Search

Large medical image repositories present challenges related to unstructured data. A data enrichment process allows the storage of additional information for fast identification of the content and properties of medical imaging studies. The aim of this study is to develop a metadata enrichment pipeline to facilitate the secondary use of medical images in a high-throughput environment. Our aim was to develop a categorization tool for the MR series to generate standardized tags that identify relevant image characteristics such as patient orientation, sequence type, weighting type, or the presence of fat suppression. Three models that make use of machine learning (ML) and DICOM tags are proposed. The dataset for their development consists of 4666 MR series from cancer patients, labeled by expert radiologists and acquired from different manufacturers, clinical centers and anatomical regions, covering as much variability as possible with the aim of making the models generalizable to other databases. Moreover, the inference performance of the end system has been evaluated on 25,596 MR series as well as the final model outputs with an external evaluation set of 1286 MR series. The weighting model achieves very reliable results with a f1 score of 88% in the validation set. Junk and chemical shift models achieved scores of 82% and 83% respectively. These results open the door to the automatic application of image post-processing and deep learning algorithms after accurate labeling, minimizing human intervention. Furthermore, the proposed solution can infer thousands of DICOM series in less than one minute. Thanks to the fast inference times provided by this solution, it fits well in a big data ecosystem, eliminating any performance issues on ingestion in a semi-real-time environment. [ABSTRACT FROM AUTHOR]

In the Netherlands, percentages of induction of labour (IOL) range from 14.3 to 41.1% in regional maternity care networks (MCNs). In this study, we focus on women's contribution in explaining this variation in range. We examine if different factors at the level of the individual woman (micro) and the level of the woman's social context (meso) are related to decision-making on IOL, and the variation. We used an online questionnaire inviting women counselled for IOL (n = 180, response rate 40%) from six different MCNs, three with a high and three with a low percentage of IOL. Factors included are, for example, attitude towards birth, reason for IOL, and social norms. Descriptive statistics and regression analyses were performed to examine the relation between the included factors and the intended decision on IOL. Our results show that only the factor women's attitude towards birth is related to the intended decision on IOL. The more women believe that birth is a medical process, the higher the odds that the intended decision is to induce labour. This may contribute to variation in IOL between individual women, but appears to contribute less to variation in IOL between MCNs. This is because the percentages of women with an intended decision for IOL do not differ within MCNs with a low or high percentage of IOL. A next step in explaining practice variation, is to examine mechanisms at the level of the individual healthcare provider (micro) and the MCN (meso). [ABSTRACT FROM AUTHOR]

Background: Postoperative delirium is a frequent complication with negative consequences for neurosurgical patients. Recorded music has been shown to reduce the incidence of delirium, however its economic benefit remains unclear. This study aimed to investigate the cost-effectiveness of perioperative music in preventing postoperative delirium. Methods: This study used data from a randomized controlled trial (Clinical Trials.gov; NCT04649450) that compared the effect of perioperative music with standard of clinical care on the occurrence of postoperative delirium in patients undergoing craniotomy at the Erasmus Medical Centre. The primary outcome of this study is the cost-effectiveness of the music intervention. A trial-based cost-effectiveness analysis (CEA) was conducted from a societal perspective. Mean costs were calculated using bootstrapping with 95% confidence intervals. Secondary outcomes included postoperative complications, mortality, cognitive functioning, and quality of life. Costs and patient outcomes were assessed separately for the initial hospital admission and long-term follow-up until 6 months after discharge. Results: This study included 91 patients in the intervention group and 93 in the control group. On average, medical costs during initial admission were lower, albeit not statistically significant, in the music group compared to the control group (€ 11,819 vs. € 13,106), mostly due to a shorter length of stay. Total costs over the 6-month period were nearly identical between the groups, at € 18,587 and € 18,571 in the music and control group, respectively. Conclusions: Pre-recorded perioperative music may be a cost-effective intervention for reducing postoperative delirium in neurosurgical patients, possibly by decreasing healthcare utilization and costs during primary admission. Further studies are needed to confirm its potential as a cost-effective intervention. [ABSTRACT FROM AUTHOR]

Background: Little attention has been paid to the generalizability of cohort studies in bipolar disorder (BD) to patient with BD in everyday clinical practice. Methods: A sample of patients with bipolar I disorder (BD-I) treated at a Dutch outpatient clinic for BD were compared with Dutch participants with BD-I of four clinical cohort studies, and participants with BD-I in a general population study in the Netherlands, on sociodemographic and clinical characteristics. Results: On many variables participants from the outpatient sample matched with those of the included studies. However, compared with participants of several of the clinical cohort studies, these outpatients were significantly younger, had an earlier age of onset of mood symptoms, and had a shorter duration of illness. Compared with participants in the general population study, outpatients had significant higher levels of education and less often lived together or were married. One cohort study reported much lower comorbidity rates of alcohol use disorders, drug use disorders, and anxiety disorders than in the outpatient sample. In contrast, comorbidity rates were higher in the population study. Limitations: Due to methodological differences between studies, comparisons between several variables was limited, and for some variables data was lacking. Conclusions: Our findings suggest that many findings from cohort studies and general population study in BD-I are generalizable to everyday clinical practice, especially mood disorder outpatient centers. However, differences between samples indicate some selection and referral bias. [ABSTRACT FROM AUTHOR]

The Wadden Sea is the world's largest intertidal area and a UNESCO World Heritage Site. Macrozoobenthic invertebrates perform key ecological functions within intertidal areas by regulating nutrient cycles, decomposing organic matter, and providing food for fish, birds and humans. To understand ecological processes and human impacts on biodiversity, the Synoptic Intertidal BEnthic Survey (SIBES) has sampled intertidal macrozoobenthos since 2008. On average 4,109 stations across 1,200 km² of Dutch Wadden Sea mudflats are sampled from June to October to quantify the benthic invertebrate community and sediment composition, including species abundance and biomass, and grain size and mud content. The dataset published now contains 51,851 sampled stations with 3,034,760 individuals of 177 species. This paper details data collection, validation and processing methods. SIBES is ongoing and data will be updated yearly. In sharing these data, we hope to enhance collaborations and understanding of the impact of various pressures on macrozoobenthic invertebrates, sediment composition, food webs, the ecosystem, and biodiversity in the Wadden Sea and other intertidal habitats. [ABSTRACT FROM AUTHOR]

Indecent exposure is often regarded as a nuisance offense and detailed studies into this topic are relatively rare. However, there is consensus that relatively high recidivism rates and risk of escalation to more severe offenses can be of serious concern among these perpetrators. This cohort study aims to increase our general knowledge on the basic characteristics of these offenses and includes all registered police cases of indecent exposure in the Netherlands between 2012 and 2020, including 6741 incidents, involving 4663 suspects and 3808 registered victims. This first study of a large cohort over a long period of time describes the basic characteristics of these incidents, the perpetrators and their victims, and visualizes the results to explore trends over time. Results show that a modal indecent exposure incident is perpetrated by a 25-year-old male, on foot, on a public road, on a Wednesday afternoon in July, masturbating and directing his genitals intentionally toward a 13-year-old girl. The age distribution of victims shows remarkable similarity to victims of sexual assault. Compared to the first year of the period studied, the number of annually reported incidents gradually declined to half in the last year of the study. Findings are discussed in light of the most prominent theories on exhibitionism. Issues and suggestions relevant to apprehension and treatment of perpetrators are identified and discussed. [ABSTRACT FROM AUTHOR]

