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Abstract Background Muscle invasive bladder cancer (MIBC) treatment combines systemic therapy and radical cystectomy (RC) or local (chemo-)radiotherapy. Response to systemic therapy is an important outcome predictor but is difficult to assess pre-operatively. Methods We analyzed multiparametric MRI (mpMRI) in consecutive MIBC patients receiving cisplatin-based neo-adjuvant chemotherapy at our institution. Two readers, blinded for pathological outcome, independently scored mpMRI before and after 2 and 4 cycles using both a qualitative 3-step method and nacVI-RADS. We analyzed accuracy of mpMRI scores to predict pathologic complete response (pCR) and inter-observer agreement. Results We analyzed 46 patients receiving NAC, 6 patients did not undergo RC after NAC and were excluded. Eleven out of 40 (28%) patients showed a pCR. mpMRI could be assessed in over 90% of patients. Radiologic complete response (rCR) using both methods was significantly associated with pCR, with an overall specificity of 96% and sensitivity of 36% and a high inter-observer agreement. rCR as assessed by the 3-step score was significantly associated with disease free survival (DFS) benefit. Conclusion The use of nacVI-RADS can predict pCR after NAC with high specificity but low sensitivity and a high inter-observer agreement. A 3-step score adds value in determining local residual disease, rCR assessed by this method could correlate with DFS benefit. mpMRI scores should be prospectively assessed in future trials of multimodal management of MIBC and can be a predictive asset in routine clinical management.

Abstract When a person listens to natural speech, the relation between features of the speech signal and the corresponding evoked electroencephalogram (EEG) is indicative of neural processing of the speech signal. Using linguistic representations of speech, we investigate the differences in neural processing between speech in a native and foreign language that is not understood. We conducted experiments using three stimuli: a comprehensible language, an incomprehensible language, and randomly shuffled words from a comprehensible language, while recording the EEG signal of native Dutch-speaking participants. We modeled the neural tracking of linguistic features of the speech signals using a deep-learning model in a match-mismatch task that relates EEG signals to speech, while accounting for lexical segmentation features reflecting acoustic processing. The deep learning model effectively classifies coherent versus nonsense languages. We also observed significant differences in tracking patterns between comprehensible and incomprehensible speech stimuli within the same language. It demonstrates the potential of deep learning frameworks in measuring speech understanding objectively.

Abstract Background The genus Geobacillus and its associated taxa have been the focal point of numerous thermophilic biotechnological investigations, both at the whole cell and enzyme level. By contrast, comparatively little research has been done on its recently delineated sister genus, Parageobacillus. Here we performed pan-genomic analyses on a subset of publicly available Parageobacillus and Saccharococcus genomes to elucidate their biotechnological potential. Results Phylogenomic analysis delineated the compared taxa into two distinct genera, Parageobacillus and Saccharococcus, with P. caldoxylosilyticus isolates clustering with S. thermophilus in the latter genus. Both genera present open pan-genomes, with the species P. toebii being characterized with the highest novel gene accrual. Diversification of the two genera is driven through the variable presence of plasmids, bacteriophages and transposable elements. Both genera present a range of potentially biotechnologically relevant features, including a source of novel antimicrobials, thermostable enzymes including DNA-active enzymes, carbohydrate active enzymes, proteases, lipases and carboxylesterases. Furthermore, they present a number of metabolic pathways pertinent to degradation of complex hydrocarbons and xenobiotics and for green energy production. Conclusions Comparative genomic analyses of Parageobacillus and Saccharococcus suggest that taxa in both of these genera can serve as a rich source of biotechnologically and industrially relevant secondary metabolites, thermostable enzymes and metabolic pathways that warrant further investigation.

Abstract The continuously reinforced concrete pavement (CRCP) system grapples with challenges such as non-uniform transverse crack patterns and the need for substantial reinforcement. Field research on the Belgian CRCP sections along motorway E313 indicates that active cracking induced by partial surface saw-cuts consistently leads to transverse crack patterns. This study introduces an innovative modification to the CRCP: the actively reinforced concrete pavement design (ARCP). The ARCP leverages partial surface saw-cuts to reduce reinforcement needs by replacing continuous-length steel bars with partial-length counterparts. The main objective of the present study is to develop a 3D finite element (FE) model capturing the active cracking behavior of ARCP under realistic external temperature variations. Comparative analysis with CRCP considers early-age crack patterns, crack strain development, and the distribution of maximum steel stress for different steel ratios (0.67%, 0.75%, and 0.85%). FE simulation results align with field data, indicating that ARCP exhibits similar early-age cracking behavior to CRCP but with a significant 24 to 42% reduction in total reinforcement. This innovation presents a promising avenue for addressing CRCP challenges while optimizing material usage in pavement construction.

IntroductionThe contribution of Cannabinoid type 1 receptor (CB1) in mitochondrial energy transduction mechanisms and mitochondrial activities awaits deeper investigations. Our study aims to assess the impact of CB1 absence on the mitochondrial compartment in the liver, focusing on both functional aspects and remodeling processes.MethodsWe used CB1−/− and CB1+/+ male mice. Cytochrome C Oxidase activity was determined polarographically. The expression and the activities of separated mitochondrial complexes and supercomplexes were performed by using Blue-Native Page, Western blotting and histochemical staining for in-gel activity. Key players of Mitochondrial Quality Control processes were measured using RT-qPCR and Western blotting. Liver fine sub-cellular ultrastructural features were analyzed by TEM analysis.Results and discussionIn the absence of CB1, several changes in the liver occur, including increased oxidative capacity, reduced complex I activity, enhanced complex IV activity, general upregulation of respiratory supercomplexes, as well as higher levels of oxidative stress. The mitochondria and cellular metabolism may be affected by these changes, increasing the risk of ROS-related damage. CB1−/− mice show upregulation of mitochondrial fusion, fission and biogenesis processes which suggests a dynamic response to the absence of CB1. Furthermore, oxidative stress disturbs mitochondrial proteostasis, initiating the mitochondrial unfolded protein response (UPRmt). We noted heightened levels of pivotal enzymes responsible for maintaining mitochondrial integrity, along with heightened expression of molecular chaperones and transcription factors associated with cellular stress reactions. Additionally, our discoveries demonstrate a synchronized reaction to cellular stress, involving both UPRmt and UPRER pathways.

Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3’-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLγ) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases.

