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Abstract Introduction Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. Methods This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients’ needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. Perspective It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. Trial registration The study is registered at ClinicalTrails.gov; NCT06418646

Post-traumatic stress disorder symptoms related to work in pediatric departments aremajor public health problems, as they directly affect health organizations, healthcare workers, and, due to the poor quality of care, the patients as well. The post-traumatic symptoms that a healthcare worker may experience are related to intrusion, avoidance, negative changes in cognition and mood, and changes in arousal and reactivity. The aim of the present investigation was to identify risk factors that contribute to the development of PTSD in pediatric healthcare workers, in order to implement necessary workplace measures. A sample of four hundred and forty-five pediatric workers at seven Greek public hospitals consented to participate in the survey. Socio-demographic data and a post-traumatic checklist (5th edition) were used to diagnose post-traumatic stress disorder. According to the results, risk factors for the development of post-traumatic symptoms include medical or nursing errors, threats to a child’s life, and incidents of workplace bullying. More specifically, 25.2% of the participants had a provisional PTSD diagnosis, 72.8%of the sample experienced an incident involving a medical or nursing error in their workplace related to the treatment or care of a child, 56% experienced an incident involving a child’s death or a threat to a child’s life due to a serious illness or injury, and 55.5% experienced an incident of workplace bullying. In addition, it was found that having a university-level education, master’s, or PhD, working in a circular shift, being assigned to a department by management rather than the worker, and dissatisfaction with salary were associated with post-traumatic stress disorder. The high rates of PTSD symptoms among participants highlight the need for prevention and management measures to protect and support the mental health of workers in pediatric departments. We propose frequent evaluations of the mental health of employees, more time for rest, incentives for professional development, utilization of their specializations and specialties, support from mental health specialists when symptoms are diagnosed, and the option for employees to change departments if they wish or if they show symptoms of mental trauma.

The seemingly innocuous description of Leah as having ‘soft’ eyes in Genesis 29:17 has captivated scholars and readers for centuries. This article advances an ironic interpretation, suggesting that Leah’s ‘soft’ eyes were not a sign of weakness but, rather, an indication of envy and malevolence, potentially contributing to fertility issues faced by her sister Rachel in terms of the ancient Near Eastern evil eye belief complex. In this context, the article delves into ancient belief systems that entwined beauty, fertility, and the malevolent gaze. Contribution: Drawing from biblical texts, historical sources, and contemporary scholarship, this article reveals the intricate layers of meaning within this minor detail.

Automated greenhouse production systems frequently employ non-destructive techniques, such as computer vision-based methods, to accurately measure plant physiological properties and monitor crop growth. By utilizing an automated image acquisition and analysis system, it becomes possible to swiftly assess the growth and health of plants throughout their entire lifecycle. This valuable information can be utilized by growers, farmers, and crop researchers who are interested in self-cultivation procedures. At the same time, such a system can alleviate the burden of daily plant photography for human photographers and crop researchers, while facilitating automated plant image acquisition for crop status monitoring. Given these considerations, the aim of this study was to develop an experimental, low-cost, 1-DOF linear robotic camera system specifically designed for automated plant photography. As an initial evaluation of the proposed system, which targets future research endeavors of simplifying the process of plant growth monitoring in a small greenhouse, the experimental setup and precise plant identification and localization are demonstrated in this work through an application on lettuce plants, imaged mostly under laboratory conditions.

As it concerns remote laboratories (RLs) for teaching microcontroller programming, the related literature reveals several common characteristics and a common architecture. Our search of the literature was constrained to papers published in the period of 2020–2023 specifically on remote laboratories related to the subject of teaching microcontroller programming of the Arduino family. The objective of this search is to present, on the one hand, the extent to which the RL platform from the Hellenic Mediterranean University (HMU-RLP) for Arduino microcontroller programming conforms to this common architecture and, on the other hand, how it extends this architecture with new features for monitoring and assessing users’ activities over remote labs in the context of pervasive and supervised learning. The HMU-RLP hosts a great number of experiments that can be practiced by RL users in the form of different scenarios provided by teachers as activities that users can perform in their self-learning process or assigned as exercises complementary to the theoretical part of a course. More importantly, it provides three types of assessments of the code users program during their experimentation with RLs. The first type monitors each action users perform over the web page offered by the RL. The second type monitors the activities of users at the hardware level. To this end, a shadow microcontroller is used that monitors the pins of the microcontroller programmed by the users. The third type automatically assesses the code uploaded by the users, checking its similarity with the prototype code uploaded by the instructors. A trained AI model is used to this end. For the assessments provided by the HMU-RLP, the experience API (xAPI) standard is exploited to store users’ learning analytics (LAs). The LAs can be processed by the instructors for the students’ evaluation and personalized learning. The xAPI reporting and visualization tools used in our prototype RLP implementation are also presented in the paper. We also discuss the planned development of such functionalities in the future for the use of the HMU-RLP as an adaptive tool for supervised distant learning.

