Tag: statistics

Drugs. 2026 Jul 29. doi: 10.1007/s40265-026-02355-5. Online ahead of print.

ABSTRACT

Inhibition of androgen receptor (AR) signaling remains the cornerstone of systemic therapy for advanced prostate cancer (PC). However, a subset of aggressive tumors either arises de novo with neuroendocrine features or emerges under treatment pressure through lineage plasticity and AR independence. These lethal states are encompassed within the spectrum of aggressive-variant prostate cancer (AVPC), an umbrella term that includes both histologically confirmed neuroendocrine prostate cancer (NEPC)-comprising de novo NEPC and treatment-emergent NEPC (t-NEPC)-and clinically or molecularly defined AVPC lacking histologic confirmation but sharing neuroendocrine-like, AR-indifferent, or small-cell features. These phenotypes are characterized by rapid progression, visceral dissemination, low or discordant prostate-specific antigen (PSA) levels relative to tumor burden, and poor prognosis. Treatment options for NEPC/AVPC remain limited and largely rely on platinum-based chemotherapy, which usually provides only modest and transient benefit. This unmet need has intensified interest in lineage-associated vulnerabilities. Delta-like ligand 3 (DLL3), an inhibitory Notch ligand with restricted expression in normal adult tissues, is aberrantly upregulated in several neuroendocrine malignancies and has emerged as a clinically actionable target. In prostate cancer, DLL3 expression is enriched in neuroendocrine tumor cells, being detected in approximately 76.6% of castration-resistant NEPC compared with only 12.5% of castration-resistant adenocarcinoma, supporting its development as both a biomarker and therapeutic vulnerability. Clinical success of DLL3-targeted therapies in small-cell lung cancer further supports evaluation of DLL3-directed strategies in NEPC and related AVPC states. This review summarizes the biological rationale, translational evidence, and emerging clinical data supporting DLL3-targeted therapies in prostate cancer. Investigational platforms include antibody-drug conjugates, bispecific and trispecific T-cell engagers, and DLL3-directed radiopharmaceuticals. Early clinical studies suggest that activity is largely confined to DLL3-expressing neuroendocrine tumors, highlighting the importance of biomarker-guided patient selection. Delta-like ligand 3-directed therapies may reshape the management of DLL3-expressing prostate cancer if ongoing efforts to refine biomarkers improve patient enrichment and optimize trial design are successfully translated into clinical practice.

PMID:42527846 | DOI:10.1007/s40265-026-02355-5

Arthroscopy. 2026 Jul 29. doi: 10.1002/arj.70409. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the abnormal knee hyperextension and coupled external rotation, varus, and anterior translation that occurs using sequential ligament and capsular sectioning in multiligamentous injuries.

METHODS: A six-degree-of-freedom robotic system measured knee hyperextension and coupled external rotation, varus, and anterior-posterior translation with selective tissue cutting in 23 cadaveric knees. Tests were performed up to 25 Nm hyperextension load before and after cutting 6 structures: oblique popliteal ligament (OPL), posterolateral capsule with the fabellofibular ligament (PLC+FFL), posteromedial capsule with posterior oblique ligament (PMC+POL), lateral collateral ligament and popliteus tendon (LCL+POP), and the anterior cruciate ligament (ACL). Sequence 1 sectioned the posterior capsular structures (OPL, PLC+FFL, and PMC+POL) followed by the LCL+POP and ACL. Sequence 2 simulated a posterolateral injury (LCL+POP) and ACL injury followed by the posterior capsular injuries (OPL, PLC+FFL, and PMC+POL).

RESULTS: In sequence 1, sectioning the posterior capsule caused statistically significant increases to hyperextension (2.5° ± 0.9°; P = .02). Additional injury of the LCL+POP and ACL significantly increased hyperextension to 7.6°± 4.4° (P < .01), external rotation to 2.7° ± 2.8° (P < .01), and varus rotation to 3.2°± 3.9° (P < .01). In sequence 2, sectioning the LCL+POP significantly increased hyperextension (1.4° ± 0.6°; P < .01) and additional ACL sectioning significantly increased hyperextension (2.1° ± 1.0°; P < .01). Further sectioning the posterior capsule significantly increased hyperextension to 6.9° ± 1.7° (P < .01), external rotation to 2.9° ± 2.3° (P < .01), and varus rotation to 2.5° ± 1.4° (P < .01).

CONCLUSIONS: Posterolateral injuries (LCL+POP and PLC+FFL) resulted in small increases in knee hyperextension, external tibial rotation, and varus rotation. Sectioning the entire posterior capsular structures (PLC+FFL, PMC+POL, and OPL) is necessary for major increases in knee hyperextension.

