CAR-T cell related HLH/MAS is an unusual manifestation of severe cytokine release syndrome (CRS) with high mortality rates and a challenging diagnosis. The establishment of specific diagnosis criteria is essential, and the combination of several techniques for CAR-T cell follow-up, allows a more precise management of this complication.

Kikuchi-Fujimoto Disease (KFD), also called histiocytic necrotizing lymphadenitis, is a rare benign self-limiting condition, commonly characterized by cervical lymphadenopathy and fever. KFD must be included in the differential diagnoses of lymphadenopathy. Clinicians and pathologists should be aware of the occurrence of this entity, for early diagnosis.

Molecular motors change conformation under the influence of light and when attached to host molecules they may find applications as sensors and switchable catalysts. Here we present a porphyrin macrocyclic host functionalized with two motor appendages for future catalytic applications. The compound is formed as a mixture of six stereoisomers (three sets of enantiomers), which have been separated by (chiral) chromatography. 1H NMR and chiral spectroscopy revealed that in one set of diastereomers the two motors interact with the cavity of the host (bound-bound), whereas in a second set one interacts and the other one does not (bound-loose). In the third set both motors do not interact with the host compound (loose-loose). The motorized hosts bind guest molecules in the order: (loose-loose) > (bound-loose) > (bound-bound). They can be switched with light to pseudo-identical diastereomers, leading to orthogonal behavior in the light-gated binding of guest molecules. Whereas the photo-isomerization of the diastereomer set loose-loose significantly lowers the binding affinity for viologen guests, the opposite is true for the diastereomer set bound-bound, i.e. the binding affinity increases. For the diastereomer set bound-loose no influence on guest binding is observed as the effect of photoisomerization on the motors is cancelled out.

Oil bodies (OBs) are micron- or submicron-sized sub-organelles widely found in plants seeds and nuts. The structure OBs is composed of a core of triglycerides covered by a phospholipid-protein layer, which ensures the stability of the OBs under extreme environmental conditions and further protects core lipids as energy reserves. As naturally pre-emulsified oil-in-water emulsions, OBs have been gradually applied to replace synthetically engineered oil droplets. In this paper, the recent research on the composition, extraction, stability, delivery system, digestion, food applications and future perspectives of plant OBs are reviewed. Recent studies have focused on the OBs surface protein identification and function, large-scale extraction techniques such as enzyme assisted, high pressure, ultrasound, and extrusion and the reconstituted OBs. Electrostatic deposition of polysaccharides significantly improves the stability of OBs emulsions. OBs emulsions have promising applications to encapsulate bioactive compounds, deliver targeted drugs, and prepare gels and edible functional films. The digestive behavior of OBs emulsions is similar to that of protein-stabilized emulsions, which can increase the satiety, effectively help reduce calorie intake and improve the bioavailability of functional factors. It has also promoted the development of simulated dairy, spices and meat products.

In this paper, a nonlocal inverse boundary value problem for a two-dimensional hyperbolic equation with overdetermination conditions is studied. To investigate the solvability of the original problem, we first consider an auxiliary inverse boundary value problem and prove its equivalence (in a certain sense) to the original problem. Then using the Fourier method, solving an equivalent problem is reduced to solving a system of integral equations and by the contraction mappings principle the existence and uniqueness theorem for auxiliary problem is proved. Further, on the basis of the equivalency of these problems the uniquely existence theorem for the classical solution of the considered inverse problem is proved and some considerations on the numerical solution for this inverse problem are presented with the examples.

