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Abstract Background Monocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models. Methods To elucidate whether changes in monocyte subsets are associated with treatment and response, we investigated peripheral blood samples of 73 postmenopausal women with estrogen receptor (ER) positive BC, who received aromatase inhibitor therapy with or without the mucin-1 vaccine tecemotide in the ABCSG34 trial. Blood was retrieved at baseline, midterm and end of therapy, and was analyzed for the distribution and ER expression of monocyte subsets by flow cytometry. Results When 40 healthy, age-matched women were compared with BC patients before treatment start, ER levels of monocytes did not differ, yet patients presented with a higher frequency of classical and fewer non-classical monocytes. Endocrine therapy triggered a significant increase in ER levels in all monocyte subsets, without affecting subset distribution. Vaccination had no overall impact on subset frequency and ER expression. Yet, a shift from intermediate to classical monocytes during therapy correlated with changes in plasma cytokines and chemokines and was significantly associated with low residual cancer burden in vaccinated patients. Without tecemotide, baseline ER levels in classical monocytes were significantly higher in women with good response to endocrine therapy. Conclusions This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination.

Abstract Background Pre-existing comorbidities increase the likelihood of post-stroke dysphagia. This study investigates comorbidity prevalence in patients with dysphagia after ischemic stroke. Methods The data of patients with acute ischemic stroke from two large representative cohorts (STROKE-CARD trial 2014–2019 and STROKE-CARD registry 2020–2022 – both study center Innsbruck, Austria) were analyzed for the presence of dysphagia at hospital admission (clinical swallowing examination). Comorbidities were assessed using the Charlson Comorbidity Index (CCI). Results Of 2054 patients with ischemic stroke, 17.2% showed dysphagia at hospital admission. Patients with dysphagia were older (77.8 ± 11.9 vs. 73.6 ± 14.3 years, p

Abstract Ion-beam radiotherapy is an advanced cancer treatment modality offering steep dose gradients and a high biological effectiveness. These gradients make the therapy vulnerable to patient-setup and anatomical changes between treatment fractions, which may go unnoticed. Charged fragments from nuclear interactions of the ion beam with the patient tissue may carry information about the treatment quality. Currently, the fragments escape the patient undetected. Inter-fractional in-vivo treatment monitoring based on these charged nuclear fragments could make ion-beam therapy safer and more efficient. We developed an ion-beam monitoring system based on 28 hybrid silicon pixel detectors (Timepix3) to measure the distribution of fragment origins in three dimensions. The system design choices as well as the ion-beam monitoring performance measurements are presented in this manuscript. A spatial resolution of $${{4}\,\hbox {mm}}$$ 4 mm along the beam axis was achieved for the measurement of individual fragment origins. Beam-range shifts of $${1.5}\,\hbox {mm}$$ 1.5 mm were identified in a clinically realistic treatment scenario with an anthropomorphic head phantom. The monitoring system is currently being used in a prospective clinical trial at the Heidelberg Ion Beam Therapy Centre for head-and-neck as well as central nervous system cancer patients.

Abstract Sepsis, marked by organ dysfunction, necessitates reliable biomarkers. Ribonuclease inhibitor 1 (RNH1), a ribonuclease (RNase) inhibitor, emerged as a potential biomarker for acute kidney injury and mortality in thoracoabdominal aortic aneurysm patients. Our study investigates RNH1 dynamics in sepsis, its links to mortality and organ dysfunction, and the interplay with RNase 1 and RNase 5. Furthermore, we explore RNH1 as a therapeutic target in sepsis-related processes like inflammation, non-canonical inflammasome activation, and iron homeostasis. We showed that RNH1 levels are significantly higher in deceased patients compared to sepsis survivors and correlate with creatine kinase, aspartate and alanine transaminase, bilirubin, serum creatinine and RNase 5, but not RNase 1. RNH1 mitigated LPS-induced TNFα and RNase 5 secretion, and relative mRNA expression of ferroptosis-associated genes HMOX1, FTH1 and HAMP in PBMCs. Monocytes were identified as the predominant type of LPS-positive PBMCs. Exogenous RNH1 attenuated LPS-induced CASP5 expression, while increasing IL-1β secretion in PBMCs and THP-1 macrophages. As RNH1 has contradictory effects on inflammation and non-canonical inflammasome activation, its use as a therapeutic agent is limited. However, RNH1 levels may play a central role in iron homeostasis during sepsis, supporting our clinical observations. Hence, RNH1 shows promise as biomarkers for renal and hepatic dysfunction and hepatocyte injury, and may be useful in predicting the outcome of septic patients.

In minimally invasive surgery, grippers are essential for tissue manipulation. However, in commercial tendon‐driven systems, challenges remain, including tendon fatigue and bulkiness. Promising alternatives are magnetically actuated systems, offering contactless steering but limited forces. To overcome this, a miniaturized, locally actuated magnetic gripper with variable stiffness is presented. The gripper employs thin planar coils (75 μm) and a radially magnetized plunger, enabling local actuation and enhanced orientation control. The variable stiffness compliant mechanism made from shape‐memory polymer facilitates different gripping strategies. In its rigid state, pulsed pulling forces of 340 mN and continuous forces of 90 mN are achieved, exceeding the gripper weight by factors of 70 and 18, respectively. The soft state, with a fast response time of 20 ms, enables soft gripping of various targets, including moving ones and rat tissue samples. Demonstrating the applicability, contactless steering and target retrieval within a stomach phantom is showcased. This study introduces promising improvements to magnetically actuated grippers for surgical procedures, addressing key challenges in current designs.

Background Living with a family member who has a long-term health condition (HC) is associated with poorer health and well-being outcomes, but the number and socio-demographics of people and families impacted by a family member who has an HC is unknown. Methods Using the Integrated Data Infrastructure (IDI), a collection of linked administrative datasets for the full New Zealand (NZ) population, we identified n= 1,043,172 families using 2013 NZ Census data, and used health data over the previous 5-years to ascertain whether people in these families (n=3,137,517) had cancer, chronic obstructive pulmonary disease, coronary health disease, diabetes, dementia, gout, stroke, traumatic brain injury (TBI) or a mental health/behavioural condition (MHBC). Results Over 60% of families included at least one person with a HC. The most common HCs were MHBCs (39.4% of families), diabetes (16.0%), and TBI (13.9%). A high proportion of multi-generation families (73.9%) included a member with a HC. Two-thirds (67.7%) of Pacific Peoples either had a HC themselves or were living with a family member who had a HC, compared with 62.3% of Europeans and 62.5% of Māori (the indigenous peoples of NZ). At the highest level of socioeconomic deprivation, 57.6% of children lived with a family member who had a HC. Conclusions Three in five NZ families were living with a HC, with differences in the proportion affected according to family composition, socio-economic status and an individuals’ ethnicity. This suggests that there are a substantial number of people at risk of the associated poor outcomes.

