Abstract: Cytochrome P450 oxidoreductase (POR) is the obligate electron donor for microsomal cytochrome P450 enzymes. Recessive mutations in the POR gene cause POR deficiency (PORD), a severe metabolic disorder characterized by skeletal malformations, ambiguous genitalia, and adrenal insufficiency. Because global POR knockout is embryonically lethal in mammalian models, the mechanistic study of PORD has historically been restricted to reconstituted biochemical assays or non-steroidogenic cellular backgrounds. Here, we describe complete biallelic POR knockout in human adrenal-derived NCI-H295R and human embryonic kidney HEK293T cells using CRISPR/Cas9. Transcriptomic and mass spectrometric steroid profiling of the adrenal clones revealed a blockade in canonical steroidogenesis, characterized by upstream accumulation of pregnenolone and progesterone, and severe depletion of downstream glucocorticoids and mineralocorticoids. Strikingly, knockout cells maintained low-level synthesis of dehydroepiandrosterone (DHEA) despite the complete absence of canonical CYP17A1 catalytic support, providing critical in vitro validation for the activation of alternative, CYP17A1-independent bypass steroidogenic pathways. Furthermore, utilizing the HEK293T platform, we evaluated the functional complementation of clinically relevant variants (A287P, R457H, P228L, and delP399_E401). Notably, the highly prevalent P228L variant exhibited selective preservation of CYP17A1 activity while severely impairing CYP19A1 aromatase function. A direct comparison between episomal overexpression and endogenous CRISPR prime editing of P228L highlighted critical differences in enzyme efficiency under native regulatory control. Finally, we establish a link between POR loss and altered intracellular Fe(II) storage, indicating perturbed ferroptotic susceptibility. These engineered human cell models provide a highly tractable platform for interrogating mutant-specific pharmacogenomics and developing targeted interventions.

Abstract: Antimicrobial resistance poses a critical global health challenge, necessitating the accelerated discovery of novel antibacterial agents. This study presents a quantitative structure–activity relationship (QSAR)-based multiclass classification framework for predicting the antimicrobial activity of β-lactam, azetidinone, and thiazolidinone derivatives. A chemically diverse library of over 220 compounds was constructed through combinatorial scaffold expansion guided by structure–activity relationship principles, with activity classified as Inactive, Moderate, or Active based on minimum inhibitory concentration (MIC) values. Molecular features were encoded using a fused descriptor set comprising Morgan fingerprints (radius 2 and 3), MACCS structural keys, and eight physicochemical descriptors, yielding a 1,199-dimensional feature vector. Class imbalance was addressed via SMOTE applied exclusively to the training set. Multiple machine learning models were developed and compared, including Random Forest, Gradient Boosting, XGBoost, a stacking ensemble, and a deep neural network with residual connections, batch normalization, and dropout regularization. Hyperparameter optimization was performed using randomized search with stratified 5-fold cross-validation. Model performance was evaluated using accuracy, weighted F1-score, balanced accuracy, and multiclass ROC-AUC. Visualization strategies including t-SNE, PCA, and feature importance analysis confirmed meaningful chemical space organization and robust structure–activity discrimination across all classifiers.

