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Recent breakthroughs in protein structure prediction have enhanced the precision and speed at which protein configurations can be determined. Additionally, molecular dynamics (MD) simulations serve as a crucial tool for capturing the conformational space of proteins, providing valuable insights into their structural fluctuations. However, the scope of MD simulations is often limited by the accessible timescales and the computational resources available, posing challenges to comprehensively exploring protein behaviors. Recently emerging approaches have focused on expanding the capability of AlphaFold2 (AF2) to predict conformational substates of protein. Here, we benchmark the performance of various workflows that have adapted AF2 for ensemble prediction and compare the obtained structures with ensembles obtained from MD simulations and NMR. We provide an overview of the levels of performance and accessible timescales that can currently be achieved with machine learning (ML) based ensemble generation. Significant minima of the free energy surfaces remain undetected., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Leaf senescence is a developmental process allowing nutrient remobilization to sink organs. Previously cysteine proteases have been found to be highly expressed during leaf senescence in different plant species. Using biochemical and immunoblotting approaches, we characterized developmental senescence of barley ( Hordeum vulgare L. var. 'GemCraft') leaves collected from 0 to 6 weeks after the onset of flowering. A decrease in total protein and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) large subunits occurred in parallel with an increase in proteolytic activity measured using the fluorogenic substrates Z-RR-AMC, Z-FR-AMC, and casein labeled with fluorescein isothiocyanate (casein-FITC). Aminopeptidase activity detected with R-AMC peaked at week 3 and then decreased, reaching a low level by week 6. Maximal proteolytic activity with Z-FR-AMC and Z-RR-AMC was detected from pH 4.0 to pH 5.5 and pH 6.5 to pH 7.4, respectively, while two pH optima (pH 3.6 to pH 4.5 and pH 6.5 to pH 7.4) were found for casein-FITC. Compound E-64, an irreversible cysteine protease inhibitor, and CAA0225, a selective cathepsin L inhibitor, effectively inhibited proteolytic activity with IC 50 values in the nanomolar range. CA-074, a selective cathepsin B inhibitor, was less potent under the same experimental conditions, with IC 50 in the micromolar range. Inhibition by leupeptin and phenylmethylsulfonyl fluoride (PMSF) was weak, and pepstatin A, an inhibitor of aspartic acid proteases, had no effect at the concentrations studied (up to 0.2 mM). Maximal proteolytic activity with the aminopeptidase substrate R-AMC was detected from pH 7.0 to pH 8.0. The pH profile of DCG-04 (a biotinylated activity probe derived from E-64) binding corresponded to that found with Z-FR-AMC, suggesting that the major active proteases are related to cathepsins B and L. Moreover, immunoblotting detected increased levels of barley SAG12 orthologs and aleurain, confirming a possible role of these enzymes in senescing leaves.

The influence of floating marine debris (FMD) on coastal and marine communities and ecosystems is undeniable, and attention is increasingly focused on ecologically and biologically important coastal areas. To protect marine life and valuable resources from FMD pollution, identifying FMD accumulation zones is recognized as a priority. One of the coastal ocean processes found governing the distribution of FMD is water convergence (frontal zones). These fronts are driven by various oceanographical factors. To date, the transport and accumulation of FMD in relation to fronts in coastal areas is poorly understood. To address this knowledge gap, we reviewed various types of ocean fronts as well as FMD accumulation along frontal zones in coastal areas defined as the region between the coastline and the shelf break. Frontogenesis (physical processes related to frontal formation) were reviewed alongside studies on FMD accumulation in frontal zones to identify physical factors that drive the pathways and accumulation in these areas. This review will contribute to our understanding of accumulation hotspots of FMD within ocean fronts and identify gaps for further research on developing a proxy for FMD hotspot identification in ecologically important coastal areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Osteopenia of prematurity is common in the neonatal intensive care unit, with an incidence of up to 54% in extremely low birthweight infants. The baseline fracture rate in our level IV midwestern neonatal intensive care unit was 13%, with poor compliance with recommended intakes of calcium, calcium:phosphorus ratio, and Vitamin D., Methods: A multidisciplinary team implemented a screening guideline through four Plan-Do-Study-Act cycles, which addressed staff education, vitamin D screening, and incorporation of calcitriol. In total, 150 patients born between October 1, 2019 and April 30, 2023 were screened for mineral intakes, laboratory abnormalities, and the development of fractures or osteopenia., Results: The incidence of fractures decreased from 13% to 5.3%. Compliance with mineral intakes improved for calcium, calcium: phosphorus ratio, and Vitamin D. Infants born after the guideline were 4.8 times less likely to develop fractures., Conclusion: Quality improvement methodology successfully decreased the rate of fractures due to osteopenia of prematurity and increased compliance with recommended mineral intakes., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Positive pressure ventilation (PPV) is crucial to the resuscitation of newborns. Although neonates often require PPV at birth, the optimal interface has not been determined. Both binasal prongs and face masks were deemed acceptable by the International Liaison Committee on Resuscitation in 2010 and have been utilized at our center since 2016; however, the choice is by provider preference. Previous studies have suggested that binasal prongs may be more effective than face masks at avoiding intubation in the delivery room. The objective of this study is to compare intubation rates of binasal prongs versus face masks for delivery room resuscitation of neonates born < 30 weeks' gestation., Study Design: This retrospective study compares delivery room intubation rates by interface for neonates < 30 weeks' gestation born between August 2016 and April 2021 at our level IV neonatal intensive care unit. Exclusion criteria included diagnosis of congenital diaphragmatic hernia, no PPV required, or no resuscitation attempted. Data collected included interface device, demographics, maternal data, delivery room data, admission data, and discharge outcomes. The three interface groups (binasal prongs, face mask, face mask, and binasal prongs) were compared utilizing chi-square, analysis of variance with post hoc analysis, and logistic regression., Results: Mean gestational ages and birth weights for the groups were 27.6 weeks and 1,126 g, 25.7 weeks and 839 g, and 27.1 weeks and 1,028 g, respectively. Neonates resuscitated with face masks were 9.9 times more likely to be intubated in the delivery room and 10.8 times more likely to be intubated at 6 hours of life compared with those resuscitated with binasal prongs after logistic regression analysis., Conclusion: The findings in our study support delivery room resuscitation with binasal prongs as a useful method in reducing the need for intubation both in the delivery room and at 6 hours of life. Further prospective studies are warranted., Key Points: · The International Liaison Committee on Resuscitation recommends multiple interface options for neonatal resuscitation.. · Vermont Oxford Network endorses nasal interface for premature infants.. · Binasal prongs are associated with lower intubation rates.., Competing Interests: None declared., (Thieme. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with a broad spectrum defined by liver biopsy. This gold standard method evaluates three features: steatosis, activity (ballooning and lobular inflammation), and fibrosis, attributing them to certain grades or stages using a semiquantitative scoring system. However, liver biopsy is subject to numerous restrictions, creating an unmet need for a reliable and reproducible method for MASLD assessment, grading, and staging. Noninvasive imaging modalities, such as magnetic resonance imaging (MRI), offer the potential to assess quantitative liver parameters. This review aims to provide an overview of the available MRI techniques for the three criteria evaluated individually by liver histology. Here, we discuss the possibility of combining multiple MRI parameters to replace liver biopsy with a holistic, multiparametric MRI protocol. In conclusion, the development and implementation of such an approach could significantly improve the diagnosis and management of MASLD, reducing the need for invasive procedures and paving the way for more personalized treatment strategies., Competing Interests: A.M.F., N.L., and H.O.C. are employees of Boehringer Ingelheim Pharma GmbH & Co. KG., (Thieme. All rights reserved.)

