Citations

Abstract Background Progressive supranuclear palsy (PSP) is a tauopathy for which there is limited understanding of epidemiological risk factors. Objective The objective of this study was to identify premorbid nonmedical and medical risk factors for PSP diagnosis in a large prospective population‐based cohort. Methods We performed a matched nested case–control study using the UK Biobank (UKB) cohort consisting of >500,000 adults aged 37 to 73 years. PSP diagnoses were identified from 2007 to censor date (August 2025) and matched 1:10 by age and sex to control subjects without parkinsonism or dementia diagnoses. We derived risk factors using an iterative logistic regression approach. Results There were 240 incident PSP diagnoses in the UKB. In the fully adjusted model, premorbid depression (odds ratio [OR], 3.22; 95% confidence interval [CI], 2.30–4.50; P < 0.001), delirium (OR, 6.76; 95% CI, 4.08–11.19; P < 0.001), and functional gastrointestinal disorders (OR, 1.91; 95% CI, 1.39–2.63; P < 0.001) were associated with increased risk. Heavy alcohol consumption was associated with higher risk compared with moderate consumption (OR, 1.65; 95% CI: 1.21–2.26; P = 0.0017). Body mass index (BMI) and alcohol consumption had nonlinear risk profiles. Cancer diagnosis was inversely associated with PSP (OR, 0.56; 95% CI, 0.40–0.79; P < 0.001). Depression and delirium diagnoses remained significant 5 to 10 years before diagnosis. Conclusions In this large prospective cohort, PSP was associated with premorbid lifestyle practices and neuropsychiatric diagnoses years before diagnosis. This suggests a long premotor phase and highlights opportunities for earlier diagnosis and further mechanistic investigation. The inverse association with cancer mirrors the relationship seen in other neurodegenerative conditions and may point toward shared mechanisms. © 2026 International Parkinson and Movement Disorder Society.

ABSTRACT Encapsulation of human pluripotent stem cells (hPSC) has high relevance for biomedical applications ranging from tissue engineering to drug screening and cellular therapies. Microcapsules serve a multitude of purposes—from promoting hPSC organization into spheroids to enabling scalable differentiation in vitro and providing immunoisolation in vivo. While multiple encapsulation strategies have been reported, there is typically a tradeoff between the structural complexity of capsules and throughput of their generation. Our paper describes a novel 3D printed microfluidic encapsulation device for fabricating structurally complex microcapsules with a hydrogel shell and aqueous core at rates of up to 1825 Hz. The use of 3D printing allowed to dramatically decrease device footprint when compared to standard soft lithography‐based microfluidic encapsulation devices. Leveraging decreased footprint and the ability to arrange fluidic networks in a 3D space, we fabricated a 10‐nozzle microencapsulation device that generated microcapsules at a rate 10‐times that of the single‐nozzle device. The novel microfluidic device was used to encapsulate hPSCs, human embryonic stem cells (hESCs), and induced pluripotent stem cells (iPSCs). Hydrogel microcapsules with aqueous core promoted hPSCs aggregation into spheroids or embryoid bodies, which maintained high levels of pluripotency. Our technology enables safe and effective encapsulation of hPSCs on a scale (billions of cells) required to treat patients.

Abstract Neuromodulatory subcortical systems (NSSs) are uniquely susceptible to dementia‐related pathology, leading to frequent molecular and behavioral impairments associated with altered function of these nuclei. Some of these systems display clear sex‐specific cytoarchitecture and signaling leading to distinct physiology and behavioral outputs in males and females, while other regions display nominal sex differences. However, the relevance of sex differences in modulating dysfunction of NSSs in Alzheimer's disease (AD) and related dementias is not well understood. This review is a joint effort by the Neuromodulatory Subcortical Systems and Sex and Gender Differences in Alzheimer's Disease Professional Interest Areas of the Alzheimer's Association. We review sex differences in NSSs, both in non‐disease states and in AD models and patients. We highlight the possible role of NSSs in driving sex‐specific AD susceptibility and potential footholds for sex‐based interventions targeting these systems. We conclude by outlining immediate and long‐term actions to address the intersection of NSSs, sex, and AD.

