Using YOLO v7 to Detect Kidney in Magnetic Resonance Imaging.

Introduction: This study explores the use of the latest You Only Look Once (YOLO V7) object detection method to enhance kidney detection in medical imaging by training and testing a modified YOLO V7 on medical image formats. Methods: Study includes 878 patients with various subtypes of renal cell carcinoma (RCC) and 206 patients with normal kidneys. A total of 5657 MRI scans for 1084 patients were retrieved. 326 patients with 1034 tumors recruited from a retrospective maintained database, and bounding boxes were drawn around their tumors. A primary model was trained on 80% of annotated cases, with 20% saved for testing (primary test set). The best primary model was then used to identify tumors in the remaining 861 patients and bounding box coordinates were generated on their scans using the model. Ten benchmark training sets were created with generated coordinates on not-segmented patients. The final model used to predict the kidney in the primary test set. We reported the positive predictive value (PPV), sensitivity, and mean average precision (mAP). Results: The primary training set showed an average PPV of 0.94 ± 0.01, sensitivity of 0.87 ± 0.04, and mAP of 0.91 ± 0.02. The best primary model yielded a PPV of 0.97, sensitivity of 0.92, and mAP of 0.95. The final model demonstrated an average PPV of 0.95 ± 0.03, sensitivity of 0.98 ± 0.004, and mAP of 0.95 ± 0.01. Conclusion: Using a semi-supervised approach with a medical image library, we developed a high-performing model for kidney detection. Further external validation is required to assess the model's generalizability.

Triple challenges - Small sample size in both exposure and control groups to scan rare maternal outcomes in a signal identification approach: A simulation study.

There is a dearth of safety data on maternal outcomes after perinatal medication exposure. Data-mining for unexpected adverse event occurrence in existing datasets is a potentially useful approach. One method, the Poisson tree-based scan statistic (TBSS), assumes that the expected outcome counts, based on incidence of outcomes in the control group, are estimated without error. This assumption may be difficult to satisfy with a small control group. Our simulation study evaluated the effect of imprecise incidence proportions from the control group on TBSS' ability to identify maternal outcomes in pregnancy research. We simulated base case analyses with "true" expected incidence proportions and compared these to imprecise incidence proportions derived from sparse control samples. We varied parameters impacting Type I error and statistical power (exposure group size, outcome's incidence proportion, and effect size). We found that imprecise incidence proportions generated by a small control group resulted in inaccurate alerting, inflation of Type I error, and removal of very rare outcomes for TBSS analysis due to "zero" background counts. Ideally, the control size should be at least several times larger than the exposure size to limit the number of false positive alerts and retain statistical power for true alerts.

Cell signaling and tissue remodeling in the pulmonary autograft after the Ross procedure: A computational study.

In the Ross procedure, a patient's pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale. The cell-scale model consists of a network model, that includes important signaling pathways and relations between relevant transcription factors and their target genes. The resulting gene activity leads to changes in the mechanical properties of the tissue, modeled as a constrained mixture of collagen, elastin and smooth muscle. The multiscale model is calibrated with findings from experiments in which seven sheep underwent the Ross procedure. The model is then validated against a different set of sheep experiments, for which a qualitative agreement between model and experiment is found. Model outcomes at the cell scale, including the activity of genes and transcription factors, also match experimentally obtained transcriptomics data.

A Prospective Study of the Diagnostic Performance of Photon-Counting CT Compared With MRI in the Characterization of Renal Masses.