Robust quantification of vegetative biomass using satellite imagery using one or more forms of machine learning (ML) has hitherto been hindered by the extent and quality of training data. Here, we showcase how ML predictive demonstrably improves when additional training data is used. We collated field datasets of pasture biomass obtained via destructive sampling, 'C-Dax' reflective measurements and rising plate meters (RPM) from ten livestock farms across four States in Australia. Remotely sensed data from the Sentinel-2 constellation was used to retrieve aboveground biomass using a novel machine learning paradigm hereafter termed "SPECTRA-FOR" (Spectral Pasture Estimation using Combined Techniques of Random-forest Algorithm for Features Optimisation and Retrieval). Using this framework, we show that the low temporal resolution of Sentinel-2 in high latitude regions with persistent cloud cover leads to extensive gaps between cloud-free images, hindering model performance and, thus, contemporaneous ability to forecast real-time pasture biomass. By leveraging the spectral consistency between Sentinel-2 and Planet Lab SuperDove to overcome this limitation, we used ten spectral bands of Sentinel-2, four bands of Sentinel-2 as a proxy for pre-2022 SuperDove (referred to as synthetic SuperDove or SSD), and the actual SuperDove (ASD), given that SuperDove imagery has a higher resolution and more frequent passage compared with Sentinel-2. Using their respective bands as input features to SPECRA-FOR, model performance for the ten bands of Sentinel-2 were R 2  = 0.87, root mean squared error (RMSE) of 439 kg DM/ha and mean absolute error (MAE) of 255 kg DM/ha, while that for SSD increased to an R 2 of 0.92, RMSE of 346 kg DM/ha and MAE = 208 kg DM/ha. The study revealed the importance of robust data mining, imagery harmonisation and model validation for accurate real-time modelling of pasture biomass with ML., Competing Interests: Declaration of competing interest The authors confirm that neither the manuscript nor any parts of its content are currently under consideration or published in another journal. All authors have approved the manuscript and agree with its submission to the Journal. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Protein folding is a fascinating, not fully understood phenomenon in biology. Molecular dynamics (MD) simulations are an invaluable tool to study conformational changes in atomistic detail, including folding and unfolding processes of proteins. However, the accuracy of the conformational ensembles derived from MD simulations inevitably relies on the quality of the underlying force field in combination with the respective water model. Here, we investigate protein folding, unfolding, and misfolding of fast-folding proteins by examining different force fields with their recommended water models, i.e., ff14SB with the TIP3P model and ff19SB with the OPC model. To this end, we generated long conventional MD simulations highlighting the perks and pitfalls of these setups. Using Markov state models, we defined kinetically independent conformational substates and emphasized their distinct characteristics, as well as their corresponding state probabilities. Surprisingly, we found substantial differences in thermodynamics and kinetics of protein folding, depending on the combination of the protein force field and water model, originating primarily from the different water models. These results emphasize the importance of carefully choosing the force field and the respective water model as they determine the accuracy of the observed dynamics of folding events. Thus, the findings support the hypothesis that the water model is at least equally important as the force field and hence needs to be considered in future studies investigating protein dynamics and folding in all areas of biophysics.

Background: Sarcopenia is characterized by low muscle strength, decreased muscle mass, and decline in physical performance. While the measurements of muscle strength and physical performance are easy to perform, an accurate evaluation of muscle mass is technically more demanding. We therefore evaluated the suitability of calf circumference (CC) as a clinical indicator for muscle mass., Methods: In a cross-sectional single-centre study, geriatric inpatients were assessed for sarcopenia according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) consensus. Calf circumference was tested for correlation with appendicular skeletal muscle mass index (ASMI). Receiver operating characteristic curves (ROC) were used to calculate the discriminatory value of the CC cut-off values to differentiate patients above and below ASMI cut-offs for sarcopenia., Results: In this study population (n = 305, age 83.5 ± 7.0 years, BMI 25.7 kg/m 2 , 65.6% female), the prevalence of sarcopenia was 22.6%. In subjects with low ASMI, mean CC was 29.5 ± 3.4 cm for females and 32.0 ± 3.4 cm for males. A positive relationship between CC and ASMI was found. The optimized cut-off value for CC to identify patients with low ASMI was <31.5 cm for females (sensitivity 78%, specificity 79%), and <33.5 cm for males (sensitivity 71%, specificity 62%)., Conclusion: In clinical settings where imaging technology for muscle mass quantification is not available, simple calf circumference measurement may be used as a dependable indicator for low muscle mass in older adults., (© 2024. The Author(s).)

Depression (DEP) and dementia of the Alzheimer's type (DAT) represent the most common neuropsychiatric disorders in elderly patients. Accurate differential diagnosis is indispensable to ensure appropriate treatment. However, DEP can yet mimic cognitive symptoms of DAT and patients with DAT often also present with depressive symptoms, impeding correct diagnosis. Machine learning (ML) approaches could eventually improve this discrimination using neuropsychological test data, but evidence is still missing. We therefore employed Support Vector Machine (SVM), Naïve Bayes (NB), Random Forest (RF) and conventional Logistic Regression (LR) to retrospectively predict the diagnoses of 189 elderly patients (68 DEP and 121 DAT) based on either the well-established Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery (CERAD-NAB) or a flexible battery approach (FLEXBAT). The best performing combination consisted of FLEXBAT and NB, correctly classifying 87.0% of patients as either DAT or DEP. However, all accuracies were similar across algorithms and test batteries (83.0% - 87.0%). Accordingly, our study is the first to show that common ML algorithms with their default parameters can accurately differentiate between patients clinically diagnosed with DAT or DEP using neuropsychological test data, but do not necessarily outperform conventional LR.