CLINICAL RELEVANCE: Posterolateral ligament injuries may not result in a positive external rotation recurvatum test as only modest increases in external rotation and varus occur with knee hyperextension. Other ligament tests including the dial test for external tibial rotation and varus loading for lateral joint opening in knee flexion are recommended.

PMID:42527843 | DOI:10.1002/arj.70409

J Gen Intern Med. 2026 Jul 29. doi: 10.1007/s11606-026-10556-7. Online ahead of print.

NO ABSTRACT

PMID:42527841 | DOI:10.1007/s11606-026-10556-7

J Gen Intern Med. 2026 Jul 29. doi: 10.1007/s11606-026-10625-x. Online ahead of print.

ABSTRACT

BACKGROUND: Emergency departments (ED) provide timely care for acute conditions and serve as a vital safety net. Longer ED wait times are associated with worse health outcomes, but differences in ED wait times by patient language remain understudied.

OBJECTIVE: Examine differences in ED wait times between English and non-English language patients and its association with ED crowding.

DESIGN: Retrospective cohort study of ED visits at an academic medical center in 2023 and 2024.

PARTICIPANTS: 73,420 ED visits among adult patients not triaged to the highest acuity categories.

MAIN MEASURES: Wait times from triage to provider assignment by patient primary language were assessed via unadjusted analyses and generalized linear models adjusting for demographic, temporal, and system factors as well as patient comorbidities and chief complaint. Language was then interacted with ED census to assess for effect modification from ED crowding. Secondary outcomes were time from provider assignment to ED disposition and rates of left without being seen (LWBS).

KEY RESULTS: Patients with a primary non-English language waited on average 6.5 min (p < 0.001) or 8.4% longer than English-primary patients for an ED provider-a difference that persisted after statistical adjustment (6.6 min, p < 0.001). Cantonese, Spanish, Russian, and Toishanese language patients experienced statistically longer wait times than English language patients. With ED census, each 10 additional patients in the ED were associated with an adjusted 2.3 min (p = 0.02) longer differential wait time for non-English language patients. Despite these differences, rates of LWBS were significantly lower for non-English language patients in both unadjusted and adjusted analyses (p < 0.001).

CONCLUSIONS: Longer ED wait times for patients with a primary non-English language reflect a health inequity affecting a disadvantaged population. The degree of disparity widened as ED census increased. Health system and policy attention is needed to address ED crowding and other factors that could contribute to this disparity.

PMID:42527840 | DOI:10.1007/s11606-026-10625-x

Pediatr Blood Cancer. 2026 Jul 29:e70438. doi: 10.1002/1545-5017.70438. Online ahead of print.

ABSTRACT

Pediatric low-grade gliomas (pLGG) are the predominant childhood central nervous system tumors. While BRAF alterations are known to drive the majority of pLGGs, a subgroup contains activating mutations or fusions involving FGFR1/2/3. FGFR is a receptor tyrosine kinase that plays a crucial role in cell growth, differentiation, and survival through interactions with fibroblast growth factors. Furthermore, FGFR has been shown to interact with the RAS/MAPK, PI3K/AKT, and JAK/STAT pathways. The current understanding of the biological behavior, clinical trajectory, and effectiveness of targeted inhibition in FGFR-altered gliomas is notably limited. We sought to define the epidemiologic characteristics, molecular features, radiographic and histologic characteristics, and clinical course of patients with FGFR-altered pLGGs. We also explored the therapeutic implications of these abnormalities in pediatric cases and highlight both current and emerging treatment strategies for pediatric patients with FGFR-altered cancers.

PMID:42527824 | DOI:10.1002/1545-5017.70438

Ophthalmic Physiol Opt. 2026 Jul 29. doi: 10.1007/s44402-026-00155-8. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether ocular dominance is associated with systematic interocular asymmetry in spherical equivalent refraction (SER) and axial length (AL) across childhood and early adulthood, and assess whether such asymmetry exceeds laterality effects.

METHODS: Data were analysed from three population-based cohorts: 728 children (6-7-year-olds) and 898 adolescents (12-13-year-olds) from Ireland and 303 young adults (25-30-year-olds) from Western Australia. Ocular dominance was assessed using sighting tests. SER was measured by cycloplegic autorefraction and AL by optical biometry. Interocular differences were evaluated using paired comparisons, concordance correlation coefficients (CCC), Deming regression, Bland-Altman analyses and mediation modelling. Analyses were stratified by refractive status and anisometropia.

