Nevin Manimala

EBioMedicine. 2026 Apr 10;127:106254. doi: 10.1016/j.ebiom.2026.106254. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic dysfunction is a major risk factor for neurodegeneration, yet the genetic architecture linking systemic metabolism to Alzheimer’s disease (AD) and Parkinson’s disease (PD) remains unclear.

METHODS: We integrated genome-wide association data for 249 circulating metabolites and proglucagon with summary statistics for AD, PD, and cardiometabolic traits. Genetic correlations, polygenic overlap, causal relationships, and shared genetic loci were quantified using linkage disequilibrium score regression, high-definition likelihood, bivariate mixture modelling, Mendelian randomisation, and conjunctional false discovery rate analyses, followed by functional and tissue-specific enrichment analyses.

FINDINGS: AD displayed a metabolic-genetic profile aligned with body mass index, type 2 diabetes, coronary artery disease, and stroke, whereas PD exhibited largely opposing patterns (Spearman’s r_s = -0.26). Mendelian randomization analyses supported causal effects of lipoprotein subclasses, glutamine, and proglucagon on AD risk, with opposite or null effects in PD. Shared loci between metabolites and AD were enriched for lipid metabolism and cholesterol transport, whereas PD-associated loci were enriched for mitochondrial function, vesicle trafficking, and stress-response signalling.

INTERPRETATION: AD and PD are shaped by fundamentally distinct metabolic-genetic architectures. Metabolically targeted interventions, particularly those modulating lipid, amino acid, and proglucagon pathways, may require disease-specific and genetically informed strategies for prevention and treatment of neurodegenerative diseases.

FUNDING: Novo Nordisk Foundation (NNF23OC0099658), Marie Skłodowska-Curie Actions (801133), the Research Council of Norway (334920, 351751, 296030, 324252, 324499, 326813), the National Institutes of Health (U24DA041123, R01AG076838, U24DA055330, OT2HL161847, 5R01MH124839-02), NordForsk (164218), South-Eastern Norway Regional Health Authority (2020060), and the European Union’s Horizon 2020 (847776, 964874, 101057454).

PMID:41966729 | DOI:10.1016/j.ebiom.2026.106254

Eur J Cancer. 2026 Apr 5;240:116732. doi: 10.1016/j.ejca.2026.116732. Online ahead of print.

ABSTRACT

INTRODUCTION: This study explores the association between income and patient- and treatment characteristics, diagnosis through screening and survival of patients with synchronous metastasized CRC.

METHODS: Patients diagnosed with stage IV CRC between 2015 and 2023 were selected from the Netherlands Cancer Registry. Income at postal code level was used (Statistics Netherlands). Multivariable logistic regression analyses were used to determine the association between income and treatment. Crude relative survival stratified for income was calculated, as well as relative excess risks of death using a multivariable generalized linear model.

RESULTS: The study included 24,666 patients, with respectively 33%, 35% and 32% having higher, intermediate and lower income. Detection through screening was more often realized in the higher income group compared to intermediate and lower income (9% vs. 8% vs.6%, p < 0.001). Among patients with single-organ metastases, higher income patients were more often treated with curative intent for metastases to the liver (40% vs. 35% vs. 29%, p < 0.001) and peritoneum (36% vs. 29% vs.22%, p < 0.001) compared to intermediate or lower income, also in multivariable analyses. Similarly, systemic therapy was given more frequently to patients with higher income than those with intermediate or lower income (56% vs. 51% vs.42%, p < 0.001). Crude 3-year relative survival was 21% (lower), 22% (intermediate) and 26% (higher income, adjusted RER higher vs. lower income: 0.93, [95%CI 0.90-0.97]; intermediate vs. lower income: 0.95, [95%CI 0.92-0.99]).

CONCLUSIONS: Patients with higher income were more likely to receive tumour directed treatment, including curative intent treatment which may result in the observed longer survival.

PMID:41966682 | DOI:10.1016/j.ejca.2026.116732

Clin Nutr. 2026 Mar 30;60:106644. doi: 10.1016/j.clnu.2026.106644. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Nutritional status and inflammatory processes serve as significant factors that contribute to the development and progression of cancer cachexia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is an emerging marker for assessing nutritional and inflammatory status, however, its association with overall survival (OS) in patients with cancer cachexia remains unknown. This study aims to explore the prognostic value of the HALP score in patients with cancer cachexia.

METHODS: This is a multicenter cohort study that includes 3150 cancer patients diagnosed with cachexia between June 2012 and December 2019. The primary outcome is overall survival (OS) and the recommended cutoff point for the HALP score is calculated using the optimal stratification method. Kaplan-Meier survival analyses and multivariable Cox regression analyses are used to explore the association between the HALP score and OS. Restricted cubic spline and stratified analysis are used to further illustrate the association between HALP score and OS.

