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This article reports changes to virus taxonomy and taxon nomenclature that were approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2024. The entire ICTV membership was invited to vote on 203 taxonomic proposals that had been approved by the ICTV Executive Committee (EC) in July 2023 at the 55th EC meeting in Jena, Germany, or in the second EC vote in November 2023. All proposals were ratified by online vote. Taxonomic additions include one new phylum (Ambiviricota), one new class, nine new orders, three new suborders, 51 new families, 18 new subfamilies, 820 new genera, and 3547 new species (excluding taxa that have been abolished). Proposals to complete the process of species name replacement to the binomial (genus + species epithet) format were ratified. Currently, a total of 14,690 virus species have been established.

Opinion 130 deals with a Request for an Opinion asking the Judicial Commission to clarify whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate. The Request is approved and an answer is given. The name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate because it is a later homonym of the validly published cyanobacterial name Rhodococcus Hansgirg 1884. The Judicial Commission also clarifies that it has the means to resolve such cases by conserving a name over an earlier homonym. It is concluded that the name Rhodococcus Zopf 1891 (Approved Lists 1980) is significantly more important than the name Rhodococcus Hansgirg 1884 and therefore the former is conserved over the latter. This makes the name Rhodococcus Zopf 1891 (Approved Lists 1980) legitimate.

Objectives: Linezolid-resistant opportunistic human pathogens Enterococcus faecalis and Enterococcus faecium are emerging health threats as limited therapeutic options remain. The aim of this study was to investigate the epidemiology, resistance mechanisms, and genetic diversity of linezolid-resistant enterococci (LRE) isolated between 2013 and 2021 and received at the Belgian National Reference Centre (NRC) for Enterococci. Methods: Linezolid susceptibility testing was performed upon request on 2458 submitted enterococci strains. Whole-genome sequencing was performed on all LRE strains. Results: Seventy-eight LRE human isolates, of which 63 (81%) E. faecalis and 15 (19%) E. faecium strains, were submitted to the Belgian NRC for Enterococci. Of the linezolid-resistant E. faecalis strains, 97% harboured the optrA gene (56% wild-type pE349) and 3% the poxtA gene. Of the linezolid-resistant E. faecium strains, 54% harboured the G2576T point mutation in the V domain of the 23S rRNA genes, 23% the poxtA, and 23% the optrA gene. Furthermore, two E. faecium strains were identified with a combination of two resistance mechanisms ([i] optrA and poxtA, and [ii] cfr(B) and G2576T point mutation, respectively). Vancomycin resistance was observed in 15% (n = 12) of the LRE. ST480 (n = 42/63 typed strains, 67%) was the most frequently detected sequence type (ST) in linezolid-resistant E. faecalis strains, while ST203 (n = 5/15 typed strains, 33%) was the most frequently detected ST in linezolid-resistant E. faecium strains. Conclusions: E. faecalis isolates harbouring optrA were the predominant LRE in Belgium, with ST480 as the most prominent multilocus sequence typing. Linezolid resistance in E. faecium could be attributed to either chromosomal mutations or transferable resistance determinants.

Abstract Objective Neurofilament heavy‐chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. Methods Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta‐analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole‐genome sequencing data. Results Fixed‐effects meta‐analysis found that rare (MAF

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.  • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing.  • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions.  • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

