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We report for the first time cylindrical galls of Youngomyia pouteriae Maia, 2001 (Diptera, Cecidomyiidae) on Pouteria caimito (Ruiz & Pav.) Radlk. (Sapotaceae) in Peru. Youngomyia pouteriae were exclusively found in the Atlantic Forest biome, in restinga areas of Rio de Janeiro state, Brazil. In this study, the geographic distribution of this galling species is extended to the western Amazon lowland rainforest in Peru.

Abstract Background Convalescent plasma (CP) reduced the mortality in COVID-19 induced ARDS (C-ARDS) patients treated in the CONFIDENT trial. As patients are immunologically heterogeneous, we hypothesized that clusters may differ in their treatment responses to CP. Methods We measured 20 cytokines, chemokines and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients of centers having accepted to participate in this secondary study. We performed descriptive statistics, unsupervised hierarchical cluster analysis, and examined the association between the clusters and CP effect on day-28 mortality. Results Of the 475 patients included in CONFIDENT, 391 (82%) were sampled, and 196/391 (50.1%) had been assigned to CP. We identified four sub-phenotypes representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients. The most contributing biomarkers in the principal component analysis were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 displayed a lower immune response, sub-phenotype-2 a higher adaptive response, sub-phenotype-3 the highest innate antiviral, pro and anti-inflammatory response, and adhesion molecule activation, and sub-phenotype-4 a higher pro and anti-inflammatory response, migration protein and adhesion molecule activation. Sub-phenotype-2 and sub-phenotype-4 had higher severity at the time of inclusion. The effect of CP treatment on mortality appeared higher than standard care in each sub-phenotype, without heterogeneity between sub-phenotypes (p = 0.97). Conclusion In patients with C-ARDS, we identified 4 sub-phenotypes based on their immune response. These sub-phenotypes were associated with different clinical profiles. The response to CP was similar across the 4 sub-phenotypes. Trial registration: Ethics Committee of the University Hospital of Liège CE 2020/239. Clinicaltrials.gov NCT04558476. Registered 2020-09-11, https://www.clinicaltrials.gov/study/NCT04558476 .

Abstract We evaluated the utility of transmission electron microscopy (TEM) in transbronchial lung cryobiopsy (TBLC) samples from 16 consecutive patients undergoing routine evaluation of fibrotic interstitial lung disease (ILD). Next to routine pathology examination, 1 to 2 TBLC samples were prepared for TEM analysis and evaluated using a Zeiss LEO EM 910. Subpleural cryobiopsies and unfrozen excision biopsies from fresh lobectomy tissue of non-ILD lung cancer patients served as controls. TEM provided high-quality images with only minor cryoartifacts as compared to controls. Furthermore, in several ILD patients we found marked microvascular endothelial abnormalities like luminal pseudopodia-like protrusions and inner surface defects. These were extensively present in four (25%), moderately present in seven (43.8%), and largely absent in five (31.3%) patients. A higher degree of TEM endothelial abnormalities was associated with younger age, non-specific interstitial pneumonia pattern, higher broncho-alveolar lavage lymphocyte count, positive autoantibodies, and lower spirometry, diffusion capacity and oxygenation biomarkers. We conclude that TEM evaluation of TBLC samples from ILD patients is feasible, while the observed microvascular alterations warrant further evaluation.

Abstract Membrane electrode assembly (MEA) cells incorporating Cu catalysts are effective for generating C2+ chemicals via the CO2 reduction reaction (CO2RR). However, the impact of MEA configuration on the inevitable reconstruction of Cu catalysts during CO2RR remains underexplored, despite its considerable potential to affect CO2RR efficacy. Herein, we demonstrate that MEA cells prompt a unique reconstruction of Cu, in contrast to H-type cells, which subsequently influences CO2RR outcomes. Utilizing three Cu-based catalysts, specifically engineered with different nanostructures, we identify contrasting selectivity trends in the production of C2+ chemicals between H-type and MEA cells. Operando X-ray absorption spectroscopy, alongside ex-situ analyses in both cell types, indicates that MEA cells facilitate the reduction of Cu2O, resulting in altered Cu surfaces compared to those in H-type cells. Time-resolved CO2RR studies, supported by Operando analysis, further highlight that significant Cu reconstruction within MEA cells is a primary factor leading to the deactivation of CO2RR into C2+ chemicals.

Abstract Palm swamp forests are wetland ecosystems typical of the Brazilian Cerrado, which in recent decades have undergone intense changes due to land use alterations and climate change. As a result of these disturbances, many palm swamps have been experiencing significant drying, which can also affect adjacent vegetation. In the present study, we evaluated whether the drying of palm swamps affects the structure of plant–herbivore networks located in adjacent savanna areas in Brazil. Our results show that savanna areas adjacent to dry zones of palm swamps have fewer interactions, fewer interacting species, and a less specialized topology, which corroborates our expectations. Our findings indicate that the drying of palm swamps also has propagated impacts on adjacent savanna vegetation, impairing more specialized interactions in these environments. On the other hand, contrary to expectations, plant–herbivore networks in dry zones displayed higher modularity, lower nestedness and lower robustness than those in wet zones, suggesting that in dry environments, species tend to compartmentalize their interactions, even with lower interaction specialization. This is the first study to investigate the impacts of environmental drying on the structure of plant–herbivore networks in tropical ecosystems, highlighting the complexity of these effects and their differential impact on specialized and generalized interactions. Understanding these dynamics is crucial for developing effective conservation and management strategies in the face of ongoing environmental changes.

Abstract Craniotomy or decompressive craniectomy are among the therapeutic options to prevent or treat secondary damage after severe brain injury. The choice of procedure depends, among other things, on the type and severity of the initial injury. It remains controversial whether both procedures influence the neurological outcome differently. Thus, estimating the risk of brain herniation and death and consequently potential organ donation remains difficult. All patients at the University Hospital Münster for whom an isolated craniotomy or decompressive craniectomy was performed as a treatment after severe brain injury between 2013 and 2022 were retrospectively included. Proportion of survivors and deceased were evaluated. Deceased were further analyzed regarding anticoagulants, comorbidities, type of brain injury, potential and utilized donation after brain death. 595 patients were identified, 296 patients survived, and 299 deceased. Proportion of decompressive craniectomy was higher than craniotomy in survivors (89% vs. 11%, p

Abstract Background Complete resection of malignant gliomas is hampered by the difficulty in distinguishing tumor cells at the infiltration zone. Fluorescence guidance with 5-ALA assists in reaching this goal. Using hyperspectral imaging, previous work characterized five fluorophores’ emission spectra in most human brain tumors. Methods In this paper, the effectiveness of these five spectra was explored for different tumor and tissue classification tasks in 184 patients (891 hyperspectral measurements) harboring low- (n = 30) and high-grade gliomas (n = 115), non-glial primary brain tumors (n = 19), radiation necrosis (n = 2), miscellaneous (n = 10) and metastases (n = 8). Four machine-learning models were trained to classify tumor type, grade, glioma margins, and IDH mutation. Results Using random forests and multilayer perceptrons, the classifiers achieve average test accuracies of 84–87%, 96.1%, 86%, and 91% respectively. All five fluorophore abundances vary between tumor margin types and tumor grades (p

