Although in vitro studies suggest that neutralization by monoclonal antibodies (mAbs) against SARS CoV2 Omicron sub lineages is reduced, in vivo virological response data are lacking. MONET (EudraCT: 2021-004188-28) was multi-centric phase 4 open-label parallel randomized clinical trial, conducted in Italy over 2022-2023, to assess the efficacy of sotrovimab (SOT), tixagevimab/cilgavimab (TIX/CIL) and Nirmatrelvir/ritonavir (NMV/r), in outpatients at high risk for severe COVID-19. The outcome (secondary in the trial protocol) was SARS-CoV-2 variation in cycle threshold (CT) values over the first 7 days (D1-D7) of the trial. CT variation was compared by trial arms using unadjusted linear regression and after controlling for age. We included 346 individuals: 116 (34%) received SOT, 113 (33%) TIX/CIL, 117 (34%) NMV/r. Main characteristics were balanced across arms. Most of the participants were infected with BA.2 (52%) or BA.4/5 (35.5%). The data carried strong evidence that the mean CT change over D1-D7 was larger in subjects receiving NMV/r vs. the other arms (p<0.001). We found no evidence that viral variant was an effect measure modifier for the contrasts of interest (p=0.14). Our analysis provides strong evidence that NMV/r exerts a greater in vivo antiviral effect than mAbs against Omicron sublineages, confirming previous in vitro data.

Norovirus (NoV) infection is a major pathogen causing acute gastroenteritis (AGE) across all age groups worldwide. Here, we report on the prevalence and genetic characteristics of NoVs in patients with AGE at diarrhea clinics in Huzhou from January 2019 to October 2023. A total of 2846 specimens were collected and tested for NoV by real-time RT-PCR. Approximately 460 specimens (16.16%) were identified as Nov positive. RNA-dependent RNA polymerase (RdRp) and capsid gene sequences of 216 viral strains were amplified and sequenced, and genotyping was performed using the RIVM online typing tool. During this period, at least 20 NoV genotypes were observed, with GII.4 Sydney being the most predominant. Phylogenetic analysis of selected strains revealed that all GII.4 Sydney[P16] strains clustered together and were closely related to strains from Beijing, Shanghai, Hangzhou, Nanjing and the United States, with nucleotide homologies ranging from 96.9% to 99.7%. Our study indicates that GII.4 Sydney is undergoing a new wave of resurgence, and becoming the main epidemic strain again, particularly when GII.4 Sydney[P16] is causing peaks in NoV positivity rates in January 2022 and October 2023. These results highlight the need for continuous long-term monitoring of GII.4 Sydney NoV variants.

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Rationale It has been demonstrated that micro- and nanoplastics (MNPs) can be found in soil, and that MNPs can be taken up by plants. In order to conduct a risk assessment for human consumption, it is necessary to have an estimate of the mass concentration of plastics in crops. A new thermal extraction and desorption coupled with gas chromatography and mass spectrometry (TED-GC/MS) method has been developed for the analysis of polystyrene in pak choi. Methods In this study, a thermogravimetric analyzer (TGA) equipped with a thermal absorption unit (TAU), was coupled with a GC system equipped with a thermal desorption unit (TDU2), a (5%-phenyl)-methylpolysiloxane GC column and a GC/MSD single quadrupole mass spectrometer. The systems were connected via an Multi Purpose Sampler (MPS). Samples were pyrolyzed in the TGA, the pyrolysis products were trapped on a PDMS polymer bar, desorbed in the TDU, separated and analysed on the GC/MS system. Results PS MNPs of different sizes were qualitatively and quantitatively determined in pak choi, The determined LOD is 0.09 µg and the LOQ is 0.28 µg PS absolute. In the plants treated with 100 nm particles 19.0 ± 6.7 µg/g DM PS and in the plants treated with 500 nm particles 64.1 ± 8.6 µg/g DM PS have been found. Conclusions This study was the first to use a TED-GC/MS method for the detection of polystyrene (PS) nanoplastics of different sizes in pak choi and thus provides an important basis for the determination and risk assessment of PS in vegetables.

