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We present a versatile optical setup for high-resolution neutron imaging with an adaptable field of view and magnification that can resolve individual neutron absorption events with an image intensifier and a CMOS camera. Its imaging performance is characterized by evaluating the resolution limits of the individual optical components and resulting design aspects are discussed. Neutron radiography measurements of a Siemens star pattern were performed in event mode acquisition comparing two common high-resolution neutron scintillators, crystalline Gadolinium Gallium Garnet (GGG) and powdered Gadolinium Oxysulfide (GOS). An analysis of the light signature caused by neutron absorption events is performed and some resulting issues for both GGG and GOS regarding optical system design are addressed. Both scintillators reach similar resolution (4-5  μ m) in event mode acquisition despite different light emission characteristics. The findings suggest that, in the case of GOS, the resolution is limited by the size of the light clusters which in turn originate from the photon scattering at the boundaries of the powder particles comprising it, while with GGG the lower light conversion efficiency makes it challenging to collect enough photons to trigger sufficient signal amplification in the image intensifier. Overall, the proposed event-based evaluation of scintillators allows for quantifying and optimizing various design parameters, which is much more complex than adopting conventional methods based on integrated images., (© 2024. The Author(s).)

Background/aim: Large extracellular vesicles (lEV) offer a unique window into the metabolism of their cells of orign and dysregulation of lipid metabolism has been described in patients with small cell lung cancer (SCLC). Therefore, metabolomic profiling of patients' lEVs may offer insight into cancer metabolism as well as new potential biomarkers for monitoring disease progression., Materials and Methods: lEVs were isolated by differential centrifugation from the peripheral blood of SCLC patients and healthy controls. Targeted mass spectrometry was used to analyze the lipid composition of lEVs. After identifying relevant metabolites, biomarker and pathway analysis were conducted., Results: SCLC patients exhibited a distinct metabolic profile compared to healthy controls. The metabolites TG(16:0:_38:3), TG(18:3_35:2), TG(16:0_40:7), Cer(d18:1/26:0), and CE(16:0) are not only able to discriminate between patients and control samples, but are also served as prognostic markers for survival. Patients with high concentrations of these metabolites showed significantly shorter survival times. Pathway analysis revealed alterations in 'sphingolipid metabolism', 'sphingolipid signaling pathway' and 'necroptosis'., Conclusion: Metabolic profiling of lEVs in SCLC patients is feasible and reveals a distinct metabolic profile. High concentrations of identified lipids are associated with poor prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Biomarkers for patients suffering from glioblastoma (GBM) are scarce. Extracellular vesicles (EV) are a promising candidate for a potential biomarker. Therefore, EV concentration could be a potential biomarker of tumor burden, volume, and prognosis., Patients and Methods: Large EV (lEV) and small EV (sEV) were isolated from 36 GBM patients' blood plasma by differential centrifugation. Nanoparticle tracking was used to measure EV concentration. Quantitative analysis of tumor volume was performed by evaluating T2/FLAIR relaxation times., Results: The mean size of lEV was 173.3 nm ± 18.2 nm, while sEV measured 148.3 ± 9.0 nm. Patients with higher lEV concentrations showed a trend towards longer overall survival (36.1 vs. 16.5 months, p=0.08). Regarding inflammatory markers, higher leukocyte count was positively correlated with higher sEV concentration (r 2 =0.3887, DF 21, p=0.0015). No significant relationship was found between lEV or sEV concentration and tumor volume., Conclusion: Overall EV concentration in the peripheral blood is not a predictor of tumor volume. sEV concentration is associated with a potential pro-inflammatory metabolism., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Patients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD., Methods: From 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as "the algorithm"; the algorithm was validated in internal and two external cohorts across elastography techniques., Results: HCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×10 9 /l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%)., Conclusions: Our algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.).

Rivers are a significant conduit for land-derived plastic litter to the ocean, bridging terrestrial and marine environments. Yet, even though they are a primary pathway, much of the plastic entering river systems is retained along the river courses. This necessitates sampling various river sections, including riverbanks, to comprehend the distribution of plastic litter in these areas. Plastic litter along the riverbanks of Rivers Sabaki and Tana in Kenya was assessed over an annual cycle. Monitoring was done in two replicates at various preselected riverbank types, to assess their contribution to retention of plastic litter. Factor and cluster analyses were used to identify the sources of plastic litter. A total of 8793 plastic litter items weighing 65.38 kg, and 8429 plastic litter items weighing 85.08 kg were cataloged at Rivers Sabaki and Tana, respectively. Apart from whole items, plastic fragments were among top-ten litter types. The plastic litter densities in River Sabaki ranged from 0.06 to 2.17 items/m 2 , with a mass range of 0.40-25.96 g/m 2 . River Tana exhibited a density range of 0.12-0.70 items/m 2 , with a mass range of 1.40-8.96 g/m 2 . On seasonal variation peak accumulation of plastic litter was observed in December 2021 for River Sabaki, and in January 2022 for River Tana. Factor and cluster analysis revealed potential sources of plastic litter at River Sabaki including: recreational activities, direct littering, dumping from informal settlements, agricultural activities, and upstream sources. For River Tana, identified sources were: illegal dumpsites, direct littering, upstream sources, fishing, and navigation activities. The insights from this research could aid policymakers combat riverine plastic pollution, ultimately benefiting the ocean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Identification of interventions to prevent coercive measures in the event of escalating crisis situations in an inpatient acute psychiatric treatment context., Methods: Content analysis of 98 joint crisis plans (JCP) using frequency analysis (secondary data analysis)., Results: In over half of the joint crisis plans, withdrawal to a low-stimulation environment (64.3%), a conversation (62.2%), and a walk (57.1%) were agreed upon as intervention for escalating crisis situations. A significant difference (p=0.020) was found in relation to the intake of (on-demand) medication, which was determined exclusively by males., Conclusions: The results provide potentially helpful suggestions for escalating crisis situations and gender-specific findings with regard to the agreed interventions., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

In sparse data meta-analyses (with few trials or zero events), conventional methods may distort results. Although better-performing one-stage methods have become available in recent years, their implementation remains limited in practice. This study examines the impact of using conventional methods compared to one-stage models by re-analysing meta-analyses from the Cochrane Database of Systematic Reviews in scenarios with zero event trials and few trials. For each scenario, we computed one-stage methods (Generalised linear mixed model [GLMM], Beta-binomial model [BBM], Bayesian binomial-normal hierarchical model using a weakly informative prior [BNHM-WIP]) and compared them with conventional methods (Peto-Odds-ratio [PETO], DerSimonian-Laird method [DL] for zero event trials; DL, Paule-Mandel [PM], Restricted maximum likelihood [REML] method for few trials). While all methods showed similar treatment effect estimates, substantial variability in statistical precision emerged. Conventional methods generally resulted in smaller confidence intervals (CIs) compared to one-stage models in the zero event situation. In the few trials scenario, the CI lengths were widest for the BBM on average and significance often changed compared to the PM and REML, despite the relatively wide CIs of the latter. In agreement with simulations and guidelines for meta-analyses with zero event trials, our results suggest that one-stage models are preferable. The best model can be either selected based on the data situation or, using a method that can be used in various situations. In the few trial situation, using BBM and additionally PM or REML for sensitivity analyses appears reasonable when conservative results are desired. Overall, our results encourage careful method selection., (© 2024 The Author(s). Research Synthesis Methods published by John Wiley & Sons Ltd.)

