Citations

Abstract Introduction Significant clinical variations exist in the definitions of acute/active vs chronic/stable Peyronie’s Disease (PD). While the American Urological Association’s 2015 guidelines define the acute phase as involving symptoms that change and the presence of pain, they do not specify a timeframe. Historically, acute-phase features include penile pain and worsening curvature, with symptom duration ranging from less than 3 to 18 months. Although temporally categorizing PD may have academic value, it may unnecessarily limit or delay treatment. In the United States, collagenase clostridium histolyticum (CCH) is the only FDA-approved treatment for adult men with PD who have a palpable plaque and a curvature deformity of at least 30 degrees. Several real-world studies suggest CCH is safe and effective during the acute phase. Objective To evaluate differences in outcomes by penile pain and symptom duration and to determine whether these factors should inform timing of CCH treatment in men with Peyronie’s disease. Methods A post hoc analysis of pooled data from 2 phase 3 randomized double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623). Men treated with CCH were stratified by baseline penile pain (Any Pain vs No Pain), based on both investigator-assessed and patient-reported measures. A subgroup analysis further stratified men with Any Pain by disease duration. The primary efficacy endpoint in the phase 3 study was the percentage change in penile curvature from baseline to week 52. A 2-sample t test was used to compare group means for each pain-related measure. Results A total of 364 CCH-treated men were included. Mean penile curvature improvements at week 52 were similar across all 4 investigator-assessed and patient-reported penile pain measures (35.0%-36.7% improvement for the No Pain group vs 32.2%-33.9% improvement for the Any Pain group, P=0.14-0.65). Among those experiencing Any Pain, no statistical differences were observed in men with disease durations that were shorter (12-18 months; 21.8%-34.8% improvement) vs longer (greater than 18 months; 31.4%-36.8% improvement, P=0.20-0.95). Conclusions This study found similar curvature improvements among men treated with CCH regardless of baseline pain or disease duration. Results align with prior studies showing no outcome differences by pain status or disease phase. These findings suggest that pain and disease duration should not be viewed as contraindications to CCH or used to guide clinical decision-making. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

ABSTRACT Purpose Abnormal restrictions at myofascial interfaces are a key factor in chronic low back pain (CLBP) with myofascial pain syndrome (MPS), but no established imaging method exists for quantitative assessment. This pilot study evaluated the clinical feasibility of MR elastography (MRE)‐based slip interface imaging (SII) for visualizing myofascial mobility in CLBP‐MPS patients versus age−/sex‐/BMI‐matched healthy participants. A new SII biomarker, maximal normalized displacement discontinuity (), was introduced, and the previously developed normalized octahedral shear strain (NOSS) map was used for comparison. Preliminary assessments of vibration‐frequency effects, repeatability, and group differences in inter‐muscular mobility were conducted. Methods MRE was conducted at 30, 60, and 90 Hz to compare with NOSS for visualizing inter‐muscular slip interfaces at the quadratus lumborum‐erector spinae (QL‐ES) and erector spinae‐multifidus (ES‐M) muscle boundaries at L3‐L4. Repeatability of and NOSS was assessed at 30 Hz (identified as the best‐performing frequency) using within‐subject coefficients of variation and a linear mixed‐effects model from within‐ and between‐day scans. Clinical feasibility was then assessed via Wilcoxon rank‐sum tests in six CLBP‐MPS patients and matched controls. Results at 30 Hz exhibited superior delineation of slip interfaces compared to higher frequencies and NOSS. demonstrated significantly lower variation and better repeatability than NOSS. Healthy participants showed continuous, well‐defined slip interfaces, whereas CLBP‐MPS patients displayed disrupted interfaces with significant mobility reduction at L4 ES‐M. Conclusion SII with lower vibration frequency and map enhances visualization of lower back myofascial mobility and shows potential for assessing differences between healthy individuals and CLBP‐MPS patients.

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.

