Category: Nevin Manimala

Clin Transl Oncol. 2025 Aug 20. doi: 10.1007/s12094-025-03999-7. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the correlation between HER2 expression levels measured by HER2 mRNA using Oncotype DX and by immunohistochemistry (IHC) in hormone receptor-positive (HR+) and HER2-negative (HER2-) early breast cancer. In addition, we assessed whether low HER2 expression is associated with distinct clinicopathological characteristics and prognosis in our series.

METHODS: We conducted a retrospective study that included 500 patients diagnosed with stage I-III HR+/HER2- breast cancer who underwent surgery and had Oncotype DX recurrence score determined between 2009 and 2023 at Hospital Clínico San Carlos, Madrid, Spain. HER2 mRNA levels obtained through Oncotype DX were compared across IHC groups (HER2 0+, HER2 1+, HER2 2+/ISH-negative). Event-free survival (EFS) was analyzed according to HER2 expression.

RESULTS: Although HER2 mRNA levels increased with higher IHC HER2 categories, variability and overlap were observed between subgroups. Median Oncotype DX recurrence scores also rose slightly across HER2 IHC groups but did not reach statistical significance. EFS did not differ between HER2 expression levels.

CONCLUSIONS: We found that HER2 mRNA measurement by Oncotype DX provides a quantitative approach to assess HER2 expression. However, its results overlap within traditional IHC categories. While HER2-low classification may have therapeutic implications for new antibody-drug conjugates, its prognostic relevance appears limited. Further studies are needed to improve HER2 quantification methods for improved clinical decision-making.

PMID:40833671 | DOI:10.1007/s12094-025-03999-7

Ann Nucl Med. 2025 Aug 20. doi: 10.1007/s12149-025-02094-9. Online ahead of print.

ABSTRACT

PURPOSE: Transarterial radioembolization (TARE) is one of the local treatment options for primary and metastatic liver tumors. However, our knowledge regarding the safety of repeated TARE remains limited. In this study, we aimed to evaluate the safety of repeated transarterial radioembolization with multi-compartment dosimetry.

METHODS: In this retrospective single-center study, we analyzed the data of the patients who were treated with at least two separate sessions of radioembolization with ⁹⁰Y microspheres. Multi-compartment and voxel-wise dosimetry was performed for every treatment session and cumulative whole-liver normal tissue absorbed radiation dose (D_norm), V20-V100 values for whole-liver normal tissue were calculated. Toxicity was assessed with Common Terminology Criteria for Adverse Events (CTCAE) grading system for alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin levels and International Normalized Ratio (INR) before and after each treatment. In addition, albumin-bilirubin (ALBI) scores, grades, and changes in ALBI score (ΔALBI) were recorded. Difference between the ALBI scores before and after the treatment was compared with Wilcoxon tests, and relationships between ΔALBI and dosimetric variables were compared using linear regression analyses.

RESULTS: A total of 24 patients (6 males, 18 females; median age: 57 years) were included in the analysis. The most common diagnosis was colorectal carcinoma liver metastases (46%). Seventeen patients (71%) underwent two TARE treatments, five (21%) underwent three, and two (8%) underwent four. The median interval between the first and second treatments was 138 days (range: 34-782), and between the second and third treatments was 210 days (range: 72-435). No CTCAE Grade 3 or 4 toxicities were observed. ALBI score analysis revealed no significant changes after the first two treatments, but a significant difference was noted after the third treatment (P = 0.043), with one patient progressing to ALBI Grade 3 with significant hypoalbuminemia. No significant relationship was found between ΔALBI and treatment intervals. ALT/AST elevations were mostly transient and mild, with only one case of Grade 2 hepatotoxicity in each of the first two treatments. In patients treated with glass microspheres in their first two treatments (n = 12), a significant linear correlation was found between cumulative D_norm and ΔALBI (R² = 0.512, P = 0.007). Cumulative dose-volume histogram parameters, particularly V30, V40, and V50, showed significant correlations with ΔALBI. However, in patients treated with resin microspheres (n = 6), no statistically significant relationship was observed between cumulative D_norm and ΔALBI (P = 0.718).

CONCLUSION: Repeated TARE with a multi-compartment personalized dosimetric approach appears to be safe for the first two cycles, with limited low-grade toxicity. However, significant increase in ALBI scores after the third treatment was observed. ALBI score changes after second TARE were associated with cumulative liver radiation exposure in patients treated with glass microspheres. Larger studies are needed to further explore predictors of hepatotoxicity in repeated TARE.