Abstract: Background: Chronic hyperglycemia promotes non-enzymatic glycation of hemoglobin, increasing oxygen affinity, shifting the oxyhemoglobin dissociation curve leftward, and inducing tissue-level pseudohypoxia a state termed glycohypoxia. This meta-synthesis quantitatively validates this concept by estimating the HbA1c-dependent change in P₅₀ and the resulting deficit in oxygen unloading, linking biochemical glycation to microvascular dysfunction. Methods: From six pivotal studies (1984–2012; N = 450 diabetic and control subjects), paired HbA1c and oxygen-release metrics (P₅₀, k, SpO₂–SaO₂ bias) were extracted. Study-specific slopes (ΔP₅₀ mmHg per 1% HbA1c) were pooled via random-effects meta-regression (REML), with sensitivity adjustment excluding 2, 3-DPG compensation. Translational modeling integrated the pooled ΔP₅₀ into the Hill equation for hemoglobin saturation across microvascular PO₂ (20–40 mmHg). Results: The pooled slope was −0.19 mmHg/% HbA1c (95% CI: −0.26 to −0.11; P < 0.001; I² = 45%), indicating a 0.5–1.3% decline in tissue oxygen unloading per 1% HbA1c rise, and a 1.5–3.9% cumulative loss from 6–9%. Independent clinical validation in 261 ventilated type 2 diabetes patients showed higher pulse oximetry versus arterial saturation for HbA1c >7% (SpO₂: 98.0 ± 2.6%, SaO₂: 96.2 ± 2.9%), despite similar PaO₂. The mean SpO₂–SaO₂ bias (1.83 ± 0.55%) correlated with HbA1c (r = 0.307, P < 0.01), confirming pseudonormoxia and leftward ODC shift. Conclusions: Glycohypoxia represents a quantifiable, reversible oxygen-delivery defect driven by HbA1c. Each 1% HbA1c rise translates to measurable hypoxic stress. Efaproxiral (RSR13; ~2.3 mg/kg per 1% HbA1c) could normalize P₅₀ and attenuate related complications by 30–55%, supporting metabolic reoxygenation as a therapeutic frontier in diabetes.

Abstract: Ginger (Zingiber officinale roscoe) is a high-value horticultural crop widely cultivated for its culinary and medicinal applications, yet its production is increasingly constrained by soil-borne diseases. Among these, Fusarium yellows, caused by Fusarium oxysporum f. sp. zingiberi (Foz), is one of the most damaging constraints in ginger-growing regions around the world, leading to progressive yellowing, vascular blockage, and decline in rhizome quality. Members of the Fusarium oxysporum species complex are known to include both pathogenic and non-pathogenic lineages that often co-occur within the same host and environment, complicating disease diagnosis and epidemiological understanding. In this study, we examined Fusarium-like isolates recovered from both symptomatic and symptomless ginger plants within Eumundi, the major ginger production region in Australia, to investigate their genetic diversity, effector gene content, and pathogenic potential. Comparative analyses revealed two genetically and functionally distinct groups: a clonal Foz lineage consistently associated with Fusarium yellows symptoms and characterised by a conserved set of Secreted In Xylem (SIX) effector genes (SIX7, SIX9, SIX10, and SIX12), and a diverse set of F. oxysporum isolates lacking these effectors. The conserved presence and co-localisation of SIX7, SIX10, and SIX12 within a 5 kb region on a 1.4 Mb contig in the Foz lineage is consistent with the retention of a stable lineage-specific effector module, likely associated with accessory genomic regions that may contribute to host specificity and pathogenicity in the Fusarium oxysporum species complex. Patho-genicity assays confirmed that only the Foz lineage induced disease, whereas non-Foz isolates were asymptomatic despite limited colonisation of host tissues. These findings highlight the coexistence of pathogenic and endophytic Fusarium lineages within ginger production systems and support the use of effector-based markers for improved detection and disease management.

Abstract: Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which clinically apparent synovitis is preceded by a prolonged preclinical phase characterized by immune dysregulation and autoantibody formation. Growing evidence implicates gut dysbiosis, impaired intestinal barrier integrity, and gut-derived immune priming as upstream contributors to RA pathogenesis, occurring years before overt joint inflammation. In parallel, Ayurveda describes Amavata as a chronic systemic disorder arising from the formation of Ama, a pathogenic burden produced by impaired digestive and metabolic function (Agni), which accumulates silently, disseminates systemically, and later localizes to the joints. Methods: This conceptual review draws on peer-reviewed biomedical and Ayurvedic literature to examine potential functional correspondences between the Ayurvedic construct of Ama in Amavata and contemporary models of gut-derived immune activation in RA, with emphasis on shared temporal and systemic features of disease development. Results: Both frameworks locate disease initiation upstream of overt inflammation and describe a prolonged preclinical phase characterized by systemic pathogenic processes. Ama is interpreted not as inflammation or tissue injury, but as a preclinical, systemic pathogenic state functionally analogous to chronic gut dysbiosis, barrier dysfunction, and immune priming described in RA. The analysis identifies a structural contrast in explanatory logic: Ayurveda integrates multiple upstream processes into a single unifying construct, whereas biomedicine analytically separates them into discrete mechanisms. The proposed mapping is heuristic and non-reductive, without asserting one-to-one equivalence or molecular translation. Conclusions: By situating both Amavata and RA within a shared preclinical, systemic disease framework, this model reinforces the importance of early, preventive intervention targeting metabolic and gut-immune dysregulation prior to irreversible joint damage. The findings demonstrate convergent reasoning across distinct medical traditions and support integrative, systems-oriented perspectives on chronic inflammatory disease initiation.

