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Indiana Emergency Medical Services Workforce November 2, 2024 - January 10, 2025 Student Data Report
No full textThis report analyzes data from the Indiana EMS Student Pulse Check survey collected between November 2, 2024, and January 10, 2025. A total of 101 EMS trainees provided information on demographics, training experience, employment intentions, and factors influencing career decisions. Respondents were predominantly male, with most identifying as White, and the majority reported no prior ambulance experience. Most students were enrolled in or had recently completed EMT programs, with estimated training costs averaging 24.60. Students commonly became aware of EMS careers through personal connections and expressed high comfort with routine EMS scenarios, though discomfort increased for emotionally complex events such as pediatric deaths. Employment preferences centered on fire departments and hospital-based ambulance services, with many seeking full-time positions. Key factors influencing job selection included location, staffing patterns, and professional development opportunities, while cost of living, commute time, and community safety were identified as important community considerations. Respondents rated health insurance, paid time off, and retirement benefits as highly important, and emphasized flexible scheduling and peer support as meaningful employment options. Geographic analysis showed that most students completed training outside their home zip code, indicating travel is common among EMS trainees
FAM134B Controls Collagen I Dynamics in Hepatic Stellate Cell-Driven Fibrosis
No full textLiver fibrosis is driven by the accumulation of scar tissue in response to injury. Activated hepatic stellate cells (HSCs) secrete fibrogenic proteins that deposit into the extracellular matrix, leading to fibrosis. Increased production of fibrogenic proteins by HSCs leads to endoplasmic reticulum (ER) stress, triggering the unfolded protein response (UPR). The UPR is important in regulating HSC activation and fibrogenesis, but mechanisms driving this regulation are unclear. A key process regulated by the UPR is degradation of misfolded proteins through various pathways, including ER-to-lysosome-associated degradation (ERLAD). ERLAD targets proteins for lysosomal degradation and can involve autophagosomes engulfing portions of the ER, termed ER-phagy. ER-phagy is implicated in degradation of misfolded fibrillar collagen, but its role in fibrogenesis is unknown. We show that collagen I levels are posttranslationally regulated by autophagy, and this correlates with ER-phagy receptor expression. Furthermore, activation of HSCs induces ER-phagy flux and expression of ER-phagy receptors, including FAM134B, in a process dependent on UPR transducer ATF6α. Loss of FAM134B decreases intracellular collagen I without affecting COL1A1 mRNA. Moreover, FAM134B deletion blocks transforming growth factor β-induced collagen I deposition despite increased secretion. Together, we show that ER-phagy receptor FAM134B is pivotal for collagen I deposition during fibrogenesis.
NEW & NOTEWORTHY: We show for the first time that TGFβ-mediated activation of HSCs induces selective autophagy of the endoplasmic reticulum (ER-phagy), through upregulation of ER-phagy receptors and ER-phagic flux. We further show that the unfolded protein response is critical for this effect. Finally, we identify the ER-phagy receptor FAM134B as a critical regulator of collagen I dynamics and fibrogenesis, with loss of FAM134B dysregulating collagen I secretion and deposition
Prognostic value of PSMA PET/CT-Based local staging in predicting biochemical recurrence after radical prostatectomy
No full textPurpose: PSMA PET/CT outperforms conventional imaging for detecting pelvic nodal and distant metastasis, but its role regarding local staging and risk stratification remains unclear. This study aims to evaluate the association between PSMA PET/CT characteristics and biochemical recurrence-free survival (BRFS) after robot-assisted radical prostatectomy (RARP) in patients with prostate cancer.
Methods: In this international multicentre retrospective study, we analyzed 476 patients with localized or locally advanced miN0 prostate cancer, staged with PSMA PET/CT and MRI before RARP (2016–2023). Predictors of BRFS were identified using univariate and multivariate Cox regression with backward elimination based on Akaike information criterion (AIC). Kaplan-Meier analysis assessed the association of clinical stage by MRI, PSMA PET, and their combination with BRFS.