PMID:40833652 | DOI:10.1007/s12149-025-02094-9

J Mol Model. 2025 Aug 20;31(9):251. doi: 10.1007/s00894-025-06481-x.

ABSTRACT

CONTEXT: hRPE65 is an essential enzyme in the retinoid visual cycle. Numerous missense variants of hRPE65 have been linked to retinal disorders, such as retinitis pigmentosa and Leber congenital amaurosis. Moreover, many hRPE65 missense mutations are currently classified as variants of uncertain significance (VUS) due to insufficient evidence for a definitive pathogenicity classification. Addressing this limitation is critical for enabling accurate diagnoses and identifying suitable candidates for gene therapy. For this reason, we developed a hRPE65-tailored computational strategy, based on a consensus of multiple in silico pathogenicity predictions, enabling a rapid and reliable evaluation of the potential pathogenic effect of over 200 hRPE65 VUS. The analysis provided valuable insights to support the reclassification of these variants and assist clinicians in assessing their suitability for gene therapy.

METHODS: In this study, we optimized our recently developed ConPath approach, which combines variant pathogenicity predictions from 19 different computational tools. In particular, we expanded the pool of predictive tools combined in the approach to 27, incorporated 3D-based methods that employ structural information for their prediction, and we refined the statistical framework for selecting the most reliable tools within an extended pool of more than 70 different methods. The tools were assessed based on their ability to discriminate pathogenic from benign hRPE65 missense mutations using an updated and expanded dataset of known hRPE65 variants. The resulting enhanced strategy, ConPath 2.0, was applied to the 210 hRPE65 VUS reported in the ClinVar database.

PMID:40833643 | DOI:10.1007/s00894-025-06481-x

World J Urol. 2025 Aug 20;43(1):505. doi: 10.1007/s00345-025-05873-1.

ABSTRACT

PURPOSE: This study focuses on the detection of human papillomavirus (HPV) in genital samples from heterosexual men, with or without HPV-like lesions, using molecular biology techniques for diagnosis and genotyping of the virus.

METHOD: A retrospective observational study was conducted with 294 male patients who visited a laboratory for molecular testing, with a presumptive clinical-epidemiological diagnosis of HPV infection, without prior HPV disease or vaccination. Samples were analyzed using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques.

RESULTS: Detection of HPV-infected men was 50.8%, with significant variability in incidence depending on the anatomical site of sampling. Fourteen high-risk HPV types were identified, along with the presence of multiple subtypes in several patients.

CONCLUSION: This study provides valuable insights into HPV incidence in men, the most prevalent genotypes, and their correlation with lesion presence. These findings may aid in developing prevention, vaccination, and control strategies for HPV in men.

PMID:40833638 | DOI:10.1007/s00345-025-05873-1

Eur J Pediatr. 2025 Aug 20;184(9):565. doi: 10.1007/s00431-025-06377-1.

ABSTRACT

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle weakness and respiratory decline due to impaired dystrophin production. Traditional spirometry, while valuable and reproducible, may pose difficulties for patients with significant muscle weakness. IOS can thus serve as a complementary, effort-independent approach, measuring respiratory system impedance, including resistance (R) and reactance (X) at various frequencies. This study aimed to evaluate IOS parameters in DMD patients, compare them with spirometry metrics, and explore their associations with clinical status, including ventilatory support use, ambulatory function, and scoliosis severity. This is a retrospective study. Clinical data, including ambulatory status (Vignos scale), bilevel positive airway pressure (BiPAP) use, the degree of Cobb angle, and spirometry and IOS measurements, were extracted from electronic medical records. Quantitative analyses included Student’s t-tests, Mann-Whitney U test, and Spearman’s rank correlation coefficients. A total of 42 DMD patients (mean age 14.3 ± 5.2 years) were included. Spirometry showed decreased forced vital capacity (FVC) in 52% and reduced FEV1/FVC in 12%. IOS revealed elevated mean R5 (120.9 ± 47.8%) and R20 (121.1 ± 33.1%) values, with significant correlations between IOS parameters (Z5Hz, R5Hz, R20Hz) and spirometry indices (FVC, FEV1, PEF, FEF25-75) (all p < 0.05). R5-R20 was positively correlated with FVC and PEF but negatively correlated with FEV1/FVC. Non-ambulatory patients and those requiring BiPAP support showed a higher R20% predicted values; however, these differences did not reach statistical significance (p = 0.068 and p = 0.123, respectively).

