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Cyclic Theory of Time 
Andriy Guk

Andriy Guk

April 23, 2025
IntroductionThe nature of time remains one of the most profound and unresolved questions in contemporary physics. Within the framework of general relativity, time is treated as a coordinate of the space-time continuum, with its direction determined by the geometry of the universe and entropic processes. In classical mechanics and most macroscopic phenomena, time is considered a linear and irreversible quantity. In contrast, quantum mechanics challenges this view by revealing nontrivial effects associated with measurement, superposition, and interference.Particularly intriguing are quantum delayed-choice experiments, which give rise to paradoxical interpretations concerning the potential retroactive influence of future events on past states. While prevailing interpretations—such as the Copenhagen framework or the multiverse hypothesis—offer partial explanations, none provides a complete ontological model that reconciles microscopic and macroscopic phenomena within a unified causal-temporal framework.This paper introduces an alternative hypothesis grounded in the cyclical nature of time and its informational essence. According to this hypothesis, the universe constitutes a closed informational system, devoid of parallel realities, in which the entire history—from the initial singularity to the end of thermodynamic time—manifests as a coherent informational configuration. The central feature of this model is a supermassive black hole that, following the culmination of cosmic expansion and entropic dissipation, begins to move backward in time. This reversal is not a playback of past events but a phase of energy accumulation, culminating in a renewed Big Bang.This conceptual framework reinterprets the arrow of time as an emergent property of a global informational structure, thereby eliminating the need for quantum randomness. The cyclical time hypothesis thus offers a potential foundation for a unified approach to time, causality, and the evolution of the universe.
[ Mucinous Versus Non-Mucinous Gastric Adenocarcinoma: A Systematic Review and Meta...
yuchen Luo
Xin-Ke Chai

yuchen Luo

and 8 more

April 23, 2025
BACKGROUND AND OBJECTIVES: Mucinous gastric adenocarcinoma (MGC) is historically linked to poor prognosis, yet literature inconsistencies necessitate systematic evaluation. This meta-analysis aims to compare clinicopathological features and survival outcomes between MGC and non-mucinous gastric adenocarcinoma (NMGC). METHODS: A systematic search (PubMed/Embase/Web of Science, up to April 2024) identified cohort/case-control studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated via random-effects models. Subgroup analyses stratified by TNM stage, sample size, geographic region, and T stage were conducted. Heterogeneity, publication bias (Begg’s/Egger’s tests), and sensitivity analyses were assessed. Study quality was appraised using the Newcastle-Ottawa Scale. RESULTS: Twenty-nine studies (163,116 patients; 4,900 MGC) revealed worse univariate overall survival for MGC (HR=1.73, 95%CI=1.48, 2.01), but significance vanished after multivariable adjustment (HR=1.09, 95%CI=0.95, 1.25). Subgroup analyses demonstrated heterogeneity: early-stage MGC (TNM I) had poorer prognosis (HR=1.53, 95%CI=1.07, 2.18), while larger cohorts (>2,000 patients) showed attenuated risk (HR=1.33 vs. 1.75 in smaller studies). MGC exhibited larger tumors, advanced T stage, and higher risks of metastasis (lymphatic, vascular, peritoneal). CONCLUSION: MGC’s prognostic impact depends on tumor stage and cofactors, not histology alone. Clinical assessment should integrate TNM stage and tumor characteristics, particularly in early-stage disease.
Machine learning enables alignment-free distance calculation and phylogenetic placeme...
Eleonora Rachtman
Yueyu Jiang

