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Article
Social Sciences
Tourism, Leisure, Sport and Hospitality

Eddy-Antonio Castillo-Montesdeoca

,

Giovanni Herrera

,

Danny Zambrano

,

Diego Sande

Abstract: Compared with international travel, where dominant frameworks emphasize cultural distance, novelty, and difference, domestic tourism in protected natural areas remains under-theorized. This study conceptualizes domestic tourism through cultural proximity and introduces the Applied Cultural Proximity Model (ACPM), which frames the tourist experience as a multidimensional experiential system in which environmental, cultural, managerial, infrastructural, and communicative elements acquire meaning within shared symbolic contexts. A sequential exploratory mixed-methods design was employed. Expert interviews informed construct development, followed by a survey of Ecuadorian domestic tourists visiting Cotopaxi National Park (n = 1,113). Confirmatory factor analysis supported a six-dimensional structure (natural, cultural, accessibility, administrative, complementary, communication), demonstrating strong reliability and convergent validity. Structural equation modelling indicated good model fit (CFI = 0.95; RMSEA = 0.064), supporting the structural adequacy of the integrated experiential system. Natural attributes show the greatest experiential prominence, while cultural and communication dimensions occupy key structural positions in symbolic engagement and meaning construction. The findings suggest a theoretical inversion of cultural distance logic: in culturally familiar settings, familiarity, continuity, and identity resonance underpin experiential coherence. The ACPM provides a validated framework for analyzing domestic tourism in culturally rich protected areas and supports sustainable, identity-sensitive destination management.

Article
Medicine and Pharmacology
Psychiatry and Mental Health

Robert Zgarbura

,

Leea Cristescu Rizea

,

Alexandru Pavel

,

Catalina Tudose

Abstract: Background: Migraine is a chronic neurological disorder associated with significant functional impairment and reduced quality of life (QoL). Repetitive transcranial magnetic stimulation (rTMS) represents a non-pharmacological treatment option, yet predictors of QoL improvement following rTMS remain poorly understood. Methods: In this exploratory observational study, 32 adults with migraine underwent 10–40 rTMS sessions. QoL was assessed at baseline and post-intervention using the WHOQOL-BREF and Migraine-Specific Quality of Life Questionnaire (Migraine-QoL). Anxiety, depression, headache impact, and disability were evaluated using HAMA, HAMD, HIT-6, and MIDAS. Changes in QoL were calculated as post-treatment minus baseline scores. Paired t-tests assessed pre–post changes, Spearman correlations explored associations with baseline variables, and linear regression identified independent predictors. Results: Both overall QoL and Migraine-QoL improved significantly following rTMS (p<0.001). Antipsychotic use was associated with greater improvement in overall QoL (p=0.026). Higher baseline HIT-6 and HAMA scores correlated with greater improvements in Migraine-QoL. In regression analyses, higher baseline headache severity and younger age independently predicted Migraine-QoL improvement, explaining 53.1% of the variance. Conclusions: rTMS was associated with meaningful QoL improvements in migraine. Baseline headache burden and age may help identify patients most likely to benefit. Larger controlled studies are needed to confirm these findings.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Ezra N. S. Lockhart

Abstract: This study develops a Constraint-Driven Model of Intelligence to explain the emergence of structured meaning in complex systems, reconciling probability and cybernetics. Building on Émile Borel’s Infinite Monkey Theorem, which illustrates the theoretical inevitability of order through unbounded stochastic processes, and Gregory Bateson’s principle of negative explanation, which frames structure as the consequence of systematically eliminated alternatives, the analysis formalizes how constraints break ergodicity and generate asymmetry. Shannon’s entropy quantifies the informational effects of constraints, while Simon’s bounded rationality and Turing’s algorithmic limits illustrate how cognitive and computational boundaries produce tractable, reproducible outcomes. Applying this model to modern artificial intelligence, the study provides a formal account of model collapse in recursive training, showing that the loss of asymmetric constraints leads to low-entropy, repetitive outputs, demonstrating the epistemic necessity of constraint-driven regulation. By comparing probabilistic and cybernetic accounts of emergence, the analysis demonstrates that structured intelligence is not an inevitable product of stochastic exploration, but arises from bounded, recursive, and selective processes. Beyond computational systems, this model is transdisciplinary, showing how constraints ranging from socioeconomic pressures to subcultural circulation shape diversity, innovation, and functional asymmetry. By formalizing the transition from maximal stochastic symmetry to meaningful asymmetry, this model establishes a generalizable cybernetic epistemology for the generation of structured intelligence and meaning across numerous domains.

