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Abstract Biological processes, though often imaged and visualized in two dimensions, inherently occur in at least three-dimensional space. As time-resolved volumetric imaging becomes increasingly accessible, there emerges a necessity for tools that empower non-specialists to process and interpret intricate datasets. We introduce ThirdPeak, an open-source tool tailored for the comprehensive analysis of two- and three-dimensional track data across various scales. Its versatile import and export options ensure seamless integration into established workflows, while the intuitive user interface allows for swift visualization and analysis of the data. When applied to live-cell diffusion data, this software demonstrates the benefits of integrating both 2D and 3D analysis, yielding valuable insights into the understanding of biological processes.

Abstract Wildlife tagging provides critical insights into animal movement ecology, physiology, and behavior amid global ecosystem changes. However, the stress induced by capture, handling, and tagging can impact post-release locomotion and activity and, consequently, the interpretation of study results. Here, we analyze post-tagging effects on 1585 individuals of 42 terrestrial mammal species using collar-collected GPS and accelerometer data. Species-specific displacements and overall dynamic body acceleration, as a proxy for activity, were assessed over 20 days post-release to quantify disturbance intensity, recovery duration, and speed. Differences were evaluated, considering species-specific traits and the human footprint of the study region. Over 70% of the analyzed species exhibited significant behavioral changes following collaring events. Herbivores traveled farther with variable activity reactions, while omnivores and carnivores were initially less active and mobile. Recovery duration proved brief, with alterations diminishing within 4–7 tracking days for most species. Herbivores, particularly males, showed quicker displacement recovery (4 days) but slower activity recovery (7 days). Individuals in high human footprint areas displayed faster recovery, indicating adaptation to human disturbance. Our findings emphasize the necessity of extending tracking periods beyond 1 week and particular caution in remote study areas or herbivore-focused research, specifically in smaller mammals.

Abstract TASK-5 (KCNK15) belongs to the acid-sensitive subfamily of two-pore domain potassium (K2P) channels, which includes TASK-1 and TASK-3. TASK-5 stands out as K2P channel for which there is no functional data available, since it was reported in 2001 as non-functional and thus “silent”. Here we show that TASK-5 channels are indeed non-functional as homodimers, but are involved in the formation of functional channel complexes with TASK-1 and TASK-3. TASK-5 negatively modulates the surface expression of TASK channels, while the heteromeric TASK-5-containing channel complexes located at the plasma membrane are characterized by changes in single-channel conductance, Gq-coupled receptor-mediated channel inhibition, and sensitivity to TASK modulators. The unique pharmacology of TASK-1/TASK-5 heterodimers, affected by a common polymorphism in KCNK15, needs to be carefully considered in the future development of drugs targeting TASK channels. Our observations provide an access to study TASK-5 at the functional level, particularly in malignant cancers associated with KCNK15.

Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor–recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically. Hence, this Delphi methodology was used to reach a consensus from a multi-disciplinary team (MDT) of experts from 15 countries on the management of HS patients undergoing imlifidase HLAi from a deceased donor (DD) KTx. This Delphi consensus provides clinical practice guidance on the use of imlifidase in the end-to-end management of HS patients undergoing an HLAi DD KTx and supports centers in the development of guidelines for the utilization and integration of imlifidase into clinical practice.

Background: Rabies in Turkey is maintained by dogs, but following a sustained spill-over, red fox mediated rabies had spread from the Aegean region to the central part of Türkiye. During the past four years from 2019 to 2023 large scale efforts used oral rabies vaccination (ORV) to control rabies in red foxes. Here, we present the results of the largest ORV campaign on the Asian continent. Methods: ORV campaigns were carried out twice a year in spring and autumn with a targeted bait density of 20–23 baits/km2. Monitoring of ORV campaigns included the GIS-based analyses of bait distribution, the assessment of bait uptake through biomarker detection and the determination of seroconversion (sero-positivity in ELISA) in the target species collected within the vaccination area. For determination of fox rabies incidence in vaccination areas as the main indicator of the performance of the ORV campaigns, epidemiological data was obtained from the national passive surveillance program. Results: Aerial bait distribution was highly accurate, with >99 % of baits being recorded from targeted zones, thus meeting the desired bait densities. Although the overall bait uptake (28.1 %; 95 %CI: 23.2–32.8) and seroprevalance (36.3 %; 95 %CI: 30.0–43.2) were low, rabies incidence drastically decreased in ORV areas and rabies was eliminated from western and central parts of Turkey, with no reported cases in foxes from ORV areas in 2022 and 2023. Conclusions: A large-scale ORV campaign against fox rabies using high quality vaccine baits and the GIS-aided and monitored bait distribution was able to control fox mediated rabies in the western and central parts of Türkiye. Rabies control both in dogs and foxes should be expanded to cover also the eastern parts of Türkiye, to become eventually rabies free.