Five sampling campaigns were conducted in the water columns of River Sabaki and Tana in Kenya, Between October 2021 and January 2023, covering a 1-year cycle, at four sites in River Sabaki (2.5 km, 3.05 km, 3.51 km, and 4.52 km) and River Tana (1.5 km, 1.8 km, 2.0 km, and 2.5 km) distant from the river mouth. The ebb and flood tides were sampled to calculate net plastic litter fluxes. Two 6350-µm seine nets were deployed in two replicates per sampling point. Factor and cluster analysis were used to investigate plastic litter sources for both rivers. The influences of rainfall on plastic abundance and mass were explored using permutational linear models. A total of 15,318 plastic litter items weighing 1.37 kg were recorded in River Sabaki, and 3741 plastic litter items weighing 0.95 kg in River Tana. The top ten captured plastic litter types sorted by abundance and mass were mostly plastic fragments. The annual net plastic litter flux to the ocean through River Sabaki amounted to 1,277,120.63 items year -1 by abundance and 22.30 kg year -1 by mass. For River Tana, the same fluxes were 207,550.76 items year -1 , and 28.09 kg year -1 , respectively. In River Sabaki, significant impacts of rainfall on plastic abundance and mass were found. River Sabaki's pollution sources included upstream reaches, fishing activities, and littering by locals and tourists. River Tana's major pollution sources were illegal dumpsites, littering, fishing, and recreational activities. This research can guide combat plastic pollution in the rivers and ultimately the ocean., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: To examine the association between intermittent fasting ("breakfast skipping") and glaucoma in the National Health and Nutrition Examination Survey (NHANES)., Patients and Methods: Retrospective, cross-sectional study of adult participants of the 2005-2008 NHANES aged 40 years and older. Intermittent fasting was defined as skipping breakfast on both days of the NHANES dietary interview. Glaucoma was defined by 1) self-reported glaucoma diagnosis, 2) cup-to-disc (CDR) ≥0.6 in at least one eye, and 3) Possible, probable or definite glaucoma based on clinical judgment of retinal imaging of individuals with CDR ≥0.6 in at least one eye. Covariates included age, sex, race/ethnicity, body mass index, blood pressure, and waist circumference. Chi-Square and Fisher Exact Test were used for categorical variables and t-test for continuous variables. All data were weighted based on the NHANES multistage sampling design., Results: The population included 7,081 individuals ≥40 years old, of whom 946 (13.4%) reported skipping breakfast on both interview days; 482 (6.8%) individuals self-reported glaucoma diagnosis, 549 (7.8%) individuals had glaucoma based on CDR ≥0.6 and 343 (6.0%) individuals had glaucoma based on clinical judgment. Diagnosis of glaucoma by all definitions was associated with older age and Black or Latinx/Hispanic ethnicity ( P =0.004) but was not associated with intermittent fasting status ( P =0.151)., Conclusions: In the 2005-2008 NHANES population, intermittent fasting, defined as breakfast skipping, was not associated with decreased risk of glaucoma diagnosis overall. Further studies are needed to examine the potential effects of intermittent fasting on glaucoma risk., Competing Interests: Conflict of interest: Andrew Chen reports research support from Janssen L.L.C. and consulting fees from Virtual Field Inc. outside of the submitted work., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In mammals, 5-methylcytosine (5mC) and Polycomb repressive complex 2 (PRC2)-deposited histone 3 lysine 27 trimethylation (H3K27me3) are generally mutually exclusive at CpG-rich regions. As mouse embryonic stem cells exit the naive pluripotent state, there is massive gain of 5mC concomitantly with restriction of broad H3K27me3 to 5mC-free, CpG-rich regions. To formally assess how 5mC shapes the H3K27me3 landscape, we profiled the epigenome of naive and differentiated cells in the presence and absence of the DNA methylation machinery. Surprisingly, we found that 5mC accumulation is not required to restrict most H3K27me3 domains. Instead, this 5mC-independent H3K27me3 restriction is mediated by aberrant expression of the PRC2 antagonist Ezhip (encoding EZH inhibitory protein). At the subset of regions where 5mC appears to genuinely supplant H3K27me3, we identified 163 candidate genes that appeared to require 5mC deposition and/or H3K27me3 depletion for their activation in differentiated cells. Using site-directed epigenome editing to directly modulate 5mC levels, we demonstrated that 5mC deposition is sufficient to antagonize H3K27me3 deposition and confer gene activation at individual candidates. Altogether, we systematically measured the antagonistic interplay between 5mC and H3K27me3 in a system that recapitulates early embryonic dynamics. Our results suggest that H3K27me3 restraint depends on 5mC, both directly and indirectly. Our study also implies a noncanonical role of 5mC in gene activation, which may be important not only for normal development but also for cancer progression, as oncogenic cells frequently exhibit dynamic replacement of 5mC for H3K27me3 and vice versa., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The continuous release of glucosinolates into the soil by Brassicaceae root exudation is a prerequisite to maintaining toxic levels of breakdown products such as isothiocyanates (ITCs). ITCs influence plant and microbial diversity in ecosystems, while fungi and Rhizobiaceae are particularly injured. Studies explaining the molecular mechanisms of the negative effects are presently limited. Therefore, we investigated the early effects of cyclic ITC goitrin on proteomes of the host and symbiotic Mesorhizobium loti in the nodules of Lotus japonicus and of free-living bacteria. In the nodules, many host proteins had a higher abundance, among them, peroxidases and pathogenesis-related PR-10 proteins functioning in the abscisic-acid-activated signaling pathway. In the microsymbiont, transporter proteins as a prominent group are enhanced; some proteins involved in N-fixation decreased. The proteomes give a report about the loss of immunity suppression resulting in the termination of symbiosis, which initiates nodule senescence. Free-living M. loti are severely damaged, indicated, i.a., by a decrease in transporter proteins, the assumed candidates for goitrin protein complex formation, and high proteolysis. The production of chicoric acid by the accompanying bacteria is inhibitory for M. loti but connected to goitrin elimination, as confirmed by mass spectrometric (MS) analysis. In summary, the nodulation process is severely affected by goitrin, causing nodule dysfunction and failed nodule development. N deficiency conditions leads to yellowish leaves and leaf abscission.

High-power Yb:InnoSlab lasers are proliferating into multiple modern application areas of laser physics ranging from plasma physics and nanolithography to driving optical parametric amplifiers for high-harmonic generation and attosecond science. Here, we present, the layout, design and first results of an optical parametric chirped-pulse amplifier system pumped by a kW-level average power Yb-InnoSlab laser. We describe the layout and concepts of the pump lasers, with particular attention to the specific design principles required for our application. In the current configuration, the pump laser delivers up to 933 W, 18.7 mJ, 1.2 ps pulses at 50 kHz repetition rate. In a first attempt this has generated above 70 W average power at 2 μm via parametric amplification. Chirped-mirror compression resulted in mJ-level pulses at 50 W and 38-fs pulse duration (5.7 cycles at 2 μm).