CONCLUSION: IOS is a feasible and valuable tool for respiratory assessment in pediatric DMD patients. The moderate correlations observed between IOS and spirometric indices suggest that IOS can provide supplementary information, enhancing the comprehensive evaluation of respiratory function in this population.

WHAT IS KNOWN: ∙ Spirometry is commonly used to assess respiratory function in DMD but requires patient effort, which can be challenging. ∙ Impulse oscillometry (IOS) offers an effort-independent method to evaluate respiratory mechanics.

WHAT IS NEW: ∙ Moderate correlations between IOS and spirometric indices can provide clinically relevant supplementary information for respiratory assessment in pediatric DMD. ∙ Combining IOS with spirometry provides a more comprehensive assessment of respiratory function in DMD.

PMID:40833624 | DOI:10.1007/s00431-025-06377-1

Support Care Cancer. 2025 Aug 20;33(9):800. doi: 10.1007/s00520-025-09825-8.

ABSTRACT

OBJECTIVE: To assess functioning and health-related quality of life (HRQoL) in patients referred to a cancer diagnostic pathway for non-specific serious symptoms, and to explore whether changes over 3 months differ among patients diagnosed with cancer, another serious diagnosis, or no serious diagnosis.

METHODS: A prospective cohort study was conducted at a hospital-based cancer diagnostic clinic. Functioning and HRQoL were assessed at baseline and after 3 months using the 36-item WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) and the EuroQol 5-Domain 5-Level (EQ-5D-5L), respectively.

RESULTS: A total of 347 patients were included, with 242 completing follow-up. At baseline, patients with another serious diagnosis reported the highest functioning difficulties (median WHODAS: 25) and lowest HRQoL (median EQ-5D-5L: 0.705). Functioning scores improved modestly across all groups at 3 months, with no statistically significant differences between them. However, HRQoL improved significantly only in patients with another serious diagnosis, compared to those with cancer or no serious diagnosis (p = 0.04).

CONCLUSION: Patients referred to a cancer diagnostic pathway for non-specific serious symptoms experience considerable functioning difficulties and reduced HRQoL at referral. While functioning improved modestly across all groups, only patients with another serious diagnosis showed a significant improvement in HRQoL. These findings highlight the need for early assessment and support for all patients in this pathway, irrespective of the final diagnosis, to ensure equitable care and timely rehabilitation when needed.

PMID:40833621 | DOI:10.1007/s00520-025-09825-8

Psychol Res. 2025 Aug 20;89(5):134. doi: 10.1007/s00426-025-02166-5.

ABSTRACT

The human visual system employs two complementary mechanisms-feature contrast enhancement and continuity maintenance-to effectively process extensive visual input. However, how these mechanisms interact to shape visual perception remains poorly understood. In this study, participants were asked to estimate the orientations of a serial of Gabor patches. Our results revealed two key perceptual biases: a cardinal bias, characterized by systematic deviations away from cardinal orientations (e.g., 0°), and serial dependence, where current estimates were attracted toward previously presented orientations. Notably, we found that the cumulative influence of cardinal bias across trials produced a repulsive history effect. When this effect was statistically removed from the estimation errors, the strength of serial dependence significantly increased. This suggests that while feature contrast enhancement and continuity maintenance generate opposing behavioral effects, they may share overlapping computational or neural processes. These mechanisms likely interact dynamically to refine and optimize visual perception. Moreover, our findings offer a robust methodological framework for isolating serial dependence effects, enabling future studies to more accurately quantify their role in perceptual decision-making. By disentangling these interacting biases, this work advances our understanding of how the visual system balances sensitivity to feature differences with the integration of perceptual history.

PMID:40833616 | DOI:10.1007/s00426-025-02166-5

Nervenarzt. 2025 Aug 20. doi: 10.1007/s00115-025-01874-y. Online ahead of print.

