Abstract:

Background: Preliminary reports have suggested a batch-dependent safety signal for COVID-19 vaccines. It is important to establish if these findings can be replicated. Methods: We used publicly available nationwide data from Germany spanning the first 3.5 years of the vaccination campaign to calculate weekly rates of spontaneously reported suspected adverse events (SAEs) per 1 000 administered vaccine doses. Results: SAE rates ranged between 2.2 and 22.8 per 1 000 doses and women accounted for 72% of all SAEs. Crucially, SAE rates for Comirnaty (Pfizer-BioNTech), Spikevax (Moderna), and Vaxzevria (AstraZeneca) were very high in the initial phase of vaccination rollout and hereafter declined precipitously. For example, SAE rates in weeks 1-4 of 2021 were 8.2, 50.8, and 620.9 per 1 000 doses of Comirnaty, Spikevax, and Vaxzevria, respectively, but fell to 4.4, 11.6, and 7.4 per 1 000 doses in weeks 12-16 of 2021. Conclusions: SAE rates in Germany were highly elevated in the initial phase of COVID-19 vaccination rollout and then fell precipitously, a pattern compatible with a batch-dependent safety signal. Furthermore, there was a considerable overrepresentation of women with SAEs. These preliminary results call for more definitive studies of batch-dependent COVID-19 vaccine safety.

Abstract:

Proper planning of athletes’ workload during training, especially in preparation for championships or other important competitions, is crucial to avoid serious health complications. Athletes are exposed to significant physical, emotional and psychological stress during training and competitions. The assessment of athletes’ physiological parameters before and after training is important not only for their athletic performance but also for their general health, both during active participation in sport and later in life. The aim of this study was to determine anthropometric characteristics and changes in the retinal vessel diameters, arterial blood pressure, heart rate, cerebrospinal fluid pressure and blood oxygenation in all handball players before and after competitive training and to relate these parameters to the most important modifiable cardiovascular risk factors. Methods. The study took place as part of training sessions in training centers. The test subjects were instructed to abstain from sport and alcohol for 24 hours, not to consume any caffeinated or carbonated drinks for 6 hours and not to eat for at least 2 hours before the measurements. Baseline measurements were carried out on all handball players. The experiments began at 18:00. On arrival, physical activity was assessed, and anthropometric measurements were taken. Participants were then asked to rest in a seated position. After a 10-minute rest, arterial blood pressure, heart ratio and blood oxygenation were measured. The retinal fundus of professional handball players was imaged immediately before and after a competitive match using a non-mydriatic fundus camera. Results. 13 handball players took part in the study. After training, the average weight of the subjects decreased by 0.515 (0.41) kg, systolic blood pressure by 3.85 (15.15) mmHg, diastolic by 4.85 (9.045) mmHg, MAP by 4.565 (7.87) mmHg, CSFP by 0.79 (1.44) mmHg, SpO2by 1.15 (1.625) %. After training, only the average heart rate increased by 38.23 (36.33) bmp. Mean retinal arterial diameter decreased slightly in both eyes, whereas mean venous diameter increased. Conclusions. We found a significant increase in mean heart rate after training, but a slight decrease in the other parameters analyzed: systolic blood pressure, diastolic blood pressure, MAP, CSFP, SpO2 and weight. We would attribute the decrease in these indicators to insufficient recovery of fluid balance. Venous measurements exhibited greater inter-individual variability that arterial measurements, with a non-significant trend toward post-exercise arterial narrowing and venous widening.

Abstract:

