To evaluate the impact of gestational diabetes mellitus (GDM) on fetal frontal lobe development, as assessed by the anteroposterior frontal diameter (APFD) and its relationships with standard cranial biometric parameters.

This case-control study included 257 singleton pregnancies between 20 and 38 + 6 week's gestation. Participants were divided into two groups: uncomplicated pregnancies (n=152) and pregnancies complicated by GDM (n=105). Ultrasound images were retrospectively analyzed to obtain APFD, occipitofrontal diameter (OFD), head circumference (HC), and transverse cerebellar diameter (TCD), as well as derived ratios (APFD/OFD, APFD/HC, and APFD/TCD). Clinical, metabolic, and perinatal data were collected.

No significant differences were observed between groups in APFD (36.9 vs. 35.5 mm, p=0.086), TCD (40.1 vs. 38.6 mm, p=0.206), or in any of the evaluated ratios, including APFD/OFD (p=0.897), APFD/HC (p=0.702), and APFD/TCD (p=0.602). These findings remained consistent after stratification by type of glycemic control (diet vs. insulin). In contrast, the GDM group exhibited higher body mass index, fasting glucose levels, estimated fetal weight, and abdominal circumference (all p<0.05), as well as lower uterine and umbilical artery pulsatility indices. No clinically relevant differences were observed in head circumference or Apgar scores.

GDM was not associated with detectable alterations in fetal frontal lobe morphometry or its proportional relationships with global cranial measurements. These findings indicate no detectable differences in fetal frontal lobe morphometry using ultrasound parameters. However, no conclusions can be drawn regarding functional or neurodevelopmental outcomes.

Diabetic retinopathy is caused by chronic hyperglycemia, which damages the retina's blood vessels and neurons. This study is aimed at identifying potential therapeutic targets for DR.

Transcriptomic and proteomic data were obtained from the Gene Expression Omnibus (GEO) and ProteomeXchange databases, respectively. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were intersected. An enrichment analysis of the overlapping genes was performed based on the DAVID database. A protein-protein interaction (PPI) network (STRING) was analyzed via Cytoscape/cytoHubba to identify key genes. Single-cell RNA-sequencing (scRNA-seq) data were processed using Seurat. Gene set enrichment analysis (GSEA) (clusterProfiler) and molecular docking (EnrichR) were performed. High glucose-induced retinal microvascular endothelial cells (RMECs) were used for functional assays.

The intersection of DEGs and DEPs yielded shared genes, enriched in the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, complement and coagulation cascades, and ECM-receptor interaction; a PPI network incorporating these genes revealed two key DR-associated highly expressed genes, COL1A1 and SERPINE1. GSEA showed that samples with high expression of these key genes were enriched in pathways such as reactome signaling by TGFB family members, inflammatory response, TGF-β signaling, and reactome cell extracellular matrix interactions. Single-cell and molecular docking analyses revealed high expression of the two key genes in fibroblasts and binding between SERPINE1 and paricalcitol, and HG induction increased their levels in RMECs, whereas knockdown of SERPINE1 repressed RMEC proliferation, migration, and invasion in vitro.

This study identifies SERPINE1 and COL1A1 as possible DR therapeutic targets, providing new insights into relevant therapeutic development.

Metastatic prostate cancer (PC) incidence has increased in US men, partly due to changes in prostate-specific antigen (PSA) screening recommendations. However, few studies have examined contemporary PSA screening practices in large US health care systems.

To describe and examine contemporary PSA testing practices associated with metastatic PC incidence.

This cohort study included veterans within the Veterans Health Administration that received a prostate needle biopsy (PNB) between January 2015 and December 2023 with follow-up through 2024, excluding those with a history of PC. Data were analyzed between July 1, 2023, and November 6, 2025.

PSA tests were retrieved from the VA Corporate Data Warehouse and categorized by age at first VA PSA (<50, 50-59, and ≥60 years) and by longest interval between consecutive VA PSA tests in the 5 years before PNB (≤24 vs >24 months). Clinical, laboratory, pathological, demographic, and census block group-level socioeconomic status data were obtained from the VA Multi-OMICS Analysis Platform for Prostate Cancer database.