Background: Myocarditis have variable clinical presentation, evolution and prognosis. Aim of our study was to evaluate the value of speckle tracking echocardiography and cardiac magnetic resonance (CMR) in the prediction of ventricular arrhythmias and other cardiovascular adverse events in patients with acute myocarditis, at hospital admission. Methods: 70 patients (62 M, 8 F; mean age 31,3±13,2) with myocarditis and preserved left ventricle ejection fraction (LVEF) were enrolled. Electrocardiogram (ECG), continuous ECG monitoring, echocardiography with measurement of global longitudinal strain of the left ventricle (GLS), mechanical dispersion (MD) and CMR with quantitative measurement of delayed enhancement (DE) were performed. Adverse events were assessed (arrhythmias, heart failure, cardiogenic shock, syncope) during in-hospital stay. Results: We found a significant greater amount of DE mass in patients with cardiac arrhythmias (p = 0,01), but not of edema (p = 0,57). GLS was significantly impaired in patients with ventricular arrhythmias (p = 0,04), conversely MD was not significantly prolonged in this setting (p = 0,16). GLS > - 19.2% (sens 100%, specif 55,7%) and a DE mass >9,9 gr (sens 100%; specif. 58,6%) had the best sensitivity and specificity to identify patients with cardiac arrhythmias. Compared to GLS, DE mass showed a stronger association with ventricular arrhythmias (p < 0,001). Conclusions: in our study DE mass and GLS were associated with ventricular arrhythmias in patients with acute myocarditis and preserved LVEF. DE showed the stronger association with the occurrence of ventricular arrhythmias.

The droplet size distribution in liquid-liquid dispersions is a complex convolution of impeller speed, impeller type, fluid properties, and flow conditions. In this work, we present three a priori modeling approaches for predicting the droplet diameter distributions as a function of system operating conditions. In the first approach, called the two-fluid approach, we use high-resolution solutions to the Navier-Stokes equations to directly model the flow of each phase and the corresponding droplet breakup/coalescence events. In the second approach, based on an Eulerian-Lagrangian model, we describe the dispersed fluid as individual spheres undergoing ongoing breakup and coalescence events per user-defined interaction kernels. In the third approach, called the Eulerian-Parcel model, we model a sub-set of the droplets in the Eulerian-Lagrangian model to estimate the overall behavior of the entire droplet population. We discuss output from each model within the context of predictions from first principles turbulence theory and measured data.

High dimensional models typically require a large computational overhead for multiphysics applications, which hamper their use for broad-sweeping domain interrogation. Herein, we develop a modeling framework to capture the through-plane fluid dynamic response of electrodes and flow fields in a redox flow cell, generating a computationally inexpensive two-dimensional (2D) model. We leverage a depth averaging approach that also accounts for variations in out-of-plane fluid motion and departures from Darcy’s law that arise from averaging across three-dimensions (3D). Our Resulting depth-averaged 2D model successfully predict the fluid dynamic response of arbitrary in-plane flow field geometries, with discrepancies of < 5% for both maximum velocity and pressure drop. This corresponds to reduced computational expense, as compared to 3D representations (< 1% of duration and 10% of RAM usage), providing a platform to screen and optimize a diverse set of cell geometries.

Purpose: The aim of this study was to evaluate the diagnostic accuracy of 18-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) and positron emission tomography/computed tomography (PET/CT) in imaging primary and metastatic lesions in Ewing sarcoma (ES). Methods: PubMed, Cochrane, Scopus, and Web of Science were searched for relevant studies. Data concerning 18F-FDG-PET/CT diagnostic accuracy were extracted and then analysed using Open Meta-analyst software. Reported diagnostic accuracy outcomes included sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio. Results: 31 studies with a total of 735 patients were included in this meta-analysis. The sensitivity and specificity of 18F-FDG PET/CT were: 92.6% and 74.1% for total ES lesions, 96.7% and 68.3% for ES primary lesions, 76.1% and 92.4% for lung metastasis, 83.9% and 93.2% for bone metastasis and 89.9% and 92.6% for ES recurrence respectively. Conclusion: 18F-FDG PET/CT is sensitive and accurate in diagnosing, staging, and detecting the recurrence of ES compared to non-PET imaging. It has high specificity for diagnosing recurrence of ES as well as lung and bone metastases.

Background: Primary immunodeficiency diseases (PIDs) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunological and genetic features of Thai pediatric patients with PIDs. The use of whole exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods: 36 unrelated patients with clinical and laboratory findings consistent with PIDs were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results: The median age of disease onset was 4 months (range; 1 month to 13 years) and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia, and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in PID genes were identified. The clinical usefulness of WES in PIDs was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

Behcet's Disease is a rare systemic vasculitis characterized by recurrent episodes of acute inflammation affecting blood vessels of all sizes. Symptoms include orogenital apthosis, cutaneous skin lesions, and uveitis. We present the case of a 38-year-old Nepalese man with Behcet's Disease. In Nepal, Behcet's Disease may still be under-reported.

