Glycated hemoglobin (HbA1c) is a laboratory examination recommended by the American Diabetes Association to monitor blood glucose levels in patients with diabetes mellitus. This gold standard method for testing HbA1c uses highperformance liquid chromatography (HPLC). One advantage of HbA1c testing with HPLC is the ability to detect Hb variants or hemoglobinopathies, although HbA1c results may become irrelevant in such conditions. A 49-year-old female patient came to the Ophthalmology Outpatient Clinic of Dr. Soetomo Hospital due to visual impairment in both eyes and plans for cryotherapy surgery. In preparation for the surgery, laboratory tests were performed with results of haemoglobin 12.1 g/dL, mean corpuscular volume 58.9 fL, mean corpuscular haemoglobin 19.3 pg, leukocytes 13,370/uL, platelets 399,000/uL and random blood glucose 127 mg/dL; however, HbA1c was not detected. In the HbA1c test, a 93.7% window variant was obtained. Based on blood smear evaluation, there was hypochromic microcytic anisopoikilocytosis with target cells. The electrophoresis results revealed HbA 0.7%, HbF 0.6%, HbE 94.9% and HbA2 4.7%, indicating the presence of beta thalassemia with hemoglobinopathy E. The diagnosis of hemoglobinopathy E is based on a complete blood count, peripheral blood smear and haemoglobin electrophoresis. HbA1c examination by HPLC can yield undetectable HbA1c levels in hemoglobinopathies. Monitoring blood glucose levels in such cases is also irrelevant when using HbA1c, because red blood cells have a shorter lifespan in the presence of Hb variants. Glucose monitoring in this condition can be done by periodic glucose examination, fructosamine, or glycated albumin. The HbA1c test cannot be used as a marker of glucose control in patients with hemoglobinopathy E.

ABCC8 pathogenic variants have been found to cause neonatal diabetes mellitus (NDM), maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism (CHI), depending on the nature of the mutation. Few studies have reported on the carrier frequency of CHI-related ABCC8 variants. In Singapore, the carrier rate is 1 in 754. Paternally inherited ABCC8 recessive variants have been classically associated with focal lesions causing CHI. In our case series of five patients with paternally inherited ABCC8 variants, one patient had a second maternally inherited recessive variant, making him a compound heterozygous genotype presenting with severe, neonatal onset, diffuse disease that was not responsive to diazoxide. The remaining four patients had a single paternally inherited ABCC8 variant, of which three were previously reported to be recessive variants-only 1 had a focal lesion while the rest had diffuse disease. A comprehensive review of our cases suggests that patients with paternally inherited ABCC8 variants, whether autosomal recessive, heterozygous, or associated with genetic syndromes, were heterogeneous in their clinical manifestations and cannot be reliably distinguished based on their initial clinical presentation. A deeper understanding of the genotype-phenotype correlation of ABCC8-related CHI will require further research and functional analyses. Both a genetic diagnosis and imaging using ¹⁸F-DOPA-PET should be pursued in a timely manner once diazoxide unresponsiveness has been established. Single-stage near-total pancreatectomy may be considered for patients with diffuse disease.

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a disorder affecting both the peripheral and central nervous systems. Although diabetic neuropathy has traditionally been associated with peripheral nerve damage, accumulating evidence suggests that central auditory pathways are also vulnerable to chronic hyperglycaemia. This narrative review synthesizes current evidence regarding auditory brainstem response (ABR) abnormalities in adults with T2DM, with emphasis on their pathophysiological basis, characteristic electrophysiological alterations, clinical associations, and potential diagnostic significance. A structured search of PubMed/MEDLINE, Scopus, and Google Scholar identified 10 observational studies published between 2000 and 2024 that evaluated ABR parameters in adults with T2DM. Across the included studies, the most consistent findings were prolonged wave III and wave V absolute latencies together with extended interpeak intervals (I-III, III-V, and I-V), while wave I latency remained normal in most patients, indicating predominant central auditory pathway dysfunction. A smaller proportion of studies demonstrated additional peripheral auditory nerve involvement, suggesting mixed neuropathic changes. Higher glycated haemoglobin (HbA1c) levels and longer duration of diabetes were generally associated with greater ABR abnormalities, supporting the role of cumulative metabolic injury in central neural conduction delay. Despite methodological heterogeneity and predominantly cross-sectional study designs, the evidence consistently indicates that the auditory brainstem is an early target of diabetes-related neural injury. ABR represents a non-invasive and reproducible tool with potential utility for detecting subclinical central diabetic neuropathy before overt auditory impairment becomes clinically evident. Further multicentre longitudinal studies using standardized ABR protocols are required to validate its diagnostic and prognostic value in routine clinical practice.

