Psychotic-like experiences in non-clinical subgroups with and without specific beliefs.

BACKGROUND: Assuming a transdiagnostic and extended psychosis phenotype, psychotic-like experiences (PLEs) and psychotic symptoms are on a phenomenological and temporal continuum between clinical and non-clinical populations. Recent research points towards differences in PLE proneness in different subgroups and clinical impact of different PLE subtypes. This study examines the prevalence of PLEs in three groups of individuals with and without specific sets of beliefs aiming to elucidate the question whether proneness to PLEs varies according to traditional versus less traditional supernatural beliefs. METHODS: The anonymized 16-item version of the Prodromal Questionnaire (PQ-16) was used to assess PLEs in three groups including individuals with religious beliefs (RB), belief in esoterism and paranormal phenomena (EB), and those embedded in scientific evidence approach and scepticism towards para-scientific theories (non-believers, NB). Male and female participants between 18 and 90 years were eligible for participation. RESULTS: The sample comprised 159 individuals including 41 RB individuals, 43 EB individuals, and 75 NB individuals. The mean PQ-16 score of the EB individuals (6.86 ± 4.13) was significantly higher compared to NB individuals (3.43 ± 2.99) and to RB individuals (3.38 ± 3.23) with almost twice the score (both p-values < 0.001). There was no significant difference between the PQ-16 scores of the NB group and the RB group (p = 0.935). No significant impact of age (p = 0.330) and gender (p = 0.061) was found on the PQ16-Score. Group affiliation to esoterism was associated with a higher PQ-16 score compared to group affiliation to religious beliefs (p < 0.001) and group affiliation to scepticism (p = 0.011), while the latter two did not differ significantly (p = 0.735). No significant difference was found between the three groups in the degree of distress related to the affirmatively answered PQ-16 items (p = 0.74). CONCLUSION: Under the assumption of a transdiagnostic psychosis phenotype, our findings provide more insight which subgroups within non-clinical samples have a higher likelihood of reporting PLEs.

Stem Cell Therapy Enriched Fat Grafting for the Reconstruction of Craniofacial Deficits.

Fat grafting is an effective treatment for craniofacial deformities. Stromal vascular fraction (SVF) is a concentrated form of adipose derived stem cells that can be isolated from fat. The aim of this clinical trial was to assess the impact of SVF enrichment on craniofacial fat grafting. Methods: Twelve subjects with at least two regions of craniofacial volume deficit were enrolled, and they underwent fat grafting with SVF-enriched or standard fat grafting to each area. All patients had bilateral malar regions injected with SVF-enriched graft on one side and control standard fat grafting to the contralateral side. Outcome assessments included demographic information, volume retention determined by CT scans, SVF cell populations assessed by flow cytometry, SVF cell viability, complications, and appearance ratings. Follow-up was 9 months. Results: All patients had improvement in appearance. There were no serious adverse events. There was no significant difference in volume retention between the SVF-enriched and control regions overall (50.3% versus 57.3%, P = 0.269) or comparing malar regions (51.4% versus 56.7%, P = 0.494). Patient age, smoking status, obesity, and diagnosis of diabetes did not impact volume retention. Cell viability was 77.4% ± 7.3%. Cellular subpopulations were 60.1% ± 11.2% adipose derived stem cells, 12.2 ± 7.0% endothelial cells, and 9.2% ± 4.4% pericytes. A strong positive correlation was found between CD146+ CD31-pericytes and volume retention (R = 0.863, P = 0.027). Conclusions: Autologous fat transfer for reconstruction of craniofacial defects is effective and safe, leading to reliable volume retention. However, SVF enrichment does not significantly impact volume retention.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

Semi-automated detection of ungulates using UAV imagery and reflective spectrometry.

In the field of species conservation, the use of unmanned aerial vehicles (UAV) is increasing in popularity as wildlife observation and monitoring tools. With large datasets created by UAV-based species surveying, the need arose to automate the detection process of the species. Although the use of computer learning algorithms for wildlife detection from UAV-derived imagery is an increasing trend, it depends on a large amount of imagery of the species to train the object detector effectively. However, there are alternatives like object-based image analysis (OBIA) software available if a large amount of imagery of the species is not available to develop a computer-learned object detector. The study tested the semi-automated detection of reintroduced Arabian Oryx (O. leucoryx), using the specie's coat sRGB-colour profiles as input for OBIA to identify adult O. leucoryx, applied to UAV acquired imagery. Our method uses lab-measured spectral reflection of hair sample values, collected from captive O. leucoryx as an input for OBIA ruleset to identify adult O. leucoryx from UAV survey imagery using semi-automated supervised classification. The converted mean CIE Lab reflective spectrometry colour values of n = 50 hair samples of adult O. leucoryx to 8-bit sRGB-colour profiles of the species resulted in the red-band value of 157.450, the green-band value of 151.390 and blue-band value of 140.832. The sRGB values and a minimum size permitter were added as the input of the OBIA ruleset identified adult O. leucoryx with a high degree of efficiency when applied to three UAV census datasets. Using species sRGB-colour profiles to identify re-introduced O. leucoryx and extract location data using a non-invasive UAV-based tool is a novel method with enormous application possibilities. Coat refection sRGB-colour profiles can be developed for a range of species and customised to autodetect and classify the species from remote sensing data.

