Diabetes is a dynamic disease, an ever-evolving entity. In existence for centuries, the prevalence of diabetes has increased manifold over the past few decades.¹ This evolution is associated with a change in classification, clinical features, comorbidities, complications, and clinical management strategies. These changes are what we describe as the Darwinization of diabetes. Charles Darwin was one of the most important scientists in human history. His research forms the basis of evolutionary biology. His hypothesis on natural selection, created along with Alfred Wallace, is accepted as the most important mechanism of evolution.² A similar situation occurs with diabetes.

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) syndrome is a multi-systemic genetic disorder characterized by mitochondrial dysfunction, often presenting with diverse clinical phenotypes. We report a rare case of glioblastoma (GBM) in a 60-year-old female whose MELAS manifestations were primarily metabolic and neuro-sensory. Her clinical course began at age 40 with diabetes mellitus, bilateral sensorineural hearing loss, and left ophthalmoplegia. She was diagnosed with MELAS syndrome by molecular genetic testing at age 56 following her son's diagnosis. Despite the absence of previous stroke-like episodes, she presented with an acute 2-day history of headache, vomiting and altered mental status. Brain MRI revealed a mass lesion, and subsequent gross total resection was performed. Histopathological and molecular analysis confirmed a GBM, IDH-wildtype (CNS WHO grade 4). Despite surgical resection, the patient failed to recover neurologically, remaining in a stuporous state with eye opening but inability to follow commands. She subsequently received the Stupp protocol; however, massive local recurrence with increased relative cerebral blood volume was observed within one month of treatment initiation, indicating rapid and aggressive tumor progression. This case underscores that in MELAS patients, primary brain malignancies can arise independently of typical stroke-like episodes. In addition, the unusually aggressive clinical course and rapid recurrence despite standard Stupp protocol therapy raise the possibility that altered mitochondrial metabolism may influence tumor behavior or treatment response in certain patients.

Because glucose fluctuations (GFs) are significantly associated with poor cardiovascular outcomes in patients with diabetes mellitus, we investigated their potential impact on the paracrine effects of human epicardial adipocytes on cardiomyocytes.

Human epicardial adipose tissue (EAT) biopsies and isolated EAT-derived adipocytes were used to evaluate the direct impact of GFs. Mature adipocytes were exposed to media containing normal glucose (NG), high glucose (HG), or GFs. GFs altered the expression of 595 differentially expressed genes with an effect size greater than ±50% and a statistically significant difference (P<0.05) in human epicardial adipocytes, whereas continuous HG altered the expression of only 182 genes. Among the genes affected exclusively by GFs, the top 3 most affected were IL1β, IL33, and IL8. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes treated with NG, HG, or GFs revealed that adipocytes exposed to GFs markedly increased oxidative stress in cardiomyocytes through paracrine effects. In a real-world clinical association study, IL1β mRNA expression in human EAT showed a significant positive correlation with the severity of GFs during hospitalization and with oxidative stress in the left atrial myocardium.

GFs adversely affect the paracrine secretome profile of human epicardial adipocytes. IL1β may be a critical epicardial adipocyte-derived adipokine that is upregulated by GFs.

Vitamin D deficiency is one of the most common endocrine disorders and plays a significant role in the pathogenesis of carbohydrate metabolism disturbances. Low serum 25(OH)D levels are associated with the development of insulin resistance, metabolic syndrome, prediabetes, and type 2 diabetes mellitus (T2DM). However, data on the prevalence of vitamin D deficiency and its age-related characteristics in the population of Uzbekistan remain limited.

To investigate the prevalence of vitamin D deficiency in individuals with prediabetes and newly diagnosed T2DM based on screening data from the city of Andijan and the Markhamat district of the Andijan region, Uzbekistan.

A total of 3,400 individuals over 40 years of age were screened (1,800 in Markhamat district, 1,600 in Andijan city) using the FINDRISC questionnaire. Serum 25(OH)D levels, carbohydrate and lipid metabolism parameters, and HOMA-IR index were assessed in 205 subjects with prediabetes, 102 patients with newly diagnosed T2DM, and 60 controls. Prediabetes and T2DM were diagnosed according to WHO criteria.

Mean vitamin D levels were significantly lower in patients with prediabetes and T2DM compared to the control group (p&lt;0.05). The most severe deficiency was observed in patients with T2DM, especially among women and individuals aged 45-59 and 60-74 years. In Andijan city, vitamin D deficiency was detected in 100% of T2DM patients, while in Markhamat district the prevalence reached 40.3%.

Vitamin D deficiency is highly prevalent among patients with prediabetes and T2DM, with severity increasing with age and more pronounced in women. These findings highlight the need for routine monitoring of serum 25(OH)D and preventive strategies in high-risk groups.

Colorectal cancer (CRC) incidence is increasing in sub-Saharan Africa, including Nigeria, where more than half of patients die within 1 year due to late diagnosis and limited treatment. Without ready access to screening, identifying risk factors is critical. However, regional data are scarce, and it is unclear whether risk factors from high-income populations apply to Nigerians, who may have distinct clinicodemographic patterns and tumor characteristics.