Abstract Co-pyrolysis of chicken manure with tree bark was investigated to mitigate salinity and potentially toxic element (PTE) concentrations of chicken manure-derived biochar. The effect of tree bark addition (0, 25, 50, 75 and 100 wt%) on the biochar composition, surface functional groups, PTEs and polycyclic aromatic hydrocarbons (PAH) concentration in the biochar was evaluated. Biochar-induced toxicity was assessed using an in-house plant growth assay with Arabidopsis thaliana. This study shows that PTE concentrations can be controlled through co-pyrolysis. More than 50 wt% of tree bark must be added to chicken manure to reduce the concentrations below the European Biochar Certificate-AGRO (EBC-AGRO) threshold. However, the amount of PAH does not show a trend with tree bark addition. Furthermore, co-pyrolysis biochar promotes plant growth at different application concentrations, whereas pure application of 100 wt% tree bark or chicken manure biochar results in decreased growth compared to the reference. In addition, increased plant stress was observed for 100 wt% chicken manure biochar. These data indicate that co-pyrolysis of chicken manure and tree bark produces EBC-AGRO-compliant biochar with the potential to stimulate plant growth. Further studies need to assess the effect of these biochars in long-term growth experiments.

A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus. Firstly, assignments of viruses should be congruent with the best attainable reconstruction of their evolutionary histories, i.e., taxa should be monophyletic. This fundamental principle for classification of viruses is currently included in the International Committee on Taxonomy of Viruses (ICTV) code only for the rank of species. Secondly, phenotypic and ecological properties of viruses may inform, but not override, evolutionary relatedness in the placement of ranks. Thirdly, alternative classifications that consider phenotypic attributes, such as being vector-borne (e.g., "arboviruses"), infecting a certain type of host (e.g., "mycoviruses," "bacteriophages") or displaying specific pathogenicity (e.g., "human immunodeficiency viruses"), may serve important clinical and regulatory purposes but often create polyphyletic categories that do not reflect evolutionary relationships. Nevertheless, such classifications ought to be maintained if they serve the needs of specific communities or play a practical clinical or regulatory role. However, they should not be considered or called taxonomies. Finally, while an evolution-based framework enables viruses discovered by metagenomics to be incorporated into the ICTV taxonomy, there are essential requirements for quality control of the sequence data used for these assignments. Combined, these four principles will enable future development and expansion of virus taxonomy as the true evolutionary diversity of viruses becomes apparent.

To reach the estimated food demands for 2050 in decreasingly suiting climates, current agricultural techniques have to be complemented by sustainably intensified practices. The current study repurposed wheat crop residues into biochar, and investigated its potential in different plant cultivation systems, including a hydroponic cultivation of wheat. Biochars resulting from varying pyrolysis parameters including feedstock composition (straw and chaff) and temperature (450°C and 600°C), were tested using a fast plant screening method. Biochar WBC450, produced from a combination of chaff and straw at 450°C, was selected for further plant experiments, and used in a static leaching experiment in the Arabidopsis thaliana cultivation medium. Increased pH and EC were observed, together with an increase of most macronutrient (K, Mg, P, S) and a decrease of most micronutrient (Fe, Mn, Zn) concentrations. Considering plant growth, application of biochar resulted in concentration-dependent effects in both tested plant species (A. thaliana and wheat). It improved the vegetative yield across all tested cultivation systems. Increases in K and S, and concentration-dependent decreases in Fe and Na content in wheatgrass were observed. Biochar influenced the reproduction of hydroponically cultivated wheat by increasing the number of spikes and the number of seeds per spike. The antioxidative capacity of wheat grass, and the seed sugar and starch contents remained unaffected by biochar application. This study contributes to innovation in soilless cultivation approaches of staple crops, within the framework of closing waste loops for a circular bioeconomy.

Abstract Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142− /low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142− /low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.

