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Animals protect themself from microbial attacks by robust skins or a cuticle as in Caenorhabditis elegans. Nematode-trapping fungi, like Arthrobotrys flagrans, overcome the cuticle barrier and colonize the nematode body. While lytic enzymes are important for infection, small-secreted proteins (SSPs) without enzymatic activity, emerge as crucial virulence factors. Here, we characterized NipA (nematode induced protein) which A. flagrans secretes at the penetration site. In the absence of NipA, A. flagrans required more time to penetrate C. elegans. Heterologous expression of the fungal protein in the epidermis of C. elegans led to blister formation. NipA contains 13 cysteines, 12 of which are likely to form disulfide bridges, and the remaining cysteine was crucial for blister formation. We hypothesize that NipA interferes with cuticle integrity to facilitate fungal entry. Genome-wide expression analyses of C. elegans expressing NipA revealed mis-regulation of genes associated with extracellular matrix (ECM) maintenance and innate immunity., (© 2024. The Author(s).)

Strain ZW T0_25 T was isolated from an onion sample (Allium cepa var. Hytech F1) within a storage trial and proofed to be a novel, aerobic, Gram-stain negative, rod-shaped bacterial strain. Analyses of the 16S rRNA gene sequence and of the whole draft genome sequences, i.e., digital DNA-DNA hybridization (dDDH), Average Nucleotide Identity (ANI) and Average Amino Acid Identity (AAI) showed that this strain represents a new species of the genus Bosea. The genome size of strain ZW T0_25 T is 6.19 Mbp, and the GC content is 66.9%. As whole cell sugars, rhamnose, ribose and glucose were identified. Ubiquinone Q-10 is the major respiratory quinone with 97.8%. Polar lipids in strain ZW T0_25 T are composed of one phosphatidylethanolamine, one phosphatidylglycerol, one aminophospholipid, two aminolipids, one glycolipid and two phospholipids whereas the fatty acid profile predominantly consists of C18:1 w7c (63.3%), C16:1 w7c (19.5%) and C16:0 (7.1%). Phenotypic traits were tested in the wet lab as well as predicted in silico from genome data. Therefore, according to this polyphasic approach, the new name Bosea rubneri sp. nov. with the type strain ZW T0_25 T (= DSM 116094  T  = LMG 33093  T ) is proposed., (© 2024. The Author(s).)

Background: Thromboembolic complications are well known in the treatment of childhood acute lymphoblastic leukemia. Over the years it has not been possible to reach a consensus on a possible prophylaxis of thromboembolic events during intensive therapy. Only the administration of enoxaparin was able to achieve evidence in the literature to date., Methods: In this retrospective study, 173 childhood leukemia patients were treated over 20 years with a thromboembolic prophylaxis including enoxaparin and AT III during induction therapy with L-asparaginase and cortisone., Results: We here report the effectiveness of administration of enoxaparin and AT III in childhood leukemia, showing a strikingly low prevalence of deep vein thrombosis (2.9%). Especially in adolescent patients, a particularly great need for AT III was demonstrated., Conclusions: We recommend thromboembolic prophylaxis with enoxaparin and AT III substitution during induction/reinduction therapy with L-asparaginase and glucocorticosteroids, especially from adolescence onwards., (© 2024. The Author(s).)

Patients' reports of their health status are increasingly used in hematopoietic stem cell transplantation (SCT) to better understand the negative impact on symptom burden and quality of life. Little is known regarding the implementation in routine clinical care, particularly how it can be used to improve supportive care. We sought to the evaluate feasibility of capturing daily patient-reported outcomes (PROs) in the acute phase of SCT to measure physical and psychosocial symptom burden. In this single-center prospective observational study, we assessed daily PRO from conditioning to neutrophil engraftment in children (age 1 to 18 year) who underwent allogeneic or autologous SCT for malignant and nonmalignant disease. The most common acute adverse effects of chemotherapy (pain, nausea, loss of appetite, sleep disturbance, and physical performance impairment) were reported daily via ePROtect, a web-based program designed to integrate health responses. From February 2021 to March 2023, 20 children undergoing allogeneic (allo-) SCT (n = 11) or autologous (auto-) SCT (n = 9) and their proxies consented to participation, all of whom were included in this analysis. A total of 359 PRO questionnaires were completed, corresponding to a median daily completion rate of 72.7% (interquartile range, 60.4% to 83.6%). After conditioning, pain perception anticipated the rise of infectious parameters and the development of mucositis, thus initiating supportive treatment. Patients reported the strongest symptom burden at a median of 8.5 days post-transplantation. At 4 weeks post-transplantation, baseline values were restored for all symptoms. There were no significant differences between auto-SCT and allo-SCT, except for nausea and loss of appetite after administration of antithymocyte globulin in allo-SCT. This study empirically documents the daily health status of children undergoing SCT and proposes an attractive modus operandi on how continuous feedback on health-related symptoms can be integrated into daily clinical practice., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: As one of the few modifiable risk factors, the importance of dietary patterns for both disease prevention and treatment outcome in pediatric oncology has gained increasing popularity. Malnutrition is associated with lower survival rates, tolerance to treatment, and quality of life. Yet, especially in children with malignancies, nutritional deterioration is common, and pediatric cancer patients often present with inadequate intake of micro- and macronutrients alike. Despite the reported widespread use of dietary supplements, few empirical data provide a basis for clinical recommendations, and evidence for their efficacy is inconsistent. Current literature lacks a systematic approach as to how and which supplements should be recommended for specific patients, types of cancer, or during specific treatments. The aim of this review is to highlight the role of the most frequently used nutrients in pediatric malignant diseases and to give a practical guide based on current scientific evidence., Methods: A comprehensive literature search was conducted on PubMed through April 2023 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) of macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: "childhood cancer", "pediatric oncology", "nutritional status", "dietary supplements", "vitamins", "micronutrients", "calcium", "magnesium", "vitamin D", "zinc" "glutamine", "selen", and "omega-3 fatty acids". The reference lists of all relevant articles were screened to include potentially pertinent studies., Results: The present review provides a comprehensive and updated overview of the latest evidence about the role of nutrition and diet in pediatric oncology, also focusing on different nutritional interventions available for the management of the disease. We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of several micronutrients and critically interpret the findings. Possible effects and benefits of supplementation during chemotherapy are discussed, as are strategies for primary and secondary prevention., Conclusions: We here describe the obvious benefits of dietary supplementation for childhood cancer. Further large-scale clinical trials are required to verify the impacts of deficiencies and the possible benefits of supplementation and optimal dosages. (337 words).