Purpose: Patients with metastatic colorectal cancer (mCRC) undergoing systemic treatment often experience toxicities. Although exercise may improve physical fitness and quality of life and counteract treatment toxicity, knowledge in patients with mCRC is limited. The ongoing randomized controlled AMICO trial evaluates the effects of supervised exercise on clinical outcomes. The present qualitative study was a pre-planned part of this trial aiming to capture adherence, satisfaction, and perceived effects of exercise among patients with mCRC. Methods: Patients with mCRC receiving first-line systemic treatment were randomized (1:1:1) to a control group or one of two supervised exercise arms including continuous aerobic exercise with either resistance exercises or high-intensity interval training. Semi-structured interviews with patients in the exercise arms were transcribed verbatim and thematically analyzed. Descriptive data on adherence (exercise logs) and satisfaction (questionnaire) was collected to complement and contextualize the qualitative findings. Results: Twenty-one patients were interviewed. Median exercise attendance was 67% [IQR 35–91], and the median satisfaction score was 8 [IQR 8–9] out of 10. Patients valued the guidance and knowledge of the physical therapist and expressed interindividual preferences regarding training content. Patients experienced that exercise improved their physical and mental wellbeing and helped them to endure treatment. Perceived exercise barriers were treatment toxicity, physical problems, and hospital appointments. Perceived exercise facilitators included adequate tailoring and internal or external motivation. Conclusion: Patients with mCRC appreciated exercise during systemic treatment and perceived several beneficial effects, both physically and mentally. Exercise attendance varied and barriers were mainly treatment- and disease-related. Trial registration: Clinical trial.GOV ID: NCT04754672. Date of registration: 04–12-2020. [ABSTRACT FROM AUTHOR]

How people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the feasibility of using patient-specific implants (PSI) for complex shaft corrective osteotomies in multiplanar deformities of long bones in the lower extremities. Additionally, it aimed to investigate the added value of these implants by quantifying surgical accuracy on postoperative CT, comparing their outcomes to two commonly used techniques: 3D virtual visualizations and 3D-printed surgical guides. Methods: Six tibial and femoral shaft corrective osteotomies were planned and performed on three Thiel embalmed human specimen. Depending on the specimen a different respective technique was used; 1) ‘3D Visualization’ using 3D virtual plan preoperatively and free-hand corrective osteotomy techniques with standard manually contoured plates; 2) ‘3D guided’ utilizing 3D surgical guides and manually contouring of conventional implant; and 3)‘3D PSI’ utilizing a 3D surgical guide with a patient-specific implant. Accuracy of the corrections was assessed through measurements for varus/valgus angulation, ante/recurvation, rotation and osteotomy plane error as quantified on postoperative CT-scans. Results: Twelve corrective osteotomies were performed. For, the median difference between the surgical plan and postoperative CT assessment was 3.4°, 4.6°, and 2.2° for the ‘3D visualization’, ‘3D guided’, and ‘3D PSI’ methods respectively. Regarding ante/recurvation, the differences were 3.8°, 43.8°, and 1.2°, respectively. For rotation, the differences were 11.9°, 18.7°, and 3.5°, respectively. Discrepancies between planned and executed levels of osteotomy plane were 6.2 mm, 3.2 mm, and 1.4 mm, respectively. Conclusion: PSIs with 3D-printed drilling guides for complex multiplanar corrective osteotomies of femoral and tibial shaft malunions is feasible and achieves accurate corrections. This technique enables precise determination of the osteotomy plane, guides correction in all three planes, and ensures satisfactory implant fitting; thus accurately translating the virtual surgical plan into clinical practice. The 3D PSI method is beneficial for complex cases with significant multiplanar deformities in bone anatomy, particularly with rotational malalignment. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease are often requested to engage in self-monitoring sodium (i.e. salt) intake, but it is currently unknown how self-monitoring would empower them. This study aims to assess: (1) how frequent self-monitoring tools are being used during low-sodium diet self-management interventions; (2) whether self-efficacy (i.e. trust in own capability to manage the chronic disease) is associated with self-monitoring frequency; and (3) whether higher self-monitoring frequency is associated with an improvement in self-efficacy over time. Method: Data from two multicenter randomized controlled trials (ESMO [n = 151] and SUBLIME [n = 99]) among adult Dutch patients with chronic kidney disease (eGFR ≥ 20–25 mL/min/1.73 m2) were used. In both studies, routine care was compared to a 3-month low-sodium diet self-management intervention with several self-monitoring tools (online food diary, home blood pressure monitor, and urinary sodium measurement device [only ESMO]). Data was collected on usage frequency of self-monitoring tools. Frequencies during the interventions were compared between low and high baseline self-efficacy groups using the Mann-Whitney U test and T-test and associated with changes in self-efficacy during the interventions using Spearman correlation coefficients. Results: Large variations in self-monitoring frequency were observed. In both interventions, usage of self-monitoring tools was highest during the first month with sharp drops thereafter. The online food diary was the most frequently used tool. In the ESMO intervention, low baseline self-efficacy was associated with a higher usage frequency of self-monitoring tools. This finding was not confirmed in the SUBLIME intervention. No significant associations were found between usage frequency of self-monitoring tools and changes in self-efficacy over time. Conclusion: Patients with low self-efficacy might benefit most from frequent usage of self-monitoring tools when sufficient guidance and support is provided. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease due to loss of dystrophin, leading to progressive muscle wasting and physical inactivity. In this pilot study, we studied the effect of daily supplementation of the anabolic substrate beta-hydroxy-beta-methylbutyrate (HMB) on whole body protein and amino acid kinetics using novel isotope methods and daily activity in a canine model of DMD. Six DMD dogs were administered 3 g daily of HMB or placebo for 28 days according to a randomized, placebo-controlled, double-blinded crossover design. We measured pre- and post-intervention daily activity, biochemistry markers, and whole-body amino acid kinetics. We tracked daily activity with an activity monitoring device and measured plasma creatine kinase and standard clinical biochemistry panels to monitor muscle and organ function. To calculate whole body and intracellular amino acid production, we administered in the postabsorptive state an IV stable isotope solution containing 20 amino acid tracers. We collected blood before and six times after until two hours post tracer pulse administration and measured amino acid enrichments and concentrations by LC–MS/MS, subsequently followed by (non) compartmental modeling of the decay enrichment curves. Results were expressed as mean with 95% CI. Whole body production, plasma concentrations, and intra-/extracellular compartmental analyses of various amino acids were attenuated in HMB-dosed DMD dogs. Specifically, the plasma concentration of hydroxyproline (marker of collagen breakdown) was significantly higher in the placebo group compared to the HMB group. The intra- and extracellular pool sizes and flux between the two compartments of hydroxyproline was reduced in HMB treated dogs. DMD dogs treated with HMB as compared to placebo had a respective 40% increase in exertional (play) (951 [827, 1075] versus 569 [491, 647]; p < 0.0001) and 10.5% increase in non-exertional (active) activity (15,366 [14742, 15990] versus 13,806 [13148,14466]; p = 0.0016). In addition, a 6% reduction was found in rest time after HMB supplementation compared to placebo (23,857 [23,130, 24,584], versus 25,363 [24500, 26225]; p = 0.0122). Creatine kinase was not statistically different between groups. We did not observe any adverse clinical or biochemical-related effects of HMB dosing. Daily HMB supplementation in DMD dogs can safely and positively influence protein and amino acid metabolism and improve overall daily activity. [ABSTRACT FROM AUTHOR]

