods: A self-assembly of curcumin-loaded micelles (CMs) was prepared to improve the water solubility and transdermal efficiency of curcumin. Microcurrent cloth (M) was produced by Zn/Ag electrofabric printing to facilitate iontophoretic transdermal delivery. The transdermal performance of CMs combined with M was evaluated by a transdermal system and confocal microscopy. The CMs/iontophoretic combination effects on nitric oxide (NO) production and inflammatory cytokines were evaluated in Raw 264.7 cells. The wound-healing property of the combined treatment was assessed in a surgically created full-thickness circular wound mouse model.Results: Energy-dispersive X-ray spectroscopy confirmed the presence of Zn/Ag on the microcurrent cloth. The average potential of M was measured to be +214.6 mV in PBS. Large particle CMs (CM-L) prepared using surfactant/cosurfactant present a particle size of 142.9 nm with a polydispersity index of 0.319. The solubility of curcumin in CM-L was 2143.67 μg/mL, indicating 250-fold higher than native curcumin (8.68 μg/mL). The combined treatment (CM-L+M) demonstrated a significant ability to inhibit NO production and increase IL-6 and IL-10 secretion. Surprisingly, microcurrent application significantly improved 20.01-fold transdermal performance of curcumin in CM-L with an obvious escape of CM-L from follicular ducts to surrounding observed by confocal microscopy. The CM-L+M group also exhibited a better wound-closure rate (77.94% on day 4) and the regenerated collagen intensity was approximately 2.66-fold higher than the control group, with a closure rate greater than 90% on day 8 in vivo.Conclusion: Microcurrent cloth play as a promising iontophoretic transdermal drug delivery accelerator that enhances skin penetration and assists CMs to escape from follicular ducts for wound repair applications.Keywords: Zn/Ag electrofabrics, iontophoretic, self-assembly, anti-inflammatory agent, skin penetration, drug delivery

Makalah ini membandingkan kata kerja berapitan meN-...-i dan padanannya dalam bahasa Cina dari segi makna dan bentuknya. Tujuan kajian ini dilakukan adalah untuk meninjau perbezaan kata kerja berapitan meN-...-i dan padanannya, serta masalah penggunaan kamus disebabkan oleh perbezaan tersebut. Kamus dwibahasa yang dijadikan sebagai sumber data kajian ialah Kamus Umum Bahasa Melayu-Cina Serba Baru (2015). Kajian ini memanfaatkan kaedah analisis bandingan interlingual Johansson (2008), Teori Hartmann (2001) tentang perkamusan, serta pendekatan Nik Safiah et al. (2015) tentang kata kerja dan imbuhan. Hasil analisis bandingan interlingual kata kerja berapitan meN-...-i dan padanannya dalam bahasa Cina menunjukkan bahawa perbezaan yang paling ketara ialah kata kerja berapitan meN-...-i mempunyai perubahan bentuk dan pengimbuhan, tetapi hal ini tidak berlaku pada padanannya. Perbezaan tersebut menimbulkan masalah dari aspek penggunaan kamus, khususnya dari segi pemahaman tentang fungsi transitif dan makna tatabahasa yang didukung oleh apitan meN-...-i, serta jenis objek yang diterimaoleh kata kerja berapitan meN-...-i. Dapatan kajian ini turut menunjukkan bahawa penyediaan padanan kata kerja berapitan meN-...-i dalam kamus Melayu-Cina melibatkan pemindahan maklumat yang meliputi makna kata akar, fungsi transitif, makna tatabahasa imbuhan, dan jenis objek yang diterima oleh kata kerja berapitan meN-...-i. Antara maklumat tersebut, fungsi transitif dan makna tatabahasa meN-...-i merupakan aspek yang paling penting untuk menghasilkan terjemahan yang berkesan dalam kamus Melayu-Cina.

Jaboticaba (Myrciaria jaboticaba) is a recognizable and unique crop from Brazil. The fruit’s byproducts are currently being studied, given their bioactive composition and promising anti-cancer potential. It is not evident, however, if different harvesting seasons can modify the chemical profile and antioxidant capacity of jaboticaba fruit fractions. Furthermore, as there is limited data for jaboticaba’s anti-proliferative effects, additional assessments are required to improve the robustness of these findings. Therefore, this study aimed to determine the composition of the peel of jaboticaba collected in two periods (May—off-season, sample 1—and August–October—peak season, sample 2) and test the peel’s richest anthocyanin sample against colorectal cancer (CRC) cell lines. To accomplish this, proximate, spectrophotometric, and chromatographic analyses were performed in two freeze-dried samples; and anti-proliferative and/or colony-forming assays were carried out in Caco-2, HT29, and HT29-MTX cells. As a result, sample 2 showed the highest levels of polyphenols overall, including flavonoids and anthocyanins. This sample displayed significative higher contents of cyanidin-3-O-glucoside (48%) and delphinidin-3-O-glucoside (105%), in addition to a superior antioxidant capacity (23% higher). Sample 1 showed higher amounts of total protein, gallic acid (20% higher), and specific carotenoids. An aqueous extract from sample 2 was tested against CRC, showing anti-proliferative effects for Caco-2 cells at 1 and 2 mg/mL concentrations, with IC50 values of 1.2–1.3 mg/mL. Additionally, the extract was able to inhibit cell colony formation when tested at both low and high concentrations. In conclusion, jaboticaba collected in the main season stands out regarding its polyphenol composition and holds potential against cancer cell growth.

Qubits based on ions trapped in linear radio-frequency traps form a successful platform for quantum computing, due to their high fidelity of operations, all-to-all connectivity, and degree of local control. In principle, there is no fundamental limit to the number of ion-based qubits that can be confined in a single 1D register. However, in practice, there are two main issues associated with long trapped-ion crystals, that stem from the “softening” of their modes of motion, upon scaling up: high heating rates of the ions’ motion and a dense motional spectrum; both impede the performance of high-fidelity qubit operations. Here, we propose a holistic, scalable architecture for quantum computing with large ion crystals that overcomes these issues. Our method relies on dynamically operated optical potentials that instantaneously segment the ion crystal into cells of a manageable size. We show that these cells behave as nearly independent quantum registers, allowing for parallel entangling gates on all cells. The ability to reconfigure the optical potentials guarantees connectivity across the full ion crystal and also enables efficient midcircuit measurements. We study the implementation of large-scale parallel multiqubit entangling gates that operate simultaneously on all cells and present a protocol to compensate for crosstalk errors, enabling full-scale usage of an extensively large register. We illustrate that this architecture is advantageous both for fault-tolerant digital quantum computation and for analog quantum simulations.