We conducted a retrospective analysis to determine the potential reduction in treatment burden through the expansion of virtual care among children with leukemia (n = 152). Patients living in urban areas traveled median distances of 1555 km compared with 7536 km for patients living in rural areas (p < .05). For the latter group, a median reduction in travel distance of 3560 km (interquartile range [IQR], 2136-5787 km), travel time of 51 h (IQR, 26-78 h), and CO 2 emissions of 623 kg (IQR, 374-1013 kg) was estimated, if every second visit was replaced by video consultations., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Powdery Mildew of Grapevine belongs to the major diseases in viticulture and requires intensive use of fungicides. Genetic introgression of resistance factors from wild grapes from North America and, recently, China, has been successful, but wine made from those varieties is still confronted with low consumer acceptance, due to differences in taste., Results: The current work explores the potential of Vitis vinifera sylvestris, the wild ancestor of domesticated Grapevine, with respect to containing Erysiphe necator, the causative agent of Powdery Mildew. Making use of a germplasm collection comprising the entire genetic variability remaining in Germany, we show that there is considerable genetic variation in the formation of leaf surface waxes exceeding wax formation in commercial varieties., Conclusions: High wax formation correlates with reduced susceptibility to controlled infection with E. necator linked with perturbations of appressoria formation. We propose V. vinifera sylvestris as novel source for resistance breeding since it is genetically much closer to domesticated grapevine than the hitherto used sources from beyond the species barrier., (© 2023. The Author(s).)

Purpose: Serial assessment of health condition based on self-report made by children and their proxies has consistently shown a lack of congruence. The study explored the discrepancies between mother's, father's, and children's reports on health-related quality of life (HRQOL) during the first two months of pediatric cancer treatment., Methods: In this cohort study, children and parents completed the generic and cancer-specific Pediatric Quality-of-Life Inventory (PedsQL) questionnaires at initial diagnosis and in the subsequent months. Evaluation of discrepancies included intraclass correlations between mother-child and father-child dyads at different domain levels., Results: Thirty-six children with a diagnosis of cancer between May 2020 and November 2021 and their parents were included in this study. At diagnosis, mother-child dyads showed better agreement on more domains of the PedsQL Generic Core Scale than father-child dyads; moderate agreement persisted for both parents at subsequent time points on the physical domain. The disease-specific PedsQL Cancer Module revealed moderate and better agreement for mother-child dyads during active cancer therapy. In particular, agreement of mother-child dyads was pronounced for domains such as worry (0.77 [95% CI 0.52-0.89, P < 0.001]), whereas fathers tended to overestimate the child's symptom burden for most of the remaining domains of the PedsQL Cancer Module., Conclusion: This cohort study shows that both parent proxy reports can provide valid information on child's HRQOL, but that fathers tend to overestimate, particularly for non-observable domains. Proxy reports derived from mothers more closely agreed with children's HRQOL and might be more weighted, if there is uncertainty between parents., (© 2023. The Author(s).)

The novel, aerobic, Gram-stain-positive, rod-shaped bacterial strain, ZW T2&#95;19 T , was isolated from an onion sample ( Allium cepa var. Rijnsburger). Analyses of the 16S rRNA gene sequence revealed that ZW T2&#95;19 T represented a member of the genus Rathayibacter but may represent a novel species of this genus. Analyses of the whole draft genome sequences, i.e. digital DNA-DNA hybridisation (dDDH) and average nucleotide identity (ANI) of ZW T2&#95;19 T and all type strains of species of the genus Rathayibacter confirmed that ZW T2&#95;19 T represents a novel species of the genus Rathayibacter . The genome size of ZW T2&#95;19 T is 4.01 Mbp and the DNA G+C content is 71.8 mol%. Glucose, mannose, rhamnose and ribose were detected as whole-cell sugars of ZW T2&#95;19 T . The major respiratory quinone of ZW T2&#95;19 T is menaquinone MK-10, at 78.9 %. The detected peptidoglycan type in ZW T2&#95;19 T is a variant of type B2γ with {Gly} [l-diaminobutyric acid (l-DAB)/l-homoserine (l-Hse)] d-Glu-l-DAB. Polar lipids in ZW T2&#95;19 T consisted of one diphosphatidylglycerol, one phosphatidylglycerol, seven glycolipids, one phospholipid and one lipid. The fatty acid profile of ZW T2&#95;19 T predominantly consisted of anteiso-C 15 : 0 (53 %), iso-C 16 : 0 (21 %) and anteiso-C 17 : 0 (18 %). In addition, API 20NE, API 50CH, API Coryne, API ZYM, antibiotic susceptibility, haemolysis and growth at different temperatures and with different supplements was investigated. On the basis of the results obtained using this polyphasic approach, including molecular, phenotypic and biochemical analyses, we propose the novel species Rathayibacter rubneri with the type and only strain ZW T2&#95;19 T (= DSM 114294 T = LMG 32700 T ).