Objectives: To review the conceptual evolution, mechanical principles, and clinical outcomes of the Eight-Chop Technique, and to clarify its position within modern cataract surgery. Methods: A narrative review was conducted focusing on the historical development of nuclear fragmentation strategies, including sculpting-based techniques, divide-and-conquer, chop-based methods, femtosecond laser–assisted cataract surgery, and prechop techniques. Particular attention was given to the wedge-induced fracture mechanism, geometric optimization through eightfold division, and integration with modern fluidics systems. Published clinical studies and the author’s clinical data were reviewed and synthesized across a wide range of cataract subtypes. Literature relevant to nuclear fragmentation techniques and phacoemulsification fluidics was identified through searches of PubMed and Google Scholar using combinations of keywords including “phacoemulsification,” “nuclear fragmentation,” “phaco-chop,” “prechop,” “active fluidics,” and “cataract surgery.” Both original studies and review articles published in English were considered. Reference lists of relevant articles were also screened to identify additional sources. Results: In both standard cataracts and challenging conditions—including hard nuclear cataracts, white cataracts, small pupils, shallow anterior chamber, microcornea, diabetic eyes, and pseudoexfoliation syndrome—the Eight-Chop Technique consistently demonstrated reduced phaco time, cumulative dissipated energy, and irrigation volume compared with conventional techniques. Corneal endothelial cell density loss was generally limited to approximately 1–3%, even in high-risk subgroups. Postoperative intraocular pressure showed a sustained reduction over mid- to long-term follow-up. These subtype-specific outcomes are integrated in Table 1, highlighting the reproducibility and low invasiveness of the technique regardless of nuclear hardness or anterior segment anatomy. Conclusions: The Eight-Chop Technique is a segmentation-first nuclear fragmentation strategy based on complete in-the-bag prefragmentation using a wedge-induced fracture mechanism. Its compatibility with modern fluidics systems, including active fluidics systems, enhances anterior chamber stability and reinforces its minimally invasive profile. By reducing energy use, fluid load, and zonular stress, Eight-Chop Technique may represent a rational and versatile option for contemporary cataract surgery, particularly in high-risk eyes.

Abstract:

The Dongchuan District of Kunming City lies in the transition zone between the Yunnan-Guizhou Plateau and the Sichuan Basin, hosting numerous landslides that pose a serious threat to local lives and property. Therefore, compiling a comprehensive landslide inventory and analyzing the relationships between landslide spatial distribution and influencing factors are of significant importance for geological hazard prevention. This study focuses on the Dongchuan District. High-resolution remote sensing imagery was interpreted to establish a landslide inventory, and the spatial distribution and geometric characteristics of landslides were systematically analyzed. The results show that a total of 1,623 landslides were identified, covering an area of 10.36 km². Landslides predominantly occur at elevations of 1,000-2,000 m, on slopes of 20°-45°, with aspects of 255°-285°, relief between 150-400 m, annual rainfall below 825 mm, and within a distances of 1,000 m from rivers and 3,000 m from faults. Four landslide clusters were delineated along the Xiao River Fault, highlight the significant influence of the fault on the spatial distribution of landslides. Most landslides are longitudinal in planform, with travel distances (L) of 50-450 m and heights (H) from 25 to 350 m, exhibiting allometric relationships between these parameters and volume. The mean H/L ratio is 0.56 (corresponding to a mean reach angle of 29°), significantly higher than that observed in Baoshan City (mean reach angle of 21°). The results would be helpful for further understanding landslide initiation mechanisms and spatial distribution patterns on the northern margin of the Yunnan-Guizhou Plateau and providing valuable data support for subsequent landslide hazard risk assessment in this region.