Polymer-based heat exchangers can offer a promising solution for environmental sustainability due to their low energy consumption. The incorporation of microchannels and nanofluids further enhances the heat transfer performance of these heat exchangersIn this study, a polymer-based microchannel heat exchanger combined with nanofluid is simulated through the integration of an artificial neural network predictive model and a three-dimensional computational fluid dynamics model. This study unveils an advanced calculation that integrates artificial intelligence and readily-available computational software provided as the advanced calculation system. A statistical mathematics response surface method which data is used for correlating the calculation model is applied to obtain the design parameters between operating conditions and for optimal performance. The optimized results reveal that polymer-based microchannel heat exchanger combined with nanofluid is a promising innovation. The heat transfer improvement achieved a 12 % increase in the overall heat transfer coefficient by using TiO2/Water compared to Water. Moreover, a 1.03 performance index is obtained when CuO/Water nanofluid is used, a 66 horizontal parallel connecting of the polymer-based microchannel heat exchanger shows that the equipment can afford the same heat transfer performance of the metal-based microchannel heat exchanger in TiO2/Water nanofluid usage and implying a balance between heat transfer enhancement and energy consumption.

Background: We aimed to characterize patient experience with virtual care across medical specialties using validated survey data. Primary objective: to determine whether experience varied by visit modality (virtual vs. in-person) and whether relationships persisted after adjusting for patient and provider characteristics. Secondarily, among physicians with sufficient data, we compared virtual versus in-person patient experience scores at the physician level and identified characteristics associated with better experience scores for virtual care. Methods: This was a retrospective analysis of administrative databases from a large New England health care system, including all ambulatory visits from October 1, 2020 to September 30, 2021 with patient experience scores recorded. We compared experience between virtual and in-person at the visit level (score: 0?10) and the physician level for likelihood of recommending the physician to friends or family. We used a series of cross-classified hierarchical models with visits grouped by patient and by physician to decompose sources of variation. Among physicians with sufficient data, we compared physicians with higher virtual versus higher in-person net promoter score (NPS). Results: Of 378,472 visits performed by 3368 physicians, 86,878 (23%) were conducted virtually. Most scored ?9 for either modality, with a small preference for virtual versus in-person care (9.6 vs. 9.5, p?0.001). We found that more variation in scores was explained by patient than by physician (22.9% vs. 3%). Visit modality was of minimal explanatory value. Most physicians' virtual and in-person NPS were similar, and virtual visit volume was not associated. Conclusions: We found robust evidence for the parity of patient experience between virtual and in-person modalities across specialties.

Abstract The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to the dorsal striatum, which regulates goal-directed and habitual seeking. However, the role of GPe arky neurons in reward-seeking remains unknown. Here, we identified that a majority of arky neurons target the dorsolateral striatum (DLS). Using fiber photometry, we found that arky activities were higher during random interval (RI; habit) compared to random ratio (RR; goal) operant conditioning. Support vector machine analysis demonstrated that arky neuron activities have sufficient information to distinguish between RR and RI behavior. Genetic ablation of this arkyGPe→DLS circuit facilitated a shift from goal-directed to habitual behavior. Conversely, chemogenetic activation globally reduced seeking behaviors, which was blocked by systemic D1R agonism. Our findings reveal a role of this arkyGPe→DLS circuit in constraining habitual seeking in male mice, which is relevant to addictive behaviors and other compulsive disorders.

The periodontal ligament (PDL) contains a unique population of mesenchymal stem cells (MSCs), also known as PDL stem cells (PDLSCs). The regenerative properties of PDLSCs offer much potential for stem cell-based therapy, particularly for periodontal or bone regeneration. Aspirin (ASA) is a widely used nonsteroidal anti-inflammatory drug (NSAID) that has been reported to modulate a variety of diseases, such as cardiovascular, diabetes, and cancer. This review article focuses on the impacts of ASA on various stem cells. First, we will explain what constitutes PDLSCs and their derivation from periodontal tissues. Then we will discuss the mechanisms of ASA and its effect on periodontal tissues. Next, we focus on aspirin’s effects on the differentiation of various types of stem cells. Finally, we investigate the effects of ASA on growth factors that could enhance the osteoblastic potential of derived stem cells.

OBJECTIVES:. Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting. DESIGN:. Retrospective cohort study. SETTING:. Academic medical center in Minnesota. PATIENTS:. Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours. INTERVENTIONS:. None. MEASUREMENTS:. Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected. MAIN RESULTS:. Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1–4.5) and ICU length of stay of 4.9 days (3–8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1–0.3) and 30 hours (15.1–51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33–96%), while 64% (37–91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients. CONCLUSIONS:. Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy.

BackgroundThe state of Sarawak on the island of Borneo in East Malaysia, in working towards developing and strengthening cancer services through a holistic patient-centred approach, must focus on the comprehensive needs of cancer patients by taking into account the psycho-social, cultural and spiritual aspects of Sarawak's multi-ethnic, multi-cultural population.MethodsA 42-item survey questionnaire was developed and validated with a total of 443 patients. The perceived importance of information provided and level of patient satisfaction were assessed with a 5-point Likert scale in 10 domains (Diagnosis, Surgery, Radiotherapy, Systemic therapy, Clinical trials, Pain management, Treatment monitoring, Psychosocial support, Sexual care and fertility issues, and Financial support). A Spearman's rank correlation test was applied to determine the correlation between response in both item and domain categories for perceived importance and satisfaction.ResultsOverall, patients were more satisfied with information related to cancer diagnosis, treatment and surgery but less satisfied with information pertaining to sexual aspects of care and family planning, psycho-social support and financial support. The majority of patients were satisfied with the level of treatment-related information received but preferred the information to be delivered in more easily comprehendible formats. Sexual aspects of care and family planning, psychosocial support and treatment monitoring post-discharge were perceived as important but seldom addressed by health care professionals due to lack of professional counsellors, social workers and clinical nurse specialists. Many patients face financial toxicity following a cancer diagnosis, particularly when diagnosed with advanced cancer requiring complex multi-modality treatment.ConclusionCancer patients in Sarawak have various unmet information needs. Written information and educational videos in local indigenous languages may be more suitable for Sarawak's multi-ethnic population. Sexual aspects of care and family planning are challenging but essential topics to discuss, in particular due to the high prevalence of breast and cervical cancer amongst young women of reproductive age in Sarawak. Financial assessment and information on support services offered by government and non-government organisations should be provided to eligible patients. A holistic needs assessment of each patient at time of diagnosis and support through their cancer journey requires a multi-disciplinary team of medical, nursing and allied health professionals including clinical nurse specialists, pharmacists, counsellors, physiotherapists, occupational therapists, speech and language therapists, dieticians and social workers.