Ziel der Studie ist eine genaue Untersuchung der populationsnormalisierten Behandlungskosten von Orphan Drugs. Zu diesem Zweck wurde bereits im Jahr 2022 eine Studie zur Betrachtung der Therapiekosten von Orphan Drugs für die Jahre 2005 bis 2021 durchgeführt. Die Berechnungen wurden nun im Rahmen eines Studienupdates validiert, wobei die identische Grundgesamtheit herangezogen wurde. Das Update ermöglichte eine Inflationsbereinigung basierend auf dem Preisindex des Jahres 2022 sowie lückenlose Behandlungskosten nach AMNOG-Bewertung und Preisverhandlung für alle Orphan Drugs. Die Analyse zeigt, dass das AMNOG als Preisregulierungsinstrument auch bei Orphan Drugs seine Funktion erfüllt. Seit AMNOG-Einführung sind die inflationsbereinigten normalisierten Behandlungskosten für Orphan Drugs sowohl im Hinblick auf den Einführungspreis (minus 25%) als auch auf den Erstattungsbetrag (minus 6%) gesunken.

Abstract The systemic inflammatory response following acute ischaemic stroke remains incompletely understood. We characterised the circulating inflammatory profile in 173 acute ischaemic stroke patients by measuring 65 cytokines and chemokines in plasma. Participants were grouped based on their inflammatory response, determined by high-sensitivity C-reactive protein levels in the acute phase. We compared stroke patients’ profiles with 42 people experiencing spontaneous cervical artery dissection without stroke. Furthermore, variations in cytokine levels among stroke aetiologies were analysed. Follow-up samples were collected in a subgroup of ischaemic stroke patients at three and twelve months. Ischaemic stroke patients had elevated plasma levels of HGF and SDF-1α, and lower IL-4 levels, compared to spontaneous cervical artery dissection patients without stroke. Aetiology-subgroup analysis revealed reduced levels of nine cytokines/chemokines (HGF, SDF-1α, IL-2R, CD30, TNF-RII, IL-16, MIF, APRIL, SCF), and elevated levels of IL-4 and MIP-1β, in spontaneous cervical artery dissection (with or without ischaemic stroke as levels were comparable between both groups) compared to other aetiologies. The majority of cytokine/chemokine levels remained stable across the study period. Our research indicates that stroke due to large artery atherosclerosis, cardioembolism, and small vessel occlusion triggers a stronger inflammatory response than spontaneous cervical artery dissection.

With the global digitalization of services, passenger Intelligent Transportation Systems (ITSs) have emerged as transformative components, yet the practical implementation of state-of-the-art measures to ensure information security and privacy presents substantial challenges. In this article, we propose a framework for information security and privacy management. The framework is validated through two empirical studies. First, the framework is used to extract data during the literature review defining state-of-the-art aspects and measures. Second, a survey-based analysis of running passenger ITSs in selected regions of the European Union provides insights into real-life ITS implementations, enabling a thorough comparison with the proposed state-of-the-art measures. The study also showed that the proposed framework depicts some dependencies between measures, and, thus, using its matrix structure for the state of information security and privacy management in the organization helps to cross-check the usage of policies or methodologies by the organization departments. Our findings resulted in recommendations for organizations developing ITSs to enhance their information security and privacy management systems and bridge the gap between research proposals and practical implementation.

Abstract Background Point-of-care ultrasound (POCUS) is a critical diagnostic tool in various medical settings, yet its instruction in medical education is inconsistent. The Rapid Ultrasound for Shock and Hypotension (RUSH) protocol is a comprehensive diagnostic tool, but its complexity poses challenges for teaching and learning. This study evaluates the effectiveness of a single-day training in RUSH for medical students by assessing their performance in clinical scenarios. Methods In this prospective single-center observational proof-of-concept study, 16 medical students from Saarland University Medical Center underwent a single-day training in RUSH, followed by evaluations in clinical settings and on a high-fidelity simulator. Performance was assessed using a standardized scoring tool and time to complete the RUSH exam. Knowledge gain was measured with pre- and post-training written exams, and diagnostic performance was evaluated with an objective structured clinical examination (OSCE). Results Students demonstrated high performance in RUSH exam views across patients (median performance: 85–87%) and improved scanning times, although not statistically significant. They performed better on simulators than on live patients. Written exam scores significantly improved post-training, suggesting a gain in theoretical knowledge. However, more than a third of students could not complete the RUSH exam within five minutes on live patients. Conclusions Single-day RUSH training improved medical students’ theoretical knowledge and simulator performance but translating these skills to clinical settings proved challenging. The findings suggest that while short-term training can be beneficial, it may not suffice for clinical proficiency. This study underscores the need for structured and possibly longitudinal training programs to ensure skill retention and clinical applicability.

Am vergangenen Freitag einigten sich die Spitzen der Ampel-Koalition (erneut) auf einen Bundeshaushaltsentwurf für das kommende Jahr 2025. Dem voran gingen nicht nur zähe politische Debatten innerhalb der Koalition. Auch das Verfassungsrecht spielte – mal wieder – eine hervorgehobene Rolle für die Haushaltspolitik der Bundesrepublik. Im Verlauf der Debatte um den nun vorgesehenen Entwurf, der im Laufe des Jahres vom Bundestag beschlossen werden soll, zeigt sich ein weiteres Mal der übermäßige Fokus haushaltspolitischer Erwägungen auf verfassungsrechtliche Normen.