RESULTS: The median age of the included participants is 60 years and 59.3% is male. Cancer patients with cachexia have lower HALP scores which decreases with TNM staging progress. The optimal cut-off value for HALP associated with OS is 22.13. High HALP is associated with better OS in patients with cachexia (p < 0.0001) and presents in most cancer types. After adjusting for all confounders, high HALP is associated with a significant reduction in all-cause mortality (HR, 0.80, 0.71-0.89, p < 0.001). Further analysis indicates that this association varied by sex, showing greater benefit among females (HR, 0.68, 0.56-0.82, p < 0.001). High HALP shows the stronger protective effects when combined with favorable clinical characteristics (e.g., younger age, surgery, normal blood indices, etc.) corresponding to lower HALP group.

CONCLUSIONS: The HALP score is an independent prognostic factor in patients with cancer cachexia, especially among females. These findings suggest that HALP may serve as an effective prognostic indictor for cachexia patients and provide insights for clinical risk assessment and management decisions.

PMID:41966680 | DOI:10.1016/j.clnu.2026.106644

Eur Phys J E Soft Matter. 2026 Apr 12;49(4):35. doi: 10.1140/epje/s10189-026-00578-8.

ABSTRACT

The mechanical behavior of single-stranded DNA (ssDNA) controls its biological function and underpins the design of DNA-based nanodevices, yet the microscopic origin of temperature-dependent elasticity remains incompletely quantified. Here, we use the salt-aware, sequence-dependent oxDNA2 coarse-grained model to map how intra-strand stacking and temperature jointly determine ssDNA mechanics for two prototypical homopolymers, poly(dA)₅₀ and poly(dT)₅₀, across 27-100 °C at 1.0 M monovalent salt. Large ensembles of independent simulations were used to extract equilibrium observables such as persistence length $l_p$ , radius of gyration $R_g$ , end-to-end distance $R_{\text{ee}}$ , and equilibrium force-extension relations. We find that poly(dA) is substantially stiffer than poly(dT) at low temperature: $l_p$ ​ = 44.8 ± 2.0 nm at 27 °C decreases to 10.0 ± 0.7 nm at 100 °C, while poly(dT) remains comparatively flexible, varying only from 1.40 ± 0.08 nm to 1.05 ± 0.04 nm. These macroscopic changes closely track the loss of intra-strand stacking. For poly(dA), the stacking fraction decreases from 0.70 ± 0.02 to 0.20 ± 0.01, whereas poly(dT) remains weakly stacked across the full range (< 0.10). Force-extension analysis shows that the wormlike chain (WLC) model captures low-force entropic elasticity but fails at intermediate extensions in strongly stacked poly(dA), where cooperative unstacking produces excess forces of ~ 8 to 10 pN near $x\approx 0.6L$ . The normalized root-mean-square residual at 27 °C is 0.22 for poly(dA), compared to 0.03 for poly(dT). When $l_p$ is normalized by its 27 °C value, both sequences collapse onto a single master curve as a function of stacking fraction (collapse slope ≈ 3.5 ± 0.3), indicating that fractional stacking loss serves as a unifying control parameter for thermal softening. These results quantitatively link microscopic stacking statistics to macroscopic elasticity, clarify the temperature-dependent limits of continuum polymer models, and provide a mechanistic framework for interpreting single-molecule stretching and ensemble measurements of ssDNA mechanics.

PMID:41966679 | DOI:10.1140/epje/s10189-026-00578-8

Clin Transl Oncol. 2026 Apr 12. doi: 10.1007/s12094-026-04303-x. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide, accounting for more than 2.3 million new cases annually. Although chronic inflammation is a well-established risk factor for cancer, the association between mastitis and BC has not yet been clearly established. Therefore, this study aims to investigate mastitis as a potential risk factor for BC.

METHODS: We performed a random-effects meta-analysis to estimate the odds ratio (OR) and hazard ratio (HR). P values lower than 0.05 were considered statistically significant, with 95% confidence intervals (CI). Statistical analyses were conducted using R Studio software version 4.4.2, considering P < 0.05 as statistically significant.

RESULTS: Our meta-analysis included 54,216 patients, of whom 18,753 (34.6%) had mastitis, while 35,463 (65.4%) comprised the control group. Our results support that the risk of BC is higher among patients with a history of mastitis (OR: 2.12; 95% CI: 1.44-3.11; p = 0.0423). Similarly, longitudinal analysis based on total follow-up also confirmed an increased risk of BC in the mastitis group (HR: 2.0057; 95% CI: 1.1739-3.4269; p = 0.011).