Category: Hindfoot; Ankle Introduction/Purpose: Insertional Achilles Tendinopathy (IAT) is a degenerative process at the insertion of Achilles tendon onto the calcaneal tuberosity that often coexists with retrocalcaneal bursitis and Haglund’s deformity. The Zadek osteotomy, a dorsal closing wedge osteotomy of the calcaneus, has been described as a treatment option in patients with IAT that have failed conservative management. The aim of this study was to evaluate the clinical outcomes and the complications of the Zadek for the management of IAT. Methods: PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) were searched for all studies to November 2022. PRISMA guidelines were followed. The overall estimates of effect were presented as Weighted Mean Difference (WMD) and 95% confidence intervals (CIs). Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). Results: Ten studies with 232 patients were included. The AOFAS (American Orthopaedic Foot and Ankle Society) Ankle- Hindfoot Score and the VISA-A score (Victorian Institute of Sports of Australia-Achilles score) were significantly improved after the Zadek osteotomy (p < 0.00001). Pain levels were also significantly reduced (p < 0.00001). There were a total of 22 complications reported in the included studies and they were all considered minor. The most common complications were superficial wound infection and sural nerve paraesthesia. Conclusion: The Zadek osteotomy is a safe and effective procedure for patients with IAT. The osteotomy improves pain levels and functions and is associated only with minor complications and a low complication rate. There are no well-designed randomized controlled trials in the literature assessing the outcomes of a Zadek osteotomy against alternate surgical treatments and future research should focus on this.