Although total neoadjuvant therapy (TNT) is a new standard of care for locally advanced rectal cancer (LARC), there are no data to confirm the safety and efficacy of this approach in older patients. SHAPERS is a multicentre, open-label, randomised pragmatic trial, aiming to assess whether neoadjuvant short-course radiotherapy (SCRT) is a better trade-off between safety and efficacy than TNT in LARC patients aged ≥70 years. Eligible patients are randomised in a 1 : 1 ratio to SCRT followed by surgery [or watch & wait (w&w)] ± adjuvant chemotherapy or TNT (either SCRT followed by 12-18 weeks of chemotherapy, or long-course chemoradiotherapy followed or preceded by 16 weeks of chemotherapy, based on the investigator’s choice) followed by surgery (or w&w). The primary endpoint is the net treatment benefit, a multicomponent measure of treatment effect based on generalised pairwise comparisons, and defined by four prioritised outcome measures: (i) overall survival at 3 years; (ii) progression-free survival at 3 years; (iii) increased-grade peripheral sensory neuropathy at 3 years; (iv) grade ≥3 toxicities during treatment. The study sample size includes 230 eligible patients, to be recruited at 15-20 centres in Belgium. The trial is registered with ClinicalTrials.gov (NCT06052332).

ABSTRACT A collection of 161 Ralstonia isolates, including 90 isolates from persons with cystic fibrosis, 27 isolates from other human clinical samples, 8 isolates from the hospital environment, 7 isolates from industrial samples, and 19 environmental isolates, was subjected to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) identification and yielded confident species level identification scores for only 62 (39%) of the isolates, including four that proved misidentified subsequently. Whole-genome sequence analysis of 32 representative isolates for which no confident MALDI-TOF MS species level identification was obtained revealed the presence of seven novel Ralstonia species, including three and four that were isolated from cystic fibrosis or other human clinical samples, respectively, and provided the basis for updating an in-house MALDI-TOF MS database. A reanalysis of all mass spectra with the updated MALDI-TOF MS database increased the percentage of isolates with confident species level identification up to 77%. The antimicrobial susceptibility of 30 isolates mainly representing novel human clinical and environmental Ralstonia species was tested toward 17 antimicrobial agents and demonstrated that the novel Ralstonia species were generally multi-resistant, yet susceptible to trimethoprim/sulfamethoxazole, ciprofloxacin, and tigecycline. An analysis of genomic antimicrobial resistance genes in 32 novel and publicly available genome sequences revealed broadly distributed beta-lactam resistance determinants.IMPORTANCEThe present study demonstrated that a commercial matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification database can be tailored to improve the identification of Ralstonia species. It also revealed the presence of seven novel Ralstonia species, including three and four that were isolated from cystic fibrosis or other human clinical samples, respectively. An analysis of minimum inhibitory concentration values demonstrated that the novel Ralstonia species were generally multi-resistant but susceptible to trimethoprim/sulfamethoxazole, ciprofloxacin, and tigecycline.

Microalgae have rigid, complex cell walls hindering direct lipid extraction. Cell disruption techniques are used to rupture these cellular structures to increase lipid extraction. Researchers investigating the downstream processing of microalgae do not always have access to microalgal cultivation systems to generate large amounts of fresh microalgal biomass. Using resuspended freeze-dried microalgal biomass as a model laboratory system for concentrated fresh biomass during cell disruption experiments offers greater flexibility in experimental planning and omits investment costs of microalgal cultivation equipment. So far, it however remains unclear whether freeze-dried resuspended biomass can be used as a model laboratory system to represent concentrated fresh biomass during cell disruption and lipid extraction experiments. This paper thus evaluated the suitability of resuspended freeze-dried Nannochloropsis as a model laboratory system for concentrated fresh Nannochloropsis during cell disruption. Ultrasound assisted cell disruption was used as example cell disruption technique and lipid extraction efficiency and free fatty acid content were investigated. Tap water and 3% sodium chloride are both suitable resuspension media for the resuspension of freeze-dried Nannochloropsis. Resuspension duration should be limited (< 120 min) to prevent the formation of free fatty acids. The condition of the biomass (concentrated fresh, or resuspended freeze-dried) prior to ultrasound assisted cell disruption did not influence the resulting lipid extraction efficiency. Resuspended freeze-dried Nannochloropsis biomass in tap water or 3% sodium chloride can thus be used as a model laboratory system for fresh microalgal biomass during research on ultrasound assisted lipid extraction. The generalization of the results to other cultivation conditions, cell disruption techniques, components of interest or microalgal species should be carefully assessed.

