Artificial Intelligence vs. Doctors: Diagnosing Necrotizing Enterocolitis on Abdominal Radiographs.

BACKGROUND: Radiographic diagnosis of necrotizing enterocolitis (NEC) is challenging. Deep learning models may improve accuracy by recognizing subtle imaging patterns. We hypothesized it would perform with comparable accuracy to that of senior surgical residents. METHODS: This cohort study compiled 494 anteroposterior neonatal abdominal radiographs (214 images NEC, 280 other) and randomly divided them into training, validation, and test sets. Transfer learning was utilized to fine-tune a ResNet-50 deep convolutional neural network (DCNN) pre-trained on ImageNet. Gradient-weighted Class Activation Mapping (Grad-CAM) heatmaps visualized image regions of greatest relevance to the pretrained neural network. Senior surgery residents at a single institution examined the test set. Resident and DCNN ability to identify pneumatosis on radiographic images were measured via area under the receiver operating curves (AUROC) and compared using DeLong's method. RESULTS: The pretrained neural network achieved AUROC of 0.918 (95% CI, 0.837-0.978) with an accuracy of 87.8% with five false negative and one false positive prediction. Heatmaps confirmed appropriate image region emphasis by the pretrained neural network. Senior surgical residents had a median area under the receiver operating curve of 0.896, ranging from 0.778 (95% CI 0.615-0.941) to 0.991 (95% CI 0.971-0.999) with zero to five false negatives and one to eleven false positive predictions. The deep convolutional neural network performed comparably to each surgical resident's performance (p > 0.05 for all comparisons). CONCLUSIONS: A deep convolutional neural network trained to recognize pneumatosis can quickly and accurately assist clinicians in promptly identifying NEC in clinical practice. LEVEL OF EVIDENCE: III (study type: Study of Diagnostic Test, study of nonconsecutive patients without a universally applied "gold standard").

Burnout in Graduate Medical Education: Uncovering Resident Burnout Profiles Using Cluster Analysis.

Background: Burnout is common among residents and negatively impacts patient care and professional development. Residents vary in terms of their experience of burnout. Our objective was to employ cluster analysis, a statistical method of separating participants into discrete groups based on response patterns, to uncover resident burnout profiles using the exhaustion and engagement sub-scales of the Oldenburg Burnout Inventory (OLBI) in a cross-sectional, multispecialty survey of United States medical residents. Methods: The 2017 ACGME resident survey provided residents with an optional, anonymous addendum containing 3 engagement and 3 exhaustion items from the OBLI, a 2-item depression screen (PHQ-2), general queries about health and satisfaction, and whether respondents would still choose medicine as a career. Gaussian finite mixture models were fit to exhaustion and disengagement scores, with the resultant clusters compared across PHQ-2 depression screen results. Other variables were used to demonstrate evidence for the validity and utility of this approach. Results: From 14 088 responses, 4 clusters were identified as statistically and theoretically distinct: Highly Engaged (25.8% of respondents), Engaged (55.2%), Disengaged (9.4%), and Highly Exhausted (9.5%). Only 2% of Highly Engaged respondents screened positive for depression, compared with 8% of Engaged respondents, 29% of Disengaged respondents, and 53% of Highly Exhausted respondents. Similar patterns emerged for the general query about health, satisfaction, and whether respondents would choose medicine as a career again. Conclusion: Clustering based on exhaustion and disengagement scores differentiated residents into 4 meaningful groups. Interventions that mitigate resident burnout should account for differences among clusters.

Antibiotic dip and irrigation solutions confer increased antimicrobial efficacy of inflatable penile prosthesis hydrophilic surfaces compared with 0.05% chlorhexidine gluconate.