Febrile neutropenia secondary to chemotherapy is one of the most critical complications in cancer treatment. The aim of this study was to determine if an increase in the percentage of immature platelet fraction (IPF%) might predict early neutrophil recovery following cytostatic-dependent aplasia. A retrospective cohort study compared serial complete blood counts and the level of C-reactive protein (CRP) following induction chemotherapy for Ewing sarcoma and Non-Ewing sarcoma patients. The measurements were taken on a Sysmex XE-2100 instrument. A total of 287 paired samples from 28 children after the first cycle of chemotherapy were analyzed to test if an increase in the IPF% anticipated the CRP peak and recovery of neutrophil count. The chemotherapy associated nadir of neutrophils, reticulocytes and platelets was reached at 9.7 ± 1.5, 11.0 ± 1.7 and 11.9 ± 0.9 days (mean ± SD) respectively, in Ewing sarcoma patients. Still in severe neutropenia, IPF% was the first parameter that significantly increased and anticipated the CRP peak (11.9 ± 1.6 days, mean ± SD). The IPF% continuously increased (maximum = 6.56% ± 2.8%, mean ± SD) and peaked at 12.2 ± 1.4 days (mean ± SD) after commencement of chemotherapy. Compared to neutrophil recovery (14.6 ± 1.4 days, mean ± SD), the IPF% peak was anticipated by 2.4 days (p = 0.0085). Although variably treated, in non-Ewing sarcoma patients the effect was similar and the IPF% peak anticipated neutrophil recovery by 6.8 ± 4.7 days (p < 0.01). IPF% increased significantly at > 48 h before neutrophil recovery in patients treated with chemotherapy. IPF% is an inexpensive parameter and may be valuable in the management of febrile neutropenia., (© 2023. The Author(s).)

Infections in hematopoietic stem cell transplant (HSCT) remain one of the major causes for morbidity and mortality, and it is still unclear whether knowledge of microbial colonization is important. In this single-center study, we collected weekly surveillance cultures in pediatric recipients of allogenic HSCT from five different body regions and tested for bacteria and fungi. Between January 2010 and December 2021, we collected 1095 swabs from 57 recipients of allogeneic HSCTs (median age: 7.5 years, IQR 1−3: 2.5−11.9). The incidence of positive microbiological cultures (n = 220; 20.1%) differed according to the anatomic localization (p < 0.001) and was most frequent in the anal region (n = 98), followed by the genital, pharyngeal and nasal regions (n = 55, n = 37 and n = 16, respectively). Gram-positive bacteria (70.4%) were the most commonly isolated organisms, followed by fungi (18.6%), Gram-negative (5.5%), non-fermenting bacteria (1.4%), and other flora (4.1%). No association with increased risk of infection (n = 32) or septicemia (n = 7) was noted. Over time, we did not observe any increase in bacterial resistance. We conclude that there is no benefit to surveillance of microbial colonization by culture-based techniques in pediatric HSCT. Sequencing methods might enhance the detection of pathogens, but its role is still to be defined.

Pearlescent pigments are used as colourants to increase the attractiveness of food products, especially in the patisserie and confectionery sector. They can be seen as composite materials and consist of thin potassium aluminium silicate (E 555, mica) platelets as carrier material, coated with a thin metal oxide layer of TiO 2 (E 171) and/or iron oxides (E 172). The European Food Safety Authority stated in 2020 that mica-based pearlescent pigments as a whole should be evaluated as new food additives. Obtaining dependable data for particle size and layer thickness of these pigments is crucial both for the demanded food additive evaluation itself and also for the nanomaterial labelling assessment of products containing these food colourants according to the 'Food Information to Consumers' regulation. Since it was found in a previous study on TiO 2 -containing pearlescent pigments (silver and golden coloured) that the coating consisted of nanoscaled constituent titanium oxide particles, in this follow-up study we investigated whether Fe 2 O 3 -containing pearlescent pigments exhibit a similar nanostructured morphology. For this purpose, five commercially-available food products containing these pigments were investigated. Static light scattering and flow particle image analysis were used as screening methods to determine the mica platelet size. Scanning electron microscopy combined with energy-dispersive X-ray spectroscopy was used for nanostructure analysis of the metal oxide coating. The carrier mica platelets were 34-96 µm in diameter and 300-800 nm thick. The coating thickness was found to be in the range of 75-105 nm, with the constituent round shaped iron oxide particles contained therein having a minimum Feret diameter of 37-64 nm.

Wax esters are considered to have a dominant contribution in the gelling properties of wax-based oleogels. To understand their gelling behavior, oleogels of seven different wax esters (total carbon number from 30 to 46; c = 10% [ m / m ]) in medium-chain triglycerides oil were characterized. Scanning electron microscopy revealed that wax esters crystallize in rhombic platelets with a thickness of 80 to 115 monomolecular layers. Bright field microscopy showed that the regularity and face length of the crystals increased with the total carbon number and molecular symmetry of the respective wax ester. Oscillatory rheology was used to characterize the gel rigidity (Gmax*). Here, wax ester oleogels with smaller total carbon numbers yielded higher Gmax* values than those of wax esters with higher total carbon numbers. The gel rigidity (Gmax*) inversely correlated with the crystal face length. Smaller and optically less well-defined platelets promoted higher gel rigidities. In the case of the microstructure of a specific oleogel composition being manipulated by a variation in the cooling rates (0.8; 5; 10 K/min), this relationship persisted. The information compiled in this manuscript further elucidates the crystallization behavior of wax esters in oleogels. This contributes to the understanding of the composition-structure-functionality relationship of wax-based oleogels supporting future food applications.

