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The fact that neutrinos carry a non-vanishing rest mass is evidence ofphysics beyond the Standard Model of elementary particles. Their absolute massbears important relevance from particle physics to cosmology. In this work, wereport on the search for the effective electron antineutrino mass with theKATRIN experiment. KATRIN performs precision spectroscopy of the tritium$\beta$-decay close to the kinematic endpoint. Based on the first fiveneutrino-mass measurement campaigns, we derive a best-fit value of $m_u^{2} ={-0.14^{+0.13}_{-0.15}}~\mathrm{eV^2}$, resulting in an upper limit of $m_u <{0.45}~\mathrm{eV}$ at 90 % confidence level. With six times the statistics ofprevious data sets, amounting to 36 million electrons collected in 259measurement days, a substantial reduction of the background level and improvedsystematic uncertainties, this result tightens KATRIN's previous bound by afactor of almost two.

Abstract Investments in “Clean water and sanitation” drive a transition from irrigation with untreated to irrigation with treated wastewater. While this transition reduces many health risks, it may decrease crop yields, and soil carbon storage, cause a release of accumulated pollutants from soils, and increase the spread of antibiotic resistance in the environment. A holistic view on multiple SDGs is necessary to maximize benefits and minimize risks of wastewater treatment for irrigation.

While there is much knowledge about local neuronal circuitry, considerably less is known about how neuronal input is integrated and combined across neuronal networks to encode higher order brain functions. One challenge lies in the large number of complex neural interactions. Neural networks use oscillating activity for information exchange between distributed nodes. To better understand building principles underlying the observation of synchronized oscillatory activity in a large-scale network, we developed a reductionistic neuronal network model. Fundamental building principles are laterally and temporally interconnected virtual nodes (microcircuits), wherein each node was modeled as a local oscillator. By this building principle, the neuronal network model can integrate information in time and space. The simulation gives rise to a wave interference pattern that spreads over all simulated columns in form of a travelling wave. The model design stabilizes states of efficient information processing across all participating neuronal equivalents. Model-specific oscillatory patterns, generated by complex input stimuli, were similar to electrophysiological high-frequency signals that we could confirm in the primate visual cortex during a visual perception task. Important oscillatory model pre-runners, limitations and strength of our reductionistic model are discussed. Our simple scalable model shows unique integration properties and successfully reproduces a variety of biological phenomena such as harmonics, coherence patterns, frequency-speed relationships, and oscillatory activities. We suggest that our scalable model simulates aspects of a basic building principle underlying oscillatory, large-scale integration of information in small and large brains.

Background: People with intellectual disabilities may experience frailty earlier than the general population. This scoping review aimed to investigate how frailty is defined, assessed, and managed in adults with an intellectual disability; factors associated with frailty; and the potential impact of COVID-19 on frailty identification and management. Method: Databases were searched from January 2016 to July 2023 for studies that investigated frailty in individuals with intellectual disabilities. Results: Twenty studies met the inclusion criteria. Frailty prevalence varied between 9% and 84%. Greater severity of intellectual disability, presence of Down syndrome, older age, polypharmacy, and group home living were associated with frailty. Multiagency working, trusted relationships and provision of evidence-based information may all be beneficial in frailty management. Conclusion: Frailty is common for people with intellectual disabilities and is best identified with measures specifically designed for this population. Future research should evaluate interventions to manage frailty and improve lives.

Nikolaos Gkalapis,1,2,&ast; Simon Dulz,1,&ast; Carsten Grohmann,1 Miriam Nickel,3 Christoph Schwering,3 Eva Wibbeler,3 Martin Stephan Spitzer,1 Angela Schulz,3 Yevgeniya Atiskova1 1Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 2Department of Ophthalmology, University Hospital of Martin Luther University Halle/Wittenberg, Halle (Saale), Germany; 3Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany&ast;These authors contributed equally to this workCorrespondence: Yevgeniya Atiskova, Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany, Tel +49 (0) 40 7410 – 52301, Fax +49 (0) 40 7410 – 42301, Email y.atiskova@uke.dePurpose: To investigate the presence of peripapillary retinal nerve fiber layer (pRNFL) degeneration in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease and to evaluate the role of optical coherence tomography (OCT) assessed pRNFL thickness as a biomarker for CLN2 disease progression.Patients and Methods: Forty eyes of 20 patients with genetically and enzymatically confirmed diagnosis of late-infantile CLN2 disease were included in this retrospective cohort study. All patients received 300 mg of intracerebroventricular enzyme replacement treatment (cerliponase alfa) once every two weeks. OCT imaging was performed under general anesthesia using spectral domain OCT (Heidelberg Engineering, Heidelberg, Germany). PRNFL thickness and central retinal thickness (CRT) values were manually confirmed with the Heidelberg Eye Explorer software. Corresponding pediatric data were extracted from the DEM-CHILD database. Spearman correlation coefficient values (rs) were calculated between pRNFL and CRT values, age at examination, the Weill Cornell Late Infantile Neuronal Ceroid Lipofuscinosis (Weill Cornell LINCL) Scale and the Hamburg Motor and Language (HML) Scale.Results: Fourteen of 20 patients underwent serial examinations resulting in a total of 84 OCT Scans and 42 Weill Cornell LINCL and HML Scale scores. Mean age was 6.90 years and mean follow-up time was 1.38 years. Mean global pRNFL (G-pRNFL) thickness was 77.02 μm presenting a significant decrease compared to normative values from healthy children (106.45 μm; p < 0.0001). G-pRNFL displayed significant correlations towards age at examination (rs = - 0.557, p < 0.01), the Weill Cornell LINCL Scale (rs = 0.849, p < 0.01), and the HML Scale (rs = 0.833, p < 0.01). Repeated measurements indicated decreases in pRNFL thickness over time in most patients.Conclusion: Patients with late-infantile CLN2 disease exhibit early onset progressive pRNFL loss regardless of outer retinal degeneration, highlighting the potential of pRNFL as an independent ocular biomarker for retinal pathology in late-infantile CLN2 disease.Keywords: neuronal ceroid lipofuscinosis, optic nerve, optical coherence tomography, retina, neurodegeneration, eye