Background: The objective of conversion therapy is to convert unresectable locally advanced esophageal cancer into resectable condition. Chemoradiotherapy is the standard treatment; however, radiotherapy may increase surgical difficulty and complications. Recently, immunotherapy has shown significant efficacy in advanced esophageal cancer, but its specific role in neoadjuvant therapy remains unclear. This study aims to investigate the efficacy, safety, and short-term perioperative outcomes of using domestically produced PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for locally advanced ESCC. Methods: 46 patients who received neoadjuvant treatment with domestically produced PD-1 inhibitors combined with chemotherapy were selected. The retrospective analysis included patient data on dosing regimens, imaging results, pathological findings, surgical details, and adverse events associated with treatment for locally advanced ESCC. Results: After neoadjuvant chemoimmunotherapy the T, N, and TNM stages significantly regressed. The objective response rate (ORR) of 67.4% and the disease control rate (DCR) of 100%. The treatment’s safety profile was acceptable, with toxicity remaining manageable and no fatalities attributable to the therapy. 45 patients (97.8%) achieved R0 resection. The rates of major pathological response (MPR) and pathological complete response (pCR) were 56.5% and 17.4%, respectively. The rate of lymphovascular invasion was 10.9%, the rate of nerve invasion was 26.1% and the lymph node metastasis rate was 30.4%. These results indicated significant radiologic and pathologic response. Conclusion: Our results indicate that neoadjuvant chemoimmunotherapy represents a viable and promising treatment for locally advanced ESCC, without increasing surgical complexity or the risk of complications. These findings justify further studies with larger sample sizes and extended follow-up to confirm its long-term efficacy and safety.

Background: West Nile Virus (WNV) is a zoonotic virus posing significant public health challenges globally. Misinformation about WNV on digital platforms like YouTube can impede public health efforts . Objective: This study evaluates the quality of English-language YouTube content on WNV using DISCERN and Global Quality Scale (GQS) tools to assess reliability and educational value. Methods: A YouTube search was conducted on September 21, 2024, using the keyword ”West Nile virus.” After applying inclusion and exclusion criteria, 79 videos were analyzed. Video characteristics such as source, type, and duration were assessed. DISCERN and GQS were used to evaluate quality and reliability and statistical analyses performed to identify factors influencing these scores. Results: The average DISCERN score of videos was 28, indicating low quality, with 64.5% of videos scoring 1 or 2 on the GQS. Videos uploaded by healthcare professionals or academic institutions had significantly higher GQS scores. Educational videos scored higher on both DISCERN and GQS metrics compared to testimonial or other videos. Video duration positively correlated with quality scores, while the presence of supporting visuals had no significant impact. Conclusion: Most YouTube content on WNV lacks reliability and quality, emphasizing the need for increased contributions from healthcare professionals and academic institutions. Producing professional, informative videos and encouraging viewers to rely on verified sources are critical for combating misinformation and improving public health communication.

Climate change, marked by prolonged periods of extreme summer drought coupled with heat, presents a significant challenge for chestnut forests. Genomic insight into drought tolerance in Castanea sativa is essential for enhancing the adaptation of this species to climate change. However, progress in this area has been hindered by the lack of a genome reference. To address this limitation, we developed a comprehensive drought tolerance gene atlas by leveraging publicly available databases and the high homology between the Quercus and Castanea genera. Candidate genes were identified through a mapping approach using short-read sequence databases and validated via Sanger sequencing. Our method enabled the successful reconstruction of coding sequences and the identification of genetic variability in C. sativa. Two genes encoding an oleosin-like protein and a two-component response regulator exhibited significant sequence differences, suggesting their involvement in adaptive stress responses. These genes emerge as promising targets for future research and potential genetic markers for drought tolerance. The resulting gene atlas provides valuable insights into drought tolerance and supports the development of molecular markers for more targeted and effective conservation and breeding strategies.