Introduction: Mortality in children with hemato-oncologic disease admitted to a pediatric intensive care unit (PICU) is higher compared to the general population. The reasons for this fact remain unexplored. The aim of this study was to assess outcomes and trends in hemato-oncologic patients admitted to a PICU, with analytical emphasis on emergency admissions., Methods: Patients with a hemato-oncologic diagnosis admitted to a tertiary care university hospital PICU between 1 January 2009 and 31 December 2019 were retrospectively analyzed. Additionally, patient mortality 6 months after PICU admission and follow-up mortality until 31 December 2020 were recorded., Measurements and Main Results: We reviewed a total of 701 PICU admissions of 338 children with hemato-oncologic disease, of which 28.5% were emergency admissions with 200 admissions of 122 patients. Of these, 22 patients died, representing a patient mortality of 18.0% and an admission mortality of 11.0% in this group. Follow-up patient mortality was 25.4% in emergency-admitted children. Multivariable analysis revealed severe neutropenia at admission and invasive mechanical ventilation (IMV) as independent risk factors for PICU death ( p = 0.029 and p = 0.002). The total number of PICU admissions of hemato-oncologic patients rose notably over time, from 44 in 2009 to 125 in 2019., Conclusion: Although a high proportion of emergency PICU admissions of hemato-oncologic patients required intensive organ support, mortality seemed to be lower than previously reported. Moreover, in this study, total PICU admissions of the respective children rose notably over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pechlaner, Kropshofer, Crazzolara, Hetzer, Pechlaner and Cortina.)

Importance: Patient-reported outcome measurements (PROMs) are emerging as an important component of adult cancer care, but little has been done with regard to PROMs for pediatric cancer care., Objectives: To identify pediatric patients with cancer who are at risk of severe adverse effects of treatment and provide individualized supportive care using PROMs., Design, Setting, and Participants: This single-center cohort study with PROMs implemented in daily clinical routine was conducted from May 1, 2020, to November 15, 2021, among pediatric patients with a cancer diagnosis or their proxies. Inclusion criteria were treatment with chemotherapy and at least 30 days of active participation. Patients were followed up until completion of therapy or through ongoing therapy until November 15, 2021; data were analyzed from November 15, 2021, through January 31, 2022., Exposures: Cancer treatment, including chemotherapy, surgery, and radiotherapy., Main Outcomes and Measures: The primary outcome was occurrence and severity of ubiquitous complications of cancer treatment, such as nausea, appetite loss, pain, sleep disturbance, and deterioration of physical functioning. The secondary outcome was the identification of early and appropriate clinical interventions based on detection of cancer-related symptoms via PROMs., Results: A total of 4410 daily PROMs from 7082 therapy days for 40 children (35 children aged 5-18 years and 5 proxies for children aged 1-4 years) (median age, 9.1 [IQR, 6.3-12.2] years; 26 [65.0%] male) were analyzed during a median follow-up of 145.5 (IQR, 103.8-244.5) days. All participants were White. The overall median completion rate was 60.1% (IQR, 37.9%-81.0%); this rate was slightly lower during home care vs inpatient stay (57.5% [IQR, 30.7%-85.9%] vs 65.0% [IQR, 49.6%-92.5%], respectively; P = .01), with a decreasing trend over time (65.6% [IQR, 51.6%-85.9%] for the first 90 days vs 42.9% [IQR, 29.3%-82.3%] for beyond 90 days; P < .001). Severe symptoms were reported on 657 days (14.9%); most symptoms were associated with physical functioning, followed by pain, sleep disturbance, and nausea and appetite loss. In total, 321 adverse events (AEs) and cases of health deterioration were documented, and PROMs were completed for 251 (78.2%) of these events. Across all AEs, self-reported pain was the most useful marker, particularly when analyzed on the day before onset, and was associated with an odds ratio of 3.65 (95% CI, 1.54-8.62; P = .005) for the presence of mucositis., Conclusions and Relevance: The findings of this cohort study suggest that PROMs reflect daily symptoms in pediatric patients with cancer and assist in clinical management and intervention for AEs.

Here we present the description of a novel Pseudomonas species, designated Pseudomonas rustica sp. nov., which was isolated from raw milk samples obtained from Germany. Results of initial 16S rRNA gene sequence analysis assigned the strain into the genus Pseudomonas and showed Pseudomonas helmanticensis , Pseudomonas neuropathica and Pseudomonas atagonensis to be its closest relatives. Further studies including sequence analysis of the rpoB gene, multi-gene phylogenetic tree reconstruction, whole-genome sequence comparisons, cellular fatty acid analysis and chemotaxonomic characterization showed a clear separation from the known Pseudomonas species. Isolate MBT-4 T was closely related to Pseudomonas helmanticensis , 'Pseudomonas crudilactis ' and Pseudomonas neuropathica with average nucleotide identities based on blast values of 88.8, 88.8 and 88.6%, respectively. Therefore, the strain can be classified into the Pseudomonas koreensis subgroup of the Pseudomonas fluorescens group. The G+C content of strain MBT-4 T was 58.9 mol%. The strain was catalase- and oxidase-positive, while the β-galactosidase reaction was negative. Growth occurred between 4 and 30 °C and at pH values from pH 6.0 to 8.0. In conclusion, strain MBT-4 T belongs to a novel species, for which the name Pseudomonas rustica sp. nov. is proposed. The type strain is MBT-4 T (=DSM 112348 T =LMG 32241 T ) and strain MBT-17 is also a representative of this species.