Abstract: Background: Aging is shaped by interdependent molecular processes captured by the hallmarks framework, in which epigenetic alterations stand out as a potentially modifiable regulatory layer. DNA methylation (DNAm) patterns change with age and can be summarized by epigenetic clocks that estimate biological age, pace of aging, and risk-related phenotypes. Yet, the extent to which interventions reproducibly modulate DNAm-based biomarkers across tissues and species remains uncertain. Methods: A systematized review of longitudinal intervention studies (2010–2025; English/Spanish) was conducted in PubMed, Scopus, and Cochrane CENTRAL, with selection documented using PRISMA. Human eligibility included randomized controlled trials (RCTs), non-randomized controlled studies, and pre–post designs (n≥10; adults ≥18 years). Preclinical eligibility included longitudinal mammalian studies (n≥5 per group). Outcomes were changes in DNAm-based epigenetic age (years) and/or pace of aging (e.g., DunedinPACE). Data were extracted into a standardized matrix (clock, tissue, effect direction/magnitude, safety, RoB_overall) and synthesized narratively; meta-analysis was not performed due to heterogeneity. Results: Thirty-five longitudinal studies were included (29 human, 6 preclinical). Lifestyle interventions in humans generally showed modest effects, with more consistent signals when exposure was sustained and accompanied by plausible physiological changes (e.g., prolonged calorie restriction affecting DunedinPACE, with effect sizes up to d=−0.43 at 12 months and d=−0.40 at 24 months in higher-adherence participants). Exogenous compounds showed higher heterogeneity and mixed evidence, including robust null epigenetic findings in some trials (e.g., metformin adjusted ITT differences ranging from −0.91 to +0.82 years across clocks, all p≥0.18) alongside favorable signals in smaller analytic subsets or open-label settings (e.g., bezisterim sub-study with reductions of −3.68 years in SkinBloodAge, −5.00 in Hannum, and −4.77 in InflammAge). Blood/circulation-derived interventions produced some of the largest reported effect sizes but also raised interpretation challenges: therapeutic plasma exchange with a sham arm reported epigenetic age decreases of ~1.3–2.6 years depending on the clock and regimen, with pronounced shifts in immune/inflammation-sensitive clocks; the apparent benefits waned after treatment cessation. Unexpectedly, repeated plasmapheresis in donors was associated with increases in several clocks and DunedinPACE per procedure (~+0.16–0.26 years per session across GrimAge-family clocks and ~0.003±0.001 DunedinPACE units per session). In rodents, plasma fractions/exosome-rich preparations and heterochronic parabiosis reported large percentage reductions across tissues, with strong dependence on exposure duration and concerns about translational uncertainty (up to ~77.6% in liver and ~68.2% in blood in one plasma-fraction study). Evidence for partial reprogramming (OSKM) was limited to a single rat study with small, near-significant trends in hippocampus-based clocks (two-sided p=0.064–0.088 across three clocks). Conclusions: DNAm-based epigenetic biomarkers are modifiable by interventions in mammals, but effects are heterogeneous and depend on the intervention, clock construct (age vs pace/risk signatures), biological matrix, tissue, follow-up duration, and study design. A single notion of “epigenetic rejuvenation” is not supported; instead, intervention effects appear domain-specific and must be interpreted in relation to what each clock measures.

Abstract:

This paper addresses the practical challenge of inadequate motivation for energy enterprises to reduce pollution and carbon emissions in the context of increasing environmental pollution and carbon emissions. From the perspective of the informal institution of reputation incentives, this paper constructs a tripartite evolutionary game model involving energy enterprises, the public and the government. Through theoretical derivation and numerical simulation, the paper systematically analyzes the influence path of reputational gains and losses on enterprises' technological transformation decisions, and examines the moderating effects of key parameters such as transformation costs and government subsidies. The conclusions are as follows: (1) The reputation incentive mechanism regulates the cost-profit structure of enterprises through the dual effects of reputation gains and losses, and has a significant driving effect on the technological transformation and pollution reduction and carbon emission reduction of energy enterprises. (2) The three-party strategy exhibits dynamic dependence and collaborative evolution characteristics. The system converges to the ideal equilibrium of enterprise transformation, public participation, and government empowerment, depending on the relative magnitudes and coupling relationships of key parameters such as transformation costs. (3) Government subsidies provide short-term incentives for enterprises to undergo transformation, but they also impose long-term constraints. Therefore, government subsidies need to be combined with the reputation incentive mechanism to achieve sustainable governance. These findings provide a theoretical foundation and practical reference for designing incentive-compatible policy combinations and promoting the deep low-carbon transformation of energy enterprises.

Abstract: Keith numbers form a rare class of integers defined by a digit-generated linear recurrence in which the original number reappears within its own sequence. Although known for several decades, their structural properties and the mechanisms underlying their extreme sparsity remain poorly understood.In this work, we introduce a dynamical reformulation of Keith sequences by embedding the digit recurrence into a discrete state-space system governed by a companion matrix. Within this framework, the recurrence trajectory can be interpreted as an orbit of a finite-dimensional linear dynamical system. This representation enables the introduction of trajectory observables—including informational inertia, an admissibility field, and a stability functional—which characterize the evolution of the sequence.Using this formulation, we analyze the spectral structure of the recurrence operator and show that the reappearance of the original integer corresponds to a transient intersection between the expanding trajectory and a fixed identity hyperplane in state space. Representative numerical scans over increasing integer ranges confirm that such identity-return events are extremely rare and occur only under tightly constrained dynamical conditions.These results suggest that Keith numbers can be interpreted as non-generic return events in a linear dynamical system determined by digit-based initial conditions. The proposed framework provides a dynamical explanation for their empirical sparsity and offers a basis for studying digit recurrences using tools from dynamical systems, spectral analysis, and computational number theory.

