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Real-world clinical outcomes of intermediate-risk PAM50 (i-ROR) in HR+/HER2- early breast cancer and eligibility for adjuvant CDK4/6 inhibitors

Breast Cancer Res Treat. 2026 Jul 14;218(1):12. doi: 10.1007/s10549-026-08027-y.

ABSTRACT

INTRODUCTION: Risk-adapted strategies are central to early breast cancer (EBC) management, particularly in HR+/HER2 – disease. Prosigna/PAM50 combined with clinicopathologic factors refines prognosis, with clearer guidance at ROR extremes, while decisions in the intermediate-risk (i-ROR) group remain challenging. Although adjuvant iCDK4/6 therapy improves outcomes in high-risk patients, eligibility in i-ROR may be overlooked. This study outlines clinicopathologic features, recurrence-free survival, and iCDK4/6 eligibility in i-ROR EBC to support treatment decision-making.

METHODS: We performed a retrospective analysis of 554 EBC patients who underwent PAM50 testing at Hospital Universitario 12 de Octubre (2015-2024). Clinical, pathological, diagnostic, follow-up, and recurrence data were obtained from records. Kaplan-Meier analyses estimated RFS, while multivariate logistic regression identified predictors of chemotherapy use within i-ROR. Descriptive statistics assessed eligibility for adjuvant ribociclib (NATALEE) and abemaciclib (monarchE).

RESULTS: Among 212 i-ROR patients (38%), 71.7% were postmenopausal, 65.5% Luminal A and 34% Luminal B intrinsic subtypes, and 53.7% node-negative. 68.4% did not receive chemotherapy. There were 11 relapses, predominantly Luminal A (72.7%), node-negative (63.6%), and chemotherapy-naive (90.9%). RFS at 12, 36, and 60 months was 100%, 97.9%, and 96.9%. Chemotherapy use was associated with younger age (p = 0.006), node positivity (p = 0.021), and luminal B subtype (p = 0.001). CDK4/6 eligibility was 44.3% for NATALEE and 14.6% for monarchE, with 10.8% meeting both; chemotherapy use was higher in monarchE-eligible patients (41.9% vs. 31.9%).

CONCLUSIONS: This real-world cohort of PAM50 i-ROR HR+/HER2 – EBC patients showed excellent prognosis (5-year RFS > 96%), yet relapses still occurred, highlighting the need for improved risk stratification and consideration of adjuvant therapies, including iCDK4/6.

PMID:42446834 | DOI:10.1007/s10549-026-08027-y

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Circulating microRNAs as Promising Biomarkers in Parkinson’s Disease

Mol Neurobiol. 2026 Jul 14;63(1):758. doi: 10.1007/s12035-026-06045-x.

ABSTRACT

Our study aims to examine possible Parkinson Disease (PD)-related circulating microRNAs (miRNA) and their potential roles and use cases in screening, diagnosis, and the disease progress in Turkish population. For this purpose, we selected 7 promising candidates namely miR-16-1, miR-24-3p, miR-30a, miR-30e, miR-34a, miR-34b, miR-331 from multiple studies and bioinformatic web tools. For our study, 51 PD patients with no other severe disease except for hypertension and 20 healthy matching controls were included. Serum samples were collected from venous blood and stored properly. RNA extraction, reverse transcription and real-time polymerase chain reaction (qPCR) for each pre-determined miRNA were applied to all samples with a strong normalization method to determine expression levels. Additionally, validated miR-24-3p target genes were intersected against publicly available CSF proteomics (PXD011216), PBMC transcriptomics (GSE22491), and serum metabolomics (MTBLS10958) datasets. miR-24-3p expression was also examined in two independent miRNA datasets (GSE269775; GSE16658). Statistical analyses were done using SPSS and Qiagen GeneGlobe webtools. Between PD and the control group, miR-24-3p serum levels were found increased 1.7 times (p = 0.0001). Among patients, miR-331 serum levels changed significantly with UPDRS scores (p = 0.027). Multi-omics analysis identified 21 differentially abundant miR-24-3p target proteins in PD CSF (81% downregulated), three cross-platform concordant targets, and five metabolically linked pathways. miR-24-3p levels may differ in different biological compartments in PD. In serum, miR-24-3p may provide significant value as a diagnostic biomarker with 80.4% sensitivity and 85% specificity. miR-331 might be a candidate for predicting the severity of the disease.