Wood fuel from the agroforestry sector is one of the main strategies cited by the EU for reducing energetic dependance on foreign markets. Its sustainability, both economic and environmental, can be improved through the optimization of harvesting and chipping operations. This study was focused on the dynamic and energetic balance of the chipping phase carried out by a chipper operated by the power-take-off (PTO) of a medium-power tractor. Both machines were equipped with sensors for real-time monitoring of fuel consumption, PTO torque and speed, trunk diameter and working time during the comminution of 61 poplar trees grown in a medium rotation coppice system. The data analysis was carried out on the entire dataset (about 29,000 records) without considering their belonging to different trees. By means of proper data ordinations, it has been possible to define all the intervals in which the chipping stopped (e.g., between two trees) and to exclude them from the intervals of actual chipping. This has allowed forcomputation of operative and actual working time, as well as of the basic power required to operate the chipper and the power for actual chipping. Subsequently, the parameter values observed during actual chipping were related to the cutting diameters measured at the same instant. Subsequently, the dataset was divided according to seven diameter classes, and, for each class, the descriptive statistical indices of working time, work productivity, CO2 emissions, energy requirement and fuel consumption were calculated. Eventually, the correlation between the variations in trunk diameter and other parameters was verified both on the whole dataset and based on the class average values. The analysis made it possible to identify the conditions of greatest efficiency for the chipper. More generally, the method could help to increase the accuracy of measurements aimed at characterizing the performance of chippers from the point of view of dynamic energy requirements as well as in relation to different wood species.

Abstract Background The need for addition of external electron donors such as ethanol or lactate impairs the economic viability of chain elongation (CE) processes for the production of medium-chain carboxylates (MCC). However, using feedstocks with inherent electron donors such as silages of waste biomass can improve the economics. Moreover, the use of an appropriate inoculum is critical to the overall efficiency of the CE process, as the production of a desired MCC can significantly be influenced by the presence or absence of specific microorganisms and their metabolic interactions. Beyond, it is necessary to generate data that can be used for reactor design, simulation and optimization of a given CE process. Such data can be obtained using appropriate mathematical models to predict the dynamics of the CE process. Results In batch experiments using silages of sugar beet leaves, cassava leaves, and Elodea/wheat straw as substrates, caproate was the only MCC produced with maximum yields of 1.97, 3.48, and 0.88 g/kgVS, respectively. The MCC concentrations were accurately predicted with the modified Gompertz model. In a semi-continuous fermentation with ensiled sugar beet leaves as substrate and digestate from a biogas reactor as the sole inoculum, a prolonged lag phase of 7 days was observed for the production of MCC (C6–C8). The lag phase was significantly shortened by at least 4 days when an enriched inoculum was added to the system. With the enriched inoculum, an MCC yield of 93.67 g/kgVS and a productivity of 2.05 gMCC/L/d were achieved. Without the enriched inoculum, MCC yield and productivity were 43.30 g/kgVS and 0.95 gMCC/L/d, respectively. The higher MCC production was accompanied by higher relative abundances of Lachnospiraceae and Eubacteriaceae. Conclusions Ensiled waste biomass is a suitable substrate for MCC production using CE. For an enhanced production of MCC from ensiled sugar beet leaves, the use of an enriched inoculum is recommended for a fast process start and high production performance.

AIM: To investigate the influence of ophthalmic viscoelastic devices (OVDs) and different surgical approaches on the intraocular pressure (IOP) before and after creation of the curvilinear circular capsulorhexis (CCC) as a measure for anterior chamber stability during this maneuver. METHODS: Prospective experimental WetLab study carried out on enucleated porcine eyes. IOP was measured before and after CCC with the iCare Rebound tonometer (iCare ic200; iCare Finland Oy, Vantaa, Finland). The OVDs used were a cohesive one [Z-Hyalin, Carl Zeiss Meditec AG, Germany; hyaluronic acid (HA)] and a dispersive [Z-Celcoat, Carl Zeiss Meditec AG, Germany; hydroxy propylmethylcellulosis (HPMC)]. The CCC was created using Utrata forceps or 23 g microforceps in different combinations with the OVDs. RESULTS: Using the Utrata forceps the IOP dropped from 63.65±6.44 to 11.25±3.63 mm Hg during the CCC. The use of different OVDs made no difference. Using the 23 g microforceps the IOP dropped from 65.35±8.15 to 36.55±6.09 mm Hg. The difference between IOP drop using either Utrata forceps or 23 g microforceps was highly significant regardless of the OVD used. CONCLUSION: Using the sideport for the creation of the capsulorhexis leads to a lesser drop in IOP during this maneuver compared to the main incision in enucleated porcine eyes. The use of different OVD has no significant influence on IOP drop.

The illegal wildlife trade (IWT) is one of the largest global crime economies, directly threatening species and their habitats, and biodiversity, and indirectly the global climate, and countries’ economies. Syndicates operating within the IWT are often involved in trafficking of humans, weapons, and drugs. IWT takes place in large scale through international ports, with wildlife being smuggled inside shipping containers. Current methods to combat IWT and screen these shipping containers, such as X-ray scans, are expensive and time-consuming. Scent-detection animals present an innovative approach to combatting IWT, as animals may be better suited to distinguish between organic materials and less susceptible to visual concealment methods. Previous scent-detection work has largely focused on conservation dogs (Canis lupus familiaris). Here, we present a series of proof-of-principle studies training African giant pouched rats (Cricetomys ansorgei) to detect illegally trafficked wildlife. As initial proof-of-principle within a controlled laboratory environment, we trained rats (n=11) to detect the scent of pangolin scales (Manis spp.) and a threatened African hardwood (Dalbergia melanoxylon). In subsequent experiments, we trained these rats (n=10) to detect rhinoceros horn (family Rhinocerotidae), and elephant tusks (Loxodonta spp.). At the conclusion of these studies, rats (n=7) accurately identified all four target species (although ivory samples may have been cross-contaminated, and results should be interpreted with caution) while correctly rejecting non-target items commonly used by traffickers to conceal the presence of illicit material. Rats detected the presence of wildlife targets even when these were concealed in mixtures among non-target items. These results provide the foundation to train rats for scent-detection of illegally trafficked wildlife to combat IWT. The unique attributes of rats could allow them to complement existing screening technologies in the fight against IWT. Rats have low training and maintenance costs, flexibly work with multiple handlers, have a long lifespan, and a sophisticated sense of smell. Their small size also offers unique capabilities for the screening of shipping containers, such as being able to navigate densely packed areas or be lifted to assess contents of sealed containers by screening ventilation systems. Future directions include assessing operational feasibility of deploying rats at ports.

