Metallic Nanowires Self-Assembled in Quasi-Circular Nanomolds Templated by DNA Origami.

The self-assembly of conducting nanostructures is currently being investigated intensively in order to evaluate the feasibility of creating novel nanoelectronic devices and circuits using such pathways. In particular, methods based on so-called DNA Origami nanostructures have shown great potential in the formation of metallic nanowires. The main challenge of this method is the reproducible generation of very well-connected metallic nanostructures, which may be used as interconnects in future devices. Here, we use a novel design of nanowires with a quasi-circular cross-section as opposed to rectangular or uncontrolled cross-sections in earlier studies. We find indications that the reliability of the fabrication scheme is enhanced and the overall resistance of the wires is comparable to metallic nanostructures generated by electrochemistry or top-down methods. In addition, we observe that some of the nanowires are annealed when passing a current through them, which leads to a clear enhancement for the conductance. We envision that these nanowires provide further steps towards the successful generation of nanoelectronics using self-assembly.

Targeted engagement of ß-catenin-Ikaros complexes in refractory B-cell malignancies.

In most cell types, nuclear ß-catenin functions as prominent oncogenic driver and pairs with TCF7-family factors for transcriptional activation of MYC. Surprisingly, B-lymphoid malignancies not only lacked expression and activating lesions of ß-catenin but critically depended on GSK3ß for effective ß-catenin degradation. Our interactome studies in B-lymphoid tumors revealed that ß-catenin formed repressive complexes with lymphoid-specific Ikaros factors at the expense of TCF7. Instead of MYC-activation, ß-catenin was essential to enable Ikaros-mediated recruitment of nucleosome remodeling and deacetylation (NuRD) complexes for transcriptional repression of MYC. To leverage this previously unrecognized vulnerability of B-cell-specific repressive ß-catenin-Ikaros-complexes in refractory B-cell malignancies, we examined GSK3ß small molecule inhibitors to subvert ß-catenin degradation. Clinically approved GSK3ß-inhibitors that achieved favorable safety prof les at micromolar concentrations in clinical trials for neurological disorders and solid tumors were effective at low nanomolar concentrations in B-cell malignancies, induced massive accumulation of ß-catenin, repression of MYC and acute cell death. Preclinical in vivo treatment experiments in patient-derived xenografts validated small molecule GSK3ß-inhibitors for targeted engagement of lymphoid-specific ß-catenin-Ikaros complexes as a novel strategy to overcome conventional mechanisms of drug-resistance in refractory malignancies. HIGHLIGHTS: Unlike other cell lineages, B-cells express nuclear ß-catenin protein at low baseline levels and depend on GSK3ß for its degradation.In B-cells, ß-catenin forms unique complexes with lymphoid-specific Ikaros factors and is required for Ikaros-mediated tumor suppression and assembly of repressive NuRD complexes. CRISPR-based knockin mutation of a single Ikaros-binding motif in a lymphoid MYC superenhancer region reversed ß-catenin-dependent Myc repression and induction of cell death. The discovery of GSK3ß-dependent degradation of ß-catenin as unique B-lymphoid vulnerability provides a rationale to repurpose clinically approved GSK3ß-inhibitors for the treatment of refractory B-cell malignancies. GRAPHICAL ABSTRACT: Abundant nuclear ß-cateninß-catenin pairs with TCF7 factors for transcriptional activation of MYCB-cells rely on efficient degradation of ß-catenin by GSK3ßB-cell-specific expression of Ikaros factors Unique vulnerability in B-cell tumors: GSK3ß-inhibitors induce nuclear accumulation of ß-catenin.ß-catenin pairs with B-cell-specific Ikaros factors for transcriptional repression of MYC.

Fabrication and temperature-dependent electrical characterization of a C-shape nanowire patterned by a DNA origami.

We introduce a method based on directed molecular self-assembly to manufacture and electrically characterise C-shape gold nanowires which clearly deviate from typical linear shape due to the design of the template guiding the assembly. To this end, gold nanoparticles are arranged in the desired shape on a DNA-origami template and enhanced to form a continuous wire through electroless deposition. C-shape nanowires with a size below 150nm on a [Formula: see text] substrate are contacted with gold electrodes by means of electron beam lithography. Charge transport measurements of the nanowires show hopping, thermionic and tunneling transports at different temperatures in the 4.2K to 293K range. The different transport mechanisms indicate that the C-shape nanowires consist of metallic segments which are weakly coupled along the wires.

ReMindCare, an app for daily clinical practice in patients with first episode psychosis: A pragmatic real-world study protocol.