Background: A lower dosage of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) has shown efficacy in managing short-term toxicity and maintaining a deep molecular response in patients who fail to achieve treatment-free remission. Method: From over 700 patients with CML who were treated at two centres over the last three decades, this retrospective study identified eight patients characterised by long-term treatment failure and simultaneous prolonged significant haematologic toxicity that prevented the use of the standard tyrosine kinase inhibitor dosage. Results: Patients had a high or intermediate ELTS risk score, and most had significant comorbidities. Two patients were treated previously with busulfan, and four were aged over 70, which might explain the reduced pool of normal haematopoietic stem cells. However, concomitant myelodysplastic syndrome or the presence of clonal haematopoiesis of indeterminate potential was not demonstrated. Despite prolonged treatment failure, the survival of these patients (who were ineligible for stem cell transplantation) ranged from 45-396 months. Neither mutations in the ABL kinase domain nor additional cytogenetic abnormalities developed during the treatment of these patients, prompting speculation about the low selective pressure of low-dose tyrosine kinase inhibitors and/or the absence of mutations at diagnosis. Conclusion: It is important not to stop treatment with tyrosine kinase inhibitors at a low personalised dosage in CML patients with prolonged significant haematologic toxicity despite long-term treatment failure.

Abstract Law guarantees the entry of people with disabilities into the labor market. However, just making the vacancy possible does not guarantee the full inclusion and permanence of these people in the work environment. It is necessary that organizations be prepared and have in their culture the practice of accessibility actions that contribute to this process. This study aimed to propose accessibility actions according to the panorama of inclusion and permanence of servers with disabilities in a Federal University in the interior of Rio Grande do Sul. With a qualitative approach, of an exploratory nature, it was developed with content analysis of information from questionnaires with open questions, applied to 26 servers with disabilities at the Federal University of Santa Maria (UFSM). The results found indicate that UFSM is on the way to building an accessible University, but it still has barriers, mainly attitudinal, that can be minimized with proposed accessibility actions. In addition to understanding the panorama of inclusion and permanence of servers with disabilities in a Public University, the present study presents a proposal for accessibility actions that can provide better working conditions for people with disabilities. Also filling a gap in studies aimed at servers with disabilities and about actions that help in their real inclusion and permanence in the work environment.

It is known that 25%–30% of individuals with cutaneous psoriasis (PsC) will develop psoriatic arthritis (PsA). To date, the reasons for the development of PsA in individuals with PsC have not been identified. Furthermore, there are considerable delays in the diagnosis and treatment of PsA, which lead to joint and bone deformation and chronic pain. It is therefore important to develop more precise diagnostic and screening tools. In this narrative review of the literature, clinical risk factors and novel molecular biomarkers (genetic markers, blood and inflammatory markers, lipid, metabolite and protein biomarkers) have been evaluated. The review included 38 publications that were reported between May 2020 and May 2024. Similar to previous reviews, nail involvement was one of the strongest clinical risk factors for the development of PsA, while molecular biomarkers did not provide a clear and robust differentiation between PsC and PsA groups. The seemingly poor performance of molecular markers may be largely attributed to small study populations and heterogeneity in study designs. Data and sample sharing in large consortia such as HIPPOCRATES (Health initiatives in Psoriasis and PsOriatic arthritis ConsoRTium European States) could help to overcome the limitations of small studies and enable the development of more robust diagnostic and screening tools for PsA.

