Extramedullary plasmacytoma (EMP) is a rare plasma cell malignancy, accounting for approximately 3% of all plasma cell neoplasms. Gastric plasmacytoma, a distinct subtype of EMP arising from B lymphocytes, is extremely uncommon, representing roughly 2% of EMP cases, and lacks specific clinical manifestations. Herein, we report a 53-year-old male presenting with persistent acid reflux and heartburn. Gastroscopy identified a flat, elevated lesion in the gastric body. Endoscopic mucosal resection (EMR) was performed to obtain the lesion specimen. The diagnosis of primary solitary gastric plasmacytoma was confirmed via histopathology, immunohistochemistry, bone marrow aspiration, serum and urine free light chain assays, and positron emission tomography-computed tomography (PET-CT). We further review the clinical features, diagnostic approaches, therapeutic strategies, and prognosis of this disease, aiming to provide a reference for the diagnosis and management of rare gastric plasma cell tumors in clinical practice.

National organizations recommend formal breast cancer risk evaluation (BCRE) beginning at age 25 years; however, implementation remains inconsistent in routine clinical practice. Because BCRE frequently occurs during screening mammography visits beginning at the age of 40 years for average-risk women, younger women often remain outside established screening pathways. Gynecology practices offer an opportunity for earlier risk identification.

Within the initiative's catchment area, high-risk breast cancer evaluations historically occurred at a median age of 48 years, with few women younger than 40 years receiving formal risk evaluation.

This quality improvement initiative used a pre- to post-implementation design in an outpatient gynecology practice. Women aged 25-39 years presenting for routine well-woman visits were included. The Tyrer-Cuzick model was integrated into the intake workflow, and certified medical assistants received education on breast cancer risk factors, model use, and management of high-risk results.

A standardized workflow was developed in which BCRE was completed during patient intake before provider evaluation, allowing timely review and referral planning for high-risk patients.

Breast cancer risk evaluation was completed for 65% (n = 77) of eligible patients. Among assessed women, 14% (n = 11) were identified as high risk (≥20% lifetime risk), and all were referred for further high-risk breast cancer evaluation. Staff reported strong feasibility and acceptability of workflow integration.

Integrating the Tyrer-Cuzick model into routine gynecologic care represents a practical and scalable strategy for improving early identification of high-risk women and supporting nurse practitioner-led preventive breast cancer care.

In the past 15 years, immunotherapy has become a major strategy for cancer therapy. Tumor-infiltrating lymphocyte (TIL) therapy has been under investigation for nearly four decades and received its first Food and Drug Administration approval in 2024, when lifileucel was approved for patients with previously treated metastatic melanoma. TIL therapy is a form of cell-based immunotherapy that uses autologous T cells isolated from the tumor microenvironment, which are expanded ex vivo and reinfused to mediate tumor regression after lymphodepleting chemotherapy and high-dose interleukin-2. Current data demonstrate durable responses in a subset of heavily pretreated patients with advanced melanoma, and early clinical studies suggest activity in other immunogenic solid tumors. In this review, the historical development of TIL therapy, its current clinical applications, emerging strategies to optimize product composition and the tumor microenvironment, and the critical role of surgeons in TIL procurement and delivery are summarized.

The systematic link between cellular spatial organization and its biomechanical consequences remains a critical knowledge gap in human oncology.

To quantitatively map the cellular architecture of solid tumours and elucidate its mechanistic impact on mechanical signalling, immune infiltration, and patient survival.

We developed a scalable digital pathology framework, processing 7910 H&E whole-slide images across 21 solid tumours. A deep learning pipeline was employed to segment over 4.7 billion nuclei, enabling the calculation of cell density and nearest neighbour distance (NND) as key spatial metrics. To bridge morphology and function, we integrated these metrics with bulk RNA-seq data from 19 TCGA cohorts (n = 7401) using rigorous histological matching. Furthermore, to resolve microenvironmental heterogeneity, we performed unsupervised clustering of over 60 000 T-cell transcriptomes from independent cohorts. These findings were validated through high-resolution Visium-HD spatial transcriptomics to correlate physical proximity with localized gene expression.