Dehydrogenative coupling (DC) reactions are of importance for the construction of new carbon-element bonds in synthetic organic chemistry. In this work, we report on the synthesis and characterization of several redox-active guanidino-functionalized aromatic molecules (GFAs) for use in DC (C-C and C-O) reactions. In a systematic approach, we first characterize the new DC reagents in all relevant redox and protonation states, and compare their performance in competitive test proton-coupled electron transfer (PCET) reactions. Then, their use in four different DC reactions with different mechanisms is evaluated., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Thermophilic cyanobacteria thrive in extreme environments, making their thermoresistant enzymes valuable for industrial applications. Common habitats include hot springs, which act as evolutionary accelerators for speciation due to geographical isolation. The family Thermosynechococcaceae comprises thermophilic cyanobacteria known for their ability to thrive in high-temperature environments. These bacteria are notable for their photosynthetic capabilities, significantly contributing to primary production in extreme habitats. Members of Thermosynechococcaceae exhibit unique adaptations that allow them to perform photosynthesis efficiently at elevated temperatures, making them subjects of interest for studies on microbial ecology, evolution, and potential biotechnological applications. In this study, the genome of a thermophilic cyanobacterium, isolated from a hot spring near Okahandja in Namibia, was sequenced using a PacBio Sequel IIe long-read platform. Cultivations were performed at elevated temperatures of 40, 50, and 55°C, followed by proteome analyses based on the annotated genome. Phylogenetic investigations, informed by the 16S rRNA gene and aligned nucleotide identity (ANI), suggest that the novel cyanobacterium is a member of the family Thermosynechococcaceae. Furthermore, the new species was assigned to a separate branch, potentially representing a novel genus. Whole-genome alignments supported this finding, revealing few conserved regions and multiple genetic rearrangement events. Additionally, 129 proteins were identified as differentially expressed in a temperature-dependent manner. The results of this study broaden our understanding of cyanobacterial adaptation to extreme environments, providing a novel high-quality genome of Thermosynechococcaceae cyanobacterium sp. Okahandja and several promising candidate proteins for expression and characterization studies., (© 2024 The Author(s). MicrobiologyOpen published by John Wiley & Sons Ltd.)

Purpose: Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus. Secondary stoma closure may be life threatening and is the most common reason for late ETV failure, mostly secondary to local scarring. Local stents intended to maintain patency are rarely used. In this study, we summarize our experience using stented ETV (sETV), efficacy, and safety., Material and Methods: Data was retrospectively collected from all consecutive patients who underwent ETV with stenting at four centers. Collected data included indications for using sETV, hydrocephalic history, surgical technique, outcomes, and complications., Results: Sixty-seven cases were included. Forty had a primary sETV, and 27 had a secondary sETV (following a prior shunt, ETV, or both). The average age during surgery was 22 years. Main indications for sETV included an adjacent tumor (n = 15), thick or redundant tuber cinereum (n = 24), and prior ETV failure (n = 16). Fifty-nine patients (88%) had a successful sETV. Eight patients failed 11 ± 8 months following surgery. Reasons for failure included obstruction of the stent, reabsorption insufficiency, and CSF leak (n = 2 each), and massive hygroma and tumor spread (n = 1 each). Complications included subdural hygroma (n = 4), CSF leak (n = 2), and stent malposition (n = 1). There were no complications associated with two stent removals., Conclusion: Stented ETV appears to be feasible and safe. It may be indicated in selected cases such as patients with prior ETV failure, or as a primary treatment in cases with anatomical alterations caused by tumors or thickened tuber cinereum. Future investigations are needed to further elucidate its role in non-communicating hydrocephalus., (© 2024. The Author(s).)

Objective: The extent of resection of pediatric low-grade glioma mostly improves progression-free survival. In chiasmatic hypothalamic glioma (CHG), complete resections are limited due to the relevantly high risk of associated neurological and endocrinological deficits. Still, surgery might have its role in the framework of a multidisciplinary team (MDT) approach. We report our retrospective experience from two centers on surgical options and their impact on long-term outcomes., Methods: Medical records of surgically treated pediatric CHG patients between 2004 and 2022 were analyzed. Patient characteristics, surgical interventions, histology, and non-surgical therapy were retrieved together with outcome measures such as visual acuity, endocrine function, and survival., Results: A total of 63 patients (33 female, NF-1, n = 8) were included. Age at first diagnosis was 4.6 years (range 0.2-16.9) and cohort follow-up was 108 ± 72 months. Twenty patients were surgically treated with a biopsy and 43 patients with debulking at a median age of 6.5 years (range 0.16-16.9). Patients received a median of 2 tumor surgeries (range 1-5). Cyst drainage was accomplished in 15 patients, and 27 patients had ventriculoperitoneal shunt implantation. Non-surgical therapy was given in 69.8%. At the end of follow-up, 74.6% of patients had stable disease. The cohort had a median Karnofsky score of 90 (range 0-100). Four patients died. Hormone substitution was necessary in 30.2%, and visual acuity was impaired in 66% of patients., Conclusion: Pediatric CHG is a chronic disease due to overall high survival with multiple progressions. Surgical therapy remains a key treatment option offering biopsy, limited tumor-debulking, cyst fenestration, and hydrocephalus management in the framework of MDT decision-making. Team experience contributes to reducing possible deficits in this challenging cohort., (© 2024. The Author(s).)

Aims: Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce., Methods and Results: Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P  < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P  = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P  < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P  = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P  < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P  = 0.000) but remained negligible., Conclusion: Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Bacillus cereus group includes closely related spore-forming Gram-positive bacteria. In this group, plasmids play a crucial role in species differentiation and are essential for pathogenesis and adaptation to ecological niches. The B. cereus emetic strains are characterized by the presence of the pCER270 megaplasmid, which encodes the non-ribosomal peptide synthetase for the production of cereulide, the emetic toxin. This plasmid carries several genes that may be involved in the sporulation process. Furthermore, a transcriptomic analysis has revealed that pCER270 influences the expression of chromosome genes, particularly under sporulation conditions. In this study, we investigated the role of pCER270 on spore properties in different species of the B. cereus group. We showed that pCER270 plays a role in spore wet heat resistance and germination, with varying degrees of impact depending on the genetic background. In addition, pCER270 ensures that sporulation occurs at the appropriate time by delaying the expression of sporulation genes. This regulation of sporulation timing is controlled by the pCER270-borne Rap-Phr system, which likely regulates the phosphorylation state of Spo0A. Acquisition of the pCER270 plasmid by new strains could give them an advantage in adapting to new environments and lead to the emergence of new pathogenic strains., Importance: The acquisition of new mobile genetic elements, such as plasmids, is essential for the pathogenesis and adaptation of bacteria belonging to the Bacillus cereus group. This can confer new phenotypic traits and beneficial functions that enable bacteria to adapt to changing environments and colonize new ecological niches. Emetic B. cereus strains cause food poisoning linked to the production of cereulide, the emetic toxin whose synthesis is due to the presence of plasmid pCER270. In the environment, cereulide provides a competitive advantage in producing bacteria against various competitors or predators. This study demonstrates that pCER270 also regulates the sporulation process, resulting in spores with improved heat resistance and germination capacity. The transfer of plasmid pCER270 among different strains of the B. cereus group may enhance their adaptation to new environments. This raises the question of the emergence of new pathogenic strains, which could pose a serious threat to human health., Competing Interests: The authors declare no conflict of interest.