BACKGROUND: Chlorhexidine gluconate (CHG) (0.05%) has recently been suggested as both a dip for the hydrophilic surface and an irrigation solution in the setting of penile prosthesis (PP) surgery. AIM: The study sought to compare the antimicrobial efficacy of 0.05% CHG with vancomycin and gentamicin (VG) antibiotics as dip and/or irrigation solutions in the setting of a hydrophilic PP surface in vitro. METHODS: Sterile PPs with a hydrophilic coating were obtained. A series of experiments were performed to evaluate the efficacy of normal saline (NS), 0.05% CHG, or VG as dip and/or irrigation solutions to reduce methicillin-sensitive Staphylococcus aureus adhesion to PP surfaces. The 8-mm discs from PPs were incubated in 105 colony-forming units/mL of methicillin-sensitive S aureus for 48 hours, plated, and counted. Disc-diffusion tests were conducted by suspending 6-mm discs for 2 minutes in NS, 0.05% CHG, or VG, then placing them coated side down onto plates streaked with the following organisms: methicillin-sensitive S aureus, S epidermidis, Enterococcus, and Escherichia coli. After 24 hours of growth, zones of inhibition were measured. OUTCOMES: We found average bacterial counts (colony-forming units/mL) and zones of inhibition (mm) following a series of treatment protocols of PP discs. RESULTS: PP discs dipped in VG reduced bacterial adhesion to the implant surface >0.05% CHG (~5.5 log vs ~1.5 log; P < .01). Discs irrigated with either 0.05% CHG or NS removed all dip solution adsorbed to the hydrophilic surface, allowing bacterial growth. VG irrigation adsorbed to the hydrophilic surface even after 0.05% CHG or NS dips, reducing bacterial adherence (~3 log). Dipping and irrigating discs with VG was most effective in reducing adherent bacteria (~5.5 log) and was the only irrigation that showed antimicrobial activity. CLINICAL TRANSLATION: VG, when used both as a prophylactic dip and as an intraoperative irrigation solution for hydrophilic penile implant surfaces, has improved efficacy to 0.05% CHG and NS. STRENGTHS AND LIMITATIONS: This is the first study to compare the use of VG, 0.05% CHG, and NS as prophylactic dips and intraoperative irrigations for hydrophilic penile implant surfaces. Limitations include the use of in vitro studies, which serve as a proxy for in vivo practices and may not be entirely accurate nor translatable clinically. CONCLUSION: We demonstrated the superior efficacy of VG as a combined dip and irrigation solution for hydrophilic penile implant surfaces compared with 0.05% CHG.

Clinical characteristics and HLA associations of azithromycin-induced liver injury.

BACKGROUND: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. METHODS: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. RESULTS: Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). CONCLUSION: Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.

Outcomes of Surgical Treatment of Vaughan-Jackson Syndrome.

Background Vaughan-Jackson syndrome (VJS) is the attritional rupture of the extensor tendons secondary to arthritis or inflammation affecting the distal radioulnar joint. The surgical outcomes following Darrach's procedure and tendon transfers are not well described. The primary aim of this study was to report patient-reported functional outcome measures after surgery for VJS. Secondary aims were to report health-related quality-of-life scores, patient satisfaction, and complications Methods A single-center retrospective study was performed to identify patients who underwent surgical intervention for the management of VJS. Patient-reported outcomes were measured using the Patient-Rated Wrist and Hand Evaluation (PRWHE), Quick version of the Disability of the Arm, Shoulder, and Hand (QuickDASH), EuroQoL 5-dimensions 5-Likert (EQ-5D-5L), and calculation of the Net Promoter Score (NPS). Results We report postoperative patient-reported functional outcome measures for 12 cases of VJS treated with distal ulna excision and extensor tendon transfer. The mean age was 69 years (range: 45-87 years; standard deviation [SD]: 14.1), and eight patients were females. Five patients had rheumatoid arthritis, and there was one case each of seronegative polyarthritis, ankylosing spondylitis, and CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.) syndrome; the rest of the patients had osteoarthritis. At a mean of 53 months of follow-up, the mean PRWHE score was 34.5 (SD: 17.9), the mean QuickDASH score was 28.2 (SD: 18.6), and the mean EQ-5D-5L score was 0.71 (SD: 0.203). Ten patients were satisfied and the NPS was 42. Postoperatively eight patients had pain scores reported as none or mild, three as moderate, and one as severe. Two patients required further operations, both undergoing total wrist arthrodesis. Conclusion Although a degree of functional deficit persists after Darrach's procedure and tendon transfer for treatment of VJS, there are also high levels of patient satisfaction, a good NPS, and a low rate of operative reintervention. Level IV evidence.