Background Antimicrobial resistance (AMR) is a major global threat, driven by the misuse and overuse of antimicrobials. India faces unique challenges in combating AMR due to the absence of a national antimicrobial stewardship program (ASP). This study aimed to evaluate antimicrobial use in a general surgery ward using the metrics Defined Daily Dose (DDD) and Days of Therapy (DOT). Methods A prospective study was conducted over six months in the surgery wards of a tertiary care hospital. Of the 554 admitted patients, 217 (29.16%) were included in the study. Of these, 125 (57.60%) were male and 92 (42.40%) were female. The mean age and length of stay were 47.2 ± 16.66 years and 7.03 ± 3.25 days, respectively. Antimicrobial usage was measured using DDD and DOT per 1000 patient-days. The difference between DDD and DOT was analyzed using the Wilcoxon signed-rank test. Results The mean total antimicrobial usage was 6273.919 ± 7842.411 DDDs per 1000 patient-days and 4491.776 ± 1665.571 DOTs per 1000 patient-days. Among the 36 commonly used antimicrobials, the difference between DDD and DOT was classified as major [24 (77.42%)], moderate [5 (16.13%)], and minor [7 (22.58%)]. The Length of Therapy (LOT) was 8271.89 per 1000 patient-days, while the antimicrobial resistance rate was 9.21%. Conclusions The study identified significant discrepancies between DDD and DOT, underscoring the need to use multiple metrics to evaluate antimicrobial stewardship programs. Clinical pharmacists play a key role in monitoring antimicrobial use to mitigate resistance.

In order to resolve the contradiction between the rapid growth of wind turbines installed capacity and the lagging operation and maintenance technology. This article uses Supervisory Control And Data Acquisition (SCADA) system data to realize wind turbines fault diagnosis and early warning research. First, this article proposes a method for cleaning abnormal data in SCADA systems. It combines Density-Based Spatial Clustering of Applications with Noise (DBSCAN) and Median Absolute Deviation (MAD) to estimate the normal power range. It provides high-quality health data samples for further research, based on the results obtained. Then, for wind turbines fault diagnosis, this article designs a Lightweight Gradient Boosting Machine (LightGBM) model based on a Genetic Algorithm (GA). This model can effectively diagnose different types of faults in wind turbines. Finally, this article proposes a Multivariate State Estimation Technique (MSET) normal model based on the DBSCAN algorithm for fault warning in wind turbines. This article designs two threshold setting methods: fixed threshold and adaptive dynamic threshold. Fault warning is conducted by calculating the residuals between predicted and actual values.

Objective: To evaluate rational drug prescribing practices in the surgical wards of a tertiary care hospital using World Health Organization/ International Network of Rational Use of Drugs (WHO/INRUD) prescribing indicators. Methods: A prospective observational study was conducted in general surgery wards of a tertiary care hospital over a six-month period. A total of 249 patients aged ≥ 18 years, with a hospital stay exceeding 24 hours were included. Data on drug prescriptions, including dose, frequency, and type, were collected from patient case notes and treatment charts. WHO/INRUD prescribing indicators were used to assess; average number of drugs per encounter, percentage of drugs prescribed by generic name, percentage of patient encounters with antibiotics and injections, and percentage of drugs from the national essential drug list (NEML). Results: The average number of drugs per encounter was 9.26, significantly exceeding the optimal level of ≤3. Only 14.22% of drugs were prescribed by generic name. Antibiotics were prescribed in 99.53% of encounters, far above the WHO-recommended 30%. The percentage of encounters with injectable drugs was 85.14%, and drugs from the NEML constituted 63.50%. Conclusions: The study reveals substantial deviations from WHO guidelines, with high rates of polypharmacy, low generic prescribing, and excessive antibiotic use. These practices heighten the risk of antimicrobial resistance (AMR) and underscore the need for effective antimicrobial stewardship programs. Hospitals should implement multifaceted strategies to improve antimicrobial use and align with WHO recommendations.

The mechanisms underlying the connection between exposure to lead and cancer are not completely understood. Lead is thought to cause oxidative stress, impair DNA repair pathways, and contribute to inflammation, potentially increasing carcinogenesis. The involvement of the Symplekin in cancer biology induced by lead exposure is an emerging area of research. Symplekin is a crucial protein in RNA processing and polyadenylation and is essential for mRNA stability and translation. While the direct relationship between Symplekin and lead toxicity is not well documented, lead exposure has been linked to various cellular disruptions that can indirectly affect Symplekin function. By understanding the Symplekin's role in tight junctions, we can shed light on an innovative approach. Tight junctions assist in the maintenance and development of cell polarity by separating membrane proteins into separate domains on the basolateral and apical surfaces of epithelial cells. This polarity is necessary for cells to transport chemicals and respond efficiently to signals. Tight junctions facilitate the integration of signalling pathways that regulate cell behaviour and tissue homeostasis. Importantly, while some evidence suggests a possible link between lead exposure and cancer, more research is needed to establish conclusive connections. After recurrent exposure to lead in humans, the target organs are the haematopoietic system followed by other systems, but it is time to concentrate on the lead in the serum, which is minimal and has a high impact on systemic toxicity through tight junctions by disrupting Symplekin and associated protein homeostasis in the cells. Symplekin's involvement in mRNA processing and gene expression control places it within a larger network of cellular functions that, when interrupted, may contribute to cancer.

