The article explores the shift from Asimov's laws, centered on machine obedience, to Kasparov's laws of "hybrid intelligence". While Asimov focused on preventing harm through autonomous constraints, Kasparov emphasizes that the best performance arises from the optimal orchestration of human, machine, and process. This perspective suggests that a "weak human + machine + superior process" can outperform a "strong human + machine + inferior process". Empirical studies in radiology are consistent with this socio-technical conjecture. Studies in radiology indicate that specific collaboration protocols allow human-AI teams to surpass isolated models. Notably, research confirms that less proficient clinicians embedded in effective protocols can achieve higher accuracy than clinicians with higher baseline accuracy operating under less effective protocols. This framework views AI as a component of "superminds" - collective cognitive architectures that enhance plural decision-making. Ultimately, the value of AI is an emergent property of the organizational system. Rather than focusing solely on model accuracy, designers must create interaction protocols that calibrate trust and prevent professional deskilling. The goal is to move toward a synergy where machines help human collectives become more intelligent.
Accurate assessment of drug adherence is essential for long-term oral therapies, where self-administration is unsupervised. Conventional tools such as self-reports, electronic monitors, and even therapeutic drug monitoring often fail to detect non-adherence. Population pharmacokinetic modeling improves objectivity but typically relies on a single analyte, which may still miss hidden non-adherence. We propose a bi-analyte population pharmacokinetic-based approach that uses both the parent drug and a metabolite with distinct pharmacokinetics to enhance adherence detection and reconstruct likely dosing histories. A literature review identified spironolactone and its metabolite canrenone as suitable candidates, based on long-term use and an available population pharmacokinetic model capturing distinct elimination profiles. Virtual patients were simulated under steady-state assumptions, then exposed to various adherence scenarios. A modified Metropolis-Hastings algorithm jointly estimated individual pharmacokinetic parameters and dosing patterns by analyzing simulated drug and metabolite concentrations. The probability of taking 0, 1, or 2 tablets per day was inferred, and a posterior adherence probability was derived from the posterior distribution to quantify adherence likelihood. A receiver operating characteristic analysis was used to evaluate diagnostic performance. The combined use of parent and metabolite improved non-adherence detection compared with either alone, particularly for recent missed doses. Trough concentrations outperformed peak concentrations, especially when patients did not compensate with extra doses. This probabilistic bi-analyte approach enhances non-adherence detection and is adaptable to other pharmacokinetic settings where distinct profiles and low model variability are present.
To evaluate the short- and mid-term volume reduction rate(VRR) after percutaneous ethanol injection(PEI), at 1,3 and 6 months, in patients with cystic or predominantly cystic thyroid nodules(CNs/pCNs, respectively), conducting a systematic review and meta-analysis of published data on VRR outcomes across these intervals. A systematic search of articles published up to October 30,2025 identified studies reporting PEI treatment for CNs/pCNs.Characteristics of the study design, CNs/pCNs cohorts, and outcomes of interest(VRR at 1,3 and 6 months of follow up)were extracted.Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I2 statistic, and meta-regression and subgroup analyses to explore potential sources of heterogeneity. Six studies comprising 431 CNs/pCNs were included.The pooled VRRs at 1,3 and 6 months post-PEI were 85.18%(95% CI: 80.72-89.64),91.50%(95% CI: 88.88-94.12) and 93.11%(95% CI: 90.91-95.31),respectively. Stratifying by nodule cystic composition, the VRR at consecutive follow-up time points was significantly different between the 1- and 3-month intervals in both subgroups [CN: VRRs at 1, 3 and 6 months were 91.16% (88.38-93.93), 95.69% (94.16-97.22) and 96.02% (94.16-97.87), respectively; pCN: VRRs at 1,3 and 6 months were respectively 80.19% (77.04-83.33), 87.08% (84.95-89.2) and 90.01%(88.83-91.19)].A secondary meta-regression analysis with baseline mean volume as covariate demonstrated a significant inverse association with VRR at 1 and 3 months in pCN(p = 0.02). By providing pooled VRRs for the short- and mid-term follow-up, this meta-analysis should be regarded as an initial step, paving the way for larger, high-quality studies aimed at standardizing the PEI procedure and supporting its incorporation into future dedicated guidelines.