ABSTRACT We report the sudden onset of dyspnea and loss of consciousness and fetal bradycardia in a middle‐aged obese nulliparous woman at 39 weeks of gestation during first stage of labor leading to the decision for emergency cesarean section. Still during surgery, the mother underwent cardiac arrest. Transesophageal echocardiography during resuscitation showed right ventricular failure leading to the diagnosis of pulmonary embolism. Return of spontaneous circulation was achieved after emergency administration of thrombolysis with alteplase and cardiopulmonary resuscitation after 40 min. Severe bleeding, coagulopathy and persistent right ventricular failure resulted in persistent hemodynamic instability leading to supracervical hysterectomy and veno‐arterial extracorporal life support. Both mother and baby survived without hypoxic brain injury.

Background. Since 1998, the Swiss Organ Living-Donor Health Registry (SOL-DHR) has recorded peri- and postoperative complications of living kidney (LK) donors, as reported by all Swiss transplant centers and has collected follow-up data prospectively. Methods. We analyzed the early complications of 2379 consecutive individuals who donated a kidney between January 1998 and June 2022 and assessed their health-related quality of life (HRQoL) 1 y after donation. Results. In total, 447 early complications in 404/2379 LK donors (17.0%) were reported to the SOL-DHR. The frequency of donors with major complications (ie, Dindo-Clavien classification 3/4) was 2.4%. In total, 31 donors needed reoperation, and in 13/31 (42%), donors reoperation was necessary because of bleeding complications. Independent risk factors for major early complications were older donor age (P = 0.005) and type of surgical approach (ie, the laparoscopic retroperitoneal compared with laparoscopic transabdominal surgery; P = 0.01), but not sex. We observed a U-shaped association of body mass index, where very low/high body mass indexes had higher odds of major early complications, without reaching statistical significance. Although HRQoL was affected by kidney donation, 96.5% of donors indicated that they would donate their kidney again. The only independent risk factor for low HRQoL based on mental health scores was worsening EB after living kidney donation (P

Choledocholithiasis, characterized by the presence of stones in the common bile duct, poses significant challenges in clinical management, particularly when the stones are massive. While endoscopic methods are often effective in stone removal, complications such as the impaction of foreign bodies like Dormia baskets can occur. These complications may necessitate alternative approaches, including surgical intervention, highlighting the importance of exploring innovative interventional techniques. We report on an 89-year-old patient presenting with massive choledocholithiasis, involving complete filling of the intra- and extrahepatic bile duct system with large stones up to a maximum of 2 cm. The patient underwent interventional removal of a Dormia basket (3.5Fr. Boston Scientific, USA) impacted in the common bile duct. This procedure proved challenging due to the metallic end marker of the basket perforating through the wall of the distal common bile duct, rendering it fixed. Given the complexity of the case, a parallel approach combining percutaneous transhepatic cholangiography and drainage with simultaneous endoscopy was employed to successfully extract the fixed Dormia basket. In cases of severe choledocholithiasis complicated by the impaction of foreign bodies such as Dormia baskets, innovative interventional strategies are crucial for successful management. Our case highlights the effectiveness of a parallel approach involving percutaneous transhepatic cholangiography and drainage alongside simultaneous endoscopy in safely removing the fixed foreign body from the common bile duct. This multidisciplinary approach not only offers a viable alternative to surgical intervention but also underscores the importance of collaboration between interventional radiologists and endoscopists in optimizing patient outcomes in complex biliary interventions.

Like other volume electron microscopy approaches, automated tape-collecting ultramicrotomy (ATUM) enables imaging of serial sections deposited on thick plastic tapes by scanning electron microscopy (SEM). ATUM is unique in enabling hierarchical imaging and thus efficient screening for target structures, as needed for correlative light and electron microscopy. However, SEM of sections on tape can only access the section surface, thereby limiting the axial resolution to the typical size of cellular vesicles with an order of magnitude lower than the acquired xy resolution. In contrast, serial-section electron tomography (ET), a transmission electron microscopy-based approach, yields isotropic voxels at full EM resolution, but requires deposition of sections on electron-stable thin and fragile films, thus making screening of large section libraries difficult and prone to section loss. To combine the strength of both approaches, we developed ‘ATUM-Tomo, a hybrid method, where sections are first reversibly attached to plastic tape via a dissolvable coating, and after screening detached and transferred to the ET-compatible thin films. As a proof-of-principle, we applied correlative ATUM-Tomo to study ultrastructural features of blood-brain barrier (BBB) leakiness around microthrombi in a mouse model of traumatic brain injury. Microthrombi and associated sites of BBB leakiness were identified by confocal imaging of injected fluorescent and electron-dense nanoparticles, then relocalized by ATUM-SEM, and finally interrogated by correlative ATUM-Tomo. Overall, our new ATUM-Tomo approach will substantially advance ultrastructural analysis of biological phenomena that require cell- and tissue-level contextualization of the finest subcellular textures.