Background: Timely diagnosis of heart failure (HF) in patients with a systemic right ventricle (sRV) is difficult but important since clinical deterioration is fast once HF develops. We aimed to compare echocardiography and biomarker profile between sRV patients with and without HF and patients with a systemic left ventricle diagnosed with HF (sLV-HF). Methods and results: Eighty-seven sRV patients and 30 sLV-HF patients underwent echocardiographic evaluation and blood sampling. Compared to sRV patients without HF, sRV-HF patients had more remodeling of the subpulmonary LV (spLV) (internal diameter 3.9 cm [3.3–5.7] vs 3.4 cm [2.9–3.9], P = 0.03, posterior wall 0.93 cm [0.76–1.20] vs 0.71 cm [0.59–0.91], P = 0.006) and lower spLV systolic function: ejection fraction (59 % ± 14 vs 70 % ± 10, P = 0.011), mitral annular plane systolic excursion (1.7 cm ± 0.5 vs 2.1 cm ± 0.4, P = 0.003), fractional area change (47 % [38–58] vs 59 % [51–70], P = 0.002) and lateral strain rate (−1.2/s ± 0.46 vs −1.5/s ± 0.39, P = 0.016). Inflammatory biomarkers were higher in sRV-HF patients compared to those without HF: red cell distribution width (13.3 fL [12.8–14.1] vs 12.6 fL [12.3–13.1], P

Abstract Barley (Hordeum vulgare) is essential to global food systems and the brewing industry. Its physiological traits and microbial communities determine malt quality. Although microbes influence barley from seed health to fermentation, there is a gap in metagenomic insights during seed storage. Crucially, elucidating the changes in microbial composition associated with barley seeds is imperative for understanding how these fluctuations can impact seed health and ultimately, influence both agricultural yield and quality of barley-derived products. Whole metagenomes were sequenced from eight barley seed samples obtained at different storage time points from harvest to nine months. After binning, 82 metagenome-assembled genomes (MAGs) belonging to 26 distinct bacterial genera were assembled, with a substantial proportion of potential novel species. Most of our MAG dataset (61%) showed over 90% genome completeness. This pioneering barley seed microbial genome retrieval provides insights into species diversity and structure, laying the groundwork for understanding barley seed microbiome interactions at the genome level.

Abstract Background The facultatively anaerobic thermophile Parageobacillus thermoglucosidasius is able to produce hydrogen gas (H2) through the water–gas shift (WGS) reaction. To date this process has been evaluated under controlled conditions, with gas feedstocks comprising carbon monoxide and variable proportions of air, nitrogen and hydrogen. Ultimately, an economically viable hydrogenogenic system would make use of industrial waste/synthesis gases that contain high levels of carbon monoxide, but which may also contain contaminants such as H2, oxygen (O2) and other impurities, which may be toxic to P. thermoglucosidasius. Results We evaluated the effects of synthesis gas (syngas) mimetic feedstocks on WGS reaction-driven H2 gas production by P. thermoglucosidasius DSM 6285 in small-scale fermentations. Improved H2 gas production yields and faster onset towards hydrogen production were observed when anaerobic synthetic syngas feedstocks were used, at the expense of biomass accumulation. Furthermore, as the WGS reaction is an anoxygenic process, we evaluated the influence of O2 perturbation on P. thermoglucosidasius hydrogenogenesis. O2 supplementation improved biomass accumulation, but reduced hydrogen yields in accordance with the level of oxygen supplied. However, H2 gas production was observed at low O2 levels. Supplementation also induced rapid acetate consumption, likely to sustain growth. Conclusion The utilisation of anaerobic syngas mimetic gas feedstocks to produce H2 and the relative flexibility of the P. thermoglucosidasius WGS reaction system following O2 perturbation further supports its applicability towards more robust and continuous hydrogenogenic operation.

Abstract The integration of Augmented Reality (AR) into daily surgical practice is withheld by the correct registration of pre‐operative data. This includes intelligent 3D model superposition whilst simultaneously handling real and virtual occlusions caused by the AR overlay. Occlusions can negatively impact surgical safety and as such deteriorate rather than improve surgical care. Robotic surgery is particularly suited to tackle these integration challenges in a stepwise approach as the robotic console allows for different inputs to be displayed in parallel to the surgeon. Nevertheless, real‐time de‐occlusion requires extensive computational resources which further complicates clinical integration. This work tackles the problem of instrument occlusion and presents, to the authors’ best knowledge, the first‐in‐human on edge deployment of a real‐time binary segmentation pipeline during three robot‐assisted surgeries: partial nephrectomy, migrated endovascular stent removal, and liver metastasectomy. To this end, a state‐of‐the‐art real‐time segmentation and 3D model pipeline was implemented and presented to the surgeon during live surgery. The pipeline allows real‐time binary segmentation of 37 non‐organic surgical items, which are never occluded during AR. The application features real‐time manual 3D model manipulation for correct soft tissue alignment. The proposed pipeline can contribute towards surgical safety, ergonomics, and acceptance of AR in minimally invasive surgery.

Abstract Community-acquired Pneumonia (CAP) guidelines generally recommend to admit patients with moderate-to-severe CAP and start treatment with intravenous antibiotics. This study aims to explore the clinical outcomes of oral antibiotics in patients with moderate-to-severe CAP. We performed a nested cohort study of an observational study including all adult patients presenting to the emergency department of the Haga Teaching Hospital, the Netherlands, between April 2019 and May 2020, who had a blood culture drawn. We conducted propensity score matching with logistic and linear regression analysis to compare patients with moderate-to-severe CAP (Pneumonia Severity Index class III–V) treated with oral antibiotics to patients treated with intravenous antibiotics. Outcomes were 30-day mortality, intensive care unit admission, readmission, length of stay (LOS) and length of antibiotic treatment. Of the original 314 patients, 71 orally treated patients were matched with 102 intravenously treated patients. The mean age was 73 years and 58% were male. We found no significant differences in outcomes between the oral and intravenous group, except for an increased LOS of + 2.6 days (95% confidence interval 1.2–4.0, p value

Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.

The HYPERNETS project developed a new hyperspectral radiometer (HYPSTAR®) integrated in automated networks of water (WATERHYPERNET) and land (LANDHYPERNET) bidirectional reflectance measurements for satellite validation. In this paper, the feasibility of using LANDHYPERNET surface reflectance data for vicarious calibration of multispectral (Sentinel-2 and Landsat 8/9) and hyperspectral (PRISMA) satellites is studied. The pipeline to process bottom of atmosphere (BOA) surface reflectance HYPERNETS data to band-integrated top of atmosphere (TOA) reflectances and compare them to satellite observations is detailed. Two LANDHYPERNET sites are considered in this study: the Gobabeb HYPERNETS site in Namibia (GHNA) and Princess Elizabeth Base in Antarctica (PEAN). 36 near-simultaneous match-ups within 1 h are found where HYPERNETS and satellite data pass all quality checks. For the Gobabeb HYPERNETS site, agreement to within 5% is found with Sentinel-2 and Landsat 8/9. The differences with PRISMA are smaller than 10%. For the HYPERNETS Antarctica site, there are also a number of match-ups with good agreement to within 5% for Landsat 8/9. The majority show notable disagreement, i.e., HYPERNETS being over 10% different compared to satellite. This is due to small-scale irregularities in the wind-blown snow surface, and their shadows cast by the low Sun. A study comparing the HYPERNETS measurements against a bidirectional reflectance distribution function (BRDF) model is recommended. Overall, we confirm data from radiometrically stable HYPERNETS sites with sufficient spatial and angular homogeneity can successfully be used for vicarious calibration purposes.

