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Background: Stress levels and the prevalence of mental disorders in the general population have been rising in recent years. Chatbot-based interventions represent novel and promising digital approaches to improve health-related parameters. However, there is a lack of research on chatbot-based interventions in the area of mental health., Objective: The aim of this study was to investigate the effects of a 3-week chatbot-based intervention guided by the chatbot ELME, specifically with respect to the ability to reduce stress and improve various health-related parameters in a stressed sample., Methods: In this multicenter two-armed randomized controlled trial, 118 individuals with medium to high stress levels were randomized to the intervention group (n=59) or the treatment-as-usual control group (n=59). The ELME chatbot guided participants of the intervention group through 3 weeks of training based on the topics stress, mindfulness, and interoception, with practical and psychoeducative elements delivered in two daily interactive intervention sessions via a smartphone (approximately 10-20 minutes each). The primary outcome (perceived stress) and secondary outcomes (mindfulness; interoception or interoceptive sensibility; subjective well-being; and emotion regulation, including the subfacets reappraisal and suppression) were assessed preintervention (T1), post intervention (T2; after 3 weeks), and at follow-up (T3; after 6 weeks). During both conditions, participants also underwent ecological momentary assessments of stress and interoceptive sensibility., Results: There were no significant changes in perceived stress (β 03 =-.018, SE=.329; P=.96) and momentary stress. Mindfulness and the subfacet reappraisal significantly increased in the intervention group over time, whereas there was no change in the subfacet suppression. Well-being and momentary interoceptive sensibility increased in both groups over time., Conclusions: To gain insight into how the intervention can be improved to achieve its full potential for stress reduction, besides a longer intervention duration, specific sample subgroups should be considered. The chatbot-based intervention seems to have the potential to improve mindfulness and emotion regulation in a stressed sample. Future chatbot-based studies and interventions in health care should be designed based on the latest findings on the efficacy of rule-based and artificial intelligence-based chatbots., Trial Registration: German Clinical Trials Register DRKS00027560; https://drks.de/search/en/trial/DRKS00027560., International Registered Report Identifier (irrid): RR2-doi.org/10.3389/fdgth.2023.1046202., (©Christine Schillings, Echo Meißner, Benjamin Erb, Eileen Bendig, Dana Schultchen, Olga Pollatos. Originally published in JMIR Mental Health (https://mental.jmir.org), 28.05.2024.)

An environmentally responsive root system is crucial for plant growth and crop yield, especially in suboptimal soil conditions. This responsiveness enables the plant to exploit regions of high nutrient density while simultaneously minimizing abiotic stress. Despite the vital importance of root systems in regulating plant growth, significant gaps of knowledge exist in the mechanisms that regulate their architecture. Auxin defines both the frequency of lateral root (LR) initiation and the rate of LR outgrowth. Here, we describe a search for proteins that regulate root system architecture (RSA) by interacting directly with a key auxin transporter, PIN1. The native separation of Arabidopsis plasma membrane protein complexes identified several PIN1 co-purifying proteins. Among them, AZG1 was subsequently confirmed as a PIN1 interactor. Here, we show that, in Arabidopsis, AZG1 is a cytokinin (CK) import protein that co-localizes with and stabilizes PIN1, linking auxin and CK transport streams. AZG1 expression in LR primordia is sensitive to NaCl, and the frequency of LRs is AZG1-dependent under salt stress. This report therefore identifies a potential point for auxin:cytokinin crosstalk, which shapes RSA in response to NaCl., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Aim: Comparison of injuries to the facial and cerebral parts of the skull causing death and grievous bodily harm, resulting solely from punches to the facial area of the skull. Assessment and confrontation of both groups in terms of the final criminal-legal classification of the perpetrator's acts. Review of reasons for court judgements with a focus on the subjective elements of the prohibited act. Attempt to verify the hypothesis assuming that death or grievous bodily harm can be caused by a single punch to the facial part of the skull., Material and Methods: Final judgements passed by criminal divisions of common courts of law in cases where death or grievous bodily harm was caused by injuries to the facial and cerebral parts of the skull resulting solely from punches to the facial area of the skull. Assessment of individual cases within each group to determine similarities and differences. Comparative analysis of both groups., Results: The cause of death in cases involving injuries to the facial part of the skull was rapid suffocation following blood aspiration into the respiratory tract. However, the criminal-legal classification of the perpetrators' actions in these cases was varied. In one case, death resulted from injuries to the cerebral part of the skull, which are extremely rare as a result of a punch to the facial area within the skull. Grievous bodily harm was due to the loss of vision in the eye, typically due to eyeball rupture., Conclusions: Even though the circumstances of the injuries were similar, different mechanisms were responsible for causing death and grievous bodily harm in the victims. The most severe consequences (death and grievous bodily harm) were not caused by injuries of the same type in any of the cases studied. A single punch to the facial part of the skull may be enough to lead to either grievous bodily harm or death, but the criminal-legal assessment of punching to the face can vary greatly., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2021 by PTMSiK.)

