Search Results (4,271)

Although tomato mosaic virus (ToMV) is an economically important tobamovirus, the physiological and molecular events occurring during the asymptomatic phase of infection remain poorly understood. In this study, we investigated the early responses of Nicotiana tabacum cv. Samsun to ToMV infection using an integrated physiological, biochemical, photosynthetic, and molecular approach. Viral accumulation was quantified via RT-PCR. Oxidative stress markers, antioxidant systems, photosynthetic performance, and gene expression were analyzed at 7 days post inoculation (DPI), before visible symptoms developed. Although infected plants remained symptomless, ToMV was detected in 80% of inoculated plants. Early infection induced oxidative stress, evidenced by increased malondialdehyde content, reduced free amino acid levels, and enhanced activities of superoxide dismutase and peroxidase. Total glutathione, phenolic compounds, and phenylpropanoids remained unchanged, whereas flavonoid content decreased significantly. ToMV infection also impaired the photosynthetic apparatus, resulting in reduced chlorophyll and carotenoid contents, decreased electron transport efficiency, and increased energy dissipation within photosystem II. Gene expression analysis revealed significant upregulation of defense- and stress-related genes (WRKY1, HSP70, GR, and DHAR), as well as chloroplast-associated genes (psaA and rbcL). Correlation analyses demonstrated coordinated relationships among viral accumulation, oxidative stress, antioxidant responses, and photosynthetic performance. These findings provide new insights into the asymptomatic phase of ToMV infection and identify potential early markers of host responses to viral infection. Full article

To address the critical challenge of extracting short-period surface deformation signals induced by extreme floods from InSAR time series, this study focuses on the catastrophic flood that struck the Haihe River Basin in July 2023 (hereinafter referred to as the “23·7” flood, with a total duration of approximately 65 days) and proposes a novel method for transient deformation signal extraction. Using Sentinel-1A satellite data and the PS-InSAR technique, we constructed a multivariate composite fitting function comprising a linear trend term, annual and semi-annual seasonal terms, a step term, and a logarithmic decay term. Through nonlinear least-squares fitting, this approach achieves effective separation of long-term tectonic deformation, seasonal fluctuations, high-frequency noise, and transient flood-related signals. The results show that the W-shaped floodplain east of Xiong’an New Area does not exhibit the expected subsidence induced by water loading but instead features pronounced surface uplift of up to 30 mm. Multi-physics forward modeling reveals the underlying mechanism: the elastic subsidence caused by surface water loading, calculated via the LoadDef spherical loading theory, amounts to only ~2 mm. In contrast, forward modeling based on the GMS three-dimensional groundwater seepage model and the principle of effective stress indicates that the pore water rebound effect can produce surface uplift of up to ~36 mm. The superposition of these two effects is highly consistent with InSAR observations in terms of magnitude, direction, and spatial distribution, confirming that the flood-induced surface deformation is dominated by the pore water rebound effect driven by rapid groundwater recharge, rather than subsidence from water loading. The proposed framework extends the application potential of geodetic techniques for monitoring short-period extreme hydrological events. Full article