This paper describes a prototype network of automated in situ measurements of hyperspectral water reflectance suitable for satellite validation and water quality monitoring. Radiometric validation of satellite-derived water reflectance is essential to ensure that only reliable data, e.g., for estimating water quality parameters such as chlorophyll a concentration, reach end-users. Analysis of the differences between satellite and in situ water reflectance measurements, particularly unmasked outliers, can provide recommendations on where satellite data processing algorithms need to be improved. In a massively multi-mission context, including Newspace constellations, hyperspectral missions and missions with broad spectral bands not designed for “water colour”, the advantage of hyperspectral over multispectral in situ measurements is clear. Two hyperspectral measurement systems, PANTHYR (based on the mature TRIOS/RAMSES radiometer) and HYPSTAR® (a newly designed radiometer), have been integrated here in the WATERHYPERNET network with SI-traceable calibration and characterisation. The systems have common data acquisition protocol, data processing and quality control. The choice of validation site and viewing geometry and installation considerations are described in detail. Three demonstration cases are described: 1. PANTHYR data from two sites are used to validate Sentinel-2/MSI (A&B); 2. HYPSTAR® data at six sites are used to validate Sentinel-3/OLCI (A&B); 3. PANTHYR and HYPSTAR® data in Belgian North Sea waters are used to monitor phytoplankton parameters, including Phaeocystis globosa, over two 5 month periods. Conclusion are drawn regarding the quality of Sentinel-2/MSI and Sentinel-3/OLCI data, including indications where improvements could be made. For example, a positive bias (mean difference) is found for ACOLITE_DSF processing of Sentinel-2 in clear waters (Acqua Alta) and clues are provided on how to improve this processing. The utility of these in situ measurements, even without accompanying hyperspectral satellite data, is demonstrated for phytoplankton monitoring. The future evolution of the WATERHYPERNET network is outlined, including geographical expansion, improvements to hardware reliability and to the measurement method (including uncertainty estimation) and plans for daily distribution of near real-time data.

Background and purpose: Chemoradiotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer (LACC). In this study, we postulate that omitting an iconographical unaffected uterus (+12 mm distance from the tumour) from the treatment volume is safe and that no tumour will be found in the non-targeted uterus (NTU) leading to reduction of high-dose volumes of surrounding organs at risk (OARs) Material and Methods: In this single-arm phase 2 study, two sets of target volumes were delineated: one standard-volume (whole uterus) and an EXIT-volume (exclusion of non-tumour-bearing parts of the uterus with a minimum 12 mm margin from the tumour). All patients underwent chemoradiotherapy targeting the EXIT-volume, followed by completion hysterectomy. In 15 patients, a plan comparison between two treatment plans (PTV vs PTV_EXIT) was performed. The primary endpoint was the pathological absence of tumour involvement in the non-targeted uterus (NTU). Secondary endpoints included dosimetric impact of target volume reduction on OARs, acute and chronic toxicity, overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS). Results: In all 21 (FIGO stage I: 2; II: 14;III: 3; IV: 2) patients the NTU was pathologically negative. Ssignificant reductions in Dmean in bladder, sigmoid and rectum; V15Gy in sigmoid and rectum, V30Gy in bladder, sigmoid and rectum; V40Gy and V45Gy in bladder, bowel bag, sigmoid and rectum; V50Gy in rectum were achieved. Median follow-up was 54 months (range 7–79 months). Acute toxicity was mainly grade 2 and 5 % grade 3 urinary. The 3y- OS, PFS and LRFS were respectively 76,2%, 64,9% and 81 %. Conclusion: MRI-based exclusion of the non-tumour-bearing parts of the uterus at a minimum distance of 12 mm from the tumour out of the target volume in LACC can be done without risk of residual disease in the NTU, leading to a significant reduction of the volume of surrounding OARS treated to high doses.

PurposeHolmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry.MethodsRetrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients’ health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma.ResultsA total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries.ConclusionThis study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

Abstract Prospective audit with feedback during infectious diseases ward rounds (IDWR) is a common antimicrobial stewardship (AMS) practice on the Paediatric Intensive Care Unit (PICU). These interdisciplinary meetings rely on the quality of handover, with high risk of omission of information. We developed an electronic platform integrating infection-related patient data (COSARAPed). In the mixed PICU of a Belgian tertiary hospital we conducted an observational prospective cohort study comparing patient handovers during IDWRs using the COSARAPed-platform to those with access only to conventional resources. The quality of handover was investigated directly by assessment if the narrative was in accordance with Situation-Background-Assessment-Recommendation principles and if adequate demonstration of diagnostic information occurred, and also indirectly by registration if this was only achieved after intervention by the non-presenting AMS team members. We also recorded all AMS-recommendations. During a 6-month study period, 24 IDWRs and 82 patient presentations were assessed. We could only find a statistically significant advantage in favor of COSARAPed by indirect evaluation. We registered 92 AMS-recommendations, mainly resulting in reduced antibiotic pressure. We concluded that the IDWR is an appropriate platform for AMS on the PICU and that the utilisation of COSARAPed may enhance the quality of patient handover.

Abstract Purpose To examine implications of the COVID-19 pandemic on eating disorder (ED) features and psychopathology in female adolescents with anorexia nervosa (AN). Method In total 79 females with first-onset AN (aged 12–22 years) were included and were followed up across a period of 1 year. We assessed AN participants recruited pre-pandemic (n = 49) to those recruited peri-pandemic (n = 30). Pre- (n = 37) and peri-pandemic (n = 38) age-, and education-matched typically developing (TD) girls (n = 75) were used as a reference cohort. ED features and psychopathology were assessed at baseline. After 1 year of follow-up the association between pandemic timing and clinical course was assessed. Analyses of covariance were used to examine differences in ED features and psychopathology. Results Peri-pandemic AN participants experienced less ED symptoms at baseline compared to pre-pandemic AN participants. In particular, they were less dissatisfied with their body shape, and experienced less interpersonal insecurity. In addition, the peri-pandemic AN group met fewer DSM-IV criteria for comorbid disorders, especially anxiety disorders. In contrast, peri-pandemic AN participants had a smaller BMI increase over time. In TD girls, there were no differences at baseline in ED features and psychopathology between the pre- and peri-pandemic group. Conclusion Overall, peri-pandemic AN participants were less severely ill, compared to pre-pandemic AN participants, which may be explained by less social pressure and peer contact, and a more protective parenting style during the pandemic. Conversely, peri-pandemic AN participants had a less favorable clinical course, which may be explained by reduced access to health care facilities during the pandemic. Level of evidence Level III: Evidence obtained from well-designed cohort or case–control analytic studies.

Abstract Since the onset of the coronavirus disease (COVID-19) pandemic in Belgium, UZ/KU Leuven has played a crucial role as the National Reference Centre (NRC) for respiratory pathogens, to be the first Belgian laboratory to develop and implement laboratory developed diagnostic assays for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and later to assess the quality of commercial kits. To meet the growing demand for decentralised testing, both clinical laboratories and government-supported high-throughput platforms were gradually deployed across Belgium. Consequently, the role of the NRC transitioned from a specialised testing laboratory to strengthening capacity and coordinating quality assurance. Here, we outline the measures taken by the NRC, the national public health institute Sciensano and the executing clinical laboratories to ensure effective quality management of molecular testing throughout the initial two years of the pandemic (March 2020 to March 2022).