BackgroundOsteoarthritis of the hip joint is an increasing functional and health-related problem. The most common surgical treatment is hip replacement to reduce pain and improve function. Rehabilitation after total hip arthroplasty (THA) is not regulated in Austria and mostly depends on the patient’s own initiative and possibilities. Functional deficits, such as valgus thrust of the leg, functional Trendelenburg gait, or Duchenne limp, are characteristic symptoms before and, due to the performance learning effect prior to surgery, also after the operation. Addressing these deficits is possible through neuromuscular-focused exercise therapy. The efficacy of such therapy relies significantly on the quality of performance, the frequency of exercise, and the duration of engagement. Enhancing sustainability is achievable through increased motivation and real-time feedback (RTF) on exercise execution facilitated by digital feedback systems. ObjectiveThis study will be performed to quantify the medium-term effectiveness of digital home exercise feedback systems on functional performance following THA. MethodsA clinical trial with a cluster-randomized, 2-arm, parallel-group design with an 8-week intervention phase and subsequent follow-ups at 3 and 6 months postsurgery will be conducted. Feedback during exercising will be provided through a blended-care program, combining a supervised group exercise program with a self-developed digital feedback system for home exercise. In total, 70 patients will be recruited for baseline. The primary outcome parameters will be the frontal knee range of motion, pelvic obliquity, and lateral trunk lean. Secondary outcomes will be the sum scores of patient-reported outcomes and relevant kinematic, kinetic, and spatiotemporal parameters. ResultsThe trial started in January 2024, and the first results are anticipated to be published by June 2025. RTF-supported home exercise is expected to improve exercise execution quality and therapeutic adherence compared to using paper instructions for excise guidance. ConclusionsThe anticipated findings of this study aim to offer new insights into the effect of a blended-care program incorporating digital RTF on exercise therapy after unilateral THA, in addition to knowledge on the functional status 3 and 6 months postsurgery, for further improvement in the development of rehabilitation guidelines following THA. Trial RegistrationClinicalTrials.gov: NCT06161194; https://clinicaltrials.gov/study/NCT06161194 International Registered Report Identifier (IRRID)PRR1-10.2196/59755

IntroductionPosterior circulation stroke can lead to ataxia, manifesting in a loss of coordination and balance. Patients experience difficulty in activities of daily living and an increased risk of falling, both profoundly affecting quality of life. In individuals with neurodegenerative diseases, coordination exercises have been shown to lead to a reduction in ataxic symptoms. There is, however, limited evidence on the effect of physical therapy, specifically coordination exercises in patients with stroke-related ataxia. We therefore present a study protocol for a prospective trial.MethodsThe purpose of this trial is to investigate the effects of coordination exercises compared to standard physiotherapy on balance and walking in ataxic stroke patients. Therefore, a prospective, single-blinded randomized controlled trial is currently ongoing at the Clinical Department of Neurology, Medical University of Innsbruck, Austria, in collaboration with two local rehabilitation facilities in Austria, Hochzirl Hospital and the Clinic for Rehabilitation Münster. Balance is the primary outcome of the study as assessed using the Berg Balance Scale. Secondary outcomes are concerned with walking, risk and number of falls, independence in daily life, and quality of life, rated using appropriate scales and scores. Patients are allocated applying a 1:1 ratio and a stratified block randomization. In both groups recruited individuals undergo five 45-min treatment sessions per week, totaling 20 sessions of coordination exercises (IG) or standard physiotherapy (CG) over the course of 4 weeks. Data is collected at the baseline (T0), after the 4-week supervised practice (T1), and after another 8 weeks of independent home-based training (T2).DiscussionThis is the first randomized controlled trial investigating the effects of coordination exercises on balance and walking in people with stroke-related ataxia. As stroke guidelines emphasize the limited evidence of treatment for ataxic symptoms, this study aims to contribute further knowledge regarding tailored interventions for these patients.Clinical Trial RegistrationGerman Clinical Trials Registry (drks.de). Identifier: DRKS00020825.

The ecology of forest ecosystems depends on the composition of trees. Capturing fine-grained information on individual trees at broad scales provides a unique perspective on forest ecosystems, forest restoration, and responses to disturbance. Individual tree data at wide extents promises to increase the scale of forest analysis, biogeographic research, and ecosystem monitoring without losing details on individual species composition and abundance. Computer vision using deep neural networks can convert raw sensor data into predictions of individual canopy tree species through labeled data collected by field researchers. Using over 40,000 individual tree stems as training data, we create landscape-level species predictions for over 100 million individual trees across 24 sites in the National Ecological Observatory Network (NEON). Using hierarchical multi-temporal models fine-tuned for each geographic area, we produce open-source data available as 1 km2 shapefiles with individual tree species prediction, as well as crown location, crown area, and height of 81 canopy tree species. Site-specific models had an average performance of 79% accuracy covering an average of 6 species per site, ranging from 3 to 15 species per site. All predictions are openly archived and have been uploaded to Google Earth Engine to benefit the ecology community and overlay with other remote sensing assets. We outline the potential utility and limitations of these data in ecology and computer vision research, as well as strategies for improving predictions using targeted data sampling.

Abstract Many biological processes rely on endogenous electric fields (EFs), including tissue regeneration, cell development, wound healing, and cancer metastasis. Mimicking these biological EFs by applying external direct current stimulation (DCS) is therefore the key to many new therapeutic strategies. During DCS, the charge transfer from electrode to tissue relies on a combination of reversible and irreversible electrochemical processes, which may generate toxic or bio‐altering substances, including metal ions and reactive oxygen species (ROS). Poly(3,4‐ethylenedioxythiophene) (PEDOT) based electrodes are emerging as suitable candidates for DCS to improve biocompatibility compared to metals. This work addresses whether PEDOT electrodes can be tailored to favor reversible biocompatible charge transfer. To this end, different PEDOT formulations and their respective back electrodes are studied using cyclic voltammetry, chronopotentiometry, and direct measurements of H2O2 and O2. This combination of electrochemical methods sheds light on the time dynamics of reversible and irreversible charge transfer and the relationship between capacitance and ROS generation. The results presented here show that although all electrode materials investigated generate ROS, the onset of ROS can be delayed by increasing the electrode's capacitance via PEDOT coating, which has implications for future bioelectronic devices that allow longer reversibly driven pulse durations during DCS.

