[Prerequisite and organisation of health-care pathways for Cell and Gene therapies, using Mesenchymal Stromal Cells (MSC) or Chimeric Antigen Receptor (CAR) T cells, in patients with autoimmune systemic diseases]. / Prérequis et organisation du parcours de soins en vue de l'utilisation d'une thérapie cellulaire ou génique par cellules stromales mésenchymateuses (CSM) ou par cellules T porteuses d'un récepteur antigénique chimérique (CAR-T cells) chez les patients avec maladies auto-immunes systémiques.

First-line treatments of autoimmune systemic diseases (ARD) are based on the use of various types of immunosuppressive or immunomodulatory drugs, either alone or in association, according to standardized reference protocols. Prolonged use of these drugs in severe or refractory ARD is associated with high morbidity and increased mortality. Innovative cell therapies represent a new promising approach for patients with ARDs, with the recent clinical use of: a) mesenchymal stromal cells (MSCs), based on their immunomodulatory, antifibrotic and pro-angiogenic properties and b) Chimeric Antigen Receptors (CAR) T cell therapies T lymphocytes, where genetically modified expression of a chimeric antigen receptor (CAR-T cells). Therapeutic use of MSC or CAR-T cells, remains indications of exception in patients with severe ARDs resistant to prior standard therapies with new prerequisite and organisation of health-care pathways as compared to traditional drugs, not only for the Cell and Gene Therapy (CGT) product definition and delivery process, but also for the patient clinical management before and after administration of the CGT product. The aim of this workshop under the auspices of the French Speaking Society of Bone Marrow and Cell transplantation (SFGM-TC) working group on autoimmune diseases (MATHEC) is to describe: a) the prerequisite for French hospitals to set-up the specific health-care pathways for MSC or CART therapy in ARDs patients, in accordance with regulatory and safety needs to perform academic or industry sponsored clinical trials, and b) the care-pathway for ARD patients treated with CGT, highlighting the importance of working in tandem between the ARD and the CAR-T cell specialist all along the indication, procedures and follow-up of ARDs. Patient safety considerations are central to guidance on patient selection to be validated collectively at the multidisciplinary team meeting (MDTM) based on recent (less than 3 months) thorough patient evaluation. MSC and CAR-T procedural aspects and follow-up are then carried out within appropriately experienced and SFGM-TC accredited centres in close collaboration with the ADs specialist.

The system of radiological protection and the UN sustainable development goals.

In 2015 the United Nations issued 17 Sustainable Development Goals (SDGs) addressing a wide range of global social, economic, and environmental challenges. The main goal of this paper is to provide an understanding of how the current System of Radiological Protection relates to these SDGs. In the first part it is proposed that the current System of Radiological Protection is implicitly linked to sustainable development. This is substantiated by analysing the features of the current System as set out by the International Commission on Radiological Protection (ICRP) in its publications. In the second part it is proposed that sustainability should be considered and more explicitly addressed in the next ICRP general recommendations, as part of the currently ongoing review and revision of the current System. A few examples are given of how this could be realised, and it is proposed that this issue should be discussed and developed together with the international community interested in radiological protection.

Performance of the DASF compared to other combinations of OECD NAMs for eye hazard identification of surfactants.

Currently, the OECD has adopted three defined approaches (DAs) for eye hazard identification of non-surfactant liquids and solids (TG467) according to the three UN GHS categories (Cat.1, Cat.2, No Cat.). We are now expanding the applicability domain with a new DA for chemicals having surfactant (SF) properties (DASF). It is based on a combination of RhCE test methods (OECD TG492: EpiOcular™ EIT or SkinEthic™ HCE EIT) and a modification of the Short Time Exposure (STE, TG491) method. The aim of the current study was to compare the performance of the DASF with the performance of other NAMs currently included in the OECD TGs and with the classification based on the Draize eye test to identify potential additional DAs. The minimum performance criteria (75% Cat.1, 50% Cat.2, 70% No Cat.) used for the adoption of the DAs currently included in OECD TG467 were used for this purpose. The DASF identified 90.9% of Cat. 1 (N=23), 77.8% of Cat. 2 (N=9) and 76.0% of No Cat. (N=17) surfactants, meeting the minimum performance criteria. Some of the NAMs that are currently included in the OECD TGs seem promising methods to be part of a DA to identify Cat. 1 or No Cat. for eye hazard assessment of surfactants. However, the number of surfactants that have been tested to evaluate reliability and relevance was often too small. To date, the DASF is the only DA that has evaluated a sufficiently large number of surfactants and whose performance met the OECD acceptance criteria.