Abstract Background Vancomycin is a commonly prescribed antibiotic to treat gram-positive infections. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. However, in most countries, steady-state plasma concentrations are used as a surrogate parameter of target AUC/MIC, but this practice has some drawbacks. Hence, direct AUC-guided monitoring of vancomycin using model-informed precision dosing (MIPD) tools has been proposed for earlier attainment of target concentrations and reducing vancomycin-related nephrotoxicity. However, solid scientific evidence for these benefits in clinical practice is still lacking. This randomized controlled trial (RCT) aims to investigate the clinical utility of MIPD dosing of vancomycin administered via continuous infusion in hospitalized adults. Methods Participants from 11 wards at two Belgian hospitals are randomly allocated to the intervention group or the standard-of-care comparator group. In the intervention group, clinical pharmacists perform dose calculations using CE-labeled MIPD software and target an AUC24h of 400 to 600 mg × h/L, whereas patients in the comparator group receive standard-of-care dosing and monitoring according to the institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 48 and 72 h after start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury (AKI) during and until 48 h after stop of vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 72 and 96 h after start of vancomycin treatment, and the proportion of time within the target AUC24h/MIC of 400–600. Discussion This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment. Trial registration EudraCT number: 2021-003670-31. Registered June 28, 2021. ClinicalTrials.gov identifier: NCT05535075. Registered September 10, 2022. Protocol version 3, protocol date: April 21, 2023.

Discussing sensitive topics, such as slavery, political extremism or religion, in the history classroom presents an interesting challenge for history teachers and museum educators. The goal of this small-scale case study was to evaluate a domain-specific professional-development course for Dutch history teachers that was developed in cooperation with museum educators. This course trains teachers to explore the dynamics of and multiple perspectives on a heritage object by asking historical questions, starting from an overarching main question. We investigated: 1) to what extent trainee and experienced history teachers felt competent in teaching sensitive topics before and after the training; and 2) how three experienced history teachers discussed multiple perspectives in a follow-up lesson after the training. Results showed that teachers reported higher self-efficacy in teaching sensitive topics and that the course offered them practical ideas about how to discuss these kinds of topics in their classrooms. Lesson observations showed that the teachers applied some parts of the design principles demonstrated in the course. This article discusses how using tangible heritage objects could support history educators in negotiating sensitive issues.

Background: In partial nephrectomy for highly complex tumors with expected long ischemia time, renal hypothermia can be used to minimize ischemic parenchymal damage. Objective: To describe our case series, surgical technique, and early outcomes for robot-assisted partial nephrectomy (RAPN) using intra-arterial cold perfusion through arteriotomy. Design, setting, and participants: A retrospective analysis was conducted of ten patients with renal tumors (PADUA score 9–13) undergoing RAPN between March 2020 and March 2023 with intra-arterial cooling because of expected arterial clamping times longer than 25 min. Surgical procedure: Multiport transperitoneal RAPN with full renal mobilization and arterial, venous, and ureteral clamping was performed. After arteriotomy and venotomy, 4°C heparinized saline is administered intravascular through a Fogarty catheter to maintain renal hypothermia while performing RAPN. Measurements: Demographic data, renal function, console and ischemia times, surgical margin status, hospital stay, estimated blood loss, and complications were analyzed. Results and limitations: The median warm and cold ischemia times were 4 min (interquartile range [IQR] 3–7 min) and 60 min (IQR 33–75 min), respectively. The median rewarming ischemia time was 10.5 min (IQR 6.5–23.75 min). The median pre- and postoperative estimated glomerular filtration rate values at least 1 mo after surgery were 90 ml/min (IQR 78.35–90 ml/min) and 86.9 ml/min (IQR 62.08–90 ml/min), respectively. Limitations include small cohort size and short median follow-up (13 [IQR 9.1–32.4] mo). Conclusions: We demonstrate the feasibility and first case series for RAPN using intra-arterial renal hypothermia through arteriotomy. This approach broadens the scope for minimal invasive nephron-sparing surgery in highly complex renal masses. Patient summary: We demonstrate a minimally invasive surgical technique that reduces kidney infarction during complex kidney tumor removal where surrounding healthy kidney tissue is spared. The technique entails arterial cold fluid irrigation, which temporarily decreases renal metabolism and allows more kidneys to be salvaged.

Teaching point: Extrapelvic endometriosis involving pudendal and sciatic nerve may be a cause of lower limb pain.

This study primarily emphasizes the effect of alkaline treatment on the surface morphology, and the physical properties of extracted bamboo fibers were investigated in detail. The bamboo fibers were extracted from raw bamboo culms using a mechanical extraction process followed by roller-milling techniques. The physical properties of the extracted bamboo fibers and their chemical composition were examined based on standard requirements. The extracted and sun-dried bamboo fibers were subjected to surface modifications by treating them with a 5 wt.% NaOH solution. The process involved soaking the extracted bamboo fibers for 1 day at ambient temperature; subsequently, the alkali-treated fibers were washed with distilled water several times to remove alkali content from the fiber surface until it became neutral. Finally, the fibers were dried under the sun for a week. The alkali-treated and untreated extracted bamboo fibers underwent characterization using Fourier transform infrared spectroscopy (FTIR), Thermogravimetric analysis (TGA), X-Ray diffraction (XRD) analysis, and Scanning electron microscopy (SEM). The investigation revealed an improvement in the surface morphology of the alkali-treated extracted bamboo fibers, with a significant reduction in surface roughness, as illustrated by SEM. Test results from FTIR, XRD, and TGA indicated that the alkali-treated fibers had removed lignin and hemicellulose from their surface. This study strongly suggests that bamboo fibers prepared using these techniques could be utilized as reinforcing material in composite production.

The LANDHYPERNET and WATERHYPERNET networks (which together make up the HYPERNETS network) consist of a set of autonomous hyperspectral spectroradiometers (HYPSTAR®) acquiring fiducial reference measurements of surface reflectance at various sites covering a wide range of surface types (both land and water) for use in satellite Earth observation validation and remote sensing applications. This paper describes the processing algorithm for the HYPSTAR® data products. The hypernets_processor is a Python software package to process the LANDHYPERNET and WATERHYPERNET in-situ hyperspectral raw data, collected from the measurement network under the standard measurement protocols, to the designated products, through data transmission and conversion, application of calibration, evaluation of reflectance and other variables, and, archiving for distribution to users. In order to achieve fiducial reference measurement quality, uncertainties are propagated through each step of the processing chain, taking into account temporal and spectral error-covariance. Such detailed uncertainty information is unique for any satellite validation network. We also describe the HYPSTAR® products acquired until 2023–04–31, consisting of 12,190 LANDHYPERNET sequences and 55,514 WATERHYPERNET sequences (of which respectively 11,802 and 44,412 were successfully processed to surface reflectance).