PMID:42446817 | DOI:10.1007/s12035-026-06045-x

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Characteristics and Treatment Patterns in People with Burden of Migraine: A Subgroup Analysis of the OVERCOME Japan 2nd Study

Pain Ther. 2026 Jul 14. doi: 10.1007/s40122-026-00857-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The burden of migraine on an individual’s life is associated with an individual’s background. However, limited evidence in Japan exists on the association of age, sex, employment, income, and family caregiving with patient-reported outcomes (PROs) and migraine treatment patterns. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) 2nd study describes the migraine burden and treatment usage of individuals with migraine across these demographic subgroups.

METHODS: Participants self-reported demographic and clinical characteristics, and PRO instrument responses, such as Headache Impact Test-6, Migraine Disability Assessment Scale (MIDAS), Migraine-Specific Quality of Life Questionnaire version 2.1, Migraine Interictal Burden Scale-4 (MIBS-4), and Impact of Migraine on Partners and Adolescent Children Scale. They also reported use of over-the-counter and prescription drugs for migraine, and headache-related expenses. Descriptive statistics were reported according to sex, employment status, menstrual-related migraine status and frequency, annual personal and family income, age, and family caregiving status for the elderly.

RESULTS: Female sex, unemployment, presence of menstrual-related migraine, low personal or family income, and family caregiving for elders appeared to increase migraine burden and impact prescription drug use. Specifically, men tended to have higher triptan (11.7% vs. 8.7%) and preventive medication use (18.3% vs. 11.2%) than women; unemployed women had the highest proportion of MIDAS grade IV (14.1%); women with menstrual-related migraine appeared to have greater MIBS-4 severe burden (36.3% vs. 27.8%) than those without; and family caregivers tended to have higher MIBS-4 severe burden (39.2% vs. 26.0%) and prescription drug use than non-caregivers. Respondent sex further appeared to influence migraine burden and treatment patterns within the employment and income subgroups.

CONCLUSION: These data suggest certain sociodemographic groups may suffer from greater migraine burden and have reduced access to effective treatment and care. We hope this study’s results will help healthcare providers and societies identify such populations with migraine and address potential clinical care gaps.

PMID:42446809 | DOI:10.1007/s40122-026-00857-4

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Interrelationship between anatomical variations in mandibular teeth: a cone-beam computed tomography (CBCT) based study

Odontology. 2026 Jul 14. doi: 10.1007/s10266-026-01497-y. Online ahead of print.

ABSTRACT

This retrospective study evaluated the anatomical variations and morphological interrelationships of mandibular anterior, premolar, and first molar (MFM) teeth in a Turkish subpopulation using cone-beam computed tomography (CBCT), while categorizing and comparing root canal anatomies based on both the traditional Vertucci and contemporary Ahmed’s classification systems. The study analyzed CBCT images of 9,504 mandibular teeth from 792 patients. Root canal configurations were classified utilizing both the Vertucci and Ahmed’s systems. The study additionally evaluated root counts, distolingual root (DLR) presence in MFMs, bilateral agreement, and cross-group anatomical correlations. All anterior teeth were single-rooted but displayed significant internal morphological diversity. MFMs predominantly featured a two-rooted structure, with a DLR (Radix Entomolaris) observed in 5.3%-6.8% of cases. A significant positive correlation emerged between complex canal configurations in lateral incisors and the presence of an ipsilateral MFM DLR (p = 0.003, OR = 2.23). Males exhibited significantly higher anatomical complexity in premolars than females. Mandibular teeth demonstrate high morphological diversity and bilateral agreement. The statistically significant but weak correlation between lateral incisor canal complexity and MFM DLR presence may represent a preliminary indicator that requires further validation. Furthermore, the Ahmed’s system provides broader descriptive coverage for for defining complex root canal anatomies compared to the traditional Vertucci classification.

