A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol.

Mitochondrial fidelity is tightly linked to overall cellular homeostasis and is compromised in ageing and various pathologies1-3. Mitochondrial malfunction needs to be relayed to the cytosol, where an integrated stress response is triggered by the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) in mammalian cells4,5. eIF2α phosphorylation is mediated by the four eIF2α kinases GCN2, HRI, PERK and PKR, which are activated by diverse types of cellular stress6. However, the machinery that communicates mitochondrial perturbation to the cytosol to trigger the integrated stress response remains unknown1,2,7. Here we combine genome engineering and haploid genetics to unbiasedly identify genes that affect the induction of C/EBP homologous protein (CHOP), a key factor in the integrated stress response. We show that the mitochondrial protease OMA1 and the poorly characterized protein DELE1, together with HRI, constitute the missing pathway that is triggered by mitochondrial stress. Mechanistically, stress-induced activation of OMA1 causes DELE1 to be cleaved into a short form that accumulates in the cytosol, where it binds to and activates HRI via its C-terminal portion. Obstruction of this pathway can be beneficial or adverse depending on the type of mitochondrial perturbation. In addition to the core pathway components, our comparative genetic screening strategy identifies a suite of additional regulators. Together, these findings could be used to inform future strategies to modulate the cellular response to mitochondrial dysfunction in the context of human disease.

How can social robot use cases in healthcare be pushed - with an interoperable programming interface.

INTRODUCTION: Research into current robot middleware has revealed that most of them are either too complicated or outdated. These facts have motivated the development of a new middleware to meet the requirements of usability by non-experts. The proposed middleware is based on Android and is intended to be placed over existing robot SDKs and middleware. It runs on the android tablet of the Cruzr robot. Various toolings have been developed, such as a web component to control the robot via a webinterface, which facilitates its use. METHODS: The middleware was developed using Android Java and runs on the Cruzr tablet as an app. It features a WebSocket server that interfaces with the robot and allows control via Python or other WebSocket-compatible languages. The speech interface utilizes Google Cloud Voice text-to-speech and speech-to-text services. The interface was implemented in Python, allowing for easy integration with existing robotics development workflows, and a web interface was developed for direct control of the robot via the web. RESULTS: The new robot middleware was created and deployed on a Cruzr robot, relying on the WebSocket API and featuring a Python implementation. It supports various robot functions, such as text-to-speech, speech-to-text, navigation, displaying content and scanning bar codes. The system's architecture allows for porting the interface to other robots and platforms, showcasing its adaptability. It has been demonstrated that the middleware can be run on a Pepper robot, although not all functions have been implemented yet. The middleware was utilized to implement healthcare use cases and received good feedback. CONCLUSION: Cloud and local speech services were discussed in regard to the middleware's needs, to run without having to change any code on other robots. An outlook on how the programming interface can further be simplified by using natural text to code generators has been/is given. For other researchers using the aforementioned platforms (Cruzr, Pepper), the new middleware can be utilized for testing human-robot interaction. It can be used in a teaching setting, as well as be adapted to other robots using the same interface and philosophy regarding simple methods.

Diols, α-Ketols, and Diones as 22π Components in [2+2+2] Cycloadditions of 1,6-Diynes via Ruthenium(0)-Catalyzed Transfer Hydrogenation.

The first use of vicinal diols, ketols, or diones as 22π components in metal-catalyzed [2+2+2] cycloaddition is described. Using ruthenium(0) catalysts, 1,6-diynes form ruthenacyclopentadienes that engage transient diones in successive carbonyl addition. Transfer hydrogenolysis of the resulting ruthenium(II) diolate mediated by the diol or ketol reactant releases the cycloadduct with regeneration of ruthenium(0) and the requisite dione.

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin.

The biosynthetic precursor of redox cofactor F420, 7,8-didemethyl-8-hydroxy-5-deazariboflavin, was prepared in four steps from 6-chlorouracil, 2-chloro-4-hydroxybenzaldehyde and bis-isopropylidene protected D-ribose. The latter aldehyde was transformed to the corresponding protected ribitylamine via the oxime, which was submitted to reduction with LiAlH4. Key advantage compared to previous syntheses is the utilization of a polyol-protective group which allowed the chromatographic purification of a key-intermediate product providing the target compound with high purity.

A Geomimetic Approach to the Formation and Identification of Fossil Sterane Biomarkers in Crude Oil: 18-nor-D-homo-Androstane and 5α,14ß-Androstane.

