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Necrotizing fasciitis is a rare infection, often requiring large debridement's due to its rapid spread in the soft tissues. Reconstruction is always a challenge. We report the successful use of Integra® Dermal Regeneration Template, combined with Negative Pressure Wound Therapy and thin skin grafts, and a local flap, to reconstruct the abdominal skin in a 7-year-old boy who developed a necrotizing fasciitis after a trauma with his scooter. Stable coverage was achieved, without skin retraction and with a preserved range of motion at 1-year post-operatively.

Abstract Background Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP. Methods We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality. Results Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97). Conclusion In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes. Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476 .

Abstract Background Patellar instability is a well-known pathology in which kinematics can be investigated using metrics such as tibial tuberosity tracheal groove (TTTG), the bisect offset (BO), and the lateral patellar tilt (LPT). We used dynamic computed tomography (CT) to investigate the patellar motion of healthy subjects in weight-bearing conditions to provide normative values for TTTG, BO, and LPT, as well as to define whether BO and LPT are affected by the morphology of the trochlear groove. Methods Dynamic scanning was used to acquire images during weight-bearing in 21 adult healthy volunteers. TTTG, BO, and LPT metrics were computed between 0° and 30° of knee flexion. Sulcus angle, sulcus depth, and lateral trochlear inclination were calculated and used with the TTTG for simple linear regression models. Results All metrics gradually decreased during eccentric movement (TTTG, -6.9 mm; BO, -12.6%; LPT, -4.3°). No significant differences were observed between eccentric and concentric phases at any flexion angle for all metrics. Linear regression between kinematic metrics towards full extension showed a moderate fit between BO and TTTG (R 2 0.60, β 1.75) and BO and LPT (R 2 0.59, β 1.49), and a low fit between TTTG and LPT (R 2 0.38, β 0.53). A high impact of the TTTG distance over BO was shown in male participants (R 2 0.71, β 1.89) and patella alta individuals (R 2 0.55, β 1.91). Conclusion We provided preliminary normative values of three common metrics during weight-bearing dynamic CT and showed the substantial impact of lateralisation of the patella tendon over patella displacement. Relevance statement These normative values can be used by clinicians when evaluating knee patients using TTTG, BO, and LPT metrics. The lateralisation of the patellar tendon in subjects with patella alta or in males significantly impacts the lateral displacement of the patella. Key Points Trochlear groove morphology had no substantial impact on motion prediction. The lateralisation of the patellar tendon seems a strong predictor of lateral displacement of the patella in male participants. Participants with patella alta displayed a strong fit between the patellar lateral displacement and tilt. TTTG, BO, and LPT decreased during concentric movement. Concentric and eccentric phases did not show differences for all metrics. Graphical Abstract

Abstract Background Engineering bacteria with the purpose of optimizing the production of interesting molecules often leads to a decrease in growth due to metabolic burden or toxicity. By delaying the production in time, these negative effects on the growth can be avoided in a process called a two-stage fermentation. Main text During this two-stage fermentation process, the production stage is only activated once sufficient cell mass is obtained. Besides the possibility of using external triggers, such as chemical molecules or changing fermentation parameters to induce the production stage, there is a renewed interest towards autoinducible systems. These systems, such as quorum sensing, do not require the extra interference with the fermentation broth to start the induction. In this review, we discuss the different possibilities of both external and autoinduction methods to obtain a two-stage fermentation. Additionally, an overview is given of the tuning methods that can be applied to optimize the induction process. Finally, future challenges and prospects of (auto)inducible expression systems are discussed. Conclusion There are numerous methods to obtain a two-stage fermentation process each with their own advantages and disadvantages. Even though chemically inducible expression systems are well-established, an increasing interest is going towards autoinducible expression systems, such as quorum sensing. Although these newer techniques cannot rely on the decades of characterization and applications as is the case for chemically inducible promoters, their advantages might lead to a shift in future inducible expression systems.