Eleonora Rachtman

and 2 more

April 23, 2025
A key application of phylogenetics in ecological studies is identifying unknown sequences with respect to known ones. This goal can be formalized as assigning taxonomic labels or inserting sequences into a reference phylogenetic tree (phylogenetic placement). Much attention has been paid to the phylogenetic placement of short fragments used in amplicon sequencing or metagenomics. However, placing longer pieces of DNA, such as assembled genomes, contigs, or long reads, is less studied. Placing long sequences should be easier than short reads due to their increased signal. However, handling larger inputs poses its own challenges, including finding homologs and the computational burden. Here, we explore a phylogenetic placement method that uses k-mer frequencies to measure distances between long query sequences and reference genomes. Our proposed method, kf2vec, requires no alignment and can work on any region of the genome (needs no marker genes), thus simplifying analysis pipelines. A rich literature exists on using short k-mers frequencies to measure distances that correlate with phylogeny. Existing methods, however, have had moderate practical success despite enjoying strong theory. Instead of using predefined metrics, we train a deep neural network to estimate a distance from k-mer frequency vectors such that those distances match the path lengths on the reference phylogeny. The trained model is then used to characterize new samples. We demonstrate that kf2vec outperforms existing kmer-based approaches in distance calculation and allows accurate phylogenetic placement and taxonomic identification of new samples from various types of long sequences.
CAMERA: A Consensus study to Ascertain Minimum datasets for Ear Remote Assessments
Jonathan Lee
Joseph Cowling

Jonathan Lee

and 6 more

April 23, 2025
Introduction Remote healthcare has demonstrated benefits in providing high quality care, improving patient access, and reducing morbidity. In ear, nose, and throat surgery, there has been a recent surge in remote care driven by advancements including endoscopic otoscopy and boothless audiometry, as well as the coronavirus pandemic, but uncertainty exists regarding the minimum data needed for accurate remote diagnosis. Methods A panel of otology, audiology, general practice, and audiovestibular physicians were invited, and a literature review was undertaken to populate candidate dataset items for Round 1 of the Delphi process using the web-based software, Welphi. This was followed by two further Rounds, with controlled anonymised item-rating and qualitative feedback between rounds. Finally, a consensus meeting analysed and organised the results for dissemination of the final consensus outcomes. Results 70 studies were used to populate the questionnaire in Round 1. 34 multi-disciplinary expert panellists determined the final data items across the 3 Delphi Rounds. Experts worked at over 16 different centres across the UK. There was an average response rate of 94% across all rounds. Discussion This study highlights a multidisciplinary team’s consensus essential dataset for effective remote ear assessment. With NHS waiting lists at an all-time high, remote assessment capacity could alleviate strain and enhance patient care. This initiative will facilitate novel service and pathway redesign with the aim of ensuring all patients have access to high-quality ear assessments, regardless of location. We are also hopeful that this standardised dataset will also facilitate research and audit of remote ear services.
How we ask, how we act: A qualitative study exploring how mental health professionals...
Matthew Vaughan
Peter Kinderman

Matthew Vaughan

and 7 more

April 23, 2025
Background Growing literature recognises the impact of the circumstances in which people grow, live, work and age on the development, severity and chronicity of mental health challenges. These have been termed the ‘Social Determinants of Health’ (SDOH). Consequently, SDOH such as employment status, education, housing, and income, are key areas for intervention. However, within many healthcare contexts, these factors are not routinely recorded. Furthermore, knowledge of how mental health professionals explore and respond to these factors in their clinical practice is lacking. Objective To address the evidence gap of how SDOH are considered within day-to-day mental health care, this research will explore how mental health professionals talk about and act upon SDOH. Methods Purposive and snowball sampling was used to recruit 17 mental health professionals practising in the North-west of England. Semi-structured interviews were completed and analysed using reflexive thematic analysis. Results Five themes were identified in the data. These were: dissonance between high relevance and absent guidance; intersection between personal and professional experiences; importance of the therapeutic relationship, dealing with SDOH, and service values. Conclusions Despite the substantial impact of SDOH on service users, current exploration and responses to SDOH within mental health treatment and care are unstandardized and lacking guidance, being reliant on serendipitous practitioner awareness, motivation and organizational factors. Without formal training, guidance and systematic efforts to capture SDOH impacts, mental health services risk perpetuating inequalities. All professionals must engage in efforts to mitigate health inequities to prevent their adverse effects from persisting.
Application of dual virus spike approach to accelerate early-stage viral clearance st...
Heather Bethea Horne
Thomas B. Lindsey