AI decision support systems can assist clinicians in planning adaptive treatment strategies that can dynamically react to individuals' cancer progression for effective personalized care. However, AI's imperfections can lead to suboptimal therapeutics if clinicians over or under rely on AI. To investigate such collaborative decision-making process, we conducted a Human–AI interaction study on response-adaptive radiotherapy for non-small cell lung cancer and hepatocellular carcinoma. We investigated two levels of collaborative behavior: model-agnostic and model-specific; and found that Human–AI interaction is multifactorial and depends on the complex interrelationship between prior knowledge and preferences, patient's state, disease site, treatment modality, model transparency, and AI's learned behavior and biases. In summary, some clinicians may disregard AI recommendations due to skepticism; others will critically analyze AI recommendations on a case-by-case basis; clinicians will adjust their decisions if they find AI recommendations beneficial to patients; and clinician will disregard AI recommendations if deemed harmful or suboptimal and seek alternatives. AI decision support system non-homogenously influences clinical decisions in dynamic treatment regimen, as it depends on several factors including prior knowledge, preference, disease type, treatment modality, and AI's learned behavior and inherent biases. [ABSTRACT FROM AUTHOR]

The immunoregulatory cytokine TGF-β is pleiotropic due to the near-ubiquitous expression of the TGF-β receptors TβRI and TβRII on diverse cell types. The helminth parasite Heligmosomoides polygyrus has convergently evolved a family of TGF-β mimics (TGMs) that bind both these receptors through domains 1–3 of a 5-domain protein. One member of this family, TGM4, differs from TGF-β in acting in a cell-specific manner, failing to stimulate fibroblasts, but activating SMAD phosphorylation in macrophages. Primarily through domains 4 and 5, TGM4 interacts with multiple co-receptors, including CD44, CD49d (integrin α4) and CD206, and can up- and downmodulate macrophage responses to IL-4 and lipopolysaccharide (LPS), respectively. The dependence of TGM4 on combinatorial interactions with co-receptors is due to a moderated affinity for TβRII that is more than 100-fold lower than for TGF-β. Thus the parasite has elaborated TGF-β receptor interactions to establish cell specificity through combinatorial cis-signalling, an innovation absent from the mammalian cytokine. Synopsis: A parasite-derived mimic of TGF-β selectively targets myeloid cells, without activating fibroblasts. Combinatorial interactions with both TGF-β receptors and cell surface co-receptors confer cell type specificity that the mammalian cytokine cannot mediate. TGF-β Mimics (TGM) are modular parasite proteins which bind multiple host cell receptors. TGM4 interacts, in addition to both TGF-β receptors, with CD44, CD49d and CD206. TGM4 binding affinities are moderated so that signalling requires co-receptor engagement. TGM4 is an effective activator of immune cells but does not signal in fibroblasts with low co-receptor levels. A parasite-derived mimic of TGF-β selectively targets myeloid cells, without activating fibroblasts. Combinatorial interactions with both TGF-β receptors and cell surface co-receptors confer cell type specificity that the mammalian cytokine cannot mediate. [ABSTRACT FROM AUTHOR]

Purpose: A prospective longitudinal cohort study was performed to gain insight into the course of recovery in terms of pain, opioid consumption, and mobility in patients with a lateral compression (LC) pelvic injury. Methods: Adult patients with an LC injury, without any cognitive disorders or limited mobility and who could communicate in Dutch were asked to participate. Pain in terms of NRS (numeric rating scale, range 0–10), opioid use and mobility were recorded at eight time points: at hospital admission, and three days, one week, six weeks, three months, six months, one year and two years after the injury. A sub-analysis was performed for nonoperatively and operatively treated patients. Results: Ninety-seven patients were included, of which 23 (24%) were treated operatively and 74 (76%) conservatively. Pain at rest and exertion, were highest upon admission (mean NRS of 3.4 (SD = 2.6) and 4.4 (SD = 2.8), respectively) but decreased within six weeks (mean NRS of 0.8 (SD = 1.6) and 2.0 (2.0), respectively). After two years, the mean NRS was 0.5 (SD = 1.6) and 0.9 (SD = 2.1), respectively. Upon admission, 85% were given opioids, however only 11% used opioids after three months and 4% after two years. At three months, 35% were walking using walking aids and 58% were walking independently. After two years, 98% were walking independently. Conclusions: Pain rapidly decreased within the first six weeks. Most patients did not need opioids after three months. Furthermore, most patients were walking with walking aids after six weeks. After two years, few patients experienced pain, used opioids or had difficulties walking. [ABSTRACT FROM AUTHOR]

The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule-severing enzymes, has emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins. However, whether and how tubulin posttranslational modifications may contribute to neuronal connectivity has not yet been addressed. Here we show that the microtubule-severing proteins p60-katanin and spastin play specific roles in axon guidance during zebrafish embryogenesis and identify a key role for tubulin polyglutamylation in their functional specificity. Furthermore, our work reveals that polyglutamylases with undistinguishable activities in vitro, TTLL6 and TTLL11, play exclusive roles in motor circuit wiring by selectively tuning p60-katanin- and spastin-driven motor axon guidance. We confirm the selectivity of TTLL11 towards spastin regulation in mouse cortical neurons and establish its relevance in preventing axonal degeneration triggered by spastin haploinsufficiency. Our work thus provides mechanistic insight into the control of microtubule-driven neuronal development and homeostasis and opens new avenues for developing therapeutic strategies in spastin-associated hereditary spastic paraplegia. Synopsis: Tubulin post-translational modifications modulate recruitment and activity of microtubule severing proteins. This study shows that specific tubulin glutamylases (TTLLs) control neuronal circuit wiring and homeostasis in zebrafish and mouse by differentially regulating the activity of two microtubule-severing enzymes: p60-Katanin and Spastin. Two long-chain tubulin glutamylases with similar biochemical activity in vitro, TTLL6 and TTLL11, have distinct physiological roles in neuronal circuit wiring. TTLL11 specifically promotes spastin-dependent microtubule severing and rostral motor nerve pathfinding in zebrafish larvae. TTLL6 selectively promotes p60-Katanin activity and dorsal motor nerve pathfinding in zebrafish larvae. TTLL11-mediated microtubule polyglutamylation rescues the degenerative hallmarks of hereditary spastic paraplegia associated with spastin haploinsufficiency in mouse cortical neurons. Specific tubulin glutamylases selectively regulate the activity of p60-katanin and spastin to control motor axon navigation during zebrafish development. [ABSTRACT FROM AUTHOR]

Most research on cetacean swimming has been conducted on captive dolphins due to limited accessibility to wild cetaceans. Epibiotic barnacles have been used as indirect evidence of cetacean hydrodynamics, given their lifelong association with cetaceans and dependence on water flow. Previous studies suggested that the spatial distribution of the barnacle Xenobalanus globicipitis on the tail flukes of striped dolphins (i.e., higher load in the center and dorsal side) sheds light on dolphin hydrodynamics. The present study investigates whether these spatial patterns are shared among 13 cetacean species: 1 species of baleen whale (N=33), 3 beaked whales (N=11), and delphinids: 3 globicephalines (N=21) and 6 smaller dolphins (N=118). We found higher barnacle densities on the dorsal side of the flukes of delphinids, particularly in the smaller species (mostly subfamily Delphininae); whereas both fluke sides of the whales were equally colonized. The center of the flukes was generally a preferred settlement location for X. globicipitis, although it became less predictable in the ventral side of dolphins. Our findings conform to evidence on cetacean morphokinematics: while large odontocetes and whales have greater mobility in their torso during swimming, dolphins rely mostly on asymmetric fluke oscillation, likely favoring a set of more favorable conditions for barnacle settlement on the dorsal fluke side of dolphins (i.e., higher cyprid advection and lower shear stress). Also, the interaction of the dorsal fin vortices with the flow at the flukes could be more pronounced in dolphins. An additional effect of dolphin aerial behavior cannot be ruled out. This study provides novel indirect evidence on cetacean swimming performance, highlighting possible nuances between ecomorphological groups, and underlines that epibionts are a cost-effective tool for studying wild cetaceans. [ABSTRACT FROM AUTHOR]