Suspended sediment concentration, flux, and river discharge are essential indicators of river ecosystem health and reflect watershed-scale processes. Monitoring these variables is labor-intensive, leading to sparse and geographically biased observations and the development of models to fill in the observational gaps. These models generally use either climatological data or satellite images to estimate one of these variables. In this work, we present a novel deep learning model that can leverage multiple data sources with different temporal characteristics to produce continuous daily estimates of suspended sediment concentration (SSC), suspended sediment flux (SSF), and discharge. The model first encodes daily hydrological data from the ERA5-Land reanalysis using a Long Short-Term Memory network and water color data from Landsat satellites using a Multi-Layer Perceptron network, then merge these encoded data sources using a cross-attention decoder. We train and test the model on a large dataset of in-situ observations from 630 river sites over 43 years in the contiguous United States, covering a wide range of watersheds and conditions. We produce SSC, SSF, and discharge predictions with respective relative errors of 54\%, 73\%, and 28\%, and relative bias of -15\%, -19\%, and -3\%. We use our model to create a dataset of continuous daily SSC, SSF, and discharge for all large rivers in the contiguous United States. This new model architecture provides a valuable tool for monitoring river systems, addressing limitations of single-source models and offering a framework applicable to other Earth systems monitoring problems where integrating diverse data streams may be useful.

In this paper, a high step-up converter is presented by integration of switched capacitor and coupled inductors with quasi-z-source structure. a switched capacitor along with a pair of coupled inductors are utilized to enhance voltage gain and switch voltage stress. Also, zero current switching for switch at turn-on and for all diodes at turn- off which reduce reverse recovery problem are achieved by this technique. A passive clamp circuit is utilized to absorbing the leakage inductance energy, and improve voltage gain by placing the clamp capacitor in the charge path of the switched capacitor. Also, the main properties of quasi-z-source converter such as common ground between the output and input sides along with continuous input current is maintained. Additionally, these features are realized by proper component count in comparison with other related topologies based on quasi-z-source topology. The experimental results are extracted by a prototype circuit implemented at 300W and 100kHz to confirm the theoretical results and the proposal converter operation.

A certain level of stress is crucial for survival; however, prolonged exposure to stress may have negative health consequences. Smartwatches are a practical tool to monitor the body’s arousal state by measuring autonomic nervous system activity in daily life, commonly referred to as stress levels by the smartwatches. How these stress levels relate to emotional states, however, remains unclear. This study aimed to investigate the association between the Garmin Stress Score and both negative and positive emotional states of varying intensity. Over 28 days, Ecological Momentary Assessment (EMA) data were collected five times a day for emotional states, and Garmin Stress Score data were collected continuously, in a sample of 95 (80F) healthy young adult university students in the Netherlands. Binary and linear multilevel models were used to associate the Garmin Stress Score with the presence of emotions, and a dose-response relationship, respectively. The Garmin Stress Score was associated with high- and moderate-intensity positive emotions but not with negative or low-intensity emotions. The emotions ”calm” and ”relaxed” showed a negative dose-response relationship with average Garmin Stress Score, and a positive trend was found for ”enthusiastic.” Since the Garmin Stress Score relies on parasympathetic activation, representing the rest-and-digest state, rather than fight-or-flight, it makes sense that it is associated with states of non-relaxation. However, it was not associated with states of high arousal negative affect. This makes the term ”Stress Score” incorrect and misleading to consumers. Our findings warrant further research into emotional states, particularly those associated with high arousal negative affect. We recommend stronger collaborations between commercial companies like Garmin and researchers to enhance the accuracy of feedback provided by wearable devices and mitigate any harmful effects on consumers.