Heather Bethea Horne

and 5 more

April 23, 2025
Biotechnology products derived from cell lines carry a risk of viral infection. Given this potential risk, an assessment of the virus removal/inactivation that can be achieved by a product’s established purification process is required per ICH Q5A guidelines. This viral safety assessment is a critical component of filing an investigational new drug (IND) application for an early-stage product. A viral clearance study must evaluate purification steps in a manufacturing process that are effective in inactivating/removing viruses. The traditional approach to viral clearance studies includes spiking in one virus at a time and quantifying the level of reduction of individual virus by a validated assay for that virus. This paper discusses an approach to spiking in multiple viruses in the same load and quantifying in virus-specific assays to help accelerate the timeline to IND filing for an early-stage product while also reducing support and material requirements for executing viral clearance studies.
Brain stimulation as a therapy in Long-Covid: A Narrative Review
Ana Muñoz Jurado
Begoña Mª Escribano

Ana Muñoz Jurado

and 3 more

April 23, 2025
Long-COVID syndrome is a prevalent condition among the group of people who are infected by this virus. However, there is still no defined treatment for this syndrome. This is because long-COVID is a very heterogeneous syndrome characterized by triggering different symptoms in each patient. However, the most frequently reported symptoms are fatigue, cognitive dysfunction, anxiety and depression, which have a significant socioeconomic impact. The neurological nature of these symptoms has raised the possibility of using brain stimulation therapies for their treatment. Therefore, the objective of this literature review is to evaluate noninvasive therapies as possible treatments for this disease, highlighting the specific effects of one of these therapies, transcranial magnetic stimulation (TMS). The results of the different studies carried out so far, which have used transcranial direct current stimulation, transcutaneous vagus nerve stimulation or TMS, have shown that these techniques can be effective in treating the clinical symptoms caused by post-COVID syndrome. However, more studies are needed to evaluate the effectiveness of this type of therapy on these symptoms, since the great heterogeneity of this syndrome represents a great challenge for public health and a significant socioeconomic cost, which requires investing in the study of new treatment approaches.
PHARMACO-EPIDEMIOLOGY OF OPPORTUNISTIC INFECTIONS AMONG THE PATIENTS ON ANTI-RETROVIR...
Manjula MJ
Vikas BR

Manjula MJ

and 2 more

April 23, 2025
Background: 650,000 people died from AIDS-related illnesses worldwide in 2021. Opportunistic infections (OIs) are occurring more frequently and with progressive severity among the people infected with the Human Immunodeficiency Virus (HIV) with wide variation based on epidemiological area. Objectives: To evaluate the distribution of opportunistic infections among the patients undergoing ART and various drug use indicators, utilization patterns, interactions, adverse effects of the drugs among the patients with OIs, undergoing ART. Methodology: Ambispective study. The present study included 424 patients diagnosed with retroviral disease and on treatment at the ART center, RRMCH. Demographic data, viral load, blood investigations, and presenting complaints at each follow-up were assessed. Results: The Average age of our study population was 42.85 years, with male predominance. 4.7% (20/424) of the patients with OI had poor adherence. 89% are alive, 5% died during treatment. The rest had transferred out. 41.7% (48/115) presenting with tuberculosis was the commonest opportunistic infection, and thus, the anti-TB drugs were the most frequent drugs used. Conclusion: Management of opportunistic infections regularly is one of the crucial exploratory tools to determine the role of drugs and their changing trend; there has been a reduction in CD4 count even with newer ART drugs, and hence, the OIs.
In Silico Analysis of Heat Shock Protein Gene Expression in Indian Freshwater Fishes...
Vipul Yadav

Vipul Yadav

April 23, 2025
Heat shock proteins (HSPs) play a crucial role in cellular protection during environmental stress, particularly in aquatic organisms sensitive to temperature fluctuations and pollution. In this study, we conducted an in silico analysis of gene expression profiles of key HSP genes (HSP70, HSP90, and HSP27) in selected Indian freshwater fish species. Public gene expression data were retrieved from the NCBI Gene Expression Omnibus (GEO) and analyzed using GEO2R and other bioinformatics tools. We observed significant upregulation of HSP70 and HSP90 under thermal stress and pollutant exposure, with HSP27 showing variable expression. Phylogenetic analysis of HSP70 sequences across species was performed using MEGA11, revealing evolutionary relationships and conserved motifs. These findings underline the adaptive molecular response of freshwater fishes to environmental stress, highlighting the utility of HSP genes as potential biomarkers for aquatic health monitoring and conservation biology.
Temporal muscle and fascia transplantation for unilateral vocal fold paralysis: short...
Wenting Deng
Jiawang Tian