Abstract Hydraulic fluid power systems are essential for a range of engineering applications such as transportation, heavy industry, and robotics. The scale of the industry is such that hydraulic pumps are estimated to account for 15% of all the energy consumption in the European Union and yet the average efficiency of fluid power systems is only 22%. The digitalization of hydraulic systems offers significant advantages in terms of energy efficiency, performance, reduced maintenance, and automation. However, this requires advances in the integration of smart sensing technologies to provide real‐time feedback on the operation and health of hydraulic components. This review details developing trends in hydraulic fluid power research and provides an overview of progress related to the digitalization of these systems and their integration within an Industry 4.0 framework. The fundamentals of relevant sensor technologies and innovative approaches for integrating sensors into hydraulics systems are discussed. Methods to deliver power to the sensors and associated electronics through harvested pressure ripples are also reviewed. An outlook with respect to future directions in this field is given, including an assessment of the potential for exploiting advanced manufacturing technologies, in particular additive manufacturing, to facilitate successful sensor integration into hydraulic fluid power systems.

Summary: Impaired spatial navigation is early marker of Alzheimer’s disease (AD). We examined ability of self- and informant-reported navigation questionnaires to discriminate between clinically and biomarker-defined participants, and associations of questionnaires with navigation performance, regional brain atrophy, AD biomarkers, and biomarker status. 262 participants (cognitively normal, with subjective cognitive decline, amnestic mild cognitive impairment [aMCI], and mild dementia) and their informants completed three navigation questionnaires. Navigation performance, magnetic resonance imaging volume/thickness of AD-related brain regions, and AD biomarkers were measured. Informant-reported questionnaires distinguished between cognitively normal and impaired participants, and amyloid-β positive and negative aMCI. Lower scores were associated with worse navigation performance, greater atrophy in AD-related brain regions, and amyloid-β status. Self-reported questionnaire scores did not distinguish between the groups and were weakly associated with navigation performance. Other associations were not significant. Informant-reported navigation questionnaires may be a screening tool for early AD reflecting atrophy of AD-related brain regions and AD pathology.

Abstract Trillions of microorganisms, collectively known as the microbiome, inhabit our bodies with the gut microbiome being of particular interest in biomedical research. Bacteriophages, the dominant virome constituents, can utilize suppressor tRNAs to switch to alternative genetic codes (e.g., the UAG stop-codon is reassigned to glutamine) while infecting hosts with the standard bacterial code. However, what triggers this switch and how the bacteriophage manipulates its host is poorly understood. Here, we report the discovery of a subgroup of minimal hepatitis delta virus (HDV)-like ribozymes – theta ribozymes – potentially involved in the code switch leading to the expression of recoded lysis and structural phage genes. We demonstrate their HDV-like self-scission behavior in vitro and find them in an unreported context often located with their cleavage site adjacent to tRNAs, indicating a role in viral tRNA maturation and/or regulation. Every fifth associated tRNA is a suppressor tRNA, further strengthening our hypothesis. The vast abundance of tRNA-associated theta ribozymes – we provide 1753 unique examples – highlights the importance of small ribozymes as an alternative to large enzymes that usually process tRNA 3’-ends. Our discovery expands the short list of biological functions of small HDV-like ribozymes and introduces a previously unknown player likely involved in the code switch of certain recoded gut bacteriophages.

Currently, with the threat of quantum computer attacks, the idea of combining several same-type primitives has reemerged. This is also the case for cryptographic keys where a hybrid quantum key exchange combination allows for preserving the security guarantees of pre-quantum schemes and achieving quantum resistance of post-quantum schemes. In this article, we present a concrete 3-key combiner system implemented on a Field Programmable Gate Arrays (FPGA) platform. Our system involves a pre-quantum Key EXchange scheme (KEX), a post-quantum key encapsulation mechanism, and a Quantum Key Distribution (QKD) algorithm. The proposed 3-key combiner is proven to be secure in the quantum standard model and it is INDistinguishable under a Chosen-Ciphertext Attack (IND-CCA). Our combiner can run in small FPGA platforms due to its relatively low resources usage. In particular, the key combiner without QKD is able to output up to 1 624 keys per second and the key combiner with QKD is able to output up to 9.2 keys per second.

Triclosan and Triclocarban, preservatives widely used in cosmetics and other consumer products, underwent evaluation using a battery of new-approach methodologies in vitro (NAMs). Specifically, the Microplate Ames Test (MPF™ Test, Xenometrix, Allschwil, Switzerland) was employed to assess mutagenicity, the Comet assay in vitro on the HaCat cell line and the Mammalian Chromosome Aberration Test were utilized to evaluate genotoxicity, and the XenoScreen® YES/YAS assay was applied to investigate endocrine disruption. The chemicals did not exhibit any positive responses for mutagenicity. However, the mammalian chromosome aberration test identified both chemicals as being positive for genotoxicity at 10 µg/mL. In the Comet assay, the percentage of DNA in the tail significantly increased in a concentration-dependent manner (at 5 and 10 µg/mL for Triclosan, at 2.5, 5, and 10 µg/mL for Triclocarban). The positive response depended on the increasing concentration and the duration of exposure. Triclosan, but not Triclocarban in any of the endocrine assays performed, indicated a potential for endocrine activity in the anti-estrogenic and anti-androgenic assays. The positive in vitro results detected were obtained for concentrations relevant to final products. The alarming findings obtained with the use of new-approach methodologies (NAMs) justify the current precautionary regulatory approach, limiting the use of these preservatives.

This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm−2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment.

Background Data on impact of COVID‐19 vaccination and outcomes of patients with COVID‐19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. Methods and Results This was a retrospective analysis of patients with COVID‐19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID‐19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID‐19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007–1.417]; P=0.041). Conclusions Our study demonstrated no impact of COVID‐19 vaccination on angiographic or clinical outcome of COVID‐19–positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID‐19 was confirmed.

PimEyes ist zwar sicherheitsrechtlich bedenklich, stellt aber keine Form der Vorratsdatenspeicherung dar, wie es neulich auf dem Verfassungsblog hieß. Es handelt sich vielmehr um einen anlassbezogenen, strafprozessualen Zugriff auf private, unreguliert vorhandene Massendaten. Anhand der Rechtsprechung des Bundesverfassungsgerichts lässt sich allerdings schon jetzt in Grundzügen ableiten, welche Anforderungen der Gesetzgeber bei der noch zu schaffenden Ermächtigungsgrundlage für Software wie PimEyes wird beachten müssen.