Krach et al. dissect the molecular mechanism of the alternative splicing modulator Branaplam in Huntington’s disease. They show that the drug lowers mutant HTT protein levels and ameliorates alternative splicing pathology in an iPSC disease model.

Abstract Background The development of permanent disability in multiple sclerosis (MS) is highly variable among patients, and the exact mechanisms that contribute to this disability remain unknown. Methods Following the idea that the brain has intrinsic network organization, we investigated changes of functional networks in MS patients to identify possible links between network reorganization and remission from clinical episodes in MS. Eighteen relapsing–remitting MS patients (RRMS) in their first clinical manifestation underwent resting-state functional MRI and again during remission. We used ten template networks, identified from independent component analysis, to compare changes in network coherence for each patient compared to those of 44 healthy controls from the Human Connectome Project test–retest dataset (two-sample t- test of pre-post differences). Combining a binomial test with Monte Carlo procedures, we tested four models of how functional coherence might change between the first clinical episode and remission: a network can change its coherence (a) with itself (“one-with-self”), (b) with another network (“one-with-other”), or (c) with a set of other networks (“one-with-many”), or (d) multiple networks can change their coherence with respect to one common network (“many-with-one”). Results We found evidence supporting two of these hypotheses: coherence decreased between the Executive Control Network and several other networks (“one-with-many” hypothesis), and a set of networks altered their coherence with the Cerebellar Network (“many-with-one” hypothesis). Conclusion Given the unexpected commonality of the Cerebellar Network’s altered coherence with other networks (a finding present in more than 70% of the patients, despite their clinical heterogeneity), we conclude that remission in MS may result from learning processes mediated by the Cerebellar Network.

Abstract Background SPG11-linked hereditary spastic paraplegia is characterized by multisystem neurodegeneration leading to a complex clinical and yet incurable phenotype of progressive spasticity and weakness. Severe cognitive symptoms are present in the majority of SPG11 patients, but a systematic and multidimensional analysis of the neuropsychological phenotype in a larger cohort is lacking. While thinning of the corpus callosum is a well-known structural hallmark observed in SPG11 patients, the neuroanatomical pattern of cortical degeneration is less understood. We here aimed to integrate neuropsychological and brain morphometric measures in SPG11. Methods We examined the neuropsychological profile in 16 SPG11 patients using a defined neuropsychological testing battery. Long-term follow up testing was performed in 7 patients. Cortical and subcortical degeneration was analyzed using an approved, artificial intelligence based magnetic resonance imaging brain morphometry, comparing patients to established reference values and to matched controls. Results In SPG11 patients, verbal fluency and memory as well as frontal-executive functions were severely impaired. Later disease stages were associated with a global pattern of impairments. Interestingly, reaction times correlated significantly with disease progression. Brain morphometry showed a significant reduction of cortical and subcortical parenchymal volume following a rostro-caudal gradient in SPG11. Whereas performance in memory tasks correlated with white matter damage, verbal fluency measures showed strong associations with frontal and parietal cortical volumes. Conclusions The present data will help define neuropsychological and imaging read out parameters in early as well as in advanced clinical stages for future interventional trials in SPG11.

The genus Origanum is a well-known culinary, aromatic and medicinal taxon of the Lamiaceae family. Despite the notable progress that has been made in Lamiaceae phylogenetics and in the Nepetoideae subfamily, the genus remains insufficiently investigated concerning its interspecies evolutionary relationships. The present study provides initial insights into the phylogenetic relationships and sectional classification of Greek taxa, based on three nuclear and five chloroplast DNA regions with eight taxa and 68 samples in total. The molecular results showed all (steno) endemic species as monophyletic with high or absolute support. Additionally, O. calcaratum’s scattered distribution between three phytogeographical areas in the Aegean Archipelago is also confirmed molecularly. The molecular results also verify the close affinity of certain sections; thus, sec. Majorana is placed as a sister group of sec. Chilocalyx and sec. Amaracus with sec. Anatolicon. However, based on species sectional classification, the groups from this study differ from the sections previously recognized. Such species belong to sections Amaracus and Anatolicon, where they are either mixed together or are grouped with other sections. Regarding morphological analysis, certain non-vegetative characters are highlighted as important for the delimitation of most Greek taxa, while characters related to the calyx, when combined, are very useful for the delimitation of sections.