Abstract In recent years, researchers have emphasized the use of fractal aggregate morphology instead of the core-shell morphology in global climate models for estimating black carbon (BC) forcing. This study confirms that fractal morphology plays an important role in reducing the overestimation of aerosol light absorption calculations in the case of an urban polluted environment. During periods of high anthropogenic BC emissions at Delhi, the particle light absorption is overestimated by 50 to 200% by assumptions of both external mixing and internal core-shell mixing. While incorporating the aggregate morphology model into light absorption simulations is beneficial in such cases, it comes with a high computational burden. To address this, we propose a metric known as morphology index (MI). This index distributes the weightage between the two extreme cases of core-shell and fractal aggregate to obtain accurate particle light absorption. Long-range transported aerosols were estimated to have an MI of 0.78, and fresh local emissions had an MI of 0.48. A BC-based aerosol classification approach was developed to determine the most relevant particle size mode for light absorption. The method is based on patterns found between the correlations of the BC mass concentrations and aerosol number concentrations at the different particles sizes (BC-size correlation spectra). BC-size correlation spectra are introduced as a concept that may be used (i) independently to understand the size-dependent heterogeneous distribution of aerosol light absorption and (ii) in conjunction with MI to accurately model the optical properties of aerosols in different BC regimes.

The present work covers novel herbicidal lead structures that contain a 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine scaffold as structural key feature carrying a substituted phenyl side chain. These new compounds show good acyl-ACP thioesterase inhibition in line with strong herbicidal activity against commercially important weeds in broadacre crops, e.g., wheat and corn. The desired substituted 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines were prepared via an optimized BH3-mediated reduction involving tris(pentafluorophenyl)borane as a strong Lewis acid. Remarkably, greenhouse trials showed that some of the target compounds outlined herein display promising control of grass weed species in preemergence application, combined with a dose response window that enables partial selectivity in certain crops.

Background: Idiopathic systemic capillary leak syndrome (ISCLS) is characterized by recurrent systemic capillary leakage and hypovolemic shock. Case presentation: We report a 59-year-old Caucasian man with ISCLS and persistent hypovolemic and cardiogenic shock after COVID-19 infection. Mechanical circulatory support was provided with veno-arterial extracorporeal membrane oxygenation and a microaxial pump. Massive fluid resuscitation was needed. Subsequent complications prolonged the intensive care treatment. Mechanical circulatory support was needed for 22 days. Cardiac function eventually fully recovered, and the patient survived without neurologic compromise. Conclusions: This case of severe ISCLS triggered by COVID-19 highlights that even the most severe hypovolemic and cardiogenic shock may be reversible in ISCLS.

In IR and beyond, there is considerable debate about the ways global governance, the transnationalisation of publics, and changes in communication technologies have affected the interplay between publics and global politics. This debate is characterised by disagreements about how to conceptualise publics in the global realm—and whether or not they exist in the first place. We seek to contribute to this debate by disentangling the various meanings associated with publics in order to get a better grasp of how publics shape and are shaped by global politics. We do so in two steps. First, we distinguish four different manifestations of publics: audiences, spheres, institutions, and public interests. Second, we identify four key dynamics that affect the evolution and interplay of these manifestations in global politics: the distinction between public and private, changes in communications technologies, the politics of transparency, and the need to legitimise global governance. These interrelated dynamics reshape the publicness of global politics while sustaining the plurality of the publics that partake in it.

This article explores the degree to which commercial satellite imagery has empowered non-state actors in the politics of transparency in world politics. This question has received renewed attention in the wake of the disclosure of China’s new missile silos in 2021 as well as Russia’s war against Ukraine since 2022. The article contributes to research on this question by teasing out the competition over authority undergirding the politics of transparency. It does so in two steps: it conceptualizes the politics of transparency as involving a combination of state and non-state actors engaging in transparency efforts against another state or other states and it distinguishes four aspects of the empowerment of non-state actors in such constellations of actors: (a) the emergence of new or better disclosure devices that (b) bolster the expertise of some non-state actors, (c) giving them more influence over public debates, and (d) prompting changes in the policies of relevant actors. The article uses this framework to explore the factors that affected the degree of empowerment of non-state actors in the two cases of China’s new missile silos as well as Russia’s war against Ukraine. It highlights three factors: the interplay between state and non-state transparency makers, the polarization of public spheres, and the ability of states targeted by the transparency efforts to fragment public spheres.