Multivariable Cox models estimated hazard ratios (HRs) from time of first VA PSA to first PNB, evaluated risk of metastatic (regional or distant) vs localized PC or benign diagnosis, and adjusted for sociodemographic and clinical covariates.

There were 103 067 participants of whom 20 233 (19.6%) were younger than 50 years at first PSA, 31 546 (30.6%) were non-Hispanic Black, 58 264 (56.5%) were non-Hispanic White, and 13 277 (12.9%) had other race or ethnicity. Of all participants, 22 190 (21.5%) had a first PSA value of 1 ng/mL or less, 52 939 (51.4%) had a screening interval of 24 months or less, and 3773 (3.7%) were diagnosed with metastatic PC at time of PNB. Compared with men aged younger than 50 years at first PSA, those aged 50 to 59 years (adjusted HR [aHR], 1.27; 95% CI, 1.24-1.29) and 60 years or older (aHR, 2.37; 95% CI, 2.33-2.42) had higher risk of metastatic PC. Men with longer screening intervals had higher risk of metastatic PC (aHR, 1.14; 95% CI, 1.13-1.16). Men aged younger than 50 years with shorter screening intervals had lower rates of metastatic PC (adjusted risk ratio, 0.10; 95% CI, 0.09-0.12) compared with men aged 60 years or older with longer screening intervals.

In this cohort study, few veterans had the most favorable combinations of screening factors in relation to metastatic PC, suggesting potential for further screening optimization.

Outdoor workers in the Western United States (US), such as farm laborers, landscapers, and construction crews, face daily sun exposure far above safe limits, often up to ten times more than indoor workers, placing them at high risk for non-melanoma skin cancers and melanoma. Yet, despite decades of evidence, US regulations still do not classify solar ultraviolet (UV) radiation as a workplace hazard. Existing protections, like California&rsquo;s heat illness rules, address temperature but ignore cumulative UV burden. In contrast, countries such as Australia and Germany treat solar UV as an occupational carcinogen and require employers to provide protective clothing, shade, and worker education. In the US, prevention remains inconsistent, weakened by regulatory gaps, poor data on work-related skin cancers, and barriers such as limited sunscreen use and cultural norms. These shortcomings fall hardest on immigrant and low-wage workers, who often have the least access to protection and care. This population-level occupational health case analysis calls for urgent policy reform to recognize solar UV as a workplace hazard and adopt stronger protections to reduce preventable skin cancer disparities.

Endoscopic ultrasound-guided tissue acquisition is used to diagnose pancreatic mass lesions, but optimal needle selection remains uncertain. Reverse bevel ProCore fine needle biopsy (FNB) needles aim to enhance histologic procurement and reduce sampling burden; randomized evidence versus standard fine needle aspiration (FNA) is limited. We synthesized randomized trials to compare diagnostic performance, efficiency, and safety.

We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, Scopus, Web of Science, and ClinicalTrials.gov for randomized trials (parallel or crossover) comparing reverse bevel ProCore FNB with standard FNA in pancreatic masses. The primary outcome was diagnostic yield. Secondary outcomes included sensitivity, specificity, number of passes, sample adequacy, technical failure, and complications. Random effects meta-analysis pooled risk ratios and mean differences with 95% confidence intervals. Heterogeneity was assessed using I²; leave-one-out analyses explored high heterogeneity. Certainty of evidence was assessed with GRADE.

Five randomized trials (412 patients) were included. Diagnostic yield was equivalent (RR 0.99, 95% CI 0.94-1.05; I²=55%). Sensitivity (RR 1.03, 95% CI 0.96-1.11) and specificity (RR 1.05, 95% CI 0.87-1.27) were similar. ProCore required fewer passes (MD - 0.69, 95% CI - 1.11 to - 0.27; I²=79%). Sample adequacy was comparable (RR 1.02, 95% CI 0.90-1.16; I²=66%). Complications were uncommon (RR 1.93, 95% CI 0.57-6.58; I²=0%). Trial design did not modify diagnostic yield.

Reverse bevel ProCore FNB provides diagnostic yield comparable to standard FNA while reducing needle passes. Low to very low certainty supports individualized needle choice based on resources and tissue requirements.