Abstract: Computational methods for big data music research mostly come from the field of music information retrieval. Through feature extraction and machine learning, many practical tasks have been automated, like genre recognition and playlist generation. However, for musicological purposes, conventional features do not provide enough insight into the music production process. In this study, we evaluate how well Mel-frequency cepstral coefficients and recording studio features reveal aspects of early house and techno music from the United States of America and Germany. The explorative study is an exemplary case-study where music production plays an essential role. Further studies may reveal how much the findings transfer to other producer-driven music, like hip hop and electronic dance music.

Abstract: Engineering design increasingly uses generative AI to explore large form spaces, yet concept-driven generation is only useful if observers consistently perceive the intended attribute. We propose a ranking-based human validation layer that tests whether AI-generated concept-intensity gradients are interpretable, reliable, and usable. For each Product–Concept pair, a controlled generative workflow produced six variants intended to increase concept expression (A–F). In an online study, 26 design engineers ranked the variants by perceived intensity, with an optional not-applicable (NA) flag when category recognition failed. We analyse rankings with heatmap diagnostics, inter-observer agreement, monotonic alignment with the intended order, and Plackett–Luce aggregation with uncertainty, while using NA trends to bound operational ranges. Across nine pairs, most gradients aligned with the intended direction, but performance depended on the concept and product context, revealing both stable and failure-prone segments. The approach provides an evidence-based gate for concept implementation in AI-generative design.

Abstract: The integration of three-dimensional (3D) printing and virtual surgical planning (VSP) has introduced a new standard in spinal surgery, enabling highly individualized preoperative preparation and intraoperative execution. By virtually reconstructing patient anatomy, surgeons can identify critical vascular corridors, analyze endplate morphology, determine optimal interbody cage geometry for best anatomical fit, and predefine screw trajectories and entry points with exceptional accuracy. This level of planning reduces intraoperative uncertainty and minimizes the risk of implant malposition, particularly in anatomically complex scenarios, such as the current case report. Quantitative assessment of alignment correction can also be performed preoperatively, allowing the surgeon to model and predict postoperative spinal balance with greater precision. This technology is particularly advantageous in congenital spinal anomalies, such as hemivertebrae, where orientation can be challenging and anatomical landmarks are often distorted or partially obscured. We report the application of 3D printed patient-specific implants (PSIs) in conjunction with VSP to perform a single-level, stand-alone anterior lumbar interbody fusion (ALIF) for the treatment of congenital scoliosis due to a left hemivertebra, associated with progressive left L5/S1 foraminal stenosis. The patient presented with severe left L5 radicular pain and motor–sensory radiculopathy. The use of a PSI facilitated precise reconstruction of the spinal column, optimized implant fit and enhanced surgical accuracy in this technically complex case.

Abstract: Background/Objectives: Severe asthma in routine practice often involves long-standing disease, multimorbidity, and prior biologic failure, settings underrepresented in pivotal tezepelumab trials. This study evaluated 52 week real world effectiveness and safety of tezepelumab in a highly comorbid, predominantly T2 high, biologic experienced severe asthma cohort from the Canary Islands. Methods: TEZNERIFE is a multicenter, retrospective phase IV study including consecutive adolescents and adults with GINA Step 5 severe uncontrolled asthma treated with tezepelumab 210 mg every 4 weeks for 12 months. Clinical outcomes, lung function, type 2 biomarkers, upper airway symptoms, and Biologics Asthma Response Score (BARS) were assessed at baseline, 26 weeks, and 52 weeks. Results: Fifty six patients (mean age 53.5 years, 71% female, mean asthma duration 30 years, 84% T2 high; 71% with ≥1 prior biologic) were analyzed. ACT improved from 11.5±3.7 to 15.9±4.7 at 26 weeks and 17.5±4.7 at 52 weeks (both p<0.0001), while annualized exacerbations declined from 2.79±2.0 to 0.50±0.72 and 0.51±0.89 (both p<0.0001). Maintenance oral corticosteroid dose fell from 10.2±8.3 to 6.9±2.4 mg/day at 52 weeks (p=0.014). FEV1% predicted increased from 69.3±19.2% to 75.3±17.7% and 76.2±20.6% (p=0.004 and p=0.001), and blood eosinophils decreased from 234±231 to 146±120 and 147±110 cells/µL (p=0.001 and p=0.013). At one year, 18.9% and 67.9% were classified as good and intermediate responders by BARS; 13.2% were insufficient responders. Two patients discontinued due to non serious adverse events while no treatment related serious events occurred. Conclusions: In this difficult to treat, multimorbid, biologic experienced population, tezepelumab achieved sustained improvements in asthma control, exacerbations, lung function, eosinophilic inflammation, and corticosteroid exposure over 52 weeks, supporting upstream alarmin inhibition as a versatile strategy in complex severe asthma.