GaN epitaxially grown on Si is a material for power electronics that intrinsically shows a high density of dislocations. We show by Conductive Atomic Force Microscopy (C-AFM) and Defect Selective Etching that even for materials with similar total dislocation densities substantially different subsets of dislocations with screw component act as current leakage paths within the AlGaN barrier under forward bias. Potential reasons are discussed and it will be directly shown by an innovative experiment that current voltage forward characteristics of AlGaN/GaN Schottky diodes shift to lower absolute voltages when such dislocations are present within the device. A local lowering of the Schottky barrier height around conductive dislocations is identified and impurity segregation is assumed as responsible root cause. While dislocation related leakage current under low reverse bias could not be resolved, breakdown of AlGaN/GaN Schottky diodes under high reverse bias correlates well with observed conductive dislocations as measured by C-AFM. If such dislocations are located near the drain side of the gate edge, failure of the gate in terms of breakdown or formation of percolation paths is observed for AlGaN/GaN high electron mobility transistors.

The aim of this work is to demonstrate high breakdown voltage and low buffer trapping in superlattice GaN-on-Silicon heterostructures for high voltage applications. To this aim, we compared two structures, one based on a step-graded (SG) buffer (reference structure), and another based on a superlattice (SL). In particular, we show that: (i) the use of an SL allows us to push the vertical breakdown voltage above 1500 V on a 5 µm stack, with a simultaneous decrease in vertical leakage current, as compared to the reference GaN-based epi-structure using a thicker buffer thickness. This is ascribed to the better strain relaxation, as confirmed by X-Ray Diffraction data, and to a lower clustering of dislocations, as confirmed by Defect Selective Etching and Cathodoluminescence mappings. (ii) SL-based samples have significantly lower buffer trapping, as confirmed by substrate ramp measurements. (iii) Backgating transient analysis indicated that traps are located below the two-dimensional electron gas, and are related to C N defects. (iv) The signature of these traps is significantly reduced on devices with SL. This can be explained by the lower vertical leakage (filling of acceptors via electron injection) or by the slightly lower incorporation of C in the SL buffer, due to the slower growth process. SL-based buffers therefore represent a viable solution for the fabrication of high voltage GaN transistors on silicon substrate, and for the simultaneous reduction of trapping processes.