Hip fracture is common among older adults and is associated with considerable morbidity and mortality; it is nearly twice as common in those with dementia, who may also experience worse postfracture outcomes. Time spent at home is an important quality-of-life indicator, but this outcome has not been previously examined following hip fracture in older adults with and without dementia. To compare days at home and survival for the year after hip fracture among older adults with and without dementia and to identify factors associated with fewer days at home among those with dementia. This longitudinal cohort study used national administrative data from 100% of Medicare beneficiaries from 2012 to 2021 to identify community-dwelling older adults (aged ≥65 years) with and without dementia hospitalized for a hip fracture. Data were analyzed from January 1, 2012, to December 31, 2021. Hip fracture hospitalization. Days at home and survival at 30 days, 6 months, and 1 year after hip fracture. Among 1 756 388 Medicare beneficiaries hospitalized for hip fracture, the mean [SD] age was 82.5 [8.1] years, 1 237 193 (70.4%) were female, 65 889 [3.8%] were Black or African American, 93 362 [5.3%] were Hispanic, 1 547 090 [88.1%] were non-Hispanic White, and 513 698 (29.2%) had dementia. In the year following hip fracture, older adults with dementia died 50.3 days earlier than those without dementia (adjusted mean [SD] days, 264.6 [143.2] vs 314.9 [107.3]). Those with dementia who survived 1 year after fracture had 53.9 fewer days at home compared with those without dementia (adjusted mean [SD] days, 263.8 [129.5] vs 317.7 [72.9]) due to more time in skilled nursing (adjusted mean [SD] days, 38.2 [55.8] vs 24.2 [37.4]) and long-term care facilities (adjusted mean [SD] days, 52.5 [111.5] vs 12.4 [53.7]). Findings were similar at 1 and 6 months. Among individuals with dementia, Medicaid eligibility, rural residence, geographic region, and being aged 85 years or older were associated with the fewest days at home at 1 year. In this cohort study, older adults with dementia had shortened survival and more time in skilled nursing or long-term care facilities after hip fracture than those without dementia. Differences in days at home were associated with structural and socioeconomic factors among those with dementia, with implications for health system policy, prognostic counseling, and discussions about long-term care needs in this population.
Treatment of opioid use disorder (OUD) with buprenorphine reduces overdose and all-cause mortality, yet access and retention remain limited. Much of the literature describing barriers to buprenorphine access and retention has focused on practitioner-level or patient-level barriers, but less is known about how potential policy and payment levers may influence prescribing behaviors and treatment practices from the practitioner perspective. To explore perspectives among OUD treatment program clinicians and staff about how broader policy and payment structures influence adoption of buprenorphine treatment and low-barrier care practices that promote access and retention. In this qualitative study, semistructured interviews were conducted from December 2022 to July 2023. Participants included clinicians and staff from a range of outpatient treatment programs providing buprenorphine in Philadelphia, Pennsylvania. Interviews examined prescribing practices and the influence of policy, payment structures, and regulatory requirements on clinical care. Transcripts were analyzed using thematic content analysis. A total of 28 practitioners and staff (13 men [46%]; 11 [39%] aged 41-50 years), including medical clinicians, therapists, and other administrative staff, were interviewed. Participants included 17 physicians (61%), 7 therapists (25%), 1 advanced practice practitioner (4%), 1 administrator (4%), and 2 other staff (8%). Twenty-four participants (86%) had at least 5 years of experience treating OUD, and all clinicians had obtained a DATA-2000 waiver, also called an X-waiver, to prescribe buprenorphine. Participants viewed the X-waiver as a symbolic barrier, but identified policy factors like insurance coverage, reimbursement rates, payer policies, and licensure requirements as key variables influencing clinical practice. Clinics relied on supplemental funding to sustain care for uninsured patients. Participants reported that payer-imposed requirements, such as prior authorizations and rigid attendance-based reimbursement, undermined timely access and individualized care and that regulatory frameworks often conflicted with harm reduction principles and created staffing and documentation burdens. This qualitative study of clinicians and staff in buprenorphine treatment programs found that broader policy and payment reforms could help support low-barrier buprenorphine treatment. Enhancing reimbursement, reducing administrative burdens, and aligning licensure and payer policies with evidence-based practices may improve access and retention. These findings offer actionable insights for policymakers, payers, and health systems seeking to address persistent gaps in OUD treatment.