OBJECTIVES: The aim of this study was to assess the interreader reliability and per-RCC sensitivity of high-resolution photon-counting computed tomography (PCCT) in the detection and characterization of renal masses in comparison to MRI. MATERIALS AND METHODS: This prospective study included 24 adult patients (mean age, 52 ± 14 years; 14 females) who underwent PCCT (using an investigational whole-body CT scanner) and abdominal MRI within a 3-month time interval and underwent surgical resection (partial or radical nephrectomy) with histopathology (n = 70 lesions). Of the 24 patients, 17 had a germline mutation and the remainder were sporadic cases. Two radiologists (R1 and R2) assessed the PCCT and corresponding MRI studies with a 3-week washout period between reviews. Readers recorded the number of lesions in each patient and graded each targeted lesion's characteristic features, dimensions, and location. Data were analyzed using a 2-sample t test, Fisher exact test, and weighted kappa. RESULTS: In patients with von Hippel-Lindau mutation, R1 identified a similar number of lesions suspicious for neoplasm on both modalities (51 vs 50, P = 0.94), whereas R2 identified more suspicious lesions on PCCT scans as compared with MRI studies (80 vs 56, P = 0.12). R1 and R2 characterized more lesions as predominantly solid in MRIs (R1: 58/70 in MRI vs 52/70 in PCCT, P < 0.001; R2: 60/70 in MRI vs 55/70 in PCCT, P < 0.001). R1 and R2 performed similarly in detecting neoplastic lesions on PCCT and MRI studies (R1: 94% vs 90%, P = 0.5; R2: 73% vs 79%, P = 0.13). CONCLUSIONS: The interreader reliability and per-RCC sensitivity of PCCT scans acquired on an investigational whole-body PCCT were comparable to MRI scans in detecting and characterizing renal masses. CLINICAL RELEVANCE STATEMENT: PCCT scans have comparable performance to MRI studies while allowing for improved characterization of the internal composition of lesions due to material decomposition analysis. Future generations of this imaging modality may reveal additional advantages of PCCT over MRI.

Development of a separability index for task specific characterization of spectral computed tomography.

PURPOSE: In this work, we define a signal detection based metrology to characterize the separability of two different multi-dimensional signals in spectral CT acquisitions. METHOD: Signal response was modelled as a random process with a deterministic signal and stochastic noise component. A linear Hotelling observer was used to estimate a scalar test statistic distribution that predicts the likelihood of an intensity value belonging to a signal. Two distributions were estimated for two materials of interest and used to derive two metrics separability: a separability index (s') and the area under the curve of the test statistic distributions. Experimental and simulated data of photon-counting CT scanners were used to evaluate each metric. Experimentally, vials of iodine and gadolinium (2, 4, 8 mg/mL) were scanned at multiple tube voltages, tube currents and energy thresholds. Additionally, a simulated dataset with low tube current (10-150 mAs) and material concentrations (0.25-4 mg/mL) was generated. RESULTS: Experimental data showed that conditions favorable for low noise and expression of k-edge signal produced the highest separability. Material concentration had the greatest impact on separability. The simulated data showed that under more difficult separation conditions, difference in material concentration still had the greatest impact on separability. CONCLUSION: The results demonstrate the utility of a task specific metrology to measure the overlap in signal between different materials in spectral CT. Using experimental and simulated data, the separability index was shown to describe the relationship between image formation factors and the signal responses of material.

Predicting Intervention Use in Youth with Rare Variants in Autism-Associated Genes.

Specialized multidisciplinary supports are important for long-term outcomes for autistic youth. Although family and child factors predict service utilization in autism, little is known with respect to youth with rare, autism-associated genetic variants, who frequently have increased psychiatric, developmental, and behavioral needs. We investigate the impact of family factors on service utilization to determine whether caregiver (autistic features, education, income) and child (autistic features, sex, age, IQ, co-occurring conditions) factors predicted service type (e.g., speech, occupational, behavioral) and intensity (hours/year) among children with autism-associated variants (N = 125), some of whom also had a confirmed ASD diagnosis. Analyses revealed variability in the types of services used across a range of child demographic, behavioral, and mental health characteristics. Speech therapy was the most received service (87.2%). Importantly, behavior therapy was the least received service and post-hoc analyses revealed that use of this therapy was uniquely predicted by ASD diagnosis. However, once children received a particular service, there was largely comparable intensity of services, independent of caregiver and child factors. Findings suggest that demographic and clinical factors impact families' ability to obtain services, with less impact on the intensity of services received. The low receipt of therapies that specifically address core support needs in autism (i.e., behavior therapy) indicates more research is needed on the availability of these services for youth with autism-associated variants, particularly for those who do not meet criteria for an ASD diagnosis but do demonstrate elevated and impactful child autistic features as compared to the general population.