The levee effect poses a challenge for flood risk management. While there is research on the consequences of the levee effect in general, a detailed understanding of policies addressing residual risk is lacking. The aim of this research is to understand how coercive and cooperative policy designs are applied in spatial planning provisions dealing with residual flood risk and which context conditions influence planning authorities when deciding on a certain policy design. We applied a qualitative research approach, including expert interviews and examining relevant documents. The results show that coercive planning policies can regulate the use of areas with residual risk either by limiting the extension of building land or by prescribing flood adaptation of buildings. However, the formulation of such regulations is connected to the spatial context, the actors involved, past flood events and risk awareness. Cooperative planning policies address residual risk either as recommendations or by providing local authorities scope for decision-making when it comes to land use planning in residual risk areas. The interview partners also discussed possibilities that go beyond spatial planning, such as emergency management. The research shows the variety of policies that can offer ways of dealing with flooding beyond the expected level.

IntroductionThe present study investigates the feasibility and usability of a sensor-based eHealth treatment in psychotherapy for pediatric obsessive-compulsive disorder (OCD), and explores the promises and pitfalls of this novel approach. With eHealth interventions, therapy can be delivered in a patient's home environment, leading to a more ecologically valid symptom assessment and access to experts even in rural areas. Furthermore, sensors can help indicate a patient's emotional and physical state during treatment. Finally, using sensors during exposure with response prevention (E/RP) can help individualize therapy and prevent avoidance behavior.MethodsIn this study, we developed and subsequently evaluated a multimodal sensor-based eHealth intervention during 14 video sessions of cognitive-behavioral therapy (CBT) in 20 patients with OCD aged 12-18. During E/RP, we recorded eye movements and gaze direction via eye trackers, and an ECG chest strap captured heart rate (HR) to identify stress responses. Additionally, motion sensors detected approach and avoidance behavior.ResultsThe results indicate a promising application of sensor-supported therapy for pediatric OCD, such that the technology was well-accepted by the participants, and the therapeutic relationship was successfully established in the context of internet-based treatment. Patients, their parents, and the therapists all showed high levels of satisfaction with this form of therapy and rated the wearable approach in the home environment as helpful, with fewer OCD symptoms perceived at the end of the treatment.DiscussionThe goal of this study was to gain a better understanding of the psychological and physiological processes that occur in pediatric patients during exposure-based online treatment. In addition, 10 key considerations in preparing and conducting sensor-supported CBT for children and adolescents with OCD are explored at the end of the article. This approach has the potential to overcome limitations in eHealth interventions by allowing the real-time transmission of objective data to therapists, once challenges regarding technical support and hardware and software usability are addressed. Clinical Trial Registrationwww.ClinicalTrials.gov, identifier (NCT05291611).

BackgroundThe use of mobile tools in nursing care is indispensable. Given the importance of nurses’ acceptance of these tools in delivering effective care, this issue requires greater attention. ObjectiveThis study aims to design the Mobile Health Tool Acceptance Scale for Nurses based on the Expectation-Confirmation Theory and to evaluate it psychometrically. MethodsUsing a Waltz-based approach grounded in existing tools and the constructs of the Expectation-Confirmation Theory, the initial version of the scale was designed and evaluated for face and content validity. Construct validity was examined through exploratory factor analysis, concurrent validity, and known-group comparison. Reliability was assessed using measures of internal consistency and stability. ResultsThe initial version of the scale consisted of 33 items. During the qualitative and quantitative content validity stage, 1 item was added and 1 item was removed. Exploratory factor analysis, retaining 33 items, identified 5 factors that explained 70.53% of the variance. A significant positive correlation was found between the scores of the designed tool and nurses’ attitudes toward using mobile-based apps in nursing care (r=0.655, P

Summary: Background: Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). Findings: 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of −0.65 [−0.98, −0.31], p = 0.0002, I2 = 66.1%), higher response (OR = 0.97 [0.50, 1.44], p

Abstract Neurons in the inferotemporal (IT) cortex respond selectively to complex visual features, implying their role in object perception. However, perception is subjective and cannot be read out from neural responses; thus, bridging the causal gap between neural activity and perception demands independent characterization of perception. Historically, though, the complexity of the perceptual alterations induced by artificial stimulation of IT cortex has rendered them impossible to quantify. To address this old problem, we tasked male macaque monkeys to detect and report optical impulses delivered to their IT cortex. Combining machine learning with high-throughput behavioral optogenetics, we generated complex and highly specific images that were hard for the animal to distinguish from the state of being cortically stimulated. These images, named “perceptograms” for the first time, reveal and depict the contents of the complex hallucinatory percepts induced by local neural perturbation in IT cortex. Furthermore, we found that the nature and magnitude of these hallucinations highly depend on concurrent visual input, stimulation location, and intensity. Objective characterization of stimulation-induced perceptual events opens the door to developing a mechanistic theory of visual perception. Further, it enables us to make better visual prosthetic devices and gain a greater understanding of visual hallucinations in mental disorders.

Abstract Background Widespread inappropriate use of antimicrobial substances drives resistance development worldwide. In long-term care facilities (LTCF), antibiotics are among the most frequently prescribed medications. More than one third of antimicrobial agents prescribed in LTCFs are for urinary tract infections (UTI). We aimed to increase the number of appropriate antimicrobial treatments for UTIs in LTCFs using a multi-faceted antimicrobial stewardship intervention. Methods We performed a non-randomized cluster-controlled intervention study. Four LTCFs of the Geriatric Health Centers Graz were the intervention group, four LTCFs served as control group. The main components of the intervention were: voluntary continuing medical education for primary care physicians, distribution of a written guideline, implementation of the project homepage to distribute guidelines and videos and onsite training for nursing staff. Local nursing staff recorded data on UTI episodes in an online case report platform. Two blinded reviewers assessed whether treatments were adequate. Results 326 UTI episodes were recorded, 161 in the intervention group and 165 in the control group. During the intervention period, risk ratio for inadequate indication for treatment was 0.41 (95% CI 0.19–0.90), p = 0.025. In theintervention group, the proportion of adequate antibiotic choices increased from 42.1% in the pre-intervention period, to 45.9% during the intervention and to 51% in the post-intervention period (absolute increase of 8.9%). In the control group, the proportion was 36.4%, 33.3% and 33.3%, respectively. The numerical difference between intervention group and control group in the post-intervention period was 17.7% (difference did not reach statistical significance). There were no significant differences between the control group and intervention group in the safety outcomes (proportion of clinical failure, number of hospital admissions due to UTI and adverse events due to antimicrobial treatment). Conclusions An antimicrobial stewardship program consisting of practice guidelines, local and web-based education for nursing staff and general practitioners resulted in a significant increase in adequate treatments (in terms of decision to treat the UTI) during the intervention period. However, this difference was not maintained in the post-intervention phase. Continued efforts to improve the quality of prescriptions further are necessary. Trial registration The trial was registered at ClinicalTrials.gov NCT04798365.

