Citations

Background Subjective cognitive decline (SCD) is a preclinical condition associated with an increased risk of dementia and Alzheimer’s disease, with no consensus regarding effective therapeutic interventions to date. As the global burden of aging-related neurodegenerative diseases continues to rise, early intervention has become increasingly critical. Cognitive training has been proposed as a promising behavioral intervention; however, few studies have integrated multimodal assessments to elucidate its underlying neurobiological and psychological mechanisms, particularly within the educational system that shapes cognitive reserve and learning strategies across the lifespan. This pilot study aims to estimate effect sizes for future definitive trials, assess the feasibility and acceptability of the intervention and multimodal evaluations, and generate hypotheses regarding the relationship between recitation practice and clinical biomarkers. Methods A total of 60 individuals with subjective cognitive decline will be enrolled in a randomized, assessor-blinded, controlled pilot study. Participants will be randomly assigned to either an intervention group or a non-active control group prior to baseline assessment. The intervention group will undergo a six-month structured recitation training program. Both groups will undergo short-term follow-up after the intervention, and long-term follow-up annually post-intervention. Multimodal assessments will include neuropsychological testing, functional magnetic resonance imaging (fMRI), electroencephalography (EEG), blood biomarker profiling, gut microbiota analysis, and fecal metabolomics. Discussion This study protocol outlines a randomized, assessor-blinded, controlled pilot study designed to advance understanding of the feasibility of Chinese Classics recitation training on both physiological and psychological outcomes in individuals with subjective cognitive decline. The findings are expected to provide mechanistic insights into non-pharmacological interventions and to address the current underrepresentation of Asian populations in neuroscience research. Clinical trial registration We registered this randomized controlled trial on ClinicalTrials.gov on March 11, 2026, under the identifier NCT07463391.

ABSTRACT Background Olfactory neuroblastoma (ONB) exhibits variable recurrence patterns, with significant late recurrences occurring years after treatment. We investigated cutoff periods to define late recurrence and identified predictors that distinguish patients at risk of late recurrence from those considered cured. Methods From a multi‐institutional cohort of 219 ONB patients treated at nine centers, we analyzed 77 patients with documented recurrence. Using a 48‐month cutoff to define early (< 48 months) versus late (≥ 48 months) recurrence, we evaluated 35 clinical, anatomic, and treatment variables using Firth penalized logistic regression across three comparisons: (1) late versus early recurrence timing, (2) late recurrence versus no recurrence, and (3) early recurrence versus no recurrence. Results Thirty‐four of the 77 (44.2%) recurrences were classified as late. Among the 77 patients who recurred, smaller tumor volume (OR 0.243, p = 0.035) and lower novel Dulguerov staging (OR 0.802, p = 0.038) were associated with late, rather than early recurrence. When patients with late recurrence were compared to those who remained disease‐free, radiographic skull base bone involvement was the strongest independent predictor (OR 2.90, 95% CI 1.14–8.64, p = 0.025), and this effect strengthened after adjusting for tumor volume (OR 3.80, p = 0.029). Pathologic dural invasion (OR 3.29, p = 0.013), Kadish stage (OR 2.02, p = 0.026), and T‐stage (OR 1.32, p = 0.040) were also significant. Conclusions A 48‐month cutoff effectively stratifies ONB recurrence risk. Skull base bone involvement independently predicts recurrence when compared to nonrecurrent cases and uniquely persists as a risk factor for late recurrence. These findings establish skull base bone involvement as a novel biomarker for risk‐stratified surveillance protocols.

Background/Objectives: To develop and evaluate a deep learning-based quality control system for Lumbar Spinal Digital Radiographs (LSDR), designed to automate and improve their evaluation and reduce reliance on manual reviews. Methods: This retrospective study utilized a deep learning workflow comprising image segmentation, feature extraction, and a classification model. The dataset, including anteroposterior (AP) and lateral (LAT) X-ray images, was expanded through data augmentation techniques. Four U-Net-based models were assessed: standard U-Net, Swin-UNet, Attention U-Net, and Attention U-Net with the weight map, with the latter selected for its superior performance. Extracted features, such as brightness, contrast, and anatomical positioning, were used in an XGBoost classifier, which was evaluated using mean intersection over union (mIoU), accuracy, sensitivity, specificity, and AUC. Results: The Attention U-Net with weighted attention outperformed the other models, achieving high mIoU scores in both AP and LAT views. The XGBoost classifier achieved the best performance in classifying images as “qualified” or “unqualified,” with an AUC of approximately 0.9, high accuracy, and balanced sensitivity and specificity. This approach effectively addressed class imbalances and improved model accuracy compared to traditional machine learning models such as MLP and SVM. Conclusions: The developed automated quality control system demonstrated potential for enhancing image quality, enhancing diagnostic reliability, and optimizing clinical workflow efficiency.