Reaction Discovery Using Spectroscopic Insights from an Enzymatic C-H Amination Intermediate.

Engineered hemoproteins can selectively incorporate nitrogen from nitrene precursors like hydroxylamine, O-substituted hydroxylamines, and organic azides into organic molecules. Although iron-nitrenoids are often invoked as the reactive intermediates in these reactions, their innate reactivity and transient nature have made their characterization challenging. Here we characterize an iron-nitrosyl intermediate generated from NH2OH within a protoglobin active site that can undergo nitrogen-group transfer catalysis, using UV-vis, electron paramagnetic resonance (EPR) spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques. The mechanistic insights gained led to the discovery of aminating reagents─nitrite (NO2-), nitric oxide (NO), and nitroxyl (HNO)─that are new to both nature and synthetic chemistry. Based on the findings, we propose a catalytic cycle for C-H amination inspired by the nitrite reductase pathway. This study highlights the potential of engineered hemoproteins to access natural nitrogen sources for sustainable chemical synthesis and offers a new perspective on the use of biological nitrogen cycle intermediates in biocatalysis.

Sociodemographic biases in a commercial AI model for intracranial hemorrhage detection.

PURPOSE: To evaluate whether a commercial AI tool for intracranial hemorrhage (ICH) detection on head CT exhibited sociodemographic biases. METHODS: Our retrospective study reviewed 9736 consecutive, adult non-contrast head CT scans performed between November 2021 and February 2022 in a single healthcare system. Each CT scan was evaluated by a commercial ICH AI tool and a board-certified neuroradiologist; ground truth was defined as final radiologist determination of ICH presence/absence. After evaluating the AI tool's aggregate diagnostic performance, sub-analyses based on sociodemographic groups (age, sex, race, ethnicity, insurance status, and Area of Deprivation Index [ADI] scores) assessed for biases. χ2 test or Fisher's exact tests evaluated for statistical significance with p ≤ 0.05. RESULTS: Our patient population was 50% female (mean age 60 ± 19 years). The AI tool had an aggregate accuracy of 93% [9060/9736], sensitivity of 85% [1140/1338], specificity of 94% [7920/ 8398], positive predictive value (PPV) of 71% [1140/1618] and negative predictive value (NPV) of 98% [7920/8118]. Sociodemographic biases were identified, including lower PPV for patients who were females (67.3% [62,441/656] vs. 72.7% [699/962], p = 0.02), Black (66.7% [454/681] vs. 73.2% [686/937], p = 0.005), non-Hispanic/non-Latino (69.7% [1038/1490] vs. 95.4% [417/437]), p = 0.009), and who had Medicaid/Medicare (69.9% [754/1078]) or Private (66.5% [228/343]) primary insurance (p = 0.003). Lower sensitivity was seen for patients in the third quartile of national (78.8% [241/306], p = 0.001) and state ADI scores (79.0% [22/287], p = 0.001). CONCLUSIONS: In our healthcare system, a commercial AI tool had lower performance for ICH detection than previously reported and demonstrated several sociodemographic biases.

Early Childhood Screening Practices and Barriers: A National Survey of Primary Care Pediatricians.

BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics recommends screening during the first 3 years of life for developmental risk/delay, maternal depression, and social determinants of health (SDOH) using standardized tools. Adoption of these guidelines has been gradual, and barriers to screening are as varied as pediatric practices are themselves. METHODS: We analyzed 2019 American Academy of Pediatrics Periodic Survey data. The survey included pediatricians' screening practices for developmental delay, maternal depression, and SDOH, and barriers to screening. We used Cochran's Q and McNemar's tests to compare barriers across topics, and χ2 tests and multivariable logistic regression to examine the relationship between barriers and screening practices. RESULTS: The survey response rate was 46.9% (n = 688). Most pediatricians reported screening/surveilling for developmental delay (98.1%), maternal depression (83.2%), and SDOH (76.7%), but fewer used standardized instruments to do so (59.0%, 44.9%, 12.6%, respectively). Those not screening/only surveilling for maternal depression were more likely to report that screening is not an appropriate role for the pediatrician and difficulty prioritizing time. For SDOH, those not screening/only surveilling were more likely to report instruments not available in the electronic health record, lack of knowledge regarding referral options, and lack of treatment options for positive screens. CONCLUSIONS: Rates of standardized screening, and barriers pediatricians encounter, have important implications for improving quality of early childhood preventive care. Opportunities include expanding the primary care team and integrating screening tools into the electronic health record. Programs to support social needs and maternal mental health could be strengthened to ensure robust referral options are available.

