Citations

Abstract Polygenic risk scores (PRSs), which quantify inherited susceptibility to complex traits and diseases, have emerged as valuable tools for risk stratification and precision medicine. Despite their promise, PRS developed on European cohorts often demonstrate substantially reduced predictive accuracy in non-European populations, due to differences in genetic architecture. The disproportionate representation of European ancestry cohorts in genome-wide association studies (GWAS) leads to inequitable deployment of PRS technologies across diverse populations. Here, we introduce PRANA (Polygenic Risk Adaptation via Neural-network Architecture), a deep learning framework that adapts an existing PRS developed on one population to other ancestries. Unlike methods that require large-scale GWAS in the target population, PRANA leverages pre-trained PRS models derived from European cohorts and adapts them using modestly sized cohorts from the target population. We evaluated PRANA on seven complex traits in South Asian, East Asian and Ashkenazi Jewish populations, as well as in selected smaller East Asian subpopulations where the scarcity of training data poses a particular challenge. PRANA mostly improved predictive performance of the baseline PRS models by 5%-20% in terms of effect size (β) and Nagelkerke’s R², and, in most cases, outperformed existing cross-ancestry multi-PRS approaches. These results highlight PRANA as a scalable and practical strategy to reduce disparities in genomic risk prediction and advance the equitable application of PRS in diverse populations.

Purpose To evaluate return‐to‐sport (RTS) rates and patient‐reported outcome measures (PROMs) following hip arthroscopic labral repair for femoroacetabular impingement in active basketball players with a minimum of 2‐year follow‐up. Methods All patients who were active basketball players and underwent hip arthroscopy with labral repair for femoroacetabular impingement from 2009 to 2022 were identified. Patients were evaluated for postoperative RTS and revision surgery at a minimum 2‐year follow‐up. RTS was defined as resuming basketball participation, at any level. Modified Harris Hip Score (mHHS), Hip Outcome Score‐Activities of Daily Living (HOS‐ADL) and Sport (HOS‐Sport), and surgery satisfaction were also collected. Results Sixty‐seven hips in 54 athletes (29 male, 25 female) with a mean age of 22.2 years (range 13‐39 years) were included. Eighty‐six (86%) were recreational or high school basketball players. There was significant improvement in all PROMs from baseline to a minimum 2‐year follow‐up (all P < .001). After excluding for athletes who did not RTS for nonmedical reasons, 78% of athletes returned to basketball following hip arthroscopy. Including patients who cited nonmedical reasons for not returning, the overall RTS rate was 65%. Athletes who RTS had significantly higher mHHS ( P = .012), HOS‐ADL ( P = .006), and HOS‐Sport ( P = .002), as well as lower visual analog scale pain (2.2 vs 3.4, P = .037) than those who did not RTS. Calculated minimal clinically important difference values were 8.3 for mHHS, 7.2 for HOS‐ADL, and 13.4 for HOS‐Sport. Anchor‐based patient acceptable symptom state calculations yielded thresholds of 83.5 for mHHS, 92.6 for HOS‐ADL, and 79.2 for HOS‐Sport—with 70%, 63%, and 67% of patients achieving these thresholds, respectively. Conclusions Basketball players who undergo hip arthroscopic labral repair for femoroacetabular impingement show significant improvements in PROMs with 78% RTS rate at a minimum 2‐year follow‐up. Although many athletes discontinued basketball for reasons unrelated to the hip, 18% cited hip issues. Basketball players who successfully return to basketball report higher PROMs than nonreturners, and cohort‐specific minimal clinically important difference analysis indicates that most athletes achieve clinically meaningful improvements. Level of Evidence Level IV, therapeutic retrospective case series.

Autonomous robotic-assisted surgery (RAS) has emerged as a promising objective in biomedical technology, further enhanced by miniaturization toward microrobotic-assisted surgery (μ-RAS). This reduction in scale promises minimally invasive, partially or fully automated surgical procedures, with the potential to reduce patient recovery times, lower medical costs, and enable previously unavailable procedural options. This perspective highlights the specific advances in RAS that potentially map to the microscale (μ-RAS), organized across five surgical domains: endovascular, endoluminal, laparoscopic, ophthalmic, and orthopedic. We examine both clinical demands and technological advances in surgical robotics and identify the key innovations required for progress across these surgical fields. Our contribution is distinct in combining the perspectives of both surgical experts and bioengineering innovators, outlining a roadmap for the advancement and eventual integration of autonomous RAS and μ-RAS into mainstream surgical practice.