Abstract Background Species flocks in ancient lakes, and particularly those arising from adaptive radiation, make up the bulk of overall taxonomic and morphological diversity in these insular ecosystems. For these mostly young species assemblages, classical mitochondrial barcoding markers have so far been key to disentangle interspecific relationships. However, with the rise and further development of next-generation sequencing (NGS) methods and mapping tools, genome-wide data have become an increasingly important source of information even for non-model groups. Results Here, we provide, for the first time, a comprehensive mitogenome dataset of freshwater gastropods endemic to Sulawesi and thus of an ancient lake invertebrate species flock in general. We applied low-coverage whole-genome sequencing for a total of 78 individuals including 27 out of the 28 Tylomelania morphospecies from the Malili lake system as well as selected representatives from Lake Poso and adjacent catchments. Our aim was to assess whether mitogenomes considerably contribute to the phylogenetic resolution within this young species flock. Interestingly, we identified a high number of variable and parsimony-informative sites across the other ‘non-traditional’ mitochondrial loci. However, although the overall support was very high, the topology obtained was largely congruent with previously published single-locus phylogenies. Several clades remained unresolved and a large number of species was recovered polyphyletic, indicative of both rapid diversification and mitochondrial introgression. Conclusions This once again illustrates that, despite the higher number of characters available, mitogenomes behave like a single locus and thus can only make a limited contribution to resolving species boundaries, particularly when introgression events are involved.

Abstract The frequency scaling exponent of low-frequency excitations in microscopically small glasses, which do not allow for the existence of waves (phonons), has been in the focus of the recent literature. The density of states g(ω) of these modes obeys an ω s scaling, where the exponent s, ranging between 2 and 5, depends on the quenching protocol. The orgin of these findings remains controversal. Here we show, using heterogeneous-elasticity theory, that in a marginally-stable glass sample g(ω) follows a Debye-like scaling (s = 2), and the associated excitations (type-I) are of random-matrix type. Further, using a generalisation of the theory, we demonstrate that in more stable samples, other, (type-II) excitations prevail, which are non-irrotational oscillations, associated with local frozen-in stresses. The corresponding frequency scaling exponent s is governed by the statistics of small values of the stresses and, therefore, depends on the details of the interaction potential.

Abstract Cyclic adenosine 3’, 5’ monophosphate (cAMP)-dependent Protein Kinase A (PKA) is a multi-functional serine/threonine kinase that regulates a wide variety of physiological processes including gene transcription, metabolism, and synaptic plasticity. Genomic sequencing studies have identified both germline and somatic variants of the catalytic and regulatory subunits of PKA in patients with metabolic and neurodevelopmental disorders. In this review we discuss the classical cAMP/PKA signaling pathway and the disease phenotypes that result from PKA variants. This review highlights distinct isoform-specific cognitive deficits that occur in both PKA catalytic and regulatory subunits, and how tissue-specific distribution of these isoforms may contribute to neurodevelopmental disorders in comparison to more generalized endocrine dysfunction.

Abstract MALTA2 is the latest full-scale prototype of the MALTA family of Depleted Monolithic Active Pixel Sensors (DMAPS) produced in Tower Semiconductor 180 nm CMOS sensor imaging technology. In order to comply with the requirements of high energy physics (HEP) experiments, various process modifications and front-end changes have been implemented to achieve low power consumption, reduce random telegraph signal (RTS) noise, and optimise the charge collection geometry. Compared to its predecessors, MALTA2 targets the use of a high-resistivity, thick Czochralski (Cz) substrates in order to demonstrate radiation hardness in terms of detection efficiency and timing resolution up to 3 $$\times $$ × 10 $$^{15}$$ 15 1 MeV $$\mathrm {n_{eq}/{cm}^2}$$ n eq / cm 2 with backside metallisation to achieve good propagation of the bias voltage. This manuscript shows the results that were obtained with non-irradiated and irradiated MALTA2 samples on Cz substrates from the CERN SPS test beam campaign from 2021 to 2023 using the MALTA telescope.

IntroductionAnti-Xa serves as a clinical surrogate for assessing the efficacy and bleeding risk in patients treated with enoxaparin for thromboembolic events. Evidence from the literature and empirical observations suggest that patients are underdosed in clinical practice to avoid bleeding complications. This study aimed to investigate such underdosing of enoxaparin and its potential impact on achieving therapeutic anti-Xa levels.MethodsThis multicentric, retrospective, observational study included patients with acute ischemic stroke due to atrial fibrillation. All patients received enoxaparin in the therapeutic setting with subsequent anti-Xa measurements. The one-sample, one-tailed Wilcoxon signed-rank test was used to identify a significant difference between the doses administered and the recommended daily dose. Logistic regression model analysis was performed to identify additional predictors affecting achievement of the therapeutic anti-Xa target range. Stepwise forward-backward selection with Akaike’s information criterion as metric was applied to refine the logistic regression model.ResultsA total of 145 patients from the university hospitals of St. Pölten and Tulln in Lower Austria were included. The median daily enoxaparin dose administered was 1.23 mg/kg, resulting in an overall target range achievement rate of 66%. As compared to recommended therapeutic doses, significant underdosing of enoxaparin was evident in both participating centers (p < 0.001). The calculated threshold dose to achieve the therapeutic target range with a 90% probability was 1.5 mg/kg enoxaparin daily. Female sex was found to be a strong independent predictor of achieving a therapeutic target range (OR 9.44; 95% CI 3.40–30.05, p < 0.001).ConclusionDespite the underdosing observed in both centers, therapeutic anti-Xa levels were achieved with lower than recommended doses of enoxaparin, and women required even lower doses than men. These findings warrant further confirmation by prospective studies.

Abstract Shallow creep events provide opportunities to understand the mechanical properties and behavior of faults. However, due to physical limitations observing creep events, the precise spatio‐temporal evolution of slip during creep events is not well understood. In 2023, the Superstition Hills and Imperial faults in California each experienced centimeter‐scale slip events that were captured in unprecedented detail by satellite radar, sub‐daily Global Navigation Satellite Systems, and creepmeters. In both cases, the slip propagated along the fault over 2–3 weeks. The Superstition Hills event propagated bilaterally away from its initiation point at average velocities of ∼9 km/day, but propagation velocities were locally much higher. The ruptures were consistent with slip from tens of meters to ∼2 km depths. These slowly propagating events reveal that the shallow crust of the Imperial Valley does not obey purely velocity‐strengthening or velocity‐weakening rate‐and‐state friction, but instead requires the consideration of fault heterogeneity or fault‐frictional behaviors such as dilatant strengthening.

Abstract In this paper, we present a novel algorithm to optimize the design of Reservoir Computing using Cellular Automata models for time series applications. Besides selecting the models’ hyperparameters, the proposed algorithm particularly solves the open problem of Linear Cellular Automaton rule selection. The selection method pre-selects only a few promising candidate rules out of an exponentially growing rule space. When applied to relevant benchmark datasets, the selected rules achieve low errors, with the best rules being among the top 5% of the overall rule space. The algorithm was developed based on mathematical analysis of Linear Cellular Automaton properties and is backed by almost one million experiments, adding up to a computational runtime of nearly one year. Comparisons to other state-of-the-art time series models show that the proposed Reservoir Computing using Cellular Automata models have lower computational complexity and, at the same time, achieve lower errors. Hence, our approach reduces the time needed for training and hyperparameter optimization by up to several orders of magnitude.