Background: Despite guideline recommendations, many patients with heart failure (HF) do not receive target dosages of renin-angiotensin-aldosterone system inhibitors (RAASis) in clinical practice due, in part, to concerns about hyperkalemia (HK)., Methods and Results: This noninterventional, multinational, multicenter registry (NCT04864795; 111 sites in Europe and the USA) enrolled 2558 eligible adults with chronic HF (mostly with reduced ejection fraction [HFrEF]). Eligibility criteria included use of angiotensin-converting-enzyme inhibitor/angiotensin-II receptor blocker/angiotensin-receptor-neprilysin inhibitor, being a candidate for or treatment with a mineralocorticoid receptor antagonist, and increased risk of HK (eg, current serum potassium > 5.0 mmol/L), history of HK in the previous 24 months, or estimated glomerular filtration rate < 45 mL/min/1.73 m 2 ). Information on RAASi and other guideline-recommended therapies was collected retrospectively and prospectively (≥ 6 months). Patients were followed according to local clinical practice, without study-specific visits or interventions. The main objectives were to characterize RAASi treatment patterns compared with guideline recommendations, describe RAASi modifications following episodes of HK, and describe RAASi treatment in patients treated with patiromer. Baseline characteristics for the first 1000 patients are presented., Conclusions: CARE-HK is a multinational prospective HF registry designed to report on the management and outcomes of patients with HF at high risk for HK in routine clinical practice., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Snake venom is an ecologically relevant functional trait directly linked with a snake's fitness and survival, facilitating predation and defence. Snake venom variation occurs at all taxonomic levels, but the study at the intraspecific level is still in its early stages. The common adder ( Vipera berus ) exhibits considerable variation in colour phenotypes across its distribution range. Melanistic (fully black) individuals are the subject of myths and fairytales, and in German folklore such 'hell adders' are considered more toxic than their normally coloured conspecifics despite any formal investigation. Here, we provide the first comparative analysis of venoms from melanistic and normally coloured common adders. Specifically, we compared the venom profiles by sodium dodecylsulfate polyacrylamide gel electrophoresis and reversed-phase high-performance liquid chromatography and tested the venoms' protease, phospholipase A 2 and cytotoxic activities. Phospholipase A 2 activity was similar in both phenotypes, whereas general protease activity was higher in the melanistic venom, which was also more cytotoxic at two concentrations (6.25 and 12.5 µg ml -1 ). These minor differences between the venoms of melanistic and normally coloured adders are unlikely to be of clinical relevance in the context of human envenomation. In light of our results, the claim that melanistic adders produce more toxic venom than their normally coloured conspecifics appears rooted entirely in folklore., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

During dental scaling in dogs under general anaesthesia, contamination of the peripheral intravenous catheter (PIVC) is unavoidable due to splatter and the generated aerosol. Bacterial contamination was compared between two commonly used PIVC placement sites. Thirty-nine client-owned dogs with a minimum length from their nose to their tail base of 50 cm were randomly assigned to receive a PIVC in either their cephalic or saphenous vein. Irrespective of the PIVC placement site, brain heart infusion agar dishes were placed in the cephalic and saphenous vein areas. Their lids were closed 0, 5, and 10 min into the procedure. Contamination was measured by counting the colony-forming units after incubation on different substrates. The data were analysed with descriptive statistics, ANOVA, and ANCOVA ( p < 0.05). The cephalic vein area showed a significantly higher bacterial load than the saphenous vein area ( p ≈ 0.0) regardless of the length of the dog. Furthermore, the dorsal PIVC injection ports were sampled before and after scaling, and the colonies isolated were counted and subjected to MALDI-TOF-MS for identification. The bacteria mainly belonged to the genera Staphylococcus, Neisseria, and Bacillus. Our results suggest that for dental scaling in dogs, the PIVC should be placed in the pelvic limb whenever possible to reduce the potential risk of contamination.

The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8 ) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials., (© 2024. The Author(s).)

Ruthenium nitrosyl (Ru-NO) complexes are of interest as photoactive nitric oxide (NO) donor candidates for local therapeutic applications. NO plays a crucial regulatory role in skin homeostasis, concentration-dependently affecting processes like the proliferation, apoptosis, autophagy and redox balance. In this context, we investigated HE-10, a ruthenium-based photoinducible NO donor, for its pro-oxidant and cytotoxic effects under light and dark conditions in VH10 human foreskin fibroblast cells. We also tested its intracellular and extracellular NO-releasing function. Our study reveals a significant dose-dependent cytotoxic effect of HE-10, an increase in intracellular reactive oxygen and nitrogen species, and the occurrence of apoptosis in skin fibroblast cells. Furthermore, exposure to both increasing doses of HE-10 and white LED light led to substantial cellular events, including a significant induction of autophagy and G2/M phase cell cycle arrest. Paradoxically, these effects were not solely attributable to NO release based on DAF2-DA NO probe results, suggesting that intracellular photochemical reactions additional to NO photolysis contribute to HE-10's biological activity. This study shows that HE-10 exhibits both cytotoxic and potential therapeutic effects, depending on concentration and light exposure. These findings are crucial for developing targeted Ru-NO complex treatments for skin diseases and potentially certain types of skin cancer, where controlled NO release could be beneficial.

This study aimed to examine psychometric properties of the Adherence to Refills and Medications Scale (ARMS) in people with gout. We conducted exploratory factor analysis (EFA) and tested internal consistency (ordinal and Cronbach's alpha coefficients) and agreement (intraclass correlation coefficient (2,1)) in ARMS scores across three timepoints (baseline, 6, and 12 months) in 487 people with gout. The Kruskal-Wallis test, Spearman's rank, Kendall's tau-b correlations, and logistic regression were used to examine the criterion-related validity of the ARMS and factors associated with the ARMS. EFA suggested a one-factor structure, explaining 43.2% of total variance. High internal consistency (ordinal alpha = 0.902 at baseline) and moderate agreement in ARMS scores over time (ICCs > 0.5; p < 0.001) were observed. Lower ARMS scores (indicating better adherence) predicted achieving target serum urate (OR, 0.89; 95% CI, 0.83-0.95; p < 0.001), but not urate-lowering therapy (ULT) adherence (Proportion of Days Covered (PDC) ≥ 80%) (OR, 0.93; 95% CI, 0.81-1.05; p = 0.261). Negative correlations between ARMS and PDC were not statistically significant (Kendall's tau-b, r =  - 0.126, p = 0.078; Spearman's rho =  - 0.173, p < 0.073). Differences in median ARMS scores (IQR) of 16 (14-20), 13 (12-15), and 17.5 (15-21) in three groups of participants who reported (1) not taking ULT, (2) taking ULT and adherent, and (3) taking ULT but not adherent, respectively, were statistically significant (p < 0.001). Age was the only patient factor independently associated with optimal adherence (ARMS score = 12) (OR, 1.91; 95% CI, 1.50-2.43; p < 0.001). The ARMS is a reliable and valid measure of medication adherence behaviours in people with gout, justifying its use in gout medication adherence research., (© 2024. The Author(s).)