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia’s toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD. Six-week bile duct-ligated (BDL) rats and Sham-operated controls were treated with OP (1 g/kg, oral) for 5 weeks. Body composition, assessed by EchoMRI, and muscle protein fractional synthesis rate were evaluated. Signalling mechanisms regulating protein homeostasis, ATP content and metabolic intermediates in the tricarboxylic acid cycle (TCA) in skeletal muscle were quantified. OP treatment attenuated hyperammonemia, prevented brain edema and improved locomotor activity in BDL rats. Increased muscle ammonia, reduction in lean body mass, decreased muscle protein synthesis rate and ATP content were restored in OP-treated versus saline-treated BDL rats. TCA cycle intermediary metabolite, α-ketoglutarate, alterations of molecular markers regulating protein homeostasis including mTOR signalling and autophagy, were also preserved in muscle of OP-treated BDL rats. OP attenuated hyperammonemia, preserved muscle protein synthesis and prevented muscle mass loss in a preclinical model of CLD through restoration of perturbed signalling responses and altered TCA intermediary metabolites. Ammonia-lowering strategies have the potential for rapid clinical translation for simultaneous neuroprotection and sarcopenia prevention in patients with CLD. [ABSTRACT FROM AUTHOR]

Introduction and Objective: The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI. Methods: By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported. Results: Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors. Conclusions: By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts. [ABSTRACT FROM AUTHOR]

The left atrial appendage is a blind ending cardiac structure prone to blood stasis due to its morphology. This structure is a preferred region of thrombogenesis in relation to reduced myocardial contractility of the atrial wall. Blood stasis occurs primarily in low flow conditions. One of the tasks of echocardiography is the analysis of morphology and function of the left atrial appendage. The detection of thrombi by echocardiography is difficult and must be carried out thoroughly and carefully to avoid potential complications—especially in the context of rhythm control. The assessment of thromboembolic risk, especially in patients with unknown and presumed atrial fibrillation is a second challenge by characterizing atrial function and flow conditions in the left atrial appendage. Thus, this proposal focuses on the obvious problems of echocardiography when assessing left atrial appendage and the role of this method in planning a potential interventional closure of left atrial appendage. [ABSTRACT FROM AUTHOR]

Echocardiography in patients with atrial fibrillation is challenging due to the varying heart rate. Thus, the topic of this expert proposal focuses on an obvious gap in the current recommendations about diagnosis and treatment of atrial fibrillation (AF)—the peculiarities and difficulties of echocardiographic imaging. The assessment of systolic and diastolic function—especially in combination with valvular heart diseases—by echocardiography can basically be done by averaging the results of echocardiographic measurements of the respective parameters or by the index beat approach, which uses a representative cardiac cycle for measurement. Therefore, a distinction must be made between the functionally relevant status, which is characterized by the averaging method, and the best possible hemodynamic status, which is achieved with the most optimal left ventricular (LV) filling according to the index beat method with longer previous RR intervals. This proposal focuses on left atrial and left ventricular function and deliberately excludes problems of echocardiography when assessing left atrial appendage in terms of its complexity. Echocardiography of the left atrial appendage is therefore reserved for its own expert proposal. [ABSTRACT FROM AUTHOR]

Cyclic di-adenylate monophosphate (cyclic di-AMP) is an important second messenger in microorganisms. Cyclic di-AMP regulates bacterial cell volume and turgor via control of potassium and compatible solute transport but is also involved in many other processes, including the activation of the metazoan innate immune response to bacterial infections. We compare the activity of full-length membrane-embedded CdaA, the enzyme that synthesizes cyclic di-AMP, with the water-soluble catalytic domain CdaA-DAC. Purified CdaA from L. lactis was studied in the detergent-solubilized state, and in lipid nanodiscs and vesicles. We show that CdaA is tetrameric and the membrane-bound complex has more than 2-orders of magnitude higher activity than soluble CdaA-DAC. CdaA activity increases with pH but does not strongly depend on the salt or lipid content, factors that are crucial for the control of osmoregulatory transporters. Cryo-EM and in-silico structure prediction of CdaA show that the two DAC dimers engage in a head-to-head interaction, leading to cyclic-di-AMP formation. The inhibitor phosphoglucomutase prevents this active conformation. We observe dynamic flexibility between the catalytic and membrane domains, even in the presence of ATP or non-hydrolyzable substrate ApCpp. This is the first comprehensive functional and structural characterization of a full-length cyclic di-AMP-specific cyclase. Biochemical and structural characterization of the full-length CdaA reveals that efficient synthesis of the second messenger cyclic di-AMP requires membrane-bound cyclase enzyme. [ABSTRACT FROM AUTHOR]

Photon efficacy (PE) is defined as the photon numbers generated by 1 joule (J) of power consumption, which is a key indicator on energy efficiency of LED lighting. PE calculated by LED datasheet includes photons irradiating in all directions, therefore deviates far from the actual PE of LED grow lights in indoor farms where only photons shining on plants are counted. To measure the PEs of different types of LEDs for plant growth accurately, we designed and fabricated LED panels for 16 types of LEDs at different wavelengths and color temperatures under plant growth conditions. We characterized the LED panels by an optical spectroscopy setup, in which an optical fiber probe mapped the optical spectra of LEDs on the plant growth area to detect the photon numbers reachable to plants. We found that at plant growth conditions, the LED panels at 660, 730 and 450 nm have higher PEs of 3.84, 3.39 and 2.38 µmol/J, respectively, followed by 2.31, 2.08 and 2.03 µmol/J for white LEDs at the color temperatures of 5700 K, 5000 K and 4000 K, respectively. We further compared the LED costs and concluded that 4000 K, 3000 K, 475 nm and 5700 K LED panels are most cost-effective to build at an LED cost of 0.15 - 0.21 US$ per µmol/s. Our findings provide a good reference for plant scientists and horticulture practitioners to understand LED lighting cost at different wavelengths and color temperatures for plant growth, for them to develop the lighting recipes effectively and estimate farm operating cost more precisely. [ABSTRACT FROM AUTHOR]

In this paper, we propose an approach for the pinpoint detection of inoperable sensors based on the analysis of diagnostic parameters. The "sliding correlation" coefficients, the fourth eigenvalue, and the relative deviation of the reconstructed sensor reading may be such parameters. With the help of the above diagnostic parameters, it is possible to immediately determine the fuel assembly in which one of the direct charge sensors is presumably out of order, then analyze the level correlations between each other, and, using the restored value, make a final judgment on the performance of each altitude sensor. The developed software makes it possible to carry out an express analysis of the archive of the VVER reactor. This has scientific and practical value in the context of improving the quality of work of operational personnel and analyzing situations that require additional attention and more detailed analysis. The application of this approach can help detect malfunctions in sensors and take timely measures to prevent possible problems and emergencies, which is an important step in ensuring the safety and efficiency of the VVER reactor monitoring and control system. [ABSTRACT FROM AUTHOR]