Three non-animal-based defined approaches (DAs) for eye hazard assessment of non-surfactant liquid and solid chemicals were adopted as full replacements as OECD Test Guideline (TG 467). We now extend the applicability domain to surfactants with a new DA (DASF), which combines OECD-adopted test systems based on human 3D eye models and rabbit 2D corneal cells. The DASF has been shown to provide reliable results in predicting the eye irritation potential of 50 surfactants. The aim of the current study was to compare the performance of the DASF with the performance of other OECD TG new approach methodologies and compare it with the classification based on historical animal test data. Based on this analysis no additional DAs could be derived. Until today, the DASF is the best predicting, human-relevant DA that covers the whole range of eye irritation responses across the different surfactant classes.

Autonomy and freedom of choice: A mixed methods analysis of the endorsement of SRHR and its core principles by global agencies.

Based on an adapted version of the conceptual framework used by the Guttmacher-Lancet Commission on Sexual and Reproductive Health and Rights (SRHR), this study sought to analyse to what extent seven global agencies, five of which belong to the UN family and the other two closely linked, incorporate women's autonomy and freedom of choice in accessing services into their SRHR policies, and how they operationalize these in their global SRHR programmes that target women and adolescent girls. Twenty-nine SRHR-related policy documents published in 2013-2020 and 17 independent evaluations of global SRHR programmes in the same period were analysed. They were found to fall short of considering women's individual autonomy and choice as the two core principles of SRHR. By ignoring autonomy and choice, global SRHR programmes missed the opportunity to incorporate activities that could enhance the emancipatory empowerment of women and girls to improve their sexual and reproductive wellbeing. The study identified concrete aspects on which global agencies, in view of their respective mandates, could have pronounced themselves more explicitly and might have been more effective in implementing SRHR programmes. In light of the international gender equality and women's empowerment discourse this suggests that donor countries could hold global agencies more accountable, bilaterally or jointly, for their SRHR performance, in particular their active endorsement and application of SRHR core principles.

Interaction between angiotensin-converting enzyme gene rs4343 polymorphism, environment factors, and angiotensin II level on susceptibility to knee osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level. METHODS: Using a case-control design, we recruited 200 subjects (100 cases and 100 controls) and all were subjected to genotyping of rs4343 SNP by real-time polymerase chain reaction and assay of serum angiotensin II level by ELISA. RESULTS: G containing genotypes (AG and GG) and G allele frequencies of the ACE rs4343 polymorphism were significantly higher in the case group than that in the control group. There was significant association between ACE rs4343 genotypes and risk of knee OA under the following genetic inheritance models: GG vs. AA (P=0.003), AA vs. GG/AG (P=0.014), AG/AA vs. GG (P=0.037), and G vs. A (P<0.001). Stratified analyses showed ACE rs4343 polymorphism was evidently associated with a significantly increased risk of knee OA among those had BMI≥25% (adjusted OR=3.016; 95% CI 1.052-8.648; P=0.040). Additionally, knee OA patients with GG genotype had greater knee specific WOMAC index, Kellgren score, and serum angiotensin II level than those with AA or GA genotypes. CONCLUSION: The investigated polymorphism in the ACE gene rs4343 may reflect the risk and severity of knee OA in the Egyptian population, particularly with the GG genotype. The interaction between ACE gene rs4343 polymorphism and obesity further increased the risk of knee OA. Moreover, the higher angiotensin II level may be involved in the pathogenesis of knee OA.

GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Dose escalation with simultaneous integrated boost for un-methylated multiple glioblastoma.