Numerous types of environmental toxicants alter human metabolomics, directly or indirectly, through gut microbial dysbiosis, upsetting immune homeostasis. Environmental toxicants capable of these direct and indirect effects have included heavy metals, pesticides, herbicides, polychlorinated biphenyl (PCB) congeners, and endocrine-disrupting chemicals. The cell and molecular events induced by some diverse toxicants are reviewed, along with their potential additive, synergistic, and antagonistic effects on immune homeostasis (increasing proinflammatory immune cell activation and suppressing immunoregulation), which leads to systemic oxidative stress (OS). As people are exposed in varying degrees to countless chemicals and environmental factors over a lifetime, it is challenging to correlate specific diagnoses to any single toxicant or exposure, which is often a key challenge in linking environmental exposure to health outcomes. However, many toxicants have the common mechanistic effect of OS. The effects of toxicants are more pronounced with aging due to cumulative exposures and immunoaging (immunosenescence), with chronic low-grade inflammation referred to as “inflammaging”. The cell and molecular mechanisms of toxicants include altered calcium flux, mitochondrial dysfunction, and increased levels of damage-associated molecular patterns (alarmins) that trigger an inflammatory response and possibly promote autoimmune and neurological disorders. OS skews type-1 immunity for defenses against pathogens and cancers more toward type-2 immune responses to self-antigens (autoimmunity). The toxicants may directly affect the innate and adaptive immune cells inducing this skewing, or they may modify portions of gut microbial species and strains and their production of metabolites that indirectly affect systemic immunity. These latter toxicant influences require metabolomic analysis of the differential structures and activities of the microbial metabolites. The damaging effects of OS and inflammation disrupting immune homeostasis and leading to disorders are reviewed and discussed. The need for well-designed studies that allow for standardized comparison of exposures and related effects are emphasized, and their real-world limitations noted. Full article

Background/Objectives: Neurocognitive disorders represent a growing burden among older adults. Although respiratory vaccines have demonstrated efficacy and safety in preventing acute respiratory events, their potential impact on the development of chronic neurocognitive disorders, such as cognitive impairment, dementia, and Alzheimer’s disease (AD), has not been extensively explored. The objective of this scoping review was to synthesize and analyze the available evidence on the association between respiratory vaccination and the risk of developing cognitive impairment, dementia, and Alzheimer’s disease. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. A literature search was performed in the PubMed, Scopus, and Web of Science databases through 15 June 2026. Studies involving older adults (≥60 years), irrespective of their baseline neurocognitive status, were included. Observational studies (cohort and case–control studies) were considered. Editorials, narrative reviews, and other non-original articles were excluded. Results: Eighteen studies were included, with cohort studies being the predominant design. Four main categories of respiratory vaccines were evaluated: influenza, COVID-19, respiratory syncytial virus (RSV), and pneumococcal vaccines, in relation to the risk of cognitive impairment, dementia, and AD. Influenza vaccination was associated with a lower risk of dementia and AD, with a potential dose–response relationship observed, whereby a greater number of vaccinations was associated with a greater reduction in risk. Pneumococcal vaccination was also associated with a lower risk of dementia and AD, particularly among individuals who received a greater number of vaccine doses. In contrast, the evidence regarding COVID-19 and RSV vaccines was limited and yielded heterogeneous findings. Conclusions: Influenza and pneumococcal vaccination maybe associated with a lower risk of Alzheimer’s disease and dementia. However, the evidence regarding COVID-19 and RSV vaccines remains limited, and additional studies are needed to clarify their impact on the risk of developing neurocognitive disorders. Full article

Background/Objectives: Retinal imaging has considerable potential for monitoring Alzheimer’s disease (AD) neurodegeneration, as retinal ganglion cell dendritic atrophy within the inner plexiform layer (IPL) is an early event. We tested whether quantitative optical coherence tomography (OCT) speckle texture analysis combined with supervised machine learning could discriminate AD-related IPL alterations without exogenous contrast agents in a mouse model. Methods: Retinal explants from triple-transgenic AD mice (n = 7, aged 12 months) and C57BL/6 controls (n = 3, aged 15 months) were imaged ex vivo using a custom 1040 nm spectral-domain OCT system. Five grey-level co-occurrence matrix (GLCM) features were extracted from IPL volumes of interest (VOIs) and classified using a linear support vector machine (SVM). Results: AD and control IPL textures formed two completely separable clusters in a two-dimensional feature space defined by contrast and entropy (0°), achieving 100% VOI-level classification accuracy (95% CI: 96.4–100%). However, given the small sample size, VOI-level rather than animal-level validation, lack of histological confirmation, non-interleaved image acquisition, and differences in age/strain between groups, these results represent exploratory dataset separability rather than a validated diagnostic test. Conclusions: These findings demonstrate the feasibility of the ligand-free, texture-based OCT discrimination of IPL alterations, indicating a strong underlying optical signal. Adequately powered, in vivo longitudinal studies with matched controls, interleaved acquisition, animal-level cross-validation, and histological validation are required before any clinical translation. Full article