Proteomic profiling improves prognostic risk stratification of the Sarculator nomogram in soft tissue sarcomas of the extremities and trunk wall.

BACKGROUND: High-risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by the Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline-based therapy compared to low/intermediate-risk patients. The biology underpinning these differential treatment outcomes remain unknown. METHODS: We analysed proteomic profiles and clinical outcomes of 123 eSTS patients. A Cox model for overall survival including the Sarculator was fitted to individual data to define four risk groups. A DNA replication protein signature-Sarcoma Proteomic Module 6 (SPM6) was evaluated for association with clinicopathological factors and risk groups. SPM6 was added as a covariate together with Sarculator in a multivariable Cox model to assess improvement in prognostic risk stratification. RESULTS: DNA replication and cell cycle proteins were upregulated in high-risk versus very low-risk patients. Evaluation of the functional effects of CRISPR-Cas9 gene knockdown of proteins enriched in high-risk patients using the cancer cell line encyclopaedia database identified candidate drug targets. SPM6 was significantly associated with tumour malignancy grade (p = 1.6e-06), histology (p = 1.4e-05) and risk groups (p = 2.6e-06). Cox model analysis showed that SPM6 substantially contributed to a better calibration of the Sarculator nomogram (Index of Prediction Accuracy = 0.109 for Sarculator alone versus 0.165 for Sarculator + SPM6). CONCLUSIONS: Risk stratification of patient with STS is defined by distinct biological pathways across a range of cancer hallmarks. Incorporation of SPM6 protein signature improves prognostic risk stratification of the Sarculator nomogram. This study highlights the utility of integrating protein signatures for the development of next-generation nomograms.

Addressing Confusion and Inconsistencies Surrounding the Provider Role in Medical Cannabis Programs.

ABSTRACT: More than 40 states in the United States have established medical Cannabis programs that authorize the use of Cannabis for specific medical conditions. Initially, these medical Cannabis programs aimed to offer compassionate care primarily for terminal or rare, untreatable conditions. However, the scope of these programs has broadened to include nonterminal and more common conditions, including various medical and mental disorders. This expansion introduces several health care challenges: a lack of robust research evidence for many listed conditions, a sense of unpreparedness among providers, and a disparity in provider roles, expectations, and responsibilities across different states, leading to potential confusion. To address these issues, medical organizations need to develop expert consensus or guidelines that underscore evidence-based shared decision-making and patient monitoring standards. Medical education should also include such training. Concurrently, medical providers must prioritize evidence-based treatment over public opinion, exercise clinical judgment, and take responsibility for their recommendations.