Abstract:

Background: Pseudomonas aeruginosa is an opportunistic pathogen with both intrinsic and acquired antimicrobial resistance. High-risk clones are associated with carbapenem resistance because they frequently harbour and disseminate carbapenemase genes and other resistance determinants, enabling their persistence and spread in healthcare settings. Carbapenem-resistant strains have limited treatment options. However, genomic data on high-risk clones circulating in Ghana remain limited. Methods: This cross-sectional study was conducted between December 2023 and January 2024 in eight government hospitals in Accra, Ghana. Clinical isolates were collected from multiple specimen types and identified using standard antimicrobial susceptibility testing in accordance with CLSI guidelines to determine resistance profiles, and subsequently confirmed by MALDI-TOF-MS, Whole-genome sequencing was carried out using the Illumina NextSeq 2000 platform. Bioinformatic analyses were then conducted to determine sequence types, identify antimicrobial resistance genes and virulence factors, and assess phylogenetic relationships among the isolates. Results: High-risk international clones (ST235, ST244, ST308, and ST773) predominated. Low SNP differences (≤10 SNPs) indicated recent clonal transmission within and between hospitals. Serotype O11 was dominant and strongly associated with high-risk clones. Isolates carried multiple resistance determinants, including aminoglycoside-modifying enzymes and ESBL genes (blaCTX-M-15, blaTEM-1B) — carbapenemase genes, particularly blaNDM-1, coexisted with blaOXA-50 variants. Findings demonstrate local clonal expansion, global relatedness, and the emergence of a novel sequence type (ST5336) in Ghana. Conclusion: High-risk clones, especially ST773, are widely circulating in hospitals across Accra, indicating ongoing transmission and clonal expansion. The emergence of the novel ST5336, emphasize the urgent need for enhanced genomic surveillance and antimicrobial stewardship in Ghana. Significance of this research article: This work strengthens the evidence base needed to inform infection prevention strategies, antimicrobial stewardship programs, and the implementation of routine genomic surveillance to curb the spread of high-risk, carbapenem-resistant clones in Ghana and similar resource-limited settings.

Abstract:

The Gibbs Paradox (concerning the entropy of mixing and entropic extensivity) was explored in depth by Edwin Jaynes (1992). We take up Jaynes’ treatment, considering the special cases for which entropy is (approximately) extensive, and the general case in which it is not. We also explore the Holographic Principle which (strictly speaking) excludes the extensivity of entropy. The formalism of Quantitative Geometrical Thermodynamics shows that, being isomorphic to energy, it is entropy production (not entropy) that is extensive. As a corollary, Shannon information is also not extensive, although information production is extensive.

Abstract: According to its published mission, the European Collaborative Cloud for Cultural Heritage (ECCCH), a most recent flagship initiative of the European Commission, cur-rently being developed by the EU-funded project ECHOES, is “…a digital ecosystem designed to serve as a platform for cultural heritage professionals, researchers, and in-stitutions across Europe… to unify Europe’s fragmented cultural heritage sector through advanced digital collaboration…”. While recognizing that “…one of the most persistent challenges in the European cultural heritage sector is the dispersion of data in incom-patible formats and isolated institutional practices…”, the ECCCH advances “…a unified approach (that) will radically transform and greatly facilitate … collaborative research…”, promoting the engagement with small, peripheric Cultural Heritage (CH) institutions and providing (tangible and intangible) CH data under their custody. The article describes an experiment in assessing the readiness of available digital data on a specific type of CH objects, namely Cypriot Late Bronze Age figurines. Most of the ca. 170 figurines un-earthed were found in Cyprus, where they were also produced. Out of these, ca. a third are hosted in museums in Cyprus, and the others are dispersed in some 36 museums, primarily in the UK, museums across ten EU countries, the USA and the Russian Fed-eration. Less than half of them provide, through their digital, open-access collections catalogue, information on these figurines. The study reported here investigated the usefulness of this information for conducting synthetic research on their nature and the socio-cultural role they may have fulfilled while in use in the past. Consequently, the study explored the potential of the information provided by these museums to be inte-grated and expressed through the Heritage Digital Twin concept, at the core of the ECCCH.