Abstract Taxanes are frontline chemotherapeutics that stabilize microtubules, induce mitotic arrest, and drive tumor remission. However, their off-target effects in healthy tissues, most notably cutaneous axon degeneration underlying chemotherapy-induced peripheral neuropathy (CIPN), remain poorly understood. Here, we show that paclitaxel induces microtubule fasciculation in epidermal keratinocytes through the mitotic kinesin Eg5, thereby initiating CIPN. Mechanistically, paclitaxel enhances Eg5-dependent fasciculation of detyrosinated (stabilized) microtubules, which constrict and breach the nuclear lamina. This deformation triggers tension-dependent NADPH oxidase-mediated nuclear ROS (X-ROS) formation upstream of mmp13 transcription, a pathway we previously demonstrated drives sensory axon degeneration. Employing a cross-species framework spanning zebrafish, mice, human skin biopsies, and a breast adenocarcinoma cell line, we uncover a conserved paclitaxel–Eg5 mechanism leading to fasciculation of stable microtubules in both healthy epidermis and cancer cells. These findings highlight the dualistic nature of paclitaxel action and underscore the challenge of preserving anticancer efficacy while preventing neurotoxic side effects.

Abstract Aging increases the vulnerability of kidneys to injury and impairs their regenerative capacity. SIRT3 expression declines with aging and is associated with multiple age‐related pathologies. The expression profile and functional role of SIRT3 in renal aging remain unclear. Here, SIRT3 expression in aging kidneys is assessed and analyzed for its promoter methylation patterns using methylation‐specific PCR (MSP). It is found that aging exacerbates UUO‐induced renal fibrosis, associated with downregulated SIRT3 expression. Mechanistically, age‐related SIRT3 downregulation is mediated by hypermethylation of its promoter region. SIRT3 knockout exacerbated renal fibrosis in young mice subjected to UUO, whereas SIRT3 overexpression attenuated fibrosis in aged UUO mice. Integration of RNA‐seq and immunoprecipitation‐mass spectrometry (IP‐MS) analyses revealed that SIRT3 deficiency leads to hyperacetylation of GSK3β at lysine 15 (K15). This K15 hyperacetylation inhibited GSK3β activity, consequently stabilizing its substrate β‐catenin. Furthermore, self‐assembled PEG‐PCL‐PEG micelles are designed and synthesized to encapsulate hydrophobic honokiol (HKL). These micelles significantly enhanced the aqueous solubility and oral bioavailability of free HKL, maintained stable blood concentrations, and ultimately improved its anti‐fibrotic efficacy. These findings propose novel therapeutic strategies for managing renal fibrosis in the aging population and provide a foundation for developing new drugs and combination therapies.

Abstract Background The radiation oncology clinical practice involves many steps relying on the dynamic interplay of abundant text data. Large language models have displayed remarkable capabilities in processing complex text information. But their direct applications in specific fields like radiation oncology remain underexplored. Purpose This study aims to investigate whether fine‐tuning LLMs with domain knowledge can improve the performance on Task (1) treatment regimen generation, Task (2) treatment modality selection (photon, proton, electron, or brachytherapy), and Task (3) ICD‐10 code prediction in radiation oncology. Methods Data for 15 724 patient cases were extracted. Cases where patients had a single diagnostic record, and a clearly identifiable primary treatment plan were selected for preprocessing and manual annotation to have 7903 cases of the patient diagnosis, treatment plan, treatment modality, and ICD‐10 code. Each case was used to construct a pair consisting of patient diagnostics details and an answer (treatment regimen, treatment modality, or ICD‐10 code, respectively) for the supervised fine‐tuning of these three tasks. Open source LLaMA2‐7B and Mistral‐7B models were utilized for the fine‐tuning with the Low‐Rank Approximations method. Accuracy and ROUGE‐1 score were reported for the fine‐tuned models and original models. Clinical evaluation was performed on Task (1) by radiation oncologists, while precision, recall, and F‐1 score were evaluated for Task (2) and (3). One‐sided Wilcoxon signed‐rank tests were used to statistically analyze the results. Results Fine‐tuned LLMs outperformed original LLMs across all tasks with p value ≤ 0.001. Clinical evaluation demonstrated that over 60% of the fine‐tuned LLMs‐generated treatment regimens were clinically acceptable. Precision, recall, and F1‐score showed improved performance of fine‐tuned LLMs. Conclusion Fine‐tuned LLMs demonstrated statistically significant improvements over original LLMs upon three clinically important tasks in radiation oncology. This study explored the feasibility of applying fine‐tuned LLMs in radiation oncology, inspiring further development of utilizing LLMs to assist with radiation oncology tasks.