Purpose: Low cardiorespiratory fitness (CRF) increases the risk of postoperative morbidity and mortality following major surgery. Assessing CRF preoperatively, by measuring peak oxygen uptake (VO2peak) during cardiopulmonary exercise testing (CPET), is valuable yet not widely available. This study aimed to assess whether questionnaires could be used preoperatively to identify high-risk surgical patients. Methods: Healthy participants and patients who underwent CPET completed the FitMáx, Duke Activity Status Index (DASI), the modified 4-questions DASI (M-DASI-4Q), Veterans-Specific Activity Questionnaire (VSAQ), and Metabolic Equivalents of Task (MET) questionnaire. Questionnaire-VO2peak was compared with CPET-VO2peak. Overall performance of the questionnaires was assessed by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Furthermore, corresponding to the Youden index or pre-specified levels, sensitivity, specificity, and predictive values were determined. Results: In total, 361 participants were included. All questionnaires showed high AUC values to identify high-risk patients, defined on the basis of CPET-VO2peak thresholds. FitMáx and VSAQ demonstrated superior results compared to the other questionnaires. Based on the Youden index, the optimal questionnaire-VO2peak cut-off values were 20.6, 21.3, and 26.1 ml·kg−1·min−1 for the FitMáx and 16.3, 18.2, and 20.4 ml·kg−1·min−1 for the VSAQ corresponding to the VO2peak thresholds 16.0, 18.2 and 24.5 ml·kg−1·min−1 respectively. Conclusion: The ability to identify high-risk surgical patients preoperatively (defined by the CPET-VO2peak thresholds) by the FitMáx and the VSAQ indicates that they could be used to identify high-risk surgical patients. Patients with a poor predicted VO2peak ≤ 21.3 and ≤ 18.2 ml·kg−1·min−1, respectively for FitMáx and VSAQ, should be referred to formal preoperative (cardiopulmonary) exercise testing. Trial registration: The study was registered as NL-OMON23304 in the Overview of Medical Research in the Netherlands, retrospectively at 28–04-2020. [ABSTRACT FROM AUTHOR]

The goal of this study was to translate and adapt the original 9-item of the Contextual Assessment of Social Skills (CASS) to a Dutch version and assess its psychometric qualities. Autistic adolescents aged 12 to 18 years (n = 99) took part in a randomized controlled trial. In this study, pre-intervention data were utilized. The original CASS was adapted to ensure cultural relevance and the content validity was assessed. Data was used to assess reliability and structural validity, using confirmatory factor analysis. 4-item were added to the CASS during the adaptation to better align with the objectives of the experimental intervention. The original 9-item had inter-item correlations between.01 and.70. The Cronbach's alpha for the original 4-item total score was moderate (α =.69), while for a 7-item total score, it was high (α =.86). This 7-item total score had a sufficient model fit (Comparative Fit Index =.90). This total score had a significant correlation with the Assertion subscale of the Social Skills Improvement System-Adolescent (SSIS-A) (r = 0.26, p <.01), and the Social Responsiveness Scale-2 (SRS-2) total score (r = −.21, p =.04) indicating sufficient convergent validity. The CASS total score was not correlated with the Repetitive and Restricted Behavior scale of the SRS-2 (r = −.08, p =.43), indicating sufficient divergent validity. The Dutch CASS can be considered a conceptually sound and reliable observational instrument for assessing social conversational skills in Dutch autistic youth. Further evaluation of its feasibility when implemented in practice, outside of clinical research, is needed. Trial registration: Dutch trail register NTR6255 (NL6117) 08/02/2017 https://www.trialregister.nl/trial/6117 [ABSTRACT FROM AUTHOR]

Background: Online video consultation (OVC) is increasingly used in patient–surgeon pre-surgical and follow-up consultation but a comprehensive review assessing its benefits and downsides as compared to face-to-face (F2F) consultation is currently lacking. This systematic review evaluated the effectiveness of OVC as compared to F2F consultation. Methods: A literature search (Ovid/Medline, Embase, and Clarivate Analytics/Web of Science Core Collection) was conducted including studies comparing efficacy, patient and surgeon satisfaction, and information recall between OVC and F2F patient–surgeon consultation (inception-December 4, 2023). Results: Out of 1021 studies, 14 studies with 13,564 patients met the eligibility criteria, consisting of seven RCTs, three prospective, and four retrospective studies. Various types of surgical consultations were evaluated, including new referrals, routine follow-ups, postoperative follow-ups, and mixed consultations (both pre- and postoperative). None of the randomized trials exclusively compared OVC with F2F consultations in the high-demand preoperative setting, or assessed patient information recall. Efficacy outcomes were reported by seven studies. Among these, three RCTs showed that OVC improved efficacy in terms of waiting time (8.2 vs. 20.7 min, P = 0.01) and total appointment time (24 vs 71 min, P = 0.001, and 21.9 vs. 154.8 min, P = 0.001). Patient satisfaction was reported by 10 studies. Regarding patient satisfaction, one "mixed design" study favoured OVC (92% vs. 63%, P = 0.04), while eight studies reported similar outcomes. Conclusions: This systematic review identified some benefits of OVC such as shorter waiting and total appointment times as compared to F2F patient–surgeon consultation, although the true value of OVC remains unknown due to the limited available evidence. Future pragmatic RCTs are needed, which should include the pre-surgical consultation and assess patient information recall. [ABSTRACT FROM AUTHOR]

Although Artificial Intelligence (AI) projects are common and desired by many institutions and research teams, there are still relatively few success stories of AI in practical use for the Earth science community. Many AI practitioners in Earth science are trapped in the prototyping stage and their results have not yet been adopted by users. Many scientists are still hesitating to use AI in their research routine. This paper aims to capture the landscape of AI-powered geospatial data sciences by discussing the current and upcoming needs of the Earth and environmental community, such as what practical AI should look like, how to realize practical AI based on the current technical and data restrictions, and the expected outcome of AI projects and their long-term benefits and problems. This paper also discusses unavoidable changes in the near future concerning AI, such as the fast evolution of AI foundation models and AI laws, and how the Earth and environmental community should adapt to these changes. This paper provides an important reference to the geospatial data science community to adjust their research road maps, find best practices, boost the FAIRness (Findable, Accessible, Interoperable, and Reusable) aspects of AI research, and reasonably allocate human and computational resources to increase the practicality and efficiency of Earth AI research. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relation between pelvic symmetry, as measured by the cross-measurement technique, and patient-reported outcome measures (PROMs) in terms of functional status and health-related quality of life. Methods: In this prospective cohort study, X and Y measurements were taken according to the cross-measurement technique on AP radiographs of patients who were treated for an unstable pelvic ring injury in a level-1 trauma center. Patients completed PROMs at the time of admission (recalled pre-injury score) and one year following their injury, reporting their functional status with the Short Musculoskeletal Function Assessment (SMFA-NL), specifically the lower extremity dysfunction (LED), problems with daily activities (PDA) and mental and emotional problems (MEP) subscales, and quality of life with EuroQol-5D (EQ-5D). Subgroup analyses were also performed. PROMs were used to analyze the relation between pelvic symmetry and patient-reported outcome, using Spearman's Rank correlation coefficients. Results: A total of 130 patients (mean age 58 (SD18) years) with an unstable pelvic ring injury were included, of which 95 (73%) sustained type-B injuries and 35 (27%) type-C injuries. Sixty-three (49%) patients were treated operatively. The median pelvic symmetry ratio was 1.01 (IQR: 0.05). Weak or no correlations were found between the pelvic symmetry scores and the outcome measurements (Spearman's correlation coefficients: LED r = 0.09; PDA r = 0.11; MEP r=-0.02; and EQ-5D r=-0.08). Subgroup analyses revealed no correlations. Conclusions: No significant relation was found between pelvic symmetry, measured radiologically, and functional status and health-related quality of life, one year following an unstable pelvic ring injury. [ABSTRACT FROM AUTHOR]