This study investigated the anti-inflammatory effect of hydrophilic and lipophilic extracts from juçara fruits (Euterpe edulis Martius) through measurement of nitric oxide (NOx) and cytokines (IL-12p70, TNF-α, INF-γ, MCP-1, IL-6, and IL-10). J774 macrophages were stimulated with lipopolysaccharides (1 µg/mL) and treated with various concentrations (1-100 µg/mL) of juçara fruits extracts from crude extracts, and hexane, dichloromethane, ethyl acetate, and butanol fractions. Potential relationships between the phenolic composition of the extracts determined by LC-ESI-MS/MS and their anti-inflammatory capacity were also evaluated. Hexane and dichloromethane fractions inhibited NOx and IL-12p70 while increased IL-10. Hexane fractions also decreased IL-6 and IFN-γ production. Hexane and dichloromethane fractions showed a higher number of phenolic compounds (32 and 34, respectively) than the other extracts tested and were also the only ones that presented benzoic acid and pinocembrin. These results suggest juçara fruits compounds as potential anti-inflammatory agents, especially those of a more apolar nature., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the applicability of transplanted teeth in young patients with craniofacial anomalies., Design: Observational study., Setting: Comprehensive Centre for Cleft Palate and Craniofacial Malformations., Patients/participants: Patients with craniofacial anomalies who underwent tooth transplantation. Only children with complete clinical and radiological documentation and a follow-up period of at least 1.5 years were included., Interventions: Tooth transplantation., Main Outcome Measure(s): Retrospective evaluation of clinical records, pre- and postoperative radiographs, and operative charts. Clinical characteristics of patients, preoperative parameters and postoperative outcome parameters were collected., Results: A total of 17 patients with 23 tooth transplantations were included. The median follow-up period was 6.7 years. The pooled survival and success rates were 91%. Notably, one out of two teeth that were transplanted into the bone grafted alveolar cleft site had to be extracted, which might indicating a higher risk for this procedure. In total, two transplanted teeth had to be extracted during the follow-up period, one due to external resorption and the other one due to perio-endo lesion. One patient needed endodontic treatment due to pulp necrosis., Conclusion: We consider tooth transplantation to be a reliable and suitable procedure in the dental rehabilitation of young patients with craniofacial anomalies and fitting concomitant circumstances. We encourage craniofacial teams to reconsider this option more frequently in appropriate cases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Suicide is a leading cause of death in males aged 25-44 years, an age which often coincides with becoming a father. This review aims to synthesise the evidence of the prevalence of suicidal and self-harm ideation in fathers during the perinatal, postnatal and early parenting period., Methods: Five databases were searched (PsycINFO, Medline, Web of Science, PubMed and the Cochrane Database of Systematic Reviews) to identify papers published between 1 January 2000 and 9 March 2023. A meta-analysis was conducted to estimate the prevalence of suicidality and self-harm ideation across the included studies. Subgroup and sensitivity analyses were conducted to explore potential sources of heterogeneity., Results: A total of 4215 articles were identified, with 14 studies included in the review. The combined pooled prevalence of suicidal and self-harm ideation was 4.2% (95% CI [2.6%, 6.2%]). Prevalence estimates were higher for self-harm ideation at 5.1% (95% CI [2.6%, 6.2%]) than for suicidality at 3% (95% CI [0.9%, 6.1%])., Conclusions: This review found that a considerable proportion of fathers experience suicidal and self-harm ideation during the early years of parenting. However, the paucity of rigorous prevalence studies indicates that further research in this area is needed urgently., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

3D printing technologies such as fused filament fabrication (FFF) offer great opportunities to enable the fabrication of complex geometries without access to a workshop or knowledge of machining. By adding filler materials to the raw filaments used for FFF, the material properties of the plastic can be adapted. With the addition of neutron absorbing particles, filaments can be created that enable 3D printing of neutron shielding with arbitrary geometry. Two materials for FFF are presented with different mixing ratios of hexagonal Boron nitride (h-BN) and Polylactic acid (PLA). BNPLA25 with 25 %wt h-BN and BNPLA35 with 35 %wt h-BN are compared to the commercially available Addbor N25 material. To qualify the applicability of BNPLA25 and BNPLA35 as shielding material for neutron instrumentation, such as neutron imaging, we investigated the overall neutron attenuation, the influence of non-optimized print settings, as well as characterized the incoherent neutron scattering and the microstructure using neutron imaging, and time-of-flight small-angle-neutron-scattering. Finally, the tensile strength of the material was determined in standardized tensile tests. The measured neutron attenuation shows excellent agreement with analytical calculations, thus validating both the material composition and the calculation method. Approximately 6 mm (8 mm) BNPLA35 are needed for 1 × 10 - 3 transmission of a cold (thermal) neutron beam. Lack of extrusion due to suboptimal print settings can be compensated by increased thickness, clearly visible defects can be mitigated by 11-18% increase in thickness. Incoherent scattering is shown to be strongly reduced compared to pure PLA. The tensile strength of the material is shown not to be impacted by the h-BN filler. The good agreement between the measured attenuation and calculation, combined with the adoption of safety factor enables the quick and easy development as well as the performance estimation of shielding components. BNPLA is uniquely suited for 3D printing neutron shielding because of the combination of non-abrasive h-BN particles in standard PLA, which results in a filament that can be printed with almost any off-the-shelf printer and virtually no prior experience in 3D printing. This mitigates the slightly lower attenuation observed as compared to filaments containing B 4 C , which is highly abrasive and requires extensive additive manufacturing experience., (© 2024. The Author(s).)