PMID:42446776 | DOI:10.1007/s10266-026-01497-y

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lncRNA MEG3 and Beclin-1 as diagnostic biomarkers in serous ovarian carcinoma: molecular and immunohistochemical insights

J Mol Histol. 2026 Jul 14;57(4):234. doi: 10.1007/s10735-026-10893-1.

ABSTRACT

Serous ovarian carcinoma (SOC) is frequently diagnosed at advanced stages and is associated with poor clinical outcomes, highlighting the urgent need for reliable diagnostic and prognostic biomarkers. Long non-coding RNA MEG3 and the autophagy-related protein Beclin-1 are recognized tumor suppressors; however, their combined diagnostic relevance in SOC remains insufficiently explored. This case-control study included 24 patients with histopathologically confirmed SOC. Paired tumor and adjacent non-tumorous ovarian tissues were analyzed for lncRNA MEG3 expression using quantitative real-time PCR and for Beclin-1 protein expression using immunohistochemistry. Serum CA-125 levels were assessed by ELISA. Associations with clinicopathological parameters were evaluated, and diagnostic performance was analyzed using receiver operating characteristic (ROC) curves. Both lncRNA MEG3 and Beclin-1 were significantly downregulated in SOC tissues compared with adjacent non-cancerous tissues (P < 0.0001). Reduced expression was significantly associated with tumor grade and ascites. The relationship with FIGO stage was not uniform in this cohort and should be interpreted cautiously because of the small sample size and unequal distribution of early and advanced cases. Beclin-1 expression was notably higher in premenopausal patients and in well to moderately differentiated tumors. A strong positive correlation was observed between lncRNA MEG3 and Beclin-1 expression (r = 0.96, P < 0.001), indicating a strong statistical association rather than a proven regulatory interaction. ROC curve analysis suggested diagnostic potential for lncRNA MEG3, Beclin-1, and serum CA-125. The concurrent downregulation of lncRNA MEG3 and Beclin-1 in SOC tissues suggests that these markers may serve as promising complementary biomarkers. However, their clinical utility should be considered preliminary and requires validation in larger, multicenter cohorts with functional studies before routine clinical application can be recommended.

PMID:42446766 | DOI:10.1007/s10735-026-10893-1

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A novel pulley-vest model enables progressive resistance exercise in rats without tail loading

J Muscle Res Cell Motil. 2026 Jul 14;47(3):17. doi: 10.1007/s10974-026-09735-0.

ABSTRACT

Resistance training in rodent models is widely used to investigate muscular and cardiovascular adaptations. Traditional models often attach loads to the tail. The present study aimed to develop and validate a resistance training model for rats using a pulley system combined with a load-bearing vest, allowing progressive overload without tail attachment. Spontaneously hypertensive rats were assigned to control (CTR, n = 4) or resistance training (RT, n = 6) groups for a 10-week ladder climbing protocol. Functional and morphometric adaptations were evaluated in the soleus and flexor hallucis longus (FHL) muscles. Resistance training resulted in a significant increase in relative maximum load carried (p = 0.0007), corresponding to a 79.5% improvement in strength capacity. The RT group also showed increased relative mass of the FHL muscle (p = 0.002). Gene expression analyses did not show statistically significant differences between groups (p > 0.05). The pulley-vest system proved to be a viable and effective resistance training model for rats, allowing controlled overload while avoiding tail load attachment and potential vascular interference. This model represents a refined experimental approach for resistance training studies in rodent models, particularly in conditions where tail circulation must be preserved.