To assess whether 13 CRC risk factors identified in high-income populations are associated with CRC in adults in Nigeria.

This multicenter case-control study was conducted in 6 hospitals across 3 of Nigeria's 6 geopolitical zones, with recruitment from April 2020 to September 2024. Participants were patients newly diagnosed with CRC and cancer-free controls matched on age, sex, location, education, and recruitment site. Data were analyzed from April 2023 to November 2025.

Family history of cancer, anthropometric factors (adult height, body mass index [BMI], and somatotype or body size over the life course), physical activity, and dietary and lifestyle factors (processed meat, red meat, fruit, vegetables, fiber, alcohol, smoking, and diabetes).

The associations of risk factors with CRC were assessed using odds ratios (ORs) and 95% CIs, estimated using multivariable unconditional logistic regression.

Among 2063 participants (1103 [53.5%] male; median [IQR] age, 54 [42-64] years) enrolled, most had secondary education or higher (1756 participants [85.2%]), lived in urban areas (1817 participants [88.1%]), and were Yoruba (1524 participants [73.9%]). Cases were older than controls (median [IQR] age, 56 [45-66] vs 52 [41-63] years) but were otherwise similar. Family history of cancer (OR, 1.55; 95% CI, 1.06-2.26), adult height (OR per 5-cm increase, 1.09; 95% CI, 1.00-1.20), body size or type over the life course (tertile 3 vs tertile 1: OR, 1.88; 95% CI, 1.30-2.72), and processed meat intake (lowest vs highest tertile of intake: OR, 1.43; 95% CI, 1.07-1.91) were positively associated with CRC risk, and an inverse U-shaped association was identified between physical activity and CRC risk (OR vs first quartile of activity, quartile 2: 0.63; 95% CI, 0.44-0.88; quartile 3: 0.52; 95% CI, 0.34-0.79; quartile 4: 0.77; 95% CI, 0.58-1.02), consistent with data from high-income populations. BMI was inversely associated with CRC risk (OR vs BMI 18.5-24.9, BMI <18.5: 2.63; 95% CI, 1.79-3.86; BMI ≥30: 0.42; 95% CI, 0.28-0.63), likely reflecting prediagnostic weight loss. No associations with diabetes, smoking, or intakes of red meat, fruit, vegetables, fiber, or alcohol were observed, likely due to low prevalence or variability.

This case-control study of CRC risk factors in adults in Nigeria found CRC risk patterns similar to those observed in high-income populations. These insights offer immediate opportunity to tailor education, prevention, and early detection in the region, especially as economic development leads to lifestyles more similar to high-income populations. These data provide a foundation for prospective research and investigations in other African populations.

We evaluated the impact of chronological age on early urinary continence recovery following robot-assisted radical prostatectomy (RARP) using EPIC-26 and quantified discordance between patient-reported and surgeon-assessed continence. A total of 144 consecutive patients underwent RARP and were stratified into Group A (< 70 years, n = 74), Group B (70-<75 years, n = 36), and Group C (≥ 75 years, n = 34). Continence was assessed using EPIC-26 and independent surgeon evaluation at 1, 2, 3, 4, and 6 months postoperatively. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models; proportional hazards assumptions were verified using Schoenfeld residuals. Longitudinal domain trajectories were analyzed using generalized estimating equations (GEE). Social continence rates at 3 months were 85.1%, 72.2%, and 58.1% in Groups A, B, and C, increasing to 97.3%, 94.4%, and 77.4% at 6 months (p = 0.0004). Pad-free rates increased from 39.7%, 36.7%, and 29.4% to 77.8%, 76.7%, and 52.9% (p = 0.110). Age independently predicted delayed social continence recovery (HR 0.953, 95% CI: 0.933-0.973; p < 0.001). Recovery trajectories were slower in Group C (p = 0.008), whereas Groups A and B showed comparable trajectories. At 3 months, surgeon-assessed pad-free continence was 69.3% compared with 37.3% by EPIC-26, representing a 32-percentage-point difference with only fair agreement (κ = 0.38; p = 0.034). Although age was associated with delayed early recovery, meaningful recovery with partial narrowing of between-group differences was observed. Age alone should not automatically preclude surgical consideration in appropriately selected elderly patients, and surgeon assessments substantially overestimated patient-reported continence, supporting routine use of validated PROMs.

This review examines cardiovascular complications of multiple myeloma and anti-myeloma therapy, emphasising integrated systems-based cardiovascular management and the institutional model developed at the University College London Hospital Cardio-Oncology (CO) Centre of Excellence.

Cardiovascular vulnerability in multiple myeloma reflects baseline risk, disease-related factors, including cardiac amyloidosis, and treatment-related cardiotoxicity. A longitudinal approach should begin before therapy with multidimensional risk stratification incorporating patient, disease, and treatment factors, with intermediate- and high-risk patients referred for CO review. During treatment, active surveillance using clinical assessment, cardiac biomarkers and imaging, with vigilance for cardiac amyloidosis, enables rapid CO referral and timely intervention. Survivorship care should include annual cardiovascular review, risk-factor optimisation, and monitoring for late toxicity. Existing evidence and real-world experience support integrated CO services combining rapid-access clinics, high-volume cardiac imaging, timely decision-making, inpatient consultation, multidisciplinary collaboration, and survivorship surveillance while preserving cardiovascular health and access to effective anti-myeloma therapy.