Background Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. The levonorgestrel-releasing intrauterine system is an effective long-term treatment but is discontinued by many due to unpredictable bleeding, or adverse effects. The selective progesterone receptor modulator ulipristal acetate is used to treat symptomatic fibroids but long-term efficacy for the symptom of heavy menstrual bleeding, irrespective of presence of fibroids, is unknown. Objectives To determine whether ulipristal acetate is more effective at reducing the burden of heavy menstrual bleeding than levonorgestrel-releasing intrauterine system after 12 months of treatment in women with and without fibroids. We investigated mechanism of action of ulipristal acetate in a subset of 20 women. Design Randomised, open-label, parallel group, multicentre trial with embedded mechanistic study. Setting Ten UK hospitals. Participants Women with heavy menstrual bleeding aged 18 and over with no contraindications to levonorgestrel-releasing intrauterine system or ulipristal acetate. Interventions Three 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or continuous levonorgestrel-releasing intrauterine system following allocation in a 1 : 1 ratio using a web-based minimisation procedure. Main trial outcome measures Primary outcome was quality-of-life measured by menorrhagia multi-attribute scale at 12 months. Secondary outcomes included menstrual bleeding and patient satisfaction. Impact on fibroid size, endometrial appearance and liver function was also collected. Mechanistic study outcome Cellular markers for endometrial cell structure and function, determined from endometrial biopsies; volume of uterus and fibroids and microcirculation parameters were determined from magnetic resonance images. Results Sample size was increased from 220 to 302 as a result of temporary halt to recruitment due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate and the COVID-19 pandemic led to a premature closure of recruitment, with 118 women randomised to each treatment and 103 women completing 12-month menorrhagia multi-attribute scale scores prior to this point. Primary outcome scores substantially improved in both arms, but at 12 months there was no evidence of a difference between those receiving three cycles of ulipristal acetate [median score category: 76–99, interquartile range (51–75 to 100), n = 53] and levonorgestrel-releasing intrauterine system [median score category: 76–99, interquartile range (51–75 to 100), n = 50; adjusted odds ratio 0.55, 95% confidence interval 0.26 to 1.17; p = 0.12]. Rates of amenorrhoea were much higher in those allocated ulipristal acetate compared with the levonorgestrel-releasing intrauterine system (12 months: 64% vs. 25%, adjusted odds ratio 7.12, 95% confidence interval 2.29 to 22.2). There was no evidence of a difference in other participant-reported outcomes. There were no cases of endometrial malignancy and no hepatotoxicity due to ulipristal acetate use. Mechanistic study results Ulipristal acetate produced a reversible reduction in endometrial cell proliferation, as well as reversible alteration of other endometrial cellular markers. Ulipristal acetate did not produce a reduction in the volume of the uterus irrespective of coexisting fibroids, nor an effect on uterine microvascular blood flow. Limitations The urgent safety measures and premature closure of recruitment impacted final sample size. Conclusions We found no evidence of a difference in quality of life between the two treatments, but ulipristal acetate was superior to levonorgestrel-releasing intrauterine system at inducing amenorrhoea. Ulipristal acetate currently has restricted availability due to concerns regarding hepatotoxicity. Future work There is a need to develop new, safe, effective and fertility-sparing medical treatments for heavy menstrual bleeding. The observed acceptability and effectiveness of ulipristal acetate warrants further research into the selective progesterone receptor modulator class of pharmacological agents. Study registration This trial is registered as ISRCTN 20426843. Plain language summary What is the problem? Heavy menstrual bleeding is a common condition that affects the lives of many women. A hormone-releasing coil, fitted inside the womb, is effective in making periods lighter but can make them less regular. A medicine called ulipristal acetate or UPA, taken as a pill, has been shown to reduce rapidly menstrual bleeding in women with large, non-cancerous tumours in the womb, known as fibroids. It was not known whether UPA is effective in women who have heavy periods but do not have fibroids of any significant size. What did we plan to do? To find out which treatment was better at controlling heavy periods, 236 women were enrolled in a clinical trial where they received either the hormone coil or UPA. The choice of treatment was made at random by a computer rather than the wishes of researchers or patients, to ensure a fair comparison. Participants completed questionnaires about their symptoms and life quality at intervals up to 1 year. Twice during the trial, medicines regulatory authorities raised safety concerns about UPA causing liver problems. This resulted in the introduction of regular blood tests. The second time, recruitment to the trial stopped early. What did we find? Both treatments improved the symptoms of heavy menstrual bleeding in the majority of women. We found no evidence that UPA was better overall after 1 year of treatment, compared with the hormone coil, although fewer women on UPA continued to have periods. Laboratory studies on samples taken from the lining of the womb showed temporary changes due to UPA, which disappeared after treatment stopped. What does this mean? Both treatments improve the symptoms of menstrual bleeding and general wellbeing. Because of safety concerns UPA is not available for all women with heavy menstrual bleeding and new, safer medical treatments are needed. Scientific summary Background Heavy menstrual bleeding (HMB) is the most common gynaecological problem in women of reproductive age, affecting one in four women, and has adverse profound impact on health-related quality of life. Common causes of HMB include structural abnormalities such as uterine fibroids, adenomyosis and dysfunction of the endometrium. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a proven, effective long-term treatment but about one-third of women cease use by two years due to unpredictable bleeding, hormonal adverse effects or lack of effectiveness. Furthermore, fibroids can make the LNG-IUS less effective. Alternative medical options for HMB exist, but are either less effective or associated with unacceptable adverse effects. Surgical interventions are effective at inducing bleeding control and improving quality of life but are typically incompatible with future fertility. Effective long-term medical treatments for women with HMB are needed. A class of drugs called selective progesterone receptor modulators (SPRMs) have potential to provide an effective oral treatment for HMB. SPRMs bind with progesterone receptors, resulting in tissue-specific effects in both myometrial and overlying endometrial tissue as well as shrinking uterine fibroids. The SPRM ulipristal acetate (UPA) has been successfully used to treat fibroids, but we do not know how effective UPA is for the treatment of women with HMB who do not have fibroids. Furthermore, there are uncertainties regarding the mechanism and location of action of UPA, as well as its longer-term safety. SPRMs induce distinctive, non-physiological endometrial changes, which can be confused with endometrial hyperplasia. More recently there has been concern regarding the potential for UPA to cause drug-induced liver injury (DILI). Post marketing surveillance reports resulted in a temporary halt in UPA use in 2018 and 2020. Use of UPA has since been reinstated since January 2021, albeit in a restricted context, reflecting the paucity of existing alternatives for HMB. Given these uncertainties, we designed the UCON trial to evaluate the safety, tolerability and effectiveness of UPA on HMB and to understand its mechanism of action. Clinical objectives Primary objective: to determine whether UPA is more effective at reducing the burden of HMB symptoms than LNG-IUS after 12 months of treatment. Secondary objectives: Ascertain whether UPA use beyond 3 months’ and up to 12 months’ duration is associated with histological changes to the endometrium and, if so, whether this compromises safety. Ascertain whether UPA is more effective than LNG-IUS in relation to menstrual blood loss, sexual activity, generic quality of life, satisfaction with treatment, patient-reported adverse events, and compliance at 3, 6 and 12 months. Determine the response to UPA and LNG-IUS treatment difference in the presence of uterine fibroids in terms of (1) alleviation of HMB and (2) change in uterine/fibroid volume. Collect data on liver function in women taking UPA, once safety concerns were raised. Mechanism of action study objectives To understand how UPA causes a reduction in menstrual bleeding and uterine/fibroid volume in women with HMB, we determined whether UPA administration: Alters endometrial cell function (e.g., and not limited to, proliferation, apoptosis, expression of steroid receptors, tumour suppressors and inflammatory mediators). Reduces blood plasma flow in the endometrium, uterine myometrium and fibroid tissue. Alters the volume fraction of the extracellular matrix in these tissues. Reduces uterine and fibroid volume. Design This was a randomised, open-label, parallel group, multicentre trial with embedded mechanistic study. Methods Setting The trial recruited participants in 10 sites in NHS hospital settings across the UK between 2015 and 2020. The mechanism of action study was conducted solely at the Edinburgh site. Participants For the main trial, informed consent was sought from premenopausal women (aged 18–50 years) with self-reported HMB, no contraindications to LNG-IUS or UPA. Those with uterine size greater than equivalent 14-week size or with submucosal fibroids >2cm were excluded. Other exclusion criteria relating to use of other treatments and current health status were applied, including history of severe hepatic impairment. Screening and randomisation Participants were recruited in gynaecology clinics by research nurses who screened patient referral letters. Following consent, haemoglobin and circulating estradiol levels were assessed, clinical history elicited and transvaginal and/or abdominal ultrasound and endometrial biopsy were obtained if not previously performed. Following this, and confirmation of eligibility, randomisation was via a web-based central service based at Birmingham Clinical Trials Unit to allocate women in a 1 : 1 ratio using a minimisation algorithm. Screened patients in Edinburgh were offered the opportunity to participate in the mechanistic study. Interventions and follow-up Those allocated to UPA received three courses of treatment, each course comprising a daily 5-mg oral dose for 12 weeks followed by a four-week break. Those allocated to the LNG-IUS had it fitted in hospital or primary care. Participants allocated to UPA returned to hospital to collect their repeat prescription at 3 and 6 months, and may have been seen by a member of the care team if required. They were then seen in clinic at 12 months for ultrasound scan (USS) and haemoglobin/serum estradiol measurement. Those allocated to the LNG-IUS group attended USS at 12 months. Follow-up at interim time points was conducted by postal questionnaire. Those partaking in the mechanism of action study underwent magnetic resonance imaging (MRI) following randomisation and at the end of treatment cycles two and three. An additional endometrial biopsy was obtained at the end of treatment cycle two. Outcome measures Primary Condition-specific quality of life score as measured by the menorrhagia multi-attribute scale (MMAS) questionnaire at 12 months. Summary scores range from 0 (worst affected) to 100 (not affected). Secondary Condition-specific quality of life score as measured by MMAS at 3 and 6 months Menstrual bleeding (pictorial blood loss assessment chart)* Cycle regularity (ordinal four-point scale)* Duration of period (ordinal three option scale)* Pelvic pain during periods, intercourse and at other times (visual analogue scales; 0 = best outcome, 10 = worse outcome)* Uterine fibroid symptom and quality of life instrument (only given to women diagnosed with fibroids)* Sexual function (sexual activity questionnaire)* Generic quality of life (EQ-5D-5L)* Satisfaction with treatment outcome (five-point Likert scale) Participant rating of effect of treatment on HMB over 12 months (four-point Likert scale) Whether participant is willing to recommend the treatment to a friend (yes/no) Surgical intervention Adherence to trial treatments and reasons for changing treatment, as reported by the participant Serious adverse events and reactions Uterine volume, evidence of adenomyosis, presence of fibroids, largest fibroid volume, endometrial thickness, endometrial appearance, evidence of ovarian cysts at 12 months (USS) Endometrial biopsy at 12 months (UPA group only) Liver function tests, from 20 March 2018 every four weeks (UPA group only) Haemoglobin and serum estradiol at 12 months * assessed at 3, 6 and 12 months Mechanism of action A: Effects on cellular markers of endometrial steroid receptors and metabolising enzymes (governing local endometrial steroid [ligand] availability), cell proliferation, cell survival (apoptosis); detection of genes implicated in control of proliferation in endometrium; B: Effects on uterine/fibroid structure addressed by obtaining volume measurements for the whole uterus, and for the total volume of fibroids when present, by using high resolution structural MRI and stereology; and C: Uterine vascularity using dynamic contrast-enhanced MRI (DCE-MRI). Urgent safety measures In November 2017, the European Medicines Agency (EMA) issued an urgent drug alert for UPA due to a small number of reports of serious liver injury. A detailed investigation by the regulatory authorities was undertaken and it was found that eight reports of serious liver injury were reported in Europe from an estimated 740,000 women using UPA for uterine fibroids. Restrictions on prescribing UPA were subsequently issued and the trial sponsor implemented an urgent safety measure (USM) in February 2018, which halted recruitment. Those allocated UPA were allowed to complete their current course of UPA treatment but not commence any further outstanding courses. In addition, they commenced monthly assessment of LFTs (as well as a post treatment test approximately 2 weeks after the last course of UPA). In August 2018, the halt on UPA prescribing was lifted and recruitment to UCON resumed in October 2018 with additional safety measures in place, including exclusion of those with any history of liver disease [defined as levels of alanine transaminase (ALT) or aspartate aminotransferase (AST) of more than two times the upper limit of normal] and LFT monitoring as described above. UPA was stopped if women had an ALT or AST more than three times the upper limit of normal and a hepatology opinion was sought. In March 2020, the EMA temporarily suspended use of UPA a second time due to ongoing concerns regarding hepatotoxicity and a further USM was issued. All treatment courses of UPA were immediately stopped. In view of the second USM, the investigators, in discussion with the funder, chose premature closure of recruitment to the study but planned follow-up actions continued as per protocol. Statistical considerations The study was powered to detect a clinically useful difference in MMAS score (13 points) between the two groups at twelve months. To detect a difference of this size [0.5 standard deviations (SDs)] with 90% power (p = 0.05) would require 86 women in each group (172 in total). To allow for a 20% loss to follow-up or pregnancy, the sample size was inflated to 220 women. Following the initial USM, this figure was inflated to 302 women to ensure that there were adequate responses in the primary analysis population (defined below) to detect the same size of difference. The original planned primary analysis population comprised all participants, regardless of adherence to treatment, employing suitable regression models to estimate difference between groups. The enforced non-compliance as a result of the withdrawal of UPA had substantial implications for the validity of the data reported by participants. It was therefore necessary to redefine analysis populations, considering the restrictions that prevented women taking their courses of UPA might influence their responses and any other new potential biases that may be apparent in either group due to, for example, knowledge of the safety concerns around UPA. The primary analysis population would now comprise participants with questionnaire responses received prior to the first USM (12 February 2018), along with questionnaire responses from participants recruited following the study restart (18 October 2018) provided that the responses were returned before the second USM (17 March 2020). Results Main trial A total of 4471 women were approached for the study, with 236 consented and randomised, of whom 181 (77%) returned primary outcome data at 12 months (103 within the primary analysis population). Baseline data were comparable between groups; 92% were white, 34% had fibroids and 8% adenomyosis. In the primary analysis population, MMAS scores substantially improved in both arms, but at 12 months there was no evidence of a difference between the UPA [median score category: 76–99, IQR (51–75 to 100), n = 53] and LNG-IUS [median score category: 76–99, IQR (51–75 to 100), n = 50] groups (adjusted OR 0.55, 95% CI 0.26 to 1.17; p = 0.12). Rates of amenorrhoea where much higher in those allocated UPA compared with LNG-IUS at each time point (3 months: 56% vs. 5%, adjusted OR 29.3, 95% CI 7.37 to 116; 6 months 53% vs. 10%, adjusted OR 11.7 95% CI 3.78 to 36.0; 12 months: 64% vs. 25%, adjusted OR 7.12, 95% CI 2.29 to 22.2). There was no evidence of a difference in the other patient-reported outcomes although there was considerable uncertainty. In those with uterine fibroids, there were no changes in fibroid or uterine volume in either treatment group at 12 months. On endometrial biopsy, seven participants (8%) had evidence of progesterone receptor modulator associated endometrial changes (PAEC) at 12 months, although none was observed at a further 6 months post treatment; there were no cases of endometrial malignancy. Rates of serious adverse events were low, and no patients required admission to hospital for management of deranged liver function tests due to UPA use. Mechanism of action study Effects of UPA administration on the uterus: UPA produced a reduction in cell proliferation in the endometrium, as well as alteration of other local endometrial cellular markers (steroid receptor and steroid metabolising enzyme expression) creating a local endometrial oestrogenic environment. The effects on endometrial cellular markers were reversed upon withdrawal of UPA treatment. Stereological analysis in 19 patients showed that UPA did not produce a reduction in the volume of the uterus, irrespective of coexisting fibroids or adenomyosis. DCE-MRI in 15 patients showed that UPA appears not to have an effect on uterine blood flow. If adenomyosis was present in the uterus, there was a significant increase in plasma volume in the endometrium. However, one of the five women with adenomyosis also had fibroids. Effects of UPA administration on uterine fibroids: DCE-MRI studies showed that UPA produced an average reduction in plasma volume in 11 fibroids, which may be interpreted as being due to a reduction in extracellular matrix components. This finding was not supported by stereological analysis, which failed to show a reduction in the total volume of fibroids in eight patients. However, it should be noted that the number of subjects studied is small. Conclusions Both UPA and LNG-IUS alleviated the adverse impact of heavy menstrual bleeding on quality of life but we found no evidence of a difference between groups over 12 months. UPA was evidently superior to LNG-IUS in terms of inducing amenorrhoea. We observed no difference in reduction in the volume of the uterus, whether or not fibroids were present and no difference in change in the volume of fibroids was observed. Analysis of selected markers of endometrial cellular function demonstrated UPA modulation of the progesterone receptor, resulting in molecular and cellular alteration in steroid receptors within the endometrium, consistent with the development of a local (endometrial) oestrogenic microenvironment. Despite this, there is no evidence of pathological endometrial changes. We demonstrated that alteration in the endometrial microenvironment reverses on cessation of UPA treatment, a key factor for a medical treatment of HMB, particularly for those who wish to preserve fertility. UPA now has restricted availability due to concerns regarding hepatotoxicity. Findings from this study may offer insights into mechanism of action of other SPRM class members. New, effective and acceptable oral medical treatment options are needed to address an important unmet clinical need. Recommendations for research Further studies of medical treatments for HMB Developing other SPRMs, not associated with DILI Other hormonal/non-hormonal medical treatments for HMB Patient populations that encompass both the symptoms of HMB and underlying aetiologies, including structurally normal uterus, adenomyosis and small fibroids Study design with outcome measures impact on menstrual bleeding pattern, pelvic pain and impact on haemoglobin and iron-deficiency, as well as quality of life Qualitative studies to determine what are the most important outcomes to women who suffer HMB Study registration This trial is registered as ISRCTN 20426843. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 8. See the NIHR Journals Library website for further project information.