Floating marine debris (FMD) is one of the world's most concerning issues due to its potential impact on biodiversity, communities, and ecosystem services. FMD transport and concentrations are driven by fronts, generated by oceanographic processes, and the accumulation of FMD has been reported in gyres, eddies, tidal fronts, salinity fronts, and coastal fronts. This study explores the relationship between fronts and FMD accumulation in the Gulf of Maine (GoM) and the surrounding coastal areas (USA). Frontal edge detection algorithms were applied to sea surface temperature (SST) imagery from the Moderate-resolution Imaging Spectroradiometer (MODIS) between 2002 and 2012. Frontal location is spatially correlated with FMD concentrations collected by the Sea Education Association. Higher concentrations of FMD are associated with frontal frequencies (FF) of 5-10 %. FMD is trapped between fronts and the coastline in accumulation zones. These results highlight the need to consider coastal FMD hotspots, given these are areas of high biodiversity value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Antibodies and other new antibody-like formats have emerged as one of the most rapidly growing classes of biotherapeutic proteins. Understanding the structural features that drive antibody function and, consequently, their molecular recognition is critical for engineering antibodies. Here, we present the structural architecture of conventional IgG antibodies alongside other formats. We emphasize the importance of considering antibodies as conformational ensembles in solution instead of focusing on single-static structures because their functions and properties are strongly governed by their dynamic nature. Thus, in this review, we provide an overview of the unique structural and dynamic characteristics of antibodies with respect to their antigen recognition, biophysical properties, and effector functions. We highlight the numerous technical advances in antibody structure prediction and design, enabled by the vast number of experimentally determined high-quality structures recorded with cryo-EM, NMR, and X-ray crystallography. Lastly, we assess antibody and vaccine design strategies in the context of structure and dynamics.

Background: Delivered radiotherapy doses do not exactly match those planned for a course of treatment, largely due to inter-fraction changes in anatomy. In this study, accumulated delivered dose was calculated for a sample of cervical cancer patients, by deformably registering daily cone beam computed tomography (CBCT) images to the planning computed tomography (CT) scan. Planned and accumulated doses were compared for the clinical target volume (CTV), bladder, and rectum. Material and Methods: For 10 patients receiving 45 Gy in 25 fractions of external beam radiotherapy, daily dose distributions were calculated on CBCT. These images were deformed onto the planning CT and the dose was accumulated using Velocity 4.1 (Varian Medical Systems, Palo Alto, USA). The quality of deformable image registration was evaluated visually and by calculating Dice similarity coefficients and mean distance to agreement. Results: V95%>99% was achieved for the primary CTV in 9/10 patients for the planned dose distribution and 7/10 patients for the accumulated dose distribution. Primary CTV coverage by 95% of the prescription dose was reduced in one patient, due to an increase in anterior-posterior separation. Comparison of planned and accumulated dose volume histograms (DVHs) for the bladder and rectum found agreement within 5% at low and intermediate doses, but differences exceeded 20% at higher doses. Direct addition of CBCT DVHs was seen to be a poor estimate for the accumulated DVH at higher doses. Conclusion: Computation of delivered radiotherapy dose that accounts for inter-fraction anatomical changes is important for establishing dose-effect relationships. Updating delivered dose distributions after each fraction would support informed clinical decision making on any potential treatment interventions.

Background: High-resolution ecological momentary assessment (HR-EMA) can assess acute alcohol responses during naturalistic heavy drinking episodes. The goal of this study was to use HR-EMA to examine drinking behavior and subjective responses to alcohol in risky drinkers (moderate-severe alcohol use disorder [MS-AUD], heavy social drinkers [HD]) and light drinkers (LD). We expected that risky drinkers would endorse greater alcohol stimulation and reward, with lower sedation, than LD, even when controlling for amount of alcohol consumed., Methods: Participants (N = 112; 54% male, M ± SD age = 27.2 ± 4.2 years) completed smartphone-based HR-EMA during one typical alcohol drinking occasion and one non-alcohol-drinking occasion in their natural environment. Participants were prompted to complete next-day surveys that assessed drinking-related outcomes, study acceptability, and safety., Results: HR-EMA prompt completion rates were excellent (92% and 89% for the alcohol and nonalcohol episodes, respectively). The MS-AUD group consumed the most alcohol with the highest estimated blood alcohol concentration (eBAC) by the end of the alcohol drinking episode (0.14 g/dL) versus LD (0.02 g/dL), with HD intermediate (0.10 g/dL). Relative to LD, MS-AUD and HD endorsed greater positive effects of alcohol (stimulation, liking, and wanting)., Conclusions: This study is the first to use HR-EMA to measure and compare real-world acute alcohol responses across diverse drinker subgroups, including persons with MS-AUD. Results demonstrate that risky drinkers experience heightened pleasurable effects measured in real-time during natural-environment alcohol responses. Rather than drinking excessively to eventually achieve desirable subjective effects, risky drinkers show sensitivity to positive alcohol effects throughout a heavy drinking episode., (© 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Objectives: The case definition for multisystem inflammatory syndrome in children (MIS-C) is broad and encompasses symptoms and signs commonly seen in children with fever. Our aim was to identify clinical predictors that, independently or in combination, identify febrile children presenting to the emergency department (ED) as low risk for MIS-C., Methods: We conducted a retrospective single-center study of otherwise healthy children 2 months to 20 years of age presenting to the ED with fever and who had a laboratory evaluation for MIS-C between April 15, 2020, and October 31, 2020. We excluded children with a diagnosis of Kawasaki disease. Our outcome was an MIS-C diagnosis defined by the Centers for Disease Control and Prevention criteria. We conducted multivariable logistic regression analyses to identify variables independently associated with MIS-C., Results: Thirty-three patients with and 128 patients without MIS-C were analyzed. Of those with MIS-C, 16 of 33 (48.5%) had hypotension for age, signs of hypoperfusion, or required ionotropic support. Four variables were independently associated with the presence of MIS-C; known or suspected SARS CoV-2 exposure (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.9) and the following 3 symptoms and signs: abdominal pain on history (aOR, 4.8; 95% CI, 1.7-15.0), conjunctival injection (aOR, 15.2; 95% CI, 5.4-48.1), and rash involving the palms or soles (aOR, 12.2; 95% CI, 2.4-69.4). Children were at low risk of MIS-C if none of the 3 symptoms or signs were present (sensitivity 87.9% [95% CI, 71.8-96.6]; specificity 62.5% [53.5-70.9], negative predictive value 95.2% [88.3-98.7]). Of the 4 MIS-C patients without any of these 3 factors, 2 were ill-appearing in the ED and the other 2 had no cardiovascular involvement during their clinical course., Conclusions: A combination of 3 clinical symptoms and signs had moderate to high sensitivity and high negative predictive value for identifying febrile children at low risk of MIS-C. If validated, these factors could aid clinicians in determining the need to obtain or forego an MIS-C laboratory evaluation during SARS-CoV-2 prevalent periods in febrile children., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The Impact of Nutrition on Muscle Health in Older Individuals Abstract: The age-related change in the importance of nutrition for muscle health starts at the age of 50. Considering its effects on the mobility and physical independence of older people, the aging of the musculoskeletal system represents one of the greatest public health challenges and tasks for a demographically aging Switzerland. In particular sarcopenia, a pathological decrease in muscle strength, muscle mass and muscle function beyond the physiological age-related changes, correlates with a significantly increased risk of falls as well as increasing morbidity and mortality. Common chronic diseases related to old age not only promote additional muscle loss but also frailty, leading to an additional decline of the quality of life. General practitioners play a crucial role in the initial assessment of changing life circumstances and activity profiles of older people. Thanks to their medical care over many years they are able to identify functional impairments of their aging patients at an early stage and address them in time. This is important because the combination of a high-protein diet and exercise may be extremely effective for improving muscle health and function. Eating more proteins (taking into account the newly revised and increased daily protein requirement for healthy seniors of 1,0-1,2g/kg body weight (bw)) can significantly slow down age-related muscle loss. Depending on age and comorbidities, the daily protein requirement might be even higher (1,5 to 2,0g/kg bw). According to current studies, a minimal protein amount of 25-35g per main dish is recommended for optimal muscle growth stimulation among older individiuals. Thanks to their highly potent boosting power on myofibrillar protein synthesis rates the amino acid L-leucine and L-leucine-rich foods play an important role in elderly people's diet.