Wenting Deng

and 8 more

April 23, 2025
Background: This study investigates the use of autologous temporal muscle and fascia transplantation for the treatment of unilateral vocal fold paralysis (UVFP). Objectives: To assess the efficacy of autologous temporal muscle and fascia transplantation in treating glottic insufficiency resulting from UVFP and to evaluate its impact on treatment outcomes and prognosis. Methods: Twenty-three patients with UVFP underwent autologous temporal muscle and fascia transplantation. Preoperative and postoperative assessments were performed using dynamic laryngoscopy, vocal acoustics, and aerodynamic measurements. Results: Phonation showed improvement in all 23 patients one month after surgery, with significant enhancement observed by three months postoperatively. At six months, voice quality stabilized, with both subjective and objective measures of voice acoustics and aerodynamic parameters showing marked improvements compared to preoperative values. Notably, vocal fold structure and mucosal vibration approached normal, and glottic closure improved significantly. The subjective assessments of hoarseness, including grade, roughness, breathiness, asthenia, and strain (GRBAS), as well as Voice Handicap Index (VHI) scores, demonstrated significant improvement (p < 0.05). Additionally, vocal acoustic parameters and maximum phonation time showed significant differences from baseline (p < 0.05). Conclusion: Autologous temporal muscle and fascia transplantation is an effective treatment for UVFP, significantly improving voice quality and glottic function.
Safety-Critical Control of Impulsive Systems via Control Barrier Functions
Zihan Liu
Yuan-Hua Ni

Zihan Liu

and 1 more

April 23, 2025
This paper addresses the safety challenges in impulsive systems, where abrupt state jumps introduce significant complexities into system dynamics. A unified framework is proposed by integrating Quadratic Programming (QP), Control Barrier Functions (CBFs), and adaptive gain mechanisms to ensure system safety during impulsive events. The CBFs are constructed to enforce safety constraints by capturing the system’s continuous dynamics and the effects of discrete impulsive moments. An adaptive gain mechanism dynamically adjusts control inputs based on the magnitudes of impulses and the system’s proximity to safety boundaries, maintaining safety during instantaneous state jumps. A tailored QP formulation incorporates CBFs constraints and adaptive gain adjustments, optimizing control inputs while ensuring compliance with safety-critical requirements. Theoretical analysis establishes the boundedness, continuity, and feasibility of the adaptive gain and the overall framework. The effectiveness of the method is demonstrated through simulations on a robotic manipulator, showcasing its practical applicability.
Action or Stimulus: Individual beliefs about learned associations influence the proce...
Christine Albrecht
Marta Ghio

Christine Albrecht

and 2 more

April 23, 2025
Feedback learning seems to involve two systems: The striatal reward system, reflected in the feedback-related negativity (FRN) or reward positivity (RewP) event-related potentials (ERP) component, and the medial temporal lobe (MTL), reflected in the N170. In this study we tested the hypothesis that the former system is more involved in associating previous actions with feedback, the latter in associating previous stimuli with feedback. More specifically, we hypothesized that the engagement of these systems depends on individual beliefs in credit assignment, i.e., whether participants linked the feedback they received to actions or stimuli, possibly modulated by feedback timing. EEG data were recorded from 43 participants performing an ambiguous feedback-learning task, in which feedback could be attributed to either a performed action or a selected stimulus. One group was instructed to learn action-feedback associations, the other to learn stimulus-feedback associations. We derived an Action Index from subsequent test trials, which was high if participants favoured action-association learning and low if they favoured stimulus-association learning. We found that both FRN/RewP and N170 were influenced by individual beliefs about learned associations, with the FRN showing stronger feedback valence coding across feedback delays when participants focused on action-feedback associations. The N170, in turn, was generally reduced for stimulus-feedback associations. Prediction error coding was found for the FRN/RewP in all conditions, and for the N170 in all delayed feedback conditions. For action-feedback associations learned with delayed feedback, where both N170 and FRN/RewP were modulated, the MTL might support striatal learning by reactivating action representations.
Molecular Mimicry Between Epstein-Barr Virus and Human Herpesvirus-6 Proteins and Cen...
Abbas F. Almulla
Muslimbek Normatov