Abstract Background An accurate discrete spot scanning (DSS) beam delivery time (BDT) model is essential, particularly as 4D dynamic dose accumulation calculations rely on machine‐specific time models for reliable interplay evaluation. Purpose To derive a BDT model for a synchrotron‐based Hitachi Probeat PBS proton system from oscilloscope measurements of key BDT structures, including multi‐energy extraction (MEE) characteristics. Methods Key BDT structures were characterized using oscilloscope measurements, supplemented by delivery log files where appropriate. Spot‐to‐spot scanning trajectories were visualized using a CROSSmini 2D strip ionization chamber (Liverage Biomedical Inc, Taiwan) via the dose‐driven continuous scanning (DDCS) mode. The MEE design and MEE charge recapture efficiencies were also characterized. In addition, the impact of the number of delivered spots on both the extractable fraction of charge and MEE recapture efficiency was investigated. Results An improved synchrotron‐based BDT model was derived that incorporates dead times between radiofrequency knockout (RFK) and high‐speed steering magnet (HSST) signals. Spot‐to‐spot movement follows a “hockey‐stick”‐like behavior where the effective spot‐to‐spot move time is governed by the slower axis. An energy‐dependent variation in the number of MEE layers deliverable per spill was also observed, with fewer MEE layers per spill (1–3) was observed in low and high energy ranges compared to the mid‐energy range (4–5), deviating from the nominal vendor value of five MEE layers per spill per block. A reduction in the extractable fraction of charge was observed with an increasing number of spots per spill, while increasing the number of delivered spots in the preceding layer significantly reduced the MEE recapture efficiency. Conclusion MEE characteristics should be incorporated into synchrotron‐based time models for accurate beam delivery modeling. The methodology presented here also provides a framework for centers seeking to derive machine‐specific delivery time models for their proton systems.

Abstract Background: Diffuse pleural mesothelioma (DPM) is a highly aggressive malignancy with limited treatment options and poor prognosis. Although immune checkpoint inhibitors have improved outcomes, particularly for non-epithelioid subtypes, there remains no approved targeted therapy for mesothelioma. EGFR and MET are receptor tyrosine kinases frequently overexpressed in DPM, suggesting susceptibility to targeted antibody therapy. Amivantamab is a bispecific EGFR/MET antibody, originally developed for EGFR-mutant lung cancer, that blocks growth signals and engaging immune mechanisms. Given the high levels of EGFR and MET expression in mesothelioma, we evaluated the therapeutic potential of amivantamab in preclinical models. Methods: EGFR and MET transcript levels in DPM were analyzed using TCGA. Eight human mesothelioma cell lines were assessed by Western blotting and flow cytometry. Amivantamab binding, internalization, and signaling inhibition were examined using flow cytometry, confocal microscopy, and ligand-stimulated phosphorylation assays. Cytotoxicity and immune-effector activity were quantified using PBMCs, NK cells, and monocytes from healthy donors, along with an ADCC reporter assay. In vivo efficacy was tested in a DPM patient-derived xenograft (PDX) model in NOD/SCID-γ (NSG) mice supplemented with human NK cells and treated with amivantamab or control IgG. Results: TCGA analysis showed frequent EGFR/MET co-expression in DPM. Mesothelioma cell lines expressed higher EGFR and MET levels compared with mesothelial cells. Amivantamab strongly bound both receptors, induced receptor internalization, and inhibited EGF- and HGF-stimulated phosphorylation of EGFR, MET, and downstream AKT/ERK signaling. Direct cytotoxicity was minimal; however, the addition of PBMCs or NK cells resulted in robust, dose-dependent tumor cell killing consistent with antibody-dependent cellular cytotoxicity (ADCC). Reporter assays demonstrated 7-11-fold Fcγ receptor activation in tumor cells compared with ∼2-fold activation in non-malignant mesothelial cells. Co-culture with monocytes revealed amivantamab-induced trogocytosis, evidenced by loss of EGFR and MET from tumor-cell membranes. In the DPM PDX model, amivantamab produced 89.1% tumor-growth inhibition (TGI) relative to controls (P &lt; 0.0001), with no overt toxicity observed in treated mice. Conclusions: Dual EGFR/MET targeting with amivantamab produced potent antitumor effects in mesothelioma through coordinated receptor-signaling blockade, ADCC, and monocyte-mediated trogocytosis. These results support amivantamab as a promising targeted therapeutic strategy for EGFR/MET-positive DPM, particularly epithelioid subtypes that currently derive limited benefit from immunotherapy. Citation Format: Shinichiro Suzuki, Kaushal Parikh, Ezequiel Tolosa, Kuan-Li Wu, Jennifer Ayers-Ringler, Lin Yang, Katherine E. Smith, Farhad Kosari, Aaron S. Mansfield, . Enhancing antibody-dependent cellular cytotoxicityin mesothelioma through concurrent EGFR and MET targeting withamivantamab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5547.