We compared prostate cancer (PC) and clinically significant prostate cancer (csPC) identification performances of MRI-guided in-bore (IB) and software-fusion biopsy (SFB) techniques among small volume PI-RADS 4 index lesions.

We retrospectively reviewed 268 biopsy-naïve patients with 308 small volume PI-RADS 4 index lesions (≤ 7 mm in greatest dimension) on multiparametric prostate MRI and subsequent IB and SFB between January 2010 and December 2025. All IBs were performed by a single radiologist on 134 patients, while another radiologist and a urologist performed SFBs on the remaining 134 patients. Patient and lesion characteristics in both groups were analyzed. A multivariable binary logistic regression model was constructed to identify independent predictors of csPC.

Median age was 67 in both cohorts. Median PSA value was 5.1 and 6 ng/ml, PSA density was 0.11 and 0.09 ng/ml/cm³ in IB and SFB cohorts, respectively. Among 308 PI-RADS 4 lesions ≤ 7 mm, PC was identified in 169 (54.9%) lesions, while csPC was identified in 94 (30.8%) lesions. IB technique revealed 60.1% and 41.9% PC and csPC among 148 lesions. SFB technique revealed PC and csPC rates of 50% and 20.6%, respectively, among 160 lesions. In-bore biopsy technique (p < 0.001), PSAD (p = 0.001) and number of cores (p = 0.010) were independent predictors of csPC on multivariate analysis.

Our study indicates that a significant proportion of small PI-RADS 4 index lesions may harbor csPC. Regarding small PI-RADS 4 lesions, IB technique was superior to SFB in detection of csPC.

Sarcopenia is common among patients with renal cell carcinoma (RCC) and has been associated with poor cancer-specific (CSS) and overall survival (OS). Similarly, venous tumor thrombus (VTT) carries substantial prognostic and surgical consequences. In this study, we analyze whether sarcopenia is independently associated with CSS/OS in an expanded cohort of patients with non-metastatic RCC and VTT.

Following IRB approval, adults undergoing nephrectomy for non-metastatic RCC with VTT and available imaging within 90 days of surgery were included between 2005 and 2024. Skeletal muscle index (SMI) was then calculated using axial L3 imaging segmentation and sarcopenia determined using validated SMI thresholds. Multivariable COX proportional hazards models analyzed factors independently associated with 5-year CSS and OS.

Among 135 patients, 39 (28.9%) were sarcopenic. Sarcopenic patients were older, had lower BMIs and higher rates of Fuhrman grade 4 disease (all p < 0.01). On multivariable analysis, sarcopenia was independently associated with poor 5-year CSS (HR 4.04, 1.82-8.95, p = < 0.001) and OS (HR 2.60, 95%CI 1.41-4.79, p = 0.002). Analyzing SMI revealed protective effects with per-unit increases in skeletal muscle for both 5-year CSS (HR 0.94, 95%CI 0.91-0.98, p = 0.001) and OS (HR 0.96, 95%CI 0.93-0.99, p = 0.005).

In this study utilizing the largest number of non-metastatic RCC patients with VTT, sarcopenia maintained an independent association with worse 5-year CSS and OS. Expectedly, increases in skeletal muscle/SMI were independently associated with improved survival.