Summary: The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.

Summary: Lymphatic endothelial cells (LECs) of the lymph node (LN) parenchyma orchestrate leukocyte trafficking and peripheral T cell dynamics. T cell responses to immunotherapy largely rely on peripheral T cell recruitment in tumors. Yet, a systematic and molecular understanding of how LECs within the LNs control T cell dynamics under steady-state and tumor-bearing conditions is lacking. Intravital imaging combined with immune phenotyping shows that LEC-specific deletion of the essential autophagy gene Atg5 alters intranodal positioning of lymphocytes and accrues their persistence in the LNs by increasing the availability of the main egress signal sphingosine-1-phosphate. Single-cell RNA sequencing of tumor-draining LNs shows that loss of ATG5 remodels niche-specific LEC phenotypes involved in molecular pathways regulating lymphocyte trafficking and LEC-T cell interactions. Functionally, loss of LEC autophagy prevents recruitment of tumor-infiltrating T and natural killer cells and abrogates response to immunotherapy. Thus, an LEC-autophagy program boosts immune-checkpoint responses by guiding systemic T cell dynamics.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In line with these inherent aggressive characteristics, only a subset of patients shows a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel (N = 8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine.

Abstract Despite major improvements in immunotherapeutic strategies, the immunosuppressive tumor microenvironment remains a major obstacle for the induction of efficient antitumor responses. In this study, we show that local delivery of a bispecific Clec9A-PD-L1 targeted type I interferon (AcTaferon, AFN) overcomes this hurdle by reshaping the tumor immune landscape. Treatment with the bispecific AFN resulted in the presence of pro-immunogenic tumor-associated macrophages and neutrophils, increased motility and maturation profile of cDC1 and presence of inflammatory cDC2. Moreover, we report empowered diversity in the CD8+ T cell repertoire and induction of a shift from naive, dysfunctional CD8+ T cells towards effector, plastic cytotoxic T lymphocytes together with increased presence of NK and NKT cells as well as decreased regulatory T cell levels. These dynamic changes were associated with potent antitumor activity. Tumor clearance and immunological memory, therapeutic immunity on large established tumors and blunted tumor growth at distant sites were obtained upon co-administration of a non-curative dose of chemotherapy. Overall, this study illuminates further application of type I interferon as a safe and efficient way to reshape the suppressive tumor microenvironment and induce potent antitumor immunity; features which are of major importance in overcoming the development of metastases and tumor cell resistance to immune attack. The strategy described here has potential for application across to a broad range of cancer types.

Abstract To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ( $$\pm$$ ± standard deviation) was 44.0 ( $$\pm$$ ± 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9–10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34–96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area.

Abstract Background In the recent past, wearable devices have been used for gait rehabilitation in patients with Parkinson’s disease. The objective of this paper is to analyze the outcome of a wearable hip orthosis whose assistance adapts in real time to the patient’s gait kinematics via adaptive oscillators. In particular, this study focuses on a metric characterizing natural gait variability, i.e., the level of long-range autocorrelations (LRA) in series of stride durations. Methods Eight patients with Parkinson’s disease (Hoehn and Yahr stages 1 $$-$$ - 2.5) performed overground gait training three times per week for four consecutive weeks, assisted by a wearable hip orthosis. Gait was assessed based on performance metrics such as the hip range of motion, speed, stride length and duration, and the level of LRA in inter-stride time series assessed using the Adaptive Fractal Analysis. These metrics were measured before, directly after, and 1 month after training. Results After training, patients increased their hip range of motion, their gait speed and stride length, and decreased their stride duration. These improvements were maintained 1 month after training. Regarding long-range autocorrelations, the population’s behavior was standardized towards a metric closer to the one of healthy individuals after training, but with no retention after 1 month. Conclusion This study showed that an overground gait training with adaptive robotic assistance has the potential to improve key gait metrics that are typically affected by Parkinson’s disease and that lead to higher prevalence of fall. Trial registration: ClinicalTrials.gov Identifer NCT04314973. Registered on 11 April 2020.

