Publications by Year: 2026

BACKGROUND: To assess population-level trends in use of poly (ADP-ribose) polymerase inhibitors (PARPis) among ovarian cancer patients in the years following initial FDA approvals.

METHODS: A national, commercial and Medicare Advantage insurance claims database was used to identify patients with ovarian cancer from 2015 to 2021. Year of ovarian cancer diagnosis was categorized by initial period of PARPi approval for treatment indication (2015-2016) and expanded period of PARPi approval for treatment and maintenance indications (2017-2021). Clinical and demographic characteristics were assessed. The primary outcome was proportion of patients with PARPi dispensings. Time from first observed ovarian cancer diagnosis to first observed PARPi dispensing was calculated.

RESULTS: Of 23,165 patients with ovarian cancer, most were 65 years or older (62.8 %) and had Medicare Advantage insurance (66.2 %). More patients diagnosed in the expanded compared to the initial approval period received PARPi (9.8 % vs. 6.6 %, p < 0.0001) and within less time from diagnosis to PARPi initiation (HR: 2.31, 95 % CI 2.06, 2.59). Age over 65 was associated with lower likelihood of PARPi receipt (OR: 0.85, 95 % CI 0.74, 0.98). In the initial approval period, patients residing in non-white zip codes were more likely to receive a PARPi (OR: 1.61, 95 % CI 1.19, 2.18) and frail patients were less likely to receive a PARPi (OR: 0.41, 95 % CI 0.22, 0.78).

CONCLUSION: Since 2015, PARPi use increased among ovarian cancer patients, and time from diagnosis to PARPi receipt decreased, reflecting expanded PARPi indications over time. Monitoring demographic and clinical characteristics of PARPi recipients may help assess population-level use of novel therapeutics.

BACKGROUND: Histone deacetylases (HDACs) are epigenetic molecules responsible for regulation of gene transcription. Dysregulation of HDACs has been linked to neurodegenerative disease. Here, we used the class I HDAC PET radioligand [11C]Martinostat to quantify and map changes in the distribution of these molecules in the brain in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In this exploratory cross-sectional study, we acquired brain PET-MR with [11C]Martinostat in 14 DLB (median age 70 years (IQR 14), 21% female), 10 PD (median age 70 (8), 20% female) including four with cognitive impairment and six without, and 17 healthy control (HC) participants (median age 62 (14), 47% female). [11C]Martinostat uptake was compared amongst groups using whole brain voxel-wise analysis and targeted region of interest (ROI)-based approaches, adjusted for age and sex. Regional levels were also quantified in postmortem brain bank samples.

RESULTS: Compared to HC, [11C]Martinostat uptake in DLB was increased in precentral gyrus (ROI p = 0.044) and putamen (p < 0.001), as well as in cognitive and limbic circuitry including anterior cingulate (p = 0.042) and entorhinal cortex (p = 0.023). [11C]Martinostat uptake in DLB was decreased in inferior parietal cortex p < 0.001) compared to HC, consistent with prior observations in Alzheimer's disease. In PD, [11C]Martinostat uptake was also increased in precentral gyrus (p = 0.013), correlating with both disease duration and Hoehn and Yahr motor stage. In postmortem DLB tissue, class I HDAC levels were elevated in anterior cingulate cortex (isoform 1 p = 0.041, isoform 3 p = 0.024) and were reduced in inferior parietal cortex (isoform 1 p < 0.001).

CONCLUSIONS: The findings of this exploratory study reveal elevated levels of class I HDACs in motor cortex in PD and bidirectional changes in their regional density in the Lewy body dementias.

BACKGROUND: Females have a higher risk of incident knee osteoarthritis (KOA) than males, particularly in the lateral compartment; however, the underlying mechanisms remain unclear. We investigated whether knee flexor and extensor strength mediate the association between sex and lateral radiographic and symptomatic KOA risk.

METHODS: This cohort study utilized data from the Osteoarthritis Initiative, a longitudinal prospective study of participants aged 45–79 years. We included knees without radiographic or symptomatic KOA at baseline. Knee extensor and flexor strength were measured isometrically using a validated device (Good Strength Chair) and normalized to body mass index. Mediation analyses were performed using marginal structural models to assess the contribution of knee flexor and extensor strength to the relationship between sex and the risk of lateral radiographic and symptomatic KOA, adjusting for age, race, knee injury history, physical activity, knee alignment, cartilage volume, and hormone therapy.