Digital violence is an intentional aggression from one person to another on an ongoing basis using a digital device. The objective was to identify instruments for measuring digital violence through Systematic Literature Review (SLR). The review was conducted using the PRISMA methodology. The search was conducted in SCOPUS and Apa Psycnet databases, from the period 2018 to April 2024, the string used in the title or abstract of the articles was cyberbullying, digital violence, online violence, violence in audiovisual environments and questionnaire, interviews, measurement, instrument, interrogation. A total of 579 articles were found with information on the key words in the SCOPUS and Apa Psycnet databases. The articles were then rigorously filtered by language (English and Spanish) and 63 articles were selected that responded to the questions: What are the instruments used to measure digital violence? and What are the roles in digital violence? Likewise, 16 different questionnaires were identified to measure digital violence, being the most used the Cyberbullying Questionnaire (CBQ) and the European Cyberbullying Intervention Project Questionnaire (ECIP-Q), the two main roles were identified in the articles the victim and the bully, the most used variables in the instruments were: hitting, insulting, threatening, stealing, saying bad words, excluding or spreading rumors. Seven systematic reviews on the subject were also found. These results identify the instrument or questionnaire of digital violence that allows to know if a person has been violated or on the contrary violates people, so that when transferred to technology it can be implemented in a virtual scenario, with the benefits and advantages that this entails such as: taking advantage of the skill of adolescents in video games, their mastery of digital devices, and especially the motor and visual skills that adolescents have. Likewise, it is perceived that digital violence is on the rise, so it is necessary to implement a public policy to identify it, just as it was implemented with harassment.

l, University College London Hospital: Elizabeth Garrett Anderson Wing, London, UK

11Patient has signed consent formTitleTocilizumab in the Treatment of AOSD in the Elderly: A Case and Literature Review

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Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare hereditary arrhythmia characterized by adrenergic stress-induced polymorphic ventricular tachycardia. Supraventricular arrhythmias, including ectopic atrial tachycardia (EAT), may occur, but their management in patients with CPVT has not been well assessed. This case report presents an 11-year-old boy with CPVT who developed drug-resistant EAT. Despite treatment with beta-blockers, flecainide, and sotalol, EAT persisted. Ivabradine therapy was initiated, resolving the arrhythmia within hours. This unique case highlights ivabradine’s potential as a non-invasive alternative to ablation for EAT in CPVT. Multicenter studies are required to explore its routine use alongside beta-blockers in managing CPVT-related arrhythmias.

Left bundle branch area pacing improves outcomes in candidates to cardiac resynchronization therapy. Additional left ventricular pacing might be indicated in selected patients, but this so-called LOT-CRT approach remains complex in patients indicated with a defibrillator. We describe a new simplified technique -- Reverse LOT-CRT-D -- in this population.

Omega-type bianisotropic Huygens' metasurfaces offer a novel approach for controlling the aperture field distribution of leaky-wave antennas. This paper presents a methodology utilizing a parallel-plate waveguide with a metasurface as its top plate. Previous limitations on constant leakage factor are addressed using a slowly varying amplitude approximation in order to satisfy Maxwell's wave equation, enabling the design of the radiation pattern. A semi-analytical algorithm is employed to obtain the required multi-layer unit-cell geometries. Here, the inter-layer coupling is taken into account, enabling an efficient synthesis of these antennas. Several designs presenting different pointing angles and aperture field distributions are carried out, showing very good agreement between theory and realistic simulations without further full-wave optimization. Finally, the design process is experimentally validated through several prototypes, whose measurements are shown and discussed. These results, demonstrating straightforward semi-analytical synthesis of versatile aperture profiles, would significantly broaden the applicability of such antennas in next-generation wireless systems.