Origin and flow-mediated remodeling of the murine and human extraembryonic circulation systems.

The transduction of mechanical stimuli produced by blood flow is an important regulator of vascular development. The vitelline and umbilico-placental circulations are extraembryonic vascular systems that are required for proper embryonic development in mammalian embryos. The morphogenesis of the extraembryonic vasculature and the cardiovascular system of the embryo are hemodynamically and molecularly connected. Here we provide an overview of the establishment of the murine and human vitelline and umbilico-placental vascular systems and how blood flow influences various steps in their development. A deeper comprehension of extraembryonic vessel development may aid the establishment of stem-cell based embryo models and provide novel insights to understanding pregnancy complications related to the umbilical cord and placenta.

Guided recall of positive autobiographical memories increases anticipated pleasure and psychological resources, and reduces depressive symptoms: a replication and extension of a randomised controlled trial of brief positive cognitive-reminiscence therapy.

Reminiscence-based interventions focus on recalling autobiographical memories and reflective reasoning to develop a healthy and adaptive view of oneself and one's life. This study aimed to replicate the effects of a three-session, group-based, positive-memory version of cognitive-reminiscence therapy (CRT) on psychological resources and mental well-being and extend the findings to anticipated pleasure. The participants (N = 75, Mage = 43.7 (SD = 16.7), 60% females) were randomised to CRT or control group. Anticipated pleasure, psychological resources (schemas of positive self-esteem, self-efficacy, meaning in life, optimism), mental well-being (depression, anxiety, and stress symptoms) and theorised change processes (automatic negative thoughts, awareness of narrative identity) were assessed. Relative to the control group, the CRT group reported significantly higher anticipated pleasure (d = 0.76-0.93) and psychological resources of self-esteem, self-efficacy, and optimism (d's = 0.58-0.99) at post-CRT and follow-up, and lower depressive symptoms post-CRT and at follow-up (d = 0.56-0.67). Findings on meaning in life and negative automatic thinking were partially replicated. This study replicates findings of the effectiveness of this intervention for improving psychological resources such as self-worth, confidence and optimism and depressive symptoms, and indicates additional effects on anticipated pleasure. CRT may serve as a standalone intervention, or as an adjunct "memory booster" for interventions focused on future thinking and related anticipated reward.

Incorporation of vasa previa screening into a routine anomaly scan: A single center cohort study.

INTRODUCTION: Vasa previa (VP), defined as unprotected fetal vessels traversing the membranes over the cervix, is associated with a high perinatal mortality when undiagnosed prenatally. Conversely, prenatal diagnosis with ultrasound and cesarean delivery before the membranes rupture is associated with excellent outcomes. However, controversy exists regarding screening for VP. In the UK, routine screening for VP is not recommended. The objective of this study was to report the incidence of VP and our experience in the detection of VP with a universal screening protocol at the time of the second-trimester fetal anomaly scan with third-trimester confirmation in an unselected population of pregnancies. MATERIAL AND METHODS: We performed a single-center historical cohort study of all pregnant women who underwent routine second-trimester anomaly screening scans at West Middlesex University Hospital, London, UK, between 2012 and 2016. Over 5 years, every patient undergoing routine anomaly screening was evaluated for VP using a systematic protocol during their 20-week anomaly scan. Suspected cases of VP were rescanned in the third trimester by specialist sonographers with an interest in VP. The primary outcomes were the incidence and detection of VP. RESULTS: During the study period, 24 690 anatomy scans were performed. A total of 64 patients were identified as having potential VP at the second-trimester anomaly screening scan, of which 19 were confirmed by the specialist sonographer in the third trimester and at delivery. The screen positive rate was 0.26% (95% confidence interval [CI] 0.20%-0.32%). VP at birth was found in 19/24690 births (1:1299 [95% CI: 1:832-1:2030] births). Universal screening for VP using our protocol had a sensitivity of 100% and a specificity of 99.78% (95% CI: 99.72%-99.84%). The false-positive rate of the second-trimester screen was 0.18% (95% CI: 0.13-0.24). There were no false positives or false negatives at delivery. Of the 19 patients with confirmed VP, 17 had scheduled cesarean deliveries, and two required emergency deliveries due to antepartum hemorrhage. One baby died, giving a perinatal mortality of 5%. CONCLUSIONS: VP complicates approximately 1:1300 pregnancies. Routine screening for VP yielded a 100% detection rate. We suggest the inclusion of structured VP assessment in standard fetal anomaly screening programs.

Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions.

BACKGROUND: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. METHODS: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. RESULTS: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. CONCLUSIONS: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.

Using Claims Data to Predict Pre-Operative BMI Among Bariatric Surgery Patients: Development of the BMI Before Bariatric Surgery Scoring System (B3S3).

Background: Lack of body mass index (BMI) measurements limits the utility of claims data for bariatric surgery research, but pre-operative BMI may be imputed due to existence of weight-related diagnosis codes and BMI-related reimbursement requirements. We used a machine learning pipeline to create a claims-based scoring system to predict pre-operative BMI, as documented in the electronic health record (EHR), among patients undergoing a new bariatric surgery. Methods: Using the Optum Labs Data Warehouse, containing linked de-identified claims and EHR data for commercial or Medicare Advantage enrollees, we identified adults undergoing a new bariatric surgery between January 2011 and June 2018 with a BMI measurement in linked EHR data ≤30 days before the index surgery (n=3226). We constructed predictors from claims data and applied a machine learning pipeline to create a scoring system for pre-operative BMI, the B3S3. We evaluated the B3S3 and a simple linear regression model (benchmark) in test patients whose index surgery occurred concurrent (2011-2017) or prospective (2018) to the training data. Results: The machine learning pipeline yielded a final scoring system that included weight-related diagnosis codes, age, and number of days hospitalized and distinct drugs dispensed in the past 6 months. In concurrent test data, the B3S3 had excellent performance (R2 0.862, 95% confidence interval [CI] 0.815-0.898) and calibration. The benchmark algorithm had good performance (R2 0.750, 95% CI 0.686-0.799) and calibration but both aspects were inferior to the B3S3. Findings in prospective test data were similar. Conclusion: The B3S3 is an accessible tool that researchers can use with claims data to obtain granular and accurate predicted values of pre-operative BMI, which may enhance confounding control and investigation of effect modification by baseline obesity levels in bariatric surgery studies utilizing claims data.

Pre-operative BMI is an important potential confounder in comparative effectiveness studies of bariatric surgeries.Claims data lack clinical measurements, but insurance reimbursement requirements for bariatric surgery often result in pre-operative BMI being coded in claims data.We used a machine learning pipeline to create a model, the B3S3, to predict pre-operative BMI, as documented in the EHR, among bariatric surgery patients based on the presence of certain weight-related diagnosis codes and other patient characteristics derived from claims data.Researchers can easily use the B3S3 with claims data to obtain granular and accurate predicted values of pre-operative BMI among bariatric surgery patients.

Intravoxel incoherent motion as a surrogate marker of perfused vascular density in rat brain.