Abstract Highly pathogenic avian Influenza virus (HPAIV) has spread in an unprecedented extent globally in recent years. Despite the large reports of cases in Asia, Europe, and North America, little is known about its circulation in South America. Here, we describe the isolation, and whole genome characterization of HPAIV obtained from sampling 26 wild bird species in Peru, representing one of the largest studies in our region following the latest HPAIV introduction in South America. Out of 147 samples analyzed, 22 were positive for detection of avian influenza virus using a qRT-PCR-based assay. Following inoculation into embryonated chicken eggs, fourteen viral isolates were obtained from which nine isolates were selected for genome characterization, based on their host relevance. Our results identified the presence of HPAIV H5N1 subtype in a highly diverse wild bird species. Phylogenetic analysis revealed that these isolates correspond to the clade 2.3.4.4b, sharing a common ancestor with North American isolates and forming a monophyletic group along with isolates from Chile. Altogether, changes at the amino acid levels compared to their closest relatives indicates the virus is evolving locally, highlighting the need for constant genomic surveillance. This data evidence the chances for spillover events increases as the virus spreads into large populations of immunologically naïve avian species and adding conditions for cross species transmission.

Abstract High-grade gliomas (HGG) carry a dismal prognosis. Diagnosis comprises MRI followed by histopathological evaluation of tissue; no blood biomarker is available. Patients are subjected to serial MRIs and, if unclear, surgery for monitoring of tumor recurrence, which is laborious. MRI provides only limited diagnostic information regarding the differentiation of true tumor progression from therapy-associated side effects. 5-aminolevulinic acid (5-ALA) is routinely used for induction of protoporphyrin IX (PpIX) accumulation in malignant glioma tissue, enabling improved tumor visualization during fluorescence-guided resection (FGR). We investigated whether PpIX can also serve as a serum HGG marker to monitor relapse. Patients (HGG: n = 23 primary, pHGG; n = 5 recurrent, rHGG) undergoing FGR received 5-ALA following standard clinical procedure. The control group of eight healthy volunteers (HCTR) also received 5-ALA. Serum was collected before and repeatedly up to 72 h after drug administration. Significant PpIX accumulation in HGG was observed after 5-ALA administration (ANOVA: p = 0.005, post-hoc: HCTR vs. pHGG p = 0.029, HCTR vs. rHGG p = 0.006). Separation of HCTR from pHGG was possible when maximum serum PpIX levels were reached (CI95% of tMax). ROC analysis of serum PpIX within CI95% of tMax showed successful classification of HCTR and pHGG (AUCROC 0.943, CI95% 0.884–1.000, p

Abstract Chemoreception – the ability to smell and taste – is an essential sensory modality of most animals. The number and type of chemical stimuli that animals can perceive depends primarily on the diversity of chemoreceptors they possess and express. In vertebrates, six families of G protein-coupled receptors form the core of their chemosensory system, the olfactory/pheromone receptor gene families OR, TAAR, V1R and V2R, and the taste receptors T1R and T2R. Here, we study the vertebrate chemoreceptor gene repertoire and its evolutionary history. Through the examination of 1,527 vertebrate genomes, we uncover substantial differences in the number and composition of chemoreceptors across vertebrates. We show that the chemoreceptor gene families are co-evolving, highly dynamic, and characterized by lineage-specific expansions (for example, OR in tetrapods; TAAR, T1R in teleosts; V1R in mammals; V2R, T2R in amphibians) and losses. Overall, amphibians, followed by mammals, are the vertebrate clades with the largest chemoreceptor repertoires. While marine tetrapods feature a convergent reduction of chemoreceptor numbers, the number of OR genes correlates with habitat in mammals and birds and with migratory behavior in birds, and the taste receptor repertoire correlates with diet in mammals and with aquatic environment in fish.

Abstract The Asian Citrus Psyllid (ACP), Diaphorina citri, is a vector of the pathological bacterium Candidatus Liberibacter asiaticus (CLas), which causes the most devastating disease to the citrus industry worldwide, known as greening or huanglongbing (HLB). Earlier field tests with an acetic acid-based lure in greening-free, ‘Valencia’ citrus orange groves in California showed promising results. The same type of lures tested in São Paulo, Brazil, showed unsettling results. During the unsuccessful trials, we noticed a relatively large proportion of females in the field, ultimately leading us to test field-collected males and females for Wolbachia and CLas. The results showed high rates of Wolbachia and CLas infection in field populations. We then compared the olfactory responses of laboratory-raised, CLas-free, and CLas-infected males to acetic acid. As previously reported, CLas-uninfected males responded to acetic acid at 1 µg. Surprisingly, CLas-infected males required 50 × higher doses of the putative sex pheromone, thus explaining the failure to capture CLas-infected males in the field. CLas infection was also manifested in electrophysiological responses. Electroantennogram responses from CLas-infected ACP males were significantly higher than those obtained with uninfected males. To the best of our knowledge, this is the first report of a pathogen infection affecting a vector’s response to a sex attractant.

Abstract Background Despite improvements in surgical as well as adjuvant therapies over the last decades, the prognosis for patients with glioblastoma remains poor. Five-Aminolevulinic acid (5-ALA) induced porphyrins are already used for fluorescence-guided resection and as photosensitizer for photodynamic therapy. New findings reveal their potential use as sensitizing agents in combination with ionizing radiation. Methods We initiated a phase I/II dose escalation study, treating patients with recurrence of glioblastoma with oral 5-ALA concurrent to radiotherapy (RT). This prospective single-center study based in the University Hospital Münster aims to recruit 30 patients over 18 years of age with histologically verified recurrence of supratentorial glioblastoma in good performance status (KPS ≥ 60). Following a 3 + 3 dose-escalation design, patients having undergone re-resection will receive a 36 Gy RT including radiodynamic therapy fractions (RDT). RDT constitutes of oral administration of 5-ALA before the irradiation session. Two cohorts will additionally receive two fractions of neoadjuvant treatment three and two days before surgery. To determine the maximum tolerated dose of repeated 5-ALA-administration, the number of RDT-fractions will increase, starting with one to a maximum of eight fractions, while closely monitoring for safety and toxicity. Follow-up will be performed at two and five months after treatment. Primary endpoint will be the maximum tolerated dose (MTD) of repeated ALA-administration, secondary endpoints are event-free-, progression-free-, and overall-survival. Additionally, 5-ALA metabolites and radiobiological markers will be analysed throughout the course of therapy and tissue effects after neoadjuvant treatment will be determined in resected tissue. This protocol is in accordance with the SPIRIT guidelines for clinical trial protocols. Discussion This is the protocol of the ALA-RDT in GBM-study, the first-in-man evaluation of repeated administration of 5-ALA as a radiosensitizer for treatment of recurrent glioblastoma. Trial registration This study was approved by the local ethics committee of the Medical Association of Westphalia-Lippe and the University of Münster on 12.10.2022, the German federal institute for Drugs and medical devices on 13.10.2022 and the federal office for radiation protection on 29.08.2022. This trial was registered on the public European EudraCT database (EudraCT-No.: 2021-004631-92) and is registered under www.cliniclatrials.gov (Identifier: NCT05590689).

