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Background: The yeast Starmerella bombicola is renowned for its highly efficient sophorolipid production, reaching titers and productivities of (over) 200 g/L and 2 g/(L h), respectively. This inherent efficiency has led to the commercialization of sophorolipids. While the sophorolipid biosynthetic pathway has been elucidated a few years ago, in this study, it is revisited and true key intermediates are revealed., Results: Recently, Starmerella bombicola strains developed and evaluated in the past were reevaluated unveiling unexpected findings. The AT enzyme encoded in the sophorolipid biosynthetic gene cluster is the only described enzyme known to acetylate sophorolipids, while the SBLE enzyme encoded by the SBLE gene is described to catalyze the conversion of (acetylated) acidic sophorolipids into lactonic sophorolipids. A double knockout of both genes was described to result in the generation of bolaform sophorolipids. However, new experiments performed with respective S. bombicola strains Δsble, Δat Δsble, and ∆at revealed inconsistencies with the current understanding of the SL pathway. It was observed that the ∆sble strain produces mainly bolaform sophorolipids with higher acetylation degrees instead of acidic sophorolipids. Furthermore, the ∆at strain produces predominantly bolaform sophorolipids and lactonic sophorolipids with lower acetylation degrees, while the ∆at ∆sble strain predominantly produces bolaform sophorolipids with lower acetylation degrees. These results indicate that the AT enzyme is not the only enzyme responsible for acetylation of sophorolipids, while the SBLE enzyme performs an intramolecular transesterification reaction on bolaform glycolipids instead of an esterification reaction on acidic sophorolipids. These findings, together with recent in vitro data, led us to revise the sophorolipid biosynthetic pathway., Conclusions: Bolaform sophorolipids instead of acidic sophorolipids are the key intermediates in the biosynthetic pathway towards lactonic sophorolipids. Bolaform sophorolipids are found in very small amounts in extracellular S. bombicola wild type broths as they are very efficiently converted into lactonic sophorolipids, while acidic sophorolipids build up as they cannot be converted. Furthermore, acetylation of sophorolipids is not exclusively performed by the AT enzyme encoded in the sophorolipid biosynthetic gene cluster and acetylation of bolaform sophorolipids promotes their transesterification. These findings led to the revision of the industrially relevant sophorolipid biosynthetic pathway., (© 2024. The Author(s).)

Background: In intermediate/high risk prostate cancer, preoperative staging exams are mandatory. The aim of these imaging studies is to evaluate eventual lymph nodes involvement and/or metastatic spread of the tumor. Nevertheless, computed tomography (CT), magnetic resonance imaging (MRI), bone scan modalities have controversial sensitivity. Introduction of PET-PSMA and its use also as preoperative exam, seems to improve diagnostic accuracy due to favorable negative predictive value. The aim of this study was to evaluate the accuracy of PET-PSMA as a preoperative staging exam and its accuracy in predicting lymph nodes involvement in intermediate/high risk prostate cancer (PCa) patients., Methods: A retrospective analysis of 50 patients diagnosed with intermediate/high risk PCa between 2018 and 2022 has been performed. All patients underwent preoperative 68Ga-PSMA PET/CT prior to robot-assisted radical prostatectomy (RARP) + extended pelvic lymph node dissection (ePLND). The cohort was categorized into two groups: pathologically negative lymph nodes (pN0) vs. positive nodes (pN1). A descriptive and comparative analysis was conducted. Correlation analysis between continuous variables was performed using the Spearman's Rank Test. Using lymph nodes histopathological results as reference standard, the diagnostic performance of 68Ga-PSMA PET/CT was calculated., Results: Overall, 50 patients were included. The mean age was 63.3 years with a median prostatic specific antigen (PSA) of 7.7 ng/dL. Forty-four percent of the patients exhibited an International Society of Urological Pathology (ISUP) score of 4 or higher, and 28% had a pT3 stage. Overall, 43 (86%) patients submitted to ePLND did not present lymph node metastases (pN0), while 8 (14%) patients were pN1. PET-PSMA showed low sensitivity in detecting lymph node metastases (25%) while a high specificity in excluding lymph-node disease (88.1%) has been observed. Finally, we noted a significant positive correlation between the total SUVmax of the prostate and the initial total PSA (r=0.38; P=0.019), as well as the percentage of tumor involvement (r=0.383; P=0.022)., Conclusions: Evidence on the role of PET-PSMA in the primary staging of PCa is steadily building up. A positive correlation between SUV and prostate involvement indicates that PET-PSMA could reflect, with a good approximation, the pathological features of the prostate. However, the low sensitivity depicted remains the main limitation. Future prospective studies are needed to determine the impact on patient outcome.

