The on-surface self-assembly of molecules to form holey nanographenes is a promising approach to control the properties of the resulting 2D lattice. Usually, planar molecules are utilized to prepare ...flat, structurally confined molecular layers, with only a few recent examples of warped precursors. However, control of the superstructures is limited thus far. Herein, we report the temperature-controlled self-assembly of a bowl-shaped, acetylated C
-symmetric hexaphenyltribenzotriquinacene derivative on Cu(111). Combining scanning tunneling microscopy (STM) and density functional theory (DFT) confirms the formation of highly differing arrangements starting with π-stacked bowl-to-bowl dimers at low coverage at room temperature via chiral honeycomb structures, an intermediate trigonal superstructure, followed by a fully carbon-based, flattened hexagonal superstructure formed by on-surface deacetylation, which is proposed as a precursor for holey graphene networks with unique defect structures.
Abstract
Background and hypothesis
Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the ...incidence of hearing speech (termed speech illusions SIs) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes.
Study design
At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning.
Study results
CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P = .007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P = .043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P = .029).
Conclusions
In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes.
Background
Spaced learning has been shown to be effective in various areas like traditional knowledge or motor skill acquisition. To evaluate the impact of implementation of the spaced learning ...concept in laparoscopic training was the aim of this study.
Methods
To evaluate the effectiveness of spaced learning, subjects were asked to perform four surgeon’s square knots on a bowel model prior and post 3 h of hands-on training. All subjects were medical students and novice in laparoscopic suturing. Total time, knot stability (evaluated via tensiometer), suture accuracy, knot quality (Muresan score), and laparoscopic performance (Munz checklist) were assessed. Moreover, motivation was accessed using Questionnaire on Current Motivation.
Results
Twenty students were included in the study; after simple randomization, ten were trained using “spaced learning” concept and ten conservatively. Both groups had comparable baseline characteristics and improved after training significantly regarding all aspects assessed in this study. Subjects that trained via spaced learning were superior in terms of suture performance, knot quality, and suture strength. Ultimately, spaced learning significantly decreased anxiety and impression of challenge compared to controls.
Conclusion
The spaced learning concept is very suitable for complex motor skill acquisition like laparoscopic suturing and knot tying. It significantly improves laparoscopic performance and knot quality as shown by the knot score and suture strength. Thus, we recommend to incorporate spaced learning into training courses and surgical programs.
The composition of immune infiltrates strongly affects the prognosis of patients with colorectal cancer (CRC). Interleukin (IL)-33 and regulatory T cells (Tregs) in the tumor microenvironment have ...been separately implicated in CRC; however their contribution to intestinal carcinogenesis is still controversial. Here, we reveal that IL-33 signaling promotes CRC by changing the phenotype of Tregs. In mice with CRC, tumor-infiltrating Tregs preferentially upregulate IL-33 receptor (ST2), and IL-33/ST2 signaling positively correlates with tumor number and size. Transcriptomic and flow cytometry analyses demonstrate that ST2 expression induces a more activated and migratory phenotype in FOXP3
Tregs, which favors their accumulation in the tumor environment. Consequently, genetic ablation of St2 reduces Treg infiltration and concomitantly enhances the frequencies of effector CD8
T cells, thereby restraining CRC. Mechanistically, IL-33 curtails IL-17 production by FOXP3
Tregs and inhibits Th17 differentiation. In humans, numbers of activated ST2-expressing Tregs are increased in blood and tumor lesions of CRC patients, suggesting a similar mode of regulation. Together, these data indicate a central role of IL-33/ST2 signaling in shaping an immunosuppressive environment during intestinal tumorigenesis. Blockade of this pathway may provide a strategy to modulate the composition of CRC immune infiltrates.
Arteriovenous malformations (AVMs) are a rare congenital vascular disorder. They represent a fast-flow vascular malformation. Clinically, AVMs present a heterogenous expression and can affect every ...part of the body. Here, we will solely focus on extracranial AVMs. Generally, AVMs progress with the patient's age. Patients often suffer from pulsation, skin discoloration, pain, ulceration, bleeding, and disfigurement. Diagnostic tools include color-coded duplex sonography, MRI and CT imaging, as well as the clinical examination. 4D dynamic perfusion-computed tomography may help in the interventional planning. Digital subtraction angiography is required during interventional therapy. AVMs pose a great challenge to the treating physician. The therapy of this rare disease should be managed in an interdisciplinary center for vascular malformations. It consists of conservative measures, such as compression garments and pain medication, transcatheter or, more rarely, percutanous embolization, and surgical resection. In smaller, localized lesions, resection with primary wound closure may be feasible, whereas extensive AVMs regularly require the reconstruction of the resulting soft tissue defect and possibly affected functional structures by means of free tissue transfer. In the interdisciplinary setting required for an appropriate treatment of AVMs, extensive knowledge of the various therapies, including those from different specialties, is necessary. Therefore, this article aims to provide an overview over both the interventional and surgical therapeutic options.
Recent brain research reveals a major role of trace elements in various diseases such as multiple sclerosis, Alzheimer's and Wilson's disease. The majority of published tissue concentrations dates ...back decades, and was assessed with various methods. Little is known about hemispherical differences, the correlation of trace elements or age-dependent changes in the human brain. Thus, the aim of this study was to examine trace element concentrations in different human brain regions after whole brain formalin fixation.
549 samples of 13 brain regions were investigated in 11 deceased subjects without known history of brain pathology. Regional wet-to-dry mass ratios and concentrations of iron, copper, magnesium, manganese, calcium and zinc were determined using inductively coupled plasma mass spectrometry.
