Publications by Year: 2026

We utilized the K14-Cre Brca1f/fTp53f/f mouse model to investigate whether a pulse of PARP inhibitor (PARPi) ± an AKT inhibitor (AKTi) can prevent Brca1-related breast cancer. PARPi alone did not intercept or prevent tumor development. PARPi+AKTi intercepted tumors but did not prevent new tumors. These data confirm the efficacy of a PARPi and an inhibitor of PI3K signaling in treating BRCA1/2-related tumors, but this combination is not sufficient to prevent carcinogenesis.

OBJECTIVES: Bipolar disorder (BD) often begins in adolescence, a period marked by dynamic neurodevelopment. However, the neurobiological basis from genetic risk and subthreshold symptoms to diagnosed BD remains unclear.

METHODS: We conducted a cross-sectional analysis using data from the Recognition and Early Intervention of Prodromal Bipolar Disorders cohort (NCT01863628), including 392 participants aged 12-25 years with a balanced sexual distribution, stratified into five groups: offspring of patients with BD with (OBDs, n=48) or without (OBDns, n=62) subthreshold symptoms, individuals without BD family history but with subthreshold symptoms (nOBDs, n=63), patients diagnosed with BD (n=133) and healthy controls (HCs, n=86). Cortical thickness relative to HC was assessed using high-resolution T1-weighted images and FreeSurfer V.7.3.2. Gene expression patterns were derived from the Allen Human Brain Atlas, and partial least squares regression, along with gene enrichment analyses, were applied to link cortical alterations with underlying transcriptomic profiles.

FINDINGS: Cross-sectional analyses revealed graded cortical thickness differences across the BD risk spectrum, with patients with BD showing the most pronounced deviations and high-risk individuals with subthreshold symptoms displaying intermediate features relative to HCs. Cortical changes were significantly associated with spatial gene expression patterns, particularly in genes involved in mitochondrial ATP production, oxidative phosphorylation and synaptic signalling. Gene set enrichment revealed that BD-specific cortical thinning correlated with downregulation of excitatory synaptic pathways and excitatory neuron-related gene expression. Conversely, high-risk individuals exhibited upregulation of both excitatory and inhibitory neuronal markers. Developmental transcriptomic enrichment further linked significant genes to mid-childhood and adolescence.

DISCUSSION: By identifying distinct transcriptomic signatures associated with cortical thinning at different stages, our findings underscore the potential of transcriptomic markers for early detection and intervention in BD.

CLINICAL IMPLICATIONS: The findings highlight the potential for using transcriptomic markers for early detection and intervention, suggesting that identifying these markers could lead to improved outcomes for at-risk adolescents. This research has the potential to inform clinical practices and policies aimed at early screening and preventive strategies for BD.

BACKGROUND: Intracranial aneurysms (IAs) are more prevalent and rupture at smaller sizes in adults with sickle cell disease (SCD), compared with the general population, but evidence regarding treatment outcomes remains limited.

OBJECTIVE: To evaluate the safety and efficacy of coil embolization for unruptured IAs in adults with SCD.

METHODS: We retrospectively reviewed consecutive adults with homozygous sickle cell disease (HbSS) who underwent elective coil embolization for unruptured IAs between 2010 and 2023. Clinical, hematological, procedural, and radiological data were analyzed. Primary endpoints were immediate and long term angiographic occlusion and periprocedural complications. Durable occlusion was defined as Raymond-Roy Occlusion Classification class I-II at the last follow-up.

RESULTS: 25 patients with HbSS (median age 50 years; 76% women) with 35 aneurysms were treated. All patients received exchange transfusion to sickle hemoglobin <30%. Immediate Raymond-Roy Occlusion Classification class I-II occlusion was achieved in 33 of 35 lesions (94%; 95% CI 81% to 98%). Two complications (5.7%) occurred: one intraprocedural aneurysm perforation resulting in death 2 days after treatment and one transient ischemic event without permanent deficit. At a median follow-up of 60 months (range 12-156), durable occlusion was observed in 94% (33/35; 95% CI 81% to 98%), with two retreatments. All surviving patients were independent (modified Rankin Scale score of 0-2) at the last follow-up.

