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Abstract In medical imaging, accurate segmentation is crucial to improving diagnosis, treatment, or both. However, navigating the multitude of available architectures for automatic segmentation can be overwhelming, making it challenging to determine the appropriate type of architecture and tune the most crucial parameters during dataset optimisation. To address this problem, we examined and refined seven distinct architectures for segmenting the liver, as well as liver tumours, with a restricted training collection of 60 3D contrast-enhanced magnetic resonance images (CE-MRI) from the ATLAS dataset. Included in these architectures are convolutional neural networks (CNNs), transformers, and hybrid CNN/transformer architectures. Bayesian search techniques were used for hyperparameter tuning to hasten convergence to the optimal parameter mixes while also minimising the number of trained models. It was unexpected that hybrid models, which typically exhibit superior performance on larger datasets, would exhibit comparable performance to CNNs. The optimisation of parameters contributed to better segmentations, resulting in an average increase of 1.7% and 5.0% in liver and tumour segmentation Dice coefficients, respectively. In conclusion, the findings of this study indicate that hybrid CNN/transformer architectures may serve as a practical substitute for CNNs even in small datasets. This underscores the significance of hyperparameter optimisation.

The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance. While international guidelines list relevant pivotal trials and give recommendations for a variety of clinical scenarios, there is much room for interpretation, and several important questions remain highly debated. The goal of developing a national consensus on the use of these novel diagnostic and therapeutic strategies in order to improve disease management and eventually patient outcomes has prompted a Swiss consensus meeting. Experts from several specialties, including urology, medical oncology, radiation oncology, pathology and nuclear medicine, discussed and voted on questions of the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).

Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6–47.0%), 41.1% (38.0–44.2%), and 38.0% (34.9–41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities—79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region.

Abstract Alternaria dauci is a Dothideomycete fungus, causal agent of carrot leaf blight. As a member of the Alternaria genus, known to produce a lot of secondary metabolite toxins, A. dauci is also supposed to synthetize host specific and non-host specific toxins playing a crucial role in pathogenicity. This study provides the first reviewing of secondary metabolism genetic basis in the Alternaria genus by prediction of 55 different putative core genes. Interestingly, aldaulactone, a phytotoxic benzenediol lactone from A. dauci, was demonstrated as important in pathogenicity and in carrot partial resistance to this fungus. As nothing is known about aldaulactone biosynthesis, bioinformatic analyses on a publicly available A. dauci genome data set that were reassembled, thanks to a transcriptome data set described here, allowed to identify 19 putative secondary metabolism clusters. We exploited phylogeny to pinpoint cluster 8 as a candidate in aldaulactone biosynthesis. This cluster contains AdPKS7 and AdPKS8, homologs with genes encoding a reducing and a non-reducing polyketide synthase. Clusters containing such a pair of PKS genes have been identified in the biosynthesis of resorcylic acid lactones or dihydroxyphenylacetic acid lactones. AdPKS7 and AdPKS8 gene expression patterns correlated with aldaulactone production in different experimental conditions. The present results highly suggest that both genes are responsible for aldaulactone biosynthesis.