RNA, widely recognized as an information-carrier molecule, is capable of catalyzing essential biological processes through ribozymes. Despite their ubiquity, specific functions in a biological context and phenotypes based on the ribozymes' activity are often unknown. Here, we present the discovery of a subgroup of minimal HDV-like ribozymes, which reside 3' to viral tRNAs and appear to cleave the 3'-trailers of viral premature tRNA transcripts. This proposed tRNA-processing function is unprecedented for any ribozymes, thus, we designate this subgroup as theta ribozymes. Most theta ribozymes were identified in Caudoviricetes bacteriophages, the main constituent (>90%) of the mammalian gut virome. Intriguingly, our findings further suggest the involvement of theta ribozymes in the transition of certain bacteriophages between distinct genetic codes, thus possibly contributing to the phage lysis trigger. Our discovery expands the limited repertoire of biological functions attributed to HDV-like ribozymes and provides insights into the fascinating world of RNA catalysis.

Background The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides.Methods HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.iedb.org). Imbalanced or lost expression of HLA-I-A/B/C alleles was analyzed by transcriptome sequencing. FluoroSpot assays and TCR sequencing were used to determine peptide-specific T-cell responses.Results We show that germline homozygosity of HLA-I genes is significantly enriched in EGA patients (n=80) compared with an HLA-matched reference cohort (n=7605). Whereas the overall mutational burden is similar, the repertoire of potentially immunogenic peptides derived from TAAs and MANAs was lower in homozygous patients. Promiscuity of peptides binding to different HLA-I molecules was low for most TAAs and MANAs and in silico modeling of the homozygous to a heterozygous HLA genotype revealed normalized peptide repertoires. Transcriptome sequencing showed imbalanced expression of HLA-I alleles in 75% of heterozygous patients. Out of these, 33% showed complete loss of heterozygosity, whereas 66% had altered expression of only one or two HLA-I molecules. In a FluoroSpot assay, we determined that peptide-specific T-cell responses against NY-ESO-1 are derived from multiple peptides, which often exclusively bind only one HLA-I allele.Conclusion The high frequency of germline homozygosity in EGA patients suggests reduced cancer immunosurveillance leading to an increased cancer risk. Therapeutic targeting of allelic imbalance of HLA-I molecules should be considered in EGA.

IntroductionThis study aimed to emphasize the importance of cranial nerve (CN) palsies in spontaneous cervical artery dissection (sCeAD).MethodsA search term-based literature review was conducted on “cervical artery dissection” and “cranial nerve palsy.” English and German articles published until October 2023 were considered.ResultsCranial nerve (CN) palsy in sCeAD is evident in approximately 10% of cases. In the literature, isolated palsies of CN II, III, VII, IX, X, and XII have been reported, while CN XI palsy only occurs in combination with other lower cranial nerve palsies. Dissection type and mural hematoma localization are specific to affected CN as CN palsies of II or III are solely evident in those with steno-occlusive vessel pathologies located at more proximal segments of ICA, while those with CN palsies of IX, X, XI, and XII occur in expansive sCeAD at more distal segments. This dichotomization emphasizes the hypothesis of a different pathomechanism in CN palsy associated with sCeAD, one being hypoperfusion or microembolism (CN II, III, and VII) and the other being a local mass effect on surrounding tissue (CN IX, X, XI, and XII). Clinically, the distinction between peripheral palsies and those caused by brainstem infarction is difficult. This differentiation is key, as, according to the reviewed cases, peripheral cranial nerve palsies in sCeAD patients mostly resolve completely over time, while those due to brainstem stroke do not, making cerebrovascular imaging appraisal essential.DiscussionIt is important to consider dissections as a potential cause of peripheral CN palsies and to be aware of the appropriate diagnostic pathways. This awareness can help clinicians make an early diagnosis, offering the opportunity for primary stroke prevention.

BackgroundThe COVID-19 pandemic has highlighted the growing relevance of telehealth in health care. Assessing health care and nursing students’ telehealth competencies is crucial for its successful integration into education and practice. ObjectiveWe aimed to assess students’ perceived telehealth knowledge, skills, attitudes, and experiences. In addition, we aimed to examine students’ preferences for telehealth content and teaching methods within their curricula. MethodsWe conducted a cross-sectional web-based study in May 2022. A project-specific questionnaire, developed and refined through iterative feedback and face-validity testing, addressed topics such as demographics, personal perceptions, and professional experience with telehealth and solicited input on potential telehealth course content. Statistical analyses were conducted on surveys with at least a 50% completion rate, including descriptive statistics of categorical variables, graphical representation of results, and Kruskal Wallis tests for central tendencies in subgroup analyses. ResultsA total of 261 students from 7 bachelor’s and 4 master’s health care and nursing programs participated in the study. Most students expressed interest in telehealth (180/261, 69% very or rather interested) and recognized its importance in their education (215/261, 82.4% very or rather important). However, most participants reported limited knowledge of telehealth applications concerning their profession (only 7/261, 2.7% stated profound knowledge) and limited active telehealth experience with various telehealth applications (between 18/261, 6.9% and 63/261, 24.1%). Statistically significant differences were found between study programs regarding telehealth interest (P=.005), knowledge (P

We present a case with prolonged Lorlatinib-related dyslipidemia causing internal carotid artery stenosis, putting the patient at risk of cerebrovascular events. Through intensified lipid-lowering treatment and dose reduction of Lorlatinib, LDL-C levels decreased markedly. Surprisingly, the left sided internal carotid artery stenosis dissolved accordingly. Due to the high efficacy of the new selective tyrosine kinase inhibitors and resulting long-term treatment, it is essential to carefully follow-up and include drug specific side effect monitoring. This case emphasizes that Loraltinib-related dyslipidemia has to be taken seriously and treatment should be initiated as promptly as possible. We conclude that in cases were lipid dysregulation remains and Lorlatinib treatment has to be continued, cerebrovascular appraisal through ultrasound should be considered and, if stenosis is evident, intensified treatment regimen of dyslipidemia or dose reduction of Lorlatinib should be discussed in an interdisciplinary setting.