Endocytosis is a common process observed in most eukaryotic cells, although its complexity varies among different organisms. In Trypanosoma brucei, the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune evasion. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic internalization. The entire process of membrane recycling occurs exclusively through the flagellar pocket, an extracellular organelle situated at the posterior pole of the spindle-shaped cell. The high-speed dynamics of membrane flux in trypanosomes do not seem compatible with the conventional concept of distinct compartments for early endosomes (EE), late endosomes (LE), and recycling endosomes (RE). To investigate the underlying structural basis for the remarkably fast membrane traffic in trypanosomes, we employed advanced techniques in light and electron microscopy to examine the three-dimensional architecture of the endosomal system. Our findings reveal that the endosomal system in trypanosomes exhibits a remarkably intricate structure. Instead of being compartmentalized, it constitutes a continuous membrane system, with specific functions of the endosome segregated into membrane subdomains enriched with classical markers for EE, LE, and RE. These membrane subdomains can partly overlap or are interspersed with areas that are negative for endosomal markers. This continuous endosome allows fast membrane flux by facilitated diffusion that is not slowed by multiple fission and fusion events.

BackgroundPatients with chronic heart failure (CHF) frequently suffer from depressive comorbidity. CHF and depressive comorbidity can cause somatic symptoms. The correct attribution of somatic symptoms is important. Thus, we aimed to assess potential differences in somatic symptom severity between CHF patients with and without depressive comorbidity.MethodsWe evaluated depressive comorbidity using the Patient Health Questionnaire-9 (PHQ-9), somatic symptom severity with the Patient Health Questionnaire-15 (PHQ-15), and sociodemographic and medical variables in 308 CHF outpatients. To compare somatic symptom severity between CHF patients with and without depressive comorbidity, we conducted item-level analyses of covariance.ResultsOf the 308 participating patients, 93 (30.3%) met the PHQ-9 criteria for depressive comorbidity. These patients did not differ from those without depressive comorbidity with regard to age, sex, left ventricular function, and multimorbidity. Patients with depressive comorbidity scored significantly higher on ten out of thirteen PHQ-15 items than patients without depressive comorbidity. The largest effect sizes (0.71-0.80) were shown for symptoms of headache, chest pain, shortness of breath, and palpitations, and the latter three were potentially attributable to heart failure.ConclusionsAmong patients with CHF, somatic symptoms are more pronounced in those with depressive comorbidity than those without depressive comorbidity. This finding is especially true for cardiac symptoms independent of CHF severity. The potential interpretation of somatic symptoms as correlates of depressive comorbidity must be recognized in clinical practice.

BackgroundThis scoping review is a further step to build up the Mental Health Surveillance System for Germany. It summarizes and analyzes indicators used or described in Organization for Economic Co-operation and Development (OECD) countries for public mental health monitoring in children and adolescents aged 0–18 years.MethodsWe searched PubMed-MEDLINE, PsycINFO, Cochrane Databases, and Google Scholar from 2000 to September 2022. The search used five general keyword categories: 1) “indicators/monitoring/surveillance” at the population level, 2) “mental/psychological,” 3) “health/disorders,” 4) “children and adolescents,” and 5) 38 OECD countries. The search was complemented with an extensive grey literature search, including OECD public health institutions and an internet search using Google. A predefined set of inclusion and exclusion criteria was applied.ResultsOver 15,500 articles and documents were screened (scientific search N = 10,539, grey literature search more than 5,000). More than 700 articles and documents have been full-text assessed, with 382 being ultimately included. Out of 7,477 indicators extracted, an initial set of 6,426 indicators met our inclusion criteria for indicators. After consolidating duplicates and similar content, this initial set was categorized into 19 topics, resulting in a final set of 210 different indicators. The analysis highlighted an increasing interest in the topic since 2008, but indicators for the younger age, particularly those aged 0 to 2 years, were less readily available.ConclusionOur research provides a comprehensive understanding of the current state of mental health indicators for children and adolescents, identifying both (1) indicators of public mental health noted in a previous scoping review on adults and (2) new indicators specific to this age group. These findings contribute to the development of effective public health surveillance strategies for children and adolescents and inform future research in this field.

