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Summary: Behavioral changes play an important role for animals to cope with human-induced rapid environmental change such as biological invasions. The concept of eco-evolutionary experience (EEE) postulates that native species are more strongly impacted by non-native species the more these differ from species they have coevolved with. Also, EEE could influence the degree of innovation in new behaviors shown by native species. We conceived categorization schemes to assess both EEE and innovation and applied them to 86 records of behavioral change in native birds (n = 50), mammals (n = 19), and amphibians (n = 17). The results of this proof-of-concept study suggest an interconnectedness of EEE, innovation, and resulting population dynamics of native species. However, quantitative analyses were limited by the small size of our dataset. We encourage the use of the categorization schemes proposed here to close important knowledge gaps, so that our findings can be revisited with larger datasets in the future.

Background:. Dermal scaffolds have created a paradigm shift for burn and wound management by providing improved healing and less scarring, while improving cosmesis and functionality. Dermal regeneration template (DRT) is a bilayer membrane for dermal regeneration developed by Yannas and Burke in the 1980s. The aim of this review is to summarize clinical evidence for dermal scaffolds focusing on DRT for the management and reconstruction of burn injuries and complex wounds. Methods:. A comprehensive search of PubMed was performed from the start of indexing through November 2022. Articles reporting on DRT use in patients with burns, limb salvage, and wound reconstruction were included with focus on high-level clinical evidence. Results:. DRT has become an established alternative option for the treatment of full-thickness and deep partial-thickness burns, with improved outcomes in areas where cosmesis and functionality are important. In the management of diabetic foot ulcers, use of DRT is associated with high rates of complete wound healing with a low risk of adverse outcomes. DRT has been successfully used in traumatic and surgical wounds, showing particular benefit in deep wounds and in the reconstruction of numerous anatomical sites. Conclusions:. Considerable clinical experience has accrued with the use of DRT beyond its original application for thermal injury. A growing body of evidence from clinical studies reports the successful use of DRT to improve clinical outcomes and quality of life across clinical indications at a number of anatomical sites.

ObjectiveDespite the overall success of responsive neurostimulation (RNS) therapy for drug-resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS-ideally before device implantation-are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy.MethodsWe assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy.ResultsIctal measures of synchronizability in the high-γ band (95-105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high-γ synchronizability is inversely associated with the degree of therapeutic response.SignificanceThis study provides a proof-of-concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.

With the exponential increase in scientific publications, new conceptual and technological tools are needed to help scientists, students, managers and policy-makers to navigate and digest current scientific knowledge. Hi Knowledge is an initiative to synthesise and visualise scientific knowledge, with an initial focus on invasion biology that is currently expanding to include urban ecology, restoration ecology and freshwater ecology. In a workshop on 5-6 June 2023 in Berlin, Germany, we discussed and tested a collection of new open tools related to this initiative in order to publish, curate, explore and synthesise concepts and results in ecology. Three main themes were discussed during in-person breakout group sessions: (1) building and using open tools for knowledge curation, exploration and synthesis; (2) making open knowledge searchable and machine friendly by improving modelling and annotation of scientific knowledge; and (3) extending beyond the field of invasion biology. We report on the discussions of all twelve sessions pertaining to these themes. A main underlying goal of our workshop was to build a community of scientists involved in openly co-designing and using these tools. Overall, the participants were enthusiastic about the usefulness of these tools and discussions gravitated around improving them and finding strategies to scale-up participation by the community. Follow-up user tests and publications are planned for individual tools and topics.

Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is involved in various eosinophilic diseases. Since increased galectin expression is already detected in the placentas of mothers with gestational diabetes mellitus (GDM), this study focuses on the specific role of galectin-10 and hints at consequences for the diagnosis and therapeutic options of GDM. It is hypothesized that the difference in galectin-10 expression will raise the pathophysiological understanding of gestational diabetes. The study population consists of 80 women: 40 healthy mothers and 40 women suffering from gestational diabetes mellitus. The expression of galectin-10 was analyzed in the syncytiotrophoblast (SCT) and the decidua of the placenta via immunohistochemistry and immunofluorescence double staining. The immunoreactivity score (IRS) was used for evaluation. The results in this study were significant for an overexpression of galectin-10 in GDM placentas compared with the control group. The syncytiotrophoblast showed overexpression in the nucleus and the cytoplasm, whereas expression of galectin-10 in the decidua was significant in the cytoplasm only. This study identified the expression changes in galectin-10 in placental tissue between healthy and GDM mothers and intensified the understanding of gestational diabetes. Assuming that gestational diabetes mellitus is involved in inflammatory processes, galectin-10 might play a role in the development and maintenance of GDM. Further investigation is required to strengthen these findings.