Abstract Background Subjective perception of coercion has gained attention as an important outcome. However, little is known about its relation to patients’ appraisal of the justification of coercive measures. The present study aims to analyze the relationship between patients’ appraisal of the justification of coercive measures and their level of perceived coercion. Methods This study presents a secondary analysis of the results of a multi-center RCT conducted to evaluate the effects of post-coercion review. Patients who experienced at least one coercive measure during their hospital stay were included in the trial. Participants’ appraisal of the justification of coercive measures was categorized into patient-related and staff-related justifications. Subjective coercion was assessed using the Coercion Experience Scale (CES) and used as dependent variable in a multivariate regression model. Results 97 participants who completed the CES were included in the analysis. CES scores were significantly associated with the perception of the coercive measure as justified by staff-related factors (B = 0,540, p

Abstract Background For patients with pancreatic ductal adenocarcinoma (PDAC), surgical resection remains the only potentially curative treatment. Surgery is generally followed by postoperative chemotherapy associated with improved survival, yet neoadjuvant therapy is a rapidly emerging concept requiring to be explored and validated in terms of treatment options and oncological outcomes. In this context, stereotactic body radiation (SBRT) appears feasible and can be safely integrated into a neoadjuvant chemotherapy regimen of modified FOLFIRINOX (mFFX) with promising benefits in terms of R0 resection, local control and survival. However, the optimal therapeutic sequence is still not known, especially for borderline resectable PDAC, and the role of adding SBRT to chemotherapy in the neoadjuvant setting needs to be evaluated in randomised controlled trials. The aim of the STEREOPAC trial is to assess the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX or Gemcitabine/Nab-Paclitaxel (Gem/Nab-P) in patients with borderline resectable PDAC. Methods This is a randomised comparative multicentre phase II trial, planning to enrol patients (n = 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of Gem/Nab-P). After full disease restaging, non-progressive patients will be randomised for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55 Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient’s condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure / distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment. Discussion This trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients’ oncological outcomes. Trial registration The study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022.

Rhodococcus equi is a rare human opportunistic pathogen that has been increasingly reported in recent decades. It mainly affects immunosuppressed patients, and in particular human immunodeficiency virus (HIV)–infected patients, where it typically presents as cavitary pneumonia. Early treatment with combined and effective antimicrobials and antiretroviral therapy after prompt diagnosis is essential to ensure an optimal outcome. We present a case series of three human Rhodococcus equi infections in HIV-infected patients with advanced immune suppression, treated at the University Hospital of Antwerp, Belgium.