The chiral-induced spin selectivity (CISS) effect offers a novel paradigm for designing high-performance catalysts for spin-dependent oxygen evolution reactions (OER). Layered double hydroxides (LDHs), are widely used for oxygen evolution reaction (OER) due to their superior electrocatalytic activity and stability in alkaline environments. Here, we demonstrate that intercalating chiral phenylalanine molecules into CoFe-LDH induces spin-polarized OER via the CISS effect, while simultaneously expanding the interlayer spacing. The resulting chiral-inorganic hybrid interface directs the reaction along a lower-energy pathway, promoting the formation of triplet O2, and exhibits outstanding OER performance with a lower overpotential of 245 mV at 10 mA cm-2, as well as faster charge-transfer kinetics compared to its achiral counterpart. Using in situ XANES, in situ Raman spectroscopy, and nanoscale scanning electrochemical cell microscopy (SECCM), we further uncover the fundamental origin of this chiral-induced spin-selective behavior. This study establishes a general strategy for designing advanced, stable oxide-based electrocatalysts, where intercalated chiral molecules manipulate spin dynamics to improve reaction kinetics and selectivity.
The development of microbial communities within granular-activated carbon (GAC) transforms it into a highly effective biofilter, integrating adsorption and biodegradation processes for contaminant removal. This study evaluated the performance of an O3-biological-activated carbon (BAC)-O3 system for removal of inorganic contaminants and secondary effluents disinfection. The BAC column was packed with 50 cm of commercial GAC, reaching biological stability after approximately 45 days of operation. System efficiency was assessed based on the removal of sodium (Na), calcium (Ca), magnesium (Mg), chloride (Cl-), and boron (B). A central composite design (CCD) was employed to the treatment process, generating mathematical models, statistically validated, to determine optimal treatment conditions, leading to the selection of an O3 dosage of 4 mg L-1 before and after the BAC stage. The system effectiveness was further tested through the removal of nine metals and microbial disinfection. Results confirmed that the O3-BAC process efficiently removed inorganic contaminants, while the additional post-BAC ozonation step was essential for achieving effluent disinfection. The final treated effluent achieved quality standards suitable for non-potable restricted reuse, and its successful application in hydroponic lettuce cultivation demonstrates a promising avenue for sustainable water reuse in controlled agricultural environments.
Collagen remodeling is an emerging hallmark of breast cancer progression, offering profound insights into tumor biology and therapeutic vulnerability. While breast cancer has long been understood through the lens of genetic mutations and cellular deregulation, recent advances have emphasized the crucial role of the tumor microenvironment (TME), particularly the extracellular matrix (ECM), in directing cancer progression. As the most prevalent structural protein within the ECM, collagen plays a key role in tissue mechanics, cell signaling, and immune regulation. This review examines the current understanding of the molecular configuration and diversity of collagen types found in breast tissue, with an emphasis on the pathological alterations that occur during malignant transformation. We explore how enzymes, such as matrix metalloproteinases (MMPs) and lysyl oxidase (LOX), regulate collagen degradation and crosslinking. These processes drive ECM stiffening and the formation of aligned collagen fibers, which promote tumor invasion, angiogenesis, and immune evasion. This article also highlights tumor-associated collagen signatures (TACS) as potential diagnostic biomarkers and evaluates advanced imaging modalities, including techniques like second harmonic generation (SHG) microscopy and magnetic resonance elastography (MRE), which enable in vivo assessment of collagen remodeling. Furthermore, we review therapeutic approaches targeting collagen-modifying enzymes and emerging nanoparticle-based delivery systems designed to disrupt the fibrotic ECM and improve drug penetration. Ultimately, collagen is now recognized not merely as a structural scaffold, but as an influential factor actively involved in the progression of breast cancer. Understanding the mechanisms and clinical implications of collagen remodeling may open novel paths for personalized diagnostics and targeted therapies, offering new hope for the management of aggressive and treatment-resistant breast cancers.