A diazonium ion derived from 18-aminoandrostane rearranged upon decomposition by a carbonium and a carbenium ion to furnish a mixture of a cyclopropanated compound and two D-homo-androstenes. Hydrogenation of this mixture gave the saturated hydrocarbons, 18-nor-D-homo-androstane and 5α,14ß-androstane, which are both fossil sterane biomarkers in Neoproterozoic crude oil. The so far unknown constitution and configuration as well as the geochemical genesis were established by this experiment. The starting material for this investigation, 18-aminoandrostane, was prepared in twelve steps from androstan-17-one (12.5% overall yield) with a Barton reaction as the key step.

Using Robots in Medical Informatics Education.

Although robots have been used for quite some time in education on school and university level, we found no reports of robots being used in the teaching of medical informatics. Thus we present the timetable and structure of a one week, 2 ECTS blocked course for robots in medical informatics initiated in autumn 2022. 19 participants completed the first iteration. We report about the requirements in terms of an appropriate programming environment, the combination among robots and our medical informatics lab and the results of the student's evaluation of the first instance as well as the experiences with the two types of robots used.

Positive psychology interventions in in-patients with depression: influences of comorbidity and subjective evaluation of the training programme.

BACKGROUND: Studies on positive psychology interventions (PPIs) have frequently demonstrated benefits for healthy participants and patients. However, effect sizes are moderate, and underlying inter-individual differences in responses were rarely investigated. AIMS: We investigated whether severity of depression and subjective evaluation of PPIs are relevant sources of variance in this respect. METHOD: A 4-week group PPI programme (one 45-min session per week) was offered to 38 in-patients with depression. The control group (n = 38) was carefully matched and received treatment as usual. In the PPI group, emotional states were recorded before and after each session (responsiveness). Beck Depression Inventory-II scores at hospital admission and discharge were used to evaluate clinical effectiveness. The number of comorbidities (as an indicator of severity of disease) and patients' evaluations of the PPI sessions were used as additional independent factors for overall treatment outcome. RESULTS: The PPI induced a highly significant improvement in positive emotional state and decrease in negative emotional state, indicating responsiveness. Moreover, positive affectivity increased from week to week only in patients with a low number of comorbidities (indicating effectiveness). With respect to overall treatment outcome (Beck Depression Inventory-II scores), positive attitude toward the PPI resulted in the largest improvement. CONCLUSIONS: The results partly explain the variance in the effectiveness of PPIs. Moreover, they support the idea of personalised psychotherapy, and may inform discussion on whether patients with depression should be included in PPIs. However, additional individual characteristics should increase knowledge about individual predictors for effectiveness.

Information Capturing in Pre-Hospital Emergency Medical Settings (EMS).

Emergency medical situations are characterized by high physical, cognitive and mental demands on the paramedics on the ground. Studies suggest that crucial information such as treatments administered to patients is often documented retrospectively, during patient transport or once a patient is handed over to an emergency department. Information access may also be surprisingly difficult (e.g. patient medical history). In this paper, we focus on supporting in situ information capturing and report on a realistic laboratory-based study involving experienced paramedics that we used to explore the specific requirements and constraints of supporting in situ information capturing. Specifically, we focused on ways to use audio and visual data capture methods and how they need to be designed to better support paramedics without interfering with their work. We then use the resulting information centric perspective to argue for a roadmap towards smart emergency medical services.

Development and Validation of a Brief Measure of Self-Management Competence: The Self-Management Self-Test (SMST).

BACKGROUND: Self-management can be considered a way of dealing with oneself and relates to actions undertaken to create order, discipline, and control. The concept is closely linked to concepts of self-efficacy and self-regulation but can be distinguished from these. The Self-Management Self-Test (SMST) is a 5-item assessment scale designed to measure self-management competence in individuals with or without a psychiatric disorder (as screened using PHQ). The aim of this study was to validate the SMST in terms of convergent validity, the ability to differentiate, criterion validity, internal consistency, and test-retest reliability. METHODS: Eighty-seven adults hospitalized for treatment of major depression (clinical sample) and 595 individuals from the general population (population sample) filled out the SMST and 5 other stress-related psychometric instruments measuring similar constructs. All instruments were repeated 4 to 6 weeks later. Convergent validity, internal consistency, and test-retest reliability were tested based on data from the population sample. Convergent validity was determined by correlations with other stress-related psychometric instruments. Correlations in the range of r = -0.4 to -0.6 were expected. To test for criterion validity, the clinical sample was matched with a subsample from the population sample, consisting only of individuals without a psychiatric disorder as screened using PHQ (nonclinical subsample, n = 87). The ability to differentiate was based on receiver operating characteristic (ROC) curve analysis. RESULTS: Correlations between the SMST and the other stress-related tests were significant and in the expected direction and predominantly within the expected range (Pearson r = - 0.40 to -0.64). The correlation with the Multidimensional Fatigue Inventory-20, measuring fatigue, and with the dimensional scale for depression in the PHQ was higher than expected and referred to very similar items. Thus, convergent validity mainly lay within the expected range. Internal consistency was high (Cronbach α = 0.80), and test-retest reliability was fairly low (r = 0.71). The SMST showed a significant difference, t(157) = 7.97, P < .001, between the clinical sample (M = 9.36, SD = 3.39) and the nonclinical subsample (M = 12.94, SD = 2.47) with a large effect size (d = 1.3). The area under the ROC curve (AUC) was excellent (AUC = 0.81, SE = 0.034, P < .001), suggesting that the SMST can distinguish between the clinical and nonclinical samples. CONCLUSIONS: The SMST can be considered an effective self-rating test to assess self-management competence in individuals from the general population as well as in people with major depression. It may also be useful to detect treatment outcomes in people with major depression. The high internal consistency indicates that all 5 items are important for the test as a whole. The low test-retest reliability suggests sensitivity to change. The SMST is likely to differentiate particularly well at low levels of self-management competence, suggesting it may be a useful tool in studies investigating people with depression or other psychiatric disorders such as post-traumatic stress disorder. Furthermore, the SMST could be useful in assessing the effect of treatment interventions over time and evaluating patient-reported outcomes.