PMID:42446765 | DOI:10.1007/s10974-026-09735-0

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Quality assessment and hydrochemical control mechanism of groundwater in the Hailar Basin

Environ Geochem Health. 2026 Jul 14;48(10):459. doi: 10.1007/s10653-026-03345-y.

ABSTRACT

The study investigated groundwater quality, irrigation suitability, health risks, and hydrochemical control mechanisms in the Hailar Basin. The water quality index (WQI) was used to evaluate drinking-water suitability, while the U.S. Salinity Laboratory (USSL) diagram, Wilcox diagram, and permeability index (PI) were applied to assess irrigation suitability. Hydrogeochemical and statistical methods were used to identify the main processes controlling groundwater evolution. The results show that groundwater is mainly of the HCO3-Na·Na type in the Herhongde Sag, Cl-Na and HCO3-Na types in the Cuogang Uplift, Wuerxun Sag, and Beier Sag, HCO3-Na type in the Bayanshan Uplift, and Cl-Na type in the Hongqimuchang Sag and Xinbaolige Sag. In the study area, 13% of samples exceeded the limit for NO3, 72% for As, 90% for F, and 71% for U. Health risk assessment indicated potential non-carcinogenic risks from As, U, and F ingestion, with mean hazard index (HI) values of 18.10 for adults and 50.66 for children, and unacceptable As related carcinogenic risks. According to the WQI results, 36.84% of groundwater samples were classified as excellent or good for drinking, whereas 15.79% were very poor. The irrigation assessment indicates that groundwater presents low to moderate sodium hazard levels but moderate to extremely high salinity hazard levels, with most samples falling within the C2S1, C3S2, and C4S2. The groundwater chemistry is mainly controlled by rock weathering and evaporative crystallization, and is further influenced by arid to semi-arid climatic conditions and intensified anthropogenic activities.

PMID:42446744 | DOI:10.1007/s10653-026-03345-y

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Involvement of adiponectin in the biology of attention deficit hyperactivity disorder

Eur Child Adolesc Psychiatry. 2026 Jul 14. doi: 10.1007/s00787-026-03114-3. Online ahead of print.

ABSTRACT

We investigated the involvement of adiponectin in the development of attention-deficit/hyperactivity disorder (ADHD), using a multi-pronged approach integrating cord blood adiponectin concentrations, polygenic risk scores derived from publicly available GWAS summary statistics, and Mendelian randomization. This study aimed to evaluate both upstream genetic influences and downstream adiponectin-level associations. Using a combination of longitudinal cord blood data (N = 531) and genome-wide association studies of ADHD (N = 55,374) and adiponectin (N = 46,434), we examined observational, genetic, and associations linking adiponectin with ADHD. Lower cord blood adiponectin levels were associated with higher ADHD symptoms at ages 5-6 and 8-9, and predicted membership in the increasing-symptom trajectory group. Gene-set analysis demonstrated pathway-level overlap between ADHD and adiponectin regulation. Genetic correlation analysis showed a significant negative correlation between ADHD and adiponectin levels. Mendelian randomization provided stronger evidence for an association of ADHD on adiponectin levels. Polygenic risk score analysis also demonstrated a negative association between genetic liability for ADHD and cord blood adiponectin levels. Additionally, lower adiponectin levels were found to be associated with elevated inflammatory markers in the cord blood samples obtained from the cohort study, which may provide a potential explanation for the higher prevalence of metabolic comorbidities observed in individuals with ADHD. These findings suggest that adiponectin may be associated with the biologyof ADHD and targeting adiponectin regulation may offer a novel approach for managing ADHD and its related health risks.

PMID:42446714 | DOI:10.1007/s00787-026-03114-3

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Association between breech presentation in twins and developmental dysplasia of the hip

Orthopadie (Heidelb). 2026 Jul 14. doi: 10.1007/s00132-026-04867-0. Online ahead of print.