Helicobacter pylori (H. pylori) is a globally prevalent gastric pathogen whose increasing antimicrobial resistance has reduced the efficacy of conventional eradication regimens. Bacteriophages and phage-derived products have therefore attracted growing interest as alternative antimicrobial strategies against H. pylori. However, progress in this field remains constrained by the limited availability of cultivated phages, the underexplored reservoir of prophages and uncultivated phages, narrow host range, and poor stability under gastric conditions. In this review, we summarize the current landscape of H. pylori phage research, including both virulent and temperate phages, and discuss how genome-based mining is expanding access to previously inaccessible phage resources. We further examine recent application-oriented advances, including artificial intelligence-assisted endolysin discovery, receptor-binding protein engineering for host-range expansion, and targeted delivery platforms designed to improve phage stability and site-specific activity in the stomach. Finally, we highlight key translational barriers, including biosafety evaluation, functional validation, and in vivo efficacy. Together, these advances provide a framework for evaluating phage-based and phage-derived antimicrobial strategies for H. pylori control, while highlighting the need for rigorous functional validation, biosafety assessment, and in vivo efficacy testing.
Nursing students experience high levels of anxiety and burnout, which can impact academic performance and patient care. This study evaluated the efficacy of a 15-minute media-based music therapy (MBMT) intervention using a single-group crossover design. Seventy-three prelicensure BSN students participated. MBMT significantly reduced anxiety (p < .001, d = 0.65) and burnout (p < .001, d = 0.43) while improving instructor-rated simulation performance (p = .041, d = 0.25). Findings support MBMT as a promising intervention to mitigate stress and enhance clinical training outcomes in nursing education. Future research should explore broader applications and alternative music therapy techniques.
To evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol (PB-TURSO) and its components in slowing disease progression and improving survival in patients with amyotrophic lateral sclerosis (ALS). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies comparing PB-TURSO or its components to placebo or standard of care in adults with ALS were included. The primary outcomes were functional decline (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R]) and survival. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. A random-effects model was used for the meta-analysis, and a narrative synthesis was conducted for Tauroursodeoxycholic Acid (TUDCA) monotherapy and secondary analyses from the CENTAUR trial. Two RCTs (n = 801) were included in the meta-analysis. The pooled analysis demonstrated no statistically significant difference in either ALSFRS-R decline (mean difference [MD] 1.51, 95% confidence interval [CI] -1.01 to 4.02; P = 0.24; I² =71%) or survival (hazard ratio [HR] 0.90, 95% CI 0.73-1.11; P = 0.31; I² = 61%). A separate trial of TUDCA monotherapy ( n = 34) demonstrated significant functional benefits. Post hoc analyses of the CENTAUR trial reported a survival benefit of 6.5-10.6 months and delayed progression to major disease milestones. Biomarker analyses suggested anti-inflammatory effects. The risk of bias was moderate to high, and the certainty of evidence was rated very low by GRADE. Based on very low certainty evidence, the available RCT data do not support a definitive conclusion regarding the efficacy of PB-TURSO in ALS. Post hoc exploratory analyses suggest a potential survival benefit, which requires confirmation in adequately powered, prospectively designed trials; current results are hypothesis-generating rather than practice-defining.