Abstract Background The rapid expansion of the CRISPR toolbox through tagging effector domains to either enzymatically inactive Cas9 (dCas9) or Cas9 nickase (nCas9) has led to several promising new gene editing strategies. Recent additions include CRISPR cytosine or adenine base editors (CBEs and ABEs) and the CRISPR prime editors (PEs), in which a deaminase or reverse transcriptase are fused to nCas9, respectively. These tools hold great promise to model and correct disease-causing mutations in animal and plant models. But so far, no widely-available tools exist to automate the design of both BE and PE reagents. Results We developed PnB Designer, a web-based application for the design of pegRNAs for PEs and guide RNAs for BEs. PnB Designer makes it easy to design targeting guide RNAs for single or multiple targets on a variant or reference genome from organisms spanning multiple kingdoms. With PnB Designer, we designed pegRNAs to model all known disease causing mutations available in ClinVar. Additionally, PnB Designer can be used to design guide RNAs to install or revert a SNV, scanning the genome with one CBE and seven different ABE PAM variants and returning the best BE to use. PnB Designer is publicly accessible at http://fgcz-shiny.uzh.ch/PnBDesigner/ Conclusion With PnB Designer we created a user-friendly design tool for CRISPR PE and BE reagents, which should simplify choosing editing strategy and avoiding design complications.

It is often claimed that the use of depth psychology in the interpretation of ancient texts is irrelevant and methodologically unsound. Several typical Jungian archetypes, such as the shadow, the primordial mother, and the hero, were identified, interpreted and commented on from a post-Jungian perspective. The apocryphal Book of Baruch has typically been studied as a prime example of penitential prayer in the late Second Temple Period. In this study, the book was approached from the perspective of post-Jungian literary criticism. While Jungian literary criticism has become unfashionable as a result of Jung’s anti-feminist and anti-Semitic ideas, the usefulness of his theory to criticise itself was demonstrated. Although Jung’s work is haunted by racism, anti-feminism, and antisemitism, his work may still be useful for literary criticism from a psychological perspective. Contribution: The article demonstrated the value of the depth psychological approach to the interpretation of biblical material.

Chlorophyll meters are portable devices used to assess and improve plants’ nitrogen management and to help farmers in the determination of the health condition of plants through leaf greenness measurements. These optical electronic instruments can provide an assessment of chlorophyll content by measuring the light passing through a leaf or by measuring the light radiation reflected from its surface. However, independently of the main principle of operation and use (e.g., absorbance vs. reflectance measurements), commercial chlorophyll meters usually cost hundreds or even thousands of euros, making them inaccessible to growers and ordinary citizens who are interested in self-cultivation, farmers, crop researchers, and communities lacking resources in general. A low-cost chlorophyll meter based on light-to-voltage measurements of the remaining light after two LED light emissions through a leaf is designed, constructed, evaluated, and compared against two well-known commercial chlorophyll meters, the SPAD-502 and the atLeaf CHL Plus. Initial tests of the proposed device on lemon tree leaves and on young Brussels sprouts plant leaves revealed promising results compared to the commercial instruments. The coefficient of determination, R2, was estimated to be 0.9767 for the SPAD-502 and 0.9898 for the atLeaf-meter in lemon tree leaves samples compared to the proposed device, while for the Brussels sprouts plant, R2 was estimated to be 0.9506 and 0.9624, respectively. Further tests conducted as a preliminary evaluation of the proposed device are also presented.

Background: Small fiber neuropathy (SFN) is a severe and disabling chronic pain syndrome with no causal and limited symptomatic treatment options. Mechanistically based individual treatment is not available. We report an in-vitro predicted individualized treatment success in one therapy-refractory Caucasian patient suffering from SFN for over ten years. Methods: Intrinsic excitability of human induced pluripotent stem cell (iPSC) derived nociceptors from this patient and respective controls were recorded on multi-electrode (MEA) arrays, in the presence and absence of lacosamide. The patient's pain ratings were assessed by a visual analogue scale (10: worst pain, 0: no pain) and treatment effect was objectified by microneurography recordings of the patient's single nerve C-fibers. Findings: We identified patient-specific changes in iPSC-derived nociceptor excitability in MEA recordings, which were reverted by the FDA-approved compound lacosamide in vitro. Using this drug for individualized treatment of this patient, the patient's pain ratings decreased from 7.5 to 1.5. Consistent with the pain relief reported by the patient, microneurography recordings of the patient's single nerve fibers mirrored a reduced spontaneous nociceptor (C-fiber) activity in the patient during lacosamide treatment. Microneurography recordings yielded an objective measurement of altered peripheral nociceptor activity following treatment. Interpretation: Thus, we are here presenting one example of successful patient specific precision medicine using iPSC technology and individualized therapeutic treatment based on patient-derived sensory neurons. Keywords: Personalized therapy, Human nociceptors, Small fiber neuropathy, Microneurography, Patch-clamp, Multi-electrode-array