Abbas Almulla

and 3 more

April 23, 2025
Background: The Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) are frequently linked to neuropsychiatric illnesses such as multiple sclerosis, depression, and chronic fatigue syndrome/myalgic encephalomyelitis. These viruses may induce autoimmune reactions by molecular mimicry, leading to damage to self-epitopes in the central nervous system (CNS). Objective: This study seeks to explore the common pentapeptides present in EBV and HHV-6 viral antigens alongside various CNS-related proteins via molecular mimicry. Additionally, it will assess the immunogenicity of these shared pentapeptides in T and B cells. Method: Sequence alignment was conducted to assess molecular mimicry between 32 EBV and HHV-6 antigens and 10 CNS autoantigens. Protein sequences were obtained from UniProt, structural homology was analyzed using AlphaFold and PyMol, and shared pentapeptides were identified with Alignmentaj. Immunogenicity was assessed via the Immune Epitope Database (IEDB) for potential T- and B-cell activation. Results: A total of 91 mimicry pentapeptides were identified between viral antigens (EBV and human HHV-6), and CNS proteins. Notably, synapsin (SYN)1 exhibited the highest mimicry, sharing multiple pentapeptides with EBV nuclear antigen (EBNA)1, EBNA6, latent membrane protein (LMP)1, and early antigen diffused (EA-D) and 6 different HHV-6 antigens. Myelin proteins including myelin basic protein, myelin-associated glycoprotein, and myelin-oligodendrocyte glycoprotein also displayed shared pentapeptides with EBV/HHV-6 antigens, indicating potential immune cross-reactivity. EBNA1, EBNA2, EBNA6, LMP1, LMP2, EA-D, and BLLF1 structurally resemble CNS autoantigens and act as immunoreactive epitopes for human T and B cells. Except for EBNA2 and protein U94, all share immunogenic pentapeptide sequences with SYN1. Conclusion: EBV and HHV-6 antigens mimic CNS proteins, potentially triggering autoimmune responses via T and B cell activation. Shared pentapeptides suggest a link between viral infections and CNS autoimmunity. Further research is needed to clarify molecular mechanisms and explore targeted therapies to mitigate virus-induced neuroinflammation.
Analysis and Mining of Baloxavir Marboxil Adverse Event Signals in Elderly Patients B...
Lei Wang

Lei Wang

April 23, 2025
Objective: To identify adverse drug event (ADE) signals associated with baloxavir marboxil in patients aged ≥65 years, providing a reference for safe and rational clinical use. Methods: ADE reports listing baloxavir marboxil as the primary suspected drug were collected from the U.S. FDA Adverse Event Reporting System (FAERS) spanning 83 quarters, from the first quarter of 2004 to the third quarter of 2024. After removing duplicate reports, standardizing data, and excluding reports with unspecified ages, the data were mapped according to the various hierarchical terminologies of the Medical Dictionary for Regulatory Activities (MedDRA 27.1). The cleaned data were divided into two groups: patients aged ≥65 years and those aged <65 years. ADE signal mining for both groups was performed using four methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Results: Following data processing and analysis, 241 patients (441 ADE cases) were included in the ≥65 years group, identifying 36 preferred terms (PTs) with positive signals, including 18 novel PTs. These involved 14 system organ classes (SOCs), with the highest proportions in infections and infestations (21.84%) and nervous system disorders (16.99%). The remaining SOCs were distributed relatively evenly (1.46%–10.19%). In the <65 years group, 914 patients (2,076 ADE cases) were identified, with 56 PTs showing positive signals, including 16 novel PTs. These involved 18 SOCs, with a distribution skewed toward the top three categories: injury, poisoning, and procedural complications (39.75%); general disorders and administration site conditions (22.51%); and gastrointestinal disorders (12.77%), collectively accounting for 75.03%. Age-specific PT analysis revealed that patients aged ≥65 years were more likely to report 21 PTs, with strong associations for syncope, rhabdomyolysis, infectious pneumonia, and loss of consciousness. Patients aged <65 years were more likely to report 6 PTs, with notable signals including intentional product use issues, off-label use, vomiting, abnormal behavior, and diarrhea. Conclusion: For patients aged ≥65 years, in addition to neuropsychiatric and gastrointestinal disorders already listed in the drug label, special attention should be paid to muscle metabolism-related ADEs, such as rhabdomyolysis and related conditions like disseminated intravascular coagulation and elevated creatine phosphokinase. In the <65 years group, improper drug administration and gastrointestinal-related ADEs were more prominent during treatment.
Design of a Multi-Resonant Slot Filter Antenna for 5G Applications
Ming Hui
YongJie Wang