Operating rooms are responsible for a substantial share of hospital waste, with laparoscopic procedures being particularly resource-intensive due to their reliance on disposable instruments. In a laparoscopic cholecystectomy (LC), disposable products account for approximately 40% of emissions, with trocars being key contributors. Reusable trocars lower environmental impact and evidence suggests that costs can be reduced. Accordingly, this study compares the costs of reusable versus disposable trocars during LC in a Dutch academic hospital and develops an adaptable framework for cost evaluation in other healthcare settings. An activity-based costing analysis was conducted to estimate the per-procedure costs (i.e. per LC), including the costs for acquisition, sterilisation, storage, and waste disposal. This was based on an LC using four trocars: two 5 mm and two 12 mm trocars. Resource use was based on expert input, and unit costs were obtained from hospital procurement data. The costing framework was designed to be adaptable to different institutional contexts. Uncertainty in the cost difference was assessed using probabilistic sensitivity analysis with 1000 Monte Carlo simulations, alongside one-way, two-way, and scenario analyses. Acquisition costs per LC were substantially lower for reusable trocars (€8.15) than for disposable trocars (€89.55). Although reusable trocars incurred sterilisation costs (€13.31 per procedure), total costs, including all activities involved in LC, remained lower (€683.00 vs €751.43), resulting in savings of €68.80 per procedure. Reusable trocars were cost-saving in all sensitivity analyses. Estimated annual savings were €10,264 at institutional level (based on 150 procedures) and €1.54 million nationally (based on 22,500 procedures). Reusable trocars are cost-saving compared to disposable trocars in LC. The adaptable activity-based costing framework developed in this study enables healthcare institutions to evaluate the economic impact of reusable versus disposable surgical instruments within their own settings, supporting both cost reduction and environmental sustainability.
Group interpersonal psychotherapy (IPT-G) is effective across diverse populations and adaptable to low-resource settings. To assess whether shortened 4-session mini IPT-G vs full IPT-G delivered by lay health care workers reduces depression and improves family functioning among perinatal adolescents. This pilot randomized clinical trial of group IPT for depression used a 3-arm longitudinal type 1 implementation-effectiveness design between May 13, 2022, and April 1, 2024, at 2 primary care maternal and child health clinics in Nairobi, Kenya. The study applied a collaborative care approach within the World Health Organization (WHO) Mental Health Gap Action Programme framework for training a nonspecialist workforce, where trained nurses screened participants and supervised group sessions delivered by community health promoters collaboratively with psychologists. Participants included perinatal adolescents, aged 13 to 18 years, in their first to second trimester of pregnancy. Participants were randomized to treatment as usual (TAU [n = 44]), mini IPT-G (n = 38), or full IPT-G (n = 40). TAU involved information sheets; mini IPT-G was culturally adapted; and full IPT-G followed the WHO protocol. Primary outcomes included depression measured by the 9-item Patient Health Questionnaire (PHQ-9) and functional impairment within 1 week post intervention and at 6-month follow-up. Secondary outcomes were posttraumatic stress disorder, psychological distress, disability, and self-efficacy. Linear mixed models were used to evaluate the preliminary effectiveness of the interventions. Among the 122 adolescents included in the analysis (median age, 17 [IQR, 17-18] years), 97 (79.5%) were single, and 91 (74.6%) had at least a secondary education level. Retention included 101 participants (82.8%) at 1 week post intervention and 91 (74.6%) at 6-month follow-up. Both IPT arms demonstrated significantly greater reductions in depression than the TAU arm post intervention. Mean (SD) PHQ-9 score decreased from 12.38 (5.90) at baseline to 2.15 (1.94) in the full IPT-G arm (β vs TAU = -5.79; 95% CI, -7.67 to -3.91; P < .001), from 11.58 (4.93) to 3.94 (2.81) in the mini IPT-G arm (β vs TAU = -3.97; 95% CI -5.83 to -2.10; P < .001), and from 11.00 (4.97) to 7.94 (3.71) in the TAU arm. At 6 months, effects were attenuated. Scores in the full IPT-G arm remained significantly lower than in the TAU arm (β = -2.22; 95% CI, -4.25 to -0.18; P = .03) but not in the mini IPT-G arm (β = -1.38; 95% CI, -3.25 to 0.48; P = .15). In this trial, IPT-G delivered by nonspecialists was feasible, acceptable, and effective. Mini IPT-G improved completion rates, while full IPT-G showed more sustained benefits at follow-up. These findings support task-sharing of mental health interventions for perinatal adolescents in low-resource settings. Pan African Clinical Trial Registry Identification: PACTR202501888041900.