Dust storms are a major environmental hazard across the Arabian Peninsula, affecting air quality, human health, transportation, and infrastructure. Despite their frequency in Riyadh, event-based studies integrating aerosol optical observations, atmospheric transport analyses, potential source-region identification, and surface validation remain limited. This study characterized dust events over Riyadh during 2024–2025 using AERONET aerosol observations, NOAA Integrated Surface Database (ISD) meteorological records, HYSPLIT backward trajectories, and potential source contribution function and concentration-weighted trajectory analyses. Dust events were identified using a dual optical criterion based on aerosol optical depth (AOD) at 500 nm (AOD₅₀₀ ≥ 0.50) and the 440–870 nm Ångström exponent (≤0.50) and were compared with co-located NOAA ISD present-weather and visibility observations. Among the 34 identified dust events, 82% occurred between March and May. The events were dominated by coarse-mode aerosols, with a mean Ångström exponent of 0.28 and a mean fine-mode fraction of 0.26. Same-day dust-related present-weather reports were recorded for 26 events (76%), while the remaining eight events (24%) were classified as elevated because no dust-related present-weather code was reported at the co-located ISD station during the corresponding event day. The trajectory and source–receptor analyses showed a consistent spatial association with the Mesopotamian Basin as a major potential source region and the northern Rub’ al-Khali as a secondary potential source region. Surface wind speed was significantly and positively associated with coarse-mode aerosol loading and dust-event severity, whereas sea-level pressure showed no statistically significant association with severity. These findings provide an updated observational characterization of dust events affecting Riyadh during 2024–2025 and demonstrate the complementary value of aerosol optical observations, co-located surface records, atmospheric transport analysis, and source–receptor methods for examining dust-event characteristics and transport over central Saudi Arabia. Full article

Background and Clinical Significance: This paper presents a case of Vogt–Koyanagi–Harada (VKH)-like disease following nivolumab and ipilimumab therapy for squamous cell carcinoma of the lung, complicated by transient type 1 macular neovascularisation (MNV). Case Presentation: A 67-year-old man presented with reduced visual acuity, more pronounced in the left eye, accompanied by headache and neurosensory hearing loss for 10 days. He had been receiving combination therapy with nivolumab and ipilimumab for approximately nine weeks. Slit-lamp examination and multimodal imaging revealed multiple serous retinal detachments, choroidal folds, and bacillary layer detachment. A bilateral VKH-like syndrome was considered the most likely diagnosis, consistent with an immune-related adverse event (irAE). High-dose systemic corticosteroids were initiated, resulting in marked anatomical improvement and recovery of visual acuity. Following multidisciplinary discussion with the patient’s oncologist, ipilimumab was permanently discontinued and nivolumab was rechallenged in combination with chemotherapy after resolution of the ocular adverse events, given the progression of the underlying malignancy. Notably, optical coherence tomography angiography (OCTA) additionally demonstrated a type 1 non-exudative MNV, which resolved spontaneously during follow-up. Conclusions: Nivolumab and ipilimumab, targeting PD-1 and CTLA-4, respectively, are effective anticancer therapies but may induce immune-related adverse events involving the eye. VKH-like disease is a rare but potentially vision-threatening complication. Early recognition and prompt treatment are essential for favourable visual outcomes. In summary, this is a rare case of VKH-like disease associated with nivolumab and ipilimumab therapy, complicated by transient inflammatory type 1 MNV. Clear guidelines are needed regarding management of ocular immune-related adverse events and decisions on continuation or discontinuation of life-prolonging immunotherapy. Full article