Purpose: We explored the associations between socioeconomic status, as evaluated by the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI), and characteristics of open globe injury (OGI) in a Level I trauma center during the COVID-19 pandemic., Methods: Retrospective review of electronic medical records of patients who underwent OGI evaluation and repair at Harborview Medical Center between March/2017 and March/2021. Demographic data and patient characteristics were recorded. The SVI was obtained based on the patient's home address. Patients were grouped into the "historical" (pre-COVID) cohort, including dates from March 2017 - March 2020, and the "COVID" cohort, including dates from March 2020 - March 2021., Results: 318 patients (77.4% male) were included. Average ± S.D. age (years) and SVI scores were 44.7 ± 22.7 and 0.413 ± 0.195, respectively. SVI scores were significantly higher (more vulnerable) during the COVID-19 pandemic compared to years prior (p = 0.017), however when compared to scores for the same patients prior to the pandemic, no difference was found (p = 0.609). There was no significant difference between intentional and non-intentional trauma, work-related injuries, OGI type, presence of endophthalmitis, or ocular trauma score (p ≥ 0.293). Still, significantly fewer motor vehicle-associated (MVA) OGIs occurred during the pandemic (p = 0.041)., Conclusions: Patients with OGI during the COVID-19 pandemic had higher SVI scores, however when considering the overall effect of the pandemic, our findings are likely reflective of the societal changes at large. There was no identifiable impact on the mechanisms or characteristics of ocular injuries, except for fewer MVA injuries., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The gentle yet cost-effective drying of sensitive products in the food and pharmaceutical industries is becoming increasingly important. To maintain sensitive ingredients, color, structure, and viability of micro-organisms, often freeze-drying is the only possible way to preserve the product. As many products come in as bulk material, they are dried on heated shelves resulting in poor heat and mass transport through the bed. Resulting in a very time and cost intensive process. Therefore, efforts are being made to improve the mass and heat transport of the process. The outer mass transport through the bulk can be improved by continuous mixing of the pellets, facilitating the removal of water vapor from the condenser. In addition, the issue of limited heat transport can be addressed by using volumetric energy input from microwaves. This process is called dynamic microwave freeze-drying. As dynamic microwave freeze-drying is a combined drying and mixing process, with particle properties continuously changing during drying, it is necessary to gain a more detailed insight into the process. For this purpose, a drier is designed that is capable of in situ neutron imaging, a method sensitive to a material's hydrogen content. This paper presents the design of a pilot-scale microwave freeze dryer for in situ neutron imaging and shows the first images taken during the dynamic microwave freeze-drying of bulk particles at the Center for Energy Research, Budapest Neutron Center in Budapest, Hungary., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing., Methods: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation., Results: 19 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 17/19 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 79%. Copy number variation profiles were generated for all cases and matched EPIC results in 18/19 (95%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations., Conclusion: Methylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing., (© 2024. The Author(s).)

Primary medication non-adherence describes the situation when a first prescription for a new medication is never filled. Primary non-adherence is an important, yet understudied aspect of reduced effectiveness of pharmacotherapy. This review summarizes the frequency, impact, reasons, predictors, and interventions regarding primary non-adherence to cardiovascular/cardiometabolic drugs. The current literature reveals a high prevalence of primary non-adherence. The individual risk of primary non-adherence is determined on multiple factors, e.g., primary non-adherence of lipid-lowering drugs is higher compared to antihypertensive medications. However, the overall rate of primary non-adherence is > 10%. Additionally, this review identifies specific areas for research to better understand why patients forgo evidence-based beneficial pharmacotherapy and to explore targeted interventions. At the same time, measures to reduce primary non-adherence-once proven to be effective-may represent an important new opportunity to reduce cardiovascular diseases., (© 2023. The Author(s).)

Purpose: To propose a paradigm change for the validation procedures of medication adherence questionnaires., Methods: A total of 121 validation procedures of unique questionnaires for medication adherence were analyzed., Results: "Construct validity" and "internal consistency" were most often assessed, and test results varied largely. A more in-depth analysis indicated that the assessment of medication non-adherence included distinct but related constructs, such as the extent to which doses are missed, and the attempt to identify different facets of medication-taking behavior. Consequently, each construct requires a different measurement approach with different psychometric tests for establishing its validity and reliability., Conclusion: Results show that assessing the validity and reliability of adherence questionnaires with standard procedures including statistical tests is inconclusive. Refinement of the constructs of non-adherence is needed in pharmacy and medical practice. We suggest a distinction between the (i) extent of missed doses over the past 2 weeks, (ii) modifiable reasons for non-adherence behavior, and (iii) unmodifiable factors of non-adherence. Validation procedures and corresponding statistical methods should be selected according to the specific single constructs., (© 2024. The Author(s).)

Melanoma being one of the most common and deadliest skin cancers, has been rising since the past decade. Patients at advanced stages of the disease have very poor prognoses, as opposed to at the earlier stages. Nowadays the standard-of-care of advanced melanoma is resection followed by immune checkpoint inhibition based immunotherapy. However, a substantial proportion of patients either do not respond or develop resistances. This underscores a need for novel approaches and therapeutic targets as well as a better understanding of the mechanisms of melanoma pathogenesis. Long non-coding RNAs (lncRNAs) comprise a poorly characterized class of functional players and promising targets in promoting malignancy. Certain lncRNAs have been identified to play integral roles in melanoma progression and drug resistances, however systematic screens to uncover novel functional lncRNAs are scarce. Here, we profile differentially expressed lncRNAs in patient derived short-term metastatic cultures and BRAF-MEK-inhibition resistant cells. We conduct a focused growth-related CRISPR-inhibition screen of overexpressed lncRNAs, validate and functionally characterize lncRNA hits with respect to cellular growth, invasive capacities and apoptosis in vitro as well as the transcriptomic impact of our lead candidate the novel lncRNA XLOC&#95;030781. In sum, we extend the current knowledge of ncRNAs and their potential relevance on melanoma., Significance: Previously considered as transcriptional noise, lncRNAs have emerged as novel players in regulating many cellular aspects in health and disease including melanoma. However, the number and as well as the extent of functional significance of most lncRNAs remains elusive. We provide a comprehensive strategy to identify functionally relevant lncRNAs in melanoma by combining expression profiling with CRISPR-inhibition growths screens lowering the experimental effort. We also provide a larger resource of differentially expressed lncRNAs with potential implications in melanoma growth and invasion. Our results broaden the characterized of lncRNAs as potential targets for future therapeutic applications.

Asymmetries in the size of structures deep below the cortex explain how alpha oscillations in the brain respond to shifts in attention., Competing Interests: MS, MW No competing interests declared, (© 2024, Schulz and Wöstmann.)

Harmful algae blooms are a rare phenomenon in rivers but seem to increase with climate change and river regulation. To understand the controlling factors of cyanobacteria blooms that occurred between 2017 and 2020 over long stretches (> 250 km) of the regulated Moselle River in Western Europe, we measured physico-chemical and biological variables and compared those with a long-term dataset (1997-2016). Cyanobacteria (Microcystis) dominated the phytoplankton community in the late summers of 2017-2020 (cyano-period) with up to 110 µg Chlorophyll-a/L, but had not been observed in the river in the previous 20 years. From June to September, the average discharge in the Moselle was reduced to 69-76% and water temperature was 0.9-1.8 °C higher compared to the reference period. Nitrogen (N), phosphorus (P) and silica (Si) declined since 1997, albeit total nutrient concentrations remained above limiting conditions in the study period. Cyanobacterial blooms correlated best with low discharge, high water temperature and low nitrate. We conclude that the recent cyanobacteria blooms have been caused by dry and warm weather resulting in low flow conditions and warm water temperature in the regulated Moselle. Under current climate projections, the Moselle may serve as an example for the future of regulated temperate rivers., (© 2024. The Author(s).)