Ming Hui

and 3 more

April 23, 2025
This study proposes a broadband, high-gain, Multi-Resonant antenna design for the 5G Sub-6 GHz band, using a fusion method to effectively cover the key Sub-6 GHz frequency band. The proposed design achieves optimized performance by incorporating symbiotic and parasitic elements to enhance selectivity and etching slotlines to improve impedance matching and expand the bandwidth. Simulation results show that the antenna operates at a center frequency of 3.5 GHz, with a relative bandwidth of 16.04% (3.21–3.77 GHz) and an average gain of 9.5 dBi.
Application of Sentinel-2 multispectral images for estimating the suspended sediment...
Qasem Mahdawi
Ahmad Shanehsazzadeh

Qasem Mahdawi

and 2 more

April 23, 2025
Remote sensing (RS) techniques have been widely used in water science due to quantitatively and qualitatively development of satellite images. The advantage is pronounced for ungauged basins where climatological, hydrological and qualitative parameters are not available or unreliable. Sentinel-2 multispectral images are applied in this study to estimate the suspended sediment source and concentration (SSC) in flood events for the Laghman River in Afghanistan. Three field deployments (twice in wet and one in dry seasons) were conducted to measure the SSC for calibration purposes. The linear regression model based on Sentinel-2 band 5 (B5) is proposed as a suitable model for predicting SSC in flood events due to its simplicity that provides sufficient accuracy compared to other band combinations. The R 2 and RMSE values are 0.62 and 95.59, respectively. The appropriateness of visible and near-infrared (VNIR) bands for SSC estimation is consistent with similar results in other case studies. Based on the retrieved RS model, the source of sediment production and the spatial variations of SSC along the two upstream tributaries and the main branch of the river are investigated. The results indicate that SSC in Alingar tributary is twice as high as that of Alishing tributary and the concentration is gradually increasing downstream in the tributaries and in the main river. The trend of increase in SSC in the main river is lower than the two tributaries, which indicate that the erosion process is more active in the upstream tributaries than in the main branch.
Mobile ICT Solutions for Smart Agriculture and Food Security
Emmanuel Idowu

Emmanuel Idowu

April 23, 2025
In the digital era, the integrity, security, and transparency of data within Information and Communication Technology (ICT) systems are of critical importance. Traditional centralized data management approaches often suffer from vulnerabilities such as data breaches, unauthorized access, and lack of traceability. Blockchain technology, with its decentralized and immutable architecture, offers transformative potential for addressing these challenges. This paper explores the integration of blockchain into ICT infrastructures to enhance secure and transparent data management. Through a comprehensive literature review, theoretical modeling, and analysis of real-world use cases, we identify how blockchain applications can mitigate existing risks and improve trust in data exchange. Furthermore, the study discusses implementation challenges, such as scalability and regulatory compliance, and presents a conceptual framework illustrating blockchain's role in ICT systems. The findings suggest that blockchain not only strengthens data security but also enables verifiable, transparent operations across various sectors, including healthcare, egovernance, education, and finance.
Blockchain Applications in ICT for Secure and Transparent Data Management
Emmanuel Idowu