Background: Sinonasal malignancies (SNM) are rare cancers associated with poor prognosis and impaired quality of life (QOL). The 22-question Sino-Nasal Outcome Test (SNOT-22) has been used to assess QOL in patients with SNM. Objective: To determine the minimal clinically important difference (MCID) for the SNOT-22 in patients with SNM. Methods: About 264 patients with SNM were drawn from a prospective, longitudinal, multi-institutional study. SNOT-22 scores were collected at pre-treatment baseline and follow-up through 5 years post-treatment. Cronbach’s alpha was used to assess the internal consistency of the SNOT-22. Distribution-based approaches were used to estimate the MCID. Multivariable regression identified factors associated with SNOT-22 improvement exceeding the determined MCID. Results: Cronbach’s alpha was >.85. The estimated MCIDs were: 1.44 (Cohen’s effect size), 1.32 (standard error of the mean), 10.45 (1/2 of baseline standard deviation), and 3.67 (minimum detectable change). The mean MCID across methods was 4.22. Multivariable regression demonstrated higher odds of clinically meaningful improvement from baseline in patients with early-stage disease (odds ratio (OR) 3.510, P = .035), no neck irradiation (OR 11.050, P = .014), and neoadjuvant therapy (OR 16.667, P = .047). Conclusions: The SNOT-22 MCID was estimated as 4.22 in a large multi-center cohort of patients with SNM, suggesting that relatively small QOL changes are clinically relevant. When applying the MCID to the current cohort, advanced stage, treatment of neck disease, and not requiring neoadjuvant therapy were predictive of worse QOL.

Abstract This review aims to update recent advancements in the management and treatment of olfactory neuroblastoma (ONB) based on discussions and topics highlighted during the 2024 North American Skull Base Society session “Literature Review: What's New in Olfactory Neuroblastoma?” A systematic review was conducted using PubMed/MEDLINE, focusing on relevant studies published between January 2022 and June 2024. Data were organized into themes: prognostication and staging, surgical concepts, biomarkers/genomics, imaging, syndrome of inappropriate antidiuretic hormone release and hyponatremia, chemotherapy, and radiotherapy. Out of 289 initial records, 46 studies met eligibility criteria. Key findings include the proposed integration of Hyams grading and dural infiltration with traditional staging for better prognostic accuracy, a shift toward less invasive surgical techniques while maintaining clear resection margins, and the identification of biomarkers for improved diagnosis and targeted therapy. Advanced imaging modalities like DOTA-peptide tomography (positron emission tomography–computed tomography/magnetic resonance imaging) were highlighted for their diagnostic value. Variability in induction chemotherapy outcomes underscores the need for personalized treatment plans, and new radiotherapy techniques offer promising results with improving morbidity. Recent advancements in ONB management have enhanced prognostic accuracy, molecular diagnostics, imaging techniques, and treatment outcomes. Continuous research is necessary to optimize these strategies and further improve patient survival and quality of life.