Intravoxel incoherent motion (IVIM) MRI has emerged as a valuable technique for the assessment of tissue characteristics and perfusion. However, there is limited knowledge about the relationship between IVIM-derived measures and changes at the level of the vascular network. In this study, we investigated the potential use of IVIM MRI as a noninvasive tool for measuring changes in cerebral vascular density. Variations in quantitative immunohistochemical measurements of the vascular density across different regions in the rat brain (cortex, corpus callosum, hippocampus, thalamus, and hypothalamus) were related to the pseudo-diffusion coefficient D* and the flowing blood fraction f in healthy Wistar rats. We assessed whether region-wise differences in the vascular density are reflected by variations in the IVIM measurements and found a significant positive relationship with the pseudo-diffusion coefficient (p < 0.05, ß = 0.24). The effect of cerebrovascular alterations, such as blood-brain barrier (BBB) disruption on the perfusion-related IVIM parameters, is not well understood. Therefore, we investigated the effect of BBB disruption on the IVIM measures in a rat model of metabolic and vascular comorbidities (ZSF1 obese rat) and assessed whether this affects the relationship between the cerebral vascular density and the noninvasive IVIM measurements. We observed increased vascular permeability without detecting any differences in diffusivity, suggesting that BBB leakage is present before changes in the tissue integrity. We observed no significant difference in the relationship between cerebral vascular density and the IVIM measurements in our model of comorbidities compared with healthy normotensive rats.

Technology Characterization Through Diverse Evaluation Methodologies: Application to Thoracic Imaging in Photon-Counting Computed Tomography.

OBJECTIVE: Different methods can be used to condition imaging systems for clinical use. The purpose of this study was to assess how these methods complement one another in evaluating a system for clinical integration of an emerging technology, photon-counting computed tomography (PCCT), for thoracic imaging. METHODS: Four methods were used to assess a clinical PCCT system (NAEOTOM Alpha; Siemens Healthineers, Forchheim, Germany) across 3 reconstruction kernels (Br40f, Br48f, and Br56f). First, a phantom evaluation was performed using a computed tomography quality control phantom to characterize noise magnitude, spatial resolution, and detectability. Second, clinical images acquired using conventional and PCCT systems were used for a multi-institutional reader study where readers from 2 institutions were asked to rank their preference of images. Third, the clinical images were assessed in terms of in vivo image quality characterization of global noise index and detectability. Fourth, a virtual imaging trial was conducted using a validated simulation platform (DukeSim) that models PCCT and a virtual patient model (XCAT) with embedded lung lesions imaged under differing conditions of respiratory phase and positional displacement. Using known ground truth of the patient model, images were evaluated for quantitative biomarkers of lung intensity histograms and lesion morphology metrics. RESULTS: For the physical phantom study, the Br56f kernel was shown to have the highest resolution despite having the highest noise and lowest detectability. Readers across both institutions preferred the Br56f kernel (71% first rank) with a high interclass correlation (0.990). In vivo assessments found superior detectability for PCCT compared with conventional computed tomography but higher noise and reduced detectability with increased kernel sharpness. For the virtual imaging trial, Br40f was shown to have the best performance for histogram measures, whereas Br56f was shown to have the most precise and accurate morphology metrics. CONCLUSION: The 4 evaluation methods each have their strengths and limitations and bring complementary insight to the evaluation of PCCT. Although no method offers a complete answer, concordant findings between methods offer affirmatory confidence in a decision, whereas discordant ones offer insight for added perspective. Aggregating our findings, we concluded the Br56f kernel best for high-resolution tasks and Br40f for contrast-dependent tasks.

The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial.

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Freezing-mediated formation of supraproteins using depletion forces.