Vaccination of the reservoir species is a key component in the global fight against rabies. For wildlife reservoir species and hard to reach spillover species (e. g. ruminant farm animals), oral vaccination is the only solution. In search for a novel potent and safe oral rabies vaccine, we generated a recombinant vector virus based on lentogenic Newcastle disease virus (NDV) strain Clone 30 that expresses the glycoprotein G of rabies virus (RABV) vaccine strain SAD L16 (rNDV_GRABV). Transgene expression and virus replication was verified in avian and mammalian cells. To test immunogenicity and viral shedding, in a proof-of-concept study six goats and foxes, representing herbivore and carnivore species susceptible to rabies, each received a single dose of rNDV_GRABV (108.5 TCID50/animal) by direct oral application. For comparison, three animals received the similar dose of the empty viral vector (rNDV). All animals remained clinically inconspicuous during the trial. Viral RNA could be isolated from oral and nasal swabs until four (goats) or seven days (foxes) post vaccination, while infectious NDV could not be re-isolated. After four weeks, three out of six rNDV_GRABV vaccinated foxes developed RABV binding and virus neutralizing antibodies. Five out of six rNDV_GRABV vaccinated goats displayed RABV G specific antibodies either detected by ELISA or RFFIT. Additionally, NDV and RABV specific T cell activity was demonstrated in some of the vaccinated animals by detecting antigen specific interferon γ secretion in lymphocytes isolated from pharyngeal lymph nodes. In conclusion, the NDV vectored rabies vaccine rNDV_GRABV was safe and immunogenic after a single oral application in goats and foxes, and highlight the potential of NDV as vector for oral vaccines in mammals.

In 2021, a comprehensive dog demographic questionnaire combined with a KAP survey were conducted in the northern communal areas (NCAs) of Namibia with the aim of gaining a better understanding of dog populations, owner behaviour, and knowledge, attitudes and practices (KAP) relating to rabies. The survey of 3,726 households across the eight regions of the NCAs provided insights that will inform interventions in order to improve human rabies prevention and Namibia's dog rabies control strategy. The results showed a relatively low average human/dog ratio (HDR) of 5.4:1 indicating a surprisingly high dog population of at least 272,000 dogs in the NCAs, 93% of which appear to be owned but are free-roaming. Data analysis revealed opportunities but also highlighted needs for improvements in rabies surveillance and mass dog vaccinations. Although knowledge, attitude, and practice scores towards epidemiologic and clinical aspects, human rabies prevention, and dog rabies vaccination were deemed to be acceptable, the survey nevertheless revealed deficiencies in certain aspects in some of the population. Interestingly, data seemed to indicate relatively high dog bite incidences per 100,000 people, ranging between 262 and 1,369 and a certain number of unreported human rabies cases. Despite the very high number of dogs, only 50% of dog-owning households reported having vaccinated their dogs. In order to address these issues, the planning, announcement, and implementation of mass dog vaccination campaigns needs to be adapted to achieve adequate vaccination coverage. Another focus needs to be on rabies awareness and education if Namibia is to be significantly contributing to the global goal of "Zero by 30".

Abstract Background Recent research has suggested that an increase in temperature can negatively affect mental health and increase hospitalization for mental illness. It is not clear, however, what factors or mechanisms mediate this association. We aimed to (1) investigate the associations between ambient temperatures and bad daily mood, and (2) identify variables affecting the strength of these associations (modifiers) including the time, the day of the week and the year of the mood rating, socio-demographic characteristics, sleep quality, psychiatric disorders and the personality trait neuroticism in the community. Methods Data stemmed from the second follow-up evaluation of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne (Switzerland). The 906 participants rated their mood level four times a day during seven days using a cell phone app. Mixed-effects logistic regression was used to determine the association between daily maximum temperature and mood level. Participant ID was inserted as a random effect in the model, whereas the time of the day, the day of the week and the year were inserted as fixed effects. Models were controlled for several confounders (socio-demographic characteristics, sleep quality, weather parameters and air pollutants). Stratified analyses were conducted based on socio-demographic characteristics, sleep quality, presence of psychiatric disorders or a high neuroticism. Results Overall, the probability of having a bad mood for the entire day decreased by 7.0% (OR: 0.93: 95% CI 0.88, 0.99) for each 5 °C increase in maximum temperature. A smaller and less precise effect (-3%; OR: 0.97: 95% CI 0.91, 1.03) was found when controlling for sunshine duration. A higher association was found in participants with bipolar disorder (-23%; OR: 0.77: 95% CI 0.51, 1.17) and in participants with a high neuroticism (-13%; OR: 0.87 95% CI 0.80, 0.95), whereas the association was reversed for participants with anxiety (20%; OR: 1.20: 95% CI 0.90, 1.59), depression (18%; OR: 1.18 95% CI 0.94, 1.48) and schizophrenia (193%; OR: 2.93 95% CI 1.17, 7.73). Conclusions According to our findings, rising temperatures may positively affect mood in the general population. However, individuals with certain psychiatric disorders, such as anxiety, depression, and schizophrenia, may exhibit altered responses to heat, which may explain their increased morbidity when exposed to high temperatures. This suggests that tailored public health policies are required to protect this vulnerable population.