Results: In total 476 patients were included with a median follow-up of 18.0 months (IQR 6.9–29.3). Of the 127 BCRs, 101 (79.5%) occurred within two years post-surgery. The final multivariate model included initial PSA (10–20 vs. 20 vs. <10: HR 2.26 [95% CI 1.30–3.93]), biopsy ISUP grade group (2–3 vs. 1: HR 2.28 [95% CI 0.70–7.41]; 4–5 vs. 1: HR 3.62 [95% CI 1.12–11.65]), MRI T-stage (T3a vs. ≤T2: HR 1.19 [95% CI 0.75–1.90]; ≥T3b vs. ≤T2: HR 2.09 [95% CI 1.21–3.62]), and PSMA PET T-stage (T3a vs. ≤T2: HR 1.05 [95% CI 0.59–1.85]; ≥T3b vs. ≤T2: HR 2.75 [95% CI 1.63–4.63]). From the full model, clinical T-stage, MRI-derived index diameter, SUVmax, PSMAtotal and PSMAvol were eliminated. The 2-year BRFS was 19% (95% CI 6.7–51%) in patients with T3b disease on both MRI and PSMA PET compared to 58% (95% CI 40–84%) in those with T3b detected only on MRI (p = 0.03).
Conclusion: Clinical tumor stage assessed by PSMA PET was independently associated with BRFS in multivariate analysis, adjusting for clinical parameters and MRI-derived staging. This suggests that incorporating PSMA PET-based local staging may improve risk stratification and guide treatment decisions.
Supplementary Information: The online version contains supplementary material available at 10.1007/s00259-025-07455-0
From Pixels to Prediction: AI-Driven Detection of Free-Flap Compromise Using Clinical and Imaging Data
No full textIntroduction
Free-flap reconstruction remains a cornerstone of microsurgical reconstruction, yet flap failure and vascular compromise continue to impose a consequential clinical burden. Although preoperative imaging modalities such as Computed Tomographic Angiography (CTA) and fluorescent Indocyanine Green (ICG) imaging are commonly used to evaluate vascular anatomy, the decision-making largely relies on surgical experience. Emerging studies propose that applying artificial intelligence (AI) to imaging and clinical data may improve prediction of potential postoperative complications and guide flap selection.
Methods
A literature search was performed in PubMed and Embase to identify human studies applying neural network or machine-learning techniques to predict vascular complications, flap failure, or perfusion abnormalities using preoperative or perioperative data. The included studies reported imaging or clinical inputs, model architecture, validation methods, and predictive performance metrics such as sensitivity, specificity, and the area under the curve (AUC). Relevant data were reviewed and synthesized to assess model performance, trends, and limitations in current applications.
Results
Key findings include a study by Shi et al., who developed a random forest classifier to predict flap failure using data from 946 patients undergoing microvascular reconstruction, achieving an AUC of 0.770. Yang et al. retrospectively modeled vascular complications in 570 free-flap patients, with the neural network model performing the highest (AUC 0.828). Imaging-based investigations using hyperspectral imaging (HIS) paired with convolutional neural networks reported AUCs around 0.82 for detecting postoperative perfusion deficits. Prior HIS feasibility work demonstrated that tissue oxygenation correlates with flap compromise and may provide earlier warning than clinical assessment. Collectively, these studies show promising potential but remain limited by retrospective design, modest sample sizes, and restricted generalizability.
Conclusion
AI-enhanced imaging and machine learning-based algorithms represent a compelling frontier for improving free-flap outcomes and guiding flap choice. Translation into clinical practice will require prospective, multicenter validation and integration into preoperative planning workflows
Practice Patterns Vary Among Orthopedic, Plastic, and General Surgeons Resecting Soft Tissue Tumors of the Extremities and Pelvis
No full textBackground: Resection of extremity soft tissue tumors is common and frequently performed by orthopedic, plastic, and general surgeons. It is unknown if tumor location, Preoperative workup, and Postoperative care varies by specialty, which is the aim of this study.
Methods: A retrospective review was performed of 4,223 soft tissue tumors resected from the extremities and pelvis within a large single-state health system between 2009 and 2019. A more detailed cross-sectional review was performed on 450 tumors resected in 2016. Demographic and tumor characteristics, surgeon specialty (orthopedic, plastic, general), Preoperative workup (imaging, biopsy), and Postoperative management were collected and analyzed.
Results: General surgeons were more likely to resect tumors superficial to fascia (82.1%), compared to plastic and orthopedic surgeons (53.7% and 27.9%). Orthopedic surgeons were more likely to resect malignant tumors (28.2%) than plastic and general surgeons (14.0% and 4.5%). 16.3% of tumors resected by general surgeons had either Preoperative MRI or tissue diagnosis, compared to 42.6% for plastic surgeons and 90.5% for orthopedic surgeons (p < 0.001). Of the tumors resected by general surgeons without Preoperative MRI or tissue diagnosis, 2.6% were malignant. Finally, Postoperative documentation of neurovascular status, range of motion, and referral to physical therapy were more likely performed by orthopedic surgeons (all p < 0.001).