Abstract Evaluate the feasibility, safety and accuracy of a CT-guided robotic assistance for percutaneous needle placement in the liver. Sixty-six fiducials were surgically inserted into the liver of ten swine and used as targets for needle insertions. All CT-scan acquisitions and robotically-assisted needle insertions were coordinated with breath motion using respiratory monitoring. Skin entry and target points were defined on planning CT-scan. Then, robotically-assisted insertions of 17G needles were performed either by experienced interventional radiologists or by a novice. Post-needle insertion CT-scans were acquired to assess accuracy (3D deviation, ie. distance from needle tip to predefined target) and safety. All needle insertions (43/43; median trajectory length = 83 mm (interquartile range [IQR] 72–105 mm) could be performed in one (n = 36) or two (n = 7) attempts (100% feasibility). Blinded evaluation showed an accuracy of 3.5 ± 1.3 mm. Accuracy did not differ between novice and experienced operators (3.7 ± 1.3 versus 3.4 ± 1.2 mm, P = 0.44). Neither trajectory angulation nor trajectory length significantly impacted accuracy. No complications were encountered. Needle insertion using the robotic device was shown feasible, safe and accurate in a swine liver model. Accuracy was influenced neither by the trajectory length nor by trajectory angulations nor by operator’s experience. A prospective human clinical trial is recruiting.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Molecular imaging has found numerous applications in oncology as many tumours express or activate tumour specific target molecules or pathways. This relatively new imaging technique results in a better localisation of tumours and improved tumour staging, especially in the setting of hybrid imaging that is in combination with morphological imaging such as computed tomography. In well differentiated neuroendocrine tumours, somatostatin receptor imaging, as one of the first examples of receptor targeted imaging in humans, plays an important role in the diagnostic work-up of these patients. In poorly differentiated neuroendocrine tumours or medullary thyroid carcinoma, 18F-fluorodeoxyglucose PET/CT and dihydroxyphenylalanine PET/CT play an important role due to the limitations of the somatostatin receptor imaging in these tumour entities. These limitations prompted the development of innovations such as radiolabelled somatostatin receptor antagonists for imaging all types of NET and glucagon-like peptide-1 receptor agonists for the imaging of insulinomas. The current review summarises the actual state of knowledge in the field.

Despite increased vaccination rates, the burden, morbidity and mortality associated with vaccine preventable diseases remains high. In the Democratic Republic of the Congo (DRC), potentially unreliable data and geographically varied program provision call for a better understanding of vaccination coverage and its changes over time at the country and province level. To assess changes in the proportion of children who were fully vaccinated over time in the DRC, vaccination histories for children 12-59 months of age were obtained from both the 2007 and 2013-2014 Demographic and Health Surveys (DHS). Changes were assessed, both at the country- and province-levels, to identify potential geographic variations. Vaccination coverage improved 70% between the DHS waves: 26% compared to 44% of 12-59 month-old children met full vaccination criteria in 2007 and 2013-2014, respectively (n2007 = 3032 and n2013-14 = 6619). Similarly, there was an overall trend across both DHS waves where as year of birth increased, so did vaccination coverage. There was geographic variation in immunization changes with most central and eastern provinces increasing in coverage and most northern, western and southern provinces having decreased vaccination coverage at the second time point. Using nationally representative data, we identified significant changes over time in vaccination coverage which may help to inform future policy, interventions and research to improve vaccination rates among children in the DRC. This study is the first of its kind for the population of DRC and provides an important initial step towards better understanding trends in vaccination coverage over time.

The SARS-CoV-2 (COVID-19) pandemic has had a tremendous impact on the functionality of health systems and world affairs. We assessed knowledge, attitudes, and practices (KAPs) of healthcare workers (HCWs) in the Democratic Republic of the Congo (DRC). This was a cross-sectional study conducted in 23 referral hospitals located in three towns of the DRC (Lubumbashi, Kamina, Mbuji-Mayi). In total, 613 HCWs were surveyed using the World Health Organization’s (WHO’s) “Exposure Risk Assessment in the Context of COVID-19” questionnaire. Participants included medical doctors (27.2%) and other categories of HCWs (72.8%). The mean age was 40.3 ± 11.7 years. Over 80% (range: 83–96%) of respondents had sufficient knowledge on each of the three domains: COVID-19 symptoms, disease transmission, and patient care approach. However, attitudes and practices scores were relatively low. Only 27.7% of HCWs were willing to receive a COVID-19 vaccine when it is available, whereas 55% of HCWs complied with good practices; 49.4% wore masks consistently and, surprisingly, only 54.9% used personal protective equipment (PPE) consistently at work and during contact with patients. Knowledge level was positively associated with the use of social media as a primary source of COVID-19-related information and the category of residence, with HCWs from towns already affected by the COVID-19 epidemic being more likely to have positive attitudes (adjusted OR, 1.64; 95%CI, 1.32–2.20) and comply with good practices (aOR, 2.79; 95%CI, 1.93-4.06). This study showed that most Congolese HCWs had sufficient knowledge on COVID-19, whereas the majority did not comply with consistent PPE use. The government of the DRC should urgently take major steps in capacity building for HCWs in outbreak preparedness and supplying hospitals with PPE.

Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder due to mutations in the dystrophin gene on chromosome Xp21.1. We designed this study to determine the prevalence of left bundle branch block (LBBB), whether there is a relationship between LBBB and genetic pattern, and to assess predictive factors for acute cardiac events and mortality in adult DMD patients.We reviewed the charts of DMD followed at the Home Mechanical Ventilation Unit of the Raymond Poincare University Hospital.A total of 121 patients, aged from 18 to 41 years have been included in our study. Median vital capacity (VC) was 12% [7; 19.5] of predicted. Almost all patients were on home mechanical ventilation (95%). LBBB was present in 15 patients (13%); among them, 10 disclosed exonic deletions. After a median follow up of 6 years, 21 patients (17%) experienced acute heart failure (AHF), 7 patients (6%) supraventricular arrhythmia, 3 patients (2.4%) ventricular tachycardia, 4 patients (3%) significant electrical disturbances. LBBB was significantly associated with cardiac events (OR = 12.7; 95%CI [3.78-42.7]; p

The natural history of chronic obstructive pulmonary disease (COPD) is still not well understood. Traditionally believed to be a self-inflicted disease by smoking, now we know that not all smokers develop COPD, that other inhaled pollutants different from cigarette smoke can also cause it, and that abnormal lung development can also lead to COPD in adulthood. Likewise, the inflammatory response that characterizes COPD varies significantly between patients, and not all of them perceive symptoms (mostly breathlessness) similarly. To investigate the variability and determinants of different "individual natural histories" of COPD, we developed a theoretical, multi-stage, computational model of COPD (EASI) that integrates dynamically and represents graphically the relationships between exposure (E) to inhaled particles and gases (smoking), the biological activity (inflammatory response) of the disease (A), the severity (S) of airflow limitation (FEV1) and the impact (I) of the disease (breathlessness) in different clinical scenarios. EASI shows that the relationships between E, A, S and I vary markedly within individuals (through life) and between individuals (at the same age). It also helps to delineate some potentially relevant, but often overlooked concepts, such as disease progression, susceptibility to COPD and issues related to symptom perception. In conclusion, EASI is an initial conceptual model to interpret the longitudinal and cross-sectional relationships between E, A, S and I in different clinical scenarios. Currently, it does not have any direct clinical application, thus it requires experimental validation and further mathematical development. However, it has the potential to open novel research and teaching alternatives.

Developing therapeutic monoclonal antibodies paves the way for new strategies in oncology using targeted therapy which should improve specificity. However, due to a lack of biomarkers, a personalized therapy scheme cannot always be applied with monoclonal antibodies. As a consequence, the efficacy or side effects associated with this type of treatment often appear to be sporadic. Bevacizumab is a therapeutic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF). It is used to limit tumor vascularization. No prognosis or response biomarker is associated with this antibody, we therefore assessed whether the administration protocol could be a possible cause of heterogeneous responses (or variable efficacy). To do this, we developed a bevacizumab assay with a broad sensitivity range to measure blood bevacizumab concentrations. We then analyzed bevacizumab concentrations in 17 patients throughout the first quarter of treatment. In line with previously published data, average blood concentrations were 88+/-27 mg/L following the first dose administered, and 213+/-105 mg/L after the last (6(th)) dose administered. However, the individual values were scattered, with a mean 4-fold difference between the lowest and the highest concentration for each dose administered. We demonstrated that the bevacizumab administration schedule results in a high inter-individual variability in terms of blood concentrations. Comparison of assay data with clinical data indicates that blood concentrations above the median are associated with side effects, whereas values below the median favor inefficacy. In conclusion, bevacizumab-based therapy could benefit from a personalized administration schedule including follow-up and adjustment of circulating bevacizumab concentrations.

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, (18)F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney's test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of (18)F-DPA-714 was increased in ALS patients during the "time of diagnosis" phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.