Abstract Background The high susceptibility of carnivores to Suid Alphaherpesvirus 1 [SuAHV1, synonymous pseudorabies virus (PrV)], renders them inadvertent sentinels for the possible occurrence of Aujeszky’s disease (AD) in domestic and wild swine populations. The aim of this study was to epidemiologically analyse the occurrence of PrV infections in domestic and wild animals in Germany during the last three decades and to genetically characterise the causative PrV isolates. Methods PrV in dogs was detected using standard virological techniques including conventional and real time PCR, virus isolation or by immunohistochemistry. Available PrV isolates were characterized by partial sequencing of the open gC reading frame and the genetic traits were compared with those of archived PrV isolates from carnivores and domestic pigs from Germany before the elimination of AD in the domestic pig population. Results During 1995 and 2022, a total of 38 cases of AD in carnivores, e.g. dogs and red foxes, were laboratory confirmed. Sequencing and subsequent phylogenetic analysis of PrV isolates established a strong connection between AD cases in carnivores and the occurrence of PrV infections in European wild boars in the end phase of and after elimination of AD from the domestic pig population. While PrV infections occur at low numbers but regularly in hunting dogs, interestingly, PrV was not observed in grey wolves in Germany. In none of 682 dead-found grey wolves and wolf-dog hybrids tested from Germany during 2006–2022 could PrV infection be detected by molecular means. Conclusions Although PrV has been eliminated from domestic pigs, spillover infections in domestic and wild carnivores should always be expected given the endemic presence of PrV in wild pig populations. Since detection of PrV DNA and virus in carnivores is sporadic even in areas with high seroprevalence of PrV in wild pigs, it may not reflect the full diversity of PrV.

Abstract Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.

In this paper, we present an approach to the price-optimized charging of electric vehicles (EVs) based on energy flexibility. Fleet operators determine the minimum and the maximum power demand to charge EVs at a specific time and share this information as so-called power corridors (PCs) with an energy aggregator. The energy aggregator collects the predicted PCs from the fleet operators located in the same market area and aggregates the PCs. The energy provider periodically sends energy prices from the market to the energy aggregator, which purchases energy when its price is opportune. The energy aggregator calculates and delivers charge plans for each fleet operator involved and thus can pass along the purchase prices. The incentive design must ensure that fleet operators are better off by disclosing their flexibility data to the aggregator. This study can contribute to a new data-driven energy market communication system by providing insights on how to leverage the energy flexibility that EVs can offer to the energy system.

In a long-term immunogenicity study (1100 days post vaccination) in local Thai dogs the immune response of the oral rabies vaccine SPBN GASGAS was compared to those elicited by a commercial inactivated vaccine using immunobridging. Based on the detection of rabies virus binding (rVBA) and rabies virus neutralizing antibodies (rVNA) as measured by ELISA and Rapid Fluorescent Focus Inhibition Test (RFFIT) the long-term immune response in dogs vaccinated orally with the SPBNA GASGAS strain of rabies vaccine in a bait was non-inferior to a conventional inactivated rabies vaccine. The outcome of this study supports extending the originally claimed duration of immunity (DOI) of SPBN GASGAS after oral vaccination for dogs from 6 to 30 months.