Article
Biology and Life Sciences
Insect Science

Binbin Dong

,

Xiaoqian Yao

,

Yalan Sun

,

Chunmeng Huang

Abstract: The tomato leaf miner (Tuta absoluta) poses a significant threat to global tomato production. However, environmentally sustainable management strategies for this pest, as well as its mechanisms of insecticide resistance, remain insufficiently understood. This study employed the leaf immersion method to conduct bioassays on the early second-instar larvae of the T.absoluta to evaluate physiological responses to sublethal concentrations of the novel amide insecticide broflanilide. Subsequently, high-throughput transcriptome sequencing was performed to investigate changes in gene expression and metabolic pathways. Bioassay results determined the larval sublethal concentrations of broflanilide to be 0.136 mg/L (LC₁₀) and 0.210 mg/L (LC₃₀). Sublethal exposure significantly prolonged the larval period, reduced pupal weight, and inhibited fecundity of female adults. Transcriptomic and qPCR analyses revealed that, compared with the control (CK), expression of the vitellogenin gene Vg decreased by 15.99% and 30.27% under LC₁₀ and LC₃₀ treatments, respectively, while its receptor gene VgR decreased by 11.56% and 24.49%. Similarly, expression of chitin synthase genes chs1 and chs2 declined by 13.56% and 30.17% (chs1), and 7.85% and 19.45% (chs2), respectively. Gene expression analysis elucidated how sublethal insecticides treatment impact larval development and fecundity. Furthermore, the study revealed upregulation of cytochrome P450-mediated detoxification pathways and Toll/Imd immune signaling pathways under broflanilide stress, indicating activation of a coordinated defense response in T. absoluta. Sublethal broflanilide exposure modulated larval gene expression to balance growth, development, and stress adaptation. Such exposure exerts selective pressure on susceptible populations, potentially driving adaptive shifts in detoxification metabolism and contributing to the development of field resistance. These findings advance our understanding of the sublethal effects of novel insecticides and provide valuable insights for insecticide deployment strategies and resistance management.

Article
Computer Science and Mathematics
Geometry and Topology

Milan Matejdes

Abstract: The aim of the article is to introduce a few variants of generalized quasi-continuity of multifunctions defined on a bitopological space and to study their mutual relationship. The results known for functions are extended to multifunctions which provide a wider range of relationships, mainly in terms of upper and lower semi continuities and corresponding continuities with respect to a dual bitopology. The proof procedures are based on a notion of pseudo refinement of two topologies and the Baire property in a bitopological space. A characterization of some continuities depending on two topologies by continuities depending only on one topology and the structure of the sets of semi discontinuity points are given. The end of the article is dedicated to several interpretations that facilitate and clarify orientation in the achieved results.

Article
Physical Sciences
Acoustics

Haozhen Wen

,

Yuan Qin

,

Yang Yang

,

WenQing Yan

Abstract: Passaggio is a natural physiological phenomenon during vocal register transitions in singing, with its pitch location varying across individuals. Conventional identification methods rely on auditory judgment or voice type classification, which are inaccurate due to individual differences. In this study, a laser doppler vibrometer (LDV) and an acoustic microphone set were used to synchronously measure laryngeal surface vibration and singing voice,in order to systematically investigate singing passaggio behavior. The data indicate a stable fundamental frequency correspondence between the laryngeal vibration signal and the acoustic signal, which supports the use of amplitude ratios of low-order harmonic peaks in the laryngeal vibration spectrum as relative indicators of structural changes in laryngeal vibration. The result shows that male and female singers exhibit distinct patterns of structural change in laryngeal vibration during passaggio, while consistent patterns are observed within the same sex. For individuals, clear structural transitions in laryngeal vibration are observed at the pitch of passaggio, providing a basis for accurate identification of individual singing passaggio.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Pierre Lefèvre

,

Camille Dubois

,

Antoine Moreau

Abstract: This study formulates collaborative large language model (LLM) agents as a Decentralized Partially Observable Markov Decision Process (Dec-POMDP) and optimizes group behavior using centralized training with decentralized execution (CTDE). A group-relative policy optimization (GRPO) objective is introduced to jointly optimize solution quality, coordination consistency, and response latency. Experiments are conducted on collaborative writing and collaborative coding benchmarks comprising 6,000 multi-agent episodes with 2–4 agents per task. Compared with single-agent and prompt-only collaboration baselines, the proposed approach achieves a 3.1× reduction in task completion time, a 19.4% improvement in output consistency, and a 21.7% increase in coding test pass rate, demonstrating effective performance optimization under partial observability.