Summary: Laser speckle contrast imaging (LSCI) is an important non-invasive capability for real-time imaging for tissue-perfusion assessment. Yet, the size and weight of current clinical standard LSCI instrumentation restricts usage to mainly peripheral skin perfusion. Miniaturization of LSCI could enable hand-held instrumentation to image internal organ/tissue to produce accurate speckle-perfusion maps. We characterized a 1mm2 chip-on-tip camera for LSCI of blood perfusion in vivo and with a flow model. A dedicated optical setup was built to compare chip-on-tip camera to a high specification reference camera (GS3) for LSCI. We compared LSCI performance using a calibration standard and a flow phantom. Subsequently the camera assessed placenta perfusion in a small animal model. Lastly, a human study was conducted on the perfusion in fingertips of 13-volunteers. We demonstrate that the chip-on-tip camera can perform wide-field, in vivo, LSCI of tissue perfusion with the ability to measure physiological blood flow changes comparable with a standard reference camera.

Ehlers-Danlos syndrome (EDS) belongs to a spectrum of rare heritable connective tissue disorders and is characterised by hyperextensibility, joint hypermobility and tissue fragility. Peripheral blood mononuclear cells (PBMCs) from a vascular EDS (vEDS) patient, known as the rarest EDS subtype, carrying a heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene, which is essential for type III collagen synthesis, were reprogrammed into induced pluripotent stem cells (iPSCs). The generated iPSCs exhibit high expression of pluripotency-associated markers, possess trilineage differentiation capacity and reveal a normal karyotype. This novel patient-specific cell line enables in-depth pathophysiological studies of vEDS.

Abstract Obesity is an enormous health problem, and many patients do not respond to any of the available therapies. Deep brain stimulation (DBS) is currently investigated as a potential treatment for morbid obesity. In this study, we tested the hypothesis that high-frequency DBS targeting the nucleus accumbens (NAc) shell region reduces food intake and weight gain in mice fed a high-fat diet. We implanted male C57BL/6J mice with bilateral electrodes and a head-mounted microstimulator enabling continuous stimulation for up to 5 weeks. In successfully operated animals (n = 9 per group, high-frequency vs. sham stimulation), we investigated immediate and long-term stimulation effects on metabolic and behavioral phenotypes. Here we show that stimulation acutely induced a transient reduction in energy expenditure and locomotor activity but did not significantly affect spontaneous food intake, social interaction, anxiety or exploratory behaviors. In contrast, continuous stimulation over 5 weeks led to a decrease in food intake and thigmotaxis (the tendency to stay near walls in an open lit arena). However, chronic stimulation did not substantially change weight gain in mice fed a high-fat diet. Our results do not support the use of continuous high-frequency NAc shell DBS as a treatment for obesity. However, DBS can alter obesity-related parameters with differing short and long-term effects. Therefore, future research should employ time and context-sensitive experimental designs to assess the potential of DBS for clinical translation in this area.

Abstract The wealth of text data generated by social media has enabled new kinds of analysis of emotions with language models. These models are often trained on small and costly datasets of text annotations produced by readers who guess the emotions expressed by others in social media posts. This affects the quality of emotion identification methods due to training data size limitations and noise in the production of labels used in model development. We present LEIA, a model for emotion identification in text that has been trained on a dataset of more than 6 million posts with self-annotated emotion labels for happiness, affection, sadness, anger, and fear. LEIA is based on a word masking method that enhances the learning of emotion words during model pre-training. LEIA achieves macro-F1 values of approximately 73 on three in-domain test datasets, outperforming other supervised and unsupervised methods in a strong benchmark that shows that LEIA generalizes across posts, users, and time periods. We further perform an out-of-domain evaluation on five different datasets of social media and other sources, showing LEIA’s robust performance across media, data collection methods, and annotation schemes. Our results show that LEIA generalizes its classification of anger, happiness, and sadness beyond the domain it was trained on. LEIA can be applied in future research to provide better identification of emotions in text from the perspective of the writer.

Der deutsche Gesetzgeber hat mit dem Arzneimittelmarkt-neuordnungsgesetz (AMNOG) im Jahr 2011 das Prinzip der nutzenbasierten Preisbildung gesetzlich verankert. So orientiert sich die Preisverhandlung seitdem neben den Jahrestherapiekosten vergleichbarer Arzneimittel und Abgabepreisen in anderen EU-Ländern maßgeblich am Zusatznutzen eines Arzneimittels. Ziel des Gesetzes war es, den Preis für neue Arzneimittel mit Patentschutz bzw. neuem Unterlagenschutz im Anschluss an eine Zusatznutzenbewertung zu verhandeln. Die Nutzenbewertung erfolgt gegenüber der zweckmäßigen Vergleichstherapie (zVT). Dieser ermittelte Zusatznutzen bildet mit den zuvor benannten Kriterien die Grundlage für die Erstattungspreisverhandlung, welche auf Basis des Beschlusses des Gemeinsamen Bundesausschusses (G-BA) zwischen dem pharmazeutischen Unternehmer und dem Spitzenverband Bund der Krankenkassen (GKV-SV) geführt wird. Der hieraus resultierende Preisabschlag auf den Einführungspreis ist die Grundlage für die Berechnung der AMNOG-Einsparungen nach § 130b SGB V. Diese berechnen sich durch die Umsatzdifferenz des betrachteten realen Umsatzes (Preis entspr. Erstattungsbetragsverhandlung x Menge) und eines „fiktiven“ Umsatzes (Preis ohne Erstattungsbetragsverhandlung x Menge), welcher ohne die AMNOG-Preisverhandlungen erstattet worden wäre.