Emmanuel Idowu

April 23, 2025
In the digital era, the integrity, security, and transparency of data within Information and Communication Technology (ICT) systems are of critical importance. Traditional centralized data management approaches often suffer from vulnerabilities such as data breaches, unauthorized access, and lack of traceability. Blockchain technology, with its decentralized and immutable architecture, offers transformative potential for addressing these challenges. This paper explores the integration of blockchain into ICT infrastructures to enhance secure and transparent data management. Through a comprehensive literature review, theoretical modeling, and analysis of real-world use cases, we identify how blockchain applications can mitigate existing risks and improve trust in data exchange. Furthermore, the study discusses implementation challenges, such as scalability and regulatory compliance, and presents a conceptual framework illustrating blockchain’s role in ICT systems. The findings suggest that blockchain not only strengthens data security but also enables verifiable, transparent operations across various sectors, including healthcare, e-governance, education, and finance.Keywords : Blockchain, Information and Communication Technology (ICT), Data Security, Transparency, Decentralized Systems, Smart Contracts
Successful treatment of pediatric type III pityriasis rubra pilaris with limited-cour...
Yangzong Deji
Yangji Ciren

Yangzong Deji

and 3 more

April 23, 2025
Title pageThe type of manuscript : CASE REPORTTitle of the manuscript: Successful treatment of pediatric type III pityriasis rubra pilaris with limited-course secukinumab injectionAuthor: YangzongDeji1, YangjiCiren1, QuzongSuolang1, ZhiliangLi21Department of Dermatology and Venereology, People’s Hospital of Xizang Autonomous Region,Lhasa, China;2Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaAcknowledgment: noneStatement: the manuscript has been read and approved by all the authors, that the requirements for authorship as stated earlier in this document have been met, and that each author believes that the manuscript represents honest work.Corresponding author: ZhiliangLi, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. E-mail: pyslzl@pumcderm.cams.cn telephone number:8615298384673
Hyperkeratotic Plaque on soles with yellowish-orange hue
Sunil Jaiswal
Shraddha Uprety

Sunil Jaiswal

and 3 more

April 23, 2025
Case Image
IMDM-20 enhances neutrophilic features during DMSO-mediated differentiation of HL-60...
Jorge Andrés Cázares-Preciado
José Antonio Cruz-Cardenas

Jorge Andrés Cázares-Preciado

and 4 more

April 23, 2025
The promyelocytic HL-60 cell line can be differentiated toward neutrophil-like cells and has been historically used as a surrogate to study human neutrophil biology in vitro. Multiple differentiation protocols have been reported to generate neutrophil-like HL-60 cells, with limited consideration of how methodological variations might influence cell identity and functions. Here, we performed a systematic search of the research literature published between January 9 th 2020, and January 9 th 2025, to investigate the current heterogeneity in protocols used to differentiate HL-60 towards neutrophil-like cells. A total of 71 studies published in 5 years employed 41 distinct protocols. The 3 most prevalent conditions to maintain HL-60 cells were IMDM with 20% FBS (IMDM-20), DMEM with 10% FBS (DMEM-10), and RPMI-1640 with 10% FBS (RPMI-10). Over 90% of protocols applied 1-1.57% DMSO as differentiating agent to produce neutrophil-like cells. In the laboratory, we compared the 3 most common culture media applied during neutrophil-like cell differentiation with 1.3% DMSO over 5 and 7 days. Using IMDM-20 led to the highest proliferation rate and cell yield during differentiation. Neutrophil-like cells produced in IMDM-20 and RPMI-10 exhibited significantly higher proportions of CD15 +CD11b + cells, and significantly higher bacterial clearance compared to DMEM-10. Culture media did not affect phagocytosis, but using RPMI-10 over 5 days led to significantly higher ability to produce ROS. IMDM-20 produced significantly more IL-6 and IL-1β in culture supernatant following stimulation with immune complexes. Overall, the results support the use of IMDM-20 with 1.3% DMSO to differentiate HL-60 to study neutrophil biology in vitro.
Fluorescent Sensor Based on Stable Cd-(II) Metal-Organic Framework for Rapid and Visu...
Wenqiu Qi
Ziqing Zhang