This study aimed to determine what childbearing women want when using virtual reality as an intrapartum pain management method. Researchers performed a qualitative exploratory study using content analysis. Two focus groups were organized including pregnant women anticipating a vaginal birth and women who recently had given birth, no longer than 6 months ago. The focus groups included a 30-minute virtual reality demo. In total, 10 women participated. Five themes emerged: (1) "try, test and explore": the need to receive information and to get acquainted with virtual reality during the antenatal period; (2) "variety and diversity in physical and digital options": the preference for a variety in virtual content and view virtual reality as a complementary method to methods for intrapartum pain management; (3) "distraction versus focus": virtual reality as a method to distract from pain, from the clinical context or to help them focus; (4) "comfort both physical and digital": measures to ensure a comfortable physical and virtual experience; and (5) "birthing partner": the potential need to include partners. This study is an essential step informing the development, implementation, and research of labor-specific virtual reality and informing antenatal healthcare providers when offering women virtual reality as intrapartum pain management., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

In this study, a bioprocessing strategy was designed to valorize ultra-filtered spent sulfite liquor (UF-SSL) without prior detoxification steps as well as using it purely as a carbon source supplement to defined or complex media. Hence, a minimal medium for the bioconversion of UF-SSL with Corynebacterium glutamicum was developed and process robustness and reproducibility were validated. Process quantifiability was ensured by development of a biomass measurement technique for matrices with high water-insoluble solids and verified using elemental balancing. Mechanistic modeling based on Monod equations was used to identify batch kinetics. In a final step, scale-up of the developed process was performed to showcase process maturity towards commercialisation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Histological data on muscle fiber size and proportion in (very) young typically developing (TD) children is not well documented and data on capillarization and satellite cell content are also lacking. Aims: This study investigated the microscopic properties of the medial gastrocnemius muscle in growing TD children, grouped according to age and gender to provide normal reference values in healthy children. Methods: Microbiopsies of the medial gastrocnemius (MG) muscle were collected in 46 TD boys and girls aged 2-10 years subdivided into 4 age groups (2-4, 4-6, 6-8 and 8-10 years). Sections were immunostained to assess fiber type cross-sectional area (fCSA) and proportion, the number of satellite cells (SC), capillary to fiber ratio (C/F), capillary density for type I and II fiber (CFD), capillary domain, capillary-to-fiber perimeter exchange index (CFPE) and heterogeneity index. fCSA was normalized to fibula length 2 and the coefficient of variation (CV) was calculated to reflect fCSA intrasubject variability. Results: Absolute fCSA of all fibers increased with age (r = 0.72, p < 0.001) but more in boys (+112%, p < 0.05) than in girls (+48%, p > 0.05) Normalized fCSA, CV and fiber proportion did not differ between age groups and gender. C/F was strongly correlated with age in boys (r = 0.83, p < 0.001), and to a lesser extent in girls (r = 0.37, p = 0.115), while other capillary parameters as well as the number of SC remained stable with increasing age in boys and girls. Discussion: This study provides reference values of histological measures in MG according to age in normally growing boys and girls. These data may be used as a reference to determine disease impact and efficacy of therapeutic approach on the muscle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Andries, Deschrevel, Maes, De Beukelaer, Corvelyn, Staut, De Houwer, Costamagna, Nijs, Metsemakers, Nijs, Hens, De Wachter, Prinsen, Desloovere, Van Campenhout and Gayan-Ramirez.)