To mitigate marine debris and promote sustainable marine industries, legislation and regulations surrounding the management of marine debris have been adopted worldwide. One of the most well-known and important agreements is the International Convention for the Prevention of Pollution from Ships (MARPOL), which focuses on reducing all types of ship-sourced marine pollution. MARPOL Annex V, which deals with the disposal of solid waste, came into force on 31 December 1988. However, was only amended to include a complete ban on waste disposal as of 1 January 2013. Assessing the effectiveness of key regulations is fundamental for supporting evidence-based decisions regarding the management of our oceans. Here, we evaluated whether MARPOL Annex V translated into a decrease in the incidence of shipping- and commercial fishing-sourced debris on remote beaches in Australia using 14 years of standardised, community-driven data. From 2006 to 2020 there was a significant change over time in the density of fishing and shipping debris on Australian beaches; debris density increased up to 2013 followed by a decrease until mid-2017. Although the new regulation started in January 2013, the decrease in density was not recorded until one year later. The decline was only observed for 4 years, reinforcing the existence of lags between the implementation of international agreements and the corresponding potential reduction in debris in the environment. This provides compelling evidence that international agreements and policies by themselves are not enough to solve the debris problem, with improved implementation and enforcement also required. We discuss future perspectives and solutions to reduce ocean-sourced litter inputs into the ocean and highlight the urgent need for action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Prediction of preterm birth is a difficult task for clinicians. By examining an electrohysterogram, electrical activity of the uterus that can lead to preterm birth can be detected. Since signals associated with uterine activity are difficult to interpret for clinicians without a background in signal processing, machine learning may be a viable solution. We are the first to employ Deep Learning models, a long-short term memory and temporal convolutional network model, on electrohysterography data using the Term-Preterm Electrohysterogram database. We show that end-to-end learning achieves an AUC score of 0.58, which is comparable to machine learning models that use handcrafted features. Moreover, we evaluate the effect of adding clinical data to the model and conclude that adding the available clinical data to electrohysterography data does not result in a gain in performance. Also, we propose an interpretability framework for time series classification that is well-suited to use in case of limited data, as opposed to existing methods that require large amounts of data. Clinicians with extensive work experience as gynaecologist used our framework to provide insights on how to link our results to clinical practice and stress that in order to decrease the number of false positives, a dataset with patients at high risk of preterm birth should be collected. All code is made publicly available., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Objectives: Overuse of antibiotics in NICUs is a problem worldwide. Unnecessary antibiotic exposure leads to resistance, changes in the microbiome, and increases the risk of bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, late-onset sepsis (LOS), and mortality in neonates. We aimed to safely reduce the antibiotic usage rate (AUR) in our level IV unit by 10% by December 2018., Methods: A multidisciplinary quality improvement project took place as part of a Vermont Oxford Network initiative in 2018. Multiple interventions took place, including identification of variations in practices and subsequent standardization through the creation of early onset and LOS guidelines, mass education, improved visibility of the guidelines, and standardized documentation. The main outcome measure for this project was the AUR for infants born <35 weeks' gestation expressed as antibiotic doses per 1000 patient days., Results: The AUR decreased from a mean of 524 to 394, for a decrease of 24.8%. Results have been sustained for 3 years. Main contributors that led to the sustained success include decreasing the overall use of antibiotics for early onset sepsis, as well as the duration when cultures are negative. The number of LOS courses also decreased slightly. We noted no cases of inadequately treated sepsis resulting in subsequent positive cultures., Conclusions: Creation of guidelines with mass education and ongoing feedback/monitoring can result in a safe reduction of AUR in the NICU., (Copyright © 2023 by the American Academy of Pediatrics.)