Background: Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation. Materials and methods: We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy. Results: A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria. Conclusion: In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial.

Machine Learning Models Can Define Clinically Relevant Bone Density Subgroups based on Patient Specific Calibrated CT Scans in Patients Undergoing Reverse Shoulder Arthroplasty.

BACKGROUND: Reduced bone density is recognized as a predictor for potential complications in reverse shoulder arthroplasty (RSA). While humeral and glenoid planning based on preoperative computed tomography (CT) scans assist in implant selection and position, reproducible methods for quantifying the patients' bone density are currently not available. The purpose of this study was to perform bone density analyses including patient specific calibration in an RSA cohort based on preoperative CT imaging. It was hypothesized that preoperative CT bone density measures would provide objective quantification of the patients' humeral bone quality. METHODS: This study consisted of three parts, (1) analysis of a patient-specific calibration method in cadaveric CT scans, (2) retrospective application in a clinical RSA cohort, and (3) clustering and classification with machine learning models. Forty cadaveric shoulders were scanned in a clinical CT and compared regarding calibration with density phantoms, air muscle, and fat (patient-specific) or standard Hounsfield unit. Post-scan patient-specific calibration was used to improve the extraction of three-dimensional regions of interest for retrospective bone density analysis in a clinical RSA cohort (n=345). Machine learning models were used to improve the clustering (Hierarchical Ward) and classification (Support Vector Machine (SVM)) of low bone densities in the respective patients. RESULTS: The patient-specific calibration method demonstrated improved accuracy with excellent intraclass correlation coefficients (ICC) for cylindrical cancellous bone densities (ICC>0.75). Clustering partitioned the training data set into a high-density subgroup consisting of 96 patients and a low-density subgroup consisting of 146 patients, showing significant differences between these groups. The SVM showed optimized prediction accuracy of low and high bone densities compared to conventional statistics in the training (accuracy=91.2%; AUC=0.967) and testing (accuracy=90.5 %; AUC=0.958) data set. CONCLUSION: Preoperative CT scans can be used to quantify the proximal humeral bone quality in patients undergoing RSA. The use of machine learning models and patient-specific calibration on bone mineral density demonstrated that multiple 3D bone density scores improved the accuracy of objective preoperative bone quality assessment. The trained model could provide preoperative information to surgeons treating patients with potentially poor bone quality.

Order/Disorder Transitions Upon Protein Binding: A Unifying Perspective.

When two proteins bind to each other, this process is often accompanied by a change in their structural states (from disordered to ordered or vice versa). As it turns out, there are 10 distinct possibilities for such binding-related order/disorder transitions. Out of this number, seven scenarios have been experimentally observed, while another three remain hitherto unreported. As an example, we discuss the so-called mutual synergistic folding, whereby two disordered proteins come together to form a fully structured complex. Our bioinformatics analysis of the Protein Databank found potential new examples of this remarkable binding mechanism.

[Fatal outcome of complete resection of undifferentiated pleomorphic cardiac sarcoma : About a case]. / Évolution fatale d'une résection complète d'un sarcome cardiaque pléomorphe indifférencié : à propos d'un cas.

INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) is a very rare malignant primary cardiac tumor with a poor prognosis. OBSERVATION: A 34-year-old woman complained of dyspnea evolving in a febrile context with altered general condition: Transthoracic echocardiography (TTE) revealed a left intra-atrial mass measuring 51/26 mm in diameter. A thoracic computed tomography (CT) revealed a mass occupying the left atrium measuring 42/28/34 mm, associated with two pulmonary metastases. The cardiac mass was resected and the postoperative suites were fatal. Histological diagnosis was UPS. CONCLUSION: We present an atypical case of invasive UPS, which was surgically resected and scheduled for radio-chemotherapy with a fatal outcome.

Switzerland and the Sustainable Development Goals of the United Nations from the youngSCS Perspective.

Switzerland's commitment to the Sustainable Development Goals of the United Nations is showcased in this article with concrete examples of actions taken so far in the private and public sector. To further highlight the involvement of the chemical scientists in the implementation of the SDGs in Switzerland to date, the young-SCS also interviewed various individuals.