RESULTS: Across all age groups, right-left differences in SER and AL were minimal (mean differences <0.05 D and <0.05 mm in children and adolescents), with small, significant laterality effects observed only in young adults (-0.13 D in SER; 0.06 mm in AL). In contrast, dominant-non-dominant comparisons demonstrated consistent directional asymmetry: the dominant eye was less hyperopic/more myopic (-0.09 D at 6-7 years; -0.10 D at 12-13 years; -0.08 D at 25-30 years) and longer (0.03-0.06 mm; all p < 0.05). Deming regression and Bland-Altman analyses confirmed systematic deviation from interocular symmetry, most pronounced in childhood. Mediation analyses indicated that ocular dominance statistically explained over 85% of the observed interocular asymmetry, independent of laterality. Dominance-related asymmetry was most evident in non-myopes (SER -0.09 to -0.36 D; AL 0.03-0.06 mm), attenuated in myopia and amplified in anisometropia (SER up to -1.09 D; AL up to 0.42 mm), particularly in younger cohorts.

CONCLUSION: In this cross-sectional analysis, ocular dominance was associated with small but systematic interocular asymmetry in SER and AL across childhood and early adulthood, which exceeds laterality effects. Dominance-related asymmetry was attenuated in myopia and amplified in anisometropia. Ocular dominance should be considered when analysing interocular refractive and biometric data in research and clinical contexts.

PMID:42527823 | DOI:10.1007/s44402-026-00155-8

J Cancer Educ. 2026 Jul 29. doi: 10.1007/s13187-026-02963-5. Online ahead of print.

ABSTRACT

BACKGROUND: Podcasts are increasingly popular for health education; however, the scope and characteristics of breast cancer podcasts remain poorly defined. This study evaluates the characteristics of breast cancer podcasts, aiming to inform patient education resources.

MATERIALS AND METHODS: Twenty-five podcasts from Apple and Spotify were identified using the term “Breast Cancer” after screening against pre-determined inclusion criteria. Each podcast was transcribed and analyzed using NVivo. Extracted variables included podcast demographics, podcaster characteristics, and podcast content. Descriptive statistics and thematic analysis were performed.

RESULTS: Mean podcast length was 47.2 min (SD 22.2; range 12-106 min) and mean age was 0.6 years (SD 1.25; range 1 day to 4 years). Most podcasts originated from the United States (86%); were affiliated with personal (62%) sources; included patient (64%) and physician presenters (54%); and were targeted toward patients (74%). Interview formats predominated (72%), with a mean of 4.4 topics addressed per podcast (SD 1.2). The most covered topic was disease understanding (88%) and treatment and management (88%) while prevention was covered the least (36%). Common themes included: Living With Uncertainty, Reclaiming Control Through Knowledge, Cancer as Disruption and Trauma, Finding Strength Through Connection, and Redefining Life Beyond Cancer.

CONCLUSION: Breast cancer podcasts are predominantly patient-oriented, interview-based, and produced by personal or nonprofit sources. They emphasize experiential narratives and psychosocial themes alongside clinical information. Findings support podcasts as an adjunct to traditional patient education and underscore the need for academic and healthcare institutions to improve content accuracy and reliability.

PMID:42527821 | DOI:10.1007/s13187-026-02963-5

Spine Deform. 2026 Jul 29. doi: 10.1007/s43390-026-01514-8. Online ahead of print.

ABSTRACT

BACKGROUND: Skeletal intraoperative traction (IOT) has been proposed as an adjunct to posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) to facilitate deformity correction and reduce perioperative morbidity. However, its clinical benefit remains controversial, with conflicting evidence on radiographic outcomes and safety. This systematic review and meta-analysis aimed to determine whether skeletal IOT provides added benefit in patients undergoing one-stage PSF for AIS.

METHODS: A comprehensive search of PubMed, Embase, Scopus, Cochrane Library, and Web of Science was performed from inception to September 2025, following PRISMA guidelines. Eligible studies included patients with AIS undergoing one-stage PSF with skeletal IOT versus PSF without IOT. The primary outcomes were coronal main curve correction rate, operative time, intraoperative blood loss, and incidence of intraoperative motor-evoked potential (MEP) changes. Pooled estimates were calculated using common- and random-effects models. Between-study heterogeneity was assessed using the I² statistic.

RESULTS: Eight studies comprising 693 AIS patients were included, of which six were comparative (426 IOT group vs. 267 non-IOT group). Under the common-effect model, IOT was associated with a significantly higher main curve correction rate (MD + 3.62, 95% CI 1.75-5.48) and lower blood loss (MD – 274.1 mL, 95% CI – 540.5 to – 7.6). Neither finding was confirmed under the random-effects model, which revealed extreme between-study heterogeneity for correction rate (I² = 82.6%) and near-zero heterogeneity for blood loss (I² = 1.5%). Intraoperative MEP changes occurred in 17.3% of IOT patients versus 3.0% of non-IOT controls (RR 3.49, 95% CI 0.83-14.71); all events were transient, and no permanent neurological deficit was recorded in any study.