Abstract: Accurate short-term forecasting of key meteorological variables—air temperature, relative humidity, and wind speed—remains challenging in tropical and sub-Saharan regions due to strong diurnal cycles, seasonal variability, and non-stationary dynamics. To address these limitations, this study proposes a hybrid deep learning model combining Stationary Wavelet Transform (SWT), Multi-Head Attention (MHA), and LSTM networks. First, SWT decomposes meteorological time series into multi-scale components, capturing both low-frequency trends and high-frequency fluctuations while preserving temporal resolution. Then, the attention mechanism dynamically weights the importance of these multi-scale features across time, enhancing the model’s ability to focus on the most relevant patterns and interactions. Finally, LSTM layers model long-term dependencies and nonlinear temporal structures to generate multi-output predictions. The model is trained on hourly data enriched with lagged and statistical features. Experimental results show strong predictive performance (MAE = 1.21, RMSE = 2.01, R² = 94%), with notable improvements in modeling rapid variations, especially for wind speed and humidity. This work represents one of the first integrations of SWT, attention mechanisms, and LSTM for multi-variable forecasting in tropical climates, with practical applications in energy forecasting and precision agriculture.

Abstract: Classical subatomic particles simulations were applied to protons, neutrons and electrons to simulate a complete atom using pseudo potentials to simulate nucleus and electrons distributed around nucleus. Molecular dynamics algorithms were applied to subatomic particles to simulate a complete atom for Hydrogen, Carbon and Uranium atoms that were reported in previous studies. Further analysis of energies of Carbon atom reveals that atom has quantized discrete energy values rather than continuous energies as expected in classical simulations. Changes in atom's total energy were observed to be in step changes going to higher/lower energy states and energy values are observed to be in quantized rather than continuous. Electrons energy profiles was observed during the atom's quantum energy shifts and only one electron got affected that has step change in its energies, for short duration, leaving other electrons unaffected. To observe similar phenomenon in other atoms, Fluorine, Magnesium and Chlorine atom were considered in this study and found to have similar quantized discrete energy values properties. This study implements subatomic particles simulations using classical mechanics that explains why atom's energies are quantized in nature as observed in discrete lines in atomic emission/absorption spectrum for atoms.

Abstract: The structural strength requirements for timber buildings have been significantly tightened in the second generation of Eurocodes (EN 1990:2023, EN 1991-1-7), which poses a particular challenge for solid timber frames with a beam-and-column structure, where the transfer of tensile forces via dowel connections is inherently limited. This article presents an effective two-scale finite element method (FEM) modelling framework for assessing the strength of such frames during column removal. At the connection level, a continuous fracture mechanics model is used, based on a modified quadratic Hashin-type failure criterion, combining non-linear FEM up to peak load with post-peak behaviour defined in accordance with Eurocode 5. At the overall frame level, multi-fibre beam elements accounting for plasticity and damage, non-linear connection elements with six degrees of freedom interaction, and an element erosion method have been implemented. Both levels have been verified against published experimental data. Modelling at the joint level reproduces measured strength and stiffness values with an error of no more than 5% and corresponds to the characteristic values of Eurocode 5, second edition. Modelling at the frame level accurately reflects the non-linearity of the ‘load-displacement’ relationship, the sequence of joint failure, and the axial forces in the chain line under large displacements exceeding 390 mm. The proposed methodology demonstrates high potential for the practical design of structures in accordance with the current Eurocode provisions on reliability.