This study aims to characterize the high frequency radar and numerically simulated low-frequency filtered currents in the south-eastern Bay of Biscay (study area) using a K-means classification algorithm based on an improved Euclidean Distance calculation method that does not take missing values. The errors between observations and simulations was estimated and predicted based on this classification method. Results indicate that predominantly eastward (northward) currents over the Spanish (French) continental shelf/slope in winter and more variable currents in the west and south-west in summer. The model classification results for circulation characteristics are in relatively good agreement with HF radar results, especially for currents on the Spanish (French) shelf/slope. In addition, the probabilistic relationship between observed and modeled currents was explored, obtaining the probability of occurrence of modeled current groups when each group of observed currents occurs. Finally, predictions of model and observed current errors were made based on the classification results, and it was found that the predictions based on the classification of all data had the smallest errors, with a 17% improvement over the unclassified control experiment. This study provides a foundation for subsequent model error testing, forecast product improvement and data assimilation.

Abstract The transcriptional architecture of phages can deepen our understanding of the phage‐host infection process and can be of key importance for phage engineering and biotechnological applications. Here, we applied ONT‐cappable‐sequencing, a long‐read RNA‐sequencing technique, to study the regulatory mechanisms of Pseudomonas infecting giant phage 201ϕ2‐1. We identified 67 promoters and 132 terminators that together represent 92 transcriptional units. A full comparison of these data to the transcriptome of model Pseudomonas phage ϕKZ confirmed that the transcriptional programs of these prototypes of the Serwervirus and Phikzvirus genera are largely conserved, despite some subtle regulatory differences. Evidence supporting these shared mechanisms include the identification of highly similar sequence motifs for regulatory elements in both phages and the conservation of regulatory elements loci relative to homologous genes in each phage. Moreover, we discovered a sRNA in 201ϕ2‐1 that is highly conserved among prototype members of different giant phage genera. Sequencing of the 201ϕ2‐1 host genome resulted in its reclassification as Pseudomonas atacamensis, a close relative of the important agricultural biocontrol agent Pseudomonas chlororaphis. Finally, we conducted in vivo assays of eight 201ϕ2‐1 terminators and found them to strongly terminate transcription in P. chlororaphis. Control elements from phage transcriptional programs have a rich history for applications in biotechnology. In these studies, we demonstrate new insight into the transcriptional program of 201ϕ2‐1 and demonstrate the potential of its regulatory elements for novel and useful tools for synthetic biology circuitry.

Ocean observing systems in coastal, shelf and marginal seas collect diverse oceanographic information supporting a wide range of socioeconomic needs, but observations are necessarily sparse in space and/or time due to practical limitations. Ocean analysis and forecast systems capitalize on such observations, producing data-constrained, four-dimensional oceanographic fields. Here we review efforts to quantify the impact of ocean observations, observing platforms, and networks of platforms on model products of the physical ocean state in coastal regions. Quantitative assessment must consider a variety of issues including observation operators that sample models, error of representativeness, and correlated uncertainty in observations. Observing System Experiments, Observing System Simulation Experiments, representer functions and array modes, observation impacts, and algorithms based on artificial intelligence all offer methods to evaluate data-based model performance improvements according to metrics that characterize oceanographic features of local interest. Applications from globally distributed coastal ocean modeling systems document broad adoption of quantitative methods, generally meaningful reductions in model-data discrepancies from observation assimilation, and support for assimilation of complementary data sets, including subsurface in situ observation platforms, across diverse coastal environments.

Portable chest radiography is a valuable tool in the intensive care unit. However, the supine position causes superposition of anatomical structures resulting in less reliable detection of certain abnormalities. Recently, a portable digital tomosynthesis (pDTS) prototype with a modified motorized X-ray device was developed. We aimed to compare the diagnostic value of pDTS to standard bedside chest radiography in the diagnosis of a posterior pneumothorax. A modified motorized X-ray device was developed to perform 15 radiographic projections while translating the X-ray tube 25 cm (10 cm ramp up and 15 cm during X-ray exposure) with a total radiation dose of 0.54 mSv. This new technique of pDTS was performed in addition to standard bedside chest X-ray in a patient with a confirmed posterior hydropneumothorax. The images were compared with the standard bedside chest X-ray and computed tomography (CT) images by two experienced radiologists. The posterior hydropneumothorax previously identified with CT was visible on tomosynthesis images but not with standard bedside imaging. Combining the digital tomosynthesis technique with the portable X-ray machine could increase the diagnostic value of bedside chest radiography for the diagnosis of posterior pneumothoraces while avoiding intrahospital transport and limiting radiation exposure compared to CT.