Contusions are highly prevalent injuries in the armed forces. They can substantially impair physical performance, particularly in special operations forces, where operational readiness depends on maintaining a high level of physical fitness. Transcutaneous microcurrent therapy (TMCT) is a non-invasive intervention that has been reported to promote tissue repair. The aim of this case report was to describe the evolution of creatine kinase levels, functional outcomes, pain, and perceived well-being during TMCT following an acute traumatic contusion. Case presentation: A 34-year-old special operations military officer with an acute traumatic contusion in the dorsum of the left foot received TMCT applied over the injured area for 72 h. The device delivered a monophasic rectangular current at 21 mV and 42 μA, with a total application time of 2360 min over the 72-h observation period. CK and the Hooper Index were assessed at baseline and at 24, 48, and 72 h, whereas NPRS and LLFI were assessed at baseline and at 72 h. Over the 72-h observation period, CK decreased from 571 to 203 IU/L, the Hooper Index decreased from 15 to 12 points, the NPRS score decreased from 7 to 6 points, and the LLFI score increased from 52% to 84%. No intervention-related adverse events were reported. Conclusions: During the 72-h observation period, reductions in CK and pain and an increase in perceived lower-limb function were observed while the participant was receiving TMCT. These preliminary observations support further investigation of TMCT as a potential adjunct to standard conservative care. However, the single-case design and the absence of a control condition prevent the observed changes from being attributed to TMCT. Controlled studies are required to evaluate its efficacy and clinical applicability. Full article

Background: In recent decades, the incidence of colorectal cancer (CRC) has been rising worldwide. CRC ranks second in cancer-related mortality. The identification of reliable biomarkers for early diagnosis and prognosis prediction, along with a deeper understanding of the underlying molecular events, holds substantial promise for improving patient outcomes. The tissue inhibitor of the metalloproteinase 1 (TIMP1) gene is overexpressed in various gastrointestinal malignancies and contributes to tumor progression. However, its role in regulating the CRC tumor immune microenvironment (TIME) and its potential as a clinically actionable prognostic biomarker remain unclear. Methods: To probe how TIMP1 acts as a prognosis-related candidate biomarker in colorectal carcinoma, TCGA-derived datasets were adopted to conduct Kaplan–Meier survival assessment. We also investigated the connection between the expression abundance of TIMP1 and the infiltration of immune populations and intratumoral lymphocytes; furthermore, immune checkpoint-related genes were systematically assessed across multiple tumor types via the TISIDB and TIMER2.0 platforms, with particular emphasis on CRC. We adopted the ESTIMATE scoring system to figure out how TIMP1 gene expression correlates with the phenotypic properties of the colorectal-cancer TIME. We relied on the limma toolkit for the screening of differential transcripts from high-TIMP1 and low-TIMP1 cohorts. Enrichment assessments covering Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes entries were then carried out to predict the potential biological pathways associated with TIMP1. We constructed the protein–protein interaction map for TIMP1-interacting partners via the STRING repository. To further explore TIMP1-correlated genes, we performed Venn diagram intersection analysis combined with Spearman’s correlation test. Finally, quantitative reverse-transcription PCR was then implemented to detect TIMP1 messenger-RNA abundance inside the RKO colorectal carcinoma cell line as well as normal colonic epithelial CCD-18Co cells, which offered in vitro experimental verification for our bioinformatic outcomes. Results: According to outcome data, TIMP1 transcripts were markedly up-regulated in CRC specimens and cell lines relative to normal samples. Elevated TIMP1 expression served as a poor-prognosis indicator for overall survival (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.29–0.64, p < 0.001) and disease-specific survival (HR = 0.39, 95% CI = 0.22–0.68, p = 0.001) among colorectal-carcinoma patients. TIMP1-high and TIMP1-low groups exhibited notable differences in immune cell infiltration (CD8⁺ T, macrophage, mast, neutrophil, B, monocyte, dendritic, and CD4⁺ T cells). TIMP1 expression was also significantly correlated with tumor-infiltrating lymphocytes, key immune checkpoint genes (e.g., CD274 [PD-L1] and CTLA4), and immunomodulatory chemokines (e.g., CCL3 and CCL5). Twelve TIMP1-interacting DEGs were selected: COL5A1, FN1, PRG4, and a cluster of nine MMPs (MMP1/2/3/7/8/9/11/13/14), all of which showed significant positive correlations with TIMP1 (r = 0.31–0.63, all p < 0.001). Conclusions: TIMP1 expression correlates with features of the tumor immune microenvironment and extracellular matrix remodeling in CRC, suggesting that TIMP1 shows potential as a candidate biomarker. However, its potential as a therapeutic target warrants further experimental investigation. Full article