Cell Sorter Cleaning Practices and Their Impact on Instrument Sterility.

Cells isolated using electrostatic cell sorters are subsequently evaluated in a variety of in vitro and in vivo applications. Thus, manipulations to the cells during the pre- and post-sort processing as well as when the cells are being analyzed by and passing through the sorter fluidics has the potential to affect the experimental results. There are many variables to consider when seeking to preserve cellular integrity and function during the cell-sorting process. A previous study by the Association of Biomolecular Resource Facilities Flow Cytometry Research Group (FCRG) investigated downstream effects on different cell types as a function of sorting variables such as pressure, nozzle size, and temperature. This multisite study revealed site-to-site variability based on differential gene expression when the same cell type and sort conditions were used. These results indicated the possibility that environmental factors such as the presence of contaminants in the sorter fluidics could exhibit effects on downstream molecular assays (ie, endotoxins or RNases). In the study described here, the FCRG sought to better understand how sorters are maintained and evaluated for contaminants such as bacteria, endotoxin, and RNases. In addition, the efficacy of an endotoxin decontamination method was evaluated. The results demonstrated that the majority of sorters in shared resource laboratories are free of RNase activity and bacteria; however, many are contaminated with endotoxin. The efficacy of a hydrogen peroxide cleaning procedure was tested and found to exhibit only a short-term effectiveness in eliminating endotoxin contamination.

Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies.

The BCL2 inhibitor venetoclax has been approved to treat different hematological malignancies. Because there is no common genetic alteration causing resistance to venetoclax in chronic lymphocytic leukemia (CLL) and B-cell lymphoma, we asked if epigenetic events might be involved in venetoclax resistance. Therefore, we employed whole-exome sequencing, methylated DNA immunoprecipitation sequencing, and genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMA promoter that is methylated upon venetoclax treatment, mediating PUMA downregulation on transcript and protein level. PUMA expression and sensitivity toward venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher oxidative phosphorylation and adenosine triphosphate production, resembling the metabolic phenotype that is seen upon venetoclax resistance. Although PUMA loss is specific for acquired venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after chemotherapy-resistance, BAX is essential for sensitivity toward both venetoclax and MCL1 inhibition. As we found loss of BAX in Richter's syndrome patients after venetoclax failure, we defined BAX-mediated apoptosis to be critical for drug resistance but not for disease progression of CLL into aggressive diffuse large B-cell lymphoma in vivo. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance.

The state of the art in beyond 5G distributed massive multiple-input multiple-output communication system solutions.

Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.

Bidirectional reflectance measurement of tungsten samples to assess reflection model in WEST tokamak.

This paper presents the measurement of the bidirectional reflectance distribution function of tungsten (W) samples and the resulting reflection models in the nuclear fusion device WEST (tokamak). For this, an experimental gonio-spectrophotometer was developed to fully characterize the material's optical and thermal-radiative properties of metallic samples with different roughnesses. Ray-tracing photonic simulation was then carried out to predict the photon behavior in a fully metallic environment as a function of reflectance measurement. Low emissivity (0.1 at 4 µm) and highly specular reflectance (fitting with a Gaussian distribution around the specular direction with a small width lower than 10°) are found for W samples. These measurements have been used as input for the photonic simulation, and the resulting synthetic image reproduced the reflection features well on the upper divertor, detected in WEST infrared experimental images.

A High-Content Screening Assay for Small Molecules That Stabilize Mutant Triose Phosphate Isomerase (TPI) as Treatments for TPI Deficiency.

Triose phosphate isomerase deficiency (TPI Df) is an untreatable, childhood-onset glycolytic enzymopathy. Patients typically present with frequent infections, anemia, and muscle weakness that quickly progresses with severe neuromusclar dysfunction requiring aided mobility and often respiratory support. Life expectancy after diagnosis is typically ~5 years. There are several described pathogenic mutations that encode functional proteins; however, these proteins, which include the protein resulting from the "common" TPIE105D mutation, are unstable due to active degradation by protein quality control (PQC) pathways. Previous work has shown that elevating mutant TPI levels by genetic or pharmacological intervention can ameliorate symptoms of TPI Df in fruit flies. To identify compounds that increase levels of mutant TPI, we have developed a human embryonic kidney (HEK) stable knock-in model expressing the common TPI Df protein fused with green fluorescent protein (HEK TPIE105D-GFP). To directly address the need for lead TPI Df therapeutics, these cells were developed into an optical drug discovery platform that was implemented for high-throughput screening (HTS) and validated in 3-day variability tests, meeting HTS standards. We initially used this assay to screen the 446-member National Institutes of Health (NIH) Clinical Collection and validated two of the hits in dose-response, by limited structure-activity relationship studies with a small number of analogs, and in an orthogonal, non-optical assay in patient fibroblasts. The data form the basis for a large-scale phenotypic screening effort to discover compounds that stabilize TPI as treatments for this devastating childhood disease.