BackgroundCerebrospinal fluid (CSF) kappa free light chain (κFLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal κFLC parameter for identifying MS remains a subject of ongoing debate.ObjectivesThe aim of this study was to compare same-sample diagnostic accuracies of the κFLC index, κIgG index, CSF κFLC/IgG ratio, and isolated CSF κFLC (iCSF-κFLC) between two reference centers using different methods.MethodsPaired serum and CSF samples were analyzed for κFLC and albumin concentrations by Freelite®-Optilite (Sint-Jan Bruges hospital) and N Latex®-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis.ResultsA total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the κFLC index (Freelite®-Optilite: 7.7; N Latex®-BNII: 4.71), κIgG index (Freelite®-Optilite: 14.15, N Latex®-BNII: 12.19), and CSF κFLC/IgG ratio (Freelite®-Optilite: 2.27; N Latex®-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite®-Optilite) versus 94.6% (N Latex®-BNII) for the κFLC index, 91% (Freelite®-Optilite) versus 92.2% (N Latex®-BNII) for the κIgG index, and 81.3% (Freelite®-Optilite) versus 91.4% (N Latex®-BNII) for the CSF κFLC/IgG ratio. However, for iCSF-κFLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite®-Optilite and 90.5% for N Latex®-BNII. The diagnostic performance of the κFLC index [area under the curve (AUC) Freelite®-Optilite: 0.924; N Latex®-BNII: 0.962] and κIgG index (AUC Freelite®-Optilite: 0.929; N Latex®-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%).ConclusionsThe κFLC index and the κIgG index seem to be excellent markers for identifying MS, irrespective of the method used for κFLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-κFLC. iCSF-κFLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal κFLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on κFLC measures.

This paper demonstrates the use of a novel, autonomous hyperspectral surface reflectance data collected at Wytham Woods, United Kingdom (WWUK) as part of the LANDHYPERNET network for the validation of multispectral data from Sentinel-2, Landsat 8 and Landsat 9. The deployment of the HYPSTAR instrument at the site and the corresponding quality control of the data products is described. In addition, a methodology based upon metrological principles is outlined showing the propagation of uncertainties from the LANDHYPERNET and satellite data products to enable conformity testing of the satellite products using the satellite mission requirements. A total of 9 matchups are found for satellite validation at the site, where there is a cloud-free satellite scene and a corresponding LANDHYPERNET sequence, which has passed all quality checks, within two hours of the overpass. An analysis of the impact of the spatial variability of the site is presented and can account for up to 40% of the uncertainty associated with the in-situ surface reflectance data. There is no systematic bias in the Bottom-Of-Atmosphere reflectance data obtained from the LANDHYPERNET data in comparison to the satellite data. In the best case, differences of less than 2% are found for certain spectral bands. However, in the worst cases, relatively large differences are found which exceed 100%, this is affected by the relatively low reflectance values found in the visible bands. These differences could be caused by the spatial and temporal mismatch between the in-situ and satellite measurement, or due to shadowing caused by the flux tower. Further data quality control and assurance is needed to best choose data sets suitable for satellite validation. Incorporating a Bidirectional Reflectance Distribution Function model into the processing chain for the forest canopy is recommended. Overall, although there are areas to further characterise, the site provides a useful benchmark for which to develop techniques for validation of satellite surface reflectance products over a challenging environment.

Satellites are now routinely used for measuring water and land surface reflectance and hence environmentally relevant parameters such as aquatic chlorophyll a concentration and terrestrial vegetation indices. For each satellite mission, radiometric validation is needed at bottom of atmosphere for all spectral bands and covering all typical conditions where the satellite data will be used. Existing networks such as AERONET-OC for water and RadCalNet for land provide vital information for validation, but (AERONET-OC) do not cover all spectral bands or (RadCalNet) do not cover all surface types and viewing angles. In this Perspective Article we discuss recent advances in instrumentation, measurement methods and uncertainty estimation in the field of optical radiometry and put forward the viewpoint that a new network of automated hyperspectral radiometers is needed for multi-mission radiometric validation of water and land surface reflectance. The HYPERNETS federated network concept is described, providing a context for research papers on specific aspects of the network. This network is unique in its common approach to both land and water surfaces. The common aspects and the differences between land and water measurements are explained. Based on early enthusiasm for HYPERNETS data from validation-oriented workshops, it is our viewpoint that this new network of automated hyperspectral radiometers will be useful for multi-mission radiometric validation of water and multi-angle land surface reflectance. The HYPERNETS network has strong synergy with other measurement networks (AERONET, AERONET-OC, RadCalNet, FLUXNET, ICOS, skycam, etc.) and with optional supplementary measurements, e.g., water turbidity and fluorescence, land surface temperature and soil moisture, etc.

Objective: In the last years, robotic surgery was introduced in several different settings with good perioperative results. However, its role in the management of adrenal masses is still debated. In order to provide a contribution to this field, we described our step-by-step technique for robotic adrenalectomy (RA) and related modifications according to the type of adrenal mass treated. Methods: We retrospectively analyzed 27 consecutive patients who underwent RA at Onze-Lieve-Vrouw hospital (Aalst, Belgium) between January 2009 and October 2022. Demographic, intra- and post-operative, and pathological data were retrieved from our prospectively maintained institutional database. Continuous variables are summarized as median and interquartile range (IQR). Categorical variables are reported as frequencies (percentages). Results: Twenty-seven patients underwent RA were included in the study. Median age, body mass index, and Charlson's comorbidity index were 61 (IQR: 49–71) years, 26 (IQR: 24–29) kg/m2, and 2 (IQR: 0–3), respectively, and 16 (59.3%) patients were male. Median tumor size at computed tomography scan was 6.0 (IQR: 3.5–8.0) cm. Median operative time and blood loss were 105 (IQR: 82–120) min and 175 (IQR: 94–250) mL, respectively. No intraoperative complications were recorded. Overall postoperative complications rate was 11.1%, with a postoperative transfusion rate of 3.7%. A total of 10 (37.0%) patients harbored malignant adrenal masses. Among them, 3 (11.1%) had adrenocortical carcinoma, 6 (22.2%) secondary metastasis, and 1 (3.7%) malignant pheochromocytoma on final pathological exam. Only 1 (10.0%) patient had positive surgical margins. Conclusion: We described our step-by-step technique for RA, which can be safely performed even in case of high challenging settings as malignant tumors, pheochromocytoma, and large masses. The standardization of perioperative protocol should be encouraged to maximize the outcomes of this complex surgical procedure.

Abstract Forest edges can be important strongholds for biodiversity and play a crucial role in the protection of forest interiors against edge effects. However, their potential to host biodiversity is dependent on the structure of the forest: Abrupt edges often fail to realise this potential. Yet, methods to accurately characterise and quantify forest edge abruptness are currently lacking. Here, we combine three‐dimensional forest structural data with biodiversity monitoring to assess the influence of forest edge structure on habitat suitability. We derived several structural metrics to determine forest edge abruptness using terrestrial laser scanning and applied these to six forest edge transects in Belgium. The local soundscapes were captured using audio recording devices (Audiomoths) and quantified using acoustic indices (AIs) (metrics on the soundscape characteristics). In each transect, the dawn choruses were recorded over a period of a week, both at the edge and the interior of the forest. No correlation between the AIs and bird species richness was found. There were clear differences between transects in the structural metrics and the recorded soundscapes. Some possible relations between both were found. In this proof of concept, we demonstrated innovative techniques to semi‐automatically classify forest structure and rapidly quantify soundscape characteristics and found a weak effect of forest edge structure on bird biophony.

