Citations

Background: It is crucial to evaluate liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). Digital pathology, an automated method for quantitative fibrosis measurement, provides valuable support to pathologists by providing refined continuous metrics and addressing inter-observer variability. Although non-invasive tests (NITs) have been validated as consistent with manual pathology, the relationship between digital pathology and NITs remains unexplored. Methods: This study included 99 biopsy-proven MASLD patients. Quantitative-fibrosis (Q-Fibrosis) used second-harmonic generation/two-photon excitation fluorescence microscopy (SHG/TPEF) to quantify fibrosis parameters (q-FPs). Correlations between eight NITs and q-FPs were analyzed. Results: Using manual pathology as standard, Q-Fibrosis exhibited excellent diagnostic performance in fibrosis stages assessment with area under the receiver operating characteristic curves (AUCs) ranging from 0.924 to 0.967. In addition, magnetic resonance elastography (MRE) achieved the highest diagnostic accuracy (AUC: 0.781–0.977) among the eight NITs. Furthermore, MRE-assessed liver stiffness measurement (MRE-LSM) showed the strongest correlation with q-FPs, particularly adjusted by string length, string width, and the number of short and thick strings within the portal region. Conclusions: Both MRE and digital pathology demonstrated excellent diagnostic accuracy. MRE-LSM was primarily determined by collagen extent, location and pattern, which provide a new perspective for understanding the relationship between the change in MRE and histological fibrosis reverse.

Abstract Background Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity. Methods Pooled observational (cases: n = 5386; controls: n = 6798; studies n = 5) and genome-wide association data (cases: n = 8178; controls: n = 10 472; studies n = 5) were used. We used multivariable logistic regression models and Mendelian randomization to assess the association between physical activity and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability status, CpG island methylator phenotype status, and BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests. Results In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (Obs-per 1SD, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.90 to 0.97), with an association that was stronger in males (Obs-per 1SD, OR = 0.91, 95% CI = 0.87 to 0.96) than in females (Obs-per 1SD, OR = 0.97, 95% CI = 0.91 to 1.03; Pinteraction = .04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or Mendelian randomization analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC. Conclusions Our findings suggest that physical activity is not differentially associated with the 4 major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.

Abstract With the rapid advancements in large language model technology and the emergence of bioinformatics‐specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide‐ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and limitations inherent in BioLMs, including data privacy and security concerns, interpretability issues, biases in training data and model outputs, and domain adaptation complexities. Finally, we highlight emerging trends and future directions, offering valuable insights to guide researchers and clinicians toward advancing BioLMs for increasingly sophisticated biological and clinical applications.

Background: An extended trochanteric osteotomy (ETO) is commonly used to improve exposure and facilitate femoral component removal in revision total hip arthroplasty (THA). An additional medial corticotomy may be used in conjunction with an ETO to correct a femoral deformity, particularly varus remodeling in association with a failed femoral component. This study evaluated the outcomes of combining an ETO with a medial corticotomy in revision THA, with emphasis on implant fixation, femoral alignment, bone union, and clinical outcomes. Methods: Of the 612 ETOs performed between 2003 and 2013, 13 patients (9 men and 4 women) underwent ETO combined with a medial corticotomy to correct varus remodeling, representing 2% of all ETOs during that period. The average follow-up was 8 ± 3.5 years. The mean age at surgery was 67 ± 13.5 years. The mean body mass index was 32 ± 7.7 kg/m 2 . Radiographs were reviewed to measure preoperative and postoperative femoral deformity, time to consolidation, and femoral fixation. Clinical outcomes were evaluated using the Harris Hip Score (HHS). Results: All patients had preoperative varus femoral deformity (mean 16.3° ± 5.7°). The mean postoperative alignment was 4.3 ± 1.6° varus achieving an average correction of 12° (95% CI −15.7 to −8.3, p < 0.0001). Both the ETO and the medial corticotomy consolidated in 10 of 11 patients (91%) with available 1-year radiographs at a mean of 11 ± 7.7 months. The mean HHS improved significantly from 42 preoperatively to 82 at 5-year follow-up (p = 0.0002). Complications related to the ETO and corticotomy occurred in 4 patients (30%), including 1 intraoperative fracture, 1 postoperative greater trochanteric fracture, 1 nonunion of the medial corticotomy, and 1 postoperative wound-hematoma. All femoral components remained well fixed at final follow-up. Conclusion: The combination of ETO and medial corticotomy in revision THA effectively corrected femoral alignment in patients with a preoperative varus deformity and was associated with significant functional improvement at the final follow-up. Level of Evidence: Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Background: Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. Methods: We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. Results: Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from “low” to “high” in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. Conclusions: In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.