Based on Boolean logic, molecular keypad locks secure molecular information, typically with an optical output. Here we investigate a rare example of a molecular keypad lock with a chemical output. To this end, the light-activated release of biologically important nitric oxide from a ruthenium complex is studied, using proton concentration and photon flux as inputs. In a pH-dependent equilibrium, a nitritoruthenium(II) complex is turned into a nitrosylruthenium(II) complex, which releases nitric oxide under irradiation with visible light. The precise prediction of the output nitric oxide concentration as function of the pH and photon flux is achieved with an artificial intelligence approach, namely the adaptive neuro-fuzzy inference system. In this manner an exceptionally high level of control over the output concentration is obtained. Moreover, the provided concept to lock a chemical output as well as the output prediction may be applied to other (photo)release schemes., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Objective: Illness perceptions are views and beliefs formed in response to a health threat, and they may influence self-management behaviours and chronic disease outcomes. Despite effective medication, sub-optimal outcomes in gout are common. This study aimed to quantitatively investigate illness perceptions in gout to examine how illness perceptions relate to health outcomes., Methods: Data were obtained from a randomized controlled trial in which people with gout (n = 493) completed surveys measuring illness perceptions [Brief Illness Perception Questionnaire (B-IPQ)], gout flares, medication adherence, health-related quality of life, health-care utilization, and productivity, alongside serum urate blood tests at baseline, and at 6- and 12-month follow-ups. Multivariable linear regression identified patient factors independently associated with each B-IPQ item score. Logistic and linear regression, adjusted for age and sex, determined whether baseline B-IPQ items could predict current and future health outcomes., Results: Younger individuals and those with severe gout were more likely to experience pessimistic illness perceptions at baseline. Optimistic illness perceptions were associated with lower odds of having had at least one flare in the preceding 6 months. Every 1-point increase in B-IPQ treatment control, indicating an increasingly optimistic view that gout is treatable, decreased the odds of a recent flare prior to baseline by 33% [odds ratio (OR): 0.67; 95% CI: 0.53, 0.85; P < 0.001] and prior to the 12-month follow-up by 15% (OR: 0.85; 95% CI: 0.76,0.96; P = 0.01). Pessimistic illness perceptions also predicted poorer medication adherence, health-related quality of life, and productivity, but not serum urate levels., Conclusion: Modifying pessimistic illness perceptions, including, but not limited to, patient education, may promote prudent self-management behaviours and better outcomes in gout., Trial Registration: Australian New Zealand Clinical Trials Registry; https://www.anzctr.org.au/, ACTRN12616000455460., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Reproductive failure in dogs is often due to unknown causes, and correct diagnosis and treatment are not always achieved. This condition is associated with various congenital and acquired etiologies that develop inflammatory processes, causing an increase in the number of leukocytes within the female reproductive tract (FRT). An encounter between polymorphonuclear neutrophils (PMNs) and infectious agents or inflammation in the FRT could trigger neutrophil extracellular traps (NETs), which are associated with significantly decreased motility and damage to sperm functional parameters in other species, including humans. This study describes the interaction between canine PMNs and spermatozoa and characterizes the release of NETs, in addition to evaluating the consequences of these structures on canine sperm function. To identify and visualize NETs, May-Grünwald Giemsa staining and immunofluorescence for neutrophil elastase (NE) were performed on canine semen samples and sperm/PMN co-cultures. Sperm viability was assessed using SYBR/PI and acrosome integrity was assessed using PNA-FITC/PI by flow cytometry. The results demonstrate NETs release in native semen samples and PMN/sperm co-cultures. In addition, NETs negatively affect canine sperm function parameters. This is the first report on the ability of NETs to efficiently entrap canine spermatozoa, and to provide additional data on the adverse effects of NETs on male gametes. Therefore, NETs formation should be considered in future studies of canine reproductive failure, as these extracellular fibers and NET-derived pro-inflammatory capacities will impede proper oocyte fertilization and embryo implantation. These data will serve as a basis to explain certain reproductive failures of dogs and provide new information about triggers and molecules involved in adverse effects of NETosis for domestic pet animals.

Blooms of Prymnesium parvum, a unicellular alga globally distributed in marine and brackish environments, frequently result in massive fish kills due to the production of toxins called prymnesins by this haptophyte. In August 2022, a harmful algal bloom (HAB) of this species occurred in the lower Oder River (Poland and Germany), which caused mass mortalities of fish and other organisms. This HAB was linked to low discharge of the Oder and mining activities that caused a significant increase in salinity. In this context, we report on the molecular detection and screening of this haptophyte and its toxins in environmental samples and clonal cultures derived thereof. Both conventional PCR and droplet digital PCR assays reliably detected P. parvum in environmental samples. eDNA metabarcoding using the V4 region of the 18S rRNA gene revealed a single Prymnesium sequence variant, but failed to identify it to species level. Four clonal cultures established from environmental samples were unambiguously identified as P. parvum by molecular phylogenetics (near full-length 18S rRNA gene) and light microscopy. Phylogenetic analysis (ITS1-5.8S-ITS2 marker region) placed the cultured phylotype within a clade containing other P. parvum strains known to produce B-type prymnesins. Toxin-screening of the cultures using liquid chromatography-electrospray ionization - time of flight mass spectrometry identified B-type prymnesins, which were also detected in extracts of filter residues from water samples of the Oder collected during the HAB. Overall, our investigation provides a detailed characterization of P. parvum, including their prymnesins, during this HAB in the Oder River, contributing valuable insights into this ecological disaster. In addition, the droplet digital PCR assay established here will be useful for future monitoring of low levels of P. parvum on the Oder River or any other salt-impacted and brackish water bodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Evaluations by the statutory health insurance carriers in Germany have revealed a rising prevalence of diagnoses of mental disorders, at varying levels and to varying extents. For mental health surveillance purposes, we analyzed prevalence trends across health insurance carriers, before and during the COVID-19 pandemic and stratified by diagnosis group, sex and age., Methods: Nationwide outpatient claims data of all statutorily insured individuals for the years 2012-2022 (Nmin = 68.7 million people, Nmax = 73.7 million people) were used to determine the diagnostic prevalence of mental disorders (ICD-10 F00-F99 and five selected diagnosis groups), with stratification by sex and age. Changes over time in the spectrum of all documented mental disorders are described., Results: Over the period 2012-2022, the percentage of people with outpatient diagnoses of mental disorders rose from 33.4% to 37.9% (a relative increase of 13.4%). In the selected diagnosis groups, the trends ranged from -11.6% to +115.8% and were generally steady over time, though stronger or stagnating trends were seen in some groups from 2020 onward. Diagnostic prevalence rose to a greater extent in male (+18.3%) than in female individuals (+10.8%) over the period 2012-2022. The greatest increases (> +15%) were seen among 11- to 17-yearolds and in 60- to 84-year-olds. The composition of the diagnosis spectrum was more stable in adults than in children and adolescents., Conclusion: Trends in diagnostic prevalence differ across mental disorders and population subgroups and have changed in some diagnosis groups since the COVID-19 pandemic. Contextualizing research is needed for a better understanding of these developments.