Abstract: The pseudostem weevil Odoiporus longicollis being a major pest of banana confers a serious loss to the crop. The cellulose- and terpene-laden diet demands a high reliance on gut microbiome to platter the nutrition. Here we investigated the whole microbiome of foregut, midgut and hindgut of O. longicollis to understand the spatial distribution of microbes. In bacteria, Firmicutes: Bacilli dominated the foregut and Proteobacteria: Gammaproteobacteria was highest in midgut and hindgut. Interestingly, Erysipelotrichia was comparatively much higher in hindgut. The Enterobacteriaceae subjugated the entire gut (Klebsiella and Enterobacter) with differential distribution of Raoultella, Citrobacter and Escherichia. This is followed by Lactobacillaceae (Leuconostoc, Lactiplantibacillus etc.) in foregut and Streptococcaceae (Lactococcus) in midgut and hindgut. The primary endosymbiont Candidatus Nardonella was found to be foregut-specific. In Fungi, Ascomycota and Basidiomycota were abundant. Foregut and hindgut had an abundance of Debaryomycetaceae (Scheffersomyces, Millerozyma and Candida) and the midgut had Saccharomycodaceae (Hanseniaspora and Yarrowia). Other eukaryotes i.e., Alveolata, Apicomplexa, Oomycota, Discoba, Amoebozoa, CS clade, Euglenozoa, Heterolobosea and Perkinsozoa were distributed differentially. Hindgut was determined to be a species-rich and diversified site for whole microbiome whereas for Fungi, foregut and midgut were species-rich sites, and hindgut and foregut had higher species diversity. Varying patterns of gene counts for carbohydrate metabolism, terpene degradation and nitrogen cycle were observed with particular significance in uncovering dependent and independent modes of cellulolysis in O. longicollis. The findings improved the understanding of site-specific diversity and richness of gut microbiome in O. longicollis to prospect for its control and management.

Background: There is a concern that performing routine dental floats could result in adverse pregnancy outcomes in mares. There is a paucity of data on the effect of dentistry during pregnancy in domestic species. In women, dental prophylaxis is considered safe during pregnancy. Objectives: The objective of this study was to determine if routine dental floating was associated with adverse pregnancy outcomes in Thoroughbred broodmares. Study Design: Retrospective records analysis Methods: Clinical and farm records from 2013 to 2021 were utilized. Abortion, stillbirth and placentitis was modeled using SAS GLIMMIX procedure. Time of the dental procedure was categorized in two ways, occurring when the mares were 1) open or pregnant or 2) open, during the 1st trimester (0 – 114 days), the 2 nd trimester (115 – 228 days) or the 3 rd trimester (> 229 days) of pregnancy for separate models for each outcome. Significance was set at P < 0.05. Results: Both logistic regression models examining abortion found age of mare at the time of float remained significant, while trimester of dental procedure, farm and year float was performed were not significant. Both logistic regression models examining stillbirth found the age of the mare at the time of float remained significant, with location being significant in the first model (open or pregnant) and a tendency (0.10 > P > 0.05) in the second model (open, 1 st, 2 nd, or 3 rd trimester). Other variables in the models were not significant. Farm remained significant in both logistic models of placentitis, while age of mare at the time of float, trimester of dental float and year float was performed were not significant. Main Limitations: Not a controlled study. Conclusions: Floating a mare’s teeth during each trimester of pregnancy is a safe procedure.

The ability to produce direct DNA damage (genotoxicity) underlies the carcinogenic mode of action of various chemicals. As such, genotoxicity endpoints are typically evaluated in a regulatory-approved battery of in vitro tests with potential in vivo follow-up. Growing concern for animal welfare and implementation of new regulations which restrict the use of laboratory animals necessitated the introduction of New Approach Methodologies (NAMs). The avian egg-based (in ovo) models, the Chicken and related Turkey Egg Fetal Liver DNA Damage Assays, were developed as metabolically competent NAMs to potentially replace short-term in vivo genotoxicity assays for chemicals that are genotoxic in vitro. Both models utilize avian fetal livers for the evaluation of endpoints indicative of DNA damage produced by either direct or indirect mechanisms, specifically, the formation of nuclear DNA adducts and strand breaks. Moreover, avian embryos carry genetic and morphologic resemblance to mammals and can be used for an extensive evaluation of other endpoints including histopathology and tissue-specific genomic profiling. Avian fetal livers contain a full complement of metabolizing enzymes and are capable of bioactivation, detoxication, and elimination of xenobiotics. The comprehensive analysis of 87 and 59 chemicals assessed in the chicken and turkey models, respectively, revealed a stronger correlation with the results from in vivo assays demonstrating that in ovo models can detect the genotoxic potential of a broader range of compounds compared to in vitro assays with S9 supplementation. In conclusion, fertilized avian egg fetal liver assays offer a promising alternative to traditional in vivo genotoxicity assays.