Précis: Glaucoma patients with significant visual field defects show poorer driving performance, higher collision risks, and a greater likelihood of driving cessation. They face difficulties with lane maintenance, slower hazard responses, and self-regulation while driving. Purpose: Glaucoma is a chronic, progressive optic neuropathy associated with visual field (VF) defects, which in advanced disease has been shown to affect patients’ activities of daily living. This systematic review qualitatively analyzes existing literature that explores the impact of glaucomatous VF loss on the driving performance of glaucoma patients, the extent of driving limitation and cessation, as well as the risk of motor vehicle collisions (MVCs). Methods: A literature search of MEDLINE and Embase (via Ovid), PubMed, Cochrane Library, and Web of Science databases was performed for studies published from 2003 to 2023, with the terms “glaucoma,” “visual field defect/disorder,” and “driving,” followed by selective vetting based on inclusion criteria. Within studies, data pertaining to study design, subject demographics, VF defect characteristics, driving performance and related outcomes were extracted. Results: Initial search yielded 835 studies, with 20 studies selected. Three more studies were included through hand-searching, with a total of 23 studies included for final review. Moderate to severe VF defects resulted in poorer driving performance, with slower response times to road hazards, decreased ability for lane maintenance, and increased difficulty driving at night. Patients with more severe VF defects and with bilateral glaucoma were more likely to limit or cease driving compared with those with milder and unilateral glaucoma. A greater severity of VF loss was associated with a higher risk of MVCs. Conclusion: More severe glaucomatous VF and bilateral glaucoma is associated with worse driving performances and a higher risk of MVCs, in both simulator and real-world settings.

Background: Gluteus medius tears and atrophy cause lateral hip pain, limp, and functional impairment. We developed the “broken wing sign,” a novel physical examination test for detecting gluteus medius tendon tears and muscle degeneration. This study evaluated its diagnostic accuracy and clinical utility against magnetic resonance imaging (MRI) and intraoperative findings. Methods: We prospectively examined 59 patients (75 hips; mean age, 69.5 ± 10.8 years; 48 women) with suspected hip abductor insufficiency. The broken wing sign was tested with patients prone, the knee flexed at 90°, and the hip actively extended. A positive sign involved ≥10° of compensatory external hip rotation, visible as an inward drift of the foot, indicating gluteus medius (and resulting internal rotation) weakness. MRI served as the reference standard for classifying gluteus medius integrity as no tear, partial, full-thickness, or massive. Fatty infiltration was graded (Goutallier grades 0 to 4), quantified, and analyzed for a correlation with the examination findings. Diagnostic accuracy metrics were calculated. Results: The broken wing sign demonstrated high accuracy (sensitivity, 81.8%; specificity, 80.0%; positive predictive value [PPV], 91.8%; negative predictive value, 61.5%; diagnostic odds ratio, 17.8). An external rotation threshold of ≥30° yielded 100% specificity and 100% PPV for a tear. The sign detected acute tears with no or minimal fatty infiltration (100% sensitivity for massive tears). The degree of the external rotation angle was strongly correlated with muscle atrophy with fatty infiltration, showing 88.0% sensitivity for Goutallier grade ≥3 and 100% sensitivity for grade 4. Conclusions: The broken wing sign is clinically useful for diagnosing gluteus medius tendon tears and muscle atrophy, particularly massive tears and advanced fatty degeneration. It effectively guides MRI utilization and surgical planning, serving as a valuable initial diagnostic tool in the clinical setting. Level of Evidence: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.