Citations

Abstract Spatial transcriptomics links gene expression to tissue architecture, but detecting spatially variable genes at atlas scale remains difficult because biologically relevant patterns are multiscale, sparse, and often non-parametric. Here we show that FlashS, a frequency-domain kernel test using random Fourier features, sparse sketching, and a kurtosis-corrected null, retains Gaussian-kernel flexibility at near-linear per-gene cost without permutation. Across 50 benchmark datasets spanning 9 spatial transcriptomics platforms, F lash S achieves the highest ranking accuracy among 14 compared methods while maintaining calibrated inference under simulation and full-atlas permutation. In human heart tissue, it recovers a mitochondrial biogenesis program that co-localizes with ventricular cardiomyocytes. On the Allen Brain MERFISH atlas containing 3.94 million cells, F lash S completes in minutes on a single workstation and separates biological signal from negative-control barcodes even when p-values saturate.

Background: Femoroacetabular impingement (FAI) is a common injury experienced by basketball players. Surgical management with arthroscopic labral repair and femoral osteochondroplasty can lead to successful outcomes for athletes whose nonoperative management fails. Recent studies have demonstrated that athletes undergoing hip arthroscopy in the setting of FAI had favorable return-to-sport (RTS) and sport continuation outcomes. Purpose: To evaluate patient-reported outcome measures (PROMs) and RTS rates at minimum 5-year follow-up in basketball players after hip arthroscopy for FAI. Study Design: Case series; Level of evidence, 4. Methods: All active basketball players at the recreational, high school, and collegiate levels who underwent primary hip arthroscopy with labral repair for FAI between August 2009 and December 2019 were identified. Postoperative RTS, revision rates, and surgery satisfaction at final follow-up were evaluated. PROMs were also analyzed as follows: visual analog scale, Tegner Activity Scale, modified Harris Hip Score, Hip Outcome Score–Activities of Daily Living, and Hip Outcome Score–Sport. Results: Fifty-three patients (64 hips) were included with a mean ± SD age of 21.2 ± 6.0 years. Most athletes played recreational or high school basketball (85%), while 15% played college basketball. Forty-three patients attempted to return to basketball. Of these patients, 35 (81%) returned to basketball after surgery, with 32 (91%) returning to the same level of play. Patients who returned to basketball had significantly improved outcomes on the modified Harris Hip Score ( P = .006), Hip Outcome Score–Activities of Daily Living ( P = .007), Hip Outcome Score–Sport ( P = .004), Tegner Activity Scale ( P = .010), and visual analog scale with use ( P = .041) as compared with those who did not return. High school athletes had decreased odds of RTS when compared with recreational athletes ( P = .01). There was significant improvement in all PROMs from baseline to minimum 5-year follow-up ( P < .05). Conclusion: At minimum 5-year follow-up, basketball players demonstrated durable improvements in PROMs and an RTS rate of 81% after hip arthroscopy for FAI. The majority of athletes returned to the same level of competition. There were significantly improved PROMs in patients who returned to sport versus those who did not. High school athletes had decreased odds of RTS when compared with recreational athletes. However, body mass index, sex, age, alpha angle, and basketball position did not significantly correlate with RTS outcomes.