Abstract: Achieving carbon neutrality has become a central policy objective for emerging economies, particularly the BRICS countries—BRICS (Brazil, Russia, India, China, and South Africa)—which collectively account for a substantial share of global carbon emissions and energy consumption. The transition toward green energy, rapid technological innovation, and the expansion of green finance mechanisms are increasingly viewed as critical drivers of sustainable development and environmental improvement. However, empirical evidence integrating these three dimensions within a unified analytical framework for BRICS remains limited. This study assesses the contribution of green energy transition, technological innovation, and green finance to achieving carbon neutrality in BRICS over the period 1990–2024. The novelty of this research lies in its comprehensive modeling approach that simultaneously captures long-run dynamics, cross-sectional dependence, and heterogeneity among countries. Advanced panel econometric tech-niques, including second-generation unit root tests, panel cointegration analysis, and the pooled mean group ARDL model, are employed to ensure robust and reliable estimates. The findings reveal that green energy transition and technological innovation significantly reduce carbon emissions in both the short and long run, while green finance enhances environmental quality by facilitating low-carbon investments. Moreover, bidirectional causality is observed between green finance and technological innovation, indicating a reinforcing mechanism. Policy implications suggest that BRICS nations should strengthen green financial markets, promote clean energy technologies, and enhance regulatory frameworks to accelerate progress toward carbon neutrality. Coordinated regional cooperation and targeted innovation incentives are essential for sustainable and inclusive low-carbon growth.

Abstract: Hypospadias is a congenital malformation of the male external genitalia resulting from incomplete fusion of the urethral folds during embryonic development. The perineal form represents the most severe phenotype and is frequently associated with abnormalities such as cryptorchidism and penile hypoplasia. Although surgical correction is generally recommended in young dogs, the long-term clinical course of severe hypospadias under conservative management remains poorly documented. In this study, we describe an un-usual canine case of severe perineal hypospadias that survived to geriatric age under conservative management and subsequently developed bilateral testicular tumors arising from cryptorchid testes. Despite recurrent urinary tract infections during early life, the pa-tient maintained an acceptable quality of life with long-term supportive care, providing a rare clinical example of extended survival without surgical correction. Because no molec-ular material was available from the patient, publicly available mouse transcriptomic da-tasets related to genital tubercle development and Leydig cell differentiation were con-sulted only as contextual reference. These datasets illustrate established developmental regulators and steroidogenic pathways relevant to genital formation and testicular func-tion but do not represent direct molecular findings from the reported case. This report primarily highlights the clinical course and management of severe hypospadias in a dog, while using existing transcriptomic knowledge solely to provide biological context. The findings should therefore be interpreted as descriptive and hypothesis-generating rather than as evidence of a direct mechanistic link between developmental abnormalities and endocrine tumorigenesis.

Abstract: This integrative review examines the theoretical evolution and empirical applications of three interconnected media dependency frameworks: the foundational Uses and Dependency Model, Internet Use and Dependency adaptations, and the New Media Uses and Dependency Effect Model. Drawing on 30 peer-reviewed studies spanning five decades, the review traces how dependency theory has evolved from explaining mass media effects in centralized broadcast systems to accounting for interactive, ubiquitous, and habitual digital media use. The foundational model established that media effects emerge from goal-directed dependency relations embedded in tripartite audience–media–society relationships, with understanding, orientation, and play as primary audience goals. Internet adaptations extended these principles to digital affordances—interactivity, comprehensiveness, and perpetual availability—while shifting the unit of analysis from media systems to specific platforms.The New Media Uses and Dependency Effect Model further refined causal mechanisms by integrating habitual use as a precursor to dependency and specifying mediation pathways linking habit to cognitive, affective, and behavioral outcomes through dependency intensity. This review synthesizes theoretical continuities, identifies key innovations across models, presents comparative analyses, and discusses empirical evidence, critical limitations, and future research directions. The analysis demonstrates that while all three frameworks retain the core logic of goal-oriented dependency, they progressively incorporate finer-grained mechanisms—platform attributes, perceived utility, and habitual patterns—that enable more precise operationalization and testing in contemporary digital environments.