Abstract Background Healthcare literature suggests that leadership behavior has a profound impact on nurse work-related well-being. Yet, more research is needed to better conceptualize, measure, and analyse the concepts of leadership and well-being, and to understand the psychological mechanisms underlying this association. Combining Self-Determination and Job Demands-Resources theory, this study aims to investigate the association between engaging leadership and burnout and work engagement among nurses by focusing on two explanatory mechanisms: perceived job characteristics (job demands and resources) and intrinsic motivation. Methods A cross-sectional survey of 1117 direct care nurses (response rate = 25%) from 13 general acute care hospitals in Belgium. Validated instruments were used to measure nurses’ perceptions of engaging leadership, burnout, work engagement, intrinsic motivation and job demands and job resources. Structural equation modeling was performed to test the hypothesised model which assumed a serial mediation of job characteristics and intrinsic motivation in the relationship of engaging leadership with nurse work-related well-being. Results Confirmatory factor analysis indicated a good fit of the measurement model. The findings offer support for the hypothesized model, indicating that engaging leadership is linked to enhanced well-being, as reflected in increased work engagement, and reduced burnout. The results further showed that this association is mediated by nurses’ perceptions of job resources and intrinsic motivation. Notably, while job demands mediated the relationship between EL and nurses’ well-being, the relationship became unsignificant when including intrinsic motivation as second mediator. Conclusions Engaging leaders foster a favourable work environment for nursing staff which is not only beneficial for their work motivation but also for their work-related well-being. Engaging leadership and job resources are modifiable aspects of healthcare organisations. Interventions aimed at developing engaging leadership behaviours among nursing leaders and building job resources will help healthcare organisations to create favourable working conditions for their nurses. Trial Registration: The study described herein is funded under the European Union’s Horizon 2020 Research and Innovation programme from 2020 to 2023 (Grant Agreement 848031). The protocol of Magnet4Europe is registered in the ISRCTN registry (ISRCTN10196901).

This article deals with Eugen Gomringer’s ideograms and their translations. It points out that there is no loss of meaning in the different versions in German, French, English, and Spanish. That Gomringer succeeds in this is examined primarily through Gomringer’s medial games between white space, black letters, orality, and writing. An attempt is made to establish that Gomringer’s linguistic reduction offers the prospect of a form of transnational communication in which it is not necessary to master all the prevailing linguistic norms. Instead, it is for the audience to fill in the empty space themselves, and to discover silence and secrecy there.

The new production paradigm, Industry 4.0, seeks to improve the productivity of industries. However, to implement Industry 4.0, there is a need for high investments in modern processes/equipment, which can impact this implementation. The contribution of this paper is to present the Technology Analysis model – TAM 4.0, to support the management of manufacturing processes in deciding when to acquire new equipment/ processes or when to modernize existing ones (retrofit) to implement Industry 4.0. The model was evaluated and improved by experts using the Delphi method, being a theoretical contribution to the Industry 4.0 body of knowledge and also to practice, helping those involved in implementation projects.

Abstract Since decades, the concept of vibrational density of states in glasses has been mirrored in liquids by the instantaneous-normal-mode spectrum. In glasses instantaneous configurations are believed to be situated close to minima of the potential-energy hypersurface and all eigenvalues of the associated Hessian matrix are positive. In liquids this is no longer true, and modes corresponding to both positive and negative eigenvalues exist. The instantaneous-normal-mode spectrum has been numerically investigated in the past, and it has been demonstrated to bring important information on the liquid dynamics and transport properties. A systematic deeper theoretical understanding is now needed. Heterogeneous-elasticity theory has proven to be particularly successful in explaining many details of the low-frequency excitations in glasses, ranging from the thoroughly studied boson peak, to other anomalies related to the crossover between wave-like and random-matrix-like excitations. Here we present an extension of heterogeneous-elasticity theory to the liquid state, and show that the outcome of the theory agrees well to the results of extensive molecular-dynamics simulations of a model liquid at different temperatures. We find that the spectrum of eigenvalues $$\rho (\lambda )$$ ρ ( λ ) has a sharp maximum close to (but not at) $$\lambda =0$$ λ = 0 , and decreases monotonically with $$|\lambda |$$ | λ | on both its stable and unstable side. We show that the spectral shape strongly depends on temperature, being symmetric at high temperatures and becoming rather asymmetric at low temperatures, close to the dynamical critical temperature. Most importantly, we demonstrate that the theory naturally reproduces a surprising phenomenon, a zero-energy spectral singularity with a cusp-like character developing in the vibrational spectra upon cooling. This feature, known from a few previous numerical studies, has been generally overlooked in the past due to a misleading representation of the data. We provide a thorough analysis of this issue, based on both very accurate predictions of our theory, and computational studies of model liquid systems with extended size.

Subconcussive blast exposure has been shown to alter neurological functioning. However, the extent to which neurological dysfunction persists after blast exposure is unknown. This longitudinal study examined the potential short- and long-term effects of repeated subconcussive blast exposure on neuromotor performance from heavy weapons training in military personnel. A total of 214 participants were assessed; 137 were exposed to repeated subconcussive blasts and 77 were not exposed to blasts (controls). Participants completed a short stepping-in-place task while an Android smartphone app placed on their thigh recorded movement kinematics. We showed acute suppression of neuromotor variability 6 h after subconcussive blast exposure, followed by a rebound to levels not different from baseline at the 72 h, 2-week, and 3-month post-tests. It is postulated that this suppression of neuromotor variability results from a reduction in the functional degrees of freedom from the subconcussive neurological insult. It is important to note that this change in behavior is short-lived, with a return to pre-blast exposure movement kinematics within 72 h.

This study investigates dietary supplement use among rugby players and their general health, focusing on prevalence and underlying motivations. Involving 92 athletes, it examines the relationship between supplement usage, motivations, and health outcomes using the 36-item Short Form Health Survey and a 24-item ad hoc questionnaire. Findings reveal a high frequency of supplement usage, motivated by desires to enhance performance, appearance, and mood. Significant differences in health-related quality of life are found between users and non-users, particularly in mental health, social functioning, and emotional stability. Motivations like performance enhancement and body shape manipulation were linked to altered health perceptions, indicating the psychosocial impacts of supplementation. This study emphasizes the need to consider the holistic effects of supplements on athlete well-being, advocating for a balanced approach prioritizing both physical and mental health. It calls for increased awareness among athletes, coaches, and sports professionals about the potential risks and benefits of supplement use and the importance of informed decision-making. Additionally, it highlights the need for further research to understand the mechanisms of supplement use and its impact on athlete health, aiming to enhance sports science and promote overall athlete well-being in competitive environments.