Background: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) score has been developed to standardise prostate magnetic resonance imaging (MRI) reporting in men on active surveillance (AS) for prostate cancer (PCa). Objective: To evaluate the feasibility of PRECISE scoring and assess its diagnostic accuracy. Design, setting, and participants: All PCa patients on AS with a baseline MRI and at least one follow-up MRI scan between January 2008 and September 2022 at a single tertiary referral centre were included in a database. The follow-up protocol of the Prostate Cancer International Active Surveillance (PRIAS) study was used. All scans were retrospectively re-reported by a dedicated uroradiologist and appointed a Prostate Imaging Reporting and Data System (version 2.1) and PRECISE score. Outcome measurements and statistical analysis: Clinically significant progression was defined by histopathological upgrading (on biopsy or radical prostatectomy) to grade group ≥3 and/or evolution to T3 stage. A survival analysis was performed to assess differential progression-free survival (PFS) according to the PRECISE score. Results and limitations: A total of 188 patients were included for an analysis with a total of 358 repeat MRI scans and 144 repeat biopsies. The median follow-up was 46 mo (interquartile range 21–74). Radiological progression (PRECISE 4–5) had sensitivity, specificity, negative predictive value, and positive predictive value of, respectively, 78%, 70%, 90%, and 49% for clinically significant progression. Four-year PFS was 91% for PRECISE 1–3 versus 66% for PRECISE 4–5 (p

Abstract Acoustic and phonemic processing are understudied in aphasia, a language disorder that can affect different levels and modalities of language processing. For successful speech comprehension, processing of the speech envelope is necessary, which relates to amplitude changes over time (e.g., the rise times). Moreover, to identify speech sounds (i.e., phonemes), efficient processing of spectro-temporal changes as reflected in formant transitions is essential. Given the underrepresentation of aphasia studies on these aspects, we tested rise time processing and phoneme identification in 29 individuals with post-stroke aphasia and 23 healthy age-matched controls. We found significantly lower performance in the aphasia group than in the control group on both tasks, even when controlling for individual differences in hearing levels and cognitive functioning. Further, by conducting an individual deviance analysis, we found a low-level acoustic or phonemic processing impairment in 76% of individuals with aphasia. Additionally, we investigated whether this impairment would propagate to higher-level language processing and found that rise time processing predicts phonological processing performance in individuals with aphasia. These findings show that it is important to develop diagnostic and treatment tools that target low-level language processing mechanisms.

Abstract Due to multiple land‐cover changes, forest herb populations residing in forest patches embedded in agricultural landscapes display different ages and, thus, experience differences in genetic exchange, mutation accumulation and genetic drift. The extent of divergence in present‐day population genetic structure among these populations of different ages remains unclear, considering their diverse breeding systems and associated pollinators. Answering this question is essential to understand these species' persistence, maintenance of evolutionary potential and adaptability to changing environments. We applied a multi‐landscape setup to compare the genetic structure of forest herb populations across forest patches of different ages (18–338 years). We studied the impact on three common slow‐colonizer herb species with distinct breeding systems and associated pollinators: Polygonatum multiflorum (outcrossing, long‐distance pollinators), Anemone nemorosa (outcrossing, short‐distance pollinators) and Oxalis acetosella (mixed breeding). We aimed to assess if in general older populations displayed higher genetic diversity and lower differentiation than younger ones. We also anticipated that P. multiflorum would show the smallest while O. acetosella the largest difference, between old and young populations. We found that older populations had a higher observed heterozygosity (Ho) but a similar level of allelic richness (Ar) and expected heterozygosity (He) as younger populations, except for A. nemorosa, which exhibited higher Ar and He in younger populations. As populations aged, their pairwise genetic differentiation measured by DPS decreased independent of species identity while the other two genetic differentiation measures showed either comparable levels between old and young populations (G"ST) or inconsistency among three species (cGD). The age difference of the two populations did not explain their genetic differentiation. Synthesis: We found restricted evidence that forest herb populations with different ages differ in their genetic structure, indicating that populations of different ages can reach a similar genetic structure within decades and thus persist in the long term after habitat disturbance. Despite their distinct breeding systems and associated pollinators, the three studied species exhibited partly similar genetic patterns, suggesting that their common characteristics, such as being slow colonizers or their ability to propagate vegetatively, are important in determining their long‐term response to land‐cover change.

BackgroundCanadian health systems fare poorly in providing timely access to elective surgical care, which is crucial for quality, trust, and satisfaction.MethodsWe conducted a cross-sectional analysis of surgical wait times for adults receiving non-urgent cataract surgery, knee arthroplasty, hip arthroplasty, gallbladder surgery, and non-cancer uterine surgery in Ontario, Canada, between 2013 and 2019. We obtained data from the Wait Times Information System (WTIS) database. Inter- and intra-hospital and surgeon variations in wait time were described graphically with caterpillar plots. We used non-nested 3-level hierarchical random effects models to estimate variation partition coefficients, quantifying the proportion of wait time variance attributable to surgeons and hospitals.ResultsA total of 942,605 procedures at 107 healthcare facilities, conducted by 1,834 surgeons, were included in the analysis. We observed significant intra- and inter-provider variations in wait times across all five surgical procedures. Inter-facility median wait time varied between six-fold for gallbladder surgery and 15-fold for knee arthroplasty. Inter-surgeon variation was more pronounced, ranging from a 17-fold median wait time difference for cataract surgery to a 216-fold difference for non-cancer uterine surgery. The proportion of variation in wait times attributable to facilities ranged from 6.2% for gallbladder surgery to 23.0% for cataract surgery. In comparison, surgeon-related variation ranged from 16.0% for non-cancer uterine surgery to 28.0% for cataract surgery.ImplicationsThere is extreme variability in surgical wait times for five common, high-volume, non-urgent surgical procedures. Strategies to address surgical wait times must address the variation between service providers through better coordination of supply and demand. Approaches such as single-entry models could improve surgical system performance.

Abstract Background Cell salvage reduces allogenic blood transfusion requirements in surgery. We present a pilot study exploring the impact of anticoagulant choice, citrate or heparin, on the quality of cell salvaged blood in adults undergoing coronary artery bypass grafting (CABG). Materials and methods Elective on pump CABG patients were randomly allocated to citrate or heparin anticoagulation. We measured red blood cell characteristics and inflammation in both the blood collection reservoir and the washed red blood cell concentrate. Postoperatively, the level of biomarkers and the coagulation profile in the peripheral blood as well as the transfusion requirements of allogenic blood products were studied. Results Thirty eight patients were included, 19 in the citrate group and 19 in the heparin group. Baseline characteristics were similar. In the washed red blood cell concentrate, Mean Hb (g/dl) and Ht (%) were lower in the citrate group [Hb: 18.1 g/dL (SD 1.3) vs. 21.1 (1.6), p

Background: Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has been shown to lead to better outcomes regarding early continence compared to standard anterior RARP (SA-RARP). The goal of this study was to assess the feasibility and safety of implementing RS-RARP in a tertiary center with experience in SA-RARP. Methods: From February 2020, all newly diagnosed non-metastatic prostate cancer patients for whom RARP was indicated were evaluated for RS-RARP. Data from the first 100 RS-RARP patients were prospectively collected and compared with data from the last 100 SA-RARP patients. Patients were evaluated for Clavien Dindo grade ≥3a complications, urinary continence after 2 and 6 weeks, 3, 6 and 12 months, erectile function, positive surgical margins (PSMs) and biochemical recurrence (BCR). Results: There was no significant difference in postoperative complications at Clavien-Dindo grade ≥3a (SA-RARP: 6, RS-RARP: 4; p = 0.292). At all time points, significantly higher proportions of RS-RARP patients were continent (p < 0.001). No significant differences in postoperative potency were observed (52% vs. 59%, respectively, p = 0.608). PSMs were more frequent in the RS-RARP group (43% vs. 29%, p = 0.034), especially in locally advanced tumors (pT3: 64.6% vs. 43.8%, p = 0.041—pT2: 23.5% vs. 15.4%, p = 0.329). The one-year BCR-free survival was 82.6% vs. 81.6% in the SA-RARP and RS-RARP groups, respectively (p = 0.567). The median follow-up was 22 [18–27] vs. 24.5 [17–35] months in the RS-RARP and SA-RARP groups, respectively (p = 0.008). Conclusions: The transition from SA-RARP to RS-RARP can be safely performed by surgeons proficient in SA-RARP. Continence results after RS-RARP were significantly better at any time point. A higher proportion of PSMs was observed, although it did not result in a worse BCR-free survival.