Background: Primary spine/pelvic tumors are aggressive, and en bloc resection is often essential. While stereotactic navigation is increasingly used for instrumentation in spine surgery, its specific role in tumor resection remains incompletely defined. Purpose: We sought to describe (1) reported rates of achieving negative margins, (2) local recurrence, (3) complications attributed to navigation, and (4) comparative outcomes from studies involving nonnavigated controls. Methods: We conducted a systematic review according to preferred reporting items for systematic reviews and meta-analysis guidelines. Databases were queried for studies investigating the use of stereotactic navigation in primary spine/pelvic tumor surgery. Outcomes including surgical margin status, local recurrence, and complications were extracted and qualitatively synthesized using a best-evidence approach. Results: Twenty-one studies with 240 patients were included. The mean patient age was 46 years with follow-up of 33.4 months. Tumors were most often located in the sacrum/pelvis (81.3%), followed by the thoracic (8.3%), cervical (5.8%), and lumbar spine (4.6%). Chordoma (31.7%) and chondrosarcoma (27.1%) were the most frequently reported types. Negative surgical margins were achieved in 88.3% of cases. Local recurrence was reported in 16% of patients, with the highest observed in chondrosarcoma (32.4%). Complications occurred in 30.3% of patients; however, only 1% (2 cases) were attributed to navigation use. Two comparative studies examining navigated versus nonnavigated cohorts suggested improved bony margins and lower recurrence risk with navigation. Conclusion: Early studies suggest that stereotactic navigation may be a feasible and safe adjunct for the resection of primary spine/pelvic tumors, particularly in achieving adequate bony margins. However, the current evidence is limited to small retrospective studies with heterogeneity in methodology, tumor type, and follow-up. Level of Evidence: Level IV: Systematic review of level-III and level-IV studies.

The 2025 Voice AI Symposium represented a transition from conceptual research to clinical implementation in vocal biomarker science. Hosted by the NIH-funded Bridge2AI-Voice consortium, the meeting convened global experts to address the methodological, ethical, and translational challenges of integrating voice-based artificial intelligence (AI) into healthcare. This mini-review synthesizes symposium insights across six domains: multimodal integration, FAIR (Findable, Accessible, Interoperable, Reusable) and CARE (Collective Benefit, Authority to Control, Responsibility, Ethics) data governance, clinical translation, interdisciplinary training, and cross-sector innovation. Research presented demonstrated voice as a latent, multimodal biomarker reflecting neurological, cardiopulmonary, and psychological states, while discussions emphasized ethical data practices and human-centered design. The implementation-focused panels underscored the importance of workflow alignment and usability for adoption in real-world care. Collectively, the symposium reflects a field advancing toward translational readiness and ethical accountability, positioning voice AI as a scalable, inclusive tool for next-generation healthcare.

Abstract Radiotherapy is an established treatment for low-grade primary cutaneous B-cell lymphoma. Recommendations on its use differ internationally, which prompted our group to conduct this analysis. Twenty-two institutions participated in this international study. Patient eligibility required a diagnosis of limited (T1/T2) primary cutaneous marginal zone or follicle center lymphoma treated with radiotherapy between 1995 and 2023. Data were collected retrospectively until February 2024 within the framework of the International Lymphoma Radiation Oncology Group. Overall, 535 patients were analyzed. Predominant locations were the head (40%) and trunk (36%). Radiotherapy had a median dose of 24 Gy in fractions of 2 Gy. Complete responses were observed in 91% at a median time of 3.6 months following radiotherapy. There was no statistically significant difference between treatments ≤4 Gy and &gt;4 Gy for complete or overall response rates (P = .077 and P = .056, respectively). However, there was an inferior duration of local control with ≤4 Gy (5-year local control 73% ± 12% vs 96% ± 2%; P&lt; .001). Radiation dose was the main prognostic factor in the univariate and multivariable Cox analysis; however, higher doses did not translate into an overall survival benefit. Toxicities rarely exceeded grade 2 but were more frequent in the &gt;4 Gy group. Radiotherapy remains an effective treatment option for indolent skin lymphoma with low toxicity. High response rates are observed with low doses of ≤4 Gy. In comparison to conventional doses, these treatments have a shorter duration of local control but a favorable toxicity profile.