In single particle inductively coupled plasma mass spectrometry (spICP-MS), the transport efficiency is fundamental for the correct determination of both particle number concentration and size. In the present study, transport efficiency was systematically determined on three different days with six carefully characterised gold nanoparticle (AuNP) suspensions and in seven European and US expert laboratories using different ICP-MS instruments and spICP-MS software. Both particle size-(TES)-and particle frequency-(TEF)-methods were applied. The resulting transport efficiencies did not deviate much under ideal conditions. The TEF method however systematically resulted in lower transport efficiencies. The extent of this difference (0-300% rel. difference) depended largely on the choice and storage conditions of the nanoparticle suspensions used for the determination. The TES method is recommended when the principal measurement objective is particle size. If the main aim of the measurement is the determination of the particle number concentration, the TEF approach could be preferred as it might better account for particle losses in the sample introduction system.

Introduction: Gender plays an active role in the incidence and outcome of many infectious and malignant diseases. However, there is still no study examining sex differences for developing bloodstream infections (BSIs) in pediatric patients with cancer. We sought to identify potential gender-specific risk factors for BSIs., Methods: Data were retrospectively analyzed from 621 pediatric patients treated for childhood cancer in a tertiary single center between 1 January 2000 and 31 June 2018. After central venous access device (CVAD) placement, patients were followed up until CVAD was removed or at the most for 1 year. We calculated the gender-specific prevalence for BSIs and compared the causative bacterial strains., Results: Of 621 pediatric patients with cancer (283 girls [45.6%] and 338 boys [54.4%]), 110 patients (41 girls [37.3%] and 69 boys [62.7%]) were identified with a total of 134 BSIs. Girls and boys had a similar incidence for BSI (13%) within the first 3 months of therapy, after which the risk for BSI increased significantly for boys (34% versus 21%, boys versus girls, P = 0.025). Moreover, BSI with gram-positive bacteria affected boys nearly twice as often as girls (29.8% versus 56.5%, girls versus boys)., Conclusions: Future clinical awareness of hygiene-related BSIs in boys could be helpful in identifying areas for improvement., (© 2021. The Author(s).)

Background: Childhood patients have high risks for developing debilitating somatic and mental health side-effects as a consequence of the many different approaches employed in treating their cancer. Early recognition and close monitoring of clinical and psychological problems are essential in planning appropriate interventions and preventing further deterioration., Case: ePROtect was established as an easy-to-use application for daily self-reporting of symptoms during cancer therapy. ePROtect includes six to eight questions pertaining to seven common symptoms: appetite loss, fatigue, nausea, pain, physical functioning, cognitive impairments and sleep quality. The case of a child diagnosed with Burkitt leukemia developing chemotherapy-induced oral mucositis in home care is presented to show the therapeutic impact of early symptom detection with a daily web-based tool., Conclusion: This case highlights how electronic patient-reported outcome measures (PROM) can directly facilitate patient care in real time and might be incorporated in future clinical routine., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Several stakeholders, including patients and health care providers, suggest symptom self-reporting measurements for a more patient-directed cancer control approach. However, services tailored to measure daily reporting and implementing it in clinical care are lacking. This study aimed to evaluate the feasibility and value of daily patient-reported outcome measures (PROMs) by children receiving chemotherapy for cancer., Methods: Health status was recorded daily with a web-based child-friendly patient portal (ePROtect). Following aspects of feasibility and usability were assessed: (a) the completion rate and time, (b) user feedback on usability and satisfaction, and (c) the performed interventions if moderate to severe symptom deterioration was noted., Results: Twelve children (median age: 7.2 years) were included. A total number of 891 daily reports were collected during the study period; the median percentage of ePROtect completion days was 85.3% (interquartile range [IQR] 64.2-100.0) and 55.9% (IQR 51.9-76.9) for inpatient and outpatient stay, respectively. Mean time to complete the questionnaire was 47.6 seconds. Severe symptoms were reported in 14.7% of measurement time points, which led to prompt health care interventions in 57 cases, including extension of supportive care (n = 37) and pre-emptive inpatient admissions (n = 5). Over 80% of the patients (10/12) and their proxies (16/18) provided feedback with high rating for satisfaction (>90%) and usefulness (>80%) of ePROtect., Conclusion: Our study shows that daily symptom monitoring is feasible for all children with newly diagnosed cancer aged 5-18 years. Monitoring offers the opportunity to identify symptoms early and trigger appropriate clinical action., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