Article
Public Health and Healthcare
Public Health and Health Services

Luis Miguel Gallardo

Abstract: Background: Traditional qualitative interview methods often face limitations when applied to low-literacy, collectivist, rural communities where verbal articulation of internal experiences may be culturally unfamiliar or uncomfortable. There is a pressing need for culturally appropriate qualitative methods that facilitate narrative elicitation through accessible, non-threatening modalities.Method Description: This paper introduces the Meta Pets Method, a novel card-based narrative inquiry approach designed for community-based qualitative research in collectivist cultures. The method employs a deck of illustrated cards featuring archetypal animal characters ("Meta Pets") that serve as projective stimuli and narrative prompts. Participants select cards, project personal meanings onto the symbolic imagery, and co-construct stories that reveal inner experiences, values, and perspectives. The method integrates theoretical foundations from narrative inquiry, projective techniques, arts-based research, and visual methods.Application Context: We describe the method's development and application with rural artisan weavers in Rajasthan, India—a low-literacy, collectivist population. The Meta Pets Method facilitated rich narrative data collection where traditional interviews might have been less effective, enabling participants to externalize emotions, explore identity, and share experiences through metaphorical storytelling.Implications: The Meta Pets Method offers qualitative researchers a culturally responsive tool for narrative inquiry in diverse contexts. It addresses methodological gaps in cross-cultural research by providing an accessible, visual, and playful approach that honors collectivist values, accommodates low literacy, and reduces power differentials between researchers and participants. The method has potential applications in community-based participatory research, health research, social work, education, and international development.

Article
Computer Science and Mathematics
Computer Vision and Graphics

Venkat Bhardwaj

,

Akansha Akansha

,

G. Renuka Devi

Abstract: Forest fire poses a significant global threat, endangering ecosystems, biodiversity and the harmony of natural habitat. As the forest fires becomes more frequent and intense, the loss of natural habitat has increased rapidly. Therefore, it becomes important to detect forest fire at an early stage so that prompt and effective measures can be implemented immediately. To address this, we propose a low-cost drone-based forest fire detection and monitoring system that utilizes computer vision and deep learning for real-time forest fire detection. The proposed system uses a custom-built Quadcopter, equipped with the Raspberry pi camera module, to capture the real-time feed. These feeds are analyzed by the YOLOv11n object detection algorithm to accurately detect the fire. The proposed work utilizes an open-source dataset from Roboflow which contains 3426 images. This developed system is tested in various controlled environments demonstrating high mAP score of 93.6% in detecting wildfire. The YOLOv11n model achieves an accuracy of 92% and an approximate 8 frames per second for the test experiment. Therefore, it can be an effective tool for early wildfire detection, notifying timely alerts and aiding in rapid response, which can significantly enhance wildfire prevention and control efforts.

Article
Business, Economics and Management
Business and Management

Eleonora Tankova

,

Iva Moneva

,

Radosveta Krasteva-Hristova

,

Miglena Pencheva

,

Antonina Ivanova

Abstract: Digital transformation has become a cornerstone of circular economy (CE) strategies, yet the intersection between digital innovation and women’s entrepreneurship remains poorly understood. This study examines how digital enablers such as IoT, AI, blockchain, data analytics and platform technologies are represented in CE-related business and management research, while assessing the visibility of gender-inclusive and women-entrepreneurship perspectives. Using a bibliometric design, we retrieved and merged Scopus and Web of Science records (2015–2025), applied de-duplication and relevance screening, and conducted performance analysis and science mapping through bibliometrix (R) and VOSviewer to identify core themes, leading journals, influential authors, collaboration networks and thematic clusters. The findings show a sharp rise of digital-CE scholarship after 2018, dominated by technological perspectives on smart manufacturing, circular supply chains, digital product passports and blockchain-enabled traceability. Four stable clusters emerged: digital circular manufacturing, circular business model innovation, waste and resource management, and policy–social aspects. However, gender-related terms appear in only 1.35% of the corpus, revealing a substantial gap between academic research and EU policy priorities for inclusive digital and circular transitions. The study contributes by integrating a gender-inclusive lens into digital-CE scholarship and outlining a future research agenda that positions women entrepreneurs as critical—yet currently overlooked—actors in shaping digital circular ecosystems.