Abstract Background Fluorine-18-labeled SSAs have the potential to become the next-generation tracer in SSTR-imaging in neuroendocrine tumor (NET) patients given their logistical advantages over the current gold standard gallium-68-labeled SSAs. In particular, [18F]AlF-OC has already shown excellent clinical performance. We demonstrated in our previous report from our prospective multicenter trial that [18F]AlF-OC PET/CT outperforms [68Ga]Ga-DOTA-SSA, but histological confirmation was lacking due to ethical and practical reasons. In this second arm, we therefore aimed to provide evidence that the vast majority of [18F]AlF-OC PET lesions are in fact true NET lesions by analyzing their MR characteristics on simultaneously acquired MRI. We had a special interest in lesions solely detected by [18F]AlF-OC (“incremental lesions”). Methods Ten patients with a histologically confirmed neuroendocrine tumor (NET) and a standard-of-care [68Ga]Ga-DOTATATE PET/CT, performed within 3 months, were prospectively included. Patients underwent a whole-body PET/MRI (TOF, 3 T, GE Signa), 2 hours after IV injection of 4 MBq/kg [18F]AlF-OC. Positive PET lesions were evaluated for a corresponding lesion on MRI. The diagnostic performance of both PET tracers was evaluated by determining the detection ratio (DR) for each scan and the differential detection ratio (DDR) per patient. Results In total, 195 unique lesions were detected: 167 with [68Ga]Ga-DOTATATE and 193 with [18F]AlF-OC. The DR for [18F]AlF-OC was 99.1% versus 91.4% for [68Ga]Ga-DOTATATE, significant for non-inferiority testing (p = 0.0001). Out of these 193 [18F]AlF-OC lesions, 96.2% were confirmed by MRI to be NET lesions. Thirty-three incremental lesions were identified by [18F]AlF-OC, of which 91% were confirmed by MRI and considered true positives. Conclusion The DR of [18F]AlF-OC was numerically higher and non-inferior to the DR of [68Ga]Ga-DOTATATE. [18F]AlF-OC lesions and especially incremental lesions were confirmed as true positives by MRI in more than 90% of lesions. Taken together, these data further validate [18F]AlF-OC as a new alternative for SSTR PET in clinical practice. Trial registration ClinicalTrials.gov: NCT04552847. Registered 17 September 2020, https://beta.clinicaltrials.gov/study/NCT04552847

Abstract Background To understand mechanisms of adaptation and plasticity of pollinators and other insects a better understanding of diversity and function of their key symbionts is required. Commensalibacter is a genus of acetic acid bacterial symbionts in the gut of honey bees and other insect species, yet little information is available on the diversity and function of Commensalibacter bacteria. In the present study, whole-genome sequences of 12 Commensalibacter isolates from bumble bees, butterflies, Asian hornets and rowan berries were determined, and publicly available genome assemblies of 14 Commensalibacter strains were used in a phylogenomic and comparative genomic analysis. Results The phylogenomic analysis revealed that the 26 Commensalibacter isolates represented four species, i.e. Commensalibacter intestini and three novel species for which we propose the names Commensalibacter melissae sp. nov., Commensalibacter communis sp. nov. and Commensalibacter papalotli sp. nov. Comparative genomic analysis revealed that the four Commensalibacter species had similar genetic pathways for central metabolism characterized by a complete tricarboxylic acid cycle and pentose phosphate pathway, but their genomes differed in size, G + C content, amino acid metabolism and carbohydrate-utilizing enzymes. The reduced genome size, the large number of species-specific gene clusters, and the small number of gene clusters shared between C. melissae and other Commensalibacter species suggested a unique evolutionary process in C. melissae, the Western honey bee symbiont. Conclusion The genus Commensalibacter is a widely distributed insect symbiont that consists of multiple species, each contributing in a species specific manner to the physiology of the holobiont host.

In this study, we present a new type of polymer-free hydrogel made only from nonionic surfactants, oil, and water. Such a system is produced by taking advantage of the physicochemical behavior and interactions between nonionic surfactants and oil and water phases, according to a process close to spontaneous emulsification used in the production of nano-emulsions. Contrary to the classical process of emulsion-based gel formulation, we propose a simple one-step approach. Beyond the originality of the concept, these nanoemulgels appear as very promising systems able to encapsulate and deliver various molecules with different solubilities. In the first section, we propose a comprehensive investigation of the gel formation process and its limits through oscillatory rheological characterization, characterization of the sol/gel transitions, and gel strength. The second section is focused on the follow-up of the release of an encapsulated model hydrophilic molecule and on the impact of the rheological gel properties on the release profiles.