Hypothesis Long-acting formulations such as microparticles, injectable depots and implantable devices can realize spatiotemporally controlled delivery of protein drugs to extend their therapeutic in vivo half-lives. To efficiently encapsulate the protein drugs into such drug delivery systems, (sub)micron-sized protein particles are needed. The formation of micronized supraproteins can be induced through the synergistic combination of attractive depletion forces and freezing. The size of the supraproteins can be fine-tuned from submicron to several microns by adjusting the ice crystallization rate through the freeze-quench depth, which is set by the target temperature. Methods Supraprotein micron structures were prepared from protein solutions under various conditions in the presence and absence of nonadsorbing polyethylene glycol. Scanning electron microscopy and dynamic light scattering were employed to determine the sizes of the supraproteins and real-time total internal reflection fluorescent microscopy was used to follow the supraprotein formation during freezing. The protein secondary structure was measured before and after micronization by circular dichroism. A phase diagram of a protein-polyethylene glycol mixture was theoretically predicted to investigate whether the depletion interaction can elucidate the phase behavior. Findings Micronized protein supraparticles could be prepared in a controlled manner by rapid freeze-drying of aqueous mixtures of bovine serum albumin, horseradish peroxidase and lysozyme mixed with polyethylene glycol. Upon freezing, the temperature quench initiates a phase separation process which is reminiscent of spinodal decomposition. This demixing is subsequently arrested during droplet phase separation to form protein-rich microstructures. The final size of the generated protein microparticles is determined by a competition between phase separation and cooling rate, which can be controlled by target temperature. The experimental phase diagram of the aqueous protein-polyethylene glycol dispersion aligns with predictions from depletion theory for charged colloids and nonadsorbing polymers.

Kidney scoring surveillance: predictive machine learning models for clear cell renal cell carcinoma growth using MRI.

INTRODUCTION: Classification of clear cell renal cell carcinoma (ccRCC) growth rates in patients with Von Hippel-Lindau (VHL) syndrome has several ramifications for tumor monitoring and surgical planning. Using two separate machine-learning algorithms, we sought to produce models to predict ccRCC growth rate classes based on qualitative MRI-derived characteristics. MATERIAL AND METHODS: We used a prospectively maintained database of patients with VHL who underwent surgical resection for ccRCC between January 2015 and June 2022. We employed a threshold growth rate of 0.5 cm per year to categorize ccRCC tumors into two distinct groups-'slow-growing' and 'fast-growing'. Utilizing a questionnaire of qualitative imaging features, two radiologists assessed each lesion on different MRI sequences. Two machine-learning models, a stacked ensemble technique and a decision tree algorithm, were used to predict the tumor growth rate classes. Positive predictive value (PPV), sensitivity, and F1-score were used to evaluate the performance of the models. RESULTS: This study comprises 55 patients with VHL with 128 ccRCC tumors. Patients' median age was 48 years, and 28 patients were males. Each patient had an average of two tumors, with a median size of 2.1 cm and a median growth rate of 0.35 cm/year. The overall performance of the stacked and DT model had 0.77 ± 0.05 and 0.71 ± 0.06 accuracies, respectively. The best stacked model achieved a PPV of 0.92, a sensitivity of 0.91, and an F1-score of 0.90. CONCLUSION: This study provides valuable insight into the potential of machine-learning analysis for the determination of renal tumor growth rate in patients with VHL. This finding could be utilized as an assistive tool for the individualized screening and follow-up of this population.

Deep learning algorithm (YOLOv7) for automated renal mass detection on contrast-enhanced MRI: a 2D and 2.5D evaluation of results.

INTRODUCTION: Accurate diagnosis and treatment of kidney tumors greatly benefit from automated solutions for detection and classification on MRI. In this study, we explore the application of a deep learning algorithm, YOLOv7, for detecting kidney tumors on contrast-enhanced MRI. MATERIAL AND METHODS: We assessed the performance of YOLOv7 tumor detection on excretory phase MRIs in a large institutional cohort of patients with RCC. Tumors were segmented on MRI using ITK-SNAP and converted to bounding boxes. The cohort was randomly divided into ten benchmarks for training and testing the YOLOv7 algorithm. The model was evaluated using both 2-dimensional and a novel in-house developed 2.5-dimensional approach. Performance measures included F1, Positive Predictive Value (PPV), Sensitivity, F1 curve, PPV-Sensitivity curve, Intersection over Union (IoU), and mean average PPV (mAP). RESULTS: A total of 326 patients with 1034 tumors with 7 different pathologies were analyzed across ten benchmarks. The average 2D evaluation results were as follows: Positive Predictive Value (PPV) of 0.69 ± 0.05, sensitivity of 0.39 ± 0.02, and F1 score of 0.43 ± 0.03. For the 2.5D evaluation, the average results included a PPV of 0.72 ± 0.06, sensitivity of 0.61 ± 0.06, and F1 score of 0.66 ± 0.04. The best model performance demonstrated a 2.5D PPV of 0.75, sensitivity of 0.69, and F1 score of 0.72. CONCLUSION: Using computer vision for tumor identification is a cutting-edge and rapidly expanding subject. In this work, we showed that YOLOv7 can be utilized in the detection of kidney cancers.