Advancing COVID-19 diagnostics: rapid detection of intact SARS-CoV-2 using viability RT-PCR assay.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Commonly used methods for both clinical diagnosis of SARS-CoV-2 infection and management of infected patients involve the detection of viral RNA, but the presence of infectious virus particles is unknown. Viability PCR (v-PCR) uses a photoreactive dye to bind non-infectious RNA, ideally resulting in the detection of RNA only from intact virions. This study aimed to develop and validate a rapid v-PCR assay for distinguishing intact and compromised SARS-CoV-2. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures with decreasing percentages of intact SARS-CoV-2 (from 100% to 0%) were prepared from SARS-CoV-2 virus stock and a clinical sample. Each sample was divided into a PMAxx-treated part and a non-PMAxx-treated part. Reverse transcription-PCR (RT-PCR) using an in-house developed SARS-CoV-2 viability assay was then applied to both sample sets. The difference in intact SARS-CoV-2 was determined by subtracting the cycle threshold (Ct) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of intact SARS-CoV-2 showed increasingly lower delta Ct values as the percentage of intact SARS-CoV-2 decreased, as expected. This relationship was observed in both high and low viral load samples prepared from cultured SARS-CoV-2 virus stock, as well as for a clinical sample prepared directly from a SARS-CoV-2 positive nasopharyngeal swab. In this study, a rapid v-PCR assay has been validated that can distinguish intact from compromised SARS-CoV-2. The presence of intact virus particles, as determined by v-PCR, may indicate SARS-CoV-2 infectiousness. IMPORTANCE: This study developed a novel method that can help determine whether someone who has been diagnosed with coronavirus disease 2019 (COVID-19) is still capable of spreading the virus to others. Current tests only detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, but cannot tell whether the particles are still intact and can thus infect cells. The researchers used a dye that selectively blocks the detection of damaged virions and free RNA. They showed that this viability PCR reliably distinguishes intact SARS-CoV-2 capable of infecting from damaged SARS-CoV-2 or free RNA in both cultured virus samples and a clinical sample. Being able to quickly assess contagiousness has important implications for contact tracing and safely ending isolation precautions. This viability PCR technique provides a simple way to obtain valuable information, beyond just positive or negative test results, about the actual risk someone poses of transmitting SARS-CoV-2 through the air or surfaces they come into contact with.

Knowledge, Attitudes, and Behaviors Regarding Pneumococcal Vaccines in Adults 65 Years and Older in Primary Care in Wisconsin.

INTRODUCTION: Although shared decision-making is highly valued, its implementation in clinical practice is suboptimal. Shared decision-making was included in the Centers for Disease Control and Prevention (CDC) recommendations for the pneumococcal conjugate vaccine 13 valent for older adults. As a first step to develop and test clinician educational resources to facilitate shared decision-making for pneumococcal vaccines for older adults, we completed a needs assessment to identify knowledge gaps, attitudes, and behaviors. METHODS: Primary care clinicians, pharmacists, and patient care staff completed a questionnaire on shared decision-making and pneumococcal vaccines. After the CDC recommended new pneumococcal vaccines and eliminated the role of shared decision-making, a revised questionnaire was distributed to additional clinicians in an effort to increase the sample size. RESULTS: Knowledge of pneumococcal vaccine recommendations was high among those who responded to knowledge questions (48 of 75 respondents). Although 96% of respondents believed shared decision-making for use of pneumococcal vaccines in adults 65 years or older was feasible, 25% responded that it would be "somewhat difficult" to explain potential harms and benefits of PCV13. DISCUSSION: Although shared decision-making was reported to be feasible, challenges implementing it are ongoing. Knowledge gaps regarding pneumococcal vaccines were observed, highlighting the need for ongoing medical education with changing vaccine recommendations.

Clinical Course of TGA After Arterial Switch Operation in the Current Era.

Background: The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era. Objectives: The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events. Methods: A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined. Results: At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2). Conclusions: TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.

Critical appraisal of total gastrectomy plus total colectomy with hyperthermic intraperitoneal chemotherapy as a treatment for advanced pseudomyxoma peritonei.

BACKGROUND: The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy. METHODS: We searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low-grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival. RESULTS: Thirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p < 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014). CONCLUSIONS: A 10-year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.

Quantification of Cinpanemab (BIIB054) Binding to α- Synuclein in Cerebrospinal Fluid of Phase 1 Single Ascending Dose Samples.