The novel, anaerobic, Gram-positive, rod-shaped bacterial strain, ResAG-91 T , was isolated from a faecal sample of a male human volunteer. Analysis of the 16S rRNA gene sequence revealed that strain ResAG-91 T showed high similarity to the type strains of Adlercreutzia equolifaciens subsp. equolifaciens and Adlercreutzia equolifaciens subsp. celatus . Analysis of the whole draft genome sequences, i.e. digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI), of strain ResAG-91 T and the type strains of Adlercreutzia species revealed that strain ResAG-91 T represents a novel species of the genus Adlercreutzia . The genome size of strain ResAG-91 T is 2.8 Mbp and the G+C content is 63.3 mol%. The major respiratory quinone of strain ResAG-91 T was MMK-5 (methylmenaquinone). Major cellular fatty acids were C15 : 0 anteiso, C14 : 0 iso and C14 : 0 2-OH. Galactose and ribose were detected as major whole cell sugars. Furthermore, the peptidoglycan type of strain ResAG-91 T was A1γ with meso-diaminopimelic acid. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid, three unidentified phospholipids and five unidentified glycolipids. Strain ResAG-91 T was able to metabolize the stilbene resveratrol into dihydroresveratrol. On the basis of this polyphasic approach, including phenotypical, molecular (16S rRNA gene and whole genome sequencing) and biochemical (fatty acids, quinones, polar lipids, peptidoglycan, whole cell sugars, Rapid ID32A and API20A) analyses, we propose the novel species Adlercreutzia rubneri sp. nov. with the type and only strain ResAG-91 T (=DSM 111416 T =JCM 34176 T =LMG 31897 T ).

Introduction: Sufficient empirical antimicrobial therapy in febrile patients with cancer is challenging, owing to the limited arsenal of available antibiotics in an era of growing resistance. Because of the emergence of gram-negative bacteria resistant to ceftazidime and piperacillin, a combination antibiotic therapy was employed that uses meropenem combined with gentamicin and/or vancomycin if the patient further deteriorates., Methods: A retrospective cohort analysis was performed including all patients with catheter-associated bloodstream infections (BSIs) and treated for childhood cancer in a tertiary single centre between 1 January 2000 and 31 June 2018. We calculated the prevalence and the risk for BSIs and compared the in vitro susceptibility to various antimicrobial agents., Results: Of 653 patients with childhood cancer, 113 patients (17.3%) were identified with a total of 139 BSIs, most of them occurring in patients with leukaemia (n = 90, 64.7%) and were associated with gram-positive bacteria (60.5%). In our cohort, all BSIs with gram-negative bacteria exhibited in vitro susceptibility against meropenem alone without any signs of resistance development. The antibiotic coverage of our meropenem-based combination therapy was also highly effective for gram-positive and non-fermenting bacteria. Thus, BSI-related mortality in all 139 BSI episodes was 1.4%. Clostridium difficile infections (CDIs), as main adverse event of carbapenem usage, occurred in only 16 (2.5%) patients., Conclusion: Our meropenem-based combination therapy showed sufficient empirical antibiotic coverage in the majority of BSIs (96.4%) and did not result in an increased rate of unwanted side effects or development of antibiotic resistance.

Background: Malnutrition is common in children with cancer and is associated with adverse clinical outcomes. The need for supportive care is becoming ever more evident and the role of nutrition in oncology is still not sufficiently understood. In particular, the consequences of macro- and micronutrient deficiencies require further research. As epidemiological data suggest anti-tumoral properties of omega-3 (n-3) polyunsaturated fatty acids (PUFAs), we reviewed the role of nutrition and n-3 supplementation in pediatric oncology., Methods: A comprehensive literature search was conducted on PubMed through 5 February 2021 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) on macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: "childhood cancer", "pediatric oncology", "nutritional status", "malnutrition", and "omega-3-fatty-acids". The reference lists of all relevant articles were screened to include potentially pertinent studies., Results: We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of n-3 PUFAs and critically interpret findings. Possible effects of supplementation on the nutritional status and benefits during chemotherapy are discussed as well as strategies for primary and secondary prevention., Conclusion: We here describe the obvious benefits of omega-3 supplementation in childhood cancer. Further large scale clinical trials are required to verify potential anti-cancer effects of n-3 fatty acids.

A wide range of trendy food colourants and ready-to-eat foods containing pearlescent pigments providing glitter effects is currently on the market. These pearlescent pigments consist of mica (potassium aluminium silicate) platelets generally coated with titanium dioxide and/or iron oxides. All single components are approved food additives in the European Union (EU) (E 555, E 171 and E 172). However, the European Food Safety Authority (EFSA) has stated recently, that pearlescent pigments should be evaluated as new food additives. Food grade titanium dioxide was already shown to contain a considerable fraction of nanoparticles. Thus, the question about 'nano'-labelling of TiO 2 -containing pearlescent pigments according to the 'Novel Food' and 'Food Information to Consumers' regulations arose. In order to provide data for dealing with these issues, in this study four commercially available products of different food categories containing pearlescent pigments were characterised with focus on the structure, size and chemical composition of these pigments. The measurement methods used were flow particle image analysis (FPIA), static light scattering (SLS) and scanning electron microscopy (SEM) combined with energy-dispersive x-ray spectroscopy (EDX). After isolation from various food matrices, the glitter pigments could be easily identified and differentiated by fast FPIA screening from any remaining organic food matrix particles due to their typical platelet-like shape and transparency. The particle size distribution of the platelets was determined by means of SLS and found to be in the range of 8-167 µm. SEM was identified as the most suitable technique for the analysis of the nano-structured coating. For all constituent metal oxide particles (TiO 2 and/or Fe 2 O 3 ) a median minimum Feret diameter (F min ) of 29.9-46.8 nm was obtained by quantitative SEM image analysis.