The Güiña (Leopardus guigna), the smallest Neotropical feline, inhabits central and southern Chile and western Argentina. This communication reports the first documented instance of a güiña swimming in a marine environment, observed in the Refugio Channel, which separates Refugio Island from the mainland in Northern Patagonia, Chile. In April 2023, a local resident recorded video footage of a güiña swimming near the eastern shore of the channel, emerging from the water, shaking off, and climbing a tree to groom itself. This observation suggests that the güiña might use the seacoast when searching for food, particularly during periods of low terrestrial prey availability during the winter. The ability of the güiña to adapt to such environments underscores the species’ ecological flexibility, previously undocumented in this context, and highlights the need for integrating marine resources into the species’ conservation strategies. The video’s quality is limited due to the simplicity of the recording device, but it provides crucial visual evidence of this behavior.

Objective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of MGMT, p15, and p16 methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Results: Instability was observed in all examined epigenetic markers. MGMT methylation changed in 30% of patients, p15 methylation changed in 35%, and p16 methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Conclusions: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.

For animals to locate resources and stay safe, navigation is an essential cognitive skill. Blind people use different navigational strategies to encode the environment. Path integration significantly influences spatial navigation, which is the ongoing update of position and orientation during self-motion. This study examines two separate things: (i) how guided and non-guided strategies affect blind individuals in encoding and mentally representing a trajectory and (ii) the sensory preferences for potential navigational aids through questionnaire-based research. This study first highlights the significant role that the absence of vision plays in understanding body centered and proprioceptive cues. Furthermore, it also underscores the urgent need to develop navigation-assistive technologies customized to meet the specific needs of users.

While current anti-Spike protein (SP) vaccines have been pivotal in managing the pandemic, their limitations in delivery, storage, and the inability to provide mucosal immunization (preventing infections) highlight the ongoing necessity for research and innovation. To tackle these constraints, our research group developed a bacterial-based vaccine using a non-pathogenic E. coli Nissle 1917 (EcN) strain genetically modified to express the SARS-CoV-2 spike protein on its surface (EcN-pAIDA1-SP). We intranasally delivered the EcN-pAIDA1-SP in two doses and checked specific IgG/IgA production as well as the key immune mediators involved in the process. Moreover, following the initial and booster vaccine doses, we exposed both immunized and non-immunized mice to intranasal delivery of SARS-CoV-2 SP to assess the effectiveness of EcN-pAIDA1-SP in protecting lung tissue from the inflammation damage. We observed detectable levels of anti-SARS-CoV-2 spike IgG in serum samples and IgA in bronchoalveolar lavage fluid two weeks after the initial treatment, with peak concentrations in the respective samples on the 35th day. Moreover, immunoglobulins displayed a progressively enhanced avidity index, suggesting a selective binding to the spike protein. Finally, the pre-immunized group displayed a decrease in proinflammatory markers (TLR4, NLRP3, ILs) following SP challenge, compared to the non-immunized groups, along with better preservation of tissue morphology. Our probiotic-based technology provides an effective immunobiotic tool to protect individuals against disease and control infection spread.

Introduction Chronic obstructive pulmonary disease is a systemic disease characterized not only by respiratory symptoms but also by physical deconditioning and muscle weakness. One prominent manifestation of this disease is the decline in respiratory muscle strength. Previous studies have linked the genotypes of insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) to muscle weakness in other populations without this disease. However, there is a notable knowledge gap regarding the biological mechanisms underlying respiratory muscle weakness, particularly the role of IGF-1 and IGF-2 genotypes in this pulmonary disease. Therefore, this study aimed to investigate, for the first time, the association between IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with chronic obstructive pulmonary disease. In addition, we analyzed the relationship between oxidative stress, chronic inflammation, and vitamin D with respiratory muscle strength. Methods A cross sectional study with 61 individuals with chronic obstructive pulmonary disease. Polymerase chain reaction of gene polymorphisms IGF-1 (rs35767) and IGF-2 (rs3213221) was analyzed. Other variables, related to oxidative stress, inflammation and Vitamin D were dosed from peripheral blood. Maximal inspiratory and expiratory pressure were measured. Results The genetic polymorphisms were associated with respiratory muscle strength ( 3.0 and 3.5; = 0.57). Specific genotypes of IGF-1 and IGF-2 presented lower maximal inspiratory and expiratory pressure (

Introduction/Justification: Prostate cancer is among the most common cancers in males. The PSMA (Prostate-Specific Membrane Antigen), a protein expressed in prostate cancer cells, has been used in the control of that cancer and can also be taken up in the neovasculature of other non-prostatic tumors, where it should may be a useful tool. In a normal prostate, the neuroendocrine (NE) cells represent a smaller population than the epithelial cells and may play a role in the regulation. In cases of prostatic adenocarcinoma, a portion of the carcinomatous cell population undergoes transdifferentiation processes, becoming cells that express NE markers related to progression and poor prognosis. The carcinoembryonic antigen (CEA) is one of the main markers for monitoring patients who have undergone transdifferentiation. Studies indicate that the transdifferentiation is often accelerated by conventional androgen deprivation therapy, leading to the progression of the cancer, which highlights the need for new therapeutic strategies. Neuroendocrine tumors (NETs) are a diverse group of neoplasms originating from NE cells present in different organs. Radioactive therapy with 177Lu-DOTA is considered an innovative approach in treating NETs, specifically targeted to tumor tissues, minimizing the impact on healthy tissues. Considering the similarities between the cells of NETs and the NE cells from prostate adenocarcinoma, this report aims to demonstrate the application of 177Lu-PSMA and/or 177Lu-DOTA in a case where metachronous tumors with NE cells exist. Report: Male, 73 years old, with a neuroendocrine pancreatic cancer (since 2000) being treated with Octreotide. Was diagnosed with prostatic adenocarcinoma, Gleason 4+4=8, ECIVB (T3aN0M1b) in 2021, started androgenic deprivation with Gosserelina and Zoledronato, associated with Abiraterone+Prednisone. The PSA had decreased by 98,73% with treatment, but during the evaluation, sonographic imaging demonstrated liver lesions compatible with metastatic disease and an increase in liver enzymes, which led to the suspension of Abiraterone. A 1007-PSMA-PET/CT (from 2023) with high uptake on the pancreas, liver, and multiple bone lesions led to the therapy with 177Lu-PSMA. After the first cycle of therapy, he presented a facial flush, which was solved spontaneously. After the second cycle of 177Lu-PSMA therapy, the laboratory demonstrated a significant reduction in PSA (52,4%) and Chromogranin A (58,7%), comparing before treatment. In the second PSMA-18F PET-CT (from 2024), the pancreatic mass has reduced by 30,7% and the hepatic lobes by 15,7% in comparison with the SUV from 2023. However, bone injuries have an increase of 15,8% on SUV in the thoracic spine, which leaves the doubt of flare phenomenon or disease progression. A Ga68-DOTA-PET/CT demonstrated intense uptake at the same lesions detected by PSMA-18F PET-CT. The patient has two different possibilities of radionuclide therapy. Behold, 177Lu-PSMA can be an alternative to prostate adenocarcinoma and NET dedifferentiation due to its increase in angiogenesis, demonstrated by 1007-PSMA-PET/CT and 177Lu-DOTA due to its increased uptake on neuroendocrine cells demonstrated by Ga68-DOTA-PET/CT. Conclusion: The case demonstrates the possibility of treating prostate and neuroendocrine tumors with 177Lu-PSMA and/or 177Lu-DOTA, depending on the pathology stage.