Abstract RNA-binding proteins (RBPs) are crucial regulators of gene expression, often composed of defined domains interspersed with flexible, intrinsically disordered regions. Determining the structure of ribonucleoprotein (RNP) complexes involving such RBPs necessitates integrative structural modeling due to their lack of a single stable state. In this study, we integrate magnetic resonance, mass spectrometry, and small-angle scattering data to determine the solution structure of the polypyrimidine-tract binding protein 1 (PTBP1/hnRNP I) bound to an RNA fragment from the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). This binding, essential for enhancing the translation of viral RNA, leads to a complex structure that demonstrates RNA and protein compaction, while maintaining pronounced conformational flexibility. Acting as an RNA chaperone, PTBP1 orchestrates the IRES RNA into a few distinct conformations, exposing the RNA stems outward. This conformational diversity is likely common among RNP structures and functionally important. Our approach enables atomic-level characterization of heterogeneous RNP structures.

Cochlear implants (CIs) restore activity in the deafened auditory system via electrical stimulation of the auditory nerve. As the spread of electric current in biological tissues is rather broad, the spectral information provided by electrical CIs is limited. Optogenetic stimulation of the auditory nerve has been suggested for artificial sound coding with improved spectral selectivity, as light can be conveniently confined in space. Yet, the foundations for optogenetic sound coding strategies remain to be established. Here, we parametrized stimulus-response-relationships of the auditory pathway in gerbils for optogenetic stimulation. Upon activation of the auditory pathway by waveguide-based optogenetic stimulation of the spiral ganglion, we recorded neuronal activity of the auditory midbrain, in which neural representations of spectral, temporal, and intensity information can be found. Screening a wide range of optical stimuli and taking the properties of optical CI emitters into account, we aimed to optimize stimulus paradigms for potent and energy-efficient activation of the auditory pathway. We report that efficient optogenetic coding builds on neural integration of millisecond stimuli built from microsecond light pulses, which optimally accommodate power-efficient laser diode operation. Moreover, we performed an activity-level-dependent comparison of optogenetic and acoustic stimulation in order to estimate the dynamic range and the maximal stimulation intensity amenable to single channel optogenetic sound encoding, and indicate that it complies well with speech comprehension in a typical conversation (65 dB). Our results provide a first framework for the development of coding strategies for future optogenetic hearing restoration.

Abstract Carbon supports are ubiquitous components of heterogeneous catalysts for acetylene hydrochlorination to vinyl chloride, from commercial mercury-based systems to more sustainable metal single-atom alternatives. Their potential co-catalytic role has long been postulated but never unequivocally demonstrated. Herein, we evidence the bifunctionality of carbons and metal sites in the acetylene hydrochlorination catalytic cycle. Combining operando X-ray absorption spectroscopy with other spectroscopic and kinetic analyses, we monitor the structure of single metal atoms (Pt, Au, Ru) and carbon supports (activated, non-activated, and nitrogen-doped) from catalyst synthesis, using various procedures, to operation at different conditions. Metal atoms exclusively activate hydrogen chloride, while metal-neighboring sites in the support bind acetylene. Resolving the coordination environment of working metal atoms guides theoretical simulations in proposing potential binding sites for acetylene in the support and a viable reaction profile. Expanding from single-atom to ensemble catalysis, these results reinforce the importance of optimizing both metal and support components to leverage the distinct functions of each for advancing catalyst design.

Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective. Twenty-five subjects enrolled. The combination of ruxolitinib and exemestane was safe, though anemia requiring transfusion in 5/15 (33%) at the 25 mg dose in stage 1 led to a reduction to 15 mg twice daily in stage 2 (with no additional transfusions). Clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4-45.1); 6/25 patients demonstrated stable disease for ≥6 months. Median progression-free survival was 2.8 months (95% CI 2.6-3.9). Exploratory biomarkers revealed high levels of systemic inflammation and 60% harbored a high-risk IL-6 genotype. Pharmacodynamics demonstrated modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at a tolerable dose. Thus, ruxolitinib combined with exemestane at a tolerable dose was safe but minimally active in AI-resistant tumors of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in MBC.