Wenqiu Qi

and 6 more

April 23, 2025
Antibiotics, widely used in the fields of medicine, animal husbandry, aquaculture, and agriculture, are ubiquitously present in water systems, posing a serious threat to the ecological environment and human health. It is essential to develop a fast, sensitive and straightforward analytical method for sensing antibiotics in aqueous solution. In this work, a 3D luminescent metal-organic framework (MOF), named Cd-BTDI, has been synthesized, featuring high structural stability in water. The intense green luminescence with an emission peak at 509 nm is quite stable in aqueous and common organic solvents, providing a good foundation to fabricate a potential chemical sensor. Cd-BTDI exhibits selective and sensitive detection performance for tetracycline (TC) and oxytetracycline (OTC) antibiotics, with fast response and good anti-interference. The limits of detection (LODs) for TC and OTC are 0.071 μΜ and 0.062 μΜ, respectively. By introducing the commercially available polymer polymethyl methacrylate, a reusable sensing film can be fabricated for on-site visual detection of trace tetracycline antibiotics. In addition, Cd-BTDI can detect tetracycline antibiotics in three kinds of typical real water matrices (tap, lake and river water), showing a great potential for practical uses.
Host-parasite oxidative arms race: who will win?
Caroline Isaksson
Vaidas Palinauskas

Caroline Isaksson

and 3 more

April 22, 2025
Avian haemosporidian parasites are globally widespread with a broad repertoire of hosts. When infected, the host can either reduce the parasite burden (resistance) and/or limit the severity of parasitaemia (tolerance). Oxidative stress is known to play a pivotal role in the host’s resistance and tolerance as well as its detrimental endpoints. The rationale behind this paradox lies in the dual role of reactive oxygen species (ROS): they can have both beneficial and detrimental effects for the host, while being largely harmful to the parasite. Thus, it is in the parasite’s interest to maintain a reduced environment within the host’s cell, whereas the host needs a fine-tuned balance between generating ROS to eliminate the parasites and maintaining sufficient antioxidant levels to protect its own tissues. This dynamic is what we refer to as the host-parasite oxidative arms-race. In this study, Eurasian siskins (Spinus spinus) were experimentally infected with Plasmodium ashfordi to investigate how the fundamental antioxidant system – the glutathione redox-system – responds to infection over time compared to control birds. By combining physiological measures and gene expression data of key glutathione related genes from both the parasite and the host at different time points, we provide evidence of this oxidative arms race. The gene expression data show that the parasite actively maintains reduced intracellular environment and eliminates ROS through high expression of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione synthetase. In contrast, the host upregulates glutathione S-transferases (GSTs) and glutathione peroxidases (GPX), which reduce the physiologically active levels of the key antioxidant, glutathione. Although, the parasite seems to win the race in terms of the oxidative state of the cell, the marked decrease in parasitaemia from day 21 (45%) to 31 (15%) suggests that the host’s strategy by lowering the physiological glutathione levels is sufficient to defeat the parasite.
Deciphering branched galactomannan structures via multistage ion mobility MS and MSn...
Rania BENAZZA
Mathieu FANUEL

Rania BENAZZA

and 3 more

April 22, 2025
Rationale Hemicelluloses are abundant carbohydrate components in plant cell walls. They play a crucial structural role in binding cellulose microfibrils, in addition to other biological functions. Their high structural variability directly influences their biological properties, making it important to establish a structure–function relationship. In the case of galactomannans, this complexity relies in branching, large size, in addition to isomerism, which makes their characterization challenging. In this context, we have demonstrated that cyclic ion mobility spectrometry (IMS), combined with porous graphitic carbon (PGC) chromatography, mass spectrometry (MS) and multistage MS/MS fragmentation (IMS n), is a powerful tool for the detailed elucidation of galactomannan structures. Methods In this study, we show that our multistage IMS n sequencing approach, previously validated for homo-linear oligosaccharides, can be successfully applied to hetero-branched hemicelluloses with careful adjustments. Our approach consists of building a database library of high resolution IMS profiles of di- and tri-saccharidic fragments. Then, the sequence of the oligosaccharide of interest is retrieved by comparing the HR-IMS profile of its di- and tri-saccharide fragments with the profiles from the DB library. Results In fact, our IMS n experiments on galactomannan reveal ATD profiles matching with known reference structures, confirming the co-existence of multiple isomers. In addition, we proved that this approach could be improved by incorporating trisaccharidic fragments to our DB library, serving in the characterization of higher DP structures (DP4 in this case). Conclusions Overall, this work paves the way for the characterization of even more complex oligosaccharides, which can be potentially used for bio-based material conception.
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