This research utilises statistical modelling to explore the impact of roadway infrastructure elements, primarily those related to cross-section design, on crash occurrences in urban areas. Cross-section design is an important step in the roadway geometric design process as it influences key operational characteristics like capacity, cost, safety, and overall functionality of the transport system entity. Evaluating the influence of cross-section design on these factors is relatively straightforward, except for its impact on safety, especially in urban areas. The safety aspect has resulted in inconsistent findings in the existing literature, indicating a need for further investigation. Negative binomial (NB) models are typically employed for such investigations, given their ability to account for over-dispersion in crash data. However, the low sample mean and under-dispersion occasionally exhibited by crash data can restrict their applicability. The generalised Poisson (GP) models have been proposed as a potential alternative to NB models. This research applies GP models for developing crash prediction models for urban road segments. Simultaneously, NB models are also developed to enable a comparative assessment between the two modelling frameworks. A six-year dataset encompassing crash counts, traffic volume, and cross-section design data reveals a significant association between crash frequency and infrastructure design variables. Specifically, lane width, number of lanes, road separation, on-street parking, and posted speed limit are significant predictors of crash frequencies. Comparative analysis with NB models shows that GP models outperform in cases of low sample mean crash types and yield similar results for others. Overall, this study provides valuable insights into the relationship between road infrastructure design and crash frequency in urban environments and offers a statistical approach for predicting crash frequency that maintains a balance between interpretability and predictive power, making it more viable for practitioners and road authorities to apply in real-world road safety scenarios.

Background: Allergic rhinitis (AR) has a significant impact on the community as a whole with regard to quality of life and its relationship to allergic multi-morbidities. Appropriate diagnosis, treatment and review of the efficacy of interventions can ameliorate these effects. Yet, the importance of AR is often overlooked, and appropriate therapy is neglected. The availability of effective medications and knowledge as to management are often lacking in both public and private health systems. Methods: This review is based on a comprehensive literature search and detailed discussions by the South African Allergic Rhinitis Working Group (SAARWG). Results: The working group provided up-to-date recommendations on the epidemiology, pathology, diagnosis and management of AR, appropriate to the South African setting. Conclusion: Allergic rhinitis causes significant, often unappreciated, morbidity. It is a complex disease related to an inflammatory response to environmental allergens. Therapy involves education, evaluation of allergen sensitisation, pharmacological treatment, allergen immunotherapy (AIT) and evaluation of the success of interventions. Regular use of saline; the important role of intranasal corticosteroids, including those combined with topical antihistamines and reduction in the use of systemic steroids are key. Practitioners should have a thorough knowledge of associated morbidities and the need for specialist referral. Contribution: This review summarises the latest developments in the diagnosis and management of AR such that it is a resource that allows easy access for family practitioners and specialists alike.

Ungulate herbivory is an important driver of ecological change in forests. Here, the authors combine vegetation resurveys showing herbivory effects are highly dependent on soil eutrophication, promoting non-natives under high N-conditions, yet benefiting threatened species under low N-conditions.

Abstract Transduction of endothelial cells (EC) with a vector that expresses apolipoprotein A-I (APOAI) reduces atherosclerosis in arteries of fat-fed rabbits. However, the effects on atherosclerosis are partial and might be enhanced if APOAI expression could be increased. With a goal of developing an expression cassette that generates higher levels of APOAI mRNA in EC, we tested 4 strategies, largely in vitro: addition of 2 types of enhancers, addition of computationally identified EC-specific cis-regulatory modules (CRM), and insertion of the rabbit APOAI gene at the transcription start site (TSS) of sequences cloned from genes that are highly expressed in cultured EC. Addition of a shear stress-responsive enhancer did not increase APOAI expression. Addition of 2 copies of a Mef2c enhancer increased APOAI expression from a moderately active promoter/enhancer but decreased APOAI expression from a highly active promoter/enhancer. Of the 11 CRMs, 3 increased APOAI expression from a moderately active promoter (2–7-fold; P

Video games are frequently situated in historical worlds. In this contribution, I explore the possibilities and limitations of the video game as a medium for representing the past using two narrative strategies that can occur in video games: 'embedded narratives' and 'emergent narratives.' In doing so, I will also address perhaps the most important feature of video games: the strong focus on telling a story through the shaping of space (environmental storytelling). In this context, it is also interesting to take a foray into the museum world, where such strategies are sometimes already used to tell a non-fiction story about the past.

Probiotics have demonstrated oral health benefits by influencing the microbiome and the host. Although promising, their current use is potentially constrained by several restrictions. One such limiting factor lies in the prevailing preparation of a probiotic product. To commercialize the probiotic, a shelf stable product is achieved by temporarily inactivating the live probiotic through drying or freeze drying. Even though a lyophilized probiotic can be kept dormant for an extended period of time, their viability can be severely compromised, making their designation as probiotics questionable. Additionally, does the application of an inactive probiotic directly into the oral cavity make sense? While the dormancy may allow for survival on its way towards the gut, does it affect their capacity for oral colonisation? To evaluate this, 21 probiotic product for oral health were analysed for the number of viable (probiotic), culturable (CFU) and dead (postbiotic) cells, to verify whether the commercial products indeed contain what they proclaim. After isolating and uniformly lyophilizing three common probiotic species in a simple yet effective lyoprotective medium, the adhesion to saliva covered hydroxyapatite discs of lyophilized probiotics was compared to fresh or reactivated lyophilized probiotics. Unfortunately, many of the examined products failed to contain the claimed amounts of viable cells, but also the strains used were inadequately characterized and lacked clinical evidence for that unknown strain, questioning their label of a ‘probiotic’. Additionally, lyophilized probiotics demonstrated low adhesive capacity compared to their counterparts, prompting the question of why fresh or reactivated probiotics are not currently used.