Abstract: An extensive survey of early blight of tomato was conducted in Peshawar and Hazara divisions of Khyber Pakhtunkhwa province, during the fruit bearing period of 2014 of the crop. Comparatively more disease incidence and severity was observed in Peshawar than Hazara Division. Data also revealed that more disease was prevalent in district Haripur than Abbottabad and Mansehra. The isolates of Alternaria solani collected during the survey were different in terms of their cultural characteristics and aggressiveness. Isolates from Peshawar division showed rapid growth on Potato Dextrose Agar medium and produced higher number of spores ml−1 as compared to isolates collected from Hazara Division. Moreover these also produced the largest size lesion (20.6mm) when compared with those collected from Hazara Division. A positive linear trend was observed when lesion size was regressed over colony diameter and spores concentration indicating that isolates showing aggressiveness also showed more radial growth and produced more spores mlˉ1. The studies also confirmed the existence of cultivar specific aggressiveness amongst the isolates of A. solani in screen house experiment. Isolates adapted on respective cultivars caused high disease severity, number of lesions per plant and lesion size with concurrent reduction in yield. Isolate AsRJ previously adapted on variety Red Jambo when inoculated on the same variety produced high disease severity (64.02%) and lesion size (8.2mm), with the lowest yield (436.71g). A similar trend was observed for other isolate and cultivar combinations which could have serious implications for cultivation of a particular variety on vast acreages over time.

Abstract: Background: Knowledge management in global health is essential in response to ageing populations, increasing morbidity, and rising expectations of care. The Knowledge Model about Person Care promotes health systems organized around individuals rather than diseases. Within this framework, vulnerability—understood as the risk of physical or moral harm—can be assessed through Basic Care Variables (BVC) that determine individuals’ need and capacity for self-care. Primary care health information systems provide an opportunity to operationalize these variables at the population level. Methods: This study applies Deductive Methodology to extrapolate community-level health indicator data to population-level vulnerability measures. Using the electronic Primary Care Objective Monitoring tool (e-SOAP) from the Community of Madrid, we analyzed health and social care indicators derived from primary care clinical information systems. The mathematical architecture of selected indicators was used as an approximation to Model-Based Systems Engineering. Results: Primary care indicators enabled the identification and aggregation of community-level data reflecting BCV. The system supports multi-level analysis (regional, managerial, institutional, and professional), facilitating grouped and anonymized data extraction for future vulnerability assessment. Conclusion: A minimum set of primary care indicators can effectively estimate community vulnerability, supporting person-centred health system management and informed decision-making.

Abstract: We evaluated global radiotherapy practices in the management of early-stage (AJCC/UICC 8th edition stages I-II) glottic cancer (ESGC). A cross-sectional online survey was conducted in March 2025 across centers worldwide. Data was collected on clinical practices, including staging, CT simulation, target volumes delineation, organs-at-risk contouring, radiotherapy techniques, dose and fractionation schedules, treatment delivery techniques, and image guidance practices. A total of 181 responses were received, primarily from Asia (41.4%) and Europe (24.3%). Most respondents were from non-academic public centers (44.2%), with multidisciplinary team involvement reported by 84.5%. Head and neck CT scan was the most used staging modality (80.1%). Intensity-Modulated Radiation Therapy was the most common planning technique (82.9%). Hypofractionated radiotherapy schedules predominated for T1 (84%) and T2 (72.4%) disease. T1a was typically treated with whole-larynx target volume (72.4%). Use of ipsilateral involved vocal cord irradiation varied by geographical region (p = 0.015), being most common in North America (44.8%) and Europe (38.6%). Accelerated fractionation for T2 also differed significantly (p < 0.001), with the highest use reported in North America (41.4%). Daily Cone-Beam Computed Tomography was acquired by (58.2%). 70% of respondents expressed interest in the results of a future phase III randomized trial comparing stereotactic body radiation therapy to conventional radiotherapy. Significant global variations in radiotherapy practices for ESGC were observed, likely reflecting disparities in access and differences in institutional protocols. The development and implementation of standardized, evidence-based global guidelines are essential to harmonize care, minimize toxicity, and improve outcomes for patients with ESGC.

Abstract: The Johnson–Mehl–Avrami–Kolmogorov (JMAK) formalism provides a classical framework for describing polymer crystallization kinetics; its applicability under finite-domain confinement requires quantitative assessment. In this work, the influence of one-dimensional geometric restriction on cylindrical growth in polymer thin films is investigated using a stochastic Monte Carlo approach. The model considers site-saturated nucleation on randomly distributed cylindrical nanofibers with constant radial growth velocity under hard-wall boundary conditions. Crystallization kinetics were evaluated through automated segmented regression of the double-logarithmic JMAK representation. Under confinement, the Avrami plot departs from single-slope linearity and exhibits two successive quasi-linear regimes characterized by effective parameter pairs (n₁, ln k₁) and (n₂, ln k₂). The primary exponent n₁ remains thickness-independent, consistent with early-stage radial expansion prior to boundary interaction. The secondary exponent n₂ displays a non-monotonic dependence on reduced film thickness, reflecting the competing influence of wall-induced truncation and inter-fiber impingement on late-stage transformation. These results support a geometric interpretation in which finite-domain constraints modify effective growth dimensionality and provide a reproducible framework for analyzing dual-regime Avrami behavior in confined crystallization systems.

Abstract: Early cancer detection has historically relied on episodic, population-based screening strategies interpreted against fixed thresholds. Although effective in selected contexts, such approaches detect disease primarily after structural or biochemical abnormalities become overt. Advances in genomics, liquid biopsy, and metabolomics now permit a conceptual transition from static screening toward longitudinal, biologically calibrated surveillance. This review proposes an integrated early-detection architecture grounded in four complementary dimensions of tumorigenesis: inherited susceptibility, somatic field evolution, molecular residual disease, and functional metabolic remodeling. Germline variants establish life-course risk and recalibrate surveillance intensity. Somatic mutational signatures and field cancerization describe spatial conditioning of tissues long before overt malignancy. Circulating tumor DNA (ctDNA) provides temporal resolution by tracking clonal persistence after therapy. Extending this framework, emerging evidence from microbiome and metabolomic studies supports the hypothesis that sustained alterations in volatile organic compound (VOC) profiles may reflect early tumor–microbiome ecosystem shifts. Although a comprehensive wearable multi-gas detection device is not yet clinically available, current technological advances render continuous “volatomics” biologically plausible and conceptually aligned with trajectory-based monitoring. Rather than advocating a single transformative assay, this manuscript argues for convergence: longitudinal biomarker baselines, germline priors, tumor-informed molecular templates, ctDNA dynamics, and prospective metabolic sensing integrated within a calibrated decision system. Such a platform would function not as a replacement for established diagnostic tools, but as a stratified triage architecture capable of identifying sustained biological deviation warranting further evaluation. Early detection, in this reframed paradigm, becomes a dynamic process of recognizing evolving biological drift rather than a binary event triggered by threshold crossing.

Abstract: The Box–Cox transformation is widely used to induce approximate normality and linearity in statistical modelling. Within the Power Normal framework, it embeds non-Gaussian variables into a latent Gaussian structure where conditional relationships become linear. However, the inverse transformation does not generally preserve these functional relationships when returning to the original scale. In this paper, we formally analyze the discrepancy between the inverse image of the linear regression function in the transformed domain and the true conditional expectation in the original scale. We derive an explicit second-order decomposition showing that the conditional mean in the original scale consists of the inverse-transformed linear predictor plus a curvature-induced correction term proportional to the conditional variance. This distortion term depends explicitly on the transformation parameter and the local geometry of the inverse Box-Cox function. The analysis reveals that the loss of structural preservation under inversion is an intrinsic consequence of the nonlinear transformation and can be interpreted as a second-order Jensen-type correction. Numerical illustrations based on simulated bivariate Power Normal models confirm the theoretical findings. These results clarify a structural limitation of transformation-based Gaussian modelling and provide insight into its implications for statistical inference and applied modelling.