Purpose To investigate outcomes among patients undergoing total hip arthroplasty after hip arthroscopy (HA‐THA) compared with a matched cohort undergoing primary THA without prior arthroscopy (Only‐THA). Methods Patients who underwent THA after primary hip arthroscopic labral repair from 2009 to 2022 at a single institution were identified. Cases were propensity‐matched 1:4 to primary THA controls by age at THA, sex, body mass index (BMI), surgical approach, and year of surgery. At minimum 2‐year follow‐up, patient‐reported outcomes (PROs)—Forgotten Joint Score (FJS), modified Harris Hip Score (mHHS), and Hip Disability and Osteoarthritis Outcome Score Pain (HOOS‐Pain)—were analyzed. Results Sixty‐two hips (age: 47.5 ± 9.3 years, BMI: 29.7 ± 6.2 kg/m 2 ) were matched to 248 Only‐THA hips (age: 47.9 ± 10 years, BMI: 29.5 ± 5.8 kg/m 2 ). Although both HA‐THA and Only‐THA patients showed significant ( P < .001) postoperative improvements in PROs, HA‐THA patients reported significantly lower postoperative FJS, mHHS, HOOS‐Pain, and inferior Visual Analog Scale pain scores ( P < .001) compared with Only‐THA controls. A cohort‐specific minimal clinical important difference for mHHS was calculated as 9.6 points, with 75.7% of HA‐THA and 87.5% Only‐THA patients achieving this threshold ( P = . 077). At mean 6.6 ± 3.3 years follow‐up, HA‐THA patients with preoperative Tönnis grades 1 reported significantly decreased FJS, mHHS, and HOOS‐Pain compared with HA‐THA patients with preoperative Tönnis grade 2‐3 ( P ≤ .05). HA‐THA patients with Tönnis grade 1 also exhibited worse PROs ( P < .001) compared with Only‐THA controls. Although there were no differences in complication rates between HA‐THA and Only‐THA patients (8% vs. 5%, P = .49), all‐cause reoperation was greater amongst HA‐THA (10% vs. 2%, P = .01). Conclusions Patients undergoing THA after prior hip arthroscopy showed modestly inferior subjective outcomes at mid‐term follow up compared with an age‐matched cohort without prior arthroscopy. Although both groups showed meaningful improvement, a smaller proportion of HA‐THA patients achieved the cohort‐specific MCID for mHHS compared with Only‐THA controls. Level of Evidence Level III, retrospective cohort study.

Abstract Objective This study was undertaken to examine acute and chronic electroencephalographic (EEG) and seizure characteristics in new onset refractory status epilepticus (NORSE). Methods Multicenter inpatient and follow‐up clinical and EEG data were analyzed using International League Against Epilepsy definitions and American Clinical Neurophysiology Society (ACNS) EEG terminology. Results Forty‐four patients were included from the Yale NORSE/FIRES Biorepository (median age = 29 years, 33 female, 38 cryptogenic). Nine hundred twenty inpatient EEG days were reviewed (median = 13.5 days/patient). Presenting status epilepticus (SE) types included 24 convulsive SE (CSE), five focal–motor (FMSE), and 15 nonconvulsive (NCSE). Of 39 patients with post discharge follow‐up (median = 14.7 months), 61.5% ( n = 24) had seizures and required more antiseizure medications than seizure‐free patients (median = 4 vs. 1, p < .001). Inpatient EEG captured epileptiform discharges in all and periodic discharges in 38 patients. Seizures were captured in 38 patients: 33 electrographic (11 only electrographic) and 27 electroclinical. Total seizure burden ranged 6.5–29 615.0 min (median = 50.7). Seizures fulfilling ACNS EEG criteria for SE were captured in 20 patients; two had CSE and the remainder NCSE with coma, nine of whom also had FMSE. Inpatient seizure days (median = 50.0 vs. 15.5%, p = .004) and seizure burden (median = 42.9 vs. 0 min, p = .009) were higher in the first half of monitored days. Interictal findings were equally present and did not predict postdischarge seizures, whereas electroclinical seizures (90.9% vs. 45.5%, p = .037), seizure burden (median = 116.8 vs. 32.5 min, p = .045), and proportion of seizure days (36.3% vs. 20.0%, p = .037) did. Among 12 patients with follow‐up EEGs (median = 19.6 months post onset), posterior‐dominant rhythm (PDR) returned in nine; five had periodic discharges, and three had seizure captured. Significance Seizures are most commonly convulsive upon presentation and nonconvulsive or clinically subtle throughout the inpatient course in NORSE. Inpatient seizures, but not interictal abnormalities, occur earlier in the inpatient course and presence of electroclinical seizures, seizure burden, and proportion of seizure days but not interictal findings are associated with postdischarge seizures. Although return of PDR reflects neurological recovery, seizure persistence and EEG abnormalities post‐NORSE are common.

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 FLASH radiotherapy shows promise in reducing normal tissue toxicity while maintaining tumor control. However, preclinical and early clinical evidence reveal biological and technical uncertainties. We review preclinical and veterinary studies, highlight unexpected toxicities, and argue that the fundamental principles of precision and safety in radiotherapy—particularly conformal treatment and ALARA—remain crucial.

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.