Background: Oxidative stress is an important contributor to brain abnormalities in Down syndrome (DS), but the status of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway during early postnatal development remains poorly understood. The current study aimed to investigate whether an impairment of the NRF2 pathway is already present in the Ts65Dn mouse model of trisomy 21 at neonatal life stages and whether early treatment with astaxanthin-loaded stealth solid lipid nanoparticles (AST-SSLNs) positively impacts NRF2 signaling and reduces oxidative stress. Methods: Hippocampal NRF2 pathway components and oxidative stress markers were analyzed in neonate Ts65Dn and euploid mice. From postnatal day (P)3 to P15, mice received daily subcutaneous injections of AST-SSLNs or unloaded nanoparticles. NRF2 pathway activation, reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and safety parameters were evaluated. Results: Untreated Ts65Dn mice exhibited early impairment of the NRF2 pathway, characterized by increased BACH1, reduced NRF2 activation, and decreased HO-1 expression. Neonatal AST-SSLN treatment enhanced NRF2 activation, improved HO-1 levels, and normalized ROS accumulation, lipid peroxidation, and protein carbonylation in the hippocampus, a brain region critically impaired in DS. Treatment had no adverse effects on survival, body weight, or brain weight. Conclusions: These findings demonstrate that NRF2 pathway dysfunction is an early event in trisomy 21 and identify the neonatal period as a potential therapeutic window to counteract oxidative stress. AST-SSLNs represent a promising nanomedicine-based strategy to activate the impaired NRF2 pathway and reduce early hippocampal oxidative damage in DS. Full article

Background/Objectives: Cervical cancer (CC) is currently one of the leading causes of cancer-related mortality worldwide. Patients with advanced, recurrent, or metastatic CC, for whom treatment options are limited, are particularly at risk. Tisotumab vedotin (TV) is a first-in-class antibody–drug conjugate targeting tissue factor (TF), representing a promising therapeutic breakthrough. This systematic review aims to comprehensively evaluate the clinical efficacy, safety profile, and therapeutic potential of TV, both as monotherapy and in combination regimens, in patients with advanced cervical cancer. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Embase databases, as well as on the ClinicalTrials.gov website, for prospective clinical trials (Phases I–III) in accordance with the PRISMA 2020 guidelines. The search focused on original articles and studies published between 2019 and 2026. Four key clinical trial programmes (innovaTV 201, 204, 205, and 301), involving 548 patients, were selected. Quality assessment was performed using the Cochrane RoB 2.0 tool and the NIH tool for assessing the quality of “before-and-after” studies. Results: Objective response rates (ORR) with TV ranged from 17.8% in monotherapy to 65.8% in combination regimens, confirming its efficacy in treatment. In randomised Phase III trials, the use of TV improved overall survival compared to standard chemotherapy. Adverse effects characteristic of TV are primarily ophthalmic complications, peripheral neuropathy, and hemorrhagic events. These were managed through pre-established prophylactic and monitoring protocols. Combination therapies increased therapeutic efficacy but also raised the incidence of grade ≥ 3 adverse events occurring during treatment. Conclusions: TV offers new hope by changing the treatment algorithm for cervical cancer. As a targeted therapy, it provides an effective alternative to conventional chemotherapy in previously treated patients. It also has the potential for use in first-line multi-drug treatment regimens. Strict adherence to safety protocols is essential to minimise toxicity and ensure treatment continuity. Full article