Background: To build machine learning predictive models for surgical risk assessment of extracapsular extension (ECE) in patients with prostate cancer (PCa) before radical prostatectomy; and to compare the use of decision curve analysis (DCA) and receiver operating characteristic (ROC) metrics for selecting input feature combinations in models., Methods: This retrospective observational study included two independent data sets: 139 participants from a single institution (training), and 55 from 15 other institutions (external validation), both treated with Robotic Assisted Radical Prostatectomy (RARP). Five ML models, based on different combinations of clinical, semantic (interpreted by a radiologist) and radiomics features computed from T2W-MRI images, were built to predict extracapsular extension in the prostatectomy specimen (pECE+). DCA plots were used to rank the models' net benefit when assigning patients to prostatectomy with non-nerve-sparing surgery (NNSS) or nerve-sparing surgery (NSS), depending on the predicted ECE status. DCA model rankings were compared with those drived from ROC area under the curve (AUC)., Results: In the training data, the model using clinical, semantic, and radiomics features gave the highest net benefit values across relevant threshold probabilities, and similar decision curve was observed in the external validation data. The model ranking using the AUC was different in the discovery group and favoured the model using clinical + semantic features only., Conclusions: The combined model based on clinical, semantic and radiomic features may be used to predict pECE + in patients with PCa and results in a positive net benefit when used to choose between prostatectomy with NNS or NNSS., (© 2024. The Author(s).)

Inconsistent alterations in skeletal muscle histology have been reported in adolescents with cerebral palsy (CP) and whether alterations are present in young children and differ from older children is not yet known. This study aimed to define histological alterations in the medial gastrocnemius (MG) of ambulant CP (gross-motor classification system, GMFCS I-III) stratified in two age groups (preschool children, PS: 2-5 and school age children, SA: 6-9-yr old) compared with age-matched typically developing (TD) children. We hypothesized that alterations in muscle microscopic properties are already present in PS-CP and are GMFCS level specific. Ultrasound guided percutaneous microbiopsies were collected in 46 CP (24-PS) and 45 TD (13-PS) children. Sections were stained to determine fiber cross-sectional area (fCSA) and proportion, capillary, and satellite cell amount. Average absolute and normalized fCSA were similar in CP and TD, but a greater percentage of smaller fibers was found in CP. Coefficient of variation (CV) was significantly larger in PS-CP-GMFCS I-II and for type I fiber. In SA-CP, all fiber types contributed to the higher CV. Type IIx proportion was higher and type I was lower in PS-CP-GMFCS-III and for all SA-CP. Reduced capillary-to-fiber ratio was present in PS-CP-GMFCS II-III and in all SA-CP. Capillary fiber density was lower in SA-CP. Capillary domain was enhanced in all CP, but capillary spatial distribution was maintained as was satellite cell content. We concluded that MG histological alterations are already present in very young CP but are only partly specific for GMFCS level and age. NEW & NOTEWORTHY Inconsistent histological alterations have been reported in children with cerebral palsy (CP) but whether they are present in very young and ambulant CP children and differ from those reported in old CP children is not known. This study highlighted for the first time that enhanced muscle fiber size variability and loss of capillaries are already present in very young CP children, even in the most ambulant ones, and these alterations seem to extend with age.

Botulinum toxin-A (BoNT-A) injection is known to exert beneficial effects on muscle tone, joint mobility and gait in children with cerebral palsy (CP). However, recent animal and human studies have raised the concern that BoNT-A might be harmful to muscle integrity. In CP-children, the impact of BoNT-A on muscle structure has been poorly studied, and inconsistent results have been reported. This study was aimed at determining the time course effect of a single BoNT-A administration on medial gastrocnemius (MG) morphology in CP-children. MG microbiopsies from 12 ambulant and BoNT-A-naïve CP-children (age, 3.4 (2.3) years, ranging from 2.5 to 7.8 years; seven boys and five girls; GMFCS I = 5, II = 4 and III = 3) were collected before and 3 and 6 months after BoNT-A treatment to analyze the fiber cross-sectional area (fCSA) and proportion; capillarization; and satellite cell (SC) content. Compared with the baseline, the fCSA decreased at 3 months (-14%, NS) and increased at 6 months (+13%, NS). Fiber size variability was significantly higher at 3 months (type I: +56%, p = 0.032; type IIa: +37%, p = 0.032) and 6 months (type I: +69%, p = 0.04; type IIa: +121%, p = 0.032) compared with the baseline. The higher type I proportion seen at 3 months was still present and more pronounced at 6 months (type I: +17%, p = 0.04; type IIx: -65%, p = 0.032). The capillary fiber density was reduced at 3 months (type I: -43%, NS; type II: -44%, p = 0.0320) but normalized at 6 months. There was a non-significant increase in SC/100 fibers at 3 months (+75%, NS) and 6 months (+40%, NS) compared with the baseline. These preliminary data suggest that BoNT-A induced alterations in the MG of children with CP, which were still present 6 months after BoNT-A injection but with signs of muscle recovery.