Conclusion: Practice patterns vary significantly among orthopedic, plastic, and general surgeons treating soft tissue tumors of the extremities and pelvis. These findings highlight the need for multidisciplinary engagement and standardization of treatment algorithms and training practices across the various surgical specialties
Oblique Genomics Mixture of Experts: Prediction of Brain Disorder With Aging-Related Changes of Brain’s Structural Connectivity Under Genomic Influences
No full textDuring the process of brain aging, the changes of white matter structural connectivity are closely correlated with the cognitive traits and brain function. Genes have strong controls over this transition of structural connectivity-altering, which influences brain health and may lead to severe dementia disease, e.g., Alzheimer's disease. In this work, we introduce a novel deep-learning diagram, an oblique genomics mixture of experts(OG-MoE), designed to address the prediction of brain disease diagnosis, with awareness of the structural connectivity changes over time, and coupled with the genomics influences. By integrating genomics features into the dynamic gating router system of MoE layers, the model specializes in representing the structural connectivity components in separate parameter spaces. We pretrained the model on the self-regression task of brain connectivity predictions and then implemented multi-task supervised learning on brain disorder predictions and brain aging prediction. Compared to traditional associations analysis, this work provided a new way of discovering the soft but intricate inter-play between brain connectome phenotypes and genomic traits. It revealed the significant divergence of this correlation between the normal brain aging process and neurodegeneration
Characterizing White Matter Hyperintensity Pathology in Alzheimer's Disease Using Multimodal Imaging
No full textBackground:
White matter hyperintensities (WMHs) in Alzheimer's disease (AD) are often linked to microvascular disease, but emerging evidence suggests AD‐specific pathologies also play a role. This pilot study leverages multimodal imaging to examine WMH volume, microstructure, and perfusion, uncovering distinct vascular and AD‐related contributions through their associations with amyloid and tau.
Method:
Thirty cognitively normal (CN), 30 mild cognitive impairment (MCI), and 10 AD participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI3) underwent T1‐weighted, fluid‐attenuated inversion recovery (FLAIR), T2*‐weighted, multi‐shell diffusion MRI, arterial spin labeling (ASL) perfusion, amyloid positron emission tomography (PET), tau PET, and vascular risk assessment. WMH volume was extracted using HyperMapp3r algorithm and Lesion Segmentation Tool (LST), and associated with amyloid and tau burden. To address WMH spatial heterogeneity, imaging metrics were assessed across WMHs, perilesional regions, and adjacent normal appearing white matter (NAWM). Adjacent NAWM was chosen over whole‐brain NAWM to ensure regional comparability within the same white matter tract and reduce intra‐subject variability.
Result:
WMH volume was higher in AD compared to MCI and CN (Figure 1A), independent of age, sex, and intracranial volume (F(5, 60)=11.28, p <0.001). Amyloid burden (β=0.045, p <0.001) was a predictor of WMH volume, independent of vascular risk, while tau was not. When stratifying by amyloid beta status and vascular risk, WMH burden followed a trend where it was highest in amyloid‐positive individuals with high vascular risk (A+V+), followed by amyloid‐positive with low vascular risk (A+V‐), then amyloid‐negative with high vascular risk (A‐V+), and lowest in amyloid‐negative with low vascular risk (A‐V‐) (Figure 1B). Across all groups, WMHs showed the most microstructural damage versus perilesion and NAWM, with a consistent trend across metrics. However, the differences were significant for intracellular volume fraction, axial, radial, and mean diffusivity (Figure 2). Significant between‐group differences were found in orientation dispersion, mean, and axial diffusivity within WMHs (Figure 3).
Conclusion:
This study highlights the interplay of vascular and neurodegenerative pathologies in WMH development in AD, with amyloid burden independently contributing to WMH volume and vascular risk amplifying its effects. Future work will examine spatial WMH distribution across amyloid and vascular risk cohorts to clarify their contributions to WMH development and progression
P-386. A Phase 4 Study to Evaluate the Safety and Efficacy of Oral B/F/TAF After Discontinuing Injectable CAB + RPV
No full textBackground:
People with HIV-1 (PWH) on injectable cabotegravir + rilpivirine (CAB+RPV) may not stay on injectable antiretroviral therapy (ART) for various reasons. Given the long half-life and pharmacokinetic decay of CAB and RPV, switching to oral ART involves the overlap of ART agents. Bictegravir (BIC)/emtricitabine/tenofovir alafenamide (B/F/TAF) is a guideline-preferred once-daily oral regimen, but the overlap of the two integrase inhibitors, CAB and BIC, has not been evaluated.