Abstract Background Engineering bacterial strains to redirect the metabolism towards the production of a specific product has enabled the development of industrial biotechnology. However, rewiring the metabolism can have severe implications for a microorganism, rendering cells with stress symptoms such as a decreased growth rate, impaired protein synthesis, genetic instability and an aberrant cell size. On an industrial scale, this is reflected in processes that are not economically viable. Main text In literature, most stress symptoms are attributed to “metabolic burden”, however the actual triggers and stress mechanisms involved are poorly understood. Therefore, in this literature review, we aimed to get a better insight in how metabolic engineering affects Escherichia coli and link the observed stress symptoms to its cause. Understanding the possible implications that chosen engineering strategies have, will help to guide the reader towards optimising the envisioned process more efficiently. Conclusion This review addresses the gap in literature and discusses the triggers and effects of stress mechanisms that can be activated when (over)expressing (heterologous) proteins in Escherichia coli. It uncovers that the activation of the different stress mechanisms is complex and that many are interconnected. The reader is shown that care has to be taken when (over)expressing (heterologous) proteins as the cell’s metabolism is tightly regulated.

IntroductionAdvancements in rectal cancer (RC) treatment not only led to an increase in lives saved but also improved quality of life (QoL). Notwithstanding these benefits, RC treatment comes at the price of gastrointestinal morbidity in many patients. Health economic modelling poses an opportunity to explore the societal burden of such side-effects. This study aims to quantify radiation-induced late small bowel (SB) toxicity in survivors of RC for Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT) and Intensity Modulated Radiation Therapy – Image Guided Radiation Therapy (IMRT/IGRT).Materials and methodsMaterials and A model-based health economic evaluation was performed. The theoretical cohort consists of a case-mix of survivors of RC aged 25-99 years according to Belgian age-specific incidence rates. A societal perspective was adopted. The base case analysis was complemented with one-way deterministic analyses, deterministic scenario analyses and probabilistic sensitivity analysis (1,000 iterations). Results were presented as mean lifetime incremental cost (€) and utility (QALYs) per patient.ResultsThe analyses showed that the use of innovative radiotherapy (RT) improves lifetime QoL in survivors of RC by 0.11 QALYs and 0.05 QALYs by preferring IMRT/IGRT and IMRT over 3D-CRT, respectively. The use of IMRT/IGRT and IMRT results in an incremental cost-saving of €3,820 and €1,863 per patient, solely by radiation-induced SB toxicity, compared to 3D-CRT.Discussion and conclusionIt is important to consider late toxicity effects in decisions regarding investments and reimbursement as our analysis highlighted the potential long-term cost-savings and improved QoL of novel RT techniques in patients with rectal cancer.

Purpose: Metastatic melanoma lymph nodes (MMLns) might be challenging to detect on MR-WBI, as both MMLns and normal lymph nodes (NLns) can show restricted water diffusion. Our purpose is to assess the potential contribution of the DIXON sequence in differentiating MMLns from NLns. Material and methods: We followed a cohort of 107 patients with stage IIIb/c and IV skin melanoma for 32 months using MR-WBI with DIXON, STIR, and DWI/ADC sequences. We compared signal intensity (SI) values of MMLns and NLns in the four series of the DIXON sequence (in/out-of-phase, fat_only, and water_only series). The fat fraction (SIfat_only/SIin) and the long:short axis ratio of MMLns were calculated. The fat fraction was also calculated in the fatty hila of NLns. Results: All MMLns (8 from 7 patients) showed SIout>SIin with a mean fat fraction of 10%. In 40 normal fatty hila (25 patients), the proportion of SIout>SIin was 100% and mean fat fraction was 89% (pSIin pattern was identified in 41/113 cases from 19/40 patients. The median long:short axis ratio in MMLns was 1.13 (range 1.03–1.25). Conclusion: The combination of three features of MMLns (SIout>SIin, low-fat fraction and rounded shape) might hold promise in differentiating NLns from MMLns in patients with skin melanoma. Further research is warranted due to the small number of MMLns in our cohort.