So-Jung Kim,1,&ast; Nidhi Puranik,2,&ast; Dhananjay Yadav,3,&ast; Jun-O Jin,1 Peter CW Lee4 1Department of Microbiology, University of Ulsan College of Medicine, Seoul, 05505, South Korea; 2Department of Biochemistry & Genetics, Barkatullah University, Bhopal, Madhya Pradesh, 462026, India; 3Department of Life Science, Yeungnam University, Gyeongsan, 38541, Korea; 4Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505, South Korea&ast;These authors contributed equally to this workCorrespondence: Peter CW Lee, Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, ASAN Medical Center, Seoul, 05505, Korea, Email pclee@amc.seoul.kr Jun-O Jin, Department of Microbiology, University of Ulsan College of Medicine, Seoul, 05505, Korea, Email junojin@amc.seoul.krAbstract: Although various treatments are currently being developed, lung cancer still has a very high mortality rate. Moreover, while various strategies for the diagnosis and treatment of lung cancer are being used in clinical settings, in many cases, lung cancer does not respond to treatment and presents reducing survival rates. Cancer nanotechnology, also known as nanotechnology in cancer, is a relatively new topic of study that brings together scientists from a variety of fields, including chemistry, biology, engineering, and medicine. The use of lipid-based nanocarriers to aid drug distribution has already had a significant impact in several scientific fields. Lipid-based nanocarriers have been demonstrated to help stabilize therapeutic compounds, overcome barriers to cellular and tissue absorption, and improve in vivo drug delivery to specific target areas. For this reason, lipid-based nanocarriers are being actively researched and used for lung cancer treatment and vaccine development. This review discusses the improvements in drug delivery achieved with lipid-based nanocarriers, the obstacles that still exist with in vivo applications, and the current clinical and experimental applications of lipid-based nanocarriers in lung cancer treatment and management.Keywords: lung cancer, lipid-based nanocarriers, liposome, drug delivery system