BackgroundIt is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28).MethodsThis is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma.ResultsA total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures

Abstract Background Epigenetic alterations are a near-universal feature of human malignancy and have been detected in malignant cells as well as in easily accessible specimens such as blood and urine. These findings offer promising applications in cancer detection, subtyping, and treatment monitoring. However, much of the current evidence is based on findings in retrospective studies and may reflect epigenetic patterns that have already been influenced by the onset of the disease. Methods Studying breast cancer, we established genome-scale DNA methylation profiles of prospectively collected buffy coat samples (n = 702) from a case–control study nested within the EPIC-Heidelberg cohort using reduced representation bisulphite sequencing (RRBS). Results We observed cancer-specific DNA methylation events in buffy coat samples. Increased DNA methylation in genomic regions associated with SURF6 and REXO1/CTB31O20.3 was linked to the length of time to diagnosis in the prospectively collected buffy coat DNA from individuals who subsequently developed breast cancer. Using machine learning methods, we piloted a DNA methylation-based classifier that predicted case–control status in a held-out validation set with 76.5% accuracy, in some cases up to 15 years before clinical diagnosis of the disease. Conclusions Taken together, our findings suggest a model of gradual accumulation of cancer-associated DNA methylation patterns in peripheral blood, which may be detected long before clinical manifestation of cancer. Such changes may provide useful markers for risk stratification and, ultimately, personalized cancer prevention.

Predicting which non-native species will negatively impact biodiversity is a longstanding research priority. The Functional Response (FR; resource use in relation to availability) is a classical ecological concept that has been increasingly applied to quantify, assess and compare ecological impacts of non-native species. Despite this recent growth, an overview of applications and knowledge gaps across relevant contexts is currently lacking. We conducted a systematic review using a combination of terms regarding FR and invasion science to synthesise scientific studies that apply the FR approach in the field and to suggest new areas where it could have valuable applications. Trends of publications using FR in invasion science and publications about FR in general were compared through the Activity Index. Data were extracted from papers to reveal temporal, bibliographic, and geographic trends, patterns in study attributes such as type of interaction and habitat investigated, taxonomic groups used, and context-dependencies assessed. In total, 120 papers were included in the review. We identified substantial unevenness in the reporting of FRs in invasion science, despite a rapidly growing number of studies. To date, research has been geographically skewed towards North America and Europe, as well as towards predator-prey interactions in freshwater habitats. Most studies have focused on a few species of invertebrates and fishes. Species origin, life stage, environmental temperature and habitat complexity were the most frequently considered context-dependencies. We conclude that while the FR approach has thus far been narrowly applied, it has broad potential application in invasion science and can be used to test major hypotheses in this research field.

Abstract Kagome lattice materials are an important platform for highly frustrated magnetism as well as for a plethora of phenomena resulting from flat bands, Dirac cones and van Hove singularities in their electronic structures. We study the little known metallic magnet CrRhAs, which belongs to a vast family of materials that includes 3d, 4f, and 5f magnetic elements, as well as numerous nonmagnetic metals and insulators. Using noncollinear spin density functional calculations (mostly spin spirals), we extract a model magnetic Hamiltonian for CrRhAs. While it is dominated by an antiferromagnetic second nearest neighbor coupling in the kagome plane, the metallic nature of the compound leads to numerous nonzero longer range couplings and to important ring exchange terms. We analyze this Hamiltonian and find unusual ground states which are dominated by nearly isolated antiferromagnetic triangles that adopt 120∘ order either with positive or with negative vector chirality. We discuss the connection to the few known experimental facts about CrRhAs. Finally, we give a brief survey of other interesting magnetic members of this family of kagome compounds.

Previous research found that when participants across the lifespan could be the architect of their own stepping-stones landscapes, they create nonstandardized configurations with gap-width variation. Yet, architects often use standardized dimensions in their designs for playgrounds and outdoor fitness areas. To scrutinize why architects tend to seek for more standardized designs than the examined target users, we tested the hypothesis that the difference is caused by a different perspective during the making process. After all, landscape architects generally design on 2D maps, while the participants designed in situ. We asked 67 participants to design a stepping-stones landscape on a 2D map and 67 other participants to create the landscape in situ. Contrary to our expectations, we found no indications that designing on a 2D map leads to more standardized configurations. We end with discussing other characteristics of the design processes that could potentially explain the omnipresent standardization in design.