CONCLUSION: This meta-analysis highlights a possible association between the presence of mastitis and BC, substantially contributing to the advancement of understanding regarding risk factors for this cancer. Prospective studies using robust detection methods and paired tissue analyses are needed to confirm these findings and clarify the role of mastitis in breast tumorigenesis.

PMID:41966678 | DOI:10.1007/s12094-026-04303-x

Discov Oncol. 2026 Apr 12. doi: 10.1007/s12672-026-04909-1. Online ahead of print.

NO ABSTRACT

PMID:41966662 | DOI:10.1007/s12672-026-04909-1

EJNMMI Phys. 2026 Apr 12. doi: 10.1186/s40658-026-00867-3. Online ahead of print.

ABSTRACT

BACKGROUND: Continuous bed motion (CBM) allows flexible extension of the scan range compared to conventional step‑and‑shoot (S&S) acquisition but has not yet been evaluated in long axial field‑of‑view (LAFOV) PET/CT. This study systematically assessed the impact of CBM on image quality, noise, and quantitative performance in the Biograph Vision Quadra LAFOV PET/CT using multi‑phantom and patient scans compared to S&S.

METHODS: A uniform tube phantom and a NEMA IEC phantom, positioned centrally and off-centre, were scanned across bed speeds (2.8-50 mm/s), sensitivity modes and scan ranges (106 and 150 cm) to evaluate image uniformity, axial count profiles, noise and contrast recovery coefficients (CRC). Ten oncological patients receiving [¹⁸F]PSMA-1007 or [¹⁸F]FDG underwent sequential CBM (2.8 mm/s, 378 s) and S&S (300 s) scans. Image noise, net true counts, and liver and lesion SUV values were compared using paired statistics and Bland-Altman analysis, along with PSMA expression scores.

RESULTS: For comparable count statistics and image noise, CBM required a prolonged acquisition (378 s) to match the S&S (300 s) protocol, resulting in comparable image quality for phantoms and patients. CRC and image uniformity were preserved across all evaluated conditions, even at the FOV’s axial edge (50.5 cm) for 8.4 mm/s (22 mm sphere: CRC 76% S&S vs. 71% CBM). In patient scans, minor differences in axial count profiles, net true counts, and SUV values (SUV_mean bias – 0.1 (liver) and – 0.8 (lesions)) did not affect clinical scores.

CONCLUSIONS: The prolonged CBM protocol provides image quality and quantitative performance comparable to S&S in LAFOV PET/CT. While the reconstructed image range remains constrained by CT coverage, the patient scan comparison with 106 cm scan range, together with extended range phantom measurements, indicate that CBM can support scan range extension beyond 106 cm without compromising diagnostic accuracy.

PMID:41966653 | DOI:10.1186/s40658-026-00867-3

Abdom Radiol (NY). 2026 Apr 12. doi: 10.1007/s00261-026-05425-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the value of tumor volume reduction rate (VRR) measured by enhanced CT, compared with RECIST 1.1 criteria, in evaluating the efficacy of neoadjuvant chemotherapy combined with immunotherapy(NACI) for patients with locally advanced gastric cancer (LAGC), and its impact on prognosis.

METHODS: This retrospective study included 107 gastric adenocarcinoma patients. VRR and RECIST 1.1 response were calculated from pre-treatment and post-treatment CT. Interobserver agreement was evaluated using the intraclass correlation coefficient(ICC), while correlation with pathological tumor regression grade (TRG) and diagnostic performance (ROC analysis) were assessed. The optimal VRR cut-off was determined. Prognostic value was evaluated via survival analysis.

RESULTS: The ICC for the tumor VRR was 0.966 (95% CI: 0.951-0.977), which was significantly higher than the ICC for the tumor longest diameter reduction rate (0.701, 95% CI: 0.590-0.785). VRR showed a moderate negative correlation with TRG (r= -0.389, P < 0.001), which was significantly better than the weak correlation between RECIST 1.1 and TRG (r = 0.196, P = 0.043). The area under the curve (AUC) for VRR in predicting major pathological response was significantly higher (AUC = 0.7953) than that for RECIST 1.1 (AUC = 0.6127, P = 0.0017). Survival analysis showed that grouping based on VRR (2-year PFS: 69.4% vs. 37.8%, P = 0.018) and TRG (2-year PFS: 82.8% vs. 46.2%, P = 0.0029) significantly distinguished patient prognosis, whereas RECIST 1.1 criteria did not (P = 0.74). The combined model integrating VRR and TRG failed to provide more refined prognostic stratification. Among patients with TRG 2-3, whether VRR was greater than 47.4% did not significantly stratify prognosis (P = 0.7935).