Purpose: Automatic virtual reconstruction of complex fractures would be helpful for pre-operative surgical planning. We developed a statistical shape model (SSM) which contains data of 200 intact 3D hemipelves. It allows for quantification of shape differences and is able to reconstruct abnormal shaped pelvises. We applied our SSM to reconstruct elementary and associate type acetabular fractures and assessed the reconstruction performance of the SSM, by comparing the reconstructed shape with the intact contralateral hemipelvis. Methods: In this retrospective diagnostic imaging study, we used our SSM to virtually reconstruct fractured hemipelves of eighty-three patients with an acetabular fracture. A root mean square error (RMSE) was computed between the reconstructed shape and intact contralateral shape for the whole hemipelvis and for regions relevant for plate-fitting. These plate-fitting relevant regions were defined as: (1) Iliopectineal line length and radius; (2) ischial body line length and radius; (3) acetabular diameter, (4) quadrilateral slope and (5) weight-bearing acetabular dome. Results: The median RMSE of the whole hemipelvis of the elementary type fractures was 2.2 (1.7–2.5) mm versus 3.2 (2.2–3.9) mm for the associate type fractures (p < 0.001). The median RMSE for the plate-fitting regions of elementary type fractures was 1.7 (1.4–2.1) mm versus 2.7 (2.0–4.1) mm for associate type fractures (p < 0.001). Conclusion: Using a statistical shape model allows for accurate virtual reconstructions of elementary and associate type acetabular fractures within a clinically acceptable range, especially within regions important for plate-fitting. SSM-based reconstructions can serve as a valuable tool for pre-operative planning in clinical practice, when a template of the contralateral hemipelvis is unavailable. [ABSTRACT FROM AUTHOR]

Purpose: Direct Discharge protocols (DD) can alleviate strain on healthcare systems by reducing routine outpatient follow-up. These protocols include low-complex musculoskeletal injuries, such as isolated greenstick fractures or torus fractures of the wrist in children. While there is consensus on the effectiveness of DD, there is a lack of injury-specific powered studies. This study compares treatment satisfaction between DD and traditional treatment in children with a greenstick fracture or torus fractures of the wrist. Methods: Children with isolated torus or greenstick fractures of the distal radius or ulna were eligible for inclusion before (pre-DD cohort) and after (DD cohort) the implementation of DD in four hospitals. Traditionally, patients receive a (soft) cast and minimally one routine outpatient follow-up appointment. With DD, patients are discharged directly from the ED after receiving a brace and information, summarized in a smartphone app and a helpline for questions during recovery. The primary outcome was patient or proxy treatment satisfaction (0 to 10), and a power analysis was performed to assess non-inferiority. Secondary outcomes included complications, functional outcomes measured in Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE), primary healthcare utilisation, and secondary healthcare utilisation (follow-up appointments and imaging). Results: In total, 274 consecutive children were included to analyse the primary endpoint. Of these, 160 (58%) were male with a median age of 11 years (IQR 8 to 12). Pre-DD and DD treatment satisfaction did not vary statistically significantly for greenstick fractures (p = 0.09) and torus fractures (p = 0.93). No complications were observed. PROMIS UE showed no statistically significant differences before and after implementation of direct discharge protocol for torus (p = 0.99) or greenstick (p = 0.45) fractures. Secondary healthcare utilisation regarding follow-up was significantly lower in the DD-torus cohort compared to the pre-DD torus cohort, with a mean difference (MD) of − 1.00 follow-up appointments (95% Confidence Interval (CI) − 0.92 to − 1.13). Similar results were found in the pre DD-greenstick cohort compared to the pre-DD-greenstick cohort (MD): − 1.17 follow-up appointments, 95% CI − 1.09 to − 1.26). Conclusion: Direct Discharge is non-inferior to traditional treatment in terms of treatment satisfaction for paediatric patients with greenstick or torus fractures of the wrist compared to children treated with rigid immobilisation and routine follow-up. Furthermore, the results demonstrate no complications, comparable functional outcomes, and a statistically significant reduction of secondary healthcare utilisation, making DD a good solution to cope with strained resources for children with an isolated greenstick fracture or torus fracture of the wrist. [ABSTRACT FROM AUTHOR]

Purpose: There is a lack of literature evaluating outcomes of the ligament‐guided approach in medial unicompartmental knee arthroplasty (UKA). An improved comprehension of the distribution of coronal plane alignment of the knee (CPAK) phenotypes and sagittal tibial wear patterns and their associations with patient‐reported outcome measures (PROMs) and implant survivorship could provide insights into its further application in daily practice. Methods: A registry was reviewed for patients with a minimal 2‐year follow‐up who underwent robotic‐assisted, ligament‐guided, medial UKA between 2008 and 2016. Survivorship and postoperative PROMs were collected. CPAK phenotypes and sagittal tibial wear patterns were determined. Survivorship, Knee Injury and Osteoarthritis Outcome Score (KOOS), Kujala and patient satisfaction were compared between phenotypes and sagittal tibial wear patterns. Results: A total of 618 knees were included at a mean follow‐up of 4.1 [2.0–9.6] years. Four‐year conversion to the TKA survival rate was 98.9% [98.4%–99.3%] and 94.3% [93.3%–95.3%] for all‐cause revision. Patients with preservation of the CPAK phenotype (84.5 ± 14.9, 81.8 ± 15.5, p = 0.033) and restoration of prearthritic coronal alignment (84.1 ± 14.9, 81.7 ± 15.9, p = 0.045) had a significantly higher Kujala score. No other significant differences in survivorship or PROMs were observed between phenotypes or sagittal tibial wear patterns. Additionally, no difference in survival rates was observed between preserved or altered phenotypes. Conclusion: This study demonstrated that preservation of CPAK phenotype and preservation of prearthritic coronal alignment yielded a significantly higher Kujala score. No other significant differences in PROMs or implant survivorship were observed, suggesting that robotic‐assisted, ligament‐guided medial UKA provides equal outcomes for all observed phenotypes and sagittal tibial wear patterns in medial compartment OA as long as preoperative CPAK phenotype is preserved postoperatively. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a relatively rare but very severe gastrointestinal disease primarily affecting very preterm infants. NEC is characterized by excessive inflammation and ischemia in the intestines, and is associated with prolonged, severe visceral pain. Despite its recognition as a highly painful disease, current pain management for NEC is often inadequate, and research on optimal analgesic therapy for these patients is lacking. Insight into the mechanisms underlying intestinal pain in infants with NEC—visceral pain—could help identify the most effective analgesics for these vulnerable patients. Therefore, this comprehensive review aims to provide an overview of visceral nociception, including transduction, transmission, modulation, and experience, and discuss the implications for analgesic therapy in preterm infants with NEC. The transmission of visceral pain differs from that of somatic pain, contributing to the diffuse nature of visceral pain. Studies evaluating the effectiveness of analgesics for treating visceral pain in infants are scarce. However, research in visceral pain models highlights agents that may be particularly effective for treating visceral pain based on their mechanisms of action. Further research is necessary to determine whether agents that have shown promise for treating visceral pain in preclinical studies and adults are effective in infants with NEC as well. [ABSTRACT FROM AUTHOR]

While up to 50% of children requiring kidney replacement therapy have congenital anomalies of the kidney and urinary tract (CAKUT), they represent only a fraction of the total patient population with CAKUT. The extreme variability in clinical outcome underlines the fundamental need to devise personalized clinical management strategies for individuals with CAKUT. Better understanding of the pathophysiology of abnormal kidney and urinary tract development provides a framework for precise diagnoses and prognostication of patients, the identification of biomarkers and disease modifiers, and, thus, the development of personalized strategies for treatment. In this review, we provide a state-of-the-art overview of the currently known genetic causes, including rare variants in kidney and urinary tract development genes, genomic disorders, and common variants that have been attributed to CAKUT. Furthermore, we discuss the impact of environmental factors and their interactions with developmental genes in kidney and urinary tract malformations. Finally, we present multi-angle translational modalities to validate candidate genes and environmental factors and shed light on future strategies to better understand the molecular underpinnings of CAKUT. [ABSTRACT FROM AUTHOR]