RESULTS: A total of 5,126 eligible knees from 3,056 participants without radiographic KOA and 6,773 from 3,720 participants without symptomatic KOA were identified at baseline. Among 5,126 knees without radiographic KOA, the 8-year risks of lateral radiographic KOA were 5.9% in females and 3.4% in males, with an odds ratio (OR) of 1.72 (95% confidence interval [CI]: 1.28 to 2.31). The indirect effects of female sex on lateral radiographic KOA via flexors and extensor strength were OR = 1.14 (95% CI: 1.04 to 1.26) and 1.16 (95% CI: 1.05 to 1.27), respectively. The direct effects (not mediated through flexor/extensor strength) were OR = 1.48 (95% CI: 1.01 to 1.95) and 1.46 (95% CI: 1.01 to 1.92). Knee flexor and extensor strength mediated 31.1% and 33.9% of the total effect of sex on lateral radiographic KOA risk, respectively. Similar results were also observed for incident lateral symptomatic KOA.

CONCLUSION: The lateral radiographic and symptomatic KOA risk is higher in females than males, partly mediated by lower flexor and extensor strength. These findings suggest that enhancing knee flexor and extensor strength in females may help reduce their risk of developing lateral radiographic and symptomatic KOA.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-026-03745-6.

UNLABELLED: Antimicrobial Resistance (AMR) is a global public health threat. Several surveillance systems/networks were established to provide critical data to detect resistance patterns, guide treatments, and inform policies to mitigate AMR’s public health impact. WHONET software was developed in 1989 as a free software that manages and analyses microbiology laboratory data, entirely dedicated to antimicrobial susceptibility test results. A systematic search was conducted in five electronic databases, PubMed, ScienceDirect, Web of Science, Scopus, and Embase, from their inception until December 31st, 2024. It included all articles that reported using WHONET. From the initial 4,636 articles retrieved, 511 were included. Most studies were cross-sectional or prevalence studies (72.4%), with the majority utilizing secondary data sources (83.2%). Articles included data from 110 countries, with the highest amount coming from China, and the number of publications increased over time. Additionally, most articles included data from 2 to 3 years before publication. Of the 2160 organisms examined across the studies, Enterobacterales (43.8%), Staphylococcus spp. (12.5%) and Pseudomonas spp. (9.3%) were the most covered microorganisms. In conclusion, the review highlights the growing interest in WHONET and AMR. WHONET’s ability to leverage routine and secondary data for AMR monitoring is advantageous compared to other systems. However, expanding WHONET’s application and integrating advanced analytics are essential for enhancing its role in a comprehensive One Health approach to combat AMR, particularly in LMICs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-12420-1.

Adverse reactions from donor-recipient sex-mismatched transfusions have been reported in the field of transfusion medicine. Immature CD71+ red blood cells (CD71+ RBCs) may influence these reactions through an immunomodulatory mechanism potentially linked to enriched intracellular reactive oxygen species (ROS). This study was conducted to investigate the effect of CD71+ RBCs on erythrophagocytosis, a common in vitro test for hemolysis risk in incompatible blood transfusions. Enriched CD71+ RBCs and CD71- RBCs were exposed to allogenic peripheral blood mononuclear cells (PBMCs). CD71+ RBCs were also incubated with anti-D sensitised CD71- RBCs and PBMCs, in varying ratios, to assess any dose-dependent behaviour. An ROS scavenger, apocynin, was applied to understand how CD71+ RBCs impact erythrophagocytosis. The phagocytosis index (RBC PI or CD71+ RBC PI) was measured using image flow cytometry. Supernatant haemoglobin was examined spectrophotometrically. The enriched CD71+ RBC group showed a significantly higher RBC PI and a reduction in the monocyte number compared to the CD71- RBC group. Compared to the non-treated group, the reduction of monocyte number and the increase of the phagocytosis index of CD71+ RBCs was partially reversed in the apocynin-treated group. There were positive correlations between the dose of CD71+ RBC and CD71+ RBC PI and supernatant haemoglobin. Donated CD71+ RBCs enhance in vitro erythrophagocytosis of CD71+ RBCs in a dose-dependent manner and reduce monocyte number. This work contributes to our understanding of immature CD71+ RBCs' role in post-transfusion immunobiology.