Background: Scores can assess the severity and course of disease and predict outcome in an objective manner. This information is needed for proper risk assessment and stratification. Furthermore, scoring systems support optimal patient care, resource management and are gaining in importance in terms of artificial intelligence., Objective: This study evaluated and compared the prognostic ability of various common pediatric scoring systems (PRISM, PRISM III, PRISM IV, PIM, PIM2, PIM3, PELOD, PELOD 2) in order to determine which is the most applicable score for pediatric sepsis patients in terms of timing of disease survey and insensitivity to missing data., Methods: We retrospectively examined data from 398 patients under 18 years of age, who were diagnosed with sepsis. Scores were assessed at ICU admission and re-evaluated on the day of peak C-reactive protein. The scores were compared for their ability to predict mortality in this specific patient population and for their impairment due to missing data., Results: PIM (AUC 0.76 (0.68-0.76)), PIM2 (AUC 0.78 (0.72-0.78)) and PIM3 (AUC 0.76 (0.68-0.76)) scores together with PRSIM III (AUC 0.75 (0.68-0.75)) and PELOD 2 (AUC 0.75 (0.66-0.75)) are the most suitable scores for determining patient prognosis at ICU admission. Once sepsis is pronounced, PELOD 2 (AUC 0.84 (0.77-0.91)) and PRISM IV (AUC 0.8 (0.72-0.88)) become significantly better in their performance and count among the best prognostic scores for use at this time together with PRISM III (AUC 0.81 (0.73-0.89)). PELOD 2 is good for monitoring and, like the PIM scores, is also largely insensitive to missing values., Conclusion: Overall, PIM scores show comparatively good performance, are stable as far as timing of the disease survey is concerned, and they are also relatively stable in terms of missing parameters. PELOD 2 is best suitable for monitoring clinical course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Mirjam Bachler has received personal fees and travel grants from LFB Biomedicaments, Takeda GmbH, CSL Behring GmbH, Mitsubishi Tanabe and non-financial support from TEM International outside the submitted work., (©2020 Niederwanger et al.)

Background and Aims: Surgical resection is currently the cornerstone of liver tumor treatment in children. In adults radiofrequency ablation (RFA) is an established minimally invasive treatment option for small focal liver tumors. Multiprobe stereotactic RFA (SRFA) with intraoperative image fusion to confirm ablation margins allows treatment for large lesions. We describe our experience with SRFA in children with liver masses., Methods: SRFA was performed in 10 patients with a median age of 14 years (range 0.5-17.0 years) suffering from liver adenoma ( n  = 3), hepatocellular carcinoma ( n  = 1), hepatoblastoma ( n  = 2), myofibroblastic tumor ( n  = 1), hepatic metastases of extrahepatic tumors ( n  = 2) and infiltrative hepatic cysts associated with alveolar echinococcosis ( n  = 1). Overall, 15 lesions with a mean lesion size of 2.6 cm (range 0.7-9.5 cm) were treated in 11 sessions., Results: The technical success rate was 100%, as was the survival rate. No transient adverse effects higher than grade II (Clavien and Dindo) were encountered after interventions. The median hospital stay was 5 d (range 2-33 d). In two patients who subsequently underwent transplant hepatectomy complete ablation was histologically confirmed. Follow-up imaging studies (median 55 months, range 18-129 months) revealed no local or distant recurrence of disease in any patient., Conclusions: SRFA is an effective minimal-invasive treatment option in pediatric patients with liver tumors of different etiologies.

Background: Increasing bacterial resistance to antibiotics is a serious problem worldwide. We sought to record the acquisition of antibiotic-resistant Escherichia coli ( E. coli ) in healthy infants in Northern Thailand and investigated potential determinants., Methods: Stool samples from 142 infants after birth, at ages 2wk, 2mo, 4 to 6mo, and 1y, and parent stool samples were screened for E. coli resistance to tetracycline, ampicillin, co-trimoxazole, and cefazoline by culture, and isolates were further investigated for multiresistance by disc diffusion method. Pulsed-field gel electrophoresis was performed to identify persistent and transmitted strains. Genetic comparison of resistant and transmitted strains was done by multilocus sequence typing (MLST) and strains were further investigated for extra- and intra-intestinal virulence factors by multiplex PCR., Results: Forty-seven (33%) neonatal meconium samples contained resistant E. coli. Prevalence increased continuously: After 1y, resistance proportion (tetracycline 80%, ampicillin 72%, co-trimoxazole 66%, cefazoline 35%) almost matched those in parents. In 8 infants (6%), identical E. coli strains were found in at least 3 sampling time points (suggesting persistence). Transmission of resistant E. coli from parents to child was observed in only 8 families. MLST showed high diversity. We could not identify any virulence genes or factors associated with persistence, or transmission of resistant E. coli . Full-term, vaginal birth and birth in rural hospital were identified as risk factors for early childhood colonization with resistant E. coli ., Conclusion: One third of healthy Thai neonates harboured antibiotic-resistant E. coli in meconium. The proportion of resistant E. coli increased during the first year of life almost reaching the value in adults. We hypothesize that enhancement of infection control measures and cautious use of antibiotics may help to control further increase of resistance., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Nematode-trapping fungi (NTF) are a large and diverse group of fungi, which may switch from a saprotrophic to a predatory lifestyle if nematodes are present. Different fungi have developed different trapping devices, ranging from adhesive cells to constricting rings. After trapping, fungal hyphae penetrate the worm, secrete lytic enzymes and form a hyphal network inside the body. We sequenced the genome of Duddingtonia flagrans, a biotechnologically important NTF used to control nematode populations in fields. The 36.64 Mb genome encodes 9,927 putative proteins, among which are more than 638 predicted secreted proteins. Most secreted proteins are lytic enzymes, but more than 200 were classified as small secreted proteins (< 300 amino acids). 117 putative effector proteins were predicted, suggesting interkingdom communication during the colonization. As a first step to analyze the function of such proteins or other phenomena at the molecular level, we developed a transformation system, established the fluorescent proteins GFP and mCherry, adapted an assay to monitor protein secretion, and established gene-deletion protocols using homologous recombination or CRISPR/Cas9. One putative virulence effector protein, PefB, was transcriptionally induced during the interaction. We show that the mature protein is able to be imported into nuclei in Caenorhabditis elegans cells. In addition, we studied trap formation and show that cell-to-cell communication is required for ring closure. The availability of the genome sequence and the establishment of many molecular tools will open new avenues to studying this biotechnologically relevant nematode-trapping fungus., Competing Interests: The authors have declared that no competing interests exist.