Charge distribution studies in the epi-cadmium neutron induced fission of 235U.

For the first time, charge distribution studies have been carried out in the epi-cadmium neutron induced fission of 235U by measuring the fractional cumulative yields (FCY) and independent yields (IY) of various fission products. An off-line γ-ray spectrometric technique was used for the measurements. The average energy of the epi-cadmium neutron spectrum is 1.9 MeV. From the FCY values, the isobaric width parameter (σZ), most probable charge (ZP) and the charge polarization (ΔΖEXPT) as a function of fragment mass were obtained. Similarly, from the IY values, isotopic width parameter (σA), the most probable mass (AP) and the elemental yields (YZ) of Sn, Sb, Te, I, Xe, Cs, Ba, La, Ce and Pr were determined by using a non-linear fit. From the YZ values, the proton even-odd effect (δp) was obtained for the first time. The present data in the 235U(n, f) reaction were compared with the similar data in the 235U(nth, f) and 238U(n, f) reactions as well as of other actinides to examine the role of excitation energy and pairing effect.

Mothers' Responses to Children's Emotions and Children's Behavior: The Mediating Role of Children's Emotion Regulation.

While prior research has clearly established links between maternal responses and children's emotion regulation (ER), the implications of these links for children's behaviors, especially at school (as reported by their teachers), remain much less explored. This study examined the mediating role of children's ER in the relationship between maternal reactions to both negative and positive emotions of children and the subsequent behaviors of these children at school. Participants included 56 Portuguese school-aged children (31 boys and 25 girls, aged 6-10 years, mean age = 8.27, SD = 1.27), their mothers (aged 26-55 years, mean age = 38.33, SD = 6.68), and their teachers (n = 7 female teachers) in a multi-informant study. Mothers provided reports on their responses to their children's emotions and their perceptions of the children's ER and lability/negativity, while teachers assessed the children's behavior in the classroom. The results indicated that punitive maternal reactions were associated with greater child lability/negativity, which in turn correlated with increased conduct problems and hyperactivity at school. Conversely, maternal encouragement of expression was linked to reduced lability/negativity, which was associated with fewer emotional symptoms at school. Additionally, maternal problem-focused reactions and guided/empowering responses were associated with reduced child lability/negativity, which in turn correlated with fewer conduct problems and less hyperactivity at school. These findings suggest that maternal responses to children's emotions can significantly influence children's behaviors in the classroom via mechanisms involving children's ER.

Enhancing affordability and profit in a non-cooperative, coordinated, hypothetical pediatric vaccine market via sequential optimization.

This study considers a hypothetical global pediatric vaccine market where multiple coordinating entities make optimal procurement decisions on behalf of countries with different purchasing power. Each entity aims to improve affordability for its countries while maintaining a profitable market for vaccine producers. This study analyzes the effect of several factors on affordability and profitability, including the number of non-cooperative coordinating entities making procuring decisions, the number of market segments in which countries are grouped for tiered pricing purposes, how producers recover fixed production costs, and the procuring order of the coordinating entities. The study relies on a framework where entities negotiate sequentially with vaccine producers using a three-stage optimization process that solves a MIP and two LP problems to determine the optimal procurement plans and prices per dose that maximize savings for the entities' countries and profit for the vaccine producers. The study's results challenge current vaccine market dynamics and contribute novel alternative strategies to orchestrate the interaction of buyers, producers, and coordinating entities for enhancing affordability in a non-cooperative market. Key results show that the order in which the coordinating entities negotiate with vaccine producers and how the latter recuperate their fixed cost investments can significantly affect profitability and affordability. Furthermore, low-income countries can meet their demands more affordably by procuring vaccines through tiered pricing via entities coordinating many market segments. In contrast, upper-middle and high-income countries increase their affordability by procuring through entities with fewer and more extensive market segments. A procurement order that prioritizes entities based on the descending income level of their countries offers higher opportunities to increase affordability and profit when producers offer volume discounts.

Beyond surface: Unveiling ecological and economic ramifications of microplastic pollution in the oceans.