Giving old drugs new uses, a process known as drug repurposing, is an attractive strategy for finding therapeutic candidates for a wide number of diseases. In this context, data-driven approaches have emerged as a suitable framework to target this challenge. From molecular docking and network-based methods to omics data integration, computational techniques give invaluable insights into drug repurposing research. In the present review, we describe these methodologies and knowledge-based resources, also emphasizing the new horizons that artificial intelligence and large language models are revealing. A set of case studies illuminate the practical applications of these computational approaches to the identification of repurposing opportunities. By addressing a set of key challenges and proposing future directions, this review aims to be a resource for researchers navigating the multifaceted landscape of computational drug repurposing.

Cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis and myocardial infarction, remain the leading cause of morbidity and mortality worldwide. Aging is a predominant risk factor for CVD. Cardiovascular aging is characterized by progressive structural changes at the cellular level and functional decline within the cardiovascular system, ultimately contributing to the onset and progression of CVD. These changes include alterations in left ventricular (LV) systolic and diastolic function, an increased incidence of sinus node dysfunction, myocardial hypertrophy, arterial stiffness, and fibrosis. Therefore, understanding the molecular mechanisms underlying cardiovascular aging and identifying interventions that can slow or mitigate its progression holds significant promise for CVD prevention and treatment. Numerous epidemiological and experimental studies have consistently demonstrated that physical activity or exercise training exerts protective effects against cardiovascular aging. However, the molecular mediators and underlying mechanisms of these benefits are not completely understood. Therefore, further investigation is warranted to elucidate these mechanisms, given their potential as novel therapeutic targets. In this review, we comprehensively synthesize molecular, preclinical, clinical, and epidemiological evidence to underscore the positive effects of exercise on cardiovascular aging. This review systematically investigates how exercise modulates the key biological hallmarks of cardiovascular aging, including deterioration of protein homeostasis (proteostasis), genomic instability, epigenetic disturbances, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysregulated neurohormonal signaling. The mechanistic insights of exercise-induced adaptations presented in this review may provide a valuable foundation for future investigations, paving the design of tailored exercise regimens aimed at mitigating the progression of cardiovascular aging.

AIM: The clinical significance of histologic margin involvement by basal cell carcinoma (BCC)-associated stroma remains uncertain. This study aimed to determine the incidence of residual BCC in immediate re-excision specimens or clinical recurrence in cases managed without re-excision.

METHODS: Fifty-eight cases of BCC with stromal margin involvement diagnosed between 2016 and 2020 were retrospectively reviewed. Fifty cases underwent immediate surgical re-excision, and eight were managed with clinical observation for at least two years. Tumors were classified by histologic subtype, and stromal margin involvement was categorized as peripheral, deep, or both. Residual carcinoma on re-excision or clinical recurrence within two years was recorded.

RESULTS: Residual carcinoma was identified in 8% of re-excised cases (4/50) and occurred exclusively in tumors with a superficial component, including three pure superficial BCCs and one mixed superficial-nodular BCC; all residual tumors were of superficial subtype. No residual carcinoma was observed among 23 nodular or infiltrative BCCs that underwent re-excision. None of the eight cases managed with observation (1 superficial, 2 mixed superficial-nodular, 5 nodular) demonstrated clinical recurrence within two years. Overall, residual or recurrent disease occurred in 7% of cases (4/58). The distribution of adverse outcomes differed significantly by histologic subtype.

CONCLUSIONS: Stromal margin involvement in non-superficial BCCs is rarely associated with residual or recurrent carcinoma. Adverse outcomes were confined to tumors containing a superficial component, highlighting biologic heterogeneity among BCC subtypes. These findings suggest that routine re-excision may be unnecessary for stromal-margin-positive BCCs lacking a superficial component and support more selective, subtype-informed management.