Abstract: Livestock production remains the primary source of livelihood in the arid and semi-arid lands (ASALs) of Kenya’s lower eastern region. Despite sustained investments by governments and non-governmental organizations, the economic returns from livestock development projects have remained modest, and poverty levels persist. This study evaluated the impact of a Livestock Improvement Project (LIP) on the subjective wellbeing of agro-pastoral households in Mwala Sub-County, Machakos County. Specifically, the study assessed household subjective wellbeing and examined its contributions to livestock performance, access to agricultural credit, capacity building in livestock management, and participation in collective action. A cross-sectional study was conducted to collect household information using a structured questionnaire. A sample of 285 households was selected through stratified random sampling from 1,100 project beneficiaries organized into 45 farmer groups. Data were collected using a structured questionnaire and analyzed using descriptive and inferential statistics at a 95% confidence level (p ≤ 0.05). Household subjective wellbeing was relatively high (M = 7.3, SD = 1.2) on a 10-point scale (1=low and 10 high). Regression results indicated that subjective wellbeing was positively and significantly influenced by livestock performance (β = 0.944, p < 0.001), access to agricultural credit (β = 0.748, p < 0.001), capacity building (β = 0.878, p < 0.001), and participation in collective action (β = 0.834, p < 0.001). The study concludes that the LIP had a positive impact on household wellbeing and recommends that future livestock interventions in ASALs integrate capacity building, access to credit, and collective action to enhance sustainable livelihood outcomes. The study contributes to livestock development literature by applying the subjective wellbeing perspective to project impact evaluation.

Abstract: Three-dimensional (3D) shape recognition is a fundamental task in computer vision, where view-based methods have recently achieved state-of-the-art performance. However, effectively capturing and exploiting the rich geometric correspondences between different views remains a key challenge, as such information is crucial for accurate shape representation. Existing methods often fall short in explicitly modeling these structured correlations, which limits their ability to fully leverage discriminative shape information. To address this limitation, we propose a novel View-based Graph Convolution and Sampling Fusion Network (View-GFN). View-GFN employs a hierarchical architecture that progressively coarsens the view-graph to learn multi-scale features. In this structure, views are treated as graph nodes, and a predefined-value strategy is introduced to initialize the adjacency matrix (AM) for constructing initial node correlations. For effective graph coarsening, we develop a novel view down-sampling method based on a cluster assignment matrix. Furthermore, a Graph Convolution and Sampling Fusion (CSF) module is designed to seamlessly integrate deep feature embeddings with the topological information derived from view down-sampling. Extensive experiments on benchmark datasets, including ModelNet40 and RGB-D, demonstrate that View-GFN achieves a superior recognition accuracy of 97.8%, surpassing previous methods while reducing the number of model parameters by nearly 50%. These results validate the superiority of our hierarchical fusion strategy in capturing multi-view geometric information both effectively and efficiently.

Abstract: We develop a metamathematical analogue of special and curved relativity built from exact witness architectures. For a proposition equipped with exact positive and negative witness channels, the corresponding positive and negative terminal directions are promoted to formal terminal meta-fibers. These play the role of null directions and generate a terminal cone together with an invariant interval dσ² = dU dV = dT² − dX². This yields a flat theory, Terminal-Fiber Relativity, in which Lorentz-type transformations arise as exactly the observer changes preserving the terminal interval and the oriented terminal cone. We then reinterpret the principal barrier theorems of exact witness architecture theory as relativistic laws: the Selection Jump Theorem becomes a universal null-propagation principle; reflection collapse forbids global internal inertial charts on Π₁-universal sectors; and Tarski and diagonal barriers forbid global arithmetic charts on truth-universal sectors. The second half of the paper extends the flat theory to curved meta-relativity. We define terminal-fiber manifolds, local null charts, occupancy fields, barrier fields, and a scalar curvature law in dimension 1+1. Because ordinary Einstein dynamics is trivial in two dimensions, the curved theory is governed instead by a conformal scalar equation sourced by barrier density and mixed terminal occupancy. We also formulate a higher-rank extension and a functorial packaging from exact witness architectures to terminal-fiber geometries. The result is not an empirical substitute for spacetime physics, but a geometric invariant theory of exact recognition.