Background/Objectives: Adrenocortical carcinoma (ACC) is a rare malignancy in which overexpression of steroidogenic factor-1 (SF-1/NR5A1) and aberrant activation of canonical Wnt/β-catenin signaling are important oncogenic events. However, the extent to which these regulatory axes converge or interact at the transcriptional level remains unclear. We investigated their relationship using bulk transcriptomic and regulatory-network approaches. Methods: Regulatory network inference using RTN/ARACNe was applied to the TCGA-ACC cohort. NR5A1 and β-catenin-associated TCF/LEF regulon activities were evaluated in perturbation datasets and tested for associations with CpG island methylator phenotype (CIMP), overall survival, and gene-level interaction effects. Candidate modulators of NR5A1 activity were assessed using the MINDy algorithm. The effects of cBAF inhibition on NR5A1 regulon activity were also evaluated in H295R and CU-ACC1 cells. Results: NR5A1 knockdown repressed steroidogenic pathways, whereas β-catenin knockdown predominantly suppressed Wnt/β-catenin signaling. In TCGA-ACC, NR5A1 regulon activity was associated with CIMP-high status and overall survival. In contrast, β-catenin-related regulons were not significantly associated with CIMP-high status after adjustment for NR5A1 activity, and no significant multiplicative interaction effects were identified. Fewer than 3% of protein-coding genes showed improved fit in models including NR5A1 × TCF/LEF interaction terms, without enrichment for steroidogenic or Wnt/β-catenin-related pathways. CTNNB1 was identified as a statistically significant but low-ranking positive modulator of NR5A1 activity, whereas CTNNBIP1 was a top-decile negative modulator. cBAF inhibition was associated with NR5A1 regulon repression in both cell models. Conclusions: These findings indicate limited detectable global transcriptional convergence between NR5A1 and canonical β-catenin-related regulons in the evaluated bulk transcriptomic frameworks. Potential relationships between these pathways may depend on more localized, chromatin-dependent, protein-level, or context-specific regulatory mechanisms. NR5A1 regulon activity showed more consistent associations with CIMP-high status and clinical outcome than the β-catenin/TCF-LEF regulons in the evaluated TCGA-ACC models. The modulation patterns associated with CTNNB1 and CTNNBIP1, together with the repression of NR5A1 regulon activity following cBAF inhibition, raise the possibility that NR5A1 acts as a context-dependent regulatory node connecting oncogenic signaling and chromatin-remodeling mechanisms in ACC. These findings support further investigation into the role of chromatin-remodeling complexes in sustaining NR5A1-driven transcriptional programs in ACC. Full article

Background: The role of socioeconomic status (SES) in individual intertemporal decision-making has received widespread research attention. However, findings regarding its underlying psychological mechanisms remain inconclusive. This study investigates not only the association between SES and intertemporal decision-making but also the underlying cognitive neural mechanisms from both behavioral and electrophysiological perspectives. Methods: Individuals with high and low SES were recruited. In Experiment 1, a behavioral experiment used the Monetary Choice Questionnaire to measure delay discounting rates using the Kirby method and hierarchical Bayesian modeling, as well as choice consistency using the inverse temperature parameter of the softmax function, to examine differences in decision-making between the two groups. In Experiment 2, event-related potential techniques were employed to examine differences in dynamic neural activity during an intertemporal choice task between the high- and low-SES groups. Results: The behavioral results revealed that, in Experiment 1, the low-SES group exhibited a larger delay discounting rate than the high-SES group. The hierarchical Bayesian modeling further indicated that the low-SES group had lower choice consistency. Experiment 2 found that the low-SES group showed a significantly higher proportion of smaller-sooner (SS) choices than the high-SES group. Electroencephalographic results revealed that, compared with the high-SES group, the low-SES group exhibited larger P200 amplitudes but smaller N2 and P300 amplitudes. Within the high-SES group, the larger-later (LL) option elicited more negative N2 and larger P300 amplitudes than the SS option. Conversely, in the low-SES group, P300 amplitudes did not differ significantly between the SS and LL options during the later stage of intertemporal decision-making. Conclusions: The results showed that the low-SES group was more inclined toward immediate gains, made more random choices, displayed higher variability, relied more on intuitive heuristic strategies, and exhibited weaker cognitive control and reduced cognitive resource allocation during intertemporal decision-making. However, at the later stage, the absence of a significant difference between SS and LL options provided preliminary EEG evidence consistent with the possibility that individuals in the low-SES group did not completely disregard future outcomes. Full article