While tumours exhibited significant heterogeneity, NND, but not cell density, emerged as a primary determinant of biomechanical and immune signatures. A trend-level association was observed between lower NND and higher Hippo/YAP/TAZ pathway activity across nine matched cancer types (Spearman's ρ = -.65, p = .058, n = 9). In addition, lower NND was significantly correlated with increased CD4⁺ memory T-cell (CD4⁺ T_Mem cell) abundance (Spearman's ρ = -.86, p < .01). Single-cell analyses confirmed that CD4⁺ T_Mem cells intrinsically express mechanical stress signalling markers, which spatial transcriptomics localized to CD4⁺ T_Mem cell aggregation zones characterized by high pathway activity. Clinically, this spatial-mechanical-CD4⁺ T_Mem cell axis was associated with prognosis in breast, oesophageal, liver, and lung adenocarcinomas, where high mechanical signalling generally predicted poor outcomes but could be modulated by CD4⁺ T_Mem infiltration levels.

Our study identifies low NND as a spatial correlate of biomechanical crowding that is associated with CD4⁺ T_Mem cell programming and adverse clinical outcomes. By integrating deep learning-based spatial metrics with multi-omics, we highlight spatial mechanics as a critical, potentially targetable dimension of the tumour microenvironment for future immunotherapies.

The aim of this study was to investigate key target(s), mechanism(s) from hepatoma cells in harsh doxorubicin-resistant conditions (DRCs) from GSE125180 datasets in GEO (Gene Expression Omnibus).

The identified components can be denoted as a brightness (therapeutic mark) or darkness (resistant mark) in DRCs. The protein-protein interaction (PPI) networks were assembled to identify the relationships between upregulated and downregulated genes via STRING, and R program.

In the |log2 FC| > 1, and |log2 FC| > 2 subgroups, the uppermost target was a non-receptor tyrosine kinase (SRC) downregulated in DRCs, indicating that the dampened SRC is a therapeutic mark by doxorubicin (DOX). In contrast, in the |log2 FC| > 3 subgroup, the most significant target was Cluster of Differentiation 93 (CD93) upregulated in DRCs, suggesting that the overexpressed CD93 is a resistant mark in DRCs. Metoclopramide (MET) @ CD93 + DOX conformer is a highlighted capture to illuminate as combination therapy to overcome DRCs because MET is an inhibitor against CD93 as well as a non-competitive inhibitor on (MET @ CD93 + DOX) conformer.

These findings provide a mechanistic rationale for repurposing MET as an adjuvant agent to enhance therapeutic efficacy and overcome drug resistance in combination treatment strategies.

Clusters of epithelial cells of the fallopian tube exhibiting aberrant p53 expression, termed "p53 signatures," are detected at a relatively high frequency and have been regarded as putative precursors of high-grade serous carcinoma (HGSC). In contrast, the recently proposed "β-catenin signature" represents a distinct tubal epithelial alteration characterized by the aberrant expression of β-catenin, the biological significance of which remains unclear. To clarify the frequency and spatial relationship between the two lesions, we analyzed 30 consecutive risk-reducing salpingo-oophorectomy specimens from BRCA1/2 mutation carriers using the sectioning and extensively examining the fimbriated end protocol and performed immunohistochemical evaluation for p53, β-catenin, and Ki-67. p53 signatures and β-catenin signatures were each identified in seven cases (23%). Two cases (6.7%) harbored both lesions; however, no spatial overlap or histological continuity was observed. Neither lesion demonstrated significant associations with BRCA mutation subtype, age, body mass index, or parity. Furthermore, no cases showed serous tubal intraepithelial lesion, serous tubal intraepithelial carcinoma, or HGSC. These findings suggest that p53 signatures and β-catenin signatures may represent distinct localized epithelial alterations in the fallopian tube, although further molecular and spatial analyses are required to clarify their biological relationship.

Despite the increasing prevalence of autism spectrum disorder (ASD) in the US, underlying temporal trends in newly recorded diagnoses remain poorly understood.

To evaluate age- and sex-specific incidence trends of ASD from 2016 to 2024 and quantify the temporal patterns before and after the COVID-19 pandemic and diagnostic substitution.