We investigated the origin of vertical leakage and breakdown in GaN-on-Si epitaxial structures. In order to understand the role of the nucleation layer, AlGaN buffer, and C-doped GaN, we designed a sequential growth experiment. Specifically, we analyzed three different structures grown on silicon substrates: AlN/Si, AlGaN/AlN/Si, C:GaN/AlGaN/AlN/Si. The results demonstrate that: (i) the AlN layer grown on silicon has a breakdown field of 3.25 MV/cm, which further decreases with temperature. This value is much lower than that of highly-crystalline AlN, and the difference can be ascribed to the high density of vertical leakage paths like V-pits or threading dislocations. (ii) the AlN/Si structures show negative charge trapping, due to the injection of electrons from silicon to deep traps in AlN. (iii) adding AlGaN on top of AlN significantly reduces the defect density, thus resulting in a more uniform sample-to-sample leakage. (iv) a substantial increase in breakdown voltage is obtained only in the C:GaN/AlGaN/AlN/Si structure, that allows it to reach V BD > 800 V. (v) remarkably, during a vertical I-V sweep, the C:GaN/AlGaN/AlN/Si stack shows evidence for positive charge trapping. Holes from C:GaN are trapped at the GaN/AlGaN interface, thus bringing a positive charge storage in the buffer. For the first time, the results summarized in this paper clarify the contribution of each buffer layer to vertical leakage and breakdown.

Introduction: The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD)., Methods: We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls., Results: TOMM 40 -L/ APOE -ε4 alleles were associated with DLB (OR TOMM40 - L  = 3.61; P value = 3.23 × 10 -9 ; OR APOE -ε4  = 3.75; P value = 4.90 × 10 -10 ) and earlier age at onset of DLB (HR TOMM40 -L  = 1.33, P value = .031; HR APOE -ε4  = 1.46, P value = .004), but not with PDD. The TOMM40 -L/ APOE -ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (OR TOMM40 -L  = 4.40, P value = 1.15 × 10 -6 ; OR APOE - ε 4  = 5.65, P value = 2.97 × 10 -8 ) but was not significant in DLB without AD. Meta-analyses combining all APOE -ε4 data in DLB confirmed our findings (OR DLB  = 2.93, P value = 3.78 × 10 -99 ; OR DLB+AD  = 5.36, P value = 1.56 × 10 -47 )., Discussion: APOE -ε4/ TOMM 40 -L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB., (© 2019 The Authors.)

Aim of the Study: The aim of the study was to evaluate the prevalence of effects equivalent to moderate and severe impairment to health within the meaning of the Penal Code in patients with zygomatico-maxillo-orbital fractures and isolated orbital floor fractures. In addition, the study addressed the possibilities of applying the presented results in the preparation of medicolegal opinions in cases provided for in Articles 158 and 160 of the PC with respect to evaluating the plausibility of inflicting such bodily injuries and causing moderate and severe health impairment., Material and Methods: The study covered a total of 124 patients operated on in the then Clinic of Cranio-Maxillofacial Surgery, Medical Academy of Lodz, in 1996-2001, because of fractures involving the inferior orbital wall including zygomatico-maxillo-orbital fractures (95 cases) and isolated orbital floor fractures (29 cases). The group was analyzed in a statistical and descriptive manner., Results: All the study patients (100%) with both types of fractures involving the inferior orbital wall exhibit symptoms and disorders which, pursuant to the PC, would constitute at least moderate, or possibly even severe, impairment to health., Conclusions: Punches or kicks to the orbital region create a real danger of causing both types of orbital fracture under study, and resulting in at least moderate health impairment.

Aim of the Study: The aim of the paper is analysis of the impact of immobilization treatment of "less severe" motor organ injuries affecting soft tissues on the position of medical experts and court decisions in crimes against health. We also analysed the attitude of courts to expert opinions and present a proposal for a model of judicial and medical opinion in such cases., Material and Methods: In the study, we analysed judgments of the criminal divisions of common courts, in which the use of medical immobilization of a given part of the body or lack thereof could have an impact on the degree of health impairment determined by the medical expert., Results: Some experts consider medical immobilization to be tantamount to an impairment of the function of a body organ, and the courts rarely reject such opinions. For some experts, the key is not the actual function of the immobilized part of the musculoskeletal system after 7 days from injury, but the immobilization treatment itself, and not the time it takes. In addition, experts determine the severity of injuries when immobilization is/is not used., Conclusions: The degree of health impairment, as defined in the Penal Code, should be determined by a medical check-up carried out 7 days after the injury, with an assessment of its "biological" effects, and not by the use of immobilization treatment and the time for which it is maintained.