Abstract: To meet the requirement of the current integrated circuit industry, atomic layer etching (ALE) technology has been broadly studied and developed. By dividing the whole etching process into several independent and self-limiting sub-process, ALE can achieve etching in atomic-level precision and better control in the etching process than traditional continuous etching technology, such as reactive ion etching. In this review, the characteristics of ALE are briefly summarized and five ways to improve the performance of ALE are introduced in detail. Attentionally, the main problem of the industrial application of ALE is how to make the trade-off between the time-consuming and the quality of etching. An improved ALE method with multiple temperature windows is proposed in this paper, which can theoretically shorten the time of each etching cycle in ALE.

Abstract: Shallow, turbid coastal environments (Case 2 waters) challenge optical remote sensing due to the complex, non-covariant interaction between dissolved and particulate constituents. This study quantifies the relationship between the effective (K_eff) and the diffuse attenuation coefficient of downwelling irradiance (K_d) across 14 stations in the southern Baltic Sea, representing a transition from estuarine to open coastal waters. Using K-Means clustering and Random Forest regression, we characterised Optical Water Types (OWTs) and decoupled the specific drivers of attenuation. Results indicate that K_eff consistently exceeds K_d by a factor of 2-3, with the spectral ratio (K_eff/K_d) significantly surpassing the theoretical geometric limit of 2, particularly in the 500-650 nm window. Although total suspended matter (TSM) is the primary driver for both coefficients, K_eff exhibits heightened sensitivity to coloured dissolved organic matter absorption at 440 nm (a_CDOM (440)) due to the geometric rejection in the collimated beam; in contrast, K_d remains coupled to the broad-band scattering effects of phytoplankton. We conclude that assuming a fixed geometric relationship (K_eff ≈ 2K_d) leads to systematic errors in scattering-dominated waters, and propose a robust empirical relationship (K_eff ≈ 1.71K_d + 1.44; Pseudo R² = 0.4) to improve subsurface retrievals in shallow and optically complex coastal zones.

Abstract: This paper develops a systematic philosophical dialogue between Kantian autonomy and Buddhist ethics in relation to freedom, moral agency, and moral cultivation. And in place of a hierarchic or reductionist juxtaposition, it is rather a question of how each tradition articulates the ethical normativity it adheres to in relation to specific philosophical problems. Kantian moral reasoning connects freedom with rational self-legislation and conceives moral obligation through universal law as articulated in the Groundwork of the Metaphysics of Morals and the Critique of Practical Reason. Buddhist ethics, by contrast, understands freedom as liberation from ignorance and craving, emphasizes causal continuity, compassion and moral cultivation, and it does so without postulating an enduring self. Drawing on recent contributions in Buddhist moral philosophy particularly that of Damien Keown, Charles Goodman and Jay L. Garfield, the article argues that the two perspectives offer kairotic rather than chronological perspectives on moral agency. Kantian universal respect and autonomy are at odds with Buddhist ethics which discloses the emerging and relational character of ethical existence. The conclusion is that the concept of moral freedom is better conceptualized when understood through the combined view of rational normativity and moral cultivation.