Objectives Quantify the risk of mental health (MH)-related emergency department visits (EDVs) due to heat, in the city of Curitiba, Brazil.Design Daily time series analysis, using quasi-Poisson combined with distributed lag non-linear model on EDV for MH disorders, from 2017 to 2021.Setting All nine emergency centres from the public health system, in Curitiba.Participants 101 452 EDVs for MH disorders and suicide attempts over 5 years, from patients residing inside the territory of Curitiba.Main outcome measure Relative risk of EDV (RREDV) due to extreme mean temperature (24.5°C, 99th percentile) relative to the median (18.02°C), controlling for long-term trends, air pollution and humidity, and measuring effects delayed up to 10 days.Results Extreme heat was associated with higher single-lag EDV risk of RREDV 1.03(95% CI 1.01 to 1.05—single-lag 2), and cumulatively of RREDV 1.15 (95% CI 1.05 to 1.26—lag-cumulative 0–6). Strong risk was observed for patients with suicide attempts (RREDV 1.85, 95% CI 1.08 to 3.16) and neurotic disorders (RREDV 1.18, 95% CI 1.06 to 1.31). As to demographic subgroups, females (RREDV 1.20, 95% CI 1.08 to 1.34) and patients aged 18–64 (RREDV 1.18, 95% CI 1.07 to 1.30) were significantly endangered. Extreme heat resulted in lower risks of EDV for patients with organic disorders (RREDV 0.60, 95% CI 0.40 to 0.89), personality disorders (RREDV 0.48, 95% CI 0.26 to 0.91) and MH in general in the elderly ≥65 (RREDV 0.77, 95% CI 0.60 to 0.98). We found no significant RREDV among males and patients aged 0–17.Conclusion The risk of MH-related EDV due to heat is elevated for the entire study population, but very differentiated by subgroups. This opens avenue for adaptation policies in healthcare: such as monitoring populations at risk and establishing an early warning systems to prevent exacerbation of MH episodes and to reduce suicide attempts. Further studies are welcome, why the reported risk differences occur and what, if any, role healthcare seeking barriers might play.

Fremdsprachenunterricht so zu gestalten, dass möglichst alle Lernenden daran teilhaben können, ist einerseits eine bildungspolitische Vorgabe, andererseits mit grossen Herausforderungen verbunden. Im vorliegenden Artikel wird zunächst die anspruchsvolle Ausgangslage für die Umsetzung von inklusivem Fremdsprachenunterricht erläutert. Anschliessend wird das Rahmenmodell «Universal Design for Learning» (UDL) eingeführt und ein darauf basierendes frei verfügbares für die Umsetzung von diversitätssensiblem Fremdsprachenunterricht vorgestellt. Dank diesen Leitlinien sollen Lehrpersonen mögliche Lernbarrieren im Unterricht besser erkennen und minimieren können.

ABSTRACTA challenge when developing therapeutic antibodies is the identification of candidates with favorable pharmacokinetics (PK) early in development. A key determinant of immunoglobulin (IgG) serum half‑life in vivo is the efficiency of pH-dependent binding to the neonatal Fc receptor (FcRn). Numerous studies have proposed techniques to assess FcRn binding of IgG-based therapeutics in vitro, enabling prediction of serum half-life prior to clinical assessment. FcRn high-performance liquid chromatography (HPLC) assays FcRn binding of therapeutic IgGs across a pH gradient, allowing the correlation of IgG column retention time to the half‑life of a therapeutic IgG in vivo. However, as FcRn retention time cannot be directly compared to an in vivo parameter, modifications to FcRn-HPLC are required to enable interpretation of the data within a physiological context, to provide more accurate estimations of serum half-life. This study presents an important modification to this method, FcRn-pH-HPLC, which reproducibly measures FcRn dissociation pH, allowing correlation with previously established half-lives of therapeutic antibodies. Furthermore, the influence of incorporating various antibody modifications, binding modules, and their orientations within IgGs and bispecifics on FcRn dissociation pH was evaluated using antibodies from the redirected optimized cell killing (ROCK®) platform. Target and effector antigen-binding domain sequences, their presentation format and orientation within a bispecific antibody alter FcRn retention; tested Fc domain modifications and incorporating stabilizing disulfide bonds had minimal effect. This study may inform the generation of mono-, bi- and multi-specific antibodies with tailored half-lives based on FcRn binding properties in vitro, to differentiate antibody-based therapeutic candidates with optimal developability.

Non-typhoidal Salmonella infections (NTSI) can cause bacterial diarrhea, mostly leading to self-limiting gastroenteritis. However, in at-risk populations, NTSI can have severe complications. As transmission is most commonly foodborne, infection is rare in the breast- or bottle-fed very young. Another route is increasingly implicated, however, in newborns and infants especially: Contact with reptiles and amphibians. We describe infection with Salmonella enterica subsp. enterica ser. Monschaui (S. Monschaui), transmitted from bearded dragons, in a three-week-old boy. The boy initially appeared well, on the next morning deterioration was dramatic, with tachypnea, tachycardia, and mottled skin. Gram-negative sepsis was documented on day 2. His case prompted a review of published instances of reptile- and amphibian-associated salmonellosis (RAAS), summarized here. Association of S. Monschaui infection with exposure to reptiles and amphibians prompted inquiry into household pets. The parents had kept bearded dragons (Pogona sp.), the last of which died two weeks before the patient was born; confirmation of colonization with S. Monschaui was thus precluded. Among 63 reports (−5,000 cases) of RAAS or S. Monschaui, 62 appeared between 1995 and 2022, 10 were single case reports, and 53 were original articles with −5,000 cases; vectors included turtles, frogs, lizards, and snakes. RAAS is not a new phenomenon, but its incidence recently has risen due to the increased popularity of reptiles and amphibians as non-traditional pets. These animals can carry Salmonella sp. and transmit it to humans, posing a risk particularly to infants and other vulnerable persons. Risk mitigation requires that those bringing such pets into the home be informed of dangers associated with reptile and amphibian contact; that those selling reptiles and amphibians be mandated to inform customers comprehensively may be in order.