AIM: Despite the potential benefits of e-health interventions for patients with psychosis, the integration of these applications into the clinical workflow and analysis of their long-term effects still face significant challenges. To address these issues, we developed the ReMindCare app. This app aims to improve the treatment quality for patients with psychosis. We chose to study the app in real world and pragmatic manner to ensure results will be generalizable. METHODS: This is a naturalistic empirical study of patients in a first episode of psychosis programme. The app was purpose-designed based on two previous studies, and it offers the following assessments: (a) three daily questions regarding anxiety, sadness and irritability; and (b) 18 weekly questions about medication adherence, medication side effects, medication attitudes and prodromal symptoms. The app offers preset alerts, reminders and the ability for patients to reach out to their clinicians. Data captured by the app are linked to the electronic medical record of the patient. Patients will use the app as part of their ongoing care for a maximum period of 5 years, and assessments will occur at baseline and at the end of the first, second and fifth years of app use. RESULTS: Recruitment started in October 2018 and is still ongoing. CONCLUSIONS: The ReMindCare app represents early real-world use of digital mental health tools that offer direct integration into clinical care. High retention and compliance rates are expected, and this will in turn lead to improved quality of assessments and communication between patients and clinicians.

Natural selection maintains species despite frequent hybridization in the desert shrub Encelia.

Natural selection is an important driver of genetic and phenotypic differentiation between species. For species in which potential gene flow is high but realized gene flow is low, adaptation via natural selection may be a particularly important force maintaining species. For a recent radiation of New World desert shrubs (Encelia: Asteraceae), we use fine-scale geographic sampling and population genomics to determine patterns of gene flow across two hybrid zones formed between two independent pairs of species with parapatric distributions. After finding evidence for extremely strong selection at both hybrid zones, we use a combination of field experiments, high-resolution imaging, and physiological measurements to determine the ecological basis for selection at one of the hybrid zones. Our results identify multiple ecological mechanisms of selection (drought, salinity, herbivory, and burial) that together are sufficient to maintain species boundaries despite high rates of hybridization. Given that multiple pairs of Encelia species hybridize at ecologically divergent parapatric boundaries, such mechanisms may maintain species boundaries throughout Encelia.

ReMindCare App for Early Psychosis: Pragmatic Real World Intervention and Usability Study.

BACKGROUND: eHealth interventions are widely used in clinical trials and increasingly in care settings as well; however, their efficacy in real-world contexts remains unknown. ReMindCare is a smartphone app that has been systematically implemented in a first episode of psychosis program (FEPP) for patients with early psychosis since 2018. OBJECTIVE: The objective of this study was to assess the efficacy of ReMindCare after 19 months of use in the clinic and varying use by individual patients. METHODS: The integration of the ReMindCare app into the FEPP started in October 2018. Patients with early psychosis self-selected to the app (ReMindCare group) or treatment as usual (TAU group). The outcome variables considered were adherence to the intervention and number of relapses, hospital admissions, and visits to urgent care units. Data from 90 patients with early psychosis were analyzed: 59 in the ReMindCare group and 31 in the TAU group. The mean age of the sample was 32.8 (SD 9.4) years, 73% (66/90) were males, 91% (83/90) were White, and 81% (74/90) were single. RESULTS: Significant differences between the ReMindCare and TAU groups were found in the number of relapses, hospitalizations, and visits to urgent care units, with each showing benefits for the app. Only 20% (12/59) of patients from the ReMindCare group had a relapse, while 58% (18/31) of the TAU patients had one or more relapses (χ2=13.7, P=.001). Moreover, ReMindCare patients had fewer visits to urgent care units (χ2=7.4, P=.006) and fewer hospitalizations than TAU patients (χ2=4.6, P=.03). The mean of days using the app was 352.2 (SD 191.2; min/max: 18-594), and the mean of engagement was 84.5 (SD 16.04). CONCLUSIONS: To our knowledge, this is the first eHealth intervention that has preliminarily proven its benefits in the real-world treatment of patients with early psychosis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1111/eip.12960.

Differences in the Use and Opinions About New eHealth Technologies Among Patients With Psychosis: Structured Questionnaire.

BACKGROUND: Despite a growing interest in the use of technology in order to support the treatment of psychotic disorders, limited knowledge exists about the viability and acceptability of these eHealth interventions in relation to the clinical characteristics of patients. OBJECTIVE: The objective of this study was to assess the access and use of, as well as experiences and interest in, new technologies using a survey of patients diagnosed with early psychosis compared with a survey of patients diagnosed with chronic psychotic disorders. METHODS: We designed a structured questionnaire. This questionnaire was divided into five parts: (1) clinical and demographic information, (2) access and use of the internet, (3) use of the internet in relation to mental health, (4) experiences with technology, and (5) patients' interest in eHealth services. In total, 105 patients were recruited from early psychosis units (n=65) and recovery units (n=40). RESULTS: In this study, 84.8% (89/105) of the patients had access to the internet and 88.6% (93/105) owned an electronic internet device. In total, 71.3% (57/80) of patients who owned a mobile phone were interested in eHealth systems and 38.2% (37/97) reported negative experiences related to the internet usage. We observed differences between the groups in terms of device ownership (P=.02), the frequency of internet access (P<.001), the use of social media (P=.01), and seeking health information (P=.04); the differences were found to be higher in the early psychosis group. No differences were found between the groups in terms of the use of internet in relation to mental health, experiences and opinions about the internet, or interest in eHealth interventions (P=.43). CONCLUSIONS: The availability and use of technology for the participants in our survey were equivalent to those for the general population. The differences found between the groups in relation to the access or use of technology seemed to due to age-related factors. The use of technology involving mental health and the interest in eHealth interventions were mainly positive and equivalent between the groups. Accordingly, this group of patients is a potential target for the emerging eHealth interventions, regardless of their clinical status. However, 28.7% (23/80) of the studied patients rejected the use of internet interventions and 38.2% (37/97) had unpleasant experiences related to its usage; thus, more in-depth studies are needed to better define the profile of patients with psychosis who may benefit from eHealth treatments.