Concept Paper
Public Health and Healthcare
Public Health and Health Services

Mario J. Passaro

Abstract: Suicidal crises are often framed as discrete events or as outcomes of diagnosable syndromes. The Survival Architecture of Coping (SArC) reframes suicidality as a system state: a late-stage manifestation of an overloaded regulatory architecture. SArC defines coping capacity as an interdependent function of four coupled domains—biological regulation (sleep–recovery and autonomic dynamics), cognitive flexibility (appraisal, set-shifting, inhibitory control), relational co-regulation (access to stabilizing interpersonal feedback), and existential meaning (future-oriented value and narrative coherence). SArC posits that acute risk concentrates when activation (subjective urgency/action-readiness), often accompanied by arousal (physiological mobilization), rises as deployable coping capacity declines, compressing attention, appraisal, and behavioral options. Activation and arousal often covary but are not identical: activation denotes urgency/action-readiness, whereas arousal denotes physiological mobilization that may be high (agitation) or low (shutdown) even when activation remains escape-focused. Integrating allostatic load, attachment-based regulation, process-based psychotherapy, and arousal–appraisal approaches (Passaro, 2025a), SArC describes suicidal experience along a continuum of load–capacity imbalance: low-load contemplation, matched-load engagement, excess-load narrowing, and overload in which shutdown or collapse may be experienced as short-term relief when other downshifts fail. The model generates within-person predictions—for example, that rising activation coupled with cross-domain loss of deployable capacity precedes near-term spikes in escape appraisal—and it motivates multimodal intensive longitudinal assessment (e.g., EMA paired with sleep and autonomic indices). Clinically, SArC shifts the immediate target from ideation suppression alone to restoring deployable capacity and reopening flexible regulation across body, cognition, relationship, and meaning.

Review
Medicine and Pharmacology
Orthopedics and Sports Medicine

Dalibor Krpan

,

Alireza Monajati

,

Aliya Yasmeen

,

Adam Benn

,

Rami Atef Shenouda

,

Patrick R. Hof

,

Markus Kipp

,

Tallal C. Mamisch

,

Anna J. Schreiner

,

Nicola Maffulli

+1 authors

Abstract: Background: Musculoskeletal disorders such as osteoarthritis, chronic low back pain, radicular syndromes and osteoporosis produce major clinical burdens, and noninvasive therapies capable of reaching deep anatomical structures are increasingly needed. Nuclear magnetic resonance therapy (molecular biophysical stimulation therapy; NMRT MBST) applies resonance-based magnetic fields to deliver uniform biophysical stimulation independent of tissue depth. This review synthesizes clinical and mechanistic evidence to evaluate the therapeutic potential of NMRT MBST and contextualize it within emerging deep-tissue biophysical treatment strategies. Methods: A systematic search of PubMed, Ovid Embase and peer-reviewed, published reviews identified 15 studies, including randomized trials, imaging investigations, observational cohorts, long-term follow-ups and blinded veterinary work. Experimental literature examining cellular, metabolic and molecular responses to NMRT MBST was reviewed to align biological effects with clinical outcomes. Results: NMRT MBST is consistently reported as safe, with no treatment-emergent adverse events. Clinical findings indicate improvements in pain, function and, in selected studies, imaging or densitometric parameters across osteoarthritis, spine-related pain, radicular syndromes and osteoporosis. Placebo-controlled effects were demonstrated in finger-joint osteoarthritis and radicular pain, while one robust knee osteoarthritis trial showed no short-term superiority over placebo. Mechanistic studies have shown anti-inflammatory, mitochondrial, redox, anabolic, neurotrophic, epigenetic and circadian effects that closely parallel near-infrared photobiomodulation, supporting the concept of NMRT MBST as a deep-penetrating analogue capable of reaching tissues inaccessible to light. This positions NMRT MBST within a broader therapeutic framework in which biophysical stimulation may modulate metabolic–inflammatory–regenerative axes in deep musculoskeletal and central nervous system (CNS) structures. Conclusions: NMRT/MBST appears to be a safe and biologically coherent deep-tissue biophysical therapy with promising clinical effects. Larger trials, optimized dosing, mechanistic biomarkers and head-to-head comparisons with established modalities are needed to define its therapeutic role and to clarify how deep-acting biophysical interventions may be integrated into future musculoskeletal and CNS care.