CONCLUSIONS: (1) The tumor VRR demonstrates significantly superior observer agreement compared to the RECIST 1.1 criteria. (2) The correlation with TRG and diagnostic efficacy of VRR before and after neoadjuvant chemotherapy combined with immunotherapy are significantly superior to RECIST 1.1 criteria. (3) Regarding 2-year PFS, both VRR and TRG are effective indicators for prognostic evaluation after this treatment regimen, whereas RECIST 1.1 criteria lack statistical significance for 2-year PFS. (4) The combined model of VRR and TRG did not enable more precise prognostic stratification, indicating a need for further research.

PMID:41966643 | DOI:10.1007/s00261-026-05425-0

J Gastroenterol. 2026 Apr 12. doi: 10.1007/s00535-026-02412-6. Online ahead of print.

ABSTRACT

BACKGROUND: Durvalumab plus gemcitabine-cisplatin (GCD) has become a standard first-line therapy for advanced biliary tract cancer (BTC) following the TOPAZ-1 trial. However, whether the survival benefit observed in trial-eligible patients can be generalized to broader real-world populations remains uncertain. We evaluated the impact of TOPAZ-1 eligibility on the effectiveness of GCD in routine clinical practice.

METHODS: In this multicenter retrospective cohort study, 610 patients with unresectable or recurrent BTC treated with first-line GCD (n = 268) or gemcitabine-cisplatin (GC) (n = 342) at 19 Japanese institutions were analyzed. Patients were classified according to TOPAZ-1 eligibility criteria. Overall survival (OS) was compared between treatment groups in the entire cohort and stratified by eligibility status. Multivariable Cox models were constructed separately for eligible and ineligible patients.

RESULTS: Among 610 patients, 324 (53.1%) met TOPAZ-1 eligibility criteria. In the overall cohort, GCD was associated with longer OS than GC (median, 13.7 vs 11.3 months; p = 0.009). Among eligible patients, GCD significantly improved OS compared with GC (18.0 vs 13.1 months; p = 0.004), whereas no significant difference was observed among ineligible patients (10.8 vs 10.0 months; p = 0.675). However, the interaction between treatment and TOPAZ-1 eligibility was not statistically significant (p for interaction = 0.162).

CONCLUSIONS: In this real-world cohort, the survival benefit of GCD appeared to be primarily observed in patients meeting TOPAZ-1 eligibility criteria. Trial-based eligibility may influence the magnitude of benefit from immunochemotherapy in advanced BTC, underscoring the importance of patient selection in routine practice.

PMID:41966637 | DOI:10.1007/s00535-026-02412-6

Ultrasonics. 2026 Mar 26;165:108058. doi: 10.1016/j.ultras.2026.108058. Online ahead of print.

ABSTRACT

This study examined the effectiveness of incorporating ultrasonic mid-air haptic feedback into a three-dimensional multiple object tracking (3D-MOT). A custom-built ultrasonic phased array generated mid-air tactile stimuli within an 8 × 8 × 10 cm region, synchronized with a Unity-based interactive training game involving dynamic ball-catching tasks. This work assigned 20 healthy adult volunteers to the experimental (with haptic feedback) or control (without haptic feedback) groups. In addition, we assessed the cognitive and motor-cognitive performance before and after the intervention using lab-based and field-based cognitive control tasks (e.g., the flanker task) to examine potential transfer effects. The results showed that the experimental group demonstrated significantly faster learning progress by bleaching 26% more red spheres by day 6, and reaching performance stability 3 days earlier. Mixed-design ANOVA confirmed statistically significant differences in training trends (p = 0.035) and level scores (p = 0.051), with medium to large effect sizes. Besides, although both groups demonstrated improved cognitive control performance (i.e., reduced flanker effect in reaction time [RT]) following the intervention in the lab-based task, only the experimental group showed a further reduction in the flanker effect of RT at the perceptual-cognitive level on the field-based task (p = 0.003). This finding suggests that cognitive training with haptic feedback simulating somatosensory cortex activity may yield greater benefits for cognitive control processing during a motor task. This study showed that integrating ultrasonic haptic feedback meaningfully enhances visuospatial training outcomes, and offers a scalable, hands-free solution for cognitive rehabilitation, underscoring the promise of multisensory approaches to optimize cognitive health.

PMID:41966617 | DOI:10.1016/j.ultras.2026.108058