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Reefs are facing a global decline with sewage pollution emerging as a significant and poorly understood threat. Inadequate wastewater management and disorderly urbanization contribute to water pollution globally. Tropical Southwestern Atlantic comprises a set of oceanic Marine Protected Areas (MPAs) including the Fernando de Noronha Archipelago in Brazil, which has experienced significant population growth without expanding the sewage infrastructure. We mapped and quantified marine pollution in these MPAs, characterizing pollution sources and evaluating their effects on benthic and fish communities in 13 reef sites. We quantified nutrients, metals and metalloid, microplastics, fecal sterols, and Polycyclic Aromatic Hydrocarbons (PAHs) in both water and sediment samples. We also used isotopic tracing on macroalgae to identify the origin of organic matter and characterized benthic and fish communities, and algae biomass at each site. Pollution was more pronounced in the multiple-use area but also affected no-take areas. Effluents from wastewater treatment plants did not meet legislative standards, and reefs in the multiple-use area were enriched in orthophosphate and ammonia compared to those in the no-take area. Nitrogen isotopes in macroalgae revealed sewage-derived nitrogen throughout the multiple-use area. Nutrient enriched sites exhibited higher abundances of fast-growing and opportunistic green macroalgae, and higher biomass of brown macroalgae. The port area, within the multiple-use area, showed high PAHs, coprostanol and metal(loid) concentrations, suggesting untreated sewage and nautical chemical pollution. Microplastics were widespread in sediment and water samples. We documented the pervasive impacts of marine pollution on reef habitats even within marine protected areas in oceanic regions, demonstrating that local pollution control, sewage management and regulating procedures in port areas are critical to protect marine ecosystems. Comparisons with previous studies suggest marine pollution has substantially increased in the Archipelago in the last ten years. This is the first comprehensive assessment of marine pollution in an oceanic environment in Southwestern Atlantic, showing these isolated environments are not immune to pollution impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Internet of Things (IoT) consist of a network of interconnected nodes constantly communicating, exchanging, and transferring data over various network protocols. Intrusion detection systems using deep learning are a common method used for providing security in IoT. However, traditional deep learning IDS systems do not accurately classify the attack and also require high computation time. Thus, to solve this issue, herein, we propose an advance Intrusion detection framework using Self-Attention Progressive Generative Adversarial Network (SAPGAN) framework for detecting security threats in IoT networks. In our proposed framework, at first, the IoT data are gathered. Then, the data are fed to pre-processing. In pre-processing, it restored the missing value using Local least squares. Then the preprocessing output is fed to feature selection. At feature selection, the optimum features are compiled using a modified War Strategy Optimization Algorithm (WSOA). Based upon the optimum features, the intruders were categorized into two categories named Anomaly and Normal using the proposed framework. Numerous attacks are assembled, including camera-based flood, DDoS, RTSP brute force, etc. We have compared our proposed framework using state of the art model and efficiency of 23.19%, 27.55%, and 18.35% higher accuracy and 14.46%, 26.76%, and 13.65% lower computational time compared to traditional models., Competing Interests: Competing interests: Authors declare that there is no conflict of interest., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a chronic neurological disorder that impacts the elderly population all over the globe. Evidence suggests association between AD and metabolic disorders such as diabetes mellitus (DM) and obesity (OB). The present study is an attempt to evaluate metabolic alterations in the serum and brain through NMR spectroscopy with the aim to identify shared metabolic signatures. AD was induced in rats by stereotactic intracerebroventricular injection of oligomerized Aβ-42 peptide into the brain. DM and OB were induced by intraperitoneal injection of streptozotocin and feeding rats on a high-fat diet, respectively. The metabolic alterations obtained through 1 H NMR spectroscopy were further subjected to multivariate analysis by principal component analysis and partial least-squares discrimination for identification of metabolic signatures. In the serum, the levels of lactate and betaine were increased in AD, DM, and OB rats. On the other hand, the metabolite profile of brain indicated increase in the levels of lactate, N -acetylaspartate, and creatinine in AD, DM, and OB rats. Additionally, the concentration of neurochemicals such as glutamate, GABA, N -acetylglutamate, and myo-inositol were also elevated. The alterations in neurotransmitters and cerebral energy metabolism were accompanied by deficits in cognition assessed by Morris water maze in AD, DM, and OB rats. The perturbed metabolic profiles were accompanied by the presence of pathogenic amyloid deposits visualized by Congo red stain in the brains of AD, DM, and OB rats. Overall, the study identifies common metabolic signatures in AD, DM, and OB that may be involved in etiopathogenesis and also suggests linkages between these three conditions.

Embryonic development in humans is controlled by the Hedgehog pathway, which becomes inactive in mature tissues. Except for tissue maintenance and healing, activation of this pathway results in tumorigenesis with only a few exceptions. The drugs currently in use have shown no effectiveness in blocking the key proteins responsible for tumorigenesis. Therefore, it is crucial to find new inhibitors that can stop the abnormal activation of the pathway. A preliminary Insilco screening of naturally occurring compounds was carried out to identify potential inhibitors of the pathway. Docking of seventeen naturally occurring antitumorigenic compounds against the four key proteins of the regulatory proteins of the Hedgehog pathway using AutoDock v4.2.6 software was carried out. Liriodenine exhibited the strongest binding affinity towards three out of the four regulatory proteins (-7.61 kcal/mol with Smoothened, -8.14 kcal/mol with Patched-I, and -6.15 kcal/mol with Gli-II) of the Hedgehog pathway, whereas 2',4-dihydroxy-3-methoxychalcone displayed the highest binding affinity of -7.04 kcal/mol with the Sonic Hedgehog protein. Additional molecular dynamic simulation was conducted using Gromacs with Liriodenine and 2',4-dihydroxy-3-methoxy chalcone. Every protein-ligand complex underwent simulation using v5.1.4 software for a duration of 100 nanoseconds. The findings from the simulation indicate that Liriodenine and 2',4-dihydroxy-3-methoxy chalcone form a strong bond with their corresponding protein. Our findings show that the two aforementioned molecules have potential as new inhibitors of the pathway and should be further investigated in both invitro and in vivo experiments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities syndrome (DEGCAGS, MIM #619488) is caused by biallelic, loss-of-function (LoF) ZNF699 variants, and is characterized by variable neurodevelopmental disability, discordant organ anomalies among full siblings and infant mortality. ZNF699 encodes a KRAB zinc finger protein of unknown function. We aimed to investigate the genotype-phenotype spectrum of DEGCAGS and the possibility of a diagnostic DNA methylation episignature, to facilitate the diagnosis of a highly variable condition lacking pathognomonic clinical findings. We collected data on 30 affected individuals (12 new). GestaltMatcher analyzed fifty-three facial photographs from five individuals. In nine individuals, methylation profiling of blood-DNA was performed, and a classification model was constructed to differentiate DEGCAGS from controls. We expand the ZNF699-related molecular spectrum and show that biallelic, LoF, ZNF699 variants cause unique clinical findings with age-related presentation and a similar facial gestalt. We also identified a robust episignature for DEGCAGS syndrome. DEGCAGS syndrome is a clinically variable recessive syndrome even among siblings with a distinct methylation episignature which can be used as a screening, diagnostic and classification tool for ZNF699 variants. Analysis of differentially methylated regions suggested an effect on genes potentially implicated in the syndrome's pathogenesis., Competing Interests: Competing interests: BS is a shareholder in EpiSign Inc, company involved in commercialization of EpiSignTM technology. Ethical approval: This study was performed according to the Declaration of Helsinki and approved by the Western Norway Regional Ethics Committee (REC 604007) and the Western Ontario University Research Ethics Board (REB 106302). Written informed consent for the publication of photographs, videos and medical information was obtained from parents/legal guardians., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Background: Ticagrelor monotherapy after 1-3 months of dual antiplatelet therapy (DAPT) has shown to be effective and safe after percutaneous coronary intervention (PCI), including in patients with an ST elevation myocardial infarction (STEMI). Direct omission of aspirin could further reduce bleeding complications and may reduce the incidence and expansion of intramyocardial haemorrhage (IMH), a frequent complication after revascularisation for a STEMI., Methods: This multicentre open label pilot study randomises 200 STEMI patients within 24 hours after primary PCI and before the first subsequent dose of aspirin to ticagrelor monotherapy or ticagrelor plus aspirin for twelve months. As IMH is more frequently observed after an anterior STEMI, IMH and infarct size will be determined with cardiac magnetic resonance (CMR) imaging in 60 anterior STEMI patients. In this subgroup, blood samples will be analysed for biochemical outcomes., Results: The primary safety endpoint consists of major adverse cardiac and cerebral events, and the primary efficacy endpoint is infarct size on CMR. Secondary efficacy endpoints consist of the incidence and extent of IMH determined by CMR, and of clinical bleeding events. Other endpoints include all-cause mortality and biochemical outcomes., Conclusion: The STOP-IMH pilot study compares ticagrelor monotherapy with ticagrelor plus aspirin directly after primary PCI in 200 STEMI patients. We aim to provide a signal of safety regarding ischemic events for the direct omission of aspirin after primary PCI, and to compare the infarct size by CMR between the two treatment strategies in the first week after primary PCI., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Damman has received research grants from Abbott, Philips, and AstraZeneca. Robin Nijveldt has received research grants from Philips Volcano and Biotronik. Robert Jan M. van Geuns has received grants and personal fees from Boston Scientific, Abbott Vascular, AstraZeneca and Amgen, and grants from InfraRedx. Bimmer Claessen has received speaker and/or consultancy fees from Abbott Vascular, Abiomed, Amgen, Boston Scientific, BBraun, and Sanofi, educational grants from Boston Scientific and Abiomed, and research grants from Philips, Novo Nordisk, BBraun and Nipro/Infraredx. Niels van Royen has received research grants from Philips, Biotronik, Abbott and Medtronic and speaker fees from Abbott, RainMed, Microport and Bayer. Clemens von Birgelen reported institutional research grants from Abbott Vascular, Biotronik, and Medtronic, outside the present study. The other authors report no relationships that could be construed as a conflict of interest., (© 2024 The Authors.)