ABSTRACT

With the introduction of the 11th revision of the World Health Organization (WHO) “International Statistical Classification of Diseases and Related Health Problems” (ICD-11), structural and content-related adjustments were made to the diagnostic guidelines for affective disorders, which are presented in this review article. The update has resulted in some changes to the diagnostic classification of affective disorders, based on the American Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). The ICD-11 assigns depressive symptoms to so-called clusters, the main symptoms of depressed mood and joylessness can be accompanied by cognitive, behavioral or neurovegetative symptoms. In the case of remission of depressive episodes, the ICD-11 distinguishes between partial and complete remission. A persistent depressive disorder is present if the depressive episode lasts continuously for more than 2 years. In future, bipolar disorder will be divided into type I and type II. Manic episodes can still only be coded in the context of bipolar disorders and cannot be diagnosed as an independent, separate disorder. The concept of persistent affective disorders in the ICD-10 is abandoned, dysthymia is categorized as a depressive disorder and cyclothymia as a bipolar disorder.

PMID:40833614 | DOI:10.1007/s00115-025-01874-y

Arch Gynecol Obstet. 2025 Aug 20. doi: 10.1007/s00404-025-08151-y. Online ahead of print.

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis compared single- versus double-layer uterine closure at the time of cesarean delivery.

DATA SOURCES: MEDLINE, EMBASE, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from inception until May 2024.

STUDY ELIGIBILITY CRITERIA: We included only randomized controlled trials (RTSs) that compared single-layer versus double-layer uterine closure at the time of cesarean delivery.

STUDY APPRAISAL AND SYNTHESIS METHODS: Outcomes were analyzed using a random-effects model. Results are expressed as risk differences. The assessment of the risk of bias was performed by using the Risk of Bias 2 tool. The primary outcome was the incidence of scar defects (i.e., niche) at 6 months after delivery. The secondary outcomes were incidence of scar defects at 6 weeks and 3 months.

RESULTS: A total of 18 studies were identified by the systematic review; 11 RCTs involving 6,058 participants were included in the meta-analysis. There is no statistical difference between single-layer and double-layer uterine closure of cesarean delivery incision regarding the incidence of uterine scar defect at six weeks. Single-layer closure showed a significantly lower incidence of niche after three months (RD = – 0.02 (- 0.06, 0.02); I² = 81%, p < 0.01), and six months (RD = – 0.11, CI – 0.15, – 0.07, I² = 91%, p < 0.01).

CONCLUSIONS: Single-layer uterine closure at the time of cesarean delivery resulted in a lower uterine scar defects after three and six months compared to double-layer uterine closure.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, Unique identifier: CRD42024552495.

PMID:40833607 | DOI:10.1007/s00404-025-08151-y

Am J Biol Anthropol. 2025 Aug;187(4):e70112. doi: 10.1002/ajpa.70112.

ABSTRACT

OBJECTIVES: In the San Francisco Bay Area, Late Holocene resource intensification models predict an increase in diet breadth and a reduction in foraging efficiency associated with an increase in population, sedentism, and territoriality among fisher-hunter-gatherer populations. Here we compare bone stable carbon (δ¹³C) and nitrogen (δ¹⁵N) isotope values of sites along the eastern bay shore to interpret how ecogeographical partitioning of resources by latitude and distance from the bay reflects differential access and control of resources.

MATERIALS AND METHODS: With the support of, and in collaboration with, the Muwekma Ohlone Tribe of the San Francisco Bay Area, we analyzed bone collagen and bioapatite from 154 burials from Mánni Muwékma Kúksú Hóowok Yatiš Túnnešte-tka (CA-ALA-329) (2500-180 cal B.P.) to examine temporal changes in diet. Further, we examined the ecogeographical partitioning of resources in relation to published data from four contemporaneous sites.

RESULTS: For collagen (n = 146), δ¹³C values average -18.2‰±0.7‰ (1SD) and δ¹⁵N values average 9.8‰±1.5‰ (1SD). For bioapatite (n = 144), δ¹³C values average -13.8‰±1.0‰ (1SD). Adult males had statistically significantly higher isotope values compared to adult females, but differences were minimal (< 1.1‰). No meaningful temporal changes in diet were identified. Regional dietary differences occurred along a latitudinal gradient of the eastern bay shore.

DISCUSSION: Foraging efficiency was localized, suggesting that the exploitation of different microhabitats was critical to each tribal group. Stable isotope data complement zooarchaeological and paleobotanical data; although they reveal different aspects of subsistence practices and diet.

PMID:40832742 | DOI:10.1002/ajpa.70112