Every year, the global production of plastic waste reaches a staggering 400 million metric tons (Mt), precipitating adverse consequences for the environment, food safety, and biodiversity as it degrades into microplastics (MPs). The multifaceted nature of MP pollution, coupled with its intricate physiological impacts, underscores the pressing need for comprehensive policies and legislative frameworks. Such measures, alongside advancements in technology, hold promise in averting ecological catastrophe in the oceans. Mandated legislation represents a pivotal step towards restoring oceanic health and securing the well-being of the planet. This work offers an overview of the policy hurdles, legislative initiatives, and prospective strategies for addressing global pollution due to MP. Additionally, this work explores innovative approaches that yield fresh insights into combating plastic pollution across various sectors. Emphasizing the importance of a global plastics treaty, the article underscores its potential to galvanize collaborative efforts in mitigating MP pollution's deleterious effects on marine ecosystems. Successful implementation of such a treaty could revolutionize the plastics economy, steering it towards a circular, less polluting model operating within planetary boundaries. Failure to act decisively risks exacerbating the scourge of MP pollution and its attendant repercussions on both humanity and the environment. Central to this endeavor are the formulation, content, and execution of the treaty itself, which demand careful consideration. While recognizing that a global plastics treaty is not a panacea, it serves as a mechanism for enhancing plastics governance and elevating global ambitions towards achieving zero plastic pollution by 2040. Adopting a life cycle approach to plastic management allows for a nuanced understanding of possible trade-offs between environmental impact and economic growth, guiding the selection of optimal solutions with socio-economic implications in mind. By embracing a comprehensive strategy that integrates legislative measures and technological innovations, we can substantially reduce the influx of marine plastic litter at its sources, safeguarding the oceans for future generations.

Freud in Bulgaria: Psychoanalysis, Literature, Translation: An Experience with the Singular.

This contribution considers a monthly seminar, Literature and Psychoanalysis, that has been taking place at Sofia University (Sofia, Bulgaria) since 2017. Three of the seminar's founders reflect on the transferences between literature and psychoanalysis, and on the ways in which literature and psychoanalysis can meaningfully converse. The exchange also touches on the fate of Freud's textual legacy in communist and post-communist Bulgaria.

Primary hepatic pleomorphic liposarcoma: Case report and literature review / Liposarcoma pleomorfo hepático primario: presentación de un caso y revisión bibliográfica

Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification. (AU)

El liposarcoma hepático primario es un tumor maligno extremadamente raro, derivado de adipocitos, y forma parte del grupo de tumores mesenquimales. Presentamos el caso de un paciente masculino de 43 años con diagnóstico de liposarcoma hepático pleomorfo con ausencia de amplificación del gen MDM2. Dos años y 6 meses después de la cirugía el paciente se encuentra asintomático. El presente caso es el primer informe de esta entidad con estudio inmunohistoquímico positivo para p16, p53, S100, vimentina y ausencia de amplificación del gen MDM2. (AU)

The mediatory role of water quality on the association between extreme precipitation events and infectious diarrhea in the Yangtze River Basin, China.

Extreme precipitation is exacerbating the burden of infectious diarrhea in the context of climate change, it is necessary to identify the critical and easy-to-intervene intermediate factors for public health strategies. Water quality may be the most important mediator, while relevant empirical evidence is limited. This study aimed to examine the role of water quality in the process of infectious diarrhea caused by extreme precipitation. Weekly infectious diarrhea cases, meteorological factors and water quality data in Yangtze River Basin in China between October 29, 2007 to February 19, 2017 were obtained. Two-stage statistical models were used to estimate city-specific extreme precipitation, water quality and infectious diarrhea relationships that were pooled to derive regional estimates. A causal mediation analysis was used to assess the mediation effect of water quality. In Yangtze River Basin, extreme precipitation events had a significant impact on infectious diarrhea (Incidence Rate Ratios [IRR]: 1.027, 95% Confidence Interval [CI]: 1.013∼1.041). After extreme precipitation events, the dissolved oxygen (DO) in surface water decreased (-0.123 mg/L, 95%CI: -0.159 mg/L∼-0.086 mg/L), while the un-ionized ammonia (NH(3)-N) increased (0.004 mg/L, 95%CI: 0.001 mg/L∼0.006 mg/L). The combined overall effect of DO and NH(3)-N on infectious diarrhea showed that both low and high concentrations were associated with an increased risk of infectious diarrhea. The causal mediation analysis showed that the mediation proportion of the two water quality indexes (DO and NH(3)-N) is 70.54% (P < 0.001). To reduce the health effects of extreme precipitation, in contrast to current population-oriented health strategies, those that take into account more direct and easy-to-intervene water quality indicators should be encouraged by future policies.