Introduction: In patients undergoing percutaneous coronary intervention (PCI), personalised medicine is key to the secondary prevention of ischaemic and bleeding events. To provide an extensive overview of the quality of secondary prevention and of personalised medicine, a consortium in the southeastern region of the Netherlands has created a PCI registry: the South-East Netherlands Heart Registry (Zuid-Oost Nederland Hart Registratie, ZON-HR). Aim: To visualise and improve personalised secondary prevention post-PCI, focussing on key elements such as antiplatelet treatment, cholesterol management and comorbidities such as diabetes mellitus. Design and population: A prospective multicentre registry of all consecutive patients undergoing PCI at 4 participating PCI centres and 3 referral centres. Treatment: Interventional procedures and concomitant pharmaceutical treatment are performed in accordance with the guidelines. The ZON-HR promotes risk stratification after PCI using a simplified protocol for a personalised antiplatelet strategy. Data collection and quality: Demographics, laboratory values, baseline procedural characteristics and pharmaceutical treatment data are collected. Outcomes include thromboembolic and bleeding complications and medication changes. Data are pseudonymised, and a clinical event committee will review 20% of the adverse events (randomly selected). Strengths and weaknesses: This registry represents the entire PCI population and visualises gaps in secondary prevention. Weaknesses are the collection of outcomes and medication changes using mostly patient-reported outcomes. Conclusion: The ZON-HR is a comprehensive PCI registry that provides baseline and follow-up data of a large PCI cohort in the southeastern region of the Netherlands. The ZON-HR aims to improve secondary prevention after PCI and augment personalised treatment that focusses on key elements of secondary prevention. [ABSTRACT FROM AUTHOR]

Objectives: Screening for obstructive coronary artery disease (CAD) with coronary computed tomography angiography (CCTA) could prevent unnecessary invasive coronary angiography (ICA) procedures during work-up for trans-catheter aortic valve implantation (TAVI). CT-derived fractional flow reserve (CT-FFR) improves CCTA accuracy in chest pain patients. However, its reliability in the TAVI population is unknown. This systematic review and meta-analysis assesses CCTA and CT-FFR in TAVI candidates. Methods: PubMed, Embase and Web of Science were searched for studies regarding CCTA and/or CT-FFR in TAVI candidates. Primary endpoint was correct identification and rule-out of obstructive CAD. Results were pooled in a meta-analysis. Results: Thirty-four articles were part of the meta-analysis, reporting results for CCTA and CT-FFR in 7235 and 1269 patients, respectively. Reference standard was mostly anatomical severity of CAD. At patient level, pooled CCTA sensitivity was 94.0% and specificity 72.4%. CT-FFR sensitivity was 93.2% and specificity 70.3% with substantial variation between studies. However, in studies that compared both, CT-FFR performed better than CCTA. Sensitivity of CCTA versus CT-FFR was 74.9% versus 83.9%, and specificity was 65.5% versus 89.8%. Conclusions: Negative CCTA accurately rules out CAD in the TAVI population. CCTA could lead to significant reduction in pre-TAVI ICA, but false positives remain high. Diagnostic accuracy of CT-FFR was comparable to that of CCTA in our meta-analyses, but in studies performing a direct comparison, CT-FFR performed better than CCTA. However, as most studies were small and used CT-FFR software exclusively available for research, a large study on CT-FFR in TAVI work-up using commercially available CT-FFR software would be appropriate before considering routine implementation. Key Points: QuestionCoronary artery disease (CAD) screening with invasive coronary angiography before trans-catheter aortic valve implantation (TAVI) is often retrospectively unnecessary, revealing no obstructive CAD. FindingsCoronary CTA ruled out CAD in approximately half of TAVI candidates. CT-derived fractional flow reserve (CT-FFR) performed similarly overall but better than coronary CTA in direct comparison. Clinical relevanceAddition of coronary CTA to TAVI planning-CT to screen for obstructive CAD could reduce negative invasive coronary angiographies in TAVI work-up. CT-FFR could reduce false-positive coronary CTA results, improving its gatekeeper function in this population, but more data is necessary. [ABSTRACT FROM AUTHOR]

This study aims to quantify stress exposure related to clinical stressors in preterm infants during NICU admission and identify risk factors for high stress exposure. In this national cohort study, preterm infants (gestational age < 29 weeks) were prospectively followed during the first 28 days of their admission to one of the 10 NICUs in the Netherlands. The NeO-stress score, consisting of 38 clinical stressors graded with a severity index, was applied to describe stress exposure. We assessed the impact of infant characteristics at birth and postnatal age on NeO-stress scores using linear mixed modelling. In total, 446 infants were included with a median gestational age of 27+2 weeks (IQR 26+2–28+2). The median NeO-stress score per day was 61 (IQR 39–87) and highest (74, IQR 52–101) on the day of admission. Nasal/oral (37%) and endotracheal (14%) suctioning were key contributors to the cumulative NeO-stress scores. Linear mixed modelling showed that lower gestational age (B = -0.69, 95% CI − 0.94–0.44, p < 0.001), no antenatal administration of corticosteroids (B = 13.2, 95% CI 3.2–23.1, p = 0.010) and lower 5-min Apgar score (B = − 1.6, 95% CI − 3.0–0.25, p = 0.02) were significantly related with higher daily NeO-stress scores. Our model predicts that the NeO-stress score increases over time for the youngest infants. Conclusion: Stress exposure in preterm infants during NICU admission varies over time with infants with the lowest gestational age at risk for experiencing the highest levels of stress throughout NICU admission. This highlights the importance stress reduction and provides opportunities for future interventions aimed at reducing stress exposure. What is Known: • Preterm birth and admission to a Neonatal Intensive Care Unit is very stressful. • High stress exposure in neonatal life is associated with adverse long term outcome. What is New: • Stress exposure is highest in infants with the youngest gestational ages where it remains high or even increases during the first month of life. • Lower gestational age, no antenatal administration of corticosteroids and lower 5-min Apgar score were significantly related with higher daily NeO-stress scores. [ABSTRACT FROM AUTHOR]

Background: Superparamagnetic iron oxide nanoparticles (SPIO) are emerging as a viable alternative to technetium and blue dye. Our study was designed to evaluate the correlation between SPIO dose, injection site, and timing with sentinel lymph node (SLN) detection and iron content in retrieved SLNs. Methods: This study combined individual patient data from three Dutch and five Swedish studies. Associations between SLN detection and dose, site, and timeframe of SPIO injection were examined. The iron content for each retrieved SLNs with or without metastases were calculated according to a predefined look up table based on probe counts and sensitivity setting. Analyses were conducted by using multivariable logistic and linear regression models using generalized estimating equation. Results: A total of 908 patients were included. The detection between the magnetic technique (96.6%) and the radioactive technique was comparable (96.6% vs. 96.8%, p = 0.75). The 1.0-mL SPIO dose was associated with the highest, and <0.5 mL of SPIO was associated with the lowest patient-based detection (100.0 and 96.6% respectively). An intratumoural injection was found to be less favourable compared with peritumoural and subareolar, whereas injection >168 hours before surgery demonstrated the highest patient-based detection. Conclusions: The noninferiority of SPIO compared with technetium99m ± BD has been proven by several studies. A dose of 1 mL, around the areola, with a longer exposure time, appears to increase the SPIO uptake in the nodes and SLN detection. Metastatic burden in SLNs did not significantly impact the uptake of SPIO. [ABSTRACT FROM AUTHOR]

Imaging systems are inherently prone to aberrations. We present an optimization method to design two-dimensional (2D) freeform reflectors that minimize aberrations for various parallel ray beams incident on the optical system. We iteratively design reflectors using inverse methods from non-imaging optics and optimize them to obtain a system that produces minimal aberrations. This is done by minimizing a merit function that quantifies aberrations and is dependent on the energy distributions at the source and target of an optical system, which are input parameters essential for inverse freeform design. The proposed method is tested for two configurations: a single-reflector system and a double-reflector system. Classical designs consisting of aspheric elements are well-known for their ability to minimize aberrations. We compare the performance of our freeform optical elements with classical designs. The optimized freeform designs outperform the classical designs in both configurations. [ABSTRACT FROM AUTHOR]