Postoperative recovery for patients with oral cancer is an arduous process, relying heavily on the involvement of caregivers, who often lack formal training or support. To address this gap, we developed the Cancer Caregiver Support System (CCSS)-a low-cost, mobile-accessible platform designed to empower caregivers with culturally tailored guidance. A randomized pilot study was conducted at Homi Bhabha Cancer Hospital and Research Centre (HBCH & RC), (Unit of Tata Memorial Centre, Mumbai) Muzaffarpur, by enrolling 75 postoperative oral cancer patients and their primary caregivers. Participants were randomized into two arms: Arm A received standard care plus the CCSS intervention (A Hindi-language website, printed recovery booklet, and moderated WhatsApp group); Arm B received standard care alone. Primary endpoints included 30-day morbidity and duration of nasogastric tube (NGT) dependency. Secondary endpoints included caregiver burden using the Zarit Burden Interview (ZBI) and swallowing outcomes as measured by Functional Oral Intake Scale (FOIS) scores. Tertiary endpoints included unscheduled follow-ups and readmissions. While 30-day morbidity, delay in NGT weaning, and FOIS scores were comparable across arms, caregivers in the intervention arm reported significantly lower burden (mean ZBI score: 12.26 vs 17.53; P = 0.021) and fewer unplanned follow-ups (mean: 1.23 vs 2.64; P < 0.001). Readmission rates remained low in both groups. The CCSS intervention demonstrated feasibility and acceptability, with early signals of benefit in reducing caregiver strain and postdischarge disruptions. This pilot study underscores the potential of context-sensitive, digitally enabled caregiver support in resource-constrained oncology settings. Further scale-up and integration with AI-driven personalization are planned.
Urban river restoration requires understanding water-ecosystem coupling. This study investigated microhabitat construction effects across five Beijing river basins and a demonstration site. At 47 basin-wide monitoring sites (2024-2025), BOD5 and CODmn decreased (p < 0.01), while phytoplankton increased (p < 0.001), reflecting persistent eutrophication. TN was the strongest predictor of biodiversity (r = -0.773, p < 0.0001). PCA showed PC1 and PC2 explained 73.88% of total variance (PC1: 40.24%, PC2: 33.64%). At the Jinghe River demonstration site, integrated restoration was associated with 80.5% phytoplankton reduction (t = -4.690, p = 0.0001), transparency improved from 40-50 cm to 70-100 cm, and submerged vegetation exceeded 40%. Due to the observational design without control sites, causal attribution cannot be established; the results demonstrate associations between integrated restoration (∼200 yuan/m2) and improved ecological conditions, offering a cost-effective nature-based solution for water-scarce megacities.