Cortical gray matter revealed higher water content (wet-to-dry mass ratios 5.84–6.40) than white matter regions (wet-to-dry mass ratios 2.95–3.05). Element concentrations displayed specific regional differences. Good linear correlation of concentrations between elements was found for iron/copper as well as for manganese/magnesium (Spearman's rank correlation coefficient 0.74 and 0.65, respectively). Significant inter-hemispherical differences were found for copper in occipital white matter, for magnesium and calcium in putamen and for iron and copper in temporal white matter. An age dependent increase was seen in cortical gray matter for calcium, for magnesium in all regions except in cortical gray matter, for copper in substantia nigra and for zinc in occipital cortex.
The presented trace element concentrations can serve as a fundamental basis for further brain research. Wet-to-dry mass ratios allow a comparison with reference data from other studies.
Abstract
Background
The high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the ...relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis.
Method
Three hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms.
Results
Strong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change.
Conclusions
Findings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.
Aims/hypothesis
The euglycaemic–hyperinsulinaemic clamp (EIC) is the reference standard for the measurement of whole-body insulin sensitivity but is laborious and expensive to perform. We aimed to ...assess the incremental value of high-throughput plasma proteomic profiling in developing signatures correlating with the
M
value derived from the EIC.
Methods
We measured 828 proteins in the fasting plasma of 966 participants from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study and 745 participants from the Uppsala Longitudinal Study of Adult Men (ULSAM) using a high-throughput proximity extension assay. We used the least absolute shrinkage and selection operator (LASSO) approach using clinical variables and protein measures as features. Models were tested within and across cohorts. Our primary model performance metric was the proportion of the
M
value variance explained (
R
2
).
Results
A standard LASSO model incorporating 53 proteins in addition to routinely available clinical variables increased the
M
value
R
2
from 0.237 (95% CI 0.178, 0.303) to 0.456 (0.372, 0.536) in RISC. A similar pattern was observed in ULSAM, in which the
M
value
R
2
increased from 0.443 (0.360, 0.530) to 0.632 (0.569, 0.698) with the addition of 61 proteins. Models trained in one cohort and tested in the other also demonstrated significant improvements in
R
2
despite differences in baseline cohort characteristics and clamp methodology (RISC to ULSAM: 0.491 0.433, 0.539 for 51 proteins; ULSAM to RISC: 0.369 0.331, 0.416 for 67 proteins). A randomised LASSO and stability selection algorithm selected only two proteins per cohort (three unique proteins), which improved
R
2
but to a lesser degree than in standard LASSO models: 0.352 (0.266, 0.439) in RISC and 0.495 (0.404, 0.585) in ULSAM. Reductions in improvements of
R
2
with randomised LASSO and stability selection were less marked in cross-cohort analyses (RISC to ULSAM
R
2
0.444 0.391, 0.497; ULSAM to RISC
R
2
0.348 0.300, 0.396). Models of proteins alone were as effective as models that included both clinical variables and proteins using either standard or randomised LASSO. The single most consistently selected protein across all analyses and models was IGF-binding protein 2.
Conclusions/interpretation
A plasma proteomic signature identified using a standard LASSO approach improves the cross-sectional estimation of the
M
value over routine clinical variables. However, a small subset of these proteins identified using a stability selection algorithm affords much of this improvement, especially when considering cross-cohort analyses. Our approach provides opportunities to improve the identification of insulin-resistant individuals at risk of insulin resistance-related adverse health consequences.
Graphical Abstract
Objective
Bioabsorbable magnesium-based alloy screws release gas upon resorption. The resulting findings in the adjacent soft tissues and joints may mimic infection. The aim of the study was to ...evaluate the ultrasound (US) findings in soft tissues and joints during screw resorption.
Methods
Prospectively acquired US studies from pediatric patients treated with magnesium screws were evaluated for screw head visibility, posterior acoustic shadowing, twinkling artifact, foreign body granuloma, gas (soft tissue, intra-articular), alterations of the skin and subcutaneous fat, perifascial fluid, localized fluid collections, hypervascularization, and joint effusion.
Results
Sixty-six US studies of 28 pediatric patients (
n
female
= 9,
n
male
= 19) were included. The mean age of the patients at the time of surgery was 10.84 years; the mean time between surgery and ultrasound was 128.3 days (range = 6–468 days). The screw head and posterior acoustic shadowing were visible in 100% of the studies, twinkling artifact in 6.1%, foreign body granuloma in 92.4%, gas locules in soft tissue in 100% and intra-articular in 18.2%, hyperechogenicity of the subcutaneous fat in 90.9%, cobblestoning of the subcutaneous fat in 24.2%, loss of normal differentiation between the epidermis/dermis and the subcutaneous fat in 57.6%, localized fluid collection in 9.9%, perifascial fluid in 12.1%, hypervascularization in 27.3%, and joint effusion in 18.2%.
Conclusion
US findings in pediatric patients treated with magnesium screws strongly resemble infection, but are normal findings in the setting of screw resorption.
Clinical relevance statement
Bioabsorbable magnesium-based alloy screws release gas during resorption. The resulting US findings in the adjacent soft tissues and joints in pediatric patients may mimic infection, but are normal findings.
Key Points
•
Bioabsorbable magnesium-based alloy screws release gas upon resorption
.
•
The resulting ultrasound findings in children’s soft tissues and joints closely resemble those of soft tissue infection or osteosynthesis-associated infection
.
•
Be familiar with these ultrasound findings in order to avoid inadvertently misdiagnosing a soft tissue infection or osteosynthesis-associated infection
.
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