Abstract: Antibody-dependent enhancement (ADE) is a paradoxical immunological phenomenon in which pre-existing antibodies facilitate viral entry into host cells rather than conferring protection. ADE has been extensively characterised in flaviviral systems, most notably dengue virus (DENV), and presents a significant challenge for vaccine development and antibody-based therapeutic design. In coronavirus infections, ADE operates through both classical Fc gamma receptor (FcγR)-mediated pathways and an intrinsic signalling mechanism involving inhibitory FcγRIIb-mediated suppression of the type I interferon (IFN-I) response. Of critical translational relevance is the proposed cooperative FcγR–angiotensin-converting enzyme 2 (ACE2) entry model for SARS-CoV-2, wherein virus–antibody immune complexes simultaneously engage ACE2 through the viral spike receptor-binding domain (RBD) and FcγRIIa through the antibody Fc region on the same macrophage surface. This cooperative dual-receptor engagement may stabilise virion attachment, augment endosomal uptake, and trigger downstream signalling cascades that suppress antiviral immunity, potentially contributing to severe COVID-19 immunopathology. Feline infectious peritonitis virus (FIPV) represents one of the most rigorously documented biological systems in which antibody-mediated macrophage infection directly determines systemic disease outcome, providing a critical comparative framework for understanding coronavirus ADE across species. This comprehensive review integrates current knowledge of FcγR biology, coronavirus cell entry mechanisms, intracellular signalling cascades, cytokine dysregulation, comparative veterinary immunopathology, and nano-engineered immunomodulatory platforms for ADE-safe vaccine development. We critically evaluate lipid nanoparticle mRNA vaccines, virus-like particles, and polymeric nanoparticle systems as rational strategies to elicit selective neutralising antibody responses while mitigating ADE risk. We also highlight key unresolved mechanistic questions and future research directions essential for the development of safer vaccines and therapeutics against both current and emerging coronaviruses in human and veterinary medicine.

Abstract: Pneumocystis jirovecii is an opportunistic fungal pathogen responsible for Pneumocystis pneumonia (PCP), a severe infection that remains a major cause of morbidity and mortality among immunocompromised patients, particularly in non-HIV immunosuppressed populations. Despite its recognized clinical relevance and inclusion in the World Health Organization’s Fungal Priority Pathogens List, important gaps persist in its diagnosis, epidemiology, and therapeutic management. This study provides a comprehensive bibliometric analysis of global scientific production on P. jirovecii using Scopus as the primary data source. Publications were evaluated for temporal trends, document types, authorship patterns, in-stitutional productivity, collaboration networks, funding sources, the-matic evolution, and journal distribution, with additional comparison against other major pneumonia-associated pathogens. A total of 27,396 articles published between 1916 and 2025 were identified. Over the last 50 years, scientific output increased from 10,382 publications in 1975–2000 to 16,496 in 2001–2025, representing an overall growth of 58.9%. Early research expansion was strongly shaped by the HIV/AIDS epidemic, whereas the post-2000 period reflected advances in molecular diagnostics, taxonomic clarification, and broader attention to non-HIV immunosuppressed populations. Although the field has become more diversified and clinically integrated, persistent structural inequities and underinvestment continue to limit progress, particularly in low- and middle-income settings.

Abstract:

Patient-derived organoids have emerged as valuable platforms for modeling tumor biology and evaluating therapeutic responses. However, their application in squamous cell carcinomas remains limited. Therefore, in this study, organoid cultures were established from patients with colorectal adenocarcinoma and oral squamous cell carcinoma using a standardized protocol, and their biological and functional characteristics were evaluated. Tumor specimens were obtained from five patients with colorectal adenocarcinoma and two patients with oral squamous cell carcinoma. Organoids were successfully established in four of five colorectal cancer cases (80%) and in one of two oral squamous cell carcinoma cases (50%). The established organoids preserved key histological and immunophenotypic features of the parental tumors, and xenograft experiments confirmed in vivo tumorigenicity and the maintenance of tumor morphology. Moreover, whole genome sequencing of a colorectal cancer-derived organoid revealed chromosomal instability and pathogenic alterations in APC, NRAS (p.Q61H), and TP53. Furthermore, drug sensitivity screening identified distinct response profiles among organoid lines. Overall, this study demonstrated that organoids can be established from both adenocarcinomas and squamous cell carcinomas using a simple common protocol. Moreover, a rare NRAS Q61-mutant colorectal cancer organoid was established. This provides a valuable model for biological studies and therapeutic development of NRAS-mutant colorectal cancer.