Study of uricase-polynorbornene conjugates derived from grafting-from ring-opening metathesis polymerization.

PEGylation has been the 'gold standard' in bioconjugation due to its ability to improve the pharmacokinetics and pharmacodynamics of native proteins. However, growing clinical evidence of hypersensitivity reactions to PEG due to pre-existing anti-PEG antibodies in healthy humans have raised concerns. Advancements in controlled polymerization techniques and conjugation chemistries have paved the way for the development of protein-polymer conjugates that can circumvent these adverse reactions while retaining the benefits of such modifications. Herein, we show the development of polynorbornene based bioconjugates of therapeutically relevant urate oxidase (UO) enzymes used in the treatment of gout synthesized by grafting-from ring-opening metathesis polymerization (ROMP). Notably, these conjugates exhibit comparable levels of bioactivity to PEGylated UO and demonstrate increased stability across varying temperatures and pH conditions. Immune recognition of conjugates by anti-UO antibodies reveal low protein immunogenicity following the conjugation process. Additionally, UO conjugates employing zwitterionic polynorbornene successfully avoid recognition by anti-PEG antibodies, further highlighting a potential replacement for PEG.

Non-Invasive Tumor Grade Evaluation in Von Hippel-Lindau-Associated Clear Cell Renal Cell Carcinoma: A Magnetic Resonance Imaging-Based Study.

BACKGROUND: Pathology grading is an essential step for the treatment and evaluation of the prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To investigate the utility of texture analysis in evaluating Fuhrman grades of renal tumors in patients with Von Hippel-Lindau (VHL)-associated ccRCC, aiming to improve non-invasive diagnosis and personalized treatment. STUDY TYPE: Retrospective analysis of a prospectively maintained cohort. POPULATION: One hundred and thirty-six patients, 84 (61%) males and 52 (39%) females with pathology-proven ccRCC with a mean age of 52.8 ± 12.7 from 2010 to 2023. FIELD STRENGTH AND SEQUENCES: 1.5 and 3 T MRIs. Segmentations were performed on the T1-weighted 3-minute delayed sequence and then registered on pre-contrast, T1-weighted arterial and venous sequences. ASSESSMENT: A total of 404 lesions, 345 low-grade tumors, and 59 high-grade tumors were segmented using ITK-SNAP on a T1-weighted 3-minute delayed sequence of MRI. Radiomics features were extracted from pre-contrast, T1-weighted arterial, venous, and delayed post-contrast sequences. Preprocessing techniques were employed to address class imbalances. Features were then rescaled to normalize the numeric values. We developed a stacked model combining random forest and XGBoost to assess tumor grades using radiomics signatures. STATISTICAL TESTS: The model's performance was evaluated using positive predictive value (PPV), sensitivity, F1 score, area under the curve of receiver operating characteristic curve, and Matthews correlation coefficient. Using Monte Carlo technique, the average performance of 100 benchmarks of 85% train and 15% test was reported. RESULTS: The best model displayed an accuracy of 0.79. For low-grade tumor detection, a sensitivity of 0.79, a PPV of 0.95, and an F1 score of 0.86 were obtained. For high-grade tumor detection, a sensitivity of 0.78, PPV of 0.39, and F1 score of 0.52 were reported. DATA CONCLUSION: Radiomics analysis shows promise in classifying pathology grades non-invasively for patients with VHL-associated ccRCC, potentially leading to better diagnosis and personalized treatment. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.