Purpose: As osteoporosis is still underdiagnosed by clinicians and radiologists, the aim of the present study was to assess the performance of an Artificial intelligence (AI)-based Convolutional Neuronal Network (CNN)-Algorithm for the detection of low bone density on routine non-contrast chest CT in comparison to clinical reports using DEXA scans as reference., Method: This retrospective cross-sectional study included patients who underwent non-contrast chest CT and DEXA between April 2018 and June 2018 (n = 109, 19 men, mean age: 67.7 years). CT studies were evaluated for thoracic vertebral bone pathologies using a CNN-Algorithm, which calculates the attenuation profile of the spine. The content of the radiological reports was evaluated for the description of osteoporosis or osteopenia. DEXA was used as the reference standard. To estimate correlation the Spearman test was used and the comparison of the different groups was performed using the Wilcoxon rank sum test. Diagnostic was evaluated by performing a receiver operating characteristic curve analysis., Results: The DEXA examination revealed normal bone density in 42 patients, while 49 patients had osteopenia and 7 osteoporosis. There was a statistically significant correlation between the mean CNN-based attenuation of the thoracic spine and the bone density measured on the DEXA in the hip (r = 0.51, p < 0.001) and lumbar spine (r = 0.34, p = 0.01). The mean attenuation was significantly higher in patients with normal bone density (172 ± 44.5 HU) compared to those with osteopenia or osteoporosis (125.2 ± 33.8 HU), (p < 0.0001). Diagnostic performance in distinguishing normal from abnormal bone density was higher using the CNN-based vertebral attenuation (accuracy 0.75, sensitivity: 0.93, specificity: 0.61) compared to clinical reports (accuracy 0.51, sensitivity: 0.14, specificity: 0.53)., Conclusion: CNN-based evaluation of bone density may provide additional value over standard clinical reports for the detection of osteopenia and osteoporosis in patients undergoing routine non-contrast chest CT scans. This additional value could improve identification of fracture risk and subsequent treatment., Competing Interests: Declaration of Competing Interest U.J.S. received research grants/support from Astellas, Bayer, Bracco, Elucid BioImaging, Guerbet, Heartflow, and Siemens; personal fees from Bayer and Guerbet; consultancy fees from Elucid BioImaging, GE, and Guerbet; speaker honorarium from HeartFlow and Siemens Healthineers. A.V.S. receives research support from Siemens, and is a consultant for Elucid Bioimaging. The other coauthors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Subjective responses to alcohol play a key role in the development and maintenance of risky drinking and alcohol use disorder (AUD). The social and environmental context where drinking occurs may moderate alcohol's subjective effects, but ecologically valid studies of these associations are limited. The present study used high-resolution ecological momentary assessment (HR-EMA) targeting real-world binge drinking episodes to examine associations among drinking context, alcohol consumption, and subjective responses to alcohol., Method: Young adult heavy drinkers ( N = 61; 57% male) completed two smartphone-based, 3-hr HR-EMA of drinking context (social context and location), alcohol use, and subjective responses (alcohol stimulation, sedation, feeling, liking, and wanting more). Analyses examined the associations between drinking context and subjective alcohol responses, accounting for demographic characteristics and individual differences in alcohol consumption., Results: Most (85%) participants reported binge drinking during real-world drinking events. Estimated blood alcohol concentration (eBAC) and alcohol stimulation and reward (liking, wanting) were greater when participants drank with others (vs. alone) and in a bar/restaurant (vs. other location). Sedation was higher when drinking alone versus with others., Conclusions: The present study extends prior laboratory-based research and shows that subjective responses during naturalistic binge drinking episodes may be influenced by drinking context. Drinking with others and in bars and restaurants may increase alcohol consumption, enhance alcohol's rewarding effects, and lead to more alcohol-related harm in at-risk drinkers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Advances in structural biology and the exponential increase in the amount of high-quality experimental structural data available in the Protein Data Bank has motivated numerous studies to tackle the grand challenge of predicting protein structures. In 2020 AlphaFold2 revolutionized the field using a combination of artificial intelligence and the evolutionary information contained in multiple sequence alignments. Antibodies are one of the most important classes of biotherapeutic proteins. Accurate structure models are a prerequisite to advance biophysical property predictions and consequently antibody design. Specialized tools used to predict antibody structures based on different principles have profited from current advances in protein structure prediction based on artificial intelligence. Here, we emphasize the importance of reliable protein structure models and highlight the enormous advances in the field, but we also aim to increase awareness that protein structure models, and in particular antibody models, may suffer from structural inaccuracies, namely incorrect cis-amide bonds, wrong stereochemistry or clashes. We show that these inaccuracies affect biophysical property predictions such as surface hydrophobicity. Thus, we stress the importance of carefully reviewing protein structure models before investing further computing power and setting up experiments. To facilitate the assessment of model quality, we provide a tool "TopModel" to validate structure models.

Leaf senescence is a developmental process allowing nutrient remobilization to sink organs. We characterized flag leaf senescence at 7, 14, and 21 d past anthesis in two near-isogenic barley lines varying in the allelic state of the HvNAM1 transcription factor gene, which influences senescence timing. Metabolomics and microscopy indicated that, as senescence progressed, thylakoid lipids were transiently converted to neutral lipids accumulating in lipid droplets. Senescing leaves also exhibited an accumulation of sugars including glucose, while nitrogen compounds (nucleobases, nucleotides, and amino acids) decreased. RNA-Seq analysis suggested lipid catabolism via β-oxidation and the glyoxylate cycle, producing carbon skeletons and feeding respiration as a replacement of the diminished carbon supply from photosynthesis. Comparison of the two barley lines highlighted a more prominent up-regulation of heat stress transcription factor- and chaperone-encoding genes in the late-senescing line, suggesting a role for these genes in the control of leaf longevity. While numerous genes with putative roles in nitrogen remobilization were up-regulated in both lines, several peptidases, nucleases, and nitrogen transporters were more highly induced in the early-senescing line; this finding identifies processes and specific candidates which may affect nitrogen remobilization from senescing barley leaves, downstream of the HvNAM1 transcription factor., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sharks and other cartilaginous fish produce new antigen receptor (IgNAR) antibodies, as key part of their humoral immune response and are the phylogenetically oldest living organisms that possess an immunoglobulin (Ig)-based adaptive immune system. IgNAR antibodies are naturally occurring heavy-chain-only antibodies, that recognize antigens with their single domain variable regions (VNARs). In this study, we structurally and biophysically elucidate the effect of antibody humanization of a previously published spiny dogfish VNAR (parent E06), which binds with high affinity to the human serum albumin (HSA). We analyze different humanization variants together with the parental E06 VNAR and the human Vκ1 light chain germline DPK9 antibody to characterize the influence of point mutations in the framework and the antigen binding site on the specificity of VNARs as reported by Kovalenko et al. We find substantially higher flexibility in the humanized variants, reflected in a broader conformational space and a higher conformational entropy, as well as population shifts of the dominant binding site ensembles in solution. A further variant, in which some mutations are reverted, largely restores the conformational stability and the dominant binding minimum of the parent E06. We also identify differences in surface hydrophobicity between the human Vκ1 light chain germline DPK9 antibody, the parent VNAR E06 and the humanized variants. Additional simulations of VNAR-HSA complexes of the parent E06 VNAR and a humanized variant reveal that the parent VNAR features a substantially stronger network of stabilizing interactions. Thus, we conclude that a structural and dynamic understanding of the VNAR binding site upon humanization is a key aspect in antibody humanization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fernández-Quintero, Fischer, Kokot, Waibl, Seidler and Liedl.)