Impact of three different peak picking software tools on the quality of untargeted metabolomics data.

Data quality and control parameters are becoming more important in metabolomics. For peak picking, open-source or commercial solutions are used. Other publications consider different software solutions or data acquisition types for peak picking, a combination, including proposed and new quality parameters for the process of peak picking, does not exist. This study tries to examine the performance of three different software in terms of reproducibility and quality of their output while also considering new quality parameters to gain a better understanding of resulting feature lists in metabolomics data. We saw best recovery of spiked analytes in MS-DIAL. Reproducibility over multiple projects was good among all software. The total number of features found was consistent for DDA and full scan acquisition in MS-DIAL but full scan data leading to considerably more features in MZmine and Progenesis Qi. Feature linearity proved to be a good quality parameter. Features in MS-DIAL and MZmine, showed good linearity while Progenesis Qi produced large variation, especially in full scan data. Peak width proved to be a very powerful filtering criteria revealing many features in MZmine and Progenesis Qi to be of questionable peak width. Additionally, full scan data appears to produce a disproportionally higher number of short features. This parameter is not yet available in MS-DIAL. Finally, the manual classification of true positive features proved MS-DIAL to perform significantly better in DDA data (62 % true positive) than the two other software in either mode. We showed that currently popular solutions MS-DIAL and MZmine perform well in targeted analysis of spiked analytes as well as in classic untargeted analysis. The commercially available solution Progenesis Qi does not hold any advantage over the two in terms of quality parameters, of which we proposed peak width as a new parameter and showed that already proposed parameters such as feature linearity in samples of increasing concentration are advisable to use.

Global Water Challenges in Sub-Saharan Africa and how to strengthen science-policy dialogues on transboundary governance and cooperation.

The United Nations Water Conference 2023 highlighted the need for concrete actions to boost integrated water resources management for achieving the Sustainable Development Goals and called for strategies to enhance cooperation among stakeholders. Technical cooperation between countries and institutions in transboundary systems, e.g., on environmental data collection, is an effective way to promote international diplomacy and prevent disputes between riparian states. Still, establishing collaborations to inform bilateral dialogues on the identification of environmental challenges, their causes, and development priorities may be a difficult task in itself. This is particularly true in the African context because of limited resources and lack of data. In this paper, we analyse the case of nine transboundary river basins in Sub-Saharan Africa to identify which water-management challenges are perceived as most important by the different riparian countries from a policy and scientific perspective. Our insights are based on the most up-to-date scientific papers, open access reports and technical literature, river basin authority's strategy papers, projects' summary reports, and national policy documents. We also complement these sources with the pieces of information we gained through collaborations with regional and local experts, and management bodies (such as river basin authorities). We highlight the current water-related conflicts and the gap between the priorities identified by the scientific community and different riparian countries on how to tackle hydro-climatic change and improve food and energy security, human and environmental health. Based on our experience, we discuss some keys to building trust among stakeholders, strengthening cooperation, and identifying shared water-governance measures in transboundary river basins. They are: (i) connect science and policy to provide sound knowledge for the right questions, (ii) value local knowledge and exploit the complementarity of different perspectives, (iii) consider multiple spatial scales and multi-level stakeholders to leave no one behind, (iv) promote a culture which values trade-offs and handles complexity, and (v) co-create data and knowledge to facilitate stakeholder dialogue from problem definition to intervention identification.