Introduction: Compulsory admissions are associated with feelings of fear, humiliation and powerlessness. The number of compulsory admissions in Germany and other high-income countries has increased in recent years. Peer support has been shown to increase the self-efficacy of individuals with mental health conditions in acute crises and to reduce the use of coercive measures in clinical settings. The objective of this study is to reduce the number of compulsory admissions by involving peer support workers (PSWs) in acute mental health crises in outreach and outpatient settings., Methods and Analysis: This one-year intervention is an exploratory, cluster randomised study. Trained PSWs will join the public crisis intervention services (CIS) in two of five regions (the intervention regions) in the city of Bremen (Germany). PSWs will participate in crisis interventions and aspects of the mental health services. They will be involved in developing and conducting an antistigma training for police officers. The remaining three regions will serve as control regions. All individuals aged 18 and older who experience an acute mental health crisis during the operating hours of the regional CIS in the city of Bremen (around 2000 in previous years) will be included in the study. Semistructured interviews will be conducted with PSWs, 30 patients from control and intervention regions, as well as two focus group discussions with CIS staff. A descriptive comparison between all participants in the intervention and control regions will assess the proportion of compulsory admissions in crisis interventions during the baseline and intervention years, including an analysis of temporal changes., Ethics and Dissemination: This study was approved by the Ethics Committee of the University of Bremen (file 2022-09) on 20 June 2022. The results will be presented via scientific conferences, scientific journals and communicated to policy-makers and practitioners., Trial Registration Number: DRKS00029377., Competing Interests: Competing interests: DB and MS are employed at the hospital Bremen-Ost, GENO. The crisis intervention services are organized and carried out by GENO on behalf of the ministry of health Bremen.PH is employed at the department of Health, Bremen. In the research project, the department ofhealth advises and oversees GENO regarding the implementation of peer support in the crisis intervention services. JU is employed at the ministry of health, women and consumer protection in Bremen. In his function as head of the department of mental health and addiction, he is the technical supervisor of the crisis intervention services. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The field of pharmaceutical 3D printing is growing over the past year, with Spitam® as the first 3D printed dosage form on the market. Showing the suitability of a binder jetting process for dosage forms. Although the development of inks for pharmaceutical field is more trail and error based, focusing on the Z -number as key parameter to judge the printability of an ink. To generate a more knowledgeable based ink development an approach from electronics printing was transferred to the field of pharmaceutical binder jetting. Therefore, a dimensionless space was used to investigate the limits of printability for the used Spectra S Class SL-128 piezo print head using solvent based inks. The jettability of inks could now be judged based on the capillary and weber number. Addition of different polymers into the ink narrowed the printable space and showed, that the ink development purely based on Z -numbers is not suitable to predict printability. Two possible ink candidates were developed based on the droplet momentum which showed huge differences in process stability, indicating that the used polymer type and concentration has a high influence on printability and process stability. Based on the study a more knowledgeable based ink design for the field of pharmaceutical binder jetting is proposed, to shift the ink design to a more knowledgeable based and process-oriented approach., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Precise planning and execution is key for neuroendoscopic interventions, which can be based on different available aiding technologies. The aim of this retrospective study is to report a case-based use of guided neuroendoscopy and to develop a stratification algorithm for the available technologies., Methods: We reviewed consecutive neuroendoscopic cases performed at our center from 2016 to 2018. We distinguished between patients receiving a new burr hole (group A) and those with a preexisting burr hole (group B). Case-specific technical requirements for procedure planning and execution, complication rate, surgical outcome, and possible subsequent surgery were evaluated. From this experience, a stratification system was developed to tailor the available guiding technologies., Results: A total of 309 neuroendoscopic interventions in 243 patients were included in the present study. The cases included hydrocephalic (81.6%) and nonhydrocephalic (18.4%) conditions. The interventions were supported by coordinate-based (group A, n = 49; group B, n = 67), guide-based (group A, n = 42; group B, n = 0), ultrasound-guided (group A, n = 50; group B, n = 7), or navigated augmented reality-guided (group A, n = 85; group B, n = 9) techniques. The overall complication rate was 4.5%. Stratified by the surgical indication, fontanel status, entry point localization, presence of a preexisting burr hole, ventricular size, and number of targets, an approach toward image-guided neuroendoscopy is suggested., Conclusions: Planning and technical guidance is essential in neuroendoscopic procedures. The stratified decision-making algorithm for different available technologies aims to achieve lower cost and time consumption, which was found to be safe and efficient. Further investigations are warranted to deliver solid data on procedure efficiency., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to estimate adherence to urate-lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient-reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day)., Methods: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12-month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT-taking status (self-reports) and ULT-dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement., Results: Allopurinol was prescribed in 93.5% of participants taking ULT. Their self-reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self-reported dose, and 63% (24%) using WHO's DDD. Sixty-three percent of allopurinol users were identified as adherent (PDC ≥80%) using self-reported dose. There was good agreement between self-reported ULT use and PBS dispensing claims (κ = 0.708, P < .001; positive percent agreement = 90%, negative percent agreement = 82%)., Conclusions: Participant-reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Ionic liquids (ILs) have gained considerable attention due to their versatile and designable properties. ILs show great potential as antibacterial agents, but understanding the mechanism of attack on bacterial cells is essential to ensure the optimal design of IL-based biocides. The final aim is to achieve maximum efficacy while minimising toxicity and preventing resistance development in target organisms. In this study, we examined a dose-response analysis of ILs' antimicrobial activity against two pathogenic bacteria with different Gram types in terms of molecular responses on a cellular level using Fourier-transform infrared (FTIR) spectroscopy. In total, 18 ILs with different antimicrobial active motifs were evaluated on the Gram-negative enteropathogenic Escherichia coli (EPEC) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The results showed that most ILs impact bacterial proteins with increasing concentration but have a minimal effect on cellular membranes. Dose-response spectral analysis revealed a distinct ante-mortem response against certain ILs for MRSA but not for EPEC. We found that at sub-lethal concentrations, MRSA actively changed their membrane composition to counteract the damaging effect induced by the ILs. This suggests a new adaptive mechanism of Gram-positive bacteria against ILs and demonstrates the need for a better understanding before using such substances as novel antimicrobials.

Biometric authentication plays a vital role in various everyday applications with increasing demands for reliability and security. However, the use of real biometric data for research raises privacy concerns and data scarcity issues. A promising approach using synthetic biometric data to address the resulting unbalanced representation and bias, as well as the limited availability of diverse datasets for the development and evaluation of biometric systems, has emerged. Methods for a parameterized generation of highly realistic synthetic data are emerging and the necessary quality metrics to prove that synthetic data can compare to real data are open research tasks. The generation of 3D synthetic face data using game engines' capabilities of generating varied realistic virtual characters is explored as a possible alternative for generating synthetic face data while maintaining reproducibility and ground truth, as opposed to other creation methods. While synthetic data offer several benefits, including improved resilience against data privacy concerns, the limitations and challenges associated with their usage are addressed. Our work shows concurrent behavior in comparing semi-synthetic data as a digital representation of a real identity with their real datasets. Despite slight asymmetrical performance in comparison with a larger database of real samples, a promising performance in face data authentication is shown, which lays the foundation for further investigations with digital avatars and the creation and analysis of fully synthetic data. Future directions for improving synthetic biometric data generation and their impact on advancing biometrics research are discussed., Competing Interests: The authors declare no conflicts of interest.