Through its pathological and genetic association to Parkinson's Disease (PD), α-synuclein (α-syn) remains a favorable therapeutic target that is being investigated using various modalities, including many passive immunotherapy approaches clinically targeting different forms of α-syn and epitopes. Whereas published studies from some immunotherapy trials have demonstrated engagement in plasma, none have shown direct drug-antigen interactions in the disease-relevant compartment, the central nervous system (CNS). Cinpanemab (BIIB054) selectively targets pathological aggregated α-syn with low affinity binding to monomeric forms. The avidity-driven binding, low drug concentration, and the very low α-syn levels plus its heterogeneous nature in cerebrospinal fluid (CSF) made it not possible to measure drug-target interactions by conventional assays. Here we overcame these challenges by using zero-length crosslinking to stabilize the BIIB054-α-syn complexes and then quantified the crosslinked complexes using a Meso Scale Discovery (MSD) electrochemiluminescence assay. CSF samples from healthy volunteers (HV, n=46) and individuals with PD (PD, n=18) from study 228HV101 (Phase I clinical trial of BIIB054), demonstrated dose- and time- dependent binding of cinpanemab to α-syn with measurable complexes detected at doses {greater than or equal to}15 mg/kg. Complex formation displayed a direct positive correlation to drug concentration (Spearman rank correlation = 0.8295 (HV), 0.8032 (PD) p < 0.0001 (HV, PD)). The observed binding of cinpanemab to α-syn in CSF is consistent with its low intrinsic affinity for α-syn monomer and provides evidence that the drug is behaving with expected binding dynamics in the central nervous system compartment. Significance Statement A zero-length cross-linking method with MSD detection was developed to enable quantification of cinpanemab-α-syn complexes in Phase 1 clinical CSF samples by preventing signal loss caused by their rapid dissociation. Observed dose- and time-dependent binding were consistent with cinpanemab's affinity for α-syn and provided confidence that the drug had engaged its target at the desired site of action. This is the first demonstration of α-syn binding by an antibody in clinical samples from the CNS.

ISLE: An Intelligent Streaming Framework for High-Throughput AI Inference in Medical Imaging.

As the adoption of artificial intelligence (AI) systems in radiology grows, the increase in demand for greater bandwidth and computational resources can lead to greater infrastructural costs for healthcare providers and AI vendors. To that end, we developed ISLE, an intelligent streaming framework to address inefficiencies in current imaging infrastructures. Our framework draws inspiration from video-on-demand platforms to intelligently stream medical images to AI vendors at an optimal resolution for inference from a single high-resolution copy using progressive encoding. We hypothesize that ISLE can dramatically reduce the bandwidth and computational requirements for AI inference, while increasing throughput (i.e., the number of scans processed by the AI system per second). We evaluate our framework by streaming chest X-rays for classification and abdomen CT scans for liver and spleen segmentation and comparing them with the original versions of each dataset. For classification, our results show that ISLE reduced data transmission and decoding time by at least 92% and 88%, respectively, while increasing throughput by more than 3.72 × . For both segmentation tasks, ISLE reduced data transmission and decoding time by at least 82% and 88%, respectively, while increasing throughput by more than 2.9 × . In all three tasks, the ISLE streamed data had no impact on the AI system's diagnostic performance (all P > 0.05). Therefore, our results indicate that our framework can address inefficiencies in current imaging infrastructures by improving data and computational efficiency of AI deployments in the clinical environment without impacting clinical decision-making using AI systems.

Magnon-phonon Fermi resonance in antiferromagnetic CoF2.

Understanding spin-lattice interactions in antiferromagnets is a critical element of the fields of antiferromagnetic spintronics and magnonics. Recently, coherent nonlinear phonon dynamics mediated by a magnon state were discovered in an antiferromagnet. Here, we suggest that a strongly coupled two-magnon-one phonon state in this prototypical system opens a novel pathway to coherently control magnon-phonon dynamics. Utilizing intense narrow-band terahertz (THz) pulses and tunable magnetic fields up to µ0Hext = 7 T, we experimentally realize the conditions of magnon-phonon Fermi resonance in antiferromagnetic CoF2. These conditions imply that both the spin and the lattice anharmonicities harvest energy from the transfer between the subsystems if the magnon eigenfrequency fm is half the frequency of the phonon 2fm = fph. Performing THz pump-infrared probe spectroscopy in conjunction with simulations, we explore the coupled magnon-phonon dynamics in the vicinity of the Fermi-resonance and reveal the corresponding fingerprints of nonlinear interaction facilitating energy exchange between these subsystems.

The Intriguing World of Vascular Remodeling, Angiogenesis, and Arteriogenesis.

Vascular remodeling is a very general feature related to angiogenesis and arteriogenesis, which are involved in neovascularization processes [...].