Abstract Measuring forest biodiversity using terrestrial surveys is expensive and can only capture common species abundance in large heterogeneous landscapes. In contrast, combining airborne imagery with computer vision can generate individual tree data at the scales of hundreds of thousands of trees. To train computer vision models, ground‐based species labels are combined with airborne reflectance data. Due to the difficulty of finding rare species in a large landscape, many classification models only include the most abundant species, leading to biased predictions at broad scales. For example, if only common species are used to train the model, this assumes that these samples are representative across the entire landscape. Extending classification models to include rare species requires targeted data collection and algorithmic improvements to overcome large data imbalances between dominant and rare taxa. We use a targeted sampling workflow to the Ordway Swisher Biological Station within the US National Ecological Observatory Network (NEON), where traditional forestry plots had identified six canopy tree species with more than 10 individuals at the site. Combining iterative model development with rare species sampling, we extend a training dataset to include 14 species. Using a multi‐temporal hierarchical model, we demonstrate the ability to include species predicted at

The purpose of this study was to determine the effectiveness of the instrument and the norms for testing the physical ability of athletes aged 13-18 years. This type of research is descriptive research with survey techniques using the test method. The population in this study were Student Education and Training Center athletes in East Nusa Tenggara Province, totaling 69 athletes consisting of 41 boys and 28 girls. The sampling technique used in this study is nonprobability sampling of 69 athletes. The instruments used in this study were the 400 meter running test, sit and reach test, power hop test and multistage fitness test. The data obtained in this study were processed using t-test statistics with a significance level (α) = 5%. The results of research based on research and tests that have been carried out have a significant effect. Judging from the results of calculating the correlation coefficient of the influence and contribution of the old and new norms, namely: for male athletes, the value of R = correlation coefficient is equal to 0.720, while the magnitude of the contribution of the new norm to the old norm is shown by the R Square value of 0.518, which is 51.8%. Whereas for female athletes, the results obtained are R = correlation coefficient of 0.921, which means that the influence is large, while the contribution of the new norm to the old norm is shown by the R Square value of 0.849, which is 84.9%. So it can be concluded that there is an effectiveness of the instruments and norms for testing the physical ability of athletes aged 13-18 years in East Nusa Tenggara Province.

Abstract Background 5-Aminovaleric acid betaine (5-AVAB) has recently been identified as a diet and microbial-dependent factor inducing obesity and hepatic steatosis in mice fed a Western diet. Accumulating evidence suggests a role in metabolic dysfunction associated with obesity, diabetes, and fatty liver disease. However, whether 5-AVAB plays a role in human disease is unclear, and human data are sparse. Methods We measured circulating 5-AVAB serum levels in 143 individuals with overweight or obesity participating in a randomized intervention study (NCT00850629) investigating the long-term effect of a weight maintenance strategy after diet-induced weight reduction. Results Higher 5-AVAB serum levels correlate with worse estimates of obesity, glucose metabolism, and hepatic steatosis after weight loss. Furthermore, higher 5-AVAB levels after weight loss independently predict detrimental changes in glucose metabolism 18 months after the successful weight reduction. Conclusion Our human data supports previous findings in rodents indicating a relevant, potentially disadvantageous function of 5-AVAB in the context of metabolic dysbalance.

Tourism demand modelling is one of the most studied areas in tourism economics, particularly focused on time series and econometric research. In this study, directly interpretable one-equation techniques are utilised, i.e. the autoregressive distributed lag model (ADLM) and the derived error correction model (ECM). To complement the sharing of information and habits in tourism, we apply regressors derived from wages, general prices, and dummies. For the Czech and Austrian data, short- as well as long-run sets of outputs act differently, regarding the specific situation. Such information can straightforwardly be applied to the effective planning of various activities covering the public and private sectors. The results are completed by the standard cointegration testing procedure and residual analysis.

Abstract Futibatinib is a covalently binding FGFR1–4 inhibitor that received US Food and Drug Administration approval for the treatment of patients with previously treated, advanced intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions/rearrangements. This phase I trial evaluated the pharmacokinetics (PKs), safety, and tolerability of futibatinib in subjects with impaired hepatic function and matched healthy volunteers. Twenty‐two subjects with hepatic impairment (8 mild [Child‐Pugh 5–6], 8 moderate [7–9], and 6 severe [10–15]) and 16 matched healthy control subjects received a single oral dose of futibatinib 20 mg. Futibatinib PKs were compared between subjects with mild/moderate/severe hepatic impairment and each corresponding control cohort and the overall control cohort. Relationships between futibatinib PKs and Child‐Pugh scores and liver function tests were examined via scatter/regression plots. Compared with matched controls, the area under the plasma concentration–time curve from time zero to infinity increased by 21%/20%/18% and the maximum plasma concentration (Cmax) increased by 43%/15%/10% in subjects with mild/moderate/severe hepatic impairment, respectively. Changes were not considered clinically relevant: geometric mean ratios were within 80%–125%, except for Cmax in subjects with mild hepatic impairment (143%). No obvious trends were observed among futibatinib PK parameters versus Child‐Pugh scores, bilirubin, albumin, international normalized ratio, and aspartate aminotransferase (all p > 0.05). Futibatinib was well‐tolerated, with only four grade 1 treatment‐emergent adverse events (mild hepatic impairment = 2 and control = 2). The results demonstrate that futibatinib dose adjustments due to mild/moderate/severe hepatic impairment are not necessary in patients receiving futibatinib 20 mg daily.

Individuals working in the field of dentistry have a high prevalence of musculoskeletal disorders (MSDs) owing to monotonous and one-sided physical exertion. Inertial measurement units (IMU) are increasingly shifting into focus for assessing postural risk at work. Therefore, the present study aimed to evaluate the effects of an ergonomic lecture and training intervention on postural risk and MSDs in dental assistant students using inertial sensor-based motion capture (MoCap). Eighteen female dental assistant students (age: 19.44 ± 6.83 years; height: 164.59 ± 5.32 cm; weight: 64.88 ± 16.52 kg; BMI: 19.70 ± 4.89 kg/m2), randomly divided into intervention (n = 9) and control (n = 9) groups, participated in the present study. The participants completed the Nordic Questionnaire on MSD prevalence, after which a 90 s MoCap with Xsens IMU was performed. A lecture on ergonomics was provided, followed by a five-week intervention for the intervention group. Follow-up assessments were performed, and 5- and 18-week follow-up MSD questionnaires were administered. Mixed analysis of variance (MANOVA) showed a significant difference in the Rapid Upper Limb Assessment (RULA) and part-scores of the upper arm and wrist. Despite a reduction in MSDs, no significant differences in the time of measurement and groups were detected after the five-week training intervention and the 18-week follow-up questionnaire. A targeted ergonomics lecture was effective for dental assistant students, and technologies such as IMU improved workplace ergonomics in dentists. Further studies with a longer measurement periods, follow-up, and larger sample sizes are recommended.