Article
Biology and Life Sciences
Anatomy and Physiology

Renato Méndez-Delcanto

,

Felipe J. Aidar

,

Alfonso López Díaz-de-Durana

,

Esteban Aedo-Muñoz

,

Ciro José Brito

,

Nuno Domingos Garrido

,

Victor Machado Reis

,

Pantelis T. Nikolaidis

Abstract: (1) Background: As Para-Powerlifting (PP) athletes need the maximum bench press concentric strength performance during competitions, the velocity of the eccentric phase could be critical to the sport's success. (2) Methods: Through eccentric tempo modification, normative, faster, and slower bench press eccentric velocities were tested on 16 experienced PP athletes. Mean propulsive velocity (MPV), maximum velocity (Vmax), and power were measured during a single bench press set at different loads (90% and 100% of 1RM) and tempos. After the bench press set, Maximal isometric force (MIF), rate of force development (RFD), impulse, variability, and maximal average force (MAF) were obtained through an isometric bench press test. (3) Results: slower and faster tempos were not different in concentric performance than a normative tempo at the 90% 1RM load. A faster tempo generated higher MPV and Vmax than a normative one at the 100% 1RM load. A normative tempo produced higher MIF than a slower tempo, and higher impulse than a faster tempo after a 90% 1RM bench press set. (4) Conclusions: PP athletes seem to have an optimized technique in submaximal loads; however, they may need faster eccentric velocities in the 100% 1RM load to improve their concentric performance.

Article
Public Health and Healthcare
Public Health and Health Services

Lindi Mathebula

,

Charles S Wiysonge

,

Sara Cooper

Abstract: Background: Childhood vaccination remains the cornerstone of public health strategy, substantially reducing global morbidity and mortality, yet suboptimal uptake persists in many settings. In South Africa, the challenge is evident, as evidenced by persistent outbreaks of vaccine-preventable diseases. Addressing localised immunisation shortfalls requires elucidating the complex interplay of factors beyond conventional access barriers. This sub-study fills an important empirical gap by thoroughly analysing the demand-side factors from the viewpoint of primary service recipients. Methods: Utilising an exploratory qualitative research design, thematic analysis was applied to interview data (n=25 caregivers) collected via a purposive sampling strategy designed to capture maximum variation in experiences within targeted low-uptake sub-districts. Interpretation of the data was systematically guided by the World Health Organization’s Behavioral and Social Drivers (BeSD) framework. The latter consists of four domains, namely, “Thinking and Feeling”, “Social Processes”, “Motivation”, and “Practical Factors”. Findings: Analysis across the BeSD domains revealed a paradox: a remarkably high level of caregiver motivation was systematically challenged by widespread practical barriers. In the Thinking and Feeling domain, widespread conviction regarding the vital benefits of vaccination co-existed with significant anxiety concerning minor side effects (e.g., pain and fever), which sometimes precipitated missed subsequent appointments. Caregivers frequently accepted immunisation as a social routine despite having limited knowledge of the diseases it prevents. Social Processes demonstrated that while decision-making authority rested primarily with mothers, compliance relied on delegating logistical responsibilities to extended family members. Critically, reports of poor communication, judgment, or negative attitudes among healthcare workers undermined trust and acted as barriers to sustained engagement. Within the Practical Factors domain, structural constraints frequently overshadowed high intent, with pervasive issues such as long waiting times and financial costs cited as the main reasons for missed appointments. Conclusion: Caregiver acceptance remains robust, but attainment of optimal coverage is constrained by systemic failures in patient-provider communication and persistent logistical barriers within the public healthcare delivery system. Strategic public health interventions must therefore move beyond addressing only attitudinal opposition to prioritise targeted efforts that mitigate structural constraints and reinforce personalised, empathetic communication to sustain caregiver confidence and adherence.