ABSTRACT

BACKGROUND: Breech presentation is considered one of the main risk factors for developmental dysplasia of the hip (DDH) in singleton pregnancies; however, data regarding twins are limited. The aim of this study was to evaluate whether breech presentation in twins is associated with abnormal hip ultrasound findings and to assess the influence of delivery mode, sex and gestational age.

METHODS: Obstetric and ultrasound data from twin births at Frankfurt University Hospital between 2010 and 2014 were retrospectively analyzed. A total of 130 twins in whom at least 1 infant with breech presentation and both infants underwent hip ultrasound according to Graf’s technique within the first 14 days after birth were included. Twins were divided into breech-breech, breech-vertex and breech-transverse groups. Hip findings were categorized as normal (Graf type Ia/Ib) or abnormal/immature (Graf type IIa or higher). Statistical analysis was performed using Fisher-Freeman-Halton exact testing.

RESULTS: No infant demonstrated manifest DDH (Graf type IIc or higher). Overall, 5.4% of infants showed physiologically immature or abnormal hip ultrasound findings classified as Graf type IIa. No significant association was found between breech presentation and abnormal hip findings; however, abnormal findings were more common in the breech-transverse group compared to the breech-breech group (p = 0.037). Infants delivered via cesarean section demonstrated a higher rate of abnormal findings than vaginally delivered infants (p = 0.041).

CONCLUSION: In this cohort, breech presentation in twins was not associated with an increased rate of abnormal hip ultrasound findings. The combination of breech and transverse presentation may represent a higher risk constellation. Due to the retrospective design and lack of a singleton control group, conclusions regarding a modifying effect of twin pregnancy on the occurrence of DDH cannot be drawn.

LEVEL OF EVIDENCE: Retrospective cohort study. Level III evidence.

PMID:42446713 | DOI:10.1007/s00132-026-04867-0

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Do DMARDs increase the risk of cancer recurrence in patients with spondyloarthritis, psoriatic arthritis and rheumatoid arthritis?

Clin Exp Rheumatol. 2026 Jul 9. doi: 10.55563/clinexprheumatol/msvat0. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess whether the use of immunosuppressants after cancer diagnosis in patients with spondyloarthritis (SpA) and rheumatoid arthritis (RA) is associated with increased risk of cancer recurrence or mortality.

METHODS: We consecutively enrolled patients with spondyloarthritis (SpA), psoriatic arthritis (PsA), or rheumatoid arthritis (RA) and concomitant invasive cancer (2015-2024). The association between treatment exposure and recurrence was estimated using time-dependent Cox proportional hazards models to prevent immortal time bias. Sensitivity analyses adjusted for age, comorbidities, and treatment history. The impact of treatment timing was assessed using varying thresholds (36, 48, 60, 72 months).

RESULTS: A total of 128 patients with inflammatory arthritis and invasive cancer were included (43 SpA, 35 PsA, 50 RA), with a median follow-up of 58.1 months. Twenty-four patients (18.7%) experienced cancer recurrence or progression. In time-dependent Cox proportional hazards models, post-cancer exposure to bDMARDs or JAK inhibitors was initially associated with a higher risk of recurrence (HR 2.79, 95% CI 1.33-5.84); however, this association was attenuated and no longer statistically significant after adjustment for age at cancer diagnosis and comorbidity burden. No significant association was observed between the timing of treatment initiation after cancer diagnosis and recurrence risk when different cut-offs (36, 48, 60, and 72 months) were tested.

CONCLUSIONS: The risk of cancer recurrence associated with post-cancer immunosuppression appears largely driven by patients’ age and comorbidities rather than the therapy itself. We found no evidence that initiating treatment within the standard 5-year safety window increases recurrence risk, supporting tailored, multidisciplinary management over rigid time thresholds.

PMID:42446710 | DOI:10.55563/clinexprheumatol/msvat0