CONCLUSIONS: Preventive coil embolization for unruptured IAs in adults with HbSS achieved high rates of durable occlusion with an overall acceptable safety profile in carefully selected cases when applied selectively within expert centers using a standardized hematologic optimization protocol.

OBJECTIVES: A recent investigation between staffing patterns in nursing homes (NH) and quality outcomes has not occurred. Our objective was to examine whether staffing levels and utilization of agency staff are associated with injurious falls in NHs.

DESIGN: Cross-sectional study.

SETTING AND PARTICIPANTS: A total of 11,183 NHs with 1,115,304 long-stay residents enrolled in Medicare fee-for-service were included (July 1, 2019-December 31, 2019).

METHODS: Staffing data and agency utilization by discipline (eg, Certified Nursing Assistants, CNAs) were obtained from Payroll Based Journal reports. Staff minutes were averaged per discipline, and agency staff percentage was calculated weekly as contract hours divided by total hours worked, per discipline. Injurious falls among long-stay residents during the 24-week study period were ascertained through Medicare Provider Analysis and Review claims. Poisson regression models were used to estimate rate of injurious falls with staff levels and agency staffing, respectively, adjusting for NH and patient-level characteristics. Models were stratified according to whether the NH had low certified nursing assistant (CNA) coverage (<2.45 hours per resident per day) vs recommended coverage (≥2.45 h/resident/d) according to the 2024 Centers for Medicare & Medicaid Service Minimum Staffing Standards for Long-Term Care Facilities.

RESULTS: Of the 11,183 NHs analyzed, 3320 (29.7%) met the proposed CNA coverage, whereas 7863 (70.3%) did not. Among NHs that achieved the recommended CNA coverage, increased CNA [incidence rate ratio (IRR), 0.84; 95% CI, 0.74-0.96] and registered nurse (IRR, 0.61; 95% CI, 0.52-0.72) staffing hours were associated with a decrease in injurious falls. In NHs that did not achieve the recommended CNA coverage, increased CNA staffing was associated with an increase in injurious falls (IRR, 1.20; 95% CI, 1.09-1.31). No association was found between agency staff use and injurious falls, except for low registered nurse agency use, defined as >0% but ≤10% of agency staff use, which was modestly associated with more falls in NHs that achieved the suggested CNA coverage (IRR, 1.15; 95% CI, 1.03-1.29).

CONCLUSIONS AND IMPLICATIONS: Although increased CNA staff levels were associated with fewer injurious falls in NHs that were well staffed, increased CNA levels were associated with an increase in injurious fall rates in low-staffed facilities. Utilization of agency staff had little impact on injurious falls. Efforts to improve quality outcomes in NHs through increasing staff hours may have a variable effect depending on an NH's baseline resource availability.

Chronic respiratory diseases (CRDs) remain one of the leading causes of preventable morbidity and disability worldwide, affecting up to one-third of the total Western population in 2025. Recognizing the substantial burden of inflammatory airway diseases such as asthma, COPD, chronic rhinosinusitis, and respiratory allergy, the European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) organized the symposium "Shaping the Future of Respiratory Care" in April 2025 in Brussels, Belgium, at the occasion of the 10-year jubilee. Featuring keynote speakers from the World Health Organization and EUFOREA, this initiative had the following aims: (1) promoting dialogue on translating innovations into daily clinical practice; (2) encouraging collaboration between the different stakeholders in the respiratory field; and (3) defining strategic priorities to transform respiratory care and arrest the CRD epidemic over the next decade. The symposium highlighted the importance of moving toward predictive, preventive, and patient-centered medicine, while supporting value-based health care systems to improve long-term patient outcomes. This report summarizes the main insights and strategic directions discussed at the meeting.