Background: The interaction between COVID-19 vaccination and immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) remains incompletely characterized. Methods: Retrospective cohort study of 139 patients with stage IV NSCLC treated with first-line ICI-based therapy, stratified by vaccination status and total doses received (0–1 vs. ≥2). Progression-free (PFS) and overall survival (OS) were analyzed by Kaplan–Meier and Cox regression; logistic regression explored factors associated with treatment-related toxicity. Results: Vaccinated patients had longer median PFS (13.0 vs. 11.0 months) and OS (29.0 vs. 24.0 months; both p < 0.001). In multivariable models these associations were attenuated and of borderline significance (OS HR = 0.83, 95% CI 0.69–0.99; PFS HR = 0.79, 95% CI 0.62–0.99). Outcomes were also more favorable with ≥2 doses (median PFS 14.0 vs. 12.0 months, p = 0.001; median OS 30.0 vs. 24.0 months, p < 0.001), and tumor mutational status was the strongest independent predictor of survival. In an exploratory model, ≥2 doses were associated with higher odds of any-grade toxicity (OR = 2.47, p = 0.037); events were predominantly low grade, with no Grade 4 or 5 toxicity. Conclusions: COVID-19 vaccination was associated with improved PFS and OS in stage IV NSCLC receiving first-line ICI therapy, with a dose-related pattern. The association was attenuated after adjustment for tumor biology and is hypothesis-generating. These findings support the safety and potential clinical relevance of vaccination in this population and underline the need for structured monitoring during immunotherapy. Prospective validation is required. Full article

Acne vulgaris is one of the most prevalent dermatological conditions, affecting up to 85% of individuals aged 11–30 years. Clascoterone cream is the first topical androgen receptor inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of acne vulgaris in patients aged 12 years and older, and the first agent in this class approved for use in both male and female patients. The aim of this narrative review is to summarize the current evidence regarding the efficacy, safety profile, and potential future applications of clascoterone in the treatment of acne vulgaris. A comprehensive literature search was conducted in PubMed/MEDLINE and ClinicalTrials.gov databases up to April 2026. Search terms included “clascoterone,” “cortexolone 17α-propionate,” and “androgen receptor inhibitor acne.” Eligible publications included randomized controlled trials, meta-analyses, open-label extension studies, retrospective analyses, case reports, and relevant review articles published in English. Clinical trial registries and regulatory agency announcements were also searched for ongoing studies and recent approval decisions. Phase 3 trials and meta-analyses demonstrate that twice-daily application of clascoterone 1% cream significantly reduces inflammatory and non-inflammatory lesion counts compared to vehicle, with efficacy sustained up to 12 months of treatment. The safety profile is favorable, with adverse events limited predominantly to mild and transient local skin reactions. Subgroup analyses have shown no significant sex-related differences in efficacy or safety, and the safety profile appears comparable between adolescents and adults. In an exploratory pooled subgroup analysis, lesion-count reductions were greater in adults than in adolescents, whereas the adjusted between-group comparison of IGA success was not statistically significant. Because no formal treatment-by-age interaction test was reported, these findings should be considered hypothesis-generating. Emerging but still incomplete data suggest potential applications in androgenetic alopecia and mild hidradenitis suppurativa. Clascoterone represents a novel addition to the therapeutic armamentarium for acne vulgaris, offering a unique mechanism of action with a favorable safety profile. Further research is warranted to establish its role in combination therapies and in other androgen-dependent dermatoses. Full article