Diabetic retinopathy (DR), a leading cause of blindness in diabetes, involves dysregulated neuroimmune crosstalk. While microglial activation and endothelial dysfunction are established in DR, the molecular mechanisms linking innate immunity to blood-retinal barrier (BRB) breakdown remain elusive.

We combined single-cell RNA sequencing (scRNA-seq) of diabetic mouse retinas with in vivo models, retinal endothelial MFSD2A overexpression, and microglial Cathepsin S (CTSS) knockdown via adeno-associated virus (AAV). Human retinal microvascular endothelial cells (HRMECs) and human microglial cells (HMC3) were subjected to high-glucose conditions combined with in vitro systems (transwell co-cultures, holographic 3D tomography). Mechanistic studies employed siRNA knockdown, plasmid overexpression, exogenous CTSS supplementation, and transcytosis assays.

scRNA-seq revealed diabetes-induced CTSS upregulation in retinal microglia (p = 0.0031) and MFSD2A downregulation in endothelial cells (p = 0.01). Microglial CTSS promoted M1 polarization (p < 0.001) and pro-inflammatory cytokine secretion (IL-1β and TNF-α, p < 0.05), while Ctss knockdown attenuated these effects (p < 0.05). CTSS activated endothelial PAR2, suppressing endothelial MFSD2A and enhancing caveolin-1-mediated transcytosis. Endothelial MFSD2A overexpression reduced vascular permeability independently of tight junction modulation (ZO-1, Occludin, Claudin-5, p > 0.05). Microglia-endothelial crosstalk was disrupted in diabetes, with ultrastructural alterations (cytoplasmic shrinkage, microglial amoeboid transformation) promoting cytotoxic interactions and exacerbate vascular endothelial damage.

Hyperglycemia induces retinal microglial activation and CTSS upregulation, disrupting microglia-endothelial crosstalk via the PAR2 pathway, suppressing endothelial MFSD2A expression, enhancing transcytosis, compromising iBRB integrity, and accelerating DR progression. Therapeutic strategies targeting microglial CTSS or endothelial MFSD2A represent promising avenues for preserving vision in diabetic patients.

Geographic proximity to clinical trials is a major barrier to trial participation, but geographic access to trials has not been specifically characterized for triple-negative breast cancer (TNBC). We evaluated the geographic distribution of TNBC treatment trials across U.S. counties and examined associated social and demographic characteristics.

All trials registered on ClinicalTrials.gov as of September 30, 2024 (n = 510,397) were queried, and active phase II and III TNBC treatment trials were identified through keyword searches. County-level population estimates from the 2018-2022 U.S. Census Bureau 5-year estimates and county adjacency data were used to evaluate trial availability and geographic access. Trial availability was examined according to sponsorship, rurality, health vulnerability, race and ethnicity, and U.S. region.

We identified 108 active TNBC trials, including 58 (54%) for metastatic and 50 (46%) for non-metastatic disease. Overall, 76% of U.S. counties had no TNBC trials, 12% had exclusively federally sponsored trials, 10% had both federally and non-federally sponsored trials, and 2% had only non-federally sponsored trials. Trial availability was significantly lower in counties with the highest health vulnerability and in rural counties, which were more likely to rely exclusively on federally sponsored trials. Counties with predominantly Black, Hispanic, and American Indian and Alaska Native populations were less likely to have TNBC trials than predominantly non-Hispanic White counties. Women in the South were more likely than women in the Northeast to have no TNBC trial available in either their county of residence or a neighboring county.

TNBC clinical trials are geographically concentrated across the United States, with substantial disparities in access affecting rural and highly vulnerable counties, counties with predominantly racial and ethnic minority populations, and women living in the South. Federally sponsored trials may play an important role in supporting trial availability in underserved areas. Expanding the geographic distribution of TNBC trials may help improve equitable access to clinical trial participation.

Liver resection with vascular reconstruction is a highly complex procedure for advanced hepatobiliary tumours. This study evaluated the postoperative and oncological outcomes of this patient cohort.