Development and Validation of a Brief Measure of Self-Management Competence: The Self-Management Self-Test (SMST).

BACKGROUND: Self-management can be considered a way of dealing with oneself and relates to actions undertaken to create order, discipline, and control. The concept is closely linked to concepts of self-efficacy and self-regulation but can be distinguished from these. The Self-Management Self-Test (SMST) is a 5-item assessment scale designed to measure self-management competence in individuals with or without a psychiatric disorder (as screened using PHQ). The aim of this study was to validate the SMST in terms of convergent validity, the ability to differentiate, criterion validity, internal consistency, and test-retest reliability. METHODS: Eighty-seven adults hospitalized for treatment of major depression (clinical sample) and 595 individuals from the general population (population sample) filled out the SMST and 5 other stress-related psychometric instruments measuring similar constructs. All instruments were repeated 4 to 6 weeks later. Convergent validity, internal consistency, and test-retest reliability were tested based on data from the population sample. Convergent validity was determined by correlations with other stress-related psychometric instruments. Correlations in the range of r = -0.4 to -0.6 were expected. To test for criterion validity, the clinical sample was matched with a subsample from the population sample, consisting only of individuals without a psychiatric disorder as screened using PHQ (nonclinical subsample, n = 87). The ability to differentiate was based on receiver operating characteristic (ROC) curve analysis. RESULTS: Correlations between the SMST and the other stress-related tests were significant and in the expected direction and predominantly within the expected range (Pearson r = -0.40 to -0.64). The correlation with the Multidimensional Fatigue Inventory-20, measuring fatigue, and with the dimensional scale for depression in the PHQ was higher than expected and referred to very similar items. Thus, convergent validity mainly lay within the expected range. Internal consistency was high (Cronbach α = 0.80), and test-retest reliability was fairly low (r = 0.71). The SMST showed a significant difference, t(157) = 7.97, P < .001, between the clinical sample (M = 9.36, SD = 3.39) and the nonclinical subsample (M = 12.94, SD = 2.47) with a large effect size (d = 1.3). The area under the ROC curve (AUC) was excellent (AUC = 0.81, SE = 0.034, P < .001), suggesting that the SMST can distinguish between the clinical and nonclinical samples. CONCLUSIONS: The SMST can be considered an effective self-rating test to assess self-management competence in individuals from the general population as well as in people with major depression. It may also be useful to detect treatment outcomes in people with major depression. The high internal consistency indicates that all 5 items are important for the test as a whole. The low test-retest reliability suggests sensitivity to change. The SMST is likely to differentiate particularly well at low levels of self-management competence, suggesting it may be a useful tool in studies investigating people with depression or other psychiatric disorders such as post-traumatic stress disorder. Furthermore, the SMST could be useful in assessing the effect of treatment interventions over time and evaluating patient-reported outcomes.

Ruthenium-catalyzed insertion of adjacent diol carbon atoms into C-C bonds: Entry to type II polyketides.

Current catalytic processes involving carbon-carbon bond activation rely on π-unsaturated coupling partners. Exploiting the concept of transfer hydrogenative coupling, we report a ruthenium(0)-catalyzed cycloaddition of benzocyclobutenones that functionalizes two adjacent saturated diol carbon-hydrogen bonds. These regio- and diastereoselective processes enable convergent construction of type II polyketide substructures.