Utilización de tecnologías móviles en pacientes con psicosis: una revisión sistemática / Use of mobile technologies in patients with psychosis: a systematic review

Hay un creciente interés en las intervenciones mobile Health (m-Health) en pacientes con psicosis. El objetivo de este estudio es realizar una revisión sistemática para analizar el estado actual de la investigación en este ámbito. La búsqueda de publicaciones se llevó a cabo siguiendo los criterios PRISMA, centrándose en aquellos estudios que utilizan tecnologías móviles en pacientes con psicosis durante el periodo de 1990 a 2016. Se seleccionó un total de 20 artículos de los 431 estudios que se encontraron. Se diferencian 3 tipos de intervenciones: 1) análisis de calidad y usabilidad; 2) mejora de la adherencia, síntomas y reducción de hospitalizaciones, y 3) análisis de la sintomatología del paciente. Conclusión: Las intervenciones m-Health son viables y resultan fáciles de utilizar para los pacientes con psicosis. Evalúan de forma más eficiente la evolución de los síntomas psicóticos y mejoran la adherencia al tratamiento, los síntomas y las hospitalizaciones. No se puede destacar una estrategia sobre las demás debido a que las diferencias en la metodología las hace difícilmente comparables (AU)

There is a growing interest in mobile Health interventions (m-Health) in patients with psychosis. The aim of this study is to conduct a systematic review in order to analysethe current state of research in this area. The search of articles was carried out following the PRISMA criteria, focusing on those studies that used mobile technologies in patients with psychosis during the period from 1990 to 2016. A total of 20 articles were selected from the 431 studies found. Three types of studies are distinguished: 1) Analysis of quality and usability, 2) Improving treatment adherence and reducing hospital admissions, and 3) Analysisof patient symptoms. Conclusions: m-Health interventions are feasible, and are easy to use for patients with psychosis. They evaluate the evolution of psychotic symptoms more efficiently, and improve adherence to treatment, as well as symptoms and hospital admissions. However, a particular strategy does not stand out over the rest, because differences in methodology make them difficult to compare (AU)

Use of mobile technologies in patients with psychosis: A systematic review. / Utilización de tecnologías móviles en pacientes con psicosis: una revisión sistemática.

There is a growing interest in mobile Health interventions (m-Health) in patients with psychosis. The aim of this study is to conduct a systematic review in order to analysethe current state of research in this area. The search of articles was carried out following the PRISMA criteria, focusing on those studies that used mobile technologies in patients with psychosis during the period from 1990 to 2016. A total of 20 articles were selected from the 431 studies found. Three types of studies are distinguished: 1) Analysis of quality and usability, 2) Improving treatment adherence and reducing hospital admissions, and 3) Analysisof patient symptoms. CONCLUSIONS: m-Health interventions are feasible, and are easy to use for patients with psychosis. They evaluate the evolution of psychotic symptoms more efficiently, and improve adherence to treatment, as well as symptoms and hospital admissions. However, a particular strategy does not stand out over the rest, because differences in methodology make them difficult to compare.

The core musculature in male prepubescent tennis players and untrained counterparts: a volumetric MRI study.

The effects of exercise on the core musculature have not been investigated in prepubescents. The main purpose of the present study was to determine the volume and degree of asymmetry of rectus abdominis, obliques and transversus abdominis, quadratus lumborum, iliopsoas, gluteus and paravertebralis muscles in prepubescent tennis players and in untrained boys. The muscle volume was determined using magnetic resonance imaging (MRI) in 7 male prepubescent tennis players and 10 untrained controls (mean age 11.0 ± 0.8 years, Tanner 1-2). After accounting for height and body weight as covariates, the tennis players had 14-34% greater volume than the controls in all the muscles analysed (P < 0.05) except in paravertebralis, dominant quadratus lumborum and non-dominant gluteus, which had similar volumes in both groups (P = NS). Compared to controls, the tennis players displayed a greater degree of asymmetry in quadratus lumborum and rectus abdominis (3% vs. 15%, P < 0.01 and 8% vs. 17%, P = 0.06, respectively). The level of asymmetry of obliques and transversus abdominis, iliopsoas, gluteus and paravertebralis muscles was similar in both groups (P = NS). In conclusion, tennis playing at prepubertal ages induces a selective hypertrophy of the core musculature and exaggerates the degree of asymmetry of quadratus lumborum and rectus abdominis compared to untrained boys.