Incorrect declaration of death is not a frequent situation in medico-legal reports, and such cases are usually of great interest. In this study the authors present a case of improper declaration of death by a physician, despite the absence of early definitive signs of death and without a full medical examination. However, the investigation of the case was dropped, and the conduct of the physician was not assessed by experts.

In this paper, we report a failure case of blue LEDs returned from a field application, and propose a practical way to identify the physical and structural reasons for the observed malfunction by a combination of different electron microscope techniques. Cathodoluminescence imaging and electron beam induced current (EBIC) imaging are employed in order to visualize conductive paths through the device in conjunction with subsequent energy dispersive x-ray analysis (EDS), revealing a metal deposition along cracks in the semiconductor layer which short-circuit the device. We demonstrate that the electron beam induced current imaging, in conjunction with other microscopic and analytical techniques at µm scale, is a powerful combination for clearly resolving and visualizing the cause of failure in the GaN LED chip. However, this represents a case study of a real application, which may not have been generally observed in laboratory testing environment., Competing Interests: The authors declare no conflict of interest.

A rare case of death of a young man due to airway obstruction in the course of angioedema (Quincke's edema). Type I hereditary angioedema due to C1 esterase inhibitor deficiency had been diagnosed in the man while he was alive. The information concerning the man's health state was given in the Public Prosecutor's decision ordering medico legal autopsy, which was extremely helpful in recognizing the cause of death., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently., Methods: We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments., Results: Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively)., Conclusion: Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies., Competing Interests: CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H.Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than $20,000. K Stefansson has received grants from deCODE.

A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following criteria. First, it has well-studied hemato-lymphoid organs and target cells similar to those of humans. Second, the human pathogens establish infection and lead to relevant diseases. Third, it is genetically inbred and can be manipulated via genetic, immunological and pharmacological means. Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle. The mouse with a reconstituted human immune system and other human target organs is a good candidate. A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years, but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv mouse. This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models. It also reviews the recent progress in the development of humanized mouse models with a functional human immune system, especially the recent progress in the immunodeficient mice that carry a defective gammaC gene. NOD/SCID/gammaC(-/-) (NOG or NSG) or the Rag2(-/-)gammaC(-/-) double knockout (DKO) mice, which lack NK as well as T and B cells (NTB-null mice), have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34(+) HSC. These NTB-hu HSC humanized models have been used to investigate HIV-1 infection, immuno-pathogenesis and therapeutic interventions. Such models, with further improvements, will contribute to study human immunology, human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo.

BRCA1 is a susceptibility gene for breast and ovarian cancer with growth-inhibitory activity for which the mechanism of action remains unclear. When introduced into cells, BRCA1 inhibits growth of some but not all cell lines. In an attempt to uncover the mechanism of growth suppression by BRCA1, we examined a panel of cell lines for their ability to reduce colony outgrowth in response to BRCA1 overexpression. Of all variables tested, only those cells with wild-type pRb were sensitive to BRCA1-induced growth suppression. In cells with an intact rb gene, inactivation of pRb by HPV E7 abrogates the growth arrest imposed by BRCA1. In accordance with these observations, we found that BRCA1 could not suppress BrdUrd uptake in primary fibroblasts from rb-/- mice and exhibited an intermediate ability to inhibit DNA synthesis in rb+/- as compared with rb+/+ cells. We further found that the BRCA1 protein complexes with the hypophosphorylated form of pRb. This binding is localized to amino acids 304-394 of BRCA1 protein and requires the ABC domain of pRb. In-frame deletion of BRCA1 fragment involved in interaction with pRb completely abolished the growth-suppressive property of BRCA1. Although it has been reported that BRCA1 interacts with p53, we find the p53 status did not affect the ability of BRCA1 to suppress colony formation. Our data suggest that the growth suppressor function of BRCA1 depends, at least in part, on Rb.