Background Difficulty tolerating the uncertainty of ambiguous or unpredictable situations may influence how patients with functional motor disorder (FMD) respond to treatment. However, only one study has examined the role of intolerance of uncertainty (IU) in FMD treatment. Objectives This study sought to expand on prior findings in a larger sample of patients with FMD who completed an intensive motor-retraining programme. Methods A consecutive cohort of 109 patients with FMD completed a 1-week intensive outpatient motor-retraining programme. Patients rated their IU using the Intolerance of Uncertainty Scale-12 and functional motor outcomes using three empirical measures before and after treatment. Univariate and multivariable analyses were conducted to (1) characterise the rate of elevated IU, (2) evaluate potential changes in IU across the programme, (3) examine whether changes in IU predict improvements in motor functioning and (4) determine if IU incrementally predicts functional improvements in patients with clinically elevated IU. Results Findings revealed that clinically elevated IU was common (yielding a base rate of 44%) and that the ‘prospective’ subtype of IU significantly decreased with 1 week of FMD treatment. Change in IU was not significantly associated with improved functional outcomes across the sample. However, change in prospective IU did predict patient-specific functional outcomes among those with clinically elevated IU ( R 2 =11%). Conclusions Findings support prior work suggesting that certain subtypes of IU are common, modifiable and related to treatment outcomes in FMD. The ‘prospective’ subtype of IU may represent an operative factor that can enhance the efficacy of existing FMD rehabilitation programmes.

Background and Aims: Upadacitinib, a selective janus kinase 1 (JAK1) inhibitor, and ustekinumab, an interleukin-12/23 inhibitor, are approved for the treatment of moderate-to-severe ulcerative colitis (UC). However, real-world data in patients with anti-tumor necrosis factor (TNF)-exposure are limited. Methods: We performed a retrospective cohort study in TriNetX US Collaborative Network. Adult patients with UC and prior anti-TNF exposure were identified. Patients who received upadacitinib or ustekinumab between April 2022 and August 2024 were stratified into two cohorts. Patients with Crohn’s disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis were excluded. Propensity-score matching was performed to balance comorbidities, medications, and labs between the two cohorts. Study outcomes included rates of corticosteroid use, colectomies, change of therapy, hospital admissions or emergency department visit, and all-cause mortality. Results: A total of 724 patients in the upadacitinib cohort and 909 in the ustekinumab cohort met the inclusion criteria. After matching, 633 patients remained in each cohort, with balanced baseline characteristics. At 1-year follow-up, the rates of corticosteroid use were 40.1% in the upadacitinib group and 48.5% in the ustekinumab group (aOR= 0.71, 95% CI: 0.69-0.89), mainly driven by differences in oral corticosteroid use (aOR= 0.73, 95% CI: 0.58-0.91). All other outcomes were comparable between the two study groups. Conclusion: In patients with ulcerative colitis and prior anti-TNF exposure, upadacitinib was associated with lower oral corticosteroid use than ustekinumab over 1 year, with no significant differences in rates of colectomy, ED visits or hospitalizations. These findings suggest a potanial higher effectiveness of upadacitinib compared with ustekinumab and may help inform treatment selection in this population.

Background: Artificial intelligence (AI) is increasingly being integrated into healthcare, with applications ranging from predictive analytics to clinical decision support. In clinical nutrition, AI tools offer opportunities to improve workflow efficiency, enhance dietary assessment, and personalize nutrition care. Despite growing interest, little is known about registered dietitian nutritionists’ (RDNs) perceptions of AI in clinical practice. The aim of the present study was to assess RDNs’ attitudes toward AI use within a large healthcare system, along with their perceived barriers in this regard. Methods: A cross-sectional survey was developed through expert review and distributed electronically via REDCap to RDNs across Mayo Clinic’s academic campuses and affiliated health system sites. The 23-item survey included Likert-scale items addressing AI’s potential utilization within clinical care, perceived benefits and risks, and readiness for adoption. Responses were summarized using descriptive statistics. Factor analysis identified underlying constructs related to AI attitudes. Differences stratified by age and years of experience were evaluated using ANOVA. Results: Of the 185 RDNs invited, 64 (35%) responded. Two factors emerged: optimism regarding AI usage (Cronbach’s α = 0.94) and skepticism about implementation (α = 0.76). The overall mean ± SD score for optimism was 0.1 ± 0.6 (neutral), while skepticism averaged 1.0 ± 0.6 (moderate). Skepticism differed by years of experience (p = 0.012), with the lowest levels observed among RDNs with ≥21 years of practice. No significant differences were observed across age groups. Discussion: RDNs demonstrated neutral attitudes toward AI use but expressed concerns about accuracy, training, and implementation challenges. Addressing these concerns through education and structured implementation strategies may facilitate successful adoption of AI in dietetic practice.