Background: Acceptance and commitment therapy (ACT) is promising in the treatment of early psychosis. Augmenting face-to-face ACT with mobile health ecological momentary interventions may increase its treatment effects and empower clients to take treatment into their own hands., Objective: This study aimed to investigate and predict treatment engagement with and acceptability of acceptance and commitment therapy in daily life (ACT-DL), a novel ecological momentary intervention for people with an ultrahigh risk state and a first episode of psychosis., Methods: In the multicenter randomized controlled trial, 148 individuals with ultrahigh risk or first-episode psychosis aged 15-65 years were randomized to treatment as usual only (control) or to ACT-DL combined with treatment as usual (experimental), consisting of 8 face-to-face sessions augmented with an ACT-based smartphone app, delivering ACT skills and techniques in daily life. For individuals in the intervention arm, we collected data on treatment engagement with and acceptability of ACT-DL during and after the intervention. Predictors of treatment engagement and acceptability included baseline demographic, clinical, and functional outcomes., Results: Participants who received ACT-DL in addition to treatment as usual (n=71) completed a mean of 6 (SD 3) sessions, with 59% (n=42) of participants completing all sessions. App engagement data (n=58) shows that, on a weekly basis, participants used the app 13 times and were compliant with 6 of 24 (25%) notifications. Distribution plots of debriefing scores (n=46) show that 85%-96% of participants reported usefulness on all acceptability items to at least some extent (scores ≥2; 1=no usefulness) and that 91% (n=42) of participants reported perceived burden by number and length of notifications (scores ≥2; 1=no burden). Multiple linear regression models were fitted to predict treatment engagement and acceptability. Ethnic minority backgrounds predicted lower notification response compliance (B=-4.37; P=.01), yet higher app usefulness (B=1.25; P=.049). Negative (B=-0.26; P=.01) and affective (B=0.14; P=.04) symptom severity predicted lower and higher ACT training usefulness, respectively. Being female (B=-1.03; P=.005) predicted lower usefulness of the ACT metaphor images on the app., Conclusions: Our results corroborate good treatment engagement with and acceptability of ACT-DL in early psychosis. We provide recommendations for future intervention optimization., Trial Registration: OMON NL46439.068.13; https://onderzoekmetmensen.nl/en/trial/24803., (©Evelyne van Aubel, Thomas Vaessen, Lotte Uyttebroek, Henrietta Steinhart, Annelie Beijer-Klippel, Tim Batink, Ruud van Winkel, Lieuwe de Haan, Mark van der Gaag, Thérèse van Amelsvoort, Machteld Marcelis, Frederike Schirmbeck, Ulrich Reininghaus, Inez Myin-Germeys. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.11.2024.)

In this study, we examine the assessment of surface roughness on turned surfaces of Ti 6Al 4V using a computer vision system. We utilize the Dual-Tree Complex Wavelet Transform (DTCWT) to break down the images of the turned surface into sub-images oriented in directions. Three different methods of feature generation have been compared, i.e., the use of Gray-Level Co-Occurrence Matrix (GLCM) and DTCWT-based extraction of second-order statistical features, DTCWT Image fusion, and the use of GLCM for feature extraction, and DTCWT image fusion using Particle Swarm Optimization (PSO) based GLCM features. Principal Component Analysis (PCA) was utilized to identify and select features. The model was developed using a Radial Basis Function Neural Network (RBFNN). Accordingly, six models were designed based on the three feature generation methods, considering all features and features selected using PCA. The RBFNN model, which incorporates DTCWT Image fusion and utilizes PSO with PCA features, achieved a training data prediction accuracy of 100% and a test data prediction accuracy of 99.13%., Competing Interests: Declarations Competing interests he authors declare no competing interests., (© 2024. The Author(s).)

A selection of formulations with different polymers and concentrations of green tea extract was conducted for application as interleafs in sliced meat products. Films were formulated using cellulose acetate, corn starch, and chitosan with the addition of 1.0, 2.5, and 5.0% green tea extract. Higher antioxidant activity was observed with the 1.0% concentration of green tea extract (P < 0.05), regardless of the formulation, with continuous release of the extract for up to 60 days and average IC 50 of 0.09 and 0.31 mg/mL for the corn starch and chitosan active films, respectively. Interleafing the sliced ham resulted in lower lipid oxidation after 60 days of storage (P < 0.05). Starch-based films with green tea extract were effective, significantly reducing lipid oxidation in sliced and interleafed cooked ham, suggesting their potential to extend the shelf life of these refrigerated products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Limited data exist on ultrathin-strut drug-eluting stent (ultrathin DES) performance in DES in-stent restenosis (ISR)., Aims: We aimed to assess the efficacy and safety of ultrathin DES compared to thin-strut DES and drug-eluting balloons (DEB) for DES-ISR., Methods: Patients from the DEB Dragon (ClinicalTrials.gov: NCT04415216) and ULTRA registries (ClinicalTrials.gov: NCT05205148) were divided into ultrathin DES, thin-strut DES, or DEB groups for DES-ISR treatment. Both propensity score matching (PSM) and inverse probability weighting (IPW) were considered to adjust the distribution of patients in each class. Cox regression was applied to the following main endpoints: device-oriented composite endpoints (DOCE; including cardiac death, target lesion revascularisation [TLR] and target vessel myocardial infarction), TLR and target vessel revascularisation (TVR)., Results: A total of 269, 541, and 557 patients received an ultrathin DES, thin-strut DES, and DEB, respectively. After 3 years of follow-up, in the IPW-adjusted overall cohort, ultrathin DES were associated with a significantly reduced risk of DOCE compared to DEBs (hazard ratio [HR] 0.353, 95% confidence interval [CI]: 0.194-0.642; p<0.001), as well as thin-strut DES (HR 0.645, 95% CI: 0.457-0.911; p=0.013). Compared to DEBs, ultrathin DES also reduced the risks of both TLR (HR 0.184, 95% CI: 0.081-0.417; p<0.001) and TVR (HR 0.188, 95% CI: 0.093-0.379; p<0.001), while thin-strut DES did not (TLR: HR 0.686, 95% CI: 0.407-1.157; p=0.157; TVR: HR 0.706, 95% CI: 0.453-1.101; p=0.124). For diffuse ISR patients, ultrathin DES reduced the risk of DOCE (HR 0.364, 95% CI: 0.188-0.705; p=0.003), as did thin-strut DES (HR 0.602, 95% CI: 0.367-0.987; p=0.044), while a reduction of TLR (HR 0.220, 95% CI: 0.091-0.531; p<0.001) and TVR (HR 0.241, 95% CI: 0.113-0.513; p<0.001) was achieved only by ultrathin DES., Conclusions: Ultrathin DES were associated with reduced DOCE, TLR and TVR risks in diffuse ISR compared to DEBs.