The syndromic form of congenital sodium diarrhea (SCSD) is caused by bi-allelic mutations in SPINT2, which encodes a Kunitz-type serine protease inhibitor (HAI-2). We report three novel SCSD patients, two novel SPINT2 mutations and review published cases. The most common findings in SCSD patients were choanal atresia (20/34) and keratitis of infantile onset (26/34). Characteristic epithelial tufts on intestinal histology were reported in 13/34 patients. Of 13 different SPINT2 variants identified in SCSD, 4 are missense variants and localize to the second Kunitz domain (KD2) of HAI-2. HAI-2 has been implicated in the regulation of the activities of several serine proteases including prostasin and matriptase, which are both important for epithelial barrier formation. No patient with bi-allelic stop mutations was identified, suggesting that at least one SPINT2 allele encoding a protein with residual HAI-2 function is necessary for survival. We show that the SCSD-associated HAI-2 variants p.Phe161Val, p.Tyr163Cys and p.Gly168Ser all display decreased ability to inhibit prostasin-catalyzed cleavage. However, the SCSD-associated HAI-2 variants inhibited matriptase as efficiently as the wild-type HAI-2. Homology modeling indicated limited solvent exposure of the mutated amino acids, suggesting that they induce misfolding of KD2. This suggests that prostasin needs to engage with an exosite motif located on KD2 in addition to the binding loop (Cys47/Arg48) located on the first Kunitz domain in order to inhibit prostasin. In conclusion our data suggests that SCSD is caused by lack of inhibition of prostasin or a similar protease in the secretory pathway or on the plasma membrane., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Vedolizumab is safe and effective in adult patients with Crohn's disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD., Methods: Twelve patients (7 female; 7 CD; 5 UC), aged 8-17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor α antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits., Results: In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p = 1,0), while median UC activity scores changed from 70 to 5 points (p < 0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups., Conclusion: These results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.

Two novel, anaerobic, Gram-positive, rod-shaped bacterial strains, ResAG-85 T and ResAG-96 T , were isolated from a faecal sample of a male human. 16S rRNA gene sequences analyses indicated that these strains represent a distinct lineage within the family Eggerthellaceae. Strain ResAG-85 T showed 92.3 % similarity to the type strains of the genera Eggerthella and Gordonibacter. Strain ResAG-96 T clustered together with Paraeggerthella hongkongensis and the newly (but not validly) published genus 'Arabia massiliensis' (94.8 % similarity). Analysis of quinones revealed that MK-5 (21 % in ResAG-85 T and 95 % in ResAG-96 T ) and MK-7 (53 % in strain ResAG-85 T ) were present, which were described for the first time for members of the Eggerthellaceae. Furthermore, MK-6 was present in both strains (25 % ResAG-85 T and 5 % in ResAG-96 T ). The polar lipids detected in ResAG-85 T and ResAG-96 T consisted of eight and six glycolipids, respectively. Both strains possessed three phospholipids, one phosphatidylglycerol and one diphosphatidylglycerol. Analysis of fatty acids revealed that the percentage of total branched fatty acids was relatively high in comparison to related strains with 42 and 50 % of strains ResAG-85 T and ResAG-96 T but comparable to the value obtained for Gordonibacter pamelaeae DSM 19378 T . On the basis of this polyphasic approach including molecular (16S rRNA gene sequencing) and biochemical methods (analysis of fatty acids, quinones, polar lipids, Rapid ID 32A and API 20A), the new genera and species Rubneribacter badeniensis with ResAG-85 T (=DSM 105129 T =JCM 32272 T ) and Enteroscipio rubneri with ResAG-96 T (=DSM 105130 T =JCM 32273 T ) as the type and only strains are described.

This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR. The viral distribution and its association with clinical symptoms were statistically analyzed. Viral pathogens were detected in 342 (91.93%) of the samples of which 28.76% were single positive and 63.17% had multiple infections. The most frequent detected viruses were rhinovirus (55.64%), respiratory syncytial virus A/B (33.06%), adenovirus (25.00%), coronavirus NL63, HKU1, OC43, and 229E (21.50%), and metapneumovirus A/B (16.12%). Children in the youngest age group (1-3 months) exhibited the highest frequencies of infection. Related to their frequency of detection, RSV A/B was the most associated pathogen with patient's demographic situation and clinical manifestations (p<0.05). Parainfluenza virus 1-4 and parechovirus were found to increase the risk of death (p<0.05). Adenovirus was statistically associated to the manifestation of gastroenteritis (p = 0.004). Rhinovirus infection increases the duration of oxygen support (p = 0.042). Coronavirus group was statistically associated with the manifestation of bronchiolitis (p = 0.009) and laryngitis (p = 0.017). Streptococcus pneumoniae DNA was detected in 143 (38.44%) of tested samples. However, only 53 samples had a concentration of C-reactive protein from equal to higher than 20 milligrams per liter, and 6 of them were single positive for Streptocuccus pneumoniae. This study confirms the high incidence of respiratory viruses in children hospitalized for acute respiratory tract infections in the Sousse area, Tunisia.