Machine learning (ML) models are valuable research tools for making accurate predictions. However, ML models often unreliably extrapolate outside their training data. We propose an uncertainty quantification method for ML models (and generally for other nonlinear models) with parameters trained by least squares regression. The uncertainty measure is based on the multiparameter delta method from statistics, which gives the standard error of the prediction. The uncertainty measure requires the gradient of the model prediction and the Hessian of the loss function, both with respect to model parameters. Both the gradient and Hessian can be readily obtained from most ML software frameworks by automatic differentiation. We show that the uncertainty measure is larger for input space regions that are not part of the training data. Therefore this method can be used to identify extrapolation and to aid in selecting training data or assessing model reliability.

Background: Bicuspid aortic valve is the most common congenital heart defect and predisposes patients to developing aortic stenosis more frequently and at a younger age than the general population. However, the influence of bicuspid aortic valve on the rate of progression of aortic stenosis remains unclear. Methods: In 236 patients (177 tricuspid aortic valve, 59 bicuspid aortic valve) matched by initial severity of mild or moderate aortic stenosis, we retrospectively analyzed baseline echocardiogram at diagnosis with latest available follow-up echocardiogram. Baseline comorbidities, annualized progression rate of hemodynamic parameters, and hazard of aortic valve replacement were compared between valve phenotypes. Results: Median echocardiographic follow-up was 2.6 (IQR 1.6-4.2) years. Patients with tricuspid aortic stenosis were significantly older with more frequent comorbid hypertension and congestive heart failure. Median annualized progression rate of mean gradient was 2.3 (IQR 0.6-5.0) mmHg/year vs. 1.5 (IQR 0.5-4.1) mmHg/year (p=0.5), and that of peak velocity was 0.14 (IQR 0-0.31) m/s/year vs. 0.10 (IQR 0.04-0.26) m/s/year (p=0.7) for tricuspid vs. bicuspid aortic valve, respectively. On multivariate analyses, bicuspid aortic valve was not significantly associated with more rapid progression of aortic stenosis. In a stepwise Cox proportional hazards model adjusted for baseline mean gradient, bicuspid aortic valve was associated with increased hazard of aortic valve replacement (HR: 1.7, 95% CI [1.0, 3.0], p=0.049). Conclusion: Bicuspid aortic valve may not significantly predispose patients to more rapid progression of mild or moderate aortic stenosis. Guidelines for echocardiographic surveillance of aortic stenosis need not be influenced by valve phenotype.

Background: For diseases with a genetic cause genomics can deliver improved diagnostics and facilitate access to targeted treatments. Drug pharmacodynamics and pharmacokinetics are often dependent on genetic variation underlying these processes. As pharmacogenomics comes of age it may be the first way in which genomics is utilised at a population level. Still required is guidance and standards of how genomic information can be communicated within the health record, and how clinicians should be alerted to variation impacting the use of medicines. Methods: The Professional Record Standards Body commissioned by National Health Service England developed guidance on using pharmacogenomics information in clinical practice. We conducted research with those implementing pharmacogenomics in England and internationally to produce guidance and recommendations for a systems-based approach. Results: A consensus viewpoint is that systems need to be in place to ensure the safe provision of pharmacogenomics information that is curated, actionable and up-to-date. Standards should be established with respect to notification and information exchange, which could impact new or existing prescribing and these must be in keeping with routine practice. Alerting systems should contribute to safer practices. Conclusion: Ensuring pharmacogenetics information is available to make use of medicines safer will require major effort of which this guidance is a beginning. Standards are required to ensure useful genomic information within the health record can be communicated to clinicians in the right format and times to be actioned successfully. A multidisciplinary group of stakeholders must be engaged in developing pharmacogenomic standards to support the most appropriate prescribing.

Primary bladder amyloidosis is a rare pathological finding. The clinical importance of this finding is that it may clinically mimic bladder cancer. The only accurate diagnostic method available till now is the histopathologic examination of tissue samples usually obtained through transurethral resection.