This retrospective multicentre study included patients undergoing liver resection with vascular reconstruction between 1990 and 2024 across 21 expert centres. Reconstructions involved the inferior vena cava, hepatic veins, portal vein, or hepatic artery. Primary endpoints were postoperative morbidity and 90-day mortality. Secondary endpoints included overall survival (OS), disease-free survival (DFS), and predictors of complications. Multivariable logistic regression, Kaplan-Meier, and Fine-Gray analyses were performed.

In all, 532 patients were included and classified according to surgical approach as in situ (455, 85.3%), ante situm (48, 9.2%), or ex situ (29, 5.5%). The most frequent indications were colorectal liver metastases (162, 30.4%), intrahepatic cholangiocarcinoma (139, 26.1%), and perihilar cholangiocarcinoma (106, 19.9%). The median operative time was 390 minutes. Clavien-Dindo ≥ IIIa occurred in 217 patients (40.8%), and the 90-day mortality rate was 9.8% (52). Portal vein reconstruction independently predicted post-hepatectomy liver failure, ascites, infectious complications, and major morbidity, whereas inferior vena cava reconstruction showed a more favourable perioperative profile. Hepatic vein reconstruction was associated with greater transfusion requirements and longer operative time. Vascular graft-related complications occurred in 22.3% (58) of reconstructions and were not associated with graft type. After excluding patients with perihilar cholangiocarcinoma (426), ante situm and ex situ procedures were associated with higher rates of Clavien-Dindo ≥ IIIa than in situ procedures (67.3% (33) and 64.3% (18) versus 35.5% (124), respectively; P < 0.001), longer intensive care unit stay (6.5 and 5 versus 3 days, respectively; P < 0.001), and higher mortality (16.3% (8) and 17.9% (5) versus 8.3% (29), respectively; P = 0.060). DFS was superior for hepatocellular carcinoma (P = 0.011), whereas perihilar cholangiocarcinoma showed a higher risk of recurrence (P = 0.022). Five-year OS was highest for sarcoma (68.8%) and hepatocellular carcinoma (42.7%).

Liver resection with vascular reconstruction is feasible in specialized centres but remains associated with substantial morbidity and mortality. The in situ approach showed the most favourable perioperative outcomes, although oncological benefit varied according to tumour biology, highlighting the importance of careful patient selection.

Gliomas are metabolically heterogeneous tumors in which mitochondria coordinate bioenergetics, biosynthesis, redox homeostasis, stress adaptation, and treatment responses. This review examines mitochondrial dependencies across glioma subtypes and cell states.

We synthesized evidence on mitochondrial integration of glucose, amino acid and protein, lipid, and nucleotide metabolism, together with mitochondrial genetics, signaling, intercellular transfer, and barriers to therapeutic translation in gliomas.

Glioma glucose metabolism does not follow a uniform Warburg phenotype. IDH-mutant gliomas exhibit D-2-hydroxyglutarate-driven metabolic and epigenetic remodeling, whereas IDH-wild-type glioblastomas contain glycolytic, oxidative phosphorylation-enriched, and adaptable stem-like states. Mitochondrial proteostasis links protein import and translation with PI3K/AKT/mTOR signaling, the ubiquitin-proteasome system, autophagy, and mitophagy. Lipid synthesis, storage, fatty acid oxidation, and cardiolipin homeostasis support metabolic adaptation. Electron transport, aspartate availability, redox balance, and dihydroorotate dehydrogenase connect mitochondria with nucleotide synthesis, DNA repair, and treatment resistance. Mitochondrial DNA alterations, mitonuclear signaling, and intercellular mitochondrial transfer further influence respiratory adaptation and tumorigenicity. Metabolic compensation and intratumoral heterogeneity limit single-target therapies, whereas clinical evidence supports genotype-directed intervention, exemplified by vorasidenib.

Effective mitochondrial targeting requires biomarkers that match metabolic dependencies to molecular subtypes and cell states while accounting for brain exposure, compensation, and toxicity.

This study aims to achieve accurate prediction of high-risk molecular subtypes of gliomas through a cross-scale Combined model, matching the model's classification metrics with patient risk stratification and exploring the underlying biological mechanisms.