BACKGROUND: Although measures of blood and tissue fatty acid (FA) concentrations are available, objective measures of dietary FA densities (grams per kilocalories) are generally lacking.

OBJECTIVES: We aimed to explore the development of biomarkers for specific and composite dietary FA densities, not including contributions from dietary supplements, using metabolite profiles from serum and 24-h urine, along with separately measured serum phospholipid FA concentrations in the Women's Health Initiative.

METHODS: Potential biomarker equations were based on linear regression of feeding study dietary FA densities on metabolite concentrations, each log-transformed, among participants in a habitual-diet human feeding study (n = 153) within the Women's Health Initiative. Corresponding biomarker equations were also considered for total SFA, MUFA, and PUFA densities and for total n-3 and n-6 PUFA densities. Dietary FA density estimates derived from these equations were evaluated by correlation with feeding study intake densities, and by other important biomarker criteria.

RESULTS: Regression cross-validated R2 values >30% for specific SFAs were 64.7 butyric, 60.9 caprioc, 48.7 caprylic, 53.0 capric, 39.9 lauric, 61.0 myristic, 42.2 palmitic, 34.2 stearic, 34.8 arachidic, 49.9 decosanoic; for specific MUFAs were 31.3 oleic; and for specific PUFAs were 51.7 linoleic, 50.1 α-linolenic, 39.7 arachidonic, 40.2 EPA, 53.5 decosapentaenoic acid, and 47.9 DHA. Corresponding values were 46.4, 52.8, 46.1, and 52.4 for total SFA, total PUFA, total n-3, and total n-6 densities. Many FA density equations had contributions from multiple metabolites, mostly serum metabolites, and from total energy expenditure. Sensitivity and specificity criteria are plausibly satisfied for proposed biomarkers, based on the feeding study design and on the sets of selected metabolites.

CONCLUSIONS: Combinations of log-transformed metabolite concentrations can lead to objective intake density estimates for multiple FAs in the diets of United States postmenopausal females, with relevance to the reliable study of dietary FA densities and chronic disease risk. This study was registered at clinicaltrials.gov as NCT00000611 https://clinicaltrials.gov/study/NCT00000611).

BACKGROUND: Telomere shortening is a biomarker for genome instability and aging, and the vulnerability of telomeric DNA to oxidative damage suggests its potential role in mediating radiotherapy (RT) side effects. This study evaluates telomere length (TL) as a biomarker for clinical radiosensitivity and adverse outcomes in thoracic RT-treated patients.

METHODS: Cancer patients receiving thoracic RT (2019-2022) were prospectively enrolled at [Anonymized for Review]. Peripheral blood mononuclear cells (PBMCs) were collected pre-RT and up to 12 months post-RT. TL was measured using quantitative PCR, and multi-pathway DNA repair capacity (DRC) was simultaneously assessed by fluorescence multiplex host cell reactivation (FM-HCR) assays. RT outcomes included patient-reported quality of life and radiation pneumonitis. Linear mixed-effects models were used to analyze TL dynamics; risk prediction models for RT outcomes were evaluated using area under the curve.

RESULTS: Pre-RT TL decreased with age (0.44% lower per year, 95% CI: 0.12%, 0.77%) and advanced cancer stage (6.87% lower per step increase of stage, 95% CI: 3.45%, 10.16%). Radical RT was associated with telomere shortening (3.7% lower, 95% CI: 0.27%, 7.07%) in PBMCs, detectable up to 6 months post-RT. Pre-RT TL strongly predicted post-RT changes, and TL dynamics outperformed static measures in predicting symptom burden and radiation pneumonitis. Positive associations were observed between TL and DRC against oxidative lesions, with A:8oxoG repair capacity mediating 12.8% of RT-induced TL shortening.

CONCLUSIONS: Lymphocyte TL can reflect individual radiosensitivity and interact with oxidative damage repair. Longitudinal assessment of TL dynamics provides additional predictive value for adverse RT outcomes compared to static measures. Further studies are needed to fully determine the clinical utility of TL.