Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of ...schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia.
Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect.
Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression.
Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.
Summary
Background
Little is known about the importance of liver fibrosis and fatty liver in HIV‐monoinfected individuals without hepatitis virus co‐infection, particularly among the Asian ...population.
Aim
To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV‐monoinfected individuals.
Methods
Eighty asymptomatic HIV‐monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV‐uninfected healthy controls. Transient elastography and proton‐magnetic resonance spectroscopy (1H‐MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin‐18).
Results
All HIV‐infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4–13 years) were stable on anti‐retrovirals (PI‐based 58.7%, NNRTI‐based 25.0% integrase‐inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness 4.9 (IQR 4.1–6.2) kPa vs. 4.2 (IQR 3.6–5.0) kPa, P < 0.001, and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29–12.41, P = 0.016). HIV‐infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected.
Conclusions
HIV‐monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV‐related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.
Abstract
Background
The aim of this review was the creation of uniform protocols to carry out and disclose First-In-Human and preliminary clinical trials of biological mitral valve replacement. The ...need for consistent methodology in these early trials was highlighted by the observation of significant variability in the methods and protocols used across different research.
Methods
An extensive search through six major databases was carried out to retrieve First-In-Human (FIH) clinical studies evaluating surgically implanted bio-prostheses in the mitral position.
Results
Following the PRISMA guideline, a systematic search identified 2082 published articles until March 2023. After removing duplicates (189), 1862 citations were screened, resulting in 22 eligible studies with 3332 patients for analysis. The mitral valve prostheses in these studies ranged from 21 to 37 mm, with the 29 mm size being most prevalent. Patient numbers varied, with the FIH subgroup including 31 patients and the older subgroup including 163 patients. Average study durations differed: the older subgroup lasted 4.57 years, the FIH subgroup 2.85 years, and the early phase studies spanned 8.05 years on average.
Conclusion
FIH clinical report is essential to assess the significance of clinical data required for a “de novo” surgical implant. In addition, understanding the performance of the device, and recognizing the difficulties associated with the innovation constitute important lessons. These insights could be beneficial for the development of bioprosthetic heart valves and formulating a protocol for an FIH clinical trial.
Neurological soft signs (NSS) are hypothesized as candidate endophenotypes for schizophrenia, but their prevalence and relations with clinical and demographic data are unknown. The authors undertook ...a quantification (meta-analysis) of the published literature on NSS in patients with schizophrenia and healthy controls. A systematic search was conducted for published articles reporting NSS and related data using standard measures in schizophrenia and healthy comparison groups.
A systematic search was conducted for published articles reporting data on the prevalence of NSS in schizophrenia using standard clinical rating scales and healthy comparison groups. Meta-analyses were performed using the Comprehensive Meta-analysis software package. Effect sizes (Cohen d) indexing the difference between schizophrenic patients and the healthy controls were calculated on the basis of reported statistics. Potential moderator variables evaluated included age of patient samples, level of education, sample sex proportions, medication doses, and negative and positive symptoms.
A total of 33 articles met inclusion criteria for the meta-analysis. A large and reliable group difference (Cohen d) indicated that, on average, a majority of patients (73%) perform outside the range of healthy subjects on aggregate NSS measures. Cognitive performance and positive and negative symptoms share 2%-10% of their variance with NSS.
NSS occur in a majority of the schizophrenia patient population and are largely distinct from symptomatic and cognitive features of the illness.
Objectives
To: (1) assess the frequency of crossmatch incompatibility in naïve feline blood transfusion recipients using two crossmatching methods, (2) measure the effect of crossmatch ...incompatibility on change in packed cell volume following transfusion, (3) assess the frequency of acute transfusion reactions and errors in blood transfusions in cats and (4) assess the impact of crossmatch incompatibility on the likelihood of transfusion reactions.
Materials and Methods
Cats being administered a first AB‐matched transfusion in a veterinary teaching hospital were prospectively recruited for this observational study. A slide agglutination method and a commercial test were both used for major and minor crossmatching. We measured increase in packed cell volume at 12 hours after transfusion relative to the mass of red blood cells given per recipient bodyweight and recorded transfusion reactions.
Results
A total of 101 cats was included. Crossmatch incompatibility was common using the slide agglutination method (27% and 10% major and minor incompatibility, respectively), but less common with the commercial test (major and minor incompatibility both 4%). Crossmatch incompatibility with any method was not associated with less effective transfusion in terms of change in packed cell volume. Transfusion reactions occurred in 20 cats, most commonly febrile non‐haemolytic transfusion reactions (n = 9) and haemolytic transfusion reactions (n = 7). The commercial test appeared to be most specific for predicting haemolytic transfusion reactions.
Clinical Significance
Transfusion reactions were fairly common but not associated with increased mortality. Use of crossmatch‐compatible blood did not lead to a greater increase in PCV at 12 hours. The commercial test may predict a haemolytic transfusion reaction.
Diagnosis of endoleak following endovascular aortic repair (EVAR) relies on manual review of multi-slice CT angiography (CTA) by physicians which is a tedious and time-consuming process that is ...susceptible to error. We evaluate the use of a deep neural network for the detection of endoleak on CTA for post-EVAR patients using a novel data efficient training approach. 50 CTAs and 20 CTAs with and without endoleak respectively were identified based on gold standard interpretation by a cardiovascular subspecialty radiologist. The Endoleak Augmentor, a custom designed augmentation method, provided robust training for the machine learning (ML) model. Predicted segmentation maps underwent post-processing to determine the presence of endoleak. The model was tested against 3 blinded general radiologists and 1 blinded subspecialist using a held-out subset (10 positive endoleak CTAs, 10 control CTAs). Model accuracy, precision and recall for endoleak diagnosis were 95%, 90% and 100% relative to reference subspecialist interpretation (AUC = 0.99). Accuracy, precision and recall was 70/70/70% for generalist1, 50/50/90% for generalist2, and 90/83/100% for generalist3. The blinded subspecialist had concordant interpretations for all test cases compared with the reference. In conclusion, our ML-based approach has similar performance for endoleak diagnosis relative to subspecialists and superior performance compared with generalists.
Chimeric antigen receptor T cell (CAR‐T) therapy holds great promise for preventing and treating deadly diseases such as cancer. However, it remains challenging to transfect and engineer primary ...immune cells for clinical cell manufacturing. Conventional tools using viral vectors and bulk electroporation suffer from low efficiency while posing risks like viral transgene integration and excessive biological perturbations. Emerging techniques using microfluidics, nanoparticles, and high‐aspect‐ratio nanostructures can overcome these challenges, and on top of that, provide universal and high‐throughput cargo delivery. Herein, the strengths and limitations of traditional and emerging materials for immune cell transfection, and commercial development of these tools, are discussed. To enhance the characterization of transfection techniques and uptake by the clinical community, a list of in vitro and in vivo assays to perform, along with relevant protocols, is recommended. The overall aim, herein, is to motivate the development of novel materials to meet rising demand in transfection for clinical CAR‐T cell manufacturing.
The therapeutic efficacy of chimeric antigen receptor immune cell therapy requires immune cells to be successfully transfected with biomolecules like oligonucleotides and proteins. The progress in immune cell transfection using emerging materials, including microfluidics, nanoparticles, and high‐aspect‐ratio nanostructures is discussed, and their promise and drawbacks against conventional tools like viral vectors and electroporation are evaluated.
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