Aligned with the EU Sustainable Development Goals 2030 (EU SDG2030), extensive research is dedicated to enhancing the sustainable use of biomass waste for the extraction of pharmaceutical and nutritional compounds, such as (poly-)phenolic compounds (PC). This study proposes an innovative one-step hydrothermal extraction (HTE) at a high temperature (120 °C), utilizing environmentally friendly acidic natural deep eutectic solvents (NADESs) to replace conventional harmful pre-treatment chemicals and organic solvents. Brewer’s spent grain (BSG) and novel malt dust (MD) biomass sources, both obtained from beer production, were characterized and studied for their potential as PC sources. HTE, paired with mild acidic malic acid/choline chloride (MA) NADES, was compared against conventional (heated and stirred maceration) and modern (microwave-assisted extraction; MAE) state-of-the-art extraction methods. The quantification of key PC in BSG and MD using liquid chromatography (HPLC) indicated that the combination of elevated temperatures and acidic NADES could provide significant improvements in PC extraction yields ranging from 251% (MD-MAC-MA: 29.3 µg/g; MD-HTE-MA: 103 µg/g) to 381% (BSG-MAC-MA: 78 µg/g; BSG-HTE-MA: 375 µg/g). The superior extraction capacity of MA NADES over non-acidic NADES (glycerol/choline chloride) and a traditional organic solvent mixture (acetone/H2O) could be attributed to in situ acid-catalysed pre-treatment facilitating the release of bound PC from lignin–hemicellulose structures. Qualitative 13C-NMR and pyro-GC-MS analysis was used to verify lignin–hemicellulose breakdown during extraction and the impact of high-temperature MA NADES extraction on the lignin–hemicellulose structure. This in situ acid NADES-catalysed high-temperature pre-treatment during PC extraction offers a potential green pre-treatment for use in cascade valorisation strategies (e.g., lignin valorisation), enabling more intensive usage of available biomass waste stream resources.

We elucidated the effect of four known T1D-susceptibility associated single nucleotide polymorphism (SNP) markers in three genes (rs12722495 and rs2104286 in IL2RA, rs689 in INS and rs2476601 in PTPN22) on CpG site methylation of their proximal promoters in different lymphocyte subsets using pyrosequencing. The study cohort comprised 25 children with newly diagnosed T1D and 25 matched healthy controls. The rs689 SNP was associated with methylation at four CpG sites in INS promoter: −234, −206, −102 and −69. At all four CpG sites, the susceptibility genotype AA was associated with a higher methylation level compared to the other genotypes. We also found an association between rs12722495 and methylation at CpG sites −373 and −356 in IL2RA promoter in B cells, where the risk genotype AA was associated with lower methylation level compared to the AG genotype. The other SNPs analyzed did not demonstrate significant associations with CpG site methylation in the examined genes. Additionally, we compared the methylation between children with T1D and controls, and found statistically significant methylation differences at CpG −135 in INS in CD8+ T cells (p = 0.034), where T1D patients had a slightly higher methylation compared to controls (87.3 ± 7.2 vs. 78.8 ± 8.9). At the other CpG sites analyzed, the methylation was similar. Our results not only confirm the association between INS methylation and rs689 discovered in earlier studies but also report this association in sorted immune cells. We also report an association between rs12722495 and IL2RA promoter methylation in B cells. These results suggest that at least part of the genetic effect of rs689 and rs12722495 on T1D pathogenesis may be conveyed by DNA methylation.

Abstract Particulate nitrate is a major component of fine particulate matter (PM2.5). Its formation may be varyingly sensitive to emissions of ammonia (NH3), nitrogen oxides (NOx ≡ NO + NO2), and volatile organic compounds (VOCs), depending on local conditions. Diagnosing these sensitivities is critical for successful air quality management. Here, we show that satellite measurements of tropospheric NH3 and NO2 columns can be used as a quick indicator of the dominant sensitivity regime through the NH3/NO2 column ratio together with the NO2 column. We demonstrate the effectiveness of this indicator with the GEOS‐Chem chemical transport model and define thresholds to separate the different sensitivity regimes. Applying the method to wintertime IASI and OMI observations in East Asia reveals that surface nitrate is dominantly VOC‐sensitive in the southern North China Plain (NCP), NOx‐sensitive in most of the East China Plain, and NH3‐sensitive in the northern NCP, southern China, and Korea.