Background ‘Definite Neuroborreliosis (NB)’ is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Objective Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. Design and methods This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. Results We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated ‘definite NB’. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant ( P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Conclusion Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Immersive technology, such as extended reality, holds promise as a tool for educating ophthalmologists about the effects of low vision and for enhancing visual rehabilitation protocols. However, immersive simulators have not been evaluated for their ability to induce changes in the oculomotor system, which is crucial for understanding the visual experiences of visually impaired individuals. This study aimed to assess the REALTER (Wearable Egocentric Altered Reality Simulator) system’s capacity to induce specific alterations in healthy individuals’ oculomotor systems under simulated low-vision conditions. We examined task performance, eye movements, and head movements in healthy participants across various simulated scenarios. Our findings suggest that REALTER can effectively elicit behaviors in healthy individuals resembling those observed in individuals with low vision. Participants with simulated binocular maculopathy demonstrated unstable fixations and a high frequency of wide saccades. Individuals with simulated homonymous hemianopsia showed a tendency to maintain a fixed head position while executing wide saccades to survey their surroundings. Simulation of tubular vision resulted in a significant reduction in saccade amplitudes. REALTER holds promise as both a training tool for ophthalmologists and a research instrument for studying low vision conditions. The simulator has the potential to enhance ophthalmologists’ comprehension of the limitations imposed by visual disabilities, thereby facilitating the development of new rehabilitation protocols.

Introduction In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC–IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis.Methods A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed.Results Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most.Conclusion Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC–IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems.

Introduction: Measures to improve nurses' work environments include ensuring adequate staffing levels, recognising the importance of nursing work, involving nurses in decision-making processes, and improving interprofessional communication. The aim of this study was to analyse the job characteristics reported by nurses and their association with the dimensions of clinical practice environments in hospitals. Methods: A cross-sectional explorative research design was employed. The Slovene-language version of the Practice Environment Scale of the Nursing Work Index (PES-NWI(SI)) and data on nurses' job characteristics were used. A total of 1,010 nurses (403 general care nurses and 605 healthcare assistants) from ten Slovenian general hospitals participated in the study. Permission to conduct the research was granted by the Commission of the Republic of Slovenia for Medical Ethics. Results: The mean score of the PES-NWI(SI) was low (2.64), and the scale reliability was 0.937. The original theoretical five-factor structure was confirmed. The regression model explained the five factors in 26–47% of cases. The explanatory variables included opportunities for advancement, educational opportunities, professional status, satisfaction with current job and work environment, independence at work, and study leave. Discussion and conclusion: The study revealed managers' inadequate ability to ensure sufficient staffing, insufficient involvement of both respondents and managers in hospital affairs, and the lack of promotion opportunities. Creating an optimal work environment for nurses is an important task for managers and leaders. National healthcare policy must consider nurses as equal healthcare professionals and nursing as both a professional and scientific discipline.

BackgroundIn recent years, the fast-paced adoption of digital health (DH) technologies has transformed health care delivery. However, this rapid evolution has also led to challenges such as uncoordinated development and information silos, impeding effective health care integration. Recognizing these challenges, nations have developed digital health strategies (DHSs), aligning with their national health priorities and guidance from global frameworks. The World Health Organization (WHO)’s Global Strategy on Digital Health 2020-2025 (GSDH) guides national DHSs. ObjectiveThis study analyzes the DHSs of Tanzania and Germany as case studies and assesses their alignment with the GSDH and identifies strengths, shortcomings, and areas for improvement. MethodsA comparative policy analysis was conducted, focusing on the DHSs of Tanzania and Germany as case studies, selected for their contrasting health care systems and cooperative history. The analysis involved a three-step process: (1) assessing consistency with the GSDH, (2) comparing similarities and differences, and (3) evaluating the incorporation of emergent technologies. Primary data sources included national eHealth policy documents and related legislation. ResultsBoth Germany’s and Tanzania’s DHSs align significantly with the WHO’s GSDH, incorporating most of its 35 elements, but each missing 5 distinct elements. Specifically, Tanzania’s DHS lacks in areas such as knowledge management and capacity building for leaders, while Germany’s strategy falls short in engaging health care service providers and beneficiaries in development phases and promoting health equity. Both countries, however, excel in other aspects like collaboration, knowledge transfer, and advancing national DHSs, reflecting their commitment to enhancing DH infrastructures. The high ratings of both countries on the Global Digital Health Monitor underscore their substantial progress in DH, although challenges persist in adopting the rapidly advancing technologies and in the need for more inclusive and comprehensive strategies. ConclusionsThis study reveals that both Tanzania and Germany have made significant strides in aligning their DHSs with the WHO’s GSDH. However, the rapid evolution of technologies like artificial intelligence and machine learning presents challenges in keeping strategies up-to-date. This study recommends the development of more comprehensive, inclusive strategies and regular revisions to align with emerging technologies and needs. The research underscores the importance of context-specific adaptations in DHSs and highlights the need for broader, strategic guidelines to direct the future development of the DH ecosystem. The WHO’s GSDH serves as a crucial blueprint for national DHSs. This comparative analysis demonstrates the value and challenges of aligning national strategies with global guidelines. Both Tanzania and Germany offer valuable insights into developing and implementing effective DHSs, highlighting the importance of continuous adaptation and context-specific considerations. Future policy assessments require in-depth knowledge of the country’s health care needs and structure, supplemented by stakeholder input for a comprehensive evaluation.

Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee’s individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

Abstract The Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) is the world’s largest and most powerful particle accelerator colliding beams of protons and lead ions at energies up to 7 Z TeV, where Z is the atomic number. ALICE is one of the experiments optimised for heavy-ion collisions. A fixed-target experiment in ALICE is being considered to collide a portion of the beam halo, split using a bent crystal inserted in the transverse hierarchy of the LHC collimation system, with an internal target placed a few metres upstream of the existing detector. This study is carried out as a part of the Physics Beyond Collider effort at CERN. Fixed-target collisions offer many physics opportunities related to hadronic matter and the quark-gluon plasma to extend the research potential of the CERN accelerator complex. Production of physics events depends on the particle flux on the target. The machine layout for the fixed-target experiment is developed to provide a flux of particles on the target high enough to exploit the full capabilities of the ALICE detector acquisition system. This paper summarises the fixed-target layout consisting of the crystal assembly, the target and the downstream absorbers. We discuss the conceptual integration of these elements within the LHC ring, the impact on ring losses, and expected performance in terms of particle flux on target.