Introduction: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [18F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms. Methods: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard. Results: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively. Discussion: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [18F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE. [ABSTRACT FROM AUTHOR]

The entrustment framework redirects assessment from considering only trainees' competence to decision-making about their readiness to perform clinical tasks independently. Since trainees and supervisors both contribute to entrustment decisions, we examined the cognitive and affective factors that underly their negotiation of trust, and whether trainee demographic characteristics may bias them. Using a document analysis approach, we adapted large language models (LLMs) to examine feedback dialogs (N = 24,187, each with an associated entrustment rating) between medical student trainees and their clinical supervisors. We compared how trainees and supervisors differentially documented feedback dialogs about similar tasks by identifying qualitative themes and quantitatively assessing their correlation with entrustment ratings. Supervisors' themes predominantly reflected skills related to patient presentations, while trainees' themes were broader—including clinical performance and personal qualities. To examine affect, we trained an LLM to measure feedback sentiment. On average, trainees used more negative language (5.3% lower probability of positive sentiment, p < 0.05) compared to supervisors, while documenting higher entrustment ratings (+ 0.08 on a 1–4 scale, p < 0.05). We also found biases tied to demographic characteristics: trainees' documentation reflected more positive sentiment in the case of male trainees (+ 1.3%, p < 0.05) and of trainees underrepresented in medicine (UIM) (+ 1.3%, p < 0.05). Entrustment ratings did not appear to reflect these biases, neither when documented by trainee nor supervisor. As such, bias appeared to influence the emotive language trainees used to document entrustment more than the degree of entrustment they experienced. Mitigating these biases is nonetheless important because they may affect trainees' assimilation into their roles and formation of trusting relationships. [ABSTRACT FROM AUTHOR]

Background and Objectives: Voriconazole administered concomitantly with flucloxacillin may result in subtherapeutic plasma concentrations as shown in a patient with Staphylococcus aureus sepsis and a probable pulmonary aspergillosis. After switching our patient to posaconazole, therapeutic concentrations were reached. The aim of this study was to first test our hypothesis that flucloxacillin competes with voriconazole not posaconazole for binding to albumin ex vivo, leading to lower total concentrations in plasma. Methods: A physiologically based pharmacokinetic (PBPK) model was then applied to predict the mechanism of action of the drug–drug interaction (DDI). The model included non-linear hepatic metabolism and the effect of a severe infectious disease on cytochrome P450 (CYP) enzymes activity. Results: The unbound voriconazole concentration remained unchanged in plasma after adding flucloxacillin, thereby rejecting our hypothesis of albumin-binding site competition. The PBPK model was able to adequately predict the plasma concentration of both voriconazole and posaconazole over time in healthy volunteers. Upregulation of CYP3A4, CYP2C9, and CYP2C19 through the pregnane X receptor (PXR) gene by flucloxacillin resulted in decreased voriconazole plasma concentrations, reflecting the DDI observations in our patient. Posaconazole metabolism was not affected, or was only limitedly affected, by the changes through the PXR gene, which agrees with the observed plasma concentrations within the target range in our patient. Conclusions: Ex vivo experiments reported that the unbound voriconazole plasma concentration remained unchanged after adding flucloxacillin. The PBPK model describes the potential mechanism driving the drug–drug and drug–disease interaction of voriconazole and flucloxacillin, highlighting the large substantial influence of flucloxacillin on the PXR gene and the influence of infection on voriconazole plasma concentrations, and suggests a more limited effect on other triazoles. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence To (1) investigate the hypothesis that there is high variability in the reported methods to derive axes and joint orientations from three‐dimensional (3D) bone models to (a) perform 3D knee‐related leg alignment analysis and (b) define coordinate systems for the femur, tibia and leg and (2) identify underlying principles that might lead to agreement on a universal 3D leg alignment analysis framework.A systematic review of the literature between January 2006 and June 2024 was performed. Articles explicitly reporting methods to derive axes and joint orientations from CT‐based 3D bone models for alignment parameters and/or coordinate systems of the femur, tibia and leg were included. Study characteristics and reported methods were extracted and presented as a qualitative synthesis.A total of 93 studies were included. There was high variability in the reported methods to derive axes and joint orientations from 3D bone models. Nevertheless, the reported methods could be categorized into four groups, and several underlying principles of the four groups could be identified. Furthermore, the definitions of femoral and tibial coordinate systems were most frequently based on the mechanical axis (femoral, 13/19 [68%]; tibial, 13/26 [50%]) and a central medial‐lateral axis (femoral, 16/19 [84%]; tibial, 12/26 [46%]); no leg coordinate system was reported. Interestingly, of the included studies that reported on leg alignment parameters (76/93, 82%), only a minority reported expressing these in a complete coordinate system (25/76, 33%).There is high variability in 3D knee‐related leg alignment analysis. Therefore, universal 3D reference values for alignment parameters cannot yet be defined, and comparison of alignment parameter values between different studies is impossible. However, several underlying principles to the reported methods were identified, which could serve to reach more agreement on a future universal 3D framework for leg alignment analysis.Level I (1). [ABSTRACT FROM AUTHOR]

This study developed a postbiotic fermentation solution for fresh oyster preservation with the use of food waste soy whey. Lactiplantibacillus plantarum 299V was able to proliferate in soy whey within 24 h without any supplementation. Pacific oysters (Magallana gigas) were immersed in the postbiotic fermentation solution and stored at 4 °C for 12 days. Pathogenic bacteria Vibrio parahaemolyticus and Salmonella enterica introduced by bioaccumulation were suppressed to levels below the detection limit (<2 log CFU/g) within 4 days. The spoilage-related microbial parameters and chemical parameters were maintained at low levels across the 12 days. Sensory evaluation revealed that the product had a positive effect on most of the participants (>60%). Overall, the postbiotic fermentation solution reported in this study enhanced the shelf life and safety of oysters in a sustainable way and could also be recognized as an innovative probiotic vehicle with potential implications for human health promotion. [ABSTRACT FROM AUTHOR]

Aim: To nuance the discussion on the suggested absence of the risk-compensation phenomenon in times of COVID-19. Subject and methods: In many countries, behavioral restrictions for COVID-19 prevention started with asking people to stay 1.5 m away from each other. To further prevent the spread of the virus, governments made it mandatory for people to wear facemasks in situations where keeping the 1.5-m distance was not possible. This triggered a discussion among behavioral scientists regarding whether making face-masks mandatory might lead to the undesirable side effect that people would be less compliant with the 1.5-m distance rule: risk compensation. Mantzari et al. (2020) published a paper claiming that risk compensation was a non-existing phenomenon. Czyprionka et al. (2020) repeated the same claim, referring to the same original publications. We performed a rapid review of the existing literature and identified 19 papers that presented original data on studies that identified the consequences of wearing a facemask. Results: The evidence for risk compensation is inconclusive. Risk compensation may occur with the encouraged use of face coverings. However, it may not always be present, especially when there are other social processes in play, such as respecting other people's choices. Conclusion: Inconclusive evidence doesn't mean that risk compensation should be ignored or that potential public health interventions shouldn't be implemented. The introduction of mandatory face masks should, therefore, always be accompanied by a theory- and evidence-based health promotion campaign to prevent the possible negative effects of distancing. Carefully applying social psychological insights to guide people in their decision to wear masks when needed and to do so correctly, may overcome potential risk compensation and thereby optimize COVID-19 preventive efforts. Highlights: The evidence for risk compensation – in this case, keeping less distance while wearing a mask for COVID-19 prevention – is inconclusive. Risk compensation should not be a reason to refrain from implementing an evidence-based health promotion intervention. The implementation of health promotion interventions should always be combined with additional interventions to reduce the chance that risk compensation will lessen the intended effect. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ornithology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)