This study describes the development and analytical validation of a DNA-based quantitative PCR (qPCR) assay for detecting the NPM1 Type A mutation (NPM1-A ^mut) in acute myeloid leukemia (AML). The assay employs a modified wild-type blocker (WTB) to preferentially suppress amplification of wild-type (WT) alleles, thereby enriching mutant targets.

The modified WTB was synthesized as a 3'-ddC-terminated LNA/DNA chimera and used together with a 6-FAM-MGB-Eclipse hydrolysis probe. The analytical performance of the WTB-qPCR assay was compared with that of an otherwise identical qPCR assay lacking WTB. Key parameters such as linearity, precision, limit of detection (LoD), and limit of quantification (LoQ) were evaluated following the guidelines outlined in CLSI EP17-A2. Concurrently, modified WTB was implemented in Sanger sequencing to improve the sensitivity of mutation detection. Incorporation of WTB yielded an LoD of 0.00302% and an LoQ of 0.00528%, corresponding to approximately 3.02 and 5.28 NPM1-A^mut copies, respectively, per 100,000 WT copies. This represented a clear improvement over the non-WTB assay. The WTB-qPCR showed excellent linearity (R² > 0.999) and precision (CV < 5%), with 100% analytical specificity and no detectable cross-reactivity. Application of modified WTB in Sanger sequencing increased analytical sensitivity to ~ 0.1% mutant allele frequency.

The modified WTB-qPCR assay offers a rapid, highly sensitive, and cost-effective DNA-based method for MRD monitoring in NPM1-A-mutated AML. Its strong analytical performance and straightforward workflow support its implementation as a routine diagnostic tool in clinical laboratories.

To investigate the benefits of listening to pre-bedtime music on sleep quality and daytime sleepiness for family caregivers of palliative care patients at home.

Multicenter, randomized controlled clinical trial. Seventy-six caregivers were randomly assigned to intervention (n = 38) and control (n = 38) groups. The intervention group listened to individually chosen music for 30 min before bedtime for 7 days, and the control group listened to pre-recorded basic nursing education messages. The primary endpoint was the change in global subjective sleep quality, evaluated via the global Pittsburgh Sleep Quality Index (PSQI) score. Secondary endpoints included daytime sleepiness (Epworth Sleepiness Scale [ESS]), accelerometer-derived sleep parameters, and client satisfaction (CSQ-8).

Significant intergroup differences favoring the music intervention were observed in the mean changes from baseline for the primary endpoint of global sleep quality (PSQI Global Score: + 0.60 vs. + 2.05 points; p = 0.006). Descriptive intergroup differences favoring the intervention were observed for subjective nighttime sleep duration (+ 0.55 h; 95% CI 0.19 to 0.94) and daytime sleepiness (ESS: -2.74 points; 95% CI -4.11 to -0.56). Post-intervention satisfaction was significantly higher in the music group (CSQ-8: 27.61 vs. 24.63 points).

Listening to pre-bedtime music maintains global subjective sleep quality for family caregivers in a home palliative care setting. Furthermore, exploratory signals suggest it may also prolong subjective sleep duration and reduce daytime sleepiness.

The study is registered at Clinical Trials.gov, NCT04491110. Date: 29 July 2020.

Pediatric oncology clinical trials (POCTs) are the cornerstone of therapeutic progress in childhood cancer. Yet, poor accrual and retention remain persistent challenges contributing to early termination of POCTs, limiting the advancement of novel therapies. These challenges reflect a convergence of system, protocol, clinician, and family-level factors, among which caregivers' psychosocial decision-making processes represent a potentially modifiable but underexplored contributor. Caregivers making POCT-related decisions must navigate complex medical information under conditions of heightened emotional distress and uncertainty. Psychosocial factors such as distress, comprehension, trust, values, and social context are known to influence decision-making. However, the field still lacks an integrated framework to explain how these factors may shape decisional trajectories and outcomes throughout POCT participation. This commentary reframes POCT enrollment not as a discrete informed-consent event, but as a dynamic, psychosocial decision-making process that unfolds over time. We present an outline of a conceptual Precision Communication Framework designed to support care teams in aligning communication priorities with caregivers' psychosocial and decisional contexts at key decision points throughout trial participation. Rather than seeking to address all causes of poor accrual or withdrawal, this framework focuses on reducing preventable decisional uncertainty and regret in contexts where psychosocial processes are central drivers of caregiver experiences. By presenting an outline of a conceptual model that would link psychosocial-decisional profiles to communication strategies to prioritize, this commentary aims to inform future empirical research and lay the groundwork for identifying communication strategies to prioritize to reduce caregiver decisional burden and promote sustained participation in POCTs.