To investigate whether muscle strength changes observed in randomised controlled trials involving people with patellofemoral pain (PFP) are associated with concurrent changes in pain and physical function. Systematic review with meta-analysis, applying a two-stage structural equation modelling approach with random-effects estimation. Randomised clinical trials assessing non-surgical and non-pharmacological interventions that reported both muscle strength and at least one clinical outcome (pain or function) in people with PFP. CINAHL, Cochrane Library, Embase, Medline and SPORTDiscus were searched from inception to April 2026. From 16,750 records screened, 82 trials met the eligibility criteria (4023 participants). Regarding self-reported pain outcomes, low to moderate evidence certainty indicated significant associations between strength improvements and pain reduction for knee extensors (r =  - 0.75, β =  - 0.21), knee flexors (r =  - 0.46, β =  - 0.14), hip abductors (r =  - 0.91, β =  - 0.31), hip adductors (r =  - 0.26, β =  - 0.19), hip external rotators (r =  - 0.24, β =  - 0.06), hip internal rotators (r =  - 0.79, β =  - 0.31) and hip extensors (r =  - 0.58, β =  - 0.26). Regarding self-reported function, low to high evidence certainty indicated that strength improvements in knee extensors (r = 0.70, β = 0.15), knee flexors (r = 0.46, β = 0.07), hip abductors (r = 0.94, β = 0.15), hip adductors (r = 0.55, β = 0.11), and hip internal rotators (r = 0.98, β = 0.06) were significantly associated with improved function. This review provides evidence that improvements in lower limb muscle strength are associated with improvements in pain and physical function among people with PFP. These findings reinforce the clinical relevance of strength-focused rehabilitation, particularly targeting the knee and hip muscles. CRD42023420875.
This study evaluated 68 third-year veterinary students' subjective and objective stress level changes at baseline (laboratory orientation session), prior to (pre-task), and following (post-task) a laboratory-simulated ovariohysterectomy (OVH) using a surgical simulation trainer. Using a pre-post experimental design, salivary alpha amylase (sAA) and cortisol (sC) samples were evaluated as markers of the students' physiologic stress response over three time points. NASA task load index (NASA-TLX) scores were correlated to salivary biomarker results. There was no association for change in salivary biomarkers accounting for age, gender, or NASA-TLX scores. However, stress levels did change based on sampling timing compared with performing the simulated OVH. sAA levels were lowest at baseline and increased post-task (p < 0.050). sC levels were highest at baseline and decreased pre-task (p < 0.016) and post-task (p < 0.001). sC levels were highest at baseline (average 77th percentile) and decreased pre-task (average 71st percentile) and post-task (average 52nd percentile). Veterinary students performing a simulated OVH demonstrated high baseline levels of subjective and objective stress. However, sC levels decreased significantly following the simulated OVH, and sAA levels followed a normal circadian rhythm following OVH completion. These findings suggested that students with adequate resources, such as a strong surgical skills foundation, can assess a surgical task as a challenge, which can result in learning. Further evaluation of implementation of surgical simulation trainers and investigation into the role of stress on performance is indicated to support this group of learners.
In emergency trauma care, artificial intelligence (AI) may aid fracture detection on radiographs, potentially reducing radiologists' workload. We evaluated the role of deep learning-based decision-support software in the reporting of trauma cases. We retrospectively analyzed 2317 trauma radiographs acquired at a single center: 1,174 images obtained from November 1 to 16, 2023, without access to the AI tool during reporting, and 1,143 images from February 1 to 13, 2024, with discretionary use of the AI output during reporting. The AI software output was compared with final radiology reports, with ground truth established by a musculoskeletal radiologist with 9 years' experience. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at both the fracture and patient levels. The dataset included 1,914 patients with 1,188 acute fractures (621 in November, 567 in February). At the fracture level, standalone AI achieved 90.7% accuracy, 87.8% sensitivity, 94.0% specificity, 94.3% PPV, and 87.2% NPV in November, 94.1%, 93.5%, 94.6%, 94.5%, and 93.6% in February, respectively. Non-AI-assisted radiologists reached 92.4%, 89.0%, 96.2%, 96.3%, and 88.7%, AI-assisted radiologists 93.4%, 90.0%, 96.7%, 96.4%, and 90.7%, respectively. At the patient level, AI's overall performance reached up to 96.5% accuracy and 95.6% sensitivity. Discrepancies between AI and radiologists occurred in 326 cases, often related to anatomical variants such as accessory ossicles. Standalone AI demonstrated near-expert accuracy and sensitivity in fracture detection at both fracture and patient levels. PPV increased with AI support, indicating more accurate detection of actual fractures. By examining discretionary real-world use of AI in trauma radiography, this study shows that clinical benefit is not guaranteed by algorithmic performance alone, as optional AI integration does not consistently improve radiologist sensitivity, underscoring a critical implementation gap in practice. Standalone AI achieves near-expert fracture detection performance in trauma radiography. Discretionary AI use does not consistently improve radiologist sensitivity. AI use reduces discrepancies, suggesting improved diagnostic consistency. Clinical benefit of AI depends on real-world implementation strategy.