The study of research proposes a systematic pattern for optimization and fabrication of a sustainable-cost effective electrochemical sensor made by Bi-CdFe 2 O 4 (BCDF) nanoparticle and graphite powder. The structural examinations of synthesized BCDF materials were analyzed by specific spectral techniques viz.; P-XRD, SEM-EDX, TEM, XPS, FT-IR and DRS techniques. The modified sensor electrode offer a significant electrochemical properties that can improve the material selectivity and sensitivity actions measured by Cyclic Voltammetric (CV) and Electrochemical Impedance Spectral (EIS) plots. We demonstrated a developed highly-purity BCDF-graphite paste electrode for sensing actions on Paracetamol and Lead (Pb 2+ ) ions under 0.1 M KCl. The excellent sensing activity towards Lead ions and Paracetamol confirmed by its redox potential peaks at scan rate of 1-5 V/s with maximum sensitivity of -0.61 V and 0.69 V respectively. The excellent photo-dye-degradation action of BCDF (98.2%) than those of host CDF (81.6%) on Rose Bengal (RB) dye was demonstrated. Its kinetic study reveals that this process follows first order kinetics and rate constants of the host (18.1 × 10 -3 min -1 ) and BCDF (39.2 × 10 -3 min -1 ) were measured. Thus, the synthesized BCDF electrode provides a new perception for developing specific nano-sensor towards detection of toxic metals., (© 2024. The Author(s).)

Lower Back Pain (LBP) is a global health issue, with increasing prevalence, partly attributed to vehicular vibrations experienced by motorcyclists. The L4 lumbar vertebra is responsible for greater mobility and flexibility of the body, but also is the most crucial body element affected by vehicular vibrations. Anthropometric properties, types of speed humps, and vehicle types are the critical variables that impact bone health during riding, need to be studied. To understand the potential zones of injury, computational simulation can be performed under the influence of vehicle vibrations while crossing different types of speed humps at varying speeds. In the present study, finite element method (FEM) is used to evaluate stress and deformation in the bone. The L4 cortical bone is modelled by considering the CT-Scan data and assumed to be homogeneous and isotropic material. Vibration data is collected using two vehicle types (Type I and Type II) on four different humps (Trapezoidal, Bitumen Semi-circular, Rubber Semi-circular, and Rumble strip). The bone's dynamic behavior is studied using FEM simulation, which involved static structural, modal and transient dynamic analyses. The findings from static analysis indicate that the most concentrated stress is located in the lower pedicle region and is an expected commonplace for injuries because of vibrations. In transient dynamic analysis, Type I vehicle showed a 25 % higher stress than Type II., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The expanding availability of real-world data (RWD) has led to an increase in both the interest and possibilities for using this information in postmarketing safety analyses and signal management. While there is enormous potential value from the safety insights generated through RWD, the analysis preparation, execution, and communication required to reliably deliver the evidence can be time consuming. Since the safety signal assessment process is a regulated and timebound process, any supporting RWD analyses require a rapid turnaround of well-designed and informative results. To address this challenge, a TransCelerate BioPharma working group was formed and developed a framework to help teams responsible for safety signal assessment overcome the challenges of working with RWD rapidly to deliver analyses within regulatory timelines. Here, a previously performed safety assessment was evaluated within the context of the developed framework to illustrate how the framework may be adopted in practice., (© 2024. The Author(s).)

Purpose: TransCelerate BioPharma surveyed its member biopharmaceutical companies to understand current practices and identify opportunities to complement safety signal assessment with rapid real-world data (RWD) analysis., Methods: A voluntary 30-question questionnaire regarding the use of RWD in safety signal assessment was disseminated to subject matter experts at all TransCelerate member companies in July 2022. Responses were blinded, aggregated, summarized, and presented., Results: Eighteen of 20 member companies provided responses to the questionnaire. Sixteen (89%) companies reported actively leveraging RWD in their signal assessment processes. Of 18 respondent companies, 8 (44%) routinely use rapid approaches to RWD analysis, 7 (39%) utilize rapid RWD analysis non-routinely or in a pilot setting, 2 (11%) are considering using rapid RWD analysis, and 1 (6%) has no plans to use rapid RWD analysis for their signal assessment. Most companies reported that RWD adds context to and improves quality of signal assessments. To conduct RWD analysis for signal assessment, 16 of 17 (94%) respondent companies utilize or plan to utilize internally available data, 8 (47%) utilize both internal and external data, and 3 (18%) utilize data networks. Respondents identified key challenges to rapidly performing RWD analyses, including data access/availability, time for analysis execution, and uncertainties regarding acceptance of minimal or non-protocolized approaches by health authorities., Conclusion: Biopharmaceutical companies reported that they see value in the use of rapid RWD analyses for complementing signal assessments. Future work is recommended to offer a framework and process for use of rapid use of RWD analyses in signal assessment., (© 2024. The Author(s).)

This article proposes a noninvasive computer-aided assessment approach based on optimized convolutional neural network for healthy and pathological voice detection. Firstly, the input voice samples are first transformed into mel-spectrogram time-frequency visual representations and fed for training the CNN model. The time-frequency image captures inherent speech variations beneficial for healthy and pathological voice sample detection. The weights and biases of trained CNN network are further optimized using artificial bee colony (ABC) optimization algorithm resulting in optimum CNN network employed for testing unseen data. The proposed approach is evaluated using three popular and publicly available datasets: SVD, AVPD and VOICED. Experimental results emphasize that proposed ABC optimized CNN model shows improved accuracy performance by 1.02% compared to conventional CNN network illustrating data-independent discriminative representation ability. Finally, gradient-weighted class activation mapping (Grad-CAM) explainable artificial intelligence (XAI) is utilized to make the decision understandable.

Background: Brassica juncea (L.) Czern is an important oilseed crop affected by various abiotic stresses like drought, heat, and salt. These stresses have detrimental effects on the crop's overall growth, development and yield. Various Transcription factors (TFs) are involved in regulation of plant stress response by modulating expression of stress-responsive genes. The myeloblastosis (MYB) TFs is one of the largest families of TFs associated with various developmental and biological processes such as plant growth, secondary metabolism, stress response etc. However, MYB TFs and their regulation by non-coding RNAs (ncRNAs) in response to stress have not been studied in B. juncea. Thus, we performed a detailed study on the MYB TF family and their interactions with miRNAs and Long non coding RNAs., Results: Computational investigation of genome and proteome data presented a comprehensive picture of the MYB genes and their protein architecture, including intron-exon organisation, conserved motif analysis, R2R3 MYB DNA-binding domains analysis, sub-cellular localization, protein-protein interaction and chromosomal locations. Phylogenetically, BjuMYBs were further classified into different subclades on the basis of topology and classification in Arabidopsis. A total of 751 MYBs were identified in B. juncea corresponding to 297 1R-BjuMYBs, 440 R2R3-BjuMYBs, 12 3R-BjuMYBs, and 2 4R-BjuMYBs types. We validated the transcriptional profiles of nine selected BjuMYBs under drought stress through RT-qPCR. Promoter analysis indicated the presence of drought-responsive cis-regulatory components. Additionally, the miRNA-MYB TF interactions was also studied, and most of the microRNAs (miRNAs) that target BjuMYBs were involved in abiotic stress response and developmental processes. Regulatory network analysis and expression patterns of lncRNA-miRNA-MYB indicated that selected long non-coding RNAs (lncRNAs) acted as strong endogenous target mimics (eTMs) of the miRNAs regulated expression of BjuMYBs under drought stress., Conclusions: The present study has established preliminary groundwork of MYB TFs and their interaction with ncRNAs in B. juncea and it will help in developing drought- tolerant Brassica crops., (© 2024. The Author(s).)

Background and Hypothesis: Sex differences in psychosis are reported across the psychosis spectrum, including in subclinical stages. An important factor in understanding these variations is the subjective experience of everyday social interactions (SI). We investigated whether the presence of psychotic experiences (PEs), as well as associated distress, differs between men and women. We focused on the role of daily-life SI quality and whether its association with PEs varies by sex., Study Design: We included adolescents from SIGMA, a general youth population study in Flanders, Belgium (n = 344; mean age = 18.7; 63.4% female). Psychotic experiences were measured using the PQ-16. We used Experience Sampling Methodology to assess daily-life SI. A multilevel model and multiple linear regressions were used to assess, respectively, the relationship between sex and SI quality and whether PEs and their association with SI quality differ between young men and women., Study Results: The results of the multilevel linear regression model indicate that the prevalence of and distress associated with PEs were higher in women. No significant difference was observed in the subjective quality of daily SI. Social interaction quality was strongly related to PEs. This association did not seem to vary for the prevalence of PEs, though women's distress about PEs appeared to be more affected by SI quality., Conclusions: Present findings highlight the role of the subjective quality of SI in subclinical psychosis. More research is needed to investigate the mechanisms through which SI quality relates to PEs, and whether these differ between young men and women., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Adipose tissue dysfunction influences the development of dyslipidemias associated with obesity, however, the mechanisms are still unclear. In this sense, the literature highlights the role of copper in cholesterol synthesis, contributing to the increase in concentrations of this lipid fraction and consequently to the manifestation of dyslipidemia. The objective of the study was to investigate the relationship between copper parameters and lipid profile markers in women with obesity. This is a cross-sectional study involving women aged 20 to 50 years divided into a case group (BMI ≥ 35 kg/m 2 ) and a control group (BMI between 18.5 and 24.9 kg/m 2 ). Copper concentrations in plasma and erythrocytes were determined by inductively coupled plasma optical emission spectrophotometry and ceruloplasmin activity by spectrophotometry. The lipid fractions were analyzed according to the enzymatic colorimetric method, using an automatic biochemical analyzer. Participants with obesity had elevated concentrations of copper in plasma and reduced concentrations in erythrocytes compared to the control group, but there was no significant difference in ceruloplasmin activity between the groups. The research does not identify a correlation between copper parameters and serum concentrations of lipid fractions, which does not allow inferring the role of copper in the manifestation of dyslipidemia in obesity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide and is recruited by most targeted protein degraders (PROTACs and molecular glues) in clinical development. Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBN midi , a construct that readily expresses from E. coli with high yields as soluble, stable protein without DDB1. We benchmark CRBN midi for wild-type functionality through a suite of biophysical techniques and solve high-resolution co-crystal structures of its binary and ternary complexes with degraders. We qualify CRBN midi as an enabling tool to accelerate structure-based discovery of the next generation of CRBN based therapeutics., (© 2024. The Author(s).)

Background : The regulation of cellular proliferation and genomic integrity is controlled by complex surveillance mechanisms known as cell cycle checkpoints. Disruptions in these checkpoints can lead to developmental defects and tumorigenesis. Methods : To better understand these mechanisms, computational modeling has been employed, resulting in a dataset of 414 mathematical models in the BioModels database. These models vary significantly in detail and simulated processes, necessitating a robust analytical approach. Results : In this study, we apply the chemical organization theory (COT) to these models to gain insights into their dynamic behaviors. COT, which handles both ordinary and partial differential equations (ODEs and PDEs), is utilized to analyze the compartmentalized structures of these models. COT's framework allows for the examination of persistent subsystems within these models, even when detailed kinetic parameters are unavailable. By computing and analyzing the lattice of organizations, we can compare and rank models based on their structural features and dynamic behavior. Conclusions : Our application of the COT reveals that models with compartmentalized organizations exhibit distinctive structural features that facilitate the understanding of phenomena such as periodicity in the cell cycle. This approach provides valuable insights into the dynamics of cell cycle control mechanisms, refining existing models and potentially guiding future research in this area.

Ocular artifacts, including blinks and saccades, pose significant challenges in the analysis of electroencephalographic (EEG) data, often obscuring crucial neural signals. This tutorial provides a comprehensive guide to the most effective methods for correcting these artifacts, with a focus on algorithms designed for both laboratory and real-world settings. We review traditional approaches, such as regression-based techniques and Independent Component Analysis (ICA), alongside more advanced methods like Artifact Subspace Reconstruction (ASR) and deep learning-based algorithms. Through detailed step-by-step instructions and comparative analysis, this tutorial equips researchers with the tools necessary to maintain the integrity of EEG data, ensuring accurate and reliable results in neurophysiological studies. The strategies discussed are particularly relevant for wearable EEG systems and real-time applications, reflecting the growing demand for robust and adaptable solutions in applied neuroscience.

Background: Semaglutide is a GLP-1 receptor agonist that provides a reduction in glycated hemoglobin and weight. The objective was to evaluate whether the use of semaglutide, in individuals with overweight or obesity, reduces cardiovascular outcomes and adverse effects (AE)., Methods: The data bases Pubmed, Lilacs, Scielo, Scopus, Web of Science and Cochrane Library were surveyed., Results: Initially, 3333 articles were found, of which 19 articles were included. An additional search included 19 studies, totaling 38 articles. Relative risk (RR) values were significant for hospitalization due to heart failure (HF) 0.24 95% CI 0.12-0.57 (n = 2; 1045 participants; I² = 0.18), death due to cardiovascular causes 0.83 95% CI 0.71-0.98 (n = 3; 24 084 participants; I² = 0.21), death from any cause 0.79 95% CI 0.70-0.89 (n = 3; 24 084 participants; I² = 0.07), coronary revascularization 0.76 95% CI 0.69-0.85 (n = 2;20 951 participants; I² = 0.41), and non-fatal myocardial infarction 0.76 95%CI 0.66-0.88 (n = 3; 24 084 participants; I² = 0.21), with a difference between the subgroups (p = 0.05), favoring the subcutaneous administration route. The RR of stroke was 0.65 95% CI 0.44-0.97 for patients with diabetes (n = 2; 6480 participants; I² = 0.66). There was no difference between the frequency of constipation and routes of administration, as well as between doses of oral semaglutide. The RR of adverse effects was only not significant for discontinuation of treatment for oral semaglutide., Conclusion: The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any cause, 24% non-fatal myocardial infarction, 24% coronary revascularization and 35% stroke (in patients with diabetes). The use of semaglutide was associated with a higher relative risk and frequency of most adverse effects evaluated., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Some studies have demonstrated the involvement of high concentrations of copper in the manifestation of insulin resistance in individuals with obesity. The objective of this study was to evaluate the copper nutritional status and its relationship with parameters of glycemic control in women with obesity. An observational case-control clinical study involving 203 women aged between 20 and 50 years, divided into two groups: obese (n = 84) and eutrophic (n = 119). Body weight, height and waist, hip and neck circumferences, dietary copper intake, copper biomarkers, determine ceruloplasmin activity and glycemic control parameters were measured. It was observed that women with obesity had higher copper concentrations in plasma and lower concentrations in erythrocytes when compared to the control group. Analysis of glycemic control parameters revealed a statistically significant difference in fasting blood glucose (p < 0.05) between groups. The study identified a significant positive correlation between plasma copper and fasting insulin values and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index (p < 0.05). The results of this study demonstrate that obese women have high copper concentrations in plasma and lower concentrations in erythrocytes. Furthermore, the significant positive correlation between plasma copper and fasting insulin and HOMA-IR index suggests the influence of this mineral on glycemic control parameters in obese women., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Drug biotransformation studies emerges as an alternative to pharmacological investigations of metabolites, development of new drug candidates with reduced investment and most efficient production. The present study aims to evaluate the capacity of biotransformation of rifampicin by the filamentous fungus Aspergillus niger ATCC 9029. After incubation for 312 h, the drug was metabolized to two molecules: an isomer (m/z 455) and the rifampicin quinone (m/z 821). The monitoring of metabolite formation was performed by high-performance liquid chromatography, followed by their identification through ultra-high-performance liquid chromatography coupled to tandem mass spectrometer. In vitro antimicrobial activity of the proposed metabolites was evaluated against Staphylococus aureus microorganism, resulting in the loss of inhibitory activity when compared with the standards, with minimum inhibitory concentration of 7.5 μg/ml. The significant biotransformation power of the ATCC 9029 strain of A. niger was confirmed in this study, making this strain a candidate for pilot studies in fermentation tanks for the enzymatic metabolization of the antimicrobial rifampicin. The unprecedented result allows us to conclude that the prospect of new biotransforming strains in species of anemophilic fungi is a promising choice., (© 2024 John Wiley & Sons Ltd.)

Exoskeletons are technologies that can help to increase or improve mobility, dexterity, and strength. They can be used as assistive devices, to restore lost affordances, or for rehabilitation. While mechanical exoskeletons are passive and rely on the body's power for movement, powered exoskeletons are active mechanical systems that can assist or enhance a user's capacity, including in strength and performance. They also offer scope to augment or enhance beyond simple medical support, with potential in the future for superhuman power and strength. While these technologies present promising clinical opportunities, including for those who want to regain walking capacity, they also bring ethical questions, such as about data privacy and accessibility. In addition, the physical features of the technology can prove mentally, physically, and financially demanding, and may be deployed in contexts where user choice and autonomy is constrained. In this article, we discuss these issues, and raise some pertinent ethical questions, not all of which can be easily answered. We touch upon medical and therapeutic uses, for industrial and workplace settings, and in military contexts specially, given these are contexts where such technology may be required or even imposed. We argue that reasonable optimism for such technologies needs to be tempered by sufficient ethical assessment to identify and address barriers to research, development, and use. As well as managing any impacts and expectations for the health and wellbeing of users, the potential impact on autonomy and the risk of coercion, we have to consider what kind of data may be recorded or used, and the risk that these technologies could exacerbate existing inequalities or harms., (© 2024 The Author(s). Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Site-directed mutagenesis was employed to investigate the structure-function relationship of nattokinase (NK) and its effect on the enzymatic activity, thermostability, pH tolerance, and fibrinolytic properties of NK. Specific mutations (T270S, V271I, E262D, and A259T) were introduced within the nk gene, targeting regions predicted to be involved in substrate binding. The NK(E262D) mutant exhibited a significant increase in enzymatic activity (2-fold) and catalytic efficiency (2.2-fold) as assessed by N-Succinyl-Ala-Ala-Pro-Phe p-nitroanilide (Suc-AAPF-pNA) hydrolysis, compared to the wild type. In silico analysis supported these findings, demonstrating lower binding energy for the NK(E262D) mutant, suggesting stronger fibrin affinity. Thermostability assays revealed that NK(E262D) and NK(A259T) displayed exceptional stability, retaining enzyme activity at 60 °C. All mutants exhibited a broader pH tolerance range (pH 5.0-10.0) compared to the wild-type NK. The fibrinolytic activity assay revealed that the E262D mutant possessed the highest fibrinolytic activity (2414 U/mg), surpassing the wild-type. This study reported an NK variant with improved enzymatic activity, thermostability, and fibrinolytic properties., Competing Interests: Declaration of competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background/objectives: Given the importance of emotion recognition for communication purposes, and the impairment for such skill in CI users despite impressive language performances, the aim of the present study was to investigate the neural correlates of emotion recognition skills, apart from language, in adult unilateral CI (UCI) users during a music in noise (happy/sad) recognition task. Furthermore, asymmetry was investigated through electroencephalographic (EEG) rhythm, given the traditional concept of hemispheric lateralization for emotional processing, and the intrinsic asymmetry due to the clinical UCI condition., Methods: Twenty adult UCI users and eight normal hearing (NH) controls were recruited. EEG gamma and alpha band power was assessed as there is evidence of a relationship between gamma and emotional response and between alpha asymmetry and tendency to approach or withdraw from stimuli. The TAS-20 questionnaire (alexithymia) was completed by the participants., Results: The results showed no effect of background noise, while supporting that gamma activity related to emotion processing shows alterations in the UCI group compared to the NH group, and that these alterations are also modulated by the etiology of deafness. In particular, relative higher gamma activity in the CI side corresponds to positive processes, correlated with higher emotion recognition abilities, whereas gamma activity in the non-CI side may be related to positive processes inversely correlated with alexithymia and also inversely correlated with age; a correlation between TAS-20 scores and age was found only in the NH group., Conclusions: EEG gamma activity appears to be fundamental to the processing of the emotional aspect of music and also to the psychocognitive emotion-related component in adults with CI.

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 10 6  cells/rat doses. A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index). Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways., Competing Interests: Declaration of competing interest I declare that I have no conflicts of interest relevant to this work." The authors declare that they have no financial or non-financial conflicts of interest related to this research." The authors report no conflicts of interest in this work. The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The focus on quantitative indicators-number of publications and grants, journal impact factors, Hirsch-index-has become pervasive in research management, funding systems, and research and publication practices (SES). Accountability through performance measurement has become the gold standard to increase productivity and (cost-) efficiency in academia. Scientific careers are strongly shaped by the push to produce more in a veritable 'publish or perish' culture. To this end, we investigated the perspectives of biomedical researchers on responsible assessment criteria that foster responsible conduct of research., Methods: We performed a qualitative focus group study among 3 University medical centers in the Netherlands. In these centers, we performed 2 randomly selected groups of early career researchers (PhD and postdoc level & senior researchers (associate and full professors) from these 3 institutions and explored how relational responsibilities relate to responsible conduct of research and inquired how potential (formal) assessment criteria could correspond with these responsibilities., Results: In this study we highlighted what is considered responsible research among junior and senior researchers in the Netherlands and how this can be assessed in formal assessment criteria. The participants reflected on responsible research and highlighted several academic responsibilities (such as supervision, collaboration and teaching) that are often overlooked and that are considered a crucial prerequisite for responsible research. As these responsibilities pertain to intercollegiate relations, we henceforth refer to them as relational. After our systematic analysis of these relational responsibilities, participants suggested some ideas to improve current assessment criteria. We focused on how these duties can be reflected in multidimensional, concrete and sustainable assessment criteria. Focus group participants emphasized the importance of assessing team science (both individual as collective), suggested the use of a narrative in researcher assessment and valued the use of 360 degrees assessment of researchers. Participants believed that these alternative assessments, centered on relational responsibilities, could help in fostering responsible research practices. However, participants stressed that unclarity about the new assessment criteria would only cause more publication stress and insecurity about evaluation of their performance., Conclusion: Our study suggests that relational responsibilities should ideally play a more prominent role in future assessment criteria as they correspond with and aspire the practice of responsible research. Our participants gave several suggestions how to make these skills quantifiable and assessable in future assessment criteria. However, the development of these criteria is still in its infancy, implementation can cause uncertainties among those assessed and consequently, future research should focus on how to make these criteria more tangible, concrete and applicable in daily practice to make them applicable to measure and assess responsible research practices in institutions., Trial Registration: Open Science Framework https://osf.io/9tjda/., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tijdink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cytoplasmic inclusion bodies (IBs) are a common feature of single-stranded, non-segmented, negative-strand RNA virus (Mononegavirales) infections and are thought to be regions of active virus transcription and replication. Here we followed the dynamics of IB formation and maintenance in cells infected with persistent and lytic/acute variants of the paramyxovirus, parainfluenza virus type 5 (PIV5). We show that there is a rapid increase in the number of small inclusions bodies up until approximately 12 h post-infection. Thereafter the number of inclusion bodies decreases but they increase in size, presumably due to the fusion of these liquid organelles that can be disrupted by osmotically shocking cells. No obvious differences were observed at these times between inclusion body formation in cells infected with lytic/acute and persistent viruses. IBs are also readily detected in cells persistently infected with PIV5, including in cells in which there is little or no ongoing virus transcription or replication. In situ hybridization shows that genomic RNA is primarily located in IBs, whilst viral mRNA is more diffusely distributed throughout the cytoplasm. Some, but not all, IBs show incorporation of 5-ethynyl-uridine (5EU), which is integrated into newly synthesized RNA, at early times post-infection. These results strongly suggest that, although genomic RNA is present in all IBs, IBs are not continuously active sites of virus transcription and replication. Disruption of IBs by osmotically shocking persistently infected cells does not increase virus protein synthesis, suggesting that in persistently infected cells most of the virus genomes are in a repressed state. The role of IBs in PIV5 replication and the establishment and maintenance of persistence is discussed.

Purpose: The concept of a Design Space (DSp) was introduced in ICH Q8 as a tool within the quality-by-design (QbD) approach to pharmaceutical development with the intent of being globally applicable. However, there appears to be variance in the regulatory agency expectations in pharmaceutical product filing and implementation of DSp. This paper presents some of the current industry perspective on design space., Methods: The Utilization of Design Space for Filings (UDSpF) Working Group in the Innovation and Quality (IQ) Consortium conducted a survey to establish a baseline for the current understanding of DSp among IQ member companies and assess the similarities and/or differences in strategies when filing a DSp. The survey focused on how IQ member companies approach DSp development, the primary drivers for the DSp, the presentation of the DSp in the filing, DSp verification and the benefits and flexibility anticipated and/or realized., Results: A total of 14 responses were received and analyzed representing a small sample size but a large proportion of the innovator industry/large pharmaceutical companies. The survey results revealed that DSp is not yet a commonplace for small molecule drug products and may not even be utilized as much in large molecule drug products. The benefits of DSp, with respect to enhanced process understanding, are well understood by the sponsors; however, the benefits of filed DSp with respect to manufacturing flexibility are not fully realized in the commercial lifecycle of the product. There are also challenges in gaining consistent buy-in/value proposition for DSp among cross-functional teams within organizations., Conclusions: There are still gaps in design space implementation for its full benefit in the pharmaceutical industry. The WG has presented a unified view from member companies on the approach to DSp considering when/where the DSp experiments are conducted and on the extent of the DSp development proposed in a dossier., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The nucleocapsid component of SARS-CoV2 is involved in the viral genome packaging. GammaP.1(Brazil) and the 20 C-US(USA) variants had a high frequency of the P80R and P67S mutations respectively in the RNA-binding domain of the nucleocapsid. Since RNA-binding domain participates in the electrostatic interactions with the viral genome, the study of the effects of proline substitutions on the flexibility of the protein will be meaningful. It evinced that the trajectory of the wildtype and mutants was stable during the simulation and exhibited distinct changes in the flexibility of the protein. Moreover, the beta-hairpin loop region of the protein structures exhibited high amplitude fluctuations and dominant motions. Additionally, modulations were detected in the drug binding site. Besides, the extent of correlation and anti-correlation motions involving the protruding region, helix, and the other RNA binding sites differed between the wildtype and mutants. The secondary structure analysis disclosed the variation in the occurrence pattern of the secondary structure elements between the proteins. Protein-ssRNA interaction analysis was also done to detect the amino acid contacts with ssRNA. R44, R59, and Y61 residues of the wildtype and P80R mutant exhibited different duration contacts with the ssRNA. It was also noticed that R44, R59, and Y61 of the wildtype and P80R formed hydrogen bonds with the ssRNA. However in P67S, residues T43, R44, R45, R40, R59, and R41 displayed contacts and formed hydrogen bonds with ssRNA. Binding free energy was also calculated and was lowest for P67S than wildtype andP80R. Thus, proline substitutions influence the structure of the RNA-binding domain and may modulate viral genome packaging besides the host-immune response.Communicated by Ramaswamy H. Sarma.

Exposure to different environmental factors, social and socioeconomic factors promotes development of the early-life adversity (ELA) phenotype. The persistence of this phenotype across generations is an interesting phenomenon that remains unexplored. Of late many studies have focused on disease-associated outcomes of ELA following exposure during childhood but the persistence of epigenetic imprints transmitted by ELA exposed parents to their offspring remains poorly described. It is possible that both parents are able to transmit ELA-associated genetic imprints to their offspring via transgenerational inheritance mechanisms. Here, we highlight the role of the mother and father in the biological process of conception, from epigenetic reprogramming cycles to later environmental exposures. We explain some of the known determinants of ELA (pollution, socioeconomic challenges, infections, etc.) and their disease-associated outcomes. Finally, we highlight the role of epigenetics, mitochondria and ncRNAs as mechanisms mediating transgenerational inheritance. Whether these transgenerational inheritance mechanisms occur in the human context remains unclear but there is a large body of suggestive evidence in non-human models that points out to its existence., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Mechanisms behind multiple organ involvement in lupus, is still an enigma for researchers. Mitochondrial dysfunction and oxidative stress are known to be important aspects in lupus etiology however, their role in lupus organ manifestation is yet to be understood. The present study is based on the understanding of interplay between AMPK/PGC-1α/SIRT-1 axis, mitochondrial complexes, and anti-oxidants levels, which might be involved in lupus organ pathology., Methodology: Pristane-induced Balb/c mice lupus model (PIL) was utilised and evaluation of anti-oxidants, mitochondrial complexes, pro-inflammatory cytokines levels, biochemical parameters were performed by standard procedures. Tissues were studied by haematoxylin and eosin staining followed by immunohistochemistry. The AMPK/PGC-1α/SIRT-1 expression was analysed by using qPCR and flowcytometry. Analysis of reactive oxygen species (ROS) among WBCs was performed by using various dyes (DCFDA, Mitosox, JC-1) on flowcytometry., Result: Significant presence of immune complexes (Tissue sections), ANA (Serum), and pro-inflammatory cytokines (plasma), diminished anti-oxidants and altered biochemical parameters depict the altered pathology in PIL which was accompanied by dysregulated mitochondrial complex activity. Differential expression of the AMPK/PGC-1α/SIRT-1 axis was detected in tissue and correlation with mitochondrial and antioxidant activity emerged as negative in PIL group while positive in controls. Close association was observed between ROS, mitochondrial membrane potential, and AMPK/PGC-1α/SIRT-1 axis in WBCs., Conclusion: This study concludes that mitochondria play a dual role in lupus organ pathology, contributing to organ damage while also potentially protecting against damage through the regulation of interactions between antioxidants and the AMPK axis expression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Antennas with higher gain and efficiency deliver superior performance across a wide frequency range. Achieving these characteristics at high frequencies while keeping a compact size necessitates sophisticated design approaches. This research presents a substrate-integrated waveguide (SIW) cavity-backed slotted patch antenna (SPA) tailored for the 28 GHz and 34 GHz frequency bands. Additionally, a linear tapered slot antenna is designed with a compact profile of 27.5 mm × 7.5 mm × 0.254 mm. The SIWs are implemented using vias on the outer profile of the antenna, and circular and rectangular slots are etched on the radiating surface. The goal of optimizing the antenna geometry is to enhance return loss within the desired frequency bandwidth, which means the Genetic Algorithm (GA) will determine the optimal antenna shape to achieve lower return loss than the original design within this bandwidth. The antenna exhibits dual resonance at 28 GHz and 38 GHz in the millimeter-wave range, providing an impedance bandwidth of 211 MHz (27.72 GHz-27.94 GHz) at 28 GHz and 127 MHz (37.88 GHz-37.98 GHz) centered at 38 GHz. The proposed antenna demonstrates gains of 8.04 dBi and 9.72 dBi at these operating bands. A prototype of the antenna is fabricated on RT/duroid 5880 and its characteristics are measured. The overall VSWR of the antenna ranges from 1 to 2, with a radiation efficiency of 94 %. The proposed antenna achieves dual-band performance with increased directivity and stable gain, exhibiting enhanced electric field distribution, radiation patterns, and reflection coefficient (S11), all of which contribute to a comprehensive understanding of the antenna's performance. This study compares the designed antenna's performance to that of the fabricated prototype. The proposed antenna is ideal for 5G applications due to its small size, broad spectral coverage, and excellent gain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Microbial challenge in-use studies are performed to evaluate the potential for microbial proliferation in preservative-free single-dose biological products after first puncture and potential accidental contamination during dose preparation (e.g., reconstitution or dilution) and storage. These studies, in addition to physicochemical in-use stability assessments, are used as part of product registration to define in-use hold times in Prescribing Information and in the pharmacy manual in the case of clinical products. There are no formal guidance documents describing regulator expectations on how to conduct microbial challenge in-use studies and interpret microbial data to assign in-use storage hold times. In lieu of guidance, US Food and Drug Administration (FDA) regulators have authored publications and presentations describing regulator expectations. Insufficient or unavailable microbial challenge data can result in shortened in-use hold times, thus microbial challenge data enables flexibility for health care providers (HCPs) and patients while ensuring patient safety. A cross-industry/FDA in-use microbial working group was formed through the Innovation & Quality (IQ) Consortium to gain alignment among industry practice and regulator expectations. The working group assessed regulatory guidance, current industry practice via a blinded survey of IQ Consortium member companies, and scientific rationale to align on recommendations for experimental design, execution of microbial challenge in-use studies, and a decision tree for microbial data interpretation to assign in-use hold times. Besides the study execution and data interpretation, additional considerations are discussed including the use of platform data for clinical stage products, closed system transfer devices (CSTDs), transport of dose solutions, long infusion times, and the use of USP <797> by HCPs for preparing sterile drugs for administration. The recommendations provided in this article will help streamline biological product development, ensure consistency on assignment of in-use hold times in biological product labels across industry, and provide maximum allowable flexibility to HCPs and patients while ensuring patient safety., (© PDA, Inc. 2024.)

This study aimed to describe the prevalence of HTLV-1/2 in quilombola communities in the state of Pará and investigate the possible sociodemographic risk factors associated with the infection, as well as to trace the occurrence of the familial transmission of the virus. A total of 310 individuals living in eight quilombos located in the state of Pará (northern Brazil) were investigated for the presence of anti-HTLV-1/2 antibodies using an enzyme-linked immunosorbent assay (ELISA), and positive samples were confirmed using Western blot and/or real-time quantitative polymerase chain reaction (qPCR). Participants answered a questionnaire about sociodemographic aspects and risk factors for infection. Anti-HTLV-1/2 antibodies were detected in two individuals (one man and one woman), for an overall seroprevalence of 0.65%. Both individuals belonged to the community of São José de Icatú. The search for intrafamilial infection identified two other infected women, which increased the general prevalence of HTLV-1 among the Icatú to 6.25% (4/64). Western blot and qPCR confirmed their HTLV-1 infection, and phylogenetic analysis demonstrated that the isolates were of the cosmopolitan subtype and transcontinental subgroup. Epidemiological investigation of the cases revealed that the three women, at some point in their lives, had a relationship with the infected male individual. HTLV-1 is transmitted silently between individuals in the community of São José de Icatú with a present or past family relationship, stressing the need for screening and laboratory diagnosis to prevent further dissemination of the virus and surveillance of disease emergence.

Immunochemotherapy has been the mainstay of treatment for newly diagnosed diffuse large B-cell lymphoma (ndDLBCL) yet is inadequate for many patients. In this work, we perform unsupervised clustering on transcriptomic features from a large cohort of ndDLBCL patients and identify seven clusters, one called A7 with poor prognosis, and develop a classifier to identify these clusters in independent ndDLBCL cohorts. This high-risk cluster is enriched for activated B-cell cell-of-origin, low immune infiltration, high MYC expression, and copy number aberrations. We compare and contrast our methodology with recent DLBCL classifiers to contextualize our clusters and show improved prognostic utility. Finally, using pre-clinical models, we demonstrate a mechanistic rationale for IKZF1/3 degraders such as lenalidomide to overcome the low immune infiltration phenotype of A7 by inducing T-cell trafficking into tumors and upregulating MHC I and II on tumor cells, and demonstrate that TCF4 is an important regulator of MYC-related biology in A7., (© 2024. The Author(s).)

Background: Effective teamwork is crucial to providing safe and high-quality patient care, especially in acute care. Crew Resource Management (CRM) principles are often used for training teamwork in these situations, with escape rooms forming a promising new tool. However, little is known about escape room design characteristics and their effect on learning outcomes. We investigated the current status of design characteristics and their effect on learning outcomes for escape room-based CRM/teamwork training for acute care professionals. We also aimed to identify gaps in literature to guide further research., Methods: Multiple databases were searched for studies describing the design and effect of escape rooms aimed training CRM/teamwork in acute care professionals and in situations that share characteristics. A standardized process was used for screening and selection. An evidence table that included study characteristics, design characteristics and effect of the escape room on learning outcomes was used to extract data. Learning outcomes were graded according to IPE expanded typology of Kirkpatrick's levels of learning outcome and Medical Education Research Study Quality Instrument (MERSQI) scores were calculated to assess methodology., Results: Fourteen studies were included. Common design characteristics were a team size of 4-6 participants, a 40-minute time limit, linear puzzle organization and use of briefing and structured debriefing. Information on alignment was only available in five studies and reporting on several other educational and escape room design characteristics was low. Twelve studies evaluated the effect of the escape room on teamwork: nine evaluated reaction (Kirkpatrick level 1; n = 9), two evaluated learning (Kirkpatrick level 2) and one evaluated both. Overall effect on teamwork was overtly positive, with little difference between studies. Together with a mean MERSQI score of 7.0, this precluded connecting specific design characteristics to the effect on learning outcomes., Conclusions: There is insufficient evidence if and how design characteristics affect learning outcomes in escape rooms aimed at training CRM/teamwork in acute care professionals. Alignment of teamwork with learning goals is insufficiently reported. More complete reporting of escape rooms aimed at training CRM/teamwork in acute care professionals is needed, with a research focus on maximizing learning potential through design., (© 2024. The Author(s).)

Background and Hypotheses: Affective recovery, operationalized as the time needed for affect to return to baseline levels after daily stressors, may be a putative momentary representation of resilience. This study aimed to investigate affective recovery in positive and negative affect across subclinical and clinical stages of psychosis and whether this is associated with exposure to childhood trauma (sexual, physical, and emotional abuse)., Study Design: We used survival analysis to predict the time-to-recovery from a daily event-related stressor in a pooled sample of 3 previously conducted experience sampling studies including 113 individuals with first-episode psychosis, 162 at-risk individuals, and 94 controls., Study Results: Negative affective recovery (ie, return to baseline following an increase in negative affect) was longer in individuals with first-episode psychosis compared with controls (hazard ratio [HR] = 1.71, 95% confidence interval [CI; 1.03, 2.61], P = .04) and in at-risk individuals exposed to high vs low levels of emotional abuse (HR = 1.31, 95% CI [1.06, 1.62], P = .01). Positive affective recovery (ie, return to baseline following a decrease in positive affect) did not differ between groups and was not associated with childhood trauma., Conclusions: Our results give first indications that negative affective recovery may be a putative momentary representation of resilience across stages of psychosis and may be amplified in at-risk individuals with prior experiences of emotional abuse. Understanding how affective recovery contributes to the development of psychosis may help identify new targets for prevention and intervention to buffer risk or foster resilience in daily life., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Cochlear implants (CI) allow deaf patients to improve language perception and improving their emotional valence assessment. Electroencephalographic (EEG) measures were employed so far to improve CI programming reliability and to evaluate listening effort in auditory tasks, which are particularly useful in conditions when subjective evaluations are scarcely appliable or reliable. Unfortunately, the presence of CI on the scalp introduces an electrical artifact coupled to EEG signals that masks physiological features recorded by electrodes close to the site of implant. Currently, methods for CI artifact removal have been developed for very specific EEG montages or protocols, while others require many scalp electrodes. In this study, we propose a method based on the Multi-channel Wiener filter (MWF) to overcome those shortcomings. Nine children with unilateral CI and nine age-matched normal hearing children (control) participated in the study. EEG data were acquired on a relatively low number of electrodes ( n = 16) during resting condition and during an auditory task. The obtained results obtained allowed to characterize CI artifact on the affected electrode and to significantly reduce, if not remove it through MWF filtering. Moreover, the results indicate, by comparing the two sample populations, that the EEG data loss is minimal in CI users after filtering, and that data maintain EEG physiological characteristics.

The current analytical study is dedicated to the boundary layer regime where heat and mass transfer rates are ruled by natural convection. A rectangular enclosure filled with a combination of an arbitrary buoyancy ratio has an Oseen-linear solution, and the position of Beavers and Joseph's condition is employed at the porous fluid interface. Thermal radiation's interaction with a porous lining influences overall heat transfer in a system. Porous linings and radiation are employed in many applications, such as furnaces, insulation, heat exchangers, solar energy collecting and storage, and heat control in electronics. The effect of slip and radiation is to increase the flow rate because of the reduction in friction at the surface. It indicates the fact that temperature and concentration are rapidly lowering. As the slip parameter and radiation parameter increase, the heat and mass transport increase due to the rise in velocity. The Nusselt and Sherwood numbers reach their maximum when the radiation parameter, Rayleigh number, and slip parameter are increased. The findings of the Nusslet number and Sherwood numbers are related to the finite situations of the slip parameter tending to infinity, the radiation parameter going to zero and the angle 90°., (© 2024. The Author(s).)

Cardiac tumors are rare and encompass a variety of presentations. Clinica symptoms are usually nonspecific, but they can present as obstructive, embolic, or constitutional symptoms. Treatment options and prognosis vary highly depending on the subtype, tumor size, and location. Surgical resection is usually the first-line therapy, except for cardiac lymphomas, and provides favorable long-term prognosis in most benign tumors. Cardiac sarcomas, however, are usually diagnosed in advanced stages, and the treatment relies on a multimodal approach with chemotherapy and radiotherapy. Metastatic cardiac tumors are usually related to advanced disease and carry an overall poor prognosis.

Vagal innervation is well known to be crucial to the maintenance of cardiac health, and to protect and recover the heart from injury. Only recently has this role been shown to depend on the activity of the underappreciated dorsal motor nucleus of the vagus (DMV). By combining neural tracing, transcriptomics, and anatomical mapping in male and female Sprague-Dawley rats, we characterize cardiac-specific neuronal phenotypes in the DMV. We find that the DMV cardiac-projecting neurons differentially express pituitary adenylate cyclase-activating polypeptide (PACAP), cocaine- and amphetamine-regulated transcript (CART), and synucleins, as well as evidence that they participate in neuromodulatory co-expression involving catecholamines. The significance of these findings is enhanced by previous knowledge of the role of PACAP at the heart and of the other neuromodulators in peripheral vagal targets., Competing Interests: All the authors declare no competing interests., (© 2024 The Authors.)

A Mycobacterium smegmatis transcriptional regulator, MSMEG&#95;5850, and its ortholog in M. tuberculosis, rv0775 were annotated as putative TetR Family Transcriptional Regulators. Our previous study revealed MSMEG&#95;5850 is involved in global transcriptional regulation in M. smegmatis and the presence of gene product supported the survival of bacteria during nutritional starvation. Phylogenetic analysis showed that MSMEG&#95;5850 diverged early in comparison to its counterparts in virulent strains. Therefore, the expression pattern of MSMEG&#95;5850 and its counterpart, rv0775, was compared during various in-vitro growth and stress conditions. Expression of MSMEG&#95;5850 was induced under different environmental stresses while no change in expression was observed under mid-exponential and stationary phases. No expression of rv0775 was observed under any stress condition tested, while the gene was expressed during the mid-exponential phase that declined in the stationary phase. The effect of MSMEG&#95;5850 on the survival of M. smegmatis under stress conditions and growth pattern was studied using wild type, knockout, and supplemented strain. Deletion of MSMEG&#95;5850 resulted in altered colony morphology, biofilm/pellicle formation, and growth pattern of M. smegmatis. The survival rate of wild-type MSMEG&#95;5850 was higher in comparison to knockout under different environmental stresses. Overall, this study suggested the role of MSMEG&#95;5850 in the growth and adaptation/survival of M. smegmatis under stress conditions., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

This article proposes a dual mode dual-polarized antenna configuration for IRNSS and fifth generation (5G) applications, operating at a frequency of 3.5 GHz based on characteristic mode analysis (CMA), and aims to provide broadband dual-polarized functionality. The original design of the antenna is a traditional patch antenna, and its dual-polarized features are determined using characteristic mode analysis. The full-wave method is used to stimulate both orthogonal modes using a 50 Ω coaxial input line at 3.5 GHz. In this design, the circular patch has been extended into an elliptical patch through a process of mode separation. The circular patch exhibits resonance at a frequency of 2.5 GHz, whereas the extended elliptical radiator demonstrates two resonance modes at 2.5 GHz and 3.5 GHz. The operational mechanism is elucidated by modal analysis and characteristic angle. This antenna operates on two different frequencies at the 2.5 GHz IRNSS band with horizontal polarization and the 3.5 GHz 5G service with vertical polarization. The maximum gain achieved with these frequency ranges is 5.31 dBi and 4.72 dBi, respectively. A ring resonator is chosen to improve the axial ratio and impedance bandwidth of the suggested prototype. The antenna's ground plane is shaped like a rectangle and features a V-shaped slot in the radiating patch. The antenna's physical footprint is 50 mm × 50 mm × 1.6 mm and an FR4 dielectric substrate serves as its foundation. Through its interaction with a PIN diode, the diode modifies the polarization of the antenna. The antenna functions as a right-handed circular polarization (RHCP), when the diode is operational. The bandwidth from 4.3 to 7.5 GHz is covered. On the other hand, it generates linear polarization (LP) between 4.2 and 5.3 GHz. The experimental antenna is evaluated and examined for its performance characteristics. The simulations are carried out utilizing the CST simulator. A prototype antenna has been manufactured and its performance has been validated against simulated findings., (© 2024. The Author(s).)

This study investigates the photophysical properties of a nitrobenzene-substituted 1,3,4-oxadiazole derivative (OX-NO) using both theoretical and experimental methods. The impact of the solvent on OX-NO absorption and fluorescence spectra, as well as its fluorescence quantum yield, was initially studied. A noticeable bathochromic shift in the Stokes shift indicated a π→ π* transition within the molecules. Solute-solvent interactions were analysed using Catalan parameters, distinguishing between specific and nonspecific interactions. Excited state dipole moments were derived from Lippert's, Bakshiev's, and Chamma Viallet's equations, showing increased polarity in the excited state compared to the ground state. Ground state dipole moments were determined via solvatochromic shift methods and ab initio techniques. Additionally, detailed analyses of bond length, angles, dihedral angles, Mulliken charge distribution, and HOMO-LUMO energy gap were conducted using the DFT-B3LYP-6-311G basis set in Gaussian-09 W. The energy band gap values obtained from theoretical calculations and experimental methods (cyclic voltammetry and UV-Visible spectroscopy) exhibited excellent agreement. Reactive sites such as electrophilic and nucleophilic regions were identified through total electron density, electrostatic maps, molecular electrostatic potential, and 3D plots using DFT computational analysis. Global descriptors were employed to characterize the compounds' chemical reactivity comprehensively. The observed photophysical attributes underscore the potential of these fluorophores in various applications like organic light-emitting diodes, solar cells, and chemosensors. This study contributes crucial insights into the optoelectronic properties of nitrobenzene-substituted 1,3,4-oxadiazole derivatives, paving the way for their future integration in advanced technological domains., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)