Article
Medicine and Pharmacology
Other

Berna Yıldırım

,

Burcu Biltekin

,

Mete Hakan Karalök

,

Ayhan Bilir

Abstract: Background/Objectives: Endometrial cancer frequently develops resistance to thera-py, partly due to the ability of tumor cells to adapt to cellular stress through non-apoptotic mechanisms. Mitochondrial dysfunction and cytoskeletal remodeling are increasingly recognized as key components of stress adaptation; however, their structural relationship under pharmacological stress in three-dimensional (3D) tumor models remains poorly characterized. The present study aimed to investigate the ul-trastructural and phenotypic effects of lithium chloride (LiCl)–induced stress in 3D endometrial cancer spheroids, with a particular focus on mitochondrial alterations and intermediate filament organization. Methods: Three-dimensional spheroids gen-erated from Ishikawa endometrial cancer cells were exposed to lithium chloride at concentrations of 1, 10, or 50 mM for defined time periods. Cell viability, proliferative activity, and clonogenic capacity were assessed using Trypan Blue exclusion, BrdU in-corporation, and soft agar assays. Ultrastructural changes were examined by trans-mission electron microscopy to evaluate mitochondrial morphology, cytoplasmic or-ganization, and intermediate filament distribution. Results: LiCl exposure resulted in a dose- and time-dependent reduction in cell viability, proliferation, and clonogenic potential in 3D spheroids. Ultrastructural analysis revealed pronounced mitochondrial swelling, cristae disorganization, and membrane-associated mitochondrial alterations. These changes were consistently accompanied by conspicuous accumulation and re-organization of intermediate filaments in close spatial proximity to damaged mito-chondria. Across all experimental conditions, classical apoptotic ultrastructural fea-tures, including chromatin condensation and apoptotic body formation, were not ob-served, despite substantial organelle-level alterations. Conclusions: Together, these observations indicate that lithium chloride elicits a stress phenotype in 3D endometrial cancer spheroids that primarily manifests at the organelle and cytoskeletal levels, ra-ther than through classical apoptotic execution. Although descriptive in nature, the present study highlights intermediate filament accumulation as a prominent structural feature of lithium-induced mitochondrial stress and establishes a structural reference point for future studies aimed at dissecting mitochondrial–cytoskeletal interplay dur-ing pharmacological stress in endometrial cancer.

Article
Engineering
Electrical and Electronic Engineering

Mehmet Zahid Erel

Abstract: Thermoelectric generators (TEGs) enable compact waste-heat energy harvesting but require high-gain DC–DC conversion due to their low output voltage for microgrid interfacing. This work proposes a novel TEG-supplied two-stage architecture consisting of a perturb and observe (P&O)-based MPPT boost converter followed by a modified Z-source converter regulated through an advanced control strategy. The modified Z-source topology enables high voltage gain without extreme duty ratios and mitigates switching losses by eliminating diode-related reverse-recovery effects via synchronous operation. To enhance dynamic performance, an advanced model predictive control (MPC) approach is adopted and benchmarked against conventional MPC and sliding mode control (SMC). Simulation results under hot-surface temperature variations demonstrate that the proposed system maintains stable 400-V DC bus regulation at a 100-W output level. In contrast, conventional MPC exhibits switching-frequency deviations that increase switching losses during transients, while conventional SMC suffers from significant voltage deviations. After the temperature variation tests, the proposed control strategy is subjected to a ±20% load test, in which it maintains 400-V regulation with nearly fixed-frequency operation, confirming its superior dynamic suitability for TEG-based systems operating at 50 kHz. The proposed innovative design provides a new perspective for TEG researchers while supporting sustainable waste-heat energy utilization.

Article
Computer Science and Mathematics
Computer Science

Sheriff Adefolarin Adepoju

,

Mildred Aiwanno-Ose Adepoju

Abstract: eBPF is increasingly used around databases, but prior systems and papers often conflate goals and therefore blur the trade space: instrumentation versus control versus in-kernel state. This impedes principled comparisons and hides the kernel constraints that determine feasibility. We present a unified analysis organized into three modes of database–kernel integration via eBPF: observability (deriving DB-relevant signals from kernel and user-space hooks), policy injection (installing workload-specific cache and networking policies at kernel choke points), and kernel-resident state (providing safe transactional state semantics for eBPF programs beyond raw maps). For each mode, we characterized the hook placement, state model, and verifier/synchronization/portability constraints that shape feasibility, and then analyzed representative systems (programmable page-cache policies, XDP ingress offload, and ACID key-value with WAL export) against this framework. We show where microsecond overheads compound to core-scale costs when user-kernel crossings dominate tail latency and which integration mode fits the workload patterns. The outcome is a decision framework that guides when to measure, when to specialize the kernel policy, and when to introduce the kernel-resident state, enabling reproducible performance work without custom kernels.