Implanted microelectrodes offer a direct method for electrically interfacing with individual neurons in vivo. A major challenge preventing long-term deployment of such interfaces is the degradation of recording quality over time. This is especially evident when targeting deep brain structures, as surgical access is challenging and invasive, and depth probes are subjected to elevated levels of micro-motion. To address these challenges, miniaturization and biomimetic softness are emerging as effective strategies to improve stability and biointegration of neural implants. Here, we propose a penetrating probe design that couples the miniaturization, contact density, and manufacturability of microfabricated electrode arrays on flexible polyimide, with a micrometric soft-shell encapsulation. The latter leverages a zwitterionic hydrogel coating to achieve tissue-level mechanics and an anti-fouling surface. We design, develop, and validate a surgical insertion strategy and the associated tooling, enabling implantation of soft depth probes in the gigantocellular (Gi) nucleus of a rat model. We show stable, high signal-to-noise ratio neurophysiological recordings for at least 8 weeks. We further demonstrate a multimodal system to study the cortico-brainstem circuitry in transgenic mice using optogenetic cortical neuromodulation coupled to brainstem electrophysiology. Our results demonstrate that hybrid soft-flex microfabrication technology can increase the longevity and the quality of chronic neural recordings in hard-to-reach deep neural circuits.
Glioblastoma multiforme (GBM) remains an aggressive brain malignancy with dismal prognosis despite current standard-of-care therapies. The gastrin-releasing peptide receptor (GRPR) is overexpressed in gliomas and represents a potential therapeutic target. However, systemic radionuclide delivery is limited by poor tumor penetration and off-target toxicity. GRPR expression and prognostic relevance were analyzed using Chinese Glioma Genome Atlas and a clinical-trial dataset, respectively at the transcriptomic and protein levels. [177Lu]Lu-RM26, a lutetium-177-labeled GRPR-targeting antagonist, was evaluated in vitro, and administered intratumorally via convection-enhanced delivery in an orthotopic GL261Fluc+ glioblastoma model. Pharmacokinetic characteristics, including tumor retention and biodistribution, were evaluated by serial single-photon emission computed tomography and gamma-counting. Efficacy was assessed by tumor volume, bioluminescence signal, and overall survival. Safety was evaluated through body weight monitoring, neurological scoring, rotarod testing, hematology, and immunohistochemical staining. Mechanistic insights were obtained via bulk RNA-sequencing and Western blotting. Higher GRPR expression correlated with poorer-prognosis glioma subtypes and reduced survival. In vitro assays showed dose-dependent inhibition of GL261Fluc+ cell viability, proliferation, and invasion. Locoregional [177Lu]Lu-RM26 administration led to prolonged tumor retention (74.7 h), high absorbed dose (2.71 × 106 mGy·MBq- 1), and minimal off-target uptake. Treated mice exhibited marked tumor growth inhibition, reduced bioluminescence signal, and extended survival compared to controls. No significant short-term systemic toxicity or neurological impairment was observed. Transcriptome and Western blotting findings were consistent with DNA replication stalling and G2/M arrest. Locoregional [177Lu]Lu-RM26 therapy enables sustained, tumor-specific β-radiation with minimal systemic exposure, representing a promising locoregional strategy for GRPR-positive GBM.