Abstract COVID-19 can induce neurological sequelae, negatively affecting the quality of life. Unravelling this illness's impact on structural brain connectivity, white-matter microstructure (WMM), and cognitive performance may help elucidate its implications. This cross-sectional study aimed to investigate differences in these factors between former hospitalised COVID-19 patients (COV) and healthy controls. Group differences in structural brain connectivity were explored using Welch-two sample t-tests and two-sample Mann–Whitney U tests. Multivariate linear models were constructed (one per region) to examine fixel-based group differences. Differences in cognitive performance between groups were investigated using Wilcoxon Rank Sum tests. Possible effects of bundle-specific FD measures on cognitive performance were explored using a two-group path model. No differences in whole-brain structural organisation were found. Bundle-specific metrics showed reduced fiber density (p = 0.012, Hedges’ g = 0.884) and fiber density cross-section (p = 0.007, Hedges’ g = 0.945) in the motor segment of the corpus callosum in COV compared to healthy controls. Cognitive performance on the motor praxis and digit symbol substitution tests was worse in COV than healthy controls (p

Abstract Background The literature considers sclerotherapy to be a safe and effective treatment for benign thyroid cysts. No subsequent diagnostic problems have been reported as a complication. We report the occurrence of focal inflammation after said therapy, mimicking a thyroid malignancy. Case presentation We report a case of a young male with a solitary strongly suspicious lesion in the thyroid. The patient had undergone prior sclerotherapy of a thyroid cyst with Doxycycline. The lesion appeared to be a focal area of inflammation and thus iatrogenic in nature. Systemic use of doxycycline is known to sometimes cause a non-immune chemical thyroiditis, dubbed as black thyroid due to the intense black discoloration of the thyroid. It might be that the instillation of doxycycline was responsible for a similar, more localized area of thyroiditis. Conclusions For the work-up of a solitary suspicious thyroid lesion, the medical history of the patient should always be considered. In case of prior ipsilateral sclerotherapy, a reactive inflammatory response may mimic thyroid malignancy. A fine needle aspiration should be performed to exclude thyroid cancer. Treatment is not necessary; the process appears to be self-limiting as evidenced in the follow-up of this case.

Abstract Critical limb ischemia is associated with high mortality and major amputations. Intra-arterial digital subtraction angiography (IADSA) has been the reference standard but has some shortcomings including the two-dimensional projection and the lack of tissue perfusion information. The aim of this exploratory study is to examine four-dimensional computed tomography (4DCT) angiography and perfusion imaging using low-volume intra-arterial contrast injections for an improved anatomic and hemodynamic assessment in patients with foot ulcers. Three patients underwent a low-volume (2 mL) intra-arterial contrast-enhanced 4DCT examination combined with a diagnostic IADSA. An automated assessment of blood flow and tissue perfusion from the 4DCT data was performed. Vascular structures and corresponding blood flows were successfully assessed and correlated well with the IADSA results. Perfusion values of the affected tissue were significantly higher compared to the unaffected tissue. The proposed 4DCT protocol combined with the minimal usage of contrast agent (2 mL) provides superior images compared to IADSA as three phases (arterial, perfusion, and venous) are captured. The obtained parameters could allow for an improved diagnosis of critical limb ischemia as both the proximal vasculature and the extent of the perfusion deficit in the microvasculature can be assessed. Relevance statement Intra-arterial 4DCT allows for assessing three phases (arterial, perfusion and venous) using minimal contrast (2 mL). This method could lead to an improved diagnosis of critical limb ischemia as both proximal vasculature and the extent of the perfusion deficit are assessed. Trial registration ISRCTN, ISRCTN95737449. Registered 14 March 2023—retrospectively registered, https://www.isrctn.com/ISRCTN95737449 Key points • Three phases (arterial, perfusion, and venous) are obtained from 2 mL intra-arterial 4DCT. • The obtained hemodynamic parameters correlated well with the IADSA findings. • 4DCT surpassed IADSA in terms of assessment of venous blood flow and inflammatory hyperperfusion. • The assessment of tissue perfusion could lead to optimizing the revascularization strategy. Graphical Abstract