Objective: To demonstrate the capability of a deep learning model to detect central retinal artery occlusion (CRAO), a retinal pathology with significant clinical urgency, using OCT data. Design: Retrospective, external validation study analyzing OCT and clinical baseline data of 2 institutions via deep learning classification analysis. Subjects: Patients presenting to the University Medical Center Tübingen and the University Medical Center Hamburg-Eppendorf in Germany. Methods: OCT data of patients suffering from CRAO, differential diagnosis with (sub) acute visual loss (central retinal vein occlusion, diabetic macular edema, nonarteritic ischemic optic neuropathy), and from controls were expertly graded and distinguished into 3 groups. Our methodological approach involved a nested multiclass five fold cross-validation classification scheme. Main Outcome Measures: Area under the curve (AUC). Results: The optimal performance of our algorithm was observed using 30 epochs, complemented by an early stopping mechanism to prevent overfitting. Our model followed a multiclass approach, distinguishing among the 3 different classes: control, CRAO, and differential diagnoses. The evaluation was conducted by the “one vs. all” area under the receiver operating characteristics curve (AUC) method. The results demonstrated AUC of 0.96 (95% confidence interval [CI], ± 0.01); 0.99 (95% CI, ± 0.00); and 0.90 (95% CI, ± 0.03) for each class, respectively. Conclusions: Our machine learning algorithm (MLA) exhibited a high AUC, as well as sensitivity and specificity in detecting CRAO and the differential classes, respectively. These findings underscore the potential for deploying MLAs in the identification of less common etiologies within an acute emergency clinical setting. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.06, corresponding to an interdye distance precision of ≤2 Å and accuracy of ≤5 Å. We further discuss the limits for detecting fluctuations in this distance range and how to identify dye perturbations. Our work demonstrates the ability of smFRET experiments to simultaneously measure distances and avoid the averaging of conformational dynamics for realistic protein systems, highlighting its importance in the expanding toolbox of integrative structural biology.

Background Patients with Kawasaki disease (KD) with coronary artery involvement require long‐term cardiac care. Although respective evidence‐based recommendations are missing, cardiac catheterization is still considered the gold standard for diagnosing detailed coronary pathology. Therefore, to better understand coronary artery pathology development, we conducted a survey to document and evaluate cardiac catheterization data in a European population. Methods and Results We retrospectively analyzed cardiac catheterization data from KD children from the year 2010 until April 2023. This registry covers basic acute‐phase clinical data, and more importantly, detailed information on morphology, distribution, and the development of coronary artery pathologies. A total of 164 mainly White patients (65% boys) were included. A relevant number of patients had no coronary artery aneurysm (CAA) at the cardiac catheterization, indicating that distal CAAs were almost exclusively detected alongside proximal CAAs. Patients with multiple CAAs revealed a significant positive correlation between the number of CAAs and their dimensions in diameter and in length. Location of the CAA within the coronary artery, age at onset of KD, or natal sex did not significantly influence CAA diameters, but CAAs were longer in older children and in boys. Conclusions That distal CAAs were only present together with proximal ones will hopefully reduce diagnostic CCs in patients with KD without echocardiographically detected proximal CAAs. Furthermore, this study gives valuable insights into dimensional specifics of CAAs in patients with KD. As an ongoing registry, future analyses will further explore long‐term outcomes and performed treatments, helping to refine clinical long‐term strategies for patients with KD. REGISTRATION URL: https://drks.de/; Unique Identifier: DRKS00031022.

In bacteria and archaea, proteins of the ParA/MinD family of ATPases regulate the spatiotemporal organization of various cellular cargoes, including cell division proteins, motility structures, chemotaxis systems, and chromosomes. In bacteria, such as Escherichia coli, MinD proteins are crucial for the correct placement of the Z-ring at mid-cell during cell division. However, previous studies have shown that none of the 4 MinD homologs present in the archaeon Haloferax volcanii have a role in cell division, suggesting that these proteins regulate different cellular processes in haloarchaea. Here, we show that while deletion of MinD2 in H. volcanii (∆minD2) does not affect cell growth or division, it impacts cell shape and motility by mispositioning the chemotaxis arrays and archaellum motors. Finally, we explore the links between MinD2 and MinD4, which has been previously shown to modulate the localization of chemosensory arrays and archaella in H. volcanii, finding that the two MinD homologues have synergistic effects in regulating the positioning of the motility machinery. Collectively, our findings identify MinD2 as an important link between cell shape and motility in H. volcanii and further our understanding of the mechanisms by which multiple MinD proteins regulate cellular functions in haloarchaea.

Abstract In February 2023, anomalously heavy rainfall caused widespread landslides in the coastal city of São Sebastião (Southeastern Brazil). This report describes the first version of a landslide inventory dataset for this event. The inventory is primarily based on the analysis of aerial images with 10 cm spatial resolution acquired immediately after the event, as well as archive images from Google Earth and PlanetScope. Delimitation of the landslides relied on a comparison of the images along with the area’s Digital Surface Model (DSM) and hydrography. The spatial vector dataset (shapefile and geopackage) contains points representing the landslide’s crowns and polygons indicating the affected area and is openly available in Zenodo.