Background and aims: Patients with Down Syndrome (DS) are frequently born with an atrioventricular septal defect (AVSD). Surgical repair of the defect aims to minimize mortality and morbidity. However, a surgical intervention, specifically in DS patients, is not without risk and a subgroup of patients underwent only conservative non-surgical treatment. Outcome data of these different approaches are scarce. The aim of this retrospective study was to compare the long-term outcome of DS patients with and without surgery for AVSD. Methods: DS patients registered with AVSD in the hospital's database from January 1980 till December 2020 were selected. Patient characteristics, peri-operative if appropriate, and follow-up data were obtained from the medical files. Results: In total, 72 unrepaired (36 male, 50%) and 134 repaired patients (61 male, 46%) were included. After a maximum of 60 years of follow-up, the all-cause mortality was 45.8% and 17.1%, respectively. Thirty-six percent and 13%, respectively, were labeled as non-cardiovascular death. Mean survival time for unrepaired AVSD was 40.7 years (95% CI 36.1–45.2) and for repaired AVSD 38.5 years (95% CI 35.3–41.6) (Log rank p = 0.465). However, the survival rate 35 years after birth was 62.1% for unrepaired patients versus 81.7% for repaired patients. Mortality rates were the highest the first months after surgical repair. Conclusions: The mean survival rate of Down patients, born with an AVSD, did not differ between repair or not. However, long-term survival rate was higher in patients who underwent surgical repair. Mortality was highest the first months after surgery.

Treatment of chronic wounds is challenging, and the development of different formulations based on insulin has shown efficacy due to their ability to regulate oxidative stress and inflammatory reactions. The formulation of insulin with polysaccharides in biohybrid hydrogel systems has the advantage of synergistically combining the bioactivity of the protein with the biocompatibility and hydrogel properties of polysaccharides. In this study, a hydrogel formulation containing insulin, chitosan, and hydroxypropyl methyl cellulose (Chi/HPMC/Ins) was prepared and characterized by FTIR, thermogravimetric, and gel point analyses. The in vitro cell viability and cell migration potential of the Chi/HPMC/Ins hydrogel were evaluated in human keratinocyte cells (HaCat) by MTT and wound scratch assay. The hydrogel was applied to excisional full-thickness wounds in diabetic mice for twenty days for in vivo studies. Cell viability studies indicated no cytotoxicity of the Chi/HPMC/Ins hydrogel. Moreover, the Chi/HPMC/Ins hydrogel promoted faster gap closure in the scratch assay. In vivo, the wounds treated with the Chi/HPMC/Ins hydrogel resulted in faster wound closure, formation of a more organized granulation tissue, and hair follicle regeneration. These results suggest that Chi/HPMC/Ins hydrogels might promote wound healing in vitro and in vivo and could be a new potential dressing for wound healing.

This study aims to explore the complex role of cannabinoid type 1 receptor (CB1) signaling in the gastrocnemius muscle, assessing physiological processes in both CB1+/+ and CB1−/− mice. The primary focus is to enhance our understanding of how CB1 contributes to mitochondrial homeostasis. At the tissue level, CB1−/− mice exhibit a substantial miRNA-related alteration in muscle fiber composition, characterized by an enrichment of oxidative fibers. CB1 absence induces a significant increase in the oxidative capacity of muscle, supported by elevated in-gel activity of Complex I and Complex IV of the mitochondrial respiratory chain. The increased oxidative capacity is associated with elevated oxidative stress and impaired antioxidant defense systems. Analysis of mitochondrial biogenesis markers indicates an enhanced capacity for new mitochondria production in CB1−/− mice, possibly adapting to altered muscle fiber composition. Changes in mitochondrial dynamics, mitophagy response, and unfolded protein response (UPR) pathways reveal a dynamic interplay in response to CB1 absence. The interconnected mitochondrial network, influenced by increased fusion and mitochondrial UPR components, underlines the dual role of CB1 in regulating both protein quality control and the generation of new mitochondria. These findings deepen our comprehension of the CB1 impact on muscle physiology, oxidative stress, and MQC processes, highlighting cellular adaptability to CB1−/−. This study paves the way for further exploration of intricate signaling cascades and cross-talk between cellular compartments in the context of CB1 and mitochondrial homeostasis.

Chlamydia psittaci, Chlamydia gallinacea, and Chlamydia abortus are the most common Chlamydia spp. in chickens and have a confirmed or suggested zoonotic potential. No recent data are available on their prevalence and impact in the Belgian chicken industry or in the recreational chicken branch. Therefore, a cross-sectional epidemiological study was executed where samples were collected from both factory-farmed and backyard chickens. More specifically, pharyngeal chicken swabs were obtained from 20 chicken farms, 5 chicken abattoirs, and 38 different backyard locations and were analyzed using species-specific Polymerase Chain Reactions (PCRs) for the presence of the three avian Chlamydia spp. To investigate their zoonotic potential, samples were simultaneously collected from 54 backyard chicken caretakes and 37 professional chicken caretakers or abattoir employees and analyzed using species-specific PCRs as well. This study confirmed the presence of DNA of all three Chlamydia species in both the chicken industry and backyard settings. Chlamydia psittaci was the most prevalent in the industry chickens (11.0%), whereas Chlamydia gallinacea was the dominant species in the backyard chickens (14.5%). Chlamydia abortus infections were more common in the commercial chickens (9.0%) compared to the backyard chickens (2.6%). The DNA of all three species was also detected in humans (3.9% Chlamydia psittaci, 2.9% Chlamydia gallinacea, and 1.0% Chlamydia abortus).

This specific study investigates the chemical and morphological properties of naturally treated wheat straw fiber growing around in Jimma zone. The chemical composition properties including cellulose 45.43%, hemicellulose 36.50%, and lignin 21.61% were determined. The physical properties of naturally treated wheat straw fibers, such as bulk density, particle density, moisture content, and ash content, are 0.037 g/cm3, 0.194 g/cm3, 10.04%, and 1.44%, respectively. The chemical functional group of naturally treated wheat straw fiber was established by Fourier transform infrared spectroscopy (FTIR), crystallinity index is calculated by X-ray powder diffraction (×RD) analysis, and the thermogravimetric analysis (TGA) result ensures that the naturally treated wheat straw has thermally withstood up to 314.35°C. A fiber’s surface morphology shows the presence of shallow pores, which increase the surface roughness of the fiber; this contributes to increased contact surface area, which ensures better fiber-matrix adherence in composite fabrication. We conclude that naturally treated wheat straw fiber has a significant value in fiber reinforced concrete technology as reinforcement materials in concrete composites formation by incorporating optimum percentage to reduce the limitation of concrete and to enhance the mechanical properties of concrete.

Abstract Most studies investigating the effects of climatological factors on microbial community composition and diversity focus on comparisons of geographically distinct environments (e.g., cold vs hot deserts) or across various temporal scales. Mountain regions provide unique environments to explore relationships between various environmental factors and soil microorganisms given their range of microclimatic conditions and vegetation types. This study investigated micro‐topographically (i.e., north‐/south‐facing slope aspects and flat plateau between them) controlled microbial diversity and community structures across a Lesotho mountain summit. Amplicon sequence analysis revealed that the north‐ and south‐facing slopes were dominated by more Proteobacteria and Bacteroidetes, while the plateau was dominated by more Acidobacteria. Fungi from the phylum Chytridiomycota more strongly dominated the plateau and the north‐facing slope than the south‐facing slope. Slope aspect, through its direct influence on air and soil micro‐climatology and plant diversity, significantly affects bacterial and fungal community structures at this location. These results provide original insight into soil microbial diversity in the Lesotho highlands and offer an opportunity to project the likely response of soil microorganisms to future climate warming in highly variable mountain environments such as the Lesotho highlands.