In the present work, a methodology for the low-cost crafting of an interactive layered dashboard is proposed. Our aim is that the tangible surface be constructed using domestic materials that are easily available in every household. Several tests were performed on different capacitive materials before the selection of the most suitable one for use as a capacitive touch sensor. Various calibration methods were evaluated so that the behavior of the constructed capacitive touch sensors is smooth and reliable. The layered approach is achieved by a menu of few touch buttons on the left side of the dashboard. Thus, various different layers of content can be projected over the same construction, offering extendibility and ease of use to the users. For demonstration purposes, we developed an entertaining plus an educational application of projection mapping for the pervasive and interactive projection of multimedia content to the users of the presented tangible interface. The whole design and implementation approach are thoroughly analyzed in the paper and are presented through the illustration and application of various multimedia layers over the dashboard. An evaluation of the final construction proves the feasibility of the proposed work.

Dendritic dysfunction is an early event in α-synuclein (α-syn) mediated neurodegeneration. Altered postsynaptic potential and loss of dendritic spines have been observed in different in vitro and in vivo models of synucleinopathies. The integration of newborn neurons into the hippocampus offers the possibility to study dendrite and spine formation in an adult environment. Specifically, survival of hippocampal adult newborn neurons is regulated by synaptic input and was reduced in a mouse model transgenic for human A53T mutant α-syn. We thus hypothesized that dendritic integration of newborn neurons is impaired in the adult hippocampus of A53T mice. We analyzed dendritic morphology of adult hippocampal neurons 1 month after retroviral labeling. Dendrite length was unchanged in the dentate gyrus of A53T transgenic mice. However, spine density and mushroom spine density of newborn neurons were severely decreased. In this mouse model, transgenic α-syn was expressed both within newborn neurons and within their environment. To specifically determine the cell autonomous effects, we analyzed cell-intrinsic overexpression of A53T α-syn using a retrovirus. Since A53T α-syn overexpressing newborn neurons exhibited decreased spine density 1 month after labeling, we conclude that cell-intrinsic A53T α-syn impairs postsynaptic integration of adult hippocampal newborn neurons. Our findings further support the role of postsynaptic degeneration as an early feature in synucleinopathies and provide a model system to study underlying mechanisms.

Transcriptional adaptation is a recently described phenomenon by which a mutation in one gene leads to the transcriptional modulation of related genes, termed adapting genes. At the molecular level, it has been proposed that the mutant mRNA, rather than the loss of protein function, activates this response. While several examples of transcriptional adaptation have been reported in zebrafish embryos and in mouse cell lines, it is not known whether this phenomenon is observed across metazoans. Here we report transcriptional adaptation in C. elegans, and find that this process requires factors involved in mutant mRNA decay, as in zebrafish and mouse. We further uncover a requirement for Argonaute proteins and Dicer, factors involved in small RNA maturation and transport into the nucleus. Altogether, these results provide evidence for transcriptional adaptation in C. elegans, a powerful model to further investigate underlying molecular mechanisms.

Background: Remote kidney damage is a sequel of hepatic ischemia–reperfusion (I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed extract with known antioxidant and hepatoprotective activity. Our study investigates the nephroprotective potential of intravenously administered silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in hepatic I/R injury. Material and methods: 63 Wistar rats were divided into three groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion); and Silibinin (200 μL intravenous silibinin administration after 45 min of ischemia). Kidney tissues were collected to determine TNF-α, M30 and histopathological changes at predetermined time intervals. Results: Comparing Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-α and M30 expression. Deterioration was observed in hyperemia/filtration of renal parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue swelling index). Intravenous silibinin administration and comparison of the Control vs. Silibinin groups showed a statistically significant decrease in TNF-α levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p = 0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in: hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p = 0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120 min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and edema (240 min - p = 0.001). Conclusion: Our study confirms that hepatic I/R injury causes remote renal damage while the intravenous administration of silibinin leads to statistically significant nephroprotective action.