ABSTRACT Objectives While maxillary sinus fungal balls (MSFB) can be associated with odontogenic conditions (MSFBO), MSFBO clinical and dental features have not been compared to odontogenic sinusitis (ODS). This multicenter study aimed to compare characteristics of MSFB, MSFBO, and ODS. Methods A multicenter international retrospective cohort study was conducted on adults with MSFBs and ODS who underwent sinus surgery. First in MSFBs, it was determined whether different dental conditions were more likely in FB versus non‐FB sides. Second, clinical features and dental pathologies were compared between MSFBO and ODS. For analyses, dental conditions were considered individually and as two groups: infectious pathologies and dental/oral procedures with indwelling metallic materials. Results After exclusions, there were 203 MSFBs and 163 ODS. Among MSFBs, 141 were MSFBOs. FB sides were associated with sinus protrusion of root canal treatment (RCT) materials ( p = 0.040) and dental implants ( p = 0.040). Compared to MSFBO, ODS patients were younger, more likely to have MS purulence (OR = 40.9, p < 0.010), more likely associated with apical periodontitis (OR = 2.59, p = 0.010) and oroantral fistulas (OR = 6.94, p = 0.020), and less likely associated with extruded RCT materials (OR = 0.01, p = 0.010) and protruded midface screws (OR < 0.01, p = 0.010). Comparing purulent MSFBO and ODS, ODS was more associated with infectious dental pathologies ( p < 0.009). Conclusion Compared to MSFBs, MSFBOs were associated with RCT extrusion and implant protrusion. Compared to MSFBOs, ODS was more likely purulent and associated with infectious dental pathologies. While ODS is often distinct from MSFBO, the two conditions can coexist, and surgeons must determine whether patients have infectious dental pathology requiring treatment with both conditions. Level of Evidence 4.

Importance With the availability of multiple classes of advanced therapies for the treatment of Crohn disease (CD), understanding the comparative safety of different therapies can inform treatment positioning. Objective To compare the risk of serious infections, venous thromboembolism (VTE), and major adverse cardiovascular events (MACE) with different advanced therapies in patients with CD. Design, Setting, and Participants This retrospective comparative effectiveness research study was conducted between January 1, 2016, and December 31, 2022, with a mean (SD) follow-up of 26.9 (2.4) months until July 1, 2024. Using an administrative claims database (OptumLabs Data Warehouse), commercially insured patients with CD, who initiated treatment with tumor necrosis factor-α (TNF) antagonists, anti-integrin agents (vedolizumab), interleukin (IL)-12/23p40 antagonists (ustekinumab), IL-23p19 antagonists (primarily risankizumab), or Janus kinase inhibitors (upadacitinib) between 2016 and 2022 and had follow-up for at least 1 year before and after treatment initiation, were included. Exposure TNF antagonists vs anti-integrin agents (vedolizumab) vs IL-12/23p40 antagonists (ustekinumab) vs IL-23p19 antagonists (risankizumab) vs Janus kinase inhibitors (upadacitinib). Main Outcomes and Measures The risk of serious infections, VTE, and MACE was compared with various advanced therapies through multinomial propensity score-based inverse probability treatment weighting, with propensity scores estimated through generalized boosted models, accounting for disease characteristics, health care utilization, comorbidities, and prior and concomitant medications, and through competing risk of mortality. Cause-specific hazard ratios (HRs) and 95% CIs for multiple treatment comparisons were calculated. Results This study included 12 245 patients with CD (mean [SD] age, 46.5 [17.5] years; 6642 females [54.2%]), who were treated with TNF antagonists (n = 5274), vedolizumab (n = 2716), ustekinumab (n = 3544), risankizumab (n = 559), or upadacitinib (n = 152). Serious infection incidence rates ranged from 5.46 (95% CI, 4.86-6.07) to 9.02 (95% CI, 6.38-11.89) per 100 person-years across therapies. After adjusting for confounding variables, there were no statistically significant differences in the risk of serious infections across different agents, including between risankizumab and ustekinumab (HR, 1.14 [95% CI, 0.78-1.67]), risankizumab and TNF antagonists (HR, 1.00 [95% CI, 0.68-1.47]), or ustekinumab and TNF antagonists (HR, 0.88 [95% CI, 0.74-1.04]). The incidence of VTE (incidence rate, 0.90 [95% CI, 0.71-1.10] to 2.33 [95% CI, 1.06-3.82] per 100 person-years) and MACE (0.68 [95% CI, 0.51-0.85] to 1.49 [95% CI, 0.43-2.76] per 100 person-years) was low, without any significant differences across agents. Conclusions and Relevance In this comparative effectiveness research study of patients with CD, no significant differences in the risks of serious infections, VTE, or MACE across various advanced therapies were found. These findings support clinical decision-making on choice of advanced therapies for most individual patients with CD to be driven primarily by comparative treatment effectiveness rather than driven by concerns of serious adverse events.