This study retrospectively collected preoperative MRI, postoperative whole-slide pathological images, molecular markers, and clinical data from 456 adult diffuse glioma patients. We separately constructed an MRI habitat prediction model, a WSI Transformer-based deep learning pathomics (PDL) model, and a Combined model. A dynamic nomogram web page for predicting high-risk molecular subtypes was developed based on the Combined model. Patients were stratified into risk groups according to the output scores of the Combined model, and Kaplan-Meier survival analysis and the Log-rank test were employed to evaluate survival differences between the groups. Additionally, differential expression and GO/KEGG enrichment analyses were further performed in the test set with available RNA-seq data to explore transcriptional features and biological processes associated with model-based risk stratification.

The Combined model demonstrated the highest AUC (Training set: 0.888, Test set: 0.836) compared to the Habitat model (Training set: 0.832, Test set: 0.798) and the PDL model (Training set: 0.852, Test set: 0.821). The high-risk and low-risk groups, stratified based on the cutoff value derived from the Combined model output scores, exhibited significant survival differences. Exploratory transcriptomic analysis showed that differentially expressed genes between the high- and low-risk groups were mainly enriched in biological processes and pathways related to the extracellular matrix and cell-matrix interactions.

The cross-scale Combined model not only enabled identification of high-risk molecular subtypes and risk stratification but also showed associations with biologically relevant transcriptional features.

To determine clinically useful indicators that distinguish IgG4-related disease (IgG4-RD) from diffuse large B-cell lymphoma (DLBCL) and to construct a predictive model that may assist early identification.

We retrospectively analyzed 19 patients with IgG4-RD and 37 with DLBCL who presented with lymphadenopathy and received treatment at the Affiliated Hospital of Xuzhou Medical University between January 2012 and October 2025. The distribution of continuous variables was checked before group comparisons. Data with an approximately normal distribution are expressed as mean ± standard deviation (mean ± SD) and were compared by independent-samples t-tests; skewed data are reported as median (interquartile range [IQR]) and were compared by the Mann-Whitney U test. Categorical variables are presented as counts and percentages (%) and were compared using the χ² test or Fisher's exact test, as appropriate. Variables significant in univariate analyses were taken forward into multivariable logistic regression. Predictive performance was evaluated by receiver operating characteristic (ROC) analysis, calibration analysis, and decision curve analysis (DCA).

Multivariable logistic regression retained lymphocyte count, serum total protein, and prothrombin time (PT) as independent predictive factors. The model yielded an area under the receiver operating characteristic curve (AUC) of 0.91 (95% confidence interval [CI]: 0.82-0.99). Its calibration curve had a mean absolute error of 0.032. Across threshold probabilities from 0.2 to 1.0, decision curve analysis indicated greater net benefit than the "treat-all" and "treat-none" approaches.

In this cohort, the predictive model showed potential to assist differentiation between IgG4-RD and DLBCL. Because the study was retrospective, single-center, and based on a limited sample, these findings should be regarded as preliminary and require confirmation in larger independent cohorts before clinical use.

This scoping review examines the available qualitative evidence from systematic and scoping reviews, and mixed-methods or qualitative studies on cancer-related discrimination.

Cancer-related discrimination was defined as direct and recurring experiences of enacted stigma, behaviours, or unfair treatment based on an individual's cancer history, current cancer diagnosis, perceived cancer risk, or cancer caregiving role. A systematic search of ProQuest databases, Cochrane CENTRAL, Scopus, APA PsycINFO, MEDLINE, and Web of Science identified peer-reviewed research published before December 13, 2025. Two independent reviewers screened studies, and data were narratively synthesised using the Health Stigma and Discrimination Framework (i.e., drivers and system-level facilitators; discrimination experiences; impacts).

In total, 116 studies met inclusion criteria, comprising 83 qualitative studies, 23 mixed-method, nine systematic reviews, and one scoping review. Cancer-related discrimination was reported across four contexts: (1) familial and social; (2) hiring and workplace; (3) insurance and welfare; and (4) healthcare. Discrimination drivers included misconceptions that cancer is contagious, employer concerns about productivity and costs, rigid welfare regulations, and reduced public empathy for cancers perceived as 'self-inflicted'. Reported experiences ranged from social exclusion and bullying, to workplace dismissals, job rejections, and barriers to insurance or financial support. In healthcare contexts, provider blame, judgement, and strained patient-clinician interactions were reported. Impacts of discrimination included self-isolation, concealment of diagnosis, internalised stigma, psychological distress, financial burden, and delayed treatment-seeking.

Cancer-related discrimination arises from cultural, institutional, and structural mechanisms, with significant impacts on quality of life and health. Coordinated policy, legal, institutional, and public education responses are required to address these challenges.