This study examines the process of using injection moulding to join two different materials to manufacture bi-component moulded products with improved performance characteristics. The two-component process, which combines the advantages of two different technologies—the high efficiency of the injection moulding process and the excellent mechanical properties of long glass fibre composites produced by resin transfer moulding (RTM) technology—offers a particular advantage and improved applicability of the prepared lightweight products in both the automotive and aerospace sectors. The composite studied here consists of Elium® thermoplastic resin (30%) reinforced with unwoven glass fibre fabric (70%) using the RTM process. The Elium® composite sample is consequently used as an insert overmoulded with polybutylene terephthalate (PBT) homopolymer reinforced with 20% w/w of short glass fibre through injection moulding. The influence of different mould temperatures and surface treatments on the adhesion between the materials used is investigated by evaluating the mechanical performance using tensile shear strength tests. It was found that while an increase in mould temperature from 40 °C to 120 °C resulted in a doubling of the initial average bond strength between untreated Elium® RTM inserts and overmoulded PBT parts (0.9 MPa), sandblasting the inserts ensured a further tripling of the bond strength of the composites to a value of 5.4 MPa.

This research investigates the micro-mechanical and tribological properties of injection-molded parts made from polypropylene. The tribological properties of polymers are a very interesting area of research. Understanding tribological processes is very crucial. Considering that the mechanical and tribological properties of injected parts are not uniform at various points of the part, this research was conducted to explain the non-homogeneity of properties along the flow path. Non-homogeneity can be influenced by numerous factors, including distance from the gate, mold and melt temperature, injection pressure, crystalline structure, cooling rate, the surface of the mold, and others. The key factor from the micro-mechanical and tribological properties point of view is the polymer morphology (degree of crystallinity and size of the skin and core layers). The morphology is influenced by polymer flow and the injection molding process conditions. Gained results indicate that the indentation method was sufficiently sensitive to capture the changes in polypropylene morphology, which is a key parameter for the resulting micro-mechanical and tribological properties of the part. It was proven that the mechanical and tribological properties are not equal in varying regions of the part. Due to cooling and process parameters, the difference in the indentation modulus in individual measurement points was up to 55%, and the tribological properties, in particular the friction coefficient, showed a difference of up to 20%. The aforementioned results indicate the impact this finding signifies for injection molding technology in technical practice. Tribological properties are a key property of the part surface and, together with micro-mechanical properties, characterize the resistance of the surface to mechanical failure of the plastic part when used in engineering applications. A suitable choice of gate location, finishing method of the cavity surface, and process parameters can ensure the improvement of mechanical and tribological properties in stressed regions of the part. This will increase the stiffness and wear resistance of the surface.

Abstract Soybean meal (SBM) is widely used in shrimp feed agro‐industry as a fish meal (FM) replacement. However, high levels of SBM may compromise animal health as a result of nutrient imbalance. This study aimed to investigate the effects of feed enzyme combination (a mixture of 6‐phytase, serine protease, and endo‐1,3(4)‐β‐glucanase) and functional immunostimulant combination (a mixture of brewer's yeast, nucleotides, vitamin C, and vitamin E) in improving the overall health of Pacific white shrimp fed soybean‐based diet. Four diets were formulated with different amounts of SBM, FM, and poultry meal (PM): 0% SBM (with 25% FM and 12.6% PM), 30% SBM (with 12.5% FM and 5.7% PM), 30% SBM plus 0.045% feed enzymes, and 30% SBM plus 0.1% functional immunostimulants. The postlarvae were fed the test diets for 45 days. Then, the body weight, survival, FCR, Vibrio spp. count, and immune responses were analyzed. The resistance of shrimp to Vibrio parahaemolyticus infection was also evaluated. The results suggest that the diet with 30% SBM was deleterious to the shrimp's health. Feed enzymes and functional immunostimulant supplements improved overall performance, immune function, and resistance to V. parahaemolyticus infection of shrimp fed the diet containing 30% SBM compared with the 30% SBM diet without feed supplements.

Reactions of thiobenzamide or thioacetamide with 4-bromo-1,1-dimethyl-1,4-dihydroisoquinoline-3(2H)-one, 4-bromoisoquinoline-1,3(2H,4H)-dione and two α-bromo(phenyl)acetamides were examined under various conditions (base, solvent, thiophile, temperature) and structure/medium features that influence product distribution (Eschenmoser coupling reaction, Hantzsch thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts.

Plant proteases are essential enzymes that play key roles during crucial phases of plant life. Some proteases are mainly involved in general protein turnover and recycle amino acids for protein synthesis. Other proteases are involved in cell signalling, cleave specific substrates and are key players during important genetically controlled molecular processes. Cathepsin B is a cysteine protease that can do both because of its exopeptidase and endopeptidase activities. Animal cathepsin B has been investigated for many years, and much is known about its mode of action and substrate preferences, but much remains to be discovered about this potent protease in plants. Cathepsin B is involved in plant development, germination, senescence, microspore embryogenesis, pathogen defence and responses to abiotic stress, including programmed cell death. This review discusses the structural features, the activity of the enzyme and the differences between the plant and animal forms. We discuss its maturation and subcellular localisation and provide a detailed overview of the involvement of cathepsin B in important plant life processes. A greater understanding of the cell signalling processes involving cathepsin B is needed for applied discoveries in plant biotechnology.

Abstract Lipofuscin (LF) is an intracellular aggregate associated with proteostatic impairments, especially prevalent in nondividing skeletal muscle fibers. Reactive oxygen species (ROS) drive LF‐formation. Resistance training (RT) improves muscle performance but also increases ROS production, potentially promoting LF‐formation. Thus, we aimed to investigate if RT of a mesocycle duration increases LF‐formation in type‐I and II muscle fibers and whether RT increases the antioxidant capacity (AOC) in terms of SOD1 and SOD2 content. An intervention group (IG) performed 14 eccentrically accented RT‐sessions within 7 weeks. Vastus lateralis muscle biopsies were collected before and after the intervention from IG as well as from a control group (CG) which refrained from RT for the same duration. LF was predominantly found near nuclei, followed by membrane‐near and a minor amount in the fiber core, with corresponding spot sizes. Overall, LF‐content was higher in type‐I than type‐II fibers (p