Chimeric antigen receptor (CAR)-based therapies have become an integral part of modern cancer care, delivering durable responses in patients with otherwise refractory hematologic malignancies. As their use has expanded, it has become increasingly clear that these immune-based treatments exert important effects on the cardiovascular system. Rather than reflecting isolated cardiac injury, CAR-associated cardiovascular complications arise from a broader inflammatory process in which immune activation, cytokine release, endothelial dysfunction, and myocardial stress are closely interconnected. Pro-inflammatory mediators such as interleukin-6, interleukin-1β, tumor necrosis factor-α, and interferon-γ play central roles in shaping these responses, particularly during cytokine release syndrome. From a clinical perspective, cardiovascular manifestations often include hypotension, arrhythmias, and transient reductions in left ventricular function, with more severe presentations occurring in patients who develop high-grade inflammatory toxicity. At the same time, advances in immune engineering are reshaping how these platforms are viewed, extending their relevance beyond toxicity alone. Preclinical studies now suggest that CAR-based approaches may be adapted to modulate cardiac fibrosis and promote myocardial repair, highlighting a potential shift from purely oncologic applications toward broader cardiovascular benefit. Placing these developments within a cardio-oncology framework emphasizes the need for careful cardiovascular assessment, longitudinal monitoring, and close collaboration between specialties.

OBJECTIVE To test the effect of physical activity on the gut microbiome and circulating short-chain fatty acids (SCFAs) among sedentary adults with prediabetes and overweight or obesity. RESEARCH DESIGN AND METHODS In a pilot and feasibility trial, we randomized 77 adults with prediabetes and a sedentary lifestyle into one of two groups: 1) intervention: invited to engage in home-based moderate-intensity walking 3×/week for 30 min/session in weeks 1–4 and for 45 min/session during weeks 5–8 of the 8-week intervention; or 2) control: maintained habitual physical activity levels. We performed metagenomic sequencing from stool collected at baseline, week 4, and week 8, with SCFAs measured from serum collected at baseline and week 8. Taxonomic and functional profiling was performed on the metagenomic reads; α-diversity metrics were subsequently derived. Linear regression assessed the difference in change between the intervention and control groups for α-diversity and SCFA levels. RESULTS We screened 1,533 participants for eligibility and consented 132. Of these, 87 entered the run-in phase, and 77 were randomized. Participants were mean (SD) 51.4 (8.9) years old, 87.7% female, and 74% non-Hispanic White. Mean fasting glucose was 103.3 (13.2) mg/dL, while mean BMI was 34.4 (5.7) kg/m2. Compared with the control group, the intervention group experienced decreased α-diversity as characterized by Shannon, Richness, and Faith diversity indices by intervention week 8 (P &lt; 0.05). Changes in SCFA levels were not statistically significant different in intervention versus control. CONCLUSIONS Randomization to a walking intervention resulted in modest gut microbiome changes among adults with overweight or obesity and prediabetes.

Transactive response DNA-binding protein of 43 kDa (TDP-43) type-A is associated with frontotemporal lobar degeneration (FTLD). In primary age-related tauopathy (PART), TDP-type-α displays similar features to FTLD-TDP type-A. We compared antemortem MRI volumes of amygdala nuclei and hippocampal subfields between 16 PART-TDP-α and 12 FTLD-TDP-A autopsy-confirmed cases. Hippocampal tail and CA1 body volumes were smaller in PART-TDP-α group, which also had smaller lateral and central amygdala nuclei compared to FTLD-TDP-A group, but differences were non-significant after FDR correction. There is no evidence suggesting that TDP-43 type-A in FTLD affects hippocampal and amygdala volume loss differently than TDP-43 type-α in PART.