Abstract Background Many potential prognostic factors for predicting kidney transplantation outcomes have been identified. However, in Switzerland, no widely accepted prognostic model or risk score for transplantation outcomes is being routinely used in clinical practice yet. We aim to develop three prediction models for the prognosis of graft survival, quality of life, and graft function following transplantation in Switzerland. Methods The clinical kidney prediction models (KIDMO) are developed with data from a national multi-center cohort study (Swiss Transplant Cohort Study; STCS) and the Swiss Organ Allocation System (SOAS). The primary outcome is the kidney graft survival (with death of recipient as competing risk); the secondary outcomes are the quality of life (patient-reported health status) at 12 months and estimated glomerular filtration rate (eGFR) slope. Organ donor, transplantation, and recipient-related clinical information will be used as predictors at the time of organ allocation. We will use a Fine & Gray subdistribution model and linear mixed-effects models for the primary and the two secondary outcomes, respectively. Model optimism, calibration, discrimination, and heterogeneity between transplant centres will be assessed using bootstrapping, internal-external cross-validation, and methods from meta-analysis. Discussion Thorough evaluation of the existing risk scores for the kidney graft survival or patient-reported outcomes has been lacking in the Swiss transplant setting. In order to be useful in clinical practice, a prognostic score needs to be valid, reliable, clinically relevant, and preferably integrated into the decision-making process to improve long-term patient outcomes and support informed decisions for clinicians and their patients. The state-of-the-art methodology by taking into account competing risks and variable selection using expert knowledge is applied to data from a nationwide prospective multi-center cohort study. Ideally, healthcare providers together with patients can predetermine the risk they are willing to accept from a deceased-donor kidney, with graft survival, quality of life, and graft function estimates available for their consideration. Study registration Open Science Framework ID: z6mvj

Advanced cutaneous squamous cell carcinoma (cSCC) can be a life-threatening disease for which effective and safe treatment in advanced stages is very limited. GP-2250 has been recently proven to have—in vitro and in vivo—antineoplastic effects on cancer cells. This study aims to investigate the potential anti-neoplastic effects of GP-2250 on the cSCC cell lines SCC13 and A431 through dose finding assessments, MTT cytotoxicity assays, cell migration assays, BrdU proliferation assays and FCM analysis. Our preliminary results have shown for the first time evidence for anti-neoplastic effects of GP-2250 on cSCC cells, enhancing cytotoxicity, attenuating cancer cell proliferation, inducing apoptosis and reducing tumour cell migration. Further investigations evaluating the modes of action of GP-2250 on cSCC cell lines are warranted in order to justify the use in vivo studies.

Abstract The most basic behavioural states of animals can be described as active or passive. While high‐resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which a combination of automatic radiotracking and machine learning is used to distinguish between active and passive behaviour in small vertebrates fitted with lightweight transmitters (3 million signals from very‐high‐frequency (VHF) telemetry from two forest‐dwelling bat species (Myotis bechsteinii [n = 52] and Nyctalus leisleri [n = 20]) to train and test a random forest model in assigning either active or passive behaviour to VHF‐tagged individuals. The generalisability of the model was demonstrated by recording and classifying the behaviour of tagged birds and by simulating the effect of different activity levels with the help of humans carrying transmitters. The model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F1 0.96–0.98). We provide an ecological case‐study demonstrating the potential of this automated monitoring tool. We used the trained models to compare differences in the daily activity patterns of two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night‐time activity of M. bechsteinii was relatively constant. These results show that subtle differences in the timing of species' activity can be distinguished using our method. Our approach can classify VHF‐signal patterns into fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radiotracking method, we provide the trained random forest models together with an R package that includes all necessary data processing functionalities. In combination with state‐of‐the‐art open‐source automated radiotracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.