Miracle-dz/UniFAR-FTUs huggingface dataset:
Synaptic Wiring of Corticostriatal Circuits in Basal Ganglia: Insights into the Pathogenesis of Neuropsychiatric Disorders

Abstract The striatum is a key hub in the basal ganglia for processing neural information from the sensory, motor, and limbic cortices. The massive and diverse cortical inputs entering the striatum allow the basal ganglia to perform a repertoire of neurological functions ranging from basic level of motor control to high level of cognition. The heterogeneity of the corticostriatal circuits, however, also renders the system susceptible to a repertoire of neurological diseases. Clinical and animal model studies have indicated that defective development of the corticostriatal circuits is linked to various neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, obsessive-compulsive disorder (OCD), autism spectrum disorder (ASD), and schizophrenia. Importantly, many neuropsychiatric disease-risk genes have been found to form the molecular building blocks of the circuit wiring at the synaptic level. It is therefore imperative to understand how corticostriatal connectivity is established during development. Here, we review the construction during development of these corticostriatal circuits at the synaptic level, which should provide important insights into the pathogenesis of neuropsychiatric disorders related to the basal ganglia and help the development of appropriate therapies for these diseases.
TDOA-Based Localization for Semi-Static Targets in NLOS Environments

We study the problem of locating semi-static targets in non-line-of-sight (NLOS) environments using multiple sets of time-difference-of-arrival (TDOA) measurements. Specific focus is placed on the correlation between TDOA measurements caused by NLOS errors. We propose an algorithm which takes this correlation into account when fusing the available TDOA measurements and achieves high accuracy in estimating both the position and the associated uncertainty. In addition, a statistical ranging error model for NLOS environments is proposed based on empirical ranging data, which substantially improves the positioning accuracy. The proposed approach is verified experimentally in an aircraft cabin and achieves seat-level accuracy for 99% of the nodes.
Comparison of arthroscopic suture-bridge technique and double-row technique for treating rotator cuff tears

Background: Rotator cuff tear is a common shoulder disorder in the elderly. Either arthroscopic double-row (DR) or suture-bridge (SB) technique for rotator cuff tear patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic SB versus DR intervention. Methods: The 7 studies were acquired from PubMed, Medline, Embase, CNKI, Google, and Cochrane Library. The data were extracted by 2 of the co-authors independently and were analyzed by RevMan5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle–Ottawa scale were used to assess risk of bias. Results: Seven studies including 1 randomized controlled trial and 6 observational studies were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of American Shoulder and Elbow Surgeons score, Constant score, visual analog scale score, and range of motion showed that the differences were not statistically significant between the 2 interventions. The difference of University of California at Los Angeles (UCLA) score was statistically significant between SB and DR intervention, and SB treatment was more effective (MD = −0.95, 95% CI = −1.70 to −0.20, P = .01). The difference of re-tear rate was statistically significant and SB treatment achieved better result than DR treatment (OR = 0.31, 95% CI = 0.15–0.64, P = .001). Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. Conclusions: Both arthroscopic SB and DR interventions had benefits in rotator cuff tear. SB treatment was more effective in UCLA score and had lower re-tear rate than DR treatment. The arthroscopic SB technique is recommended as the optical choice for rotator cuff tear.
Inhibition of calf thymus type II DNA topoisomerase by poly(ADP‐ribosylation).

The effect of poly(ADP‐ribosylation) on calf thymus topoisomerase type II reactions has been investigated. Unknotting of phage P4 head DNA, and relaxation and catenation of supercoiled PM2 DNA are inhibited. We conclude that the inhibition results from poly(ADP‐ribosylation) on the following grounds. Firstly, the enzyme poly(ADP‐ribose) (PADPR) synthetase and NAD are required, secondly, the competitive synthetase inhibitor nicotinamide abolishes topoisomerase inhibition, and thirdly, the polymer alone is not inhibitory. The mechanism of inhibition appears to be disruption of the strand cleavage reaction. A topoisomerase‐DNA complex can be formed that upon treatment with protein denaturant at low ionic strength results in strand cleavage. The amount of DNA present in such a cleavable‐complex progressively decreased following pretreatment of topoisomerase type II with PADPR synthetase and increasing concentrations of NAD. Treatment of the pre‐formed complex with NAD and PADPR synthetase had no effect on its salt‐induced dissociation. This suggests that either poly(ADP‐ribosylation) has no influence on dissociation of topoisomerase, in contrast to association, or topoisomerase is not accessible to the synthetase when bound to DNA. Similar data were obtained with calf thymus type I topoisomerase.
Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice.

AIMS Cathepsin K (CatK), an established drug target for osteoporosis, has been reported to be upregulated in atherosclerotic lesions. Due to its proteolytic activity, CatK may influence the atherosclerotic lesion composition and stability. In this study, we investigated the potential role of leucocyte CatK in atherosclerotic plaque remodelling. METHODS AND RESULTS To assess the biological role of leucocyte CatK, we used the technique of bone marrow transplantation to selectively disrupt CatK in the haematopoietic system. Total bone marrow progenitor cells from CatK(+/+), CatK(+/-), and CatK(-/-) mice were transplanted into X-ray irradiated low-density lipoprotein receptor knockout (LDLr(-/-)) mice. The selective silencing of leucocyte CatK resulted in phenotypic changes in bone formation with an increased total bone mineral density in the CatK(-/-) chimeras and an effect of gene dosage. The absence of leucocyte CatK resulted in dramatically decreased collagen and increased macrophage content of the atherosclerotic lesions while lesion size was not affected. The atherosclerotic lesions also demonstrated less elastic lamina fragmentation and a significant increase in the apoptotic and necrotic area in plaques of mice transplanted with CatK(-/-) bone marrow. CONCLUSION Leucocyte CatK is an important determinant of atherosclerotic plaque composition, vulnerability, and bone remodelling, rendering CatK an attractive target for pharmaceutical modulation in atherosclerosis and osