Abstract: Bangladesh built its modern economy on human labor: ready-made garments, a large freelancing workforce, and a mostly informal jobs base. Artificial intelligence and automation now target that routine, low-wage work. This paper asks how exposed the country is, and whether its policy response matches the threat. Using a qualitative secondary-data design, it applies the Acemoglu-Restrepo task-based model of automation to peer-reviewed studies, institutional reports, and field journalism, with each headline figure cross-validated across independent sources. A 2024 factory study records an average 30.58 percent workforce reduction where automation has arrived, concentrated in cutting and sweater lines. The displacement falls hardest on women, whose share of garment work fell from 85 percent in 1991 to 57 percent in 2023. A national AI policy exists only in draft, leaving a gap between a projected 5.38 million jobs at risk by 2041 and any enacted protection. The task-based lens explains why a labor-surplus economy with weak reinstatement capacity sits in the displacement zone, and why reskilling and industrial policy will decide the outcome.

Abstract:

Native Mexican turkeys (Meleagris gallopavo gallopavo) are an important genetic resource in family-based production systems exposed to marked regional and seasonal environmental variation. This study evaluated the effects of environmental gradients shape diet composition and hematological responses of native Mexican turkeys raised in family production systems. Fifty approximately six-month-old males were evaluated in a 5 × 2 factorial design including five physiographic regions and two seasons (rainy and dry). Crop content composition, estimated dietary nutrient composition, body weight, and hematological profile were analyzed using multivariate analysis of variance, principal component analysis (PCA), and multiple regression. Grains and energy-rich by-products predominated in the diet (58.2–76.2%), whereas the dry season increased dry plant fragments and crude fiber while reducing crude protein from 17.5 to 14.3% (p < 0.001). Body weight was greatest in the Neovolcanic Axis (5.20 kg) and lowest on the Coast (4.35 kg) (p < 0.001). Erythrocyte-related variables were higher in temperate, high-altitude regions, whereas leukocyte-related variables predominated in warmer regions (p < 0.05). PCA explained 71.3% of the total variation, identifying nutritional–productive and immunological–adaptive components. Physiographic region was the main determinant of diet composition and hematological responses, whereas the dry season intensified nutritional constraints and their effects on physiological adaptation.

Abstract: Rice leaf diseases pose a major threat to crop productivity and global food security. Therefore, rapid and accurate disease diagnosis is essential for effective crop management. Despite the advancements made by deep learning algorithms in automated disease detection, the majority of current deep learning-based models are built and evaluated on single-source datasets. Therefore, the generalization capability of these models is still questionable. In order to overcome this problem, this paper presents an interpretable deep learning approach for classifying diseases in rice leaves using ConvNeXt-Tiny and Grad-CAM. The proposed semantic class normalization technique is used to harmonize the heterogeneous data classes to form a seven-class classification system. The model performance was analyzed based on two available public datasets for rice leaf disease and a combination of both. After performing five individual runs, the average classification accuracies were calculated to be 99.13±0.37%, 95.28±0.63%, and 97.27±0.41% for Datasets 1, 2, and the combined dataset, respectively. The confusion matrix analysis indicated minor misclassification errors in the form of false positives for the disease classes which have similarities in appearance. The training and validation curves showed consistent learning with minimum overfitting. Moreover, Grad-CAM analysis confirmed the focus of the model on the disease-specific regions. These results collectively show that the combination of transfer learning, semantic class harmonization, and explainable AI is a stable platform to conduct automated rice disease detection. It is evident from these outcomes that reliable performance can be achieved even under heterogeneous imaging conditions. Consequently, there exists great potential for this approach in agricultural decision-support systems.

Abstract: Durable therapeutic response depends not only on suppressing a disease-associated pathway, but also on changing the cellular dynamics that permit pathological or drug-tolerant states to persist and re-emerge. We distinguish transient activity modulation from kinetic remodeling, defined as a change in the drift, noise, flux, stability or transition structure governing cell-state accessibility. Using MAPK signaling as a model system, we organize remodeling into five idealized modes and link each to measurable signatures, including altered occupancy, switching, hysteresis and post-withdrawal recovery. This framework provides an experimental basis for identifying interventions that produce durable state control rather than temporary pathway inhibition.

Abstract: Two diastereoisomers of bis(mepirizole)bis(isothiocyanato-K,N)cobalt(II) (1 and 2) have been isolated from the reaction of cobalt(II) thiocyanate and meperizole depending on the crystallisation solvent (ethanol, 1; acetonitrile, 2). In both crystal structures, the Co(II) ions exhibit distorted octahedral [CoN₄N’₂] environment. The analysis of the packing frameworks shows a cooperative relationship between non-classical Hbonds C(sp³)H···X (X = N, O, S, pi) and pi-hole bonds, which control the arrangement of the supramolecular 3D networks. The values of the shortest intermolecular metal-metal separation are 8.584(2) in 1 and 8.249(1) in 2. Both diatereoisomers exhibit magnetic behavior typical of mononuclear Co(II) systems with significant zero-field splitting (ZFS) values, D being 75.8(1) and 52.9(2) cm-1 for 1 and 2, respectively. Q-band EPR studies confirm the positive value for the D parameters for both compounds. Alternating current dynamic susceptibility measurements show that 1 and 2 exhibit field-induced slow relaxation of the magnetization, which is reminiscent of single-ion magnet (SIM) behavior.

Abstract: The world of dating is fraught with danger, with catfishing, gaslighting, and breadcrumbing, among the hazards encountered by those looking for romance. Of particular interest in this paper is the process of ghosting, where a partner, without warning or explanation, ceases all contact and essentially disappears from the scene. Ghosting is often perpetrated by those without a conscience with the goal of avoiding all contact. The psychological effect on the victim can be devastating and severely detrimental to their mental health and well-being in general. This paper explores some of the reasons for ghosting, and its effects, as well as outlining several high-profile case studies. There are also suggestions on how a victim or offender of ghosting should cope with their situation.

Abstract: Background/Objectives. Systemic inflammatory responses influence treatment response and oncological outcomes in patients with cancer. Growing evidence indicates that the inflammatory burden index (IBI) serves as a reliable prognostic indicator across various malignancies. However, the clinical significance of the peri-treatment inflammatory status in patients with RC undergoing preoperative chemoradiotherapy (CRT) remains unclear. Methods. We assessed the pre- and post-treatment IBI in 97 patients with rectal cancer (RC) who received preoperative CRT followed by total mesorectal excision at our institution. Results. Although no significant changes were observed in the pre- or post-CRT IBI and no associations were found with most clinicopathological factors, survival analysis revealed that a high pre-CRT IBI was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). Multivariable analysis revealed that a high pre-CRT IBI and pathological lymph node metastasis remained independent prognostic factors for both outcomes. Subgroup analysis demonstrated that the prognostic value of the peri-treatment IBI differed according to the ypN status, with the pre-CRT IBI showing particularly strong prognostic performance in patients without pathological lymph node metastasis (ypN−). Conclusion. Pre-treatment assessment of the IBI may improve risk stratification in patients with RC undergoing preoperative CRT followed by curative resection.

Abstract: Background/Purpose: To characterize the degenerative vocabulary of 500 consecutive lumbar MRI reports using a transparent, reproducible text-extraction pipeline; to quantify which descriptors distinguish included from excluded reports and which factors predict text-derived severity; and to specify a reproducible image-analysis pipeline whose formal validation against radiologist Pfirrmann grading is defined as the next step. Methods: We analyzed 500 lumbar MRI reports (386 patients; December 2018–November 2025), extracting morphological and severity keywords, segmental levels (L1–L2 to L5–S1), Modic mentions, and a custom text-derived ordinal severity (0–3). Keyword-prevalence differences were tested with the Fisher exact test under Benjamini–Hochberg false-discovery-rate control, with 95% confidence intervals (CIs) for all odds ratios (ORs) and risk differences; predictors of severity were examined by ordinal logistic regression. A MATLAB pipeline derived per-disc candidate imaging features (predicted Pfirrmann grade, normalized disc height, T2 signal index, quality control) across 316 studies. Results: 385/500 reports (77.0%) met inclusion criteria. The structured morphological-keyword field was missing in 49.4% of records, declining across years (58.6% in 2020 to 33.5% in 2025), indicating systematic reporting drift. Bulge was the dominant descriptor (53.8%); L4–L5 and L5–S1 dominated level mentions. After correction, bulge (OR 6.70, 95% CI 3.86–11.65), mild (5.08, 2.39–10.78), dehydration (9.82, 2.36–40.87) and central (8.63, 2.07–36.01) were enriched among included reports. Older age independently predicted higher severity (OR 1.48 per 10 years, 95% CI 1.29–1.70). The image pipeline produced per-disc candidate biomarkers across 316 studies. Conclusions: Free-text lumbar MRI reports encode a recognizable but heterogeneous degenerative vocabulary, sufficient for cohort construction yet inconsistent for quantitative grading; the text-derived severity is a noisy proxy. The reproducible image-analysis pipeline yields candidate biomarkers whose formal validation against an adjudicated radiologist Pfirrmann reference standard is the explicit, pre-specified next step.

Abstract: Purpose: Reproductive coercion and abuse (RCA) is defined as deliberate interference in a person’s reproductive choices. It is overwhelmingly perpetrated against women by male intimate partners. Whilst it is generally agreed that RCA is harmful to health and wellbeing, reliable evidence for its specific associations has been lacking. In this study, our aim was to identify the physical, mental, sexual and reproductive health outcomes associated with RCA, using conceptually robust, comprehensive questions that encompass both pregnancy preventing and promoting behaviors and specify perceived perpetrator intent. Methods: In this study, we drew on data from two waves of the Australian Longitudinal Study on Women’s Health (n=6322 women aged 43-48 and n=5711 women aged 28-35). We reported the percentage of women with each health outcome, grouped by whether they had ever experienced RCA. We then estimated risk ratios for the association between RCA and each health outcome, controlling for sociodemographics and other intimate partner violence (IPV). Results: We found that lifetime partner-perpetrated RCA was associated with a range of adverse health outcomes for women aged 43-48 and 28-35 including elevated risk of unintended pregnancies (adjRR=2.42, 95% CI=2.16, 2.72 among women aged 28-35), miscarriages (adjRR=1.22, 95% CI=1.05, 1.41, and adjRR=2.08, 95% CI=1.74, 2.49, respectively), terminations (adjRR=2.39, 95% CI=2.11, 2.71, and adjRR=2.97, 95% CI=2.52, 3.50, respectively), premature birth (adjRR=1.72, 95% CI=1.01, 2.93 among women aged 28-35), and perinatal mental health disorders (adjRR=1.45, 95% CI=1.21, 1.74, and adjRR=1.68, 95% CI=1.42, 1.98, respectively), even after adjusting for sociodemographic variables and other IPV. RCA was also associated with poorer physical health (adjRR=1.33, 95% CI=1.05, 1.70, and adjRR=1.30, 95% CI=1.07, 1.57, respectively) and very high psychological distress (adjRR=1.24, 95% CI=1.03, 1.48 among women aged 28-35), including anxiety and depression (adjRR=1.24, 95% CI=1.07, 1.44, and adjRR=1.13, 95% CI=1.02, 1.24, respectively) and self-harm (adjRR=2.04, 95% CI=1.17, 3.56, and adjRR=1.49, 95% CI=1.11, 1.99, respectively). Conclusions: Our findings have important implications at the policy level and for the healthcare sector, highlighting the potential harms of RCA and the need for tailored screening, early intervention and response, particularly in abortion and antenatal settings.

Abstract: Background/Objectives: Sleep disturbances are common but frequently underrecognized in multiple sclerosis (MS), independently predicting reduced quality of life and worsening fatigue, cognitive impairment, and depression. While pain, nocturia, fatigue, and mood symptoms are established contributors, cardiometabolic and inflammatory factors remain largely unexplored despite their known links to poor sleep in other populations. This study used interpretable machine learning to determine the relative contribution of disease-related, cardiometabolic, and inflammatory parameters to sleep quality, assessed by the PSQI, in patients with MS. Methods: This cross-sectional, observational, single-center cohort study enrolled adult patients with MS. Sleep quality (PSQI), daytime sleepiness (ESS), and restless legs syndrome severity (IRLS) were assessed alongside clinical, anthropometric, hemodynamic, and laboratory parameters, including inflammatory and metabolic indices. Three regression models, Support Vector Regression, Random Forest, and XGBoost, were trained on 28 predictors to predict PSQI global scores and evaluated on a independent test set, with feature contributions examined using SHAP analysis. Results: A total of 173 patients with MS were included (mean age 39.66 ± 11.86 years, 69.9% female, 90.2% RRMS), with 48.0% classified as poor sleepers (PSQI > 5) and a mean PSQI score of 6.06 ± 3.47. XGBoost achieved the best predictive performance (test R² = 0.451). SHAP analysis identified IRLS severity as the strongest predictor of PSQI across all three models, followed by EDSS score and depression in the Random Forest and XGBoost models, while daytime sleepiness (ESS) ranked consistently among the top predictors. Cardiometabolic and inflammatory parameters contributed inconsistently, with several showing effects opposite to physiological expectation. Conclusions: Sleep impairment in MS was driven mainly by restless legs syndrome severity and neurological disability, with depression also contributing in the two best-performing models. Disease-related and symptomatic factors outweighed cardiometabolic and inflammatory contributions. These findings support the value of interpretable machine learning for identifying the multifactorial drivers of sleep quality in MS.

Abstract: Evidence-based standards on environmental enrichment for lynxes under human care remains limited, despite their importance for the welfare of these wild cats and its recommendation by zoological associations. This study aimed to: (1) evaluate the scientific evidence available to guide practical decisions on lynx enrichment in controlled environment within an Evidence-Based Practice framework; and (2) examine enclosure enrichment structures use and social behaviour in a group of Eurasian lynxes. A total of seven relevant publications (3 on Lynx rufus) were identified, five of which through a scoping review. All studies reporting quantifiable outcomes indicated positive effects from at least some forms of environmental enrichment. We observed three Eurasian lynxes (Lynx lynx) housed at the Wildheart Animal Sanctuary, using the facility’s live-streaming webcams. Enclosure furnishing use by the lynxes was assessed from two-hundred opportunistically recorded instantaneous scans, while social behaviours were assessed from 200 minutes continuous recording. Lynxes used structural enrichment in more than half of the scan samples, and engaged in intra-specific affiliative behaviour. The use of the wooden turret was lower from sunrise to 12:59 pm than during other time periods (p< 0.001). Further species-specific research is needed to evaluate the effects of environmental enrichment on lynx behaviour and welfare.

Abstract: Eukaryotic genomes are organized into chromatin, a highly compact structure in which DNA is packaged into nucleosomes. Nucleosome formation, where DNA is wrapped around histone proteins, is essential for genome stability. This compaction protects DNA from damage and regulates accessibility of genes. Nucleosomes must be disassembled and reassembled during DNA replication and repair. These processes require precise regulation of histone folding, transfer, and deposition by a diverse network of histone chaperones. Chromatin assembly factor 1 (CAF-1) is a conserved histone chaperone that specifically deposits newly synthesized histones during replication-coupled and repair-coupled nucleosome assembly. The sliding clamp proliferating cell nuclear antigen (PCNA) serves as a regulatory scaffold during these processes by recruiting CAF-1 and many other proteins to sites of DNA replication and repair. Recent structural and biochemical studies have revealed increasingly complex mechanisms underlying PCNA-mediated CAF-1 recruitment, involving multiple protein interaction motifs, DNA-binding domains, and regulatory mechanisms that ensure efficient nucleosome assembly. This review summarizes current advances in understanding the molecular mechanisms by which human and yeast CAF-1 complexes are recruited to sites of DNA synthesis and how CAF-1 function is coordinated with other histone chaperones during replication and repair. These studies have provided important insights into how cells coordinate DNA metabolism with epigenome maintenance to preserve genome integrity.

Abstract: Alzheimer’s disease (AD) in humans shares several features with canine cognitive dysfunction (CCD), a disease that affects older dogs. Therefore, CCD serves as a natural model for the study of AD. Several studies have documented early pathological changes in both AD and CCD, including widespread damage to the cerebral cortex and hippocampus, with this pathology attributed to the deposition of neurotoxic proteins such as beta-amyloid. Magnetic resonance imaging (MRI) is currently the only advanced imaging modality routinely used to support the diagnosis and prognosis of CCD. However, it is not commonly applied for the diagnosis or longitudinal monitoring of aging dogs with cognitive dysfunction. MRI can detect brain atrophy, hippocampal atrophy, ventricular enlargement, widening of the cerebral sulci, lesions in the temporal lobes of the cerebral cortex, and progressive thinning of the interthalamic adhesion in dogs undergoing natural or pathological aging. Accordingly, this imaging modality may serve as a valuable diagnostic marker for CCD in both early and advanced stages.

Abstract: The mind–body problem remains a central unresolved issue in contemporary cognitive science. Although research on hemispheric asymmetry has yielded extensive knowledge about neural specialization and functional localization, it provides limited explanatory power for how lateralized neural processes become expressed as observable embodied behavior. Existing approaches typically treat bodily asymmetry either as an epiphenomenon or as a static anatomical correspondence, leaving a conceptual and operational gap between neural activity, subjective experience, and kinematic expression.This manuscript presents Subjectica, a purely theoretical neurophenomenological framework that addresses this gap by conceptualizing hemispheric asymmetry as a dynamic process of embodied cognitive orientation. Rather than positing a fixed mapping between hemispheres and body sides, the model proposes that lateralization is expressed as continuous sensorimotor organization reflecting the current interpretative orientation of the organism. Cognitive stance is therefore understood as an embodied orientation that emerges through the relative predominance of internally and externally integrated interpretative resources during contextual interpretation and becomes observable through structured asymmetries in posture, movement, and segmental motor activity.The model introduces four interrelated conceptual constructs: Personal-Oriented Left Side (PO-LS), Social-Oriented Right Side (SO-RS), Asymmetric Neurobehavioral Signal (ANS), and Body Segments (BS). Together, these constructs provide an interpretative framework linking hemispheric functional asymmetry, embodied cognitive orientation, and measurable bodily dynamics. The framework enables the analysis of lateralization as continuous probabilistic patterns of whole-body and segment-specific motor organization rather than as discrete anatomical or task-specific indicators.Subjectica is intended as a generative theoretical framework that produces testable hypotheses and operational pathways for future empirical research at the intersection of embodied cognition, hemispheric asymmetry, neurophenomenology, and embodied contextual interpretation.

Abstract: Leaf senescence progressively remodels the photosynthetic apparatus, leading to impaired electron transport and declining carbon assimilation. Here, we investigated how dark-induced senescence (DIS) and exogenous 6-benzyladenine (BA) affect photosystem function, cyclic electron flow (CEF), photosynthetic protein remodeling and CO2 assimilation in two barley (Hordeum vulgare L.) cultivars differing in senescence characteristics, Carina (spring) and Lomerit (winter). DIS markedly reduced chlorophyll content, PSI and PSII photochemistry, electron transport and CO2 assimilation in both cultivars, although the underlying mechanisms differed. Carina maintained higher CEF despite stronger PSII inhibition, whereas Lomerit exhibited a greater decline in CEF accompanied by stronger donor- and acceptor-side limitations of PSI. These physiological responses coincided with selective remodeling of proteins forming the PSI-associated electron transport network, including coordinated changes in cytochrome f, PGRL1, NdhS, FNR and photosystem antenna proteins, indicating functional reorganization of photosynthetic electron transport rather than uniform chloroplast protein degradation. BA delayed senescence by preserving chlorophyll, maintaining PSI and PSII activity, sustaining CEF and partially alleviating the decline in CO2 assimilation. The protective effects of BA were more pronounced in Carina and coincided with more effective preservation of proteins associated with PSI-dependent electron transport. Collectively, our findings identify selective stabilization of the PSI-associated electron transport network as a central mechanism underlying cytokinin-mediated delay of leaf senescence in barley and demonstrate that cultivar-dependent regulation of this network determines the effectiveness of cytokinin-mediated protection of photosynthesis.

Abstract: Paradoxically, whilst historic Environment, Culture, Heritage, and Arts (ECHA) organisations curate knowledge for the public, thousands of them lack the required operational knowledge to manage their rapidly changeable and demanding operations. Their management requires extensive up-to-date knowledge, in accessible recorded formats (knowledge artefacts) interacting with human experience. For decades, the ECHA ecosystem, ECHAsystem [EE-kah-siss-tuhm], has been in a protracted crisis resulting in reduction of service for, and closures of, thousands of these organisations. The purpose of this cross-sectional, parallel mixed methods applied research was to develop a beneficial operational knowledge curating design to improve the ECHAsystem’s organisational sustainability. The findings demonstrated that accessible and up-to-date knowledge significantly improves processes and organisational sustainability performance. It also showed that a wise, allied development of knowledge resources, and allied application of available organisational resources, produces the greatest results. The research proposed the Athena [ah-thee-NAH] de-sign: a Knowledge Alliance coordinating the Operational Wisdom Library (OWL), in-formed by 31 networks across the ECHAsystem’s habitats and operations. The design can help individuals to grow professionally, organisations to thrive, and the ECHAsystem to achieve its aspirations. The research advocates a unified ECHAsystem benefiting from collaborative application of knowledge to deliver its public-good, intergenerational, organisational sustainability objectives.

Abstract: This study examines the environmental transformation of Puerto Princesa City, Palawan, from 2014 to 2022, with particular attention to how urbanization and population growth have reshaped land cover and local climate conditions. Using remote sensing data and demographic information, the analysis tracked changes in vegetation, built-up areas, and surface temperature patterns. Over the eight years, developed land nearly doubled, expanding from 34.4 km² to 67.7 km², largely at the expense of open spaces along the urban peripheries. Rural barangays showed mixed patterns, with some experiencing stagnation or decline in population and land conversion, while others exhibited localized forest recovery. The land surface temperature rose steadily, with mean values increasing from 26.9°C in 2014 to 28.1°C in 2022, and higher temperatures were consistently recorded in densely populated urban barangays. Built-up areas showed a stronger association with rising surface temperatures compared to vegetation cover, underscoring the role of urban expansion in driving thermal changes. The urban heat island effect, though fluctuating across the study years, became more widespread by 2022, with moderate-intensity zones expanding beyond the urban core. These findings point to significant ecological and climatic shifts, emphasizing that both rural development and urban densification contribute to rising heat stress. The resulting impacts on vegetation and surface temperatures of these land cover changes emphasize the need for integrated land use planning and climate-resilient urban development strategies in Puerto Princesa City.

Abstract: One of the most important adverse consequences of antibiotic use is the development of bacterial resistance. This study investigated the prevalence and antimicrobial resistance patterns of multidrug-resistant (MDR) Escherichia coli in a tertiary care hospital during 2013–2015 and 2024, together with trends in antibiotic consumption and the molecular characteristics of resistance genes in 2024 isolates. Identification and susceptibility testing were performed using the Vitek® 2 system, antibiotic consumption was assessed according to WHO ATC/DDD methodology, and resistance genes were detected by PCR. No significant differences were observed in the total number of isolates, patients, or the proportion of E. coli isolates during 2013–2015. However, the isolation rate of MDR E. coli significantly declined from 36.9% to 30%. Total antibiotic consumption remained stable, with no correlation between consumption and MDR isolation rates, although ampicillin resistance increased significantly. In 2024, MDR E. coli accounted for 24.3% of isolates despite lower antibiotic consumption. Compared with 2015, resistance significantly increased to amoxicillin-clavulanic acid, cefotaxime, cefepime, ceftazidime, ciprofloxacin, and levofloxacin, while ceftriaxone resistance decreased. The blaCTX-M gene was detected in 53% of bloodstream isolates, indicating widespread dissemination of ESBL-producing E. coli and highlighting the need for continuous surveillance and antimicrobial stewardship.

Abstract: One of the main causes of drug resistance in malignancies is metabolic reprogramming in the tumor microenvironment (TME). To maintain growth and alter the TME, cancer cells frequently rewire their metabolism, resulting in circumstances including food deprivation, hypoxia and acidity that hinder antitumor immune responses. The TME’s immune cells also experience metabolic changes, often taking on immunosuppressive characteristics that accelerate tumor growth and dampen the effectiveness of treatment. B cells are integral to the adaptive immune response, primarily through MHC class II-mediated antigen presentation and immunoglobulin secretion. Emerging evidence indicates that the functional role of tumor-infiltrating B cells is highly heterogeneous across malignancies. While their antigen-presenting capacity is generally associated with anti-tumor immunity, the contribution of B cell-derived antibodies remains ambiguous and context-dependent. Additionally, regulatory B cell subsets (Bregs) exert immunosuppressive effect within the TME by secreting anti-inflammatory cytokines such as interleukin (IL)-10 and tumor growth factor (TGF)-β, thereby facilitating immune evasion. Herein, we summarise the current understanding of B-cell functions in tumor immunology, which may shed light on potential therapeutic strategies against cancer.

Abstract: Background: Adrenal chromaffin cells integrate cholinergic and peptidergic signaling to regulate catecholamine secretion during stress. Although pituitary adenylate cyclase-activating polypeptide (PACAP] sustains adrenal secretion during intense sympathetic activation, the systems-level mechanisms coordinating chromaffin-cell activity remain incompletely understood. Perspective: We suggest that chromaffin cells function as dynamically recruited chromaffin-cell ensembles rather than independent endocrine units. Within this framework, connexin-mediated gap junctions act as activity-dependent amplifiers that enable PACAP- and acetylcholine-dependent recruitment of progressively larger ensembles according to physiological demand. We further suggest that ensemble recruitability is continuously modified by physiological state and previous experience. Conclusions: Building upon recent evidence and our experimental observations, we propose that early-life adversity remodels hypothalamic autonomic circuits, altering subsequent PACAP-dependent recruitment of chromaffin-cell ensembles during adult stress. This unified framework integrates peptidergic signaling, gap junction plasticity, and developmental programming, generating experimentally testable hypotheses and providing a new systems-level view of sympathoadrenal regulation.