Introduction: The incidence of afibrinogenemia had not been previously reported in Algeria. Afibrinogenemia patients are prone to both haemorrhagic and thrombotic complications. Predictive markers of thrombosis in afibrinogenemia patients are not existent., Aims and Methods: Clinical and biological data from 46 afibrinogenemia patients are reported. Biological investigations included routine tests, genetics analysis and thrombin generation., Results: FGA mutations (four novel and four previously described) and FGB mutations (seven mutations; five novels) were homozygous in all but one family as a result of 28 consanguineous marriages out of 30 discrete families. Incidence of afibrinogenemia in Algeria is at least 3 per million births. Umbilical bleeding was reported in 39/46 cases and was the main discovery circumstance. We also report post trauma or post-surgery (3/46) bleeding and spontaneous deep vein thrombosis (DVT) in adulthood (1/46), as discovery circumstances. The median age (10.5-year-old) of the population reported here explains why there are few hemarthrosis and obstetrical or gynaecological complications in this series. Thrombotic events were reported in seven patients (four spontaneous). Endogenous Thrombin Potential was significantly increased in thrombosis-prone patients compared to afibrinogenemic patients with and without personal or familial history (1118 vs. 744 and 817 nM IIa × min, respectively)., Conclusion: The incidence of afibrinogenemia in Algeria is the consequence of consanguineous marriage in families carrying private mutations. The thrombin generation test (TGT) could identify, among afibrinogenemic patients, those presenting a thrombotic risk., (© 2022 John Wiley & Sons Ltd.)

Objectives: To evaluate the benefit of a prototype circulation time-based test bolus evaluation algorithm for the individualized optimal timing of contrast media (CM) delivery in patients undergoing coronary CT angiography (CCTA)., Methods: Thirty-two patients (62 ± 16 years) underwent CCTA using a prototype bolus evaluation tool to determine the optimal time-delay for CM administration. Contrast attenuation, signal-to-noise ratio (SNR), objective, and subjective image quality were evaluated by two independent radiologists. Results were compared to a control cohort (matched for age, sex, body mass index, and tube voltage) of patients who underwent CCTA using the generic test bolus peak attenuation +4 s protocol as scan delay., Results: In the study group, the mean time delay to CCTA acquisition was significantly longer (26.0 ± 2.9 s) compared to the control group (23.1 ± 3.5 s; p < 0.01). In the study group, SNR improvement was seen in the right coronary artery (17.5 vs 13; p = 0.028), the left main (15.3 vs 12.3; p = 0.027), and the left anterior descending artery (18.5 vs 14.1; p = 0.048). Subjective image quality was rated higher in the study group (4.75 ± 0.7 vs 3.64 ± 0.5; p < 0.001)., Conclusions: The prototype test bolus evaluation algorithm provided a reliable patient-specific scan delay for CCTA that ensured homogenous vascular attenuation, improvement in objective and subjective image quality, and avoidance of beam hardening artifacts., Advances in Knowledge: The prototype contrast bolus evaluation and optimization tool estimated circulation time-based time-delay improves the overall quality of CCTA.

Rationale and Objectives: Research on implementation of artificial intelligence (AI) in radiology workflows and its impact on reports remains scarce. In this study, we aim to assess if an AI platform would perform better than clinical radiology reports in evaluating noncontrast chest computed tomography (CT) scans., Materials and Methods: Consecutive patients who had undergone noncontrast chest CT were retrospectively identified. The radiology reports were reviewed in a binary fashion for reporting of pulmonary lesions, pulmonary emphysema, aortic dilatation, coronary artery calcifications (CAC), and vertebral compression fractures (VCF). CT scans were then processed using an AI platform. The reports' findings and the AI results were subsequently compared to a consensus read by two board-certificated radiologists as reference., Results: A total of 100 patients (mean age: 64.2 ± 14.8 years; 57% males) were included in this study. Aortic segmentation and calcium quantification failed to be processed by AI in 2 and 3 cases, respectively. AI showed superior diagnostic performance in identifying aortic dilatation (AI: sensitivity: 96.3%, specificity: 81.4%, AUC: 0.89) vs (Reports: sensitivity: 25.9%, specificity: 100%, AUC: 0.63), p <0.001; and CAC (AI: sensitivity: 89.8%, specificity: 100, AUC: 0.95) vs (Reports: sensitivity: 75.4%, specificity: 94.9%, AUC: 0.85), p = 0.005. Reports had better performance than AI in identifying pulmonary lesions (Reports: sensitivity: 97.6%, specificity: 100%, AUC: 0.99) vs (AI: sensitivity: 92.8%, specificity: 82.4%, AUC: 0.88), p = 0.024; and VCF (Reports: sensitivity:100%, specificity: 100%, AUC: 1.0) vs (AI: sensitivity: 100%, specificity: 63.7%, AUC: 0.82), p <0.001. A comparable diagnostic performance was noted in identifying pulmonary emphysema on AI (sensitivity: 80.6%, specificity: 66.7%. AUC: 0.74) and reports (sensitivity: 74.2%, specificity: 97.1%, AUC: 0.86), p = 0.064., Conclusion: Our results demonstrate that incorporating AI support platforms into radiology workflows can provide significant added value to clinical radiology reporting., Competing Interests: DECLARATION OF COMPETING INTEREST The other authors have no potential conflict of interest to disclose, (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute and late toxicity was analysed for prostate cancer patients with bilateral hip prostheses, who received fixed field intensity modulated radiotherapy (IMRT). The aims were (1) to establish whether toxicity rates differed from those of a control group with normal hips, (2) to develop a volumetric modulated arc therapy (VMAT) approach for patients with prostheses and (3) to compare doses to bladder and rectum for the control group, prostheses group and VMAT replans for the prostheses group., Methods: Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using Common Terminology Criteria for Adverse Events version 5.0. The incidence of grade 2 or worse (G2+) toxicity was compared using Fisher's exact test. Dose volume histograms (DVHs) and mean doses to organs at risk (OARs) were compared using signed rank tests., Results: There were 17 patients in the prostheses group and 50 in the control group. Acute and late GU toxicity was similar. G2+ late GI toxicity incidence was 31% for the prostheses group and 14% for the control group (p = 0.14). Significant differences (p < 0.05) were seen between the OAR DVHs of the prostheses group who had IMRT and the control group for a range of intermediate doses. The rectum mean dose was significantly different (p < 0.001), but no difference was seen for the bladder mean dose (p = 0.08)., Conclusions: No significant differences were seen in GU and GI toxicity incidence between patients with bilateral hip prostheses and a control group. The DVHs for bladder and rectum were significantly higher for patients with prostheses planned with IMRT. Replanning using a VMAT technique significantly reduced doses to the OARs, whilst maintaining good planning target volume coverage., (© 2022. The Author(s).)