BACKGROUND AND OBJECTIVES: Contemporary skull base surgeons must understand transcranial and endoscopic endonasal approaches to the petrous apex (PA). We provide an anatomic overview and comparison of main approaches to the PA through illustrative anatomic dissections. METHODS: On 10 sides of 5 specimens, transcranial approaches to the PA including the anterior petrosal, transcochlear, and retrosigmoid with suprameatal extension were performed. For endoscopic endonasal approaches, the transclival approach was performed in the midline of 5 specimens and its contralateral transmaxillary extension was performed on 10 sides. RESULTS: The anterior petrosal approach offers an anterolateral view of the PA bounded by petrous ridge posteromedially, internal auditory canal posterolaterally, greater superficial petrosal nerve anterolaterally, and lateral boundary of cranial nerve V, the Gasserian ganglion, and V3 anteromedially; it exposes the middle fossa and, once the PA is removed, the superomedial cerebellopontine angle. The transcochlear approach affords a lateral view of the PA defined medially and inferiorly by inferior petrosal sinus, posteriorly by posterior fossa dura, anteriorly by the petrous internal carotid artery, and superiorly by the superior petrosal sinus and middle fossa dura. Through a retrosigmoid approach, the PA is bounded by the superior petrosal sinus superiorly, the sagittal plane of cranial nerve VI medially, and the axial and sagittal plane of the internal auditory canal porus inferiorly and laterally, respectively. It affords a panoramic view of the posterior fossa and access to Meckel's cave after PA drilling. Endoscopic endonasal approaches target the anteromedial PA, and it is demarcated by a triangle consisting of cranial nerve VI posterolaterally, the paraclival segment of the internal carotid artery anteriorly, and the petroclival synchondrosis inferiorly and medially. The addition of the contralateral transmaxillary approach enhances lateral access up to the internal auditory canal. CONCLUSION: We provide a comprehensive overview of the main approaches to the PA through illustrative anatomic dissections and representative cases.

Abstract Background Abdominal arterial calcification is a well-established predictor of cardiovascular events and mortality in kidney failure. Autosomal dominant polycystic kidney disease (ADPKD), a common genetic cause of kidney failure, presents with a distinct vascular profile. However, the burden of abdominal arterial calcification in ADPKD remains inadequately characterized. Clarifying these differences may improve cardiovascular risk stratification and transplant timing. Methods We conducted a retrospective cohort study of 4088 adult patients listed for kidney transplant at three Mayo Clinic sites (2005–2024). Patients were categorized by kidney failure cause: ADPKD vs. non-ADPKD. Abdominal arterial calcification was quantified on non-contrast computed tomography (CT) scans using a modified Agatston scoring method. Propensity score matching (1:1) adjusted for age, sex, race, lipid levels, left ventricular ejection fraction, dialysis exposure, coronary artery disease, neurovascular disease, and smoking history, was performed. Abdominal arterial calcification scores were compared between matched groups, and subgroup analyses evaluated abdominal arterial calcification severity across dialysis durations in ADPKD patients. Results After matching, 309 patients with ADPKD were compared with 309 non-ADPKD chronic kidney disease (CKD) controls. Abdominal arterial calcification scores were significantly lower in the ADPKD group (median: 425.3; IQR: 0.0–2033.5) than in the non-ADPKD group (median: 1256.8; IQR: 96.5–5033.8). Among ADPKD patients, abdominal arterial calcification scores increased with dialysis duration (P &lt; .001). Conclusion ADPKD patients exhibit lower abdominal arterial calcification scores than their non-ADPKD counterparts after adjusting for clinical variables. Abdominal arterial calcification progression with dialysis highlights the importance of early transplant evaluation. This study introduces a novel adaptation of coronary calcium scoring software for quantifying abdominal calcification, offering a standardized approach to vascular risk assessment in kidney transplant candidates.