CONCLUSIONS: Skeletal IOT does not demonstrate a statistically robust benefit over standard one-stage PSF for AIS when between-study heterogeneity is appropriately accounted for. IOT is associated with a higher incidence of transient intraoperative MEP changes, underscoring the mandatory role of continuous neurophysiological monitoring when this technique is employed. Future large and high-quality prospective studies are needed to further confirm the findings of the present analysis.

PMID:42527807 | DOI:10.1007/s43390-026-01514-8

Cancer Treat Res Commun. 2026 Jul 29;48:101329. doi: 10.1016/j.ctarc.2026.101329. Online ahead of print.

ABSTRACT

BACKGROUND: Prostate cancer (PC) is the second most common solid cancer affecting men. LncRNA PCAT19 has a carcinogenic role in multiple solid and hematological cancers. Additionally, miR-195 was significantly downregulated in multiple malignancies. Moreover, ITGA6 promotes pathways that control carcinogenesis. E-cadherin is a glycoprotein involved in epithelial cell adhesion and maintaining tissue integrity. E-cadherin loss is related to epithelial-mesenchymal transition (EMT) and cancer metastasis. This preliminary study investigated the expression of PCAT19, miR-195, ITGA6, and E-cadherin in PC tissues.

SUBJECTS & METHODS: Seventy-two tissue specimens from 36 PC patients were enrolled in this study. The diseased group included 36 primary PC tissues, and the control group included 36 specimens from their non-neoplastic adjacent tissues. Gene expression of LncRNA PCAT19, miR-195, and ITGA6 in tissues was estimated by Reverse transcription- quantitative polymerase chain reaction (RT-qPCR), and E-cadherin expression was detected by immunohistochemistry.

RESULTS: A statistically significant upregulation inPCAT19 (7.92-fold) and ITGA6 (6.67-fold) gene expression and downregulation of miR-195 (4.17-fold) gene expression in tumor tissues compared to adjacent non-neoplastic tissues were recorded. During follow-up, 11 of 36 patients (30.6%) died, and disease progression occurred in 6 of 25 evaluable patients (24.0%). There was a statistically significant decrease in PCAT19 and ITGA6 and an increase in miR-195 among surviving cases compared with dead cases. Receiver operating characteristic (ROC) curve analysis revealed that PCAT19 at a cutoff of > 8.89-fold demonstrated promising discriminatory performance for advanced-stage PC, with an area under the curve (AUC) of 0.84 (95% confidence interval (CI): 0.69-0.99, P < 0.001), 70% sensitivity, 93.7% specificity, 93.3% positive predictive value, 71.4% negative predictive value, and an overall diagnostic accuracy of 80.6%. In comparison, ITGA6 (AUC = 0.73) and miR-195 (AUC = 0.71) exhibited only fair discriminatory ability.

CONCLUSION: Upregulation of PCAT19 and ITGA6, and downregulation of miR-195, in prostate cancer tissues may be associated with disease aggressiveness.

PMID:42526156 | DOI:10.1016/j.ctarc.2026.101329

Bioorg Chem. 2026 Jul 23;181:110258. doi: 10.1016/j.bioorg.2026.110258. Online ahead of print.

ABSTRACT

Circular RNAs (circRNAs) have gained recognition for their critical roles in various biological processes and are increasingly viewed as promising candidates for use in disease diagnosis and treatment strategies for complex human diseases. Despite advances in computational methods for predicting circRNA-disease associations (CDAs), existing models often fail to effectively capture both similarity metrics and higher-order mixed neighborhood information simultaneously in bio-graph networks, leading to suboptimal prediction performance. In this study, we present HSimGCDA, an enhanced graph convolutional network that leverages higher-order similarity measures to improve the prediction of CDAs. Specifically, our approach first constructs multi-similarity graph networks that integrate diverse data features of circRNAs and diseases. We then implement a higher-order similarity strategy that effectively aggregates the higher-order similarity information between nodes and their remote neighbors, thus enriching the topological information of the nodes and revealing potential features brought about by different neighboring nodes. Ultimately, a multilayer perceptron algorithm is utilized to accurately infer likely CDAs. The experimental results indicated that HSimGCDA demonstrated excellent competitiveness on the benchmark CircR2Disease dataset, achieving a prediction accuracy of 95.93% and an AUC score of 98.74%. Additionally, the ablation experiments further validated the effectiveness of the improved HSimGCDA model. Furthermore, case studies on gastric and breast cancers demonstrated that HSimGCDA successfully identified previously unrecognized circRNAs associated with these diseases. Collectively, these findings emphasize the potential of HSimGCDA as a practical tool for exploring CDA, thereby providing valuable insights into disease diagnosis and therapeutic development.

PMID:42526132 | DOI:10.1016/j.bioorg.2026.110258