Abstract Acute kidney injury (AKI) causes rapid loss of renal function with high morbidity and mortality. Our previous research showed that neuronal nitric oxide synthase (NOS1) mediates nitric oxide-dependent dilation of the afferent arteriole, inhibiting tubuloglomerular feedback (TGF), which critically regulates single nephron glomerular filtration rate (GFR). This mechanism could affect how vulnerable the organ is to ischemic injury, but this has not been directly tested. In the present study, we generated inducible macula densa (MD)-specific NOS1 knockout mice (NKCC2-Cre-NOS1 flox/flox) using a new inducible NKCC2-Cre line crossed with NOS1 flox mice. AKI was induced by 18-min bilateral renal pedicle clamping at 37°C, followed by 48-h reperfusion. Kidney injury was assessed by measuring GFR, plasma creatinine, histology, cytokines, apoptosis, fibrotic factors, and proteomics. Complete NOS1 deletion in MD cells was confirmed through NKCC2/NOS1 immunofluorescence. MD NOS1 deletion enhanced the TGF response, which was further amplified following AKI compared with control (Cre −/−). Following AKI, compared with controls (Cre −/−), NOS1 knockouts showed a significantly lower GFR (236 ± 66 to 24 ± 22 μl/min) and higher plasma creatinine levels, alongside more severe tubular damage evidenced by H&E staining. Cytokine array analysis showed chemokines such as MCP-1 and CXCL1 and macrophage marker CD68 were significantly increased; Western blot analysis showed cleaved caspase-3 levels were significantly increased, indicating enhanced apoptosis. Additionally, fibrosis markers TIMP-1, collagen-3, and α-SMA were significantly up-regulated at both mRNA and protein levels. We further observed increased hypoxia marker hypoxia-inducible factor-1α in MD-specific NOS1 knockout mice (Cre +/−). Global label-free proteomic profiling with targeted validation identified genotype-dependent responses involving haptoglobin, Tacstd2, and Cyp20a1, linking NOS1 deficiency to exaggerated inflammatory, fibrotic, and metabolic pathways. These findings highlight a novel role of MD NOS1 and TGF in AKI pathophysiology, suggesting NOS1 targeting as a therapeutic strategy. Haptoglobin was identified as a downstream plasma signal of NOS1-dependent AKI responses, indicating potential translational value.

ABSTRACT Introduction/Aims Neuromuscular ultrasound (NMUS) is becoming increasingly incorporated as a complementary tool in electrodiagnostic (EDX) medicine. Competency assessment is critical to ensure adequate quality, appropriate application, and accurate interpretation. The primary objective was to develop a competency‐based assessment tool of foundational NMUS skills among postgraduate medical trainees in a single center. Methods The assessment included written (28 multiple‐choice, short answer, or yes/no) questions and practical skills (15 prompts) sections recommended by a published consensus‐based survey to include the knowledge and skills necessary to achieve minimal competency for unsupervised practice of NMUS for common conditions. The written portion included interpretation of basic pathology. Core practical content focused on the most evaluated structures in the Mayo EDX laboratory: the median and ulnar nerves and diaphragm muscle. The practical portion was administered by a single examiner and scored with a five‐point competency‐based rating. Four experienced educators used the Angoff standard setting method to set passing scores for each section. Results Subjects included three EMG‐track clinical neurophysiology fellows who completed a NMUS lecture series with supervised hands‐on scanning and a 2‐week intra‐lab NMUS elective during fellowship. Composite scores ranged from 89% to 97%. All subjects met minimum passing scores for each section (77% and 88% for the knowledge and skills sections, respectively). Discussion This NMUS competency assessment was successfully implemented and may be incorporated into postgraduate medical trainee evaluation to ensure minimal competency in evaluation of carpal tunnel syndrome, ulnar neuropathy at the elbow, and diaphragm function. This effort integrates quality NMUS evaluations into clinical practice.