Background/Objective: Hypocalcemia is a common, treatable cause of neonatal seizures. The rapid repletion of calcium is essential for restoring normal calcium homeostasis and resolving seizure activity. The accepted approach to administer calcium to a hypocalcemic newborn is via peripheral or central intravenous (IV) access. Case Report: We discuss a case of a 2-week-old infant who presented with hypocalcemia and status epilepticus. The etiology was determined to be neonatal hypoparathyroidism secondary to maternal hyperparathyroidism. Following an initial dose of IV calcium gluconate, the seizure activity abated. However, stable peripheral intravenous access could not be maintained. After weighing the risks and benefits of placing a central venous line for calcium replacement, it was decided to use continuous nasogastric calcium carbonate at a rate of 125 mg of elemental calcium/kg/d. Ionized calcium levels were used to guide the course of the therapy. The infant remained seizure-free and was discharged on day 5 on a treatment regimen that included elemental calcium carbonate, calcitriol, and cholecalciferol. He remained seizure free since discharge and all medications were discontinued by 8 weeks of age. Discussion: Continuous enteral calcium is an effective alternate therapy for restoration of calcium homeostasis in a neonate presenting with hypocalcemic seizures in the intensive care unit (ICU). Conclusion: We propose that continuous enteral calcium be considered as an alternative approach for calcium repletion in neonatal hypocalcemic seizures, one that avoids the potential complications of peripheral or central IV calcium administration.

ObjectiveTo characterize academic urology Twitter presence and interaction by subspecialty designation. MethodsUsing Twitter application programming interface of available data, 94000 specific tweets were extracted for the analysis through the Twitter Developer Program. Academic urologists were defined based on American Urological Association (AUA) residency program registration of 143 residency programs, with a total of 2377 faculty. Two of 3-factor verification (name, location, specialty) of faculty Twitter account was used. Additional faculty information including sex, program location, and subspecialty were manually recorded. All elements of microblogging were captured through Anaconda Navigator. Analyzed tweets were further evaluated using natural language processing for sentiment association, mentions, and quote tweeted and retweeted. Network analysis based on interactions of academic urologist within specialty for given topic were analyzed using D3 in JavaScript. Analysis was performed in Python and R. ResultsWe identified 143 residency programs with a total of 2377 faculty (1975 men and 402 women). Among all faculty, 945 (39.7%) had registered Twitter accounts, with the majority being men (759 [80.40%] versus 185 [19.60%]). Although there were more male academic urologists across programs, women within academic urology were more likely to have a registered Twitter account overall (46% versus 38.5%) compared with men. When assessing registered accounts by sex, there was a peak for male faculty in 2014 (10.05% of all accounts registered) and peak for female faculty in 2015 (2.65%). There was no notable change in faculty account registration during COVID-19 (2019–2020). In 2022, oncology represented the highest total number of registered Twitter users (225), with the highest number of total tweets (24622), followers (138541), and tweets per user per day (0.32). However, andrology (50%) and reconstruction (51.3%) were 2 of the highest proportionally represented subspecialties within academic urology. Within the context of conversation surrounding a specified topic (#aua21), female pelvic medicine and reconstructive surgery (FPMRS) and endourology demonstrated the total highest number of intersubspecialty conversations. ConclusionsThere is a steady increase in Twitter representation among academic urologists, largely unaffected by COVID-19. While urologic oncology represents the largest group, andrology and reconstructive urology represent the highest proportion of their respective subspecialties. Interaction analysis highlights the variant interaction among subspecialties based on topic, with strong direct ties between endourology, FPMRS, and oncology.

Evidence is limited on how the onset of health conditions affects tobacco/nicotine use. We report analyses from adults in the U.S. PATH study relating changes in established cigarette and/or e-cigarette use between Waves 1 and 4 to onset of conditions in Waves 2 or 3.

Waste heat utilization has been prioritized especially in various industries and sectors. Many researchers have developed heat recovery processes by designing suitable waste heat recovery units (WRU), such as heat exchangers, using water as a coolants to receive heat from the waste heat fluid in the production process. The conventional heat exchanger has limitations such as its equipment size, space for installation, and flexibility. The microchannel heat exchanger is one of many ideas for resolving these limitations. Moreover, the coolant on the cold side can be upgraded by adding nanometer-sized solid particles which is called “Nanofluid”. To reduce the high investigation cost and time, a new efficient and cost-effective simulation method was selected to use for investigating the performance of a microchannel heat exchanger with nanofluids in this study. To analyze the heat recovery at low temperature, i.e. around 100–200 °C, nanofluid property predictive models were developed using an artificial neural network (ANN). Then, the predictive models were embedded and integrated into computational fluid dynamics to design a microchannel heat exchanger. It is found that the use of nanofluids improved the heat transfer efficiency of this heat exchanger. The suitable nanofluid types and concentrations were selected based on the thermal–hydraulic​ performance. Here, the 3% weight TiO2/Water fluid with a 1.03 thermal–hydraulic​ performance ratio was found to be the most promising nanofluid for using in this condition.

Pyrenophora teres f. teres (Ptt) is a severe pathogen to spring barley in Northern Europe. Ptt with relevant mutations in fungicide target proteins, sterol 14α-demethylase (CYP51A), cytochrome b (Cyt b), and succinate dehydrogenase (SDH) would put efficient disease control at risk. In the growing seasons of 2021 and 2022, 193 Ptt isolates from Estonia were analysed. In this study, mutation detection and in vitro fungicide sensitivity assays of single-spore isolates were carried out. Reduced sensitivity phenotype to mefentrifluconazole was evident in Ptt isolates with a F489L mutation in CYP51A or with 129 bp insert in the Cyp51A gene-promoter region. However, sensitivity to a prothioconazole-desthio remained high regardless of these molecular changes. The Ptt population was mostly sensitive to bixafen, fluxapyroxad, pyraclostrobin, and azoxystrobin. The sensitivity of fluxapyroxad and bixafen has been affected by two mutations, C-S135R and D-H134R, found in SDH subunits. The F129L mutation in Cyt b influenced azoxystrobin but not pyraclostrobin sensitivity. In total, 30 isolates from five fields had relevant mutations in three target protein genes simultaneously. Most of these isolates had a reduced sensitivity phenotype to mefentrifluconazole, fluxapyroxad, and azoxystrobin, while sensitivity to other tested fungicides remained high. Furthermore, possible sexual reproduction may enhance the pathogen’s fitness and help it adapt to fungicides.