Respiratory Syncytial Virus (RSV) is a common seasonal respiratory virus and an important cause of illness among infants, but the burden of RSV disease is not well described among the older population. The objective of this study was to estimate the age-specific incidence of hospital admission among over 65s due to respiratory illnesses attributable to RSV in England to inform optimal vaccine and therapeutic interventions. We used linear multiple regression to examine the effect of changes in weekly counts of respiratory pathogens on the weekly counts of respiratory hospital admissions. The study population was all patients aged 65 years or over admitted to English hospitals between 2nd August 2010 and 30th July 2017. RSV was estimated to account for a seasonal annual average of 71 (95% CI 52-90) respiratory admissions per 100,000 in adults age 65-74 and 251 (95% CI 186-316) admissions per 100,000 adults age 75+. Pneumococcus was the pathogen responsible for highest annual average respiratory admission with 448 (95% CI 310-587) admissions per 100,000 adults age 65-74 and 1010 (95%CI 527-1493) admissions per 100,000 adults aged 75+. This study shows that RSV continues to exert a significant burden of disease among older adults in England. These findings will support development of policy for the use of RSV therapeutics and vaccines in this age group.

Vertebrate colonization of land occurred multiple times, including over 50 origins of terrestrial eggs in frogs. Some environmental factors and phenotypic responses that facilitated these transitions are known, but responses to water constraints and risk of ammonia toxicity during early development are poorly understood. We tested if ammonia accumulation and dehydration risk induce a shift from ammonia to urea excretion during in early stages of four anurans, from three origins of terrestrial development. We quantified ammonia and urea concentrations during early development on land, under well-hydrated and dry conditions. Where we found urea excretion, we tested for a plastic increase under dry conditions and with ammonia accumulation in developmental environments. We assessed the potential adaptive role of urea excretion by comparing ammonia tolerance measured in 96h-LC50 tests with ammonia levels in developmental environments. Ammonia accumulated in foam nests and perivitelline fluid, increasing over development and reaching higher concentrations under dry conditions. All four species showed high ammonia tolerance, compared to fishes and aquatic-breeding frogs. Both nest-dwelling larvae of Leptodactylus fragilis and late embryos of Hyalinobatrachium fleischmanni excreted urea, showing a plastic increase under dry conditions. These two species can develop the longest on land and urea excretion appears adaptive, preventing their exposure to potentially lethal levels of ammonia. Neither late embryos of Agalychnis callidryas nor nest-dwelling larvae of Engystomops pustulosus risked toxic ammonia levels under dry conditions, and neither excreted urea. Our results suggests that an early onset of urea excretion, its increase under dry conditions, and elevated ammonia tolerance, can all help prevent ammonia toxicity during terrestrial development. High ammonia represents a general risk for development that can be exacerbated as climate change increases dehydration risk for terrestrial-breeding frogs. It may also be a cue that elicits adaptive physiological responses during early development.

Time series data are often observed in ecological monitoring. Frequently such data exhibit nonlinear trends over time potentially due to complex relationships between observed and auxiliary variables, and there may also be sudden declines over time due to major disturbances. This poses substantial challenges for modelling such data and also for model-based adaptive monitoring. We propose novel methods for finding adaptive designs for monitoring when historical data show such nonlinear patterns and sudden declines over time. This work is motivated by a coral reef monitoring program that has been established at Scott Reef; a coral reef off the Western coast of Australia. Data collected for monitoring the health of Scott Reef are considered, and semiparametric and interrupted time series modelling approaches are adopted to describe how these data vary over time. New methods are then proposed that enable adaptive monitoring designs to be found based on such modelling approaches. These methods are then applied to find future monitoring designs at Scott Reef and form a set of recommendations for future monitoring. Through applying the proposed methods, it was found that future information gain is expected to be similar across a variety of different sites, suggesting that no particular location needed to be prioritised at Scott Reef for the next monitoring phase. In addition, it was found that omitting some sampling sites/reef locations was possible without substantial loss in expected information gain, depending upon the disturbances that were observed. The resulting adaptive designs are used to provide recommendations for future monitoring in this region, and for reefs where changes to the current monitoring practices are being sought. Furthermore, as the methods used and developed throughout this study are generic in nature, this research has the potential to improve ecological monitoring more broadly where complex data are being collected over time.