As the current biotherapeutic market is dominated by antibodies, the design of different antibody formats, like bispecific antibodies, is critical to the advancement of the field. In contrast to monovalent antibodies, which consist of two identical antigen-binding sites, bispecific antibodies can target two different epitopes by containing two different antigen-binding sites. Thus, the rise of new formats as successful therapeutics has reignited the interest in advancing and facilitating the efficient production of bispecific antibodies. Here, we investigate the influence of point mutations in the antigen-binding site, the paratope, on heavy and light chain pairing preferences by using molecular dynamics simulations. In agreement with experiments, we find that specific residues in the antibody variable domain (Fv), i.e., the complementarity-determining region (CDR) L3 and H3 loops, determine heavy and light chain pairing preferences. Excitingly, we observe substantial population shifts in CDR-H3 and CDR-L3 loop conformations in solution accompanied by a decrease in bispecific IgG yield. These conformational changes in the CDR3 loops induced by point mutations also influence all other CDR loop conformations and consequentially result in different CDR loop states in solution. However, besides their effect on the obtained CDR loop ensembles, point mutations also lead to distinct interaction patterns in the V H -V L interface. By comparing the interaction patterns among all investigated variants, we observe specific contacts in the interface that drive heavy and light chain pairing. Thus, these findings have broad implications in the field of antibody engineering and design because they provide a mechanistic understanding of antibody interfaces, by identifying critical factors driving the pairing preferences, and thus can help to advance the design of bispecific antibodies.

Background: Quiescent-interval slice-selective (QISS) magnetic resonance angiography (MRA) is a non-contrast alternative for the pre-procedural assessment of patients with peripheral artery disease (PAD). However, the feasibility of pre-procedural stent size estimation using QISS MRA would merit investigation., Purpose: To evaluate the feasibility of QISS MRA for pre-procedural stent size estimation in PAD patients compared to computed tomography angiography (CTA)., Study Type: Retrospective., Subjects: Thirty-three PAD patients (68 ± 9 years, 18 men, 15 women)., Field Strength/sequence: Two-dimensional balanced steady-state free precession QISS MRA at 1.5 T and 3 T., Assessment: All patients received QISS MRA and CTA of the lower extremity run-off followed by interventional digital subtraction angiography (DSA). Stenotic lesion length and diameter were quantified (AMF and AVS with 3 and 13 years of experience in cardiovascular imaging, respectively) to estimate the dimensions of the stent necessary to restore blood flow in the treated arteries. Measured dimensions were adjusted to the closest stent size available., Statistical Tests: The Friedman test with subsequent pairwise Wilcoxon signed-rank test was used to compare the estimated stent dimensions between QISS MRA, CTA, and the physical stent size used for intervention. Intra-class correlation (ICC) analysis was performed to assess inter-reader agreement. Significant differences were considered at P < 0.05., Results: No significant difference was observed between estimated stent diameter by QISS MRA or CTA compared to physical stent diameter (8.9 ± 2.9 mm, 8.8 ± 3.0 mm, and 8.8 ± 3.8 mm, respectively; χ 2  = 1.45, P = 0.483). There was a significant underestimation of stent length for both QISS MRA and CTA, compared to physical stent length (45.8 ± 27.8 mm, 46.4 ± 29.3 mm, and 50.4 ± 34.0 mm, respectively; χ 2  = 11.96) which could be corrected when measurements were adjusted to the next available stent length (χ 2  = 2.38, P = 0.303). Inter-reader assessment showed good to excellent agreement between the readers (all ICC ≥0.81)., Data Conclusion: QISS MRA represents a reliable method for pre-procedural lesion assessment and stent diameter and length estimation in PAD patients., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Synthetic microbial communities have the potential to enable new platforms for bioproduction of biofuels and biopharmaceuticals. However, using engineered communities is often assumed to be difficult because of anticipated challenges in establishing and controlling community composition. Cross-feeding between microbial auxotrophs has the potential to facilitate coculture growth and stability through a mutualistic ecological interaction. We assessed cross-feeding between 13 Escherichia coli amino acid auxotrophs paired with a leucine auxotroph of Bacillus megaterium. We developed a minimal medium capable of supporting the growth of both bacteria and used the media to study coculture growth of the 13 interspecies pairs of auxotrophs in batch and continuous culture, as well as on semi-solid media. In batch culture, 8 of 13 pairs of auxotrophs were observed to grow in coculture. We developed a new metric to quantify the impact of cross-feeding on coculture growth. Six pairs also showed long-term stability in continuous culture, where coculture growth at different dilution rates highlighted differences in cross-feeding amongst the pairs. Finally, we found that cross-feeding-dependent growth on semi-solid media is highly stringent and enables identification of the most efficient pairs. These results demonstrate that cross-feeding is a viable approach for controlling community composition within diverse synthetic communities., (© 2021 Wiley Periodicals LLC.)