Introduction : Ces dernières années, le développement de biomatériaux à faible impact environnemental a attiré un intérêt croissant. Dans ce contexte, les nanoparticules lipidiques ont émergé comme une solution privilégiée dans la recherche et l'industrie. L'objectif de cette étude était de mettre au point des émulsions Pickering O/W stabilisées exclusivement par des nanoparticules lipidiques solides (SLNs). Ces émulsions de Pickering sont une nouvelle génération de transporteurs lipidiques, à la fois sûrs, non toxiques, biocompatibles et sensibles à la température. Matériel et Méthodes : La première partie de l'étude se concentre sur la compréhension du comportement interfacial des SLNs et les mécanismes de stabilisation associés aux nanoémulsions formulées par ultrasons. Les recherches ont exploré la couverture de surface en fonction des fractions volumiques des phases dispersées et de la taille des SLNs. La deuxième partie de l'étude aborde l'adsorption des SLNs à une interface modèle entre l'huile et l'eau, en évaluant la tension superficielle et la rhéologie. Cela a été réalisé au moyen d'une analyse de la forme d'une goutte axi-symétrique (à l'aide d'un tensiomètre de goutte), en suivant l'évolution de la tension interfaciale et du comportement rhéologique. Résultats : Ces expériences ont démontré de manière concluante que la stabilisation des nanogouttelettes est effectivement assurée par les nanoparticules, tout en mettant en lumière les limites de cette formulation. La caractérisation des dimensions et de la morphologie des émulsions a permis de confirmer nos hypothèses. Par ailleurs, nous avons procédé à la caractérisation du phénomène régissant les interactions entre les nanogouttelettes et l'interface, tout en décrivant le comportement rhéologique de la monocouche de SLNs à l'interface. Conclusion : En conclusion, les émulsions de Pickering stabilisées par les SLNs se révèlent être des nano-transporteurs de médicaments innovants et très efficaces. Elles ouvrent ainsi de nouvelles perspectives en tant que système de délivrance de médicaments sensible à la température.

Introduction : Le but de l’étude était de développer des hydrogels oraux à base de chitosane pH- sensibles, capables de libérer le phénobarbital dans l'intestin grêle du nouveau-né. Ces hydrogels amélioreraient sa biodisponibilité et son efficacité thérapeutique. Matériel et méthodes : La formulation des hydrogels a été effectuée à 37±1°C via la transition sol-gel en utilisant la méthode du tube inversé. Les hydrogels contenaient 2,45 et 2,55% de chitosane, du phénobarbital avec/sans EudragitE100. Au cours de ces expériences, nous avons étudié les énergies d’interactions mises en jeu entre les chaînes de chitosane elles-mêmes, et le chitosane avec les molécules présentes, responsables de la formation des hydrogels. Une caractérisation morphologique des hydrogels par microscopie électronique à balayage a été réalisée pour déterminer leur structure. Des études du mécanisme de libération du phénobarbital à partir d'hydrogels introduits dans des milieux mimant les valeurs de pH du tractus gastro-intestinal du nouveau-né ont été réalisées. Le dosage de la quantité de phénobarbital libérée en fonction du temps a été effectué par spectrophotométrie. Résultats : Les résultats ont montré que le temps de transition sol-gel diminuait lorsque la concentration en chitosane augmentait. La structure des hydrogels était hétérogène. La quantité de phénobarbital libérée était plus importante au pH mimant l’intestin grêle pour les hydrogels contenant 2,45% de chitosane et de l’eudragitE100. Le modèle Korsmeyer-Peppas a été utilisé pour ajuster les profils de libération du phénobarbital. Conclusion : Les hydrogels formulés ont libéré plus le phénobarbital dans le milieu mimant le pH de l’intestin grêle du nouveau-né selon une libération pulsatil