Methods:
This prospective, single-arm, open-label, interventional Phase 4 study (NCT06104306) included PWH who chose to switch from every-2-month CAB+RPV, having maintained HIV-1 RNA < 50 copies(c)/mL for ≥ 6 months at screening, to daily B/F/TAF due to intolerance, adverse events (AEs), or personal preference. Coprimary endpoints were the proportion of participants experiencing treatment-emergent Grade 3/4 study drug–related AEs and Grade 3/4 laboratory abnormalities through Week (W)12. Secondary endpoints included the proportion of participants with HIV-1 RNA ≥ 50 c/mL at W12 by missing = excluded (M=E) and discontinuation = failure (D=F) analyses, and the proportion of participants discontinuing B/F/TAF by W12.
Results:
Twenty-nine participants from North America switched to B/F/TAF around the time of their next scheduled CAB+RPV dose (Table). Median (IQR) age was 46 (34-58) years, 69% were assigned male at birth, 55.2% were White, 20.7% Black, and 37.9% Hispanic/Latine. The most common reason reported for switching from CAB+RPV to B/F/TAF was side effects (55.2%). No participants experienced treatment-emergent Grade 3/4 study drug–related AEs and 1 (3.6%) experienced treatment-emergent Grade 3/4 laboratory abnormalities (Grade 3 reduced neutrophil and total white blood cell counts), deemed unrelated to study drug, through W12. No participants had HIV-1 RNA ≥ 50 c/mL at W12 (M=E). One out of 27 participants (3.7%) had HIV-1 RNA ≥ 50 c/mL at W12 (D=F). One (3.4%) participant discontinued B/F/TAF by W12 for reasons other than efficacy/safety (they moved away).
Conclusion:
Switching from CAB+RPV to B/F/TAF was safe and efficacious in this study. The data support switching from injectable CAB+RPV to oral B/F/TAF when needed or desired
MicroRNA profiling of testicular Leydig cell tumors identifies a microRNA signature associated with malignancy and miR-196b-5p as a potentially useful biomarker
No full textApproximately 10% of testicular Leydig cell tumors (LCTs) are clinically malignant and unresponsive to systemic treatment. Predicting their clinical behavior can be problematic because there are no biomarkers that can consistently discriminate between benign and malignant LCTs. We assessed microRNA expression profiles of LCTs to identify differentially expressed microRNAs that could potentially distinguish benign from malignant neoplasms. The study consisted of two phases. In the first (discovery) phase, we interrogated 768 microRNAs in a series of 11 LCTs (six malignant and five benign) using Taqman Low-Density Array (TLDA) microRNA profiling. In the second phase, we validated the top differentially expressed microRNA targets with real-time quantitative PCR on a series of 35 LCTs (17 malignant and 18 benign), assessing their clinical performance for distinguishing malignant from benign LCTs. Target biologic pathways were analyzed using the miRTargetLink 2.0 tool. A total of 50 microRNAs were differentially regulated in malignant LCTs (27 upregulated, 23 downregulated). The top six microRNA candidates (top three upregulated and top three downregulated) were validated, showing good performance for discriminating between malignant and benign LCTs, with an area under the curve (AUC) ranging between 0.69 and 0.87. MiR-196b-5p showed the best performance, with sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 82%, 83%, 83%, 82%, and 83%, respectively. A panel (i.e. combined) analysis reached 100% sensitivity and 83% specificity. Pathway analysis revealed significant overlap in the biological process targeted by the upregulated microRNAs in malignant LCTs, including proliferation, development, metabolism, hormone synthesis, and cell death. Our results support the idea that malignant LCTs are associated with a distinct microRNA signature. MiR-196b-5p was identified as a potentially useful biomarker to distinguish benign from malignant tumors. The shared downstream targets of the top upregulated microRNAs suggest that dysregulation of cell proliferation and apoptosis underlie aggressive biologic behavior in LCTs and may offer opportunities for targeted therapies
Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers
No full textIntroduction: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined apolipoprotein E (APOE) allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer's disease dementia cases.
Methods: In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins.
Results: NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles and higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance.
Discussion: We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring cognitive resilience differ across race groups.
Highlights: Apolipoprotein E (APOE) allele frequency differs between SuperAgers and cases APOE allele frequency differs between non-Hispanic White SuperAgers and controls The relationship of APOE and non-Hispanic Black SuperAger status is unclear