Objective: To evaluate 30 day rate of major adverse cardiac events (MACE) utilizing cCTA and FFR CT for evaluation of patients presenting to the Emergency Department (ED) with acute chest pain., Materials and Methods: Patients between the ages of 18-95 years who underwent clinically indicated cCTA and FFR CT in the evaluation of acute chest pain in the emergency department were retrospectively evaluated for 30 day MACE, repeat presentation/admission for chest pain, revascularization, and additional testing., Results: A total of 59 patients underwent CCTA and subsequent FFR CT for the evaluation of acute chest pain in the ED over the enrollment period. 32 out of 59 patients (54 %) had negative FFR CT (>0.80) out of whom 18 patients (55 %) were discharged from the ED. Out of the 32 patients without functionally significant CAD by FFR CT , 32 patients (100 %) underwent no revascularization and 32 patients (100 %) had no MACE at the 30-day follow-up period., Conclusion: In this limited retrospective study, patients presenting to the ED with acute chest pain and with CCTA with subsequent FFR CT of >0.8 had no MACE at 30 days; however, for many of these patients results were not available at time of clinical decision making by the ED physician., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C., Study Design: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs., Results: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P < .0001), and increased frequency of abdominal pain (OR 12.5, 95% CI [1.65-33.24]), neck pain (536.5, [2.23-129,029]), conjunctivitis (31.3, [4.6-212.8]), oral mucosal irritation (11.8, [1.4-99.4]), extremity swelling or rash (99.9, [5-1960]), and generalized rash (7.42, [1.6-33.2]). Patients with MIS-C demonstrated lower absolute lymphocyte (P < .0001) and platelet counts (P < .05) and greater C-reactive protein concentrations (P < .001)., Conclusions: Patients treated for MIS-C due to concern for potential cardiac injury show combinations of features distinct from other febrile patients seen in outpatient clinics during the same period., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate a new contrast media (CM) injection system in patients undergoing coronary computed tomography angiography (CCTA)., Methods: Seventy-one consecutive patients (33 men and 38 women, mean age 59.0 ± 14.5 years) who underwent CCTA between February and April 2019 using the CT injection system MEDRAD Stellant FLEX (Bayer) were included retrospectively in this single-center study. Quantitative and qualitative image quality parameters were assessed, and the injection system's usability and operational efficiency were evaluated. Results were compared with a matched control group., Results: All examinations were rated as diagnostic. Usability and operational efficiency of the new injector were rated higher than that of the standard injector system, and no significant differences were found for quantitative and qualitative image quality parameters compared with the control group ( P ≥ .05)., Discussion: Software-based injection facilitates individualized CM application while maintaining high image quality standards in CCTA. Diagnostic accuracy analysis was not performed, but as image quality analysis showed no significant differences, no discrepancies regarding this issue are expected., Conclusion: This study demonstrates that the MEDRAD Stellant FLEX CT injection system allows for consistent high-quality CCTA scanning with increased usability and operational efficiency., (© 2021 American Society of Radiologic Technologists.)

Objective: To evaluate a novel fully automated mitral valve analysis software platform for cardiac computer tomography angiography (CCTA)-based structural heart therapy procedure planning., Methods: The study included 52 patients (25 women; mean age, 66.9 ± 12.4 years) who had undergone CCTA prior to transcatheter mitral valve replacement (TMVR) or surgical mitral valve intervention (replacement or repair). Therapeutically relevant mitral valve annulus parameters (projected area, circumference, trigone-to-trigone (T-T) distance, anterior-posterior (AP) diameter, and anterolateral-posteromedial (AL-PM) diameter) were measured. Results of the fully automated mitral valve analysis software platform with and without manual adjustments were compared with the reference standard of a user-driven measurement program (3mensio, Pie Medical Imaging). Measurements were compared between the fully automated software, both with and without manual adjustment, and the user-driven program using intraclass correlation coefficients (ICC). A secondary analysis included the time to obtain all measurements., Results: Fully automated measurements showed a good to excellent agreement (circumference, ICC = 0.70; projected area, ICC = 0.81; T-T distance, ICC = 0.64; AP, ICC = 0.62; and AL-PM diameter, ICC = 0.78) compared with the user-driven analysis. There was an excellent agreement between fully automated measurement with manual adjustments and user-driven analysis regarding circumference (ICC = 0.91), projected area (ICC = 0.93), T-T distance (ICC = 0.80), AP (ICC = 0.78), and AL-PM diameter (ICC = 0.79). The time required for mitral valve analysis was significantly lower using the fully automated software with manual adjustments compared with the standard assessment (134.4 ± 36.4 s vs. 304.3 ± 77.7 s) (p < 0.01)., Conclusion: The fully automated mitral valve analysis software, when combined with manual adjustments, demonstrated a strong correlation compared with the user-driven software while reducing the total time required for measurement., Key Points: • The novel software platform allows for a fully automated analysis of mitral valve structures. • An excellent agreement was found between the fully automated measurement with manual adjustments and the user-driven analysis. • The software showed quicker measurement time compared with the standard analysis of the mitral valve.

Purpose: We prospectively investigate the feasibility of a patient specific automated tube voltage selection (ATVS)-based coronary artery calcium scoring (CACS) protocol, using a kV-independent reconstruction algorithm, to achieve significant dose reductions while maintaining the overall cardiac risk classification., Methods: Forty-three patients (mean age, 61.8 ± 9.0 years; 40% male) underwent a clinically indicated CACS scan at 120kVp, as well as an additional CACS acquisition using an individualized tube voltage between 70 and 130kVp based on the ATVS selection (CARE-kV). Datasets of the additional CACS scans were reconstructed using a kV-independent algorithm that allows for calcium scoring without changing the weighting threshold of 130HU, regardless of the tube voltage chosen for image acquisition. Agatston scores and radiation dose derived from the different ATVS-based CACS studies were compared to the standard acquisition at 120kVp., Results: Thirteen patients displayed a score of 0 and were correctly identified with the ATVS protocol. Agatston scores derived from the standard 120kVp (median, 33.4; IQR, 0-289.7) and the patient-tailored kV-independent protocol (median, 47.5; IQR, 0-287.5) showed no significant differences (p = 0.094). The intra-class correlation for Agatston scores derived from the two different protocols was excellent (ICC = 0.99). The mean dose-length-product was 29.8 ± 11.9 mGy × cm using the ATVS protocol and 31.7 ± 11.4 mGy × cm using the standard 120kVp protocol (p < 0.001). Additionally, 95% of patients were classified into the same risk category (0, 1-10, 11-100, 101-400, or > 400) using the patient-tailored protocol., Conclusions: ATVS-based CACS, using a kV-independent algorithm, allows for high accuracy compared to the standard 120kVp scanning, while significantly reducing radiation dose parameters., Key Points: • ATVS allows for CT scanning with reduced radiation dose values. • KV-independent CACS is feasible at any tube voltage between 70 and 130 kVp. • ATVS applied to kV-independent CACS can significantly reduce the radiation dose.