Article
Public Health and Healthcare
Public Health and Health Services

Lou Migliorini

,

David A. Schwartz

Abstract: Background: The Bacillus Calmette–Guérin (BCG) vaccine against tuberculosis is the most widespread vaccine in the world. Discovered by French investigators Albert Calmette and Camille Guérin at the Pasteur Institute, it remains the only effective vaccine against tuberculosis infection. This report describes the recognition and identification of a previously unknown French handwritten laboratory notebook prepared by Drs. Calmette and Camille Guérin recording their experiments performed during the development of the BCG vaccine. Methods: The notebook was examined, translated into English, photographed and the experiments analyzed. Results: The laboratory notebook consists of 69 leaves written in 2 hands, one of which corresponds to that of Albert Calmette. This handwritten notebook contains details of experiments that were performed during the development of the BCG vaccine at the Pasteur Institute by Drs. Calmette and Guérin. These include experimental inoculations of rabbits and guinea pigs describing the pathology including skin lesions, inflammatory reactions, organ pathology and survival. The experiments describe varying inoculative dosages of the bacteria, and different routes of administration including intraperitoneal and subcutaneous injections and administration of bacilli in the ear. In those cases where the animal had died following inoculation of tubercle bacilli, necropsy was performed and the organs examined and the pathology findings described. It describes experimental animal deaths and results of necropsies. Conclusions: this previously unknown notebook is a highly organized and detailed record of investigations using tuberculosis in animal experiments and microbiological culture to produce a safe and effective vaccine, first used in humans in 1921.

Article
Biology and Life Sciences
Virology

Tyler Michalka

,

Abid Shah

,

Tiffany Liang

,

Maged Hemida

Abstract: Feline immunodeficiency virus (FIV) is a lentivirus sharing significant structural and pathological similarities to human immunodeficiency virus (HIV), making it a valuable surrogate model for HIV vaccine design and development. Currently, there is no available effective vaccine could protect cats against FIV infection. This study aims to use some artificial intelligence and immunoinformatic to design a novel multi-epitope DNA vaccine targeting some conserved regions of FIV’s gag, pol, and env genes. The mapped B and T-cell epitopes across the key proteins of the FIV genomes were screened for their ability to trigger strong immune responses, while avoiding allergenic or toxic responses and were linked to the immune adjuvant PADRE. Analysis of the vaccine construct revealed a stable, soluble, and biocompatible vaccine construct with a well-folded tertiary structure capable of binding toll-like receptor 9 (TLR9) and eliciting a robust humoral and cellular immune response. These results demonstrate a promising FIV vaccine candidate with potential insight into future directions in next generation HIV vaccines. Further experimental validation is required to confirm the potential protective power of these putative vaccines in the protection of cats against FIV natural field infection.

Article
Medicine and Pharmacology
Otolaryngology

Andy J Beynon

,

Mehmet K Ercan

,

Sammy M Schouten

,

Thijs TG Jansen

,

Henricus PM Kunst

Abstract: Background: A group of patients with untreated unilateral vestibular schwannoma (UVS) was observed in previous clinical trials, and the results indicated a reduction in the vestibulo-ocular reflex (VOR) on the side of lesion. However, in a subset of patients, a loss of VOR gain was also observed on the contralateral (non-tumor) side, which may indicate the presence of contralateral neural crosstalk. Methods: To understand our previous clinical findings, the present study has expanded its population to investigate whether these unexpected findings are recognized in a significantly larger population of patients with UVS (n=640). Retrospectively, mean VOR gains of all semicircular canals (SCC) were obtained using video head impulse tests (vHIT) and compared between ipsi- and contralateral side of lesion. To eliminate any potential bias resulting from procedural effects, vHIT data was also obtained from a control group of 72 healthy subjects. Results: As expected, a VOR gain reduction was identified on the side of lesion in a substantial proportion of patients with UVS, varying ranging from 19.4% (anterior SCC) to 39.7% (posterior SCC). More interesting was the observation of a significant proportion of patients (21.9%) exhibiting a significant VOR reduction in posterior semicircular canal on the contralateral side, with a strong correlation with the ipsilateral side (r = 0.70). In relation to this phenomenon, our data further demonstrates that possible crosstalk of the superior branch of the vestibular nerve is of less influence on the contralateral side VOR gains compared to that of the inferior branch. Conclusion: Firstly, a reduced VOR gain in the contralateral posterior semicircular canals was found. Secondly, correlations between the inferior vestibular branches in UVS patients were comparable to the control group. These results may support the interactions such as bilateral commissural connectivity between vestibular nuclei.

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