Abstract Introduction The N400 is an electrophysiological component that reflects lexical access and integration of words with mental representations. Methods Thirty‐five young children with a range of language capabilities (n = 21 neurotypical controls, 10 males, mean age = 6.3 ± 0.9 years; n = 14 children with autism, 12 males, mean age = 6.4 ± 1.1 years) completed an auditory semantic categorization paradigm to evoke the N400. Electroencephalograph (EEG) data were acquired with a 64‐channel electrode cap as children listened via ear inserts to binaurally presented single syllable words and decided whether the words were congruent (in) or incongruent (out) with a pre‐specified category. EEG data were filtered, epoched, and averaged referenced, and global field power (GFP) was computed. The amplitude of the N400 peak in the GFP was submitted to a multiple linear regression analysis. Results N400 amplitude was found to predict language scores only for the children with ASD who have language scores in the normal range (r2 = 0.72). Conclusions This finding that N400 amplitude only predicted language scores in children with ASD and normal language scores suggests that these children may rely more on basic semantic processing (as reflected by the N400) and less on anticipating and predicting upcoming words. This suggests preferential utilization of a bottom‐up strategy to access higher order language.

Introduction: Myelofibrosis is a rare disease. There is currently no published data reporting the demographics and outcome of myelofibrosis patients in Malaysia. We aimed to study the demographics, clinical characteristics, and outcome of our patients in Sarawak. Materials and methods : This non-interventional, retrospective, and multi-center study was conducted on secondary data of medical records collected at four Sarawak Public Hospitals. All adult myelofibrosis patients diagnosed between January 2001 and December 2021 were included. Results : A total of 63 patients (male 31) with myelofibrosis were included—47 (74.6%) primary and 16 (25.4%) secondary myelofibrosis. Eleven had antecedent polycythaemia vera, whereas five transformed from essential thrombocythaemia. The combined annual incidence rate was 0.182 per 100,000 population. The period prevalence per 100,000 population over the entire study duration was 2.502. The median age was 59.0 years (33.0–93.0). Majority had high-risk (34/63(54.0%)) and intermediate-2 risk disease (19/63(30.2%)). JAK2V617F mutation was identified in 52 patients (82.5%), followed by CALR mutation in 6 (9.5%) and negative for both mutations in 5 (7.9%). Hydroxyurea was used as first-line therapy in 41/63 (65.1%), followed by interferon (8/63(12.7%)) and ruxolitinib (4/63(6.3%)). Out of 46 patients who received second-line therapy, 18 (39.1%) were switched to ruxolitinib and 9 (19.6%) to interferon. The median age of survival for overall patients was 6.8 years. The use of ruxolitinib in myelofibrosis patients showed a better overall 5-year survival compared to the no ruxolitinib arm, despite no statistical significance ( p = 0.34). Patients who had good performance status had lower hazard of death than patients who had poor performance status (high-risk (95% confidence intervals): 0.06(0.013–0.239), p

ObjectiveThe aim of this study was to quantify radiomic changes in prostate cancer (PCa) progression on serial MRI among patients on active surveillance (AS) and evaluate their association with pathologic progression on biopsy.MethodsThis retrospective study comprised N = 121 biopsy-proven PCa patients on AS at a single institution, of whom N = 50 at baseline conformed to the inclusion criteria. ISUP Gleason Grade Groups (GGG) were obtained from 12-core TRUS-guided systematic biopsies at baseline and follow-up. A biopsy upgrade (AS+) was defined as an increase in GGG (or in number of positive cores) and no upgrade (AS−) was defined when GGG remained the same during a median period of 18 months. Of N = 50 patients at baseline, N = 30 had MRI scans available at follow-up (median interval = 18 months) and were included for delta radiomic analysis. A total of 252 radiomic features were extracted from the PCa region of interest identified by board-certified radiologists on 3T bi-parametric MRI [T2-weighted (T2W) and apparent diffusion coefficient (ADC)]. Delta radiomic features were computed as the difference of radiomic feature between baseline and follow-up scans. The association of AS+ with age, prostate-specific antigen (PSA), Prostate Imaging Reporting and Data System (PIRADS v2.1) score, and tumor size was evaluated at baseline and follow-up. Various prediction models were built using random forest (RF) classifier within a threefold cross-validation framework leveraging baseline radiomics (Cbr), baseline radiomics + baseline clinical (Cbrbcl), delta radiomics (CΔr), delta radiomics + baseline clinical (CΔrbcl), and delta radiomics + delta clinical (CΔrΔcl).ResultsAn AUC of 0.64 ± 0.09 was obtained for Cbr, which increased to 0.70 ± 0.18 with the integration of clinical variables (Cbrbcl). CΔr yielded an AUC of 0.74 ± 0.15. Integrating delta radiomics with baseline clinical variables yielded an AUC of 0.77 ± 0.23. CΔrΔclresulted in the best AUC of 0.84 ± 0.20 (p < 0.05) among all combinations.ConclusionOur preliminary findings suggest that delta radiomics were more strongly associated with upgrade events compared to PIRADS and other clinical variables. Delta radiomics on serial MRI in combination with changes in clinical variables (PSA and tumor volume) between baseline and follow-up showed the strongest association with biopsy upgrade in PCa patients on AS. Further independent multi-site validation of these preliminary findings is warranted.

(1) Background: Fluorescein sodium (Na-Fl) has been described as a safe and useful neurosurgical adjunct in adult neurooncology. However, its use has yet to be fully established in children. We designed a study to investigate the use of intraoperative Na-Fl in pediatric brain tumor surgery. (2) Methods: This is a single-institution study for pediatric brain tumor patients managed by the Neurosurgical Service, KK Women’s and Children’s Hospital. Inclusion criteria consists of patients undergoing surgery for suspected brain tumors from 3 to 19 years old. A predefined intravenous dose of 2 mg/kg of 10% Na-Fl is administered per patient. Following craniotomy, surgery is performed under alternating white light and YELLOW-560 nm filter illumination. (3) Results: A total of 21 patients with suspected brain tumours were included. Median age was 12.1 years old. For three patients (14.3%), there was no significant Na-Fl fluorescence detected and their final histologies reported a cavernoma and two radiation-induced high grade gliomas. The remaining patients (85.7%) had adequate intraoperative fluorescence for their lesions. No adverse side effects were encountered with the use of Na-Fl. (4) Conclusions: Preliminary findings demonstrate the safe and efficacious use of intraoperative Na-Fl for brain tumors as a neurosurgical adjunct in our pediatric patients.