CDH1 pathogenic variant carriers are at high lifetime risk of hereditary diffuse gastric cancer (HDGC). Endoscopic surveillance is recommended for individuals who delay risk-reducing total gastrectomy, although detection of signet ring cell carcinoma (SRCC) remains challenging. No Australian cohort has reported real-world endoscopic performance with surgical correlation in this population. We performed a 15-year retrospective cohort study of adult CDH1 carriers undergoing esophagogastroduodenoscopy (EGD) at a tertiary familial cancer centre (2008-2023). Patients presenting with symptomatic invasive gastric cancer at initial endoscopy were excluded. Most EGDs were conducted as preoperative assessments prior to risk-reducing total gastrectomy, with a minority undertaken as longitudinal surveillance. Endoscopic findings, biopsy performance, surgical pathology, and postoperative outcomes were analysed. Eighty-two CDH1 carriers from 31 families underwent 136 EGDs (median 1 per patient). SRCC was detected endoscopically in 38 patients (46.3%), predominantly via random biopsies. Overall sensitivity for SRCC detection was 67.9%, with random biopsies outperforming targeted sampling. Most lesions were identified at the initial EGD. Sixty-nine patients (84.1%) proceeded to total gastrectomy; SRCC was confirmed in 56 (81.2%), with variable tumour burden (1-73 foci). Invasive disease beyond pT1a was uncommon (2.9%). Postoperative complications occurred in 43.5%, most frequently anastomotic strictures requiring dilatation; there were no procedure-related deaths. Although occult SRCC was common, invasive malignancy beyond pT1a was infrequent, suggesting that many intramucosal lesions may have a more indolent course than previously assumed. Detection of SRCC at endoscopy remains challenging; however, these findings support a more individualized, risk-adapted approach to CDH1 management. Longer-term prospective data are required to better define SRCC progression risk and guide decisions regarding surveillance and risk-reducing surgery.

This study examined survival outcomes in patients with rare sigmoid colon adenocarcinoma, excluding rectal cancer, with a focus on the combined effects of rural-urban continuum code (RUCC) and median household income (MHI).

We analyzed the SEER dataset, which includes 93,020 patients diagnosed with this condition. Survival differences were assessed using Kaplan-Meier estimates and multivariable Cox models. Interaction effects between RUCC and MHI were evaluated, and a nomogram was developed to predict five- and 10-year survival probabilities after adjusting for covariates, with sensitivity analyses conducted to assess robustness.

A higher degree of rurality was significantly associated with an increased risk of mortality. Patients in RUCC 4 (HR: 1.13; 95% CI: 1.05-1.22) and RUCC 5 (HR: 1.14; 95% CI: 1.06-1.23) had elevated risks compared with RUCC 1. Income modified these associations. Patients in RUCC 2 with MHI above $100,000 had an 8% lower mortality risk (HR: 0.92; 95% CI: 0.83-0.98) than those in RUCC 1 with MHI below $70,000. Similarly, RUCC 4 patients with MHI $90,000-$100,000 experienced a 15% reduction (HR: 0.85; 95% CI: 0.75-0.98). Nomogram predictions indicated the most favorable survival in RUCC 2 with MHI > $100,000 (5 years > 60%; 1 -years ~ 55%), slightly lower survival in RUCC 1 with the same income (5 years 58%; 10 years 52%), and poorest survival in RUCC 4 with MHI < $70,000 (5 years 54%; 10 years 47%), with sensitivity analyses confirming consistent findings.

Survival outcomes were significantly influenced by both place of residence and socioeconomic status, with the highest survival observed among patients with higher MHI in RUCC 2 and the poorest outcomes among low-income patients in RUCC 4. These results highlight the compounded impact of rurality and socioeconomic disadvantage, underscoring the need for targeted interventions-including strengthened oncology infrastructure, and reduced structural barriers.

ATP is the primary energy currency required by living organisms. Mitochondrial oxidative phosphorylation (OxPhos) produces most of the ATP in quiescent and differentiated cells. OxPhos interruption results in analogous bioenergetic adaptations across divergent evolutionary taxa, yet this adaptation is poorly recognized. Oxygen availability is a major determinant of the source of ATP generation across most eukaryotic cell types. Acute oxygen deprivation, mitochondrial dysfunction, high energy demand, or other metabolic cues can shift relative ATP production from OxPhos to high-throughput fermentation via substrate-level phosphorylations (SLPs). Glucose-derived lactate and glutamine-derived succinate are biomarkers of cytosolic and mitochondrial SLP, respectively. The extracellular accumulation of these metabolites is observed in a broad range of biological systems, including unicellular bacteria and yeast to more complex mammalian cells, including those of the immune system, retina, and muscle. Unsurprisingly, many cancer cells accumulate excess lactate and succinate due to chronic OxPhos insufficiency. This review links ostensibly unique cases of metabolic disruption to the accumulation of lactate and succinate as biomarkers of compensatory fermentative metabolism through cytosolic and mitochondrial SLP. Fundamental principles of cellular energy and environmental adaptation are reviewed that span a broad range of biological complexity.