This retrospective cohort study used electronic health record data from a large US health care system. Analyses were conducted from October to December, 2025. The study population included 171 134 participants (stratified as children [0-9] years, adolescents [10-18] years, and adults [≥19] years) who maintained continuous engagement with the health care system, defined as having at least 1 clinical encounter annually from 2016 to 2024.

The primary outcome was the annual incidence of newly recorded diagnoses of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes F84.0 and F84.5. Temporal trends were analyzed using joinpoint regression to calculate annual percentage changes (APCs) and identify significant inflection points.

Among 171 134 participants (mean [SD] age, 26.78 [16.38], 63.8% female), females received autism diagnoses a mean (SD) of 3.4 years later than males (age at diagnosis, 15.7 years for female individuals vs 12.3 years for male individuals; P < .001). Male autism incidence remained stable or declined 2016 to 2024; female incidence increased significantly post-2020 (APC, 19.0%; 95% CI, 12.1% to 33.4%). In the pediatric cohort, decreasing annual incidence among males (APC, -2.0%; 95% CI, -3.7% to -0.3%; to APC, -2.0%, 95% CI, -3.7% to -0.3%) alongside increasing incidence for females since 2020 (APC, 17.4; 95% CI, 9.0% to 45.3%). In adolescent males, incidence declined from 2016 to 2018 (APC, -29.6%; 95% CI, -48.9% to -1.2%), and stabilized from 2018 to 2024. In adolescent females, autism incidence increased significantly between 2020 and 2024 (APC, 22.3%; 95% CI, 6.1% to 62.8%). In adult males, autism incidence showed a downward trend in the 2016 to 2024 period, while in adult females, the APC from 2016 to 2024 was positive, but the finding was not statistically significant (APC, 8.0%; 95% CI, -0.9% to 20.0%).

In this cohort study, ASD diagnoses increased disproportionately among females after 2020 while remaining stable or declining among males. These patterns suggested that increasing ASD prevalence reflected improved identification of historically underrecognized presentations rather than a uniform population-level increase. These findings highlight the need for screening strategies that address sex-specific presentations.

We examined the effect of a short-term descent to low altitude on sleep-disordered breathing (SDB) in healthy moderate altitude residents.

Forty-four healthy participants (50% females), median age 47 years, living > 1000 m (median (IQR) altitude of 1230 m (1130; 1560)), were included. Polysomnographies were carried out for two consecutive nights at the participants' home elevations and for two nights at the sleep laboratory in Chur (590 m), Switzerland, after a 2-week washout period, in accordance with a randomized crossover design. The primary outcome was time spent under 90% oxygen saturation (T90). Important secondary outcomes were nocturnal oxygen saturation (SpO₂), apnea-hypopnea index (AHI), and oxygen desaturation index (ODI). Additional outcomes were sleep stage-related parameters. The trial has been registered at clinicaltrials.gov (NCT05826808).

Mean ± SE T90 was 1 ± 2 min at 590 m and 5 ± 2 min at > 1000 m (mean difference of 4 min, 95% CI of 1 to 7, p = 0.005). At 590 m, the total AHI was 9.2 ± 1.6/h (2.3% with AHI > 30/h), ODI 6.0 ± 1.4/h, and SpO₂ 95.2 ± 0.2%. At > 1000 m, the total AHI was 14.2 ± 1.6/h (13.6% with AHI > 30/h, p = 0.025 vs. 590 m), ODI 10.0 ± 1.4/h, and SpO₂ 93.8 ± 0.2% (p < 0.001 all comparisons versus 590 m). Mean slow wave sleep on the second night at 590 m was 10.0 ± 1% and 8.0 ± 1% at > 1000 m (p = 0.001). In males, descent to low altitude showed a more significant effect on T90 (mean difference of 7 min, 95% CI of 1 to 12, p = 0.024) and REM sleep stage (mean difference of 4%TST, 95% CI of 1 to 7, p = 0.011) compared to females.

A short-term, low-altitude stay of healthy moderate altitude residents leads to a reduction in nocturnal hypoxemia and SDB, especially in males. These findings suggest that sleep-disordered breathing assessments at lower-than-living altitude might underestimate the severity of SDB in patients permanently living at moderate altitudes.

Several million people worldwide permanently live at moderate altitude. Due to the vast variety in heights worldwide, the altitude of the closest sleep laboratory might vary and be at a lower altitude, which may lead to underestimated results. Study impact: To our knowledge, the current study is the first to investigate the effect of a short-term descent to low altitude on sleep-disordered breathing (SDB) in healthy moderate altitude residents. In this paper, we show that a short-term, low-altitude stay leads to a reduction in nocturnal hypoxemia and less sleep-associated breathing disorders, especially in males. Moreover, the proportion of severe SDB is underestimated at lower-than-living sleep laboratory assessments.

To evaluate whether obstructive sleep apnea (OSA) is associated with corneal ulceration and surgical intervention, and to assess the impact of continuous positive airway pressure (CPAP) therapy on these outcomes.

This retrospective cohort study used data from the TriNetX electronic health record database. Adults aged ≥ 18 years with ≥ 1 year of ophthalmology follow-up were analyzed using nearest-neighbor propensity score matching (demographics and comorbidities standardized mean differences < 0.1). Three matched analyses were performed: OSA versus controls without OSA (n = 287,572 per group), CPAP-treated OSA versus controls with OSA without CPAP treatment (n = 100,959 per group), and CPAP-treated OSA versus controls without OSA (n = 99,909 per group). Outcomes were assessed over 20 years, excluding individuals with prior diagnoses. Risk ratios (RRs) with 95% confidence intervals (CIs) and p-values were calculated.

OSA was associated with higher incidence of corneal ulcer (0.98% vs 0.83%; RR 1.183, 95%CI 1.120-1.249), perforated corneal ulcer (0.15% vs 0.04%; RR 3.992, 95%CI 3.243-4.915), and keratoplasty (RR 1.556, 95%CI 1.427-1.696). Among OSA patients, CPAP was associated with lower incidence of perforated corneal ulcer (RR 0.730, 95%CI 0.584-0.913) and keratoplasty (RR 0.663, 95%CI 0.579-0.760), but higher incidence of dry eye (RR 1.189, 95%CI 1.172-1.206). Compared to controls, CPAP-treated OSA patients remained at elevated risk of corneal ulceration and surgical intervention.

OSA was associated with higher incidence of corneal ulceration, severe ulcer-related sequelae, and corneal surgical interventions. CPAP was associated with fewer severe ulcer complications and reduced keratoplasty utilization, but higher dry eye burden. CPAP was associated with reduced but persistent ocular risk in patients with OSA.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Self-management interventions improve health outcomes but suffer from limited accessibility and sustainability. The usage of digital interventions may offer scalable alternatives.

What is the effectiveness of self-management digital interventions in improving health-related outcomes among adults with COPD?

This umbrella review followed the JBI methodology and was registered in PROSPERO (CRD42024517476). A systematic search across multiple databases was conducted to identify relevant systematic reviews published in any language from database inception to February 2024. Effect sizes and confidence intervals reported in the included reviews were converted into equivalent odds ratios (eORs) to enable standardised comparisons across outcomes.

Thirteen systematic reviews (15 363 participants) were included, of which 11 reported meta-analyses and two provided narrative syntheses only. Self-management digital interventions improved physical activity (eOR 2·34 [95% CI 1·14-4·80]), quality of life (eOR 2·02 [1·41-2·90]), lung function (eOR 2·60 [1·04-6·50]), adherence (eOR 5·04 [2·14-11·87]), anxiety (eOR 1·43 [1·15-1·76]), and depression (eOR 1·30 [1·05-1·60]). Effects were inconclusive for dyspnoea, physical capacity, sedentary time, emergency visits, and mortality. Heterogeneity was substantial across most outcomes. The certainty of evidence according to the GRADE approach ranged from very low to moderate.

Self-management digital interventions appear effective in improving several key outcomes in COPD management. Future research should prioritise standardised methodologies and long-term evaluations to strengthen the evidence base.