Invasive species threaten biodiversity and ecosystem functioning, often causing changes in plant community composition and, thus, the functional traits of that community. Quantifying changes in traits can help us understand invasive species impacts on communities; however, both the invader and the plant community may be responding to the same environmental drivers. In North America, leafy spurge (Euphorbia esula L.) is a problematic invader that reduces plant diversity and forage production for livestock. Its documented effects on plant communities differ amongst studies, however, potentially due to differences in productivity or land management. To identify the potential effects of leafy spurge on plant communities, we quantified leafy spurge abundance, plant species richness, forage production, functional group composition and community weighted mean traits, intensively at a single site and extensively across ten sites differing in management. We then tested how leafy spurge abundance related to these variables as a function of site management activities. Leafy spurge abundance was consistently associated with fewer plant species, reduced forage production and more invasive grass. Community-weighted specific root length also consistently increased with leafy spurge abundance, suggesting that belowground competition may be important in determining co-existence with leafy spurge. Other changes were dependent on management. Native forbs were excluded as leafy spurge became more abundant, but only in grazed sites as these species were already absent from ungrazed sites. Taller plants better persisted in dense leafy spurge patches, but only in grazed sites, consistent with either facilitation of taller species via associational defences or competitive exclusion of shorter species in ungrazed sites and dense leafy spurge patches. These results show that, despite some emergent properties of invasion, management context can alter invasion impacts by causing changes in the plant community and its interactions with the invader.

Abstract Background Determine if apneic oxygenation (AO) delivered via nasal cannula during the apneic phase of tracheal intubation (TI), reduces adverse TI-associated events (TIAEs) in children. Methods AO was implemented across 14 pediatric intensive care units as a quality improvement intervention during 2016–2020. Implementation consisted of an intubation safety checklist, leadership endorsement, local champion, and data feedback to frontline clinicians. Standardized oxygen flow via nasal cannula for AO was as follows: 5 L/min for infants (

Po-Hsiu Huang,1,&ast; Yao-Ting Huang,2,&ast; Po-Hsin Lee,3– 6 Chien-Hao Tseng,7 Po-Yu Liu,5– 7 Chia-Wei Liu7 1Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Computer Science and Information Engineering, National Chung Cheng University, Chia-Yi, Taiwan; 3Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Po-Yu Liu; Chia-Wei Liu, Tel +886 4 2359 2525, Fax +886 4 2359 2525 2111, Email pyliu@vghtc.gov.tw; chiaweiliu35@gmail.comAbstract: Coinfection in COVID-19 patients is associated with worsening outcome. Among patients with COVID-19, Legionella pneumophila, a common cause of pneumonia, has been reported as a co-occurring respiratory infection. A nonspecific clinical presentation, however, makes an early diagnosis difficult. Bronchoalveolar lavage fluid was collected from a patient suffering from COVID-19 and presenting with pneumonia and sent for metagenomic analysis. Differential abundance analysis was carried out by comparing each taxon reads per million between the bronchoalveolar lavage fluid sample and the negative control. Two replicates of metagenomic sequencing were conducted on bronchoalveolar lavage fluid samples. Within each replicated sequencing, one negative control was sequenced for comparison of taxon abundance in the BALF sample. In both replicates, Legionella pneumophila was the only taxon with significantly higher abundance when compared with the negative control. PCR of the bronchoalveolar further confirmed the presence of L. pneumophila. Several studies have estimated that the incidence of Legionnaires’ disease co-infection in patients with COVID-19 infection is approximately 0% to 1.5%. There are some common characteristics of COVID-19 and co-infection with Legionnaires’ disease, making it difficult to diagnose bacterial infection early. The diagnosis of these cases is important due to the different treatments used. Current diagnostic tests for Legionnaires’ disease include conventional culture, urinary antigen for L. pneumophila serogroup 1, polymerase chain reaction, direct fluorescent antibody stain, and paired serology. The current study demonstrated that metagenomics is a promising approach that facilitated the diagnosis of Legionnaires’ disease.Keywords: Legionnaires’ disease, COVID-19, co-infection, next-generation sequencing

Dhananjay Yadav,1,* Nidhi Puranik,2,* Anju Meshram,3,* Vishal Chavda,4 Peter Chang-Whan Lee,5 Jun-O Jin6 1Department of Life Science, Yeungnam University, Gyeongsan, 38541, South Korea; 2Biological Sciences Department, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India; 3Department of Biotechnology, Kalinga University, Naya Raipur, Chhattisgarh, India; 4Department of Pathology, Stanford School of Medicine, Stanford University Medical Center, Stanford, CA, 94305, USA; 5Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea; 6Department of Microbiology, University of Ulsan College of Medicine, Seoul, 05505, South Korea*These authors contributed equally to this workCorrespondence: Peter Chang-Whan Lee, Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea, Email pclee@amc.seoul.kr Jun-O Jin, Department of Microbiology, University of Ulsan College of Medicine, Seoul, 05505, South Korea, Email junojin@amc.seoul.krAbstract: Cancer is a broad term for a group of diseases involving uncontrolled cell growth and proliferation. There is no cure for cancer despite recent significant improvements in screening, treatment, and prevention approaches. Among the available treatments, immunotherapy has been successful in targeting and killing cancer cells by stimulating or enhancing the body’s immune system. Antibody-based immunotherapeutic agents that block immune checkpoint proteins expressed by cancer cells have shown promising results. The rapid development of nanotechnology has contributed to improving the effectiveness and reducing the adverse effects of these anti-cancer immunotherapeutic agents. Recently, engineered nanomaterials have been the focus of many state-of-The-art approaches toward effective cancer treatment. In this review, the contribution of various nanomaterials such as polymeric nanoparticles, dendrimers, microspheres, and carbon nanomaterials in improving the efficiency of anti-cancer immunotherapy is discussed as well as nanostructures applied to combination cancer immunotherapy.Keywords: nanotechnology, combination therapy, cancer therapy, engineered nanomaterials, nanotoxicity, synergistic therapy

Public PreK programs are an increasingly popular policy tool to equalize early learning opportunities. Programs can be universally available or targeted to support children's readiness. At the intersection of early childhood and K-12 education, their hybrid status can be difficult for families to negotiate. Based on interviews completed in 2018, we describe how parents in a universal PreK program decided whether and where their child would attend PreK, comparing parents who chose school sites with those who did not. The part-time nature of the program was a barrier to many families, prompting us to ask whether a program is authentically universal if it is not accessible to all.

Exploratory data analysis (EDA), data visualization, and visual analytics are essential for understanding and analyzing complex datasets. In this project, we explored these techniques and their applications in data analytics. The case discusses Tableau, a powerful data visualization tool, and Google BigQuery, a cloud-based data warehouse that enables users to store, query, and analyze large datasets. It also explored the benefits and applications of both tools and their integration with other platforms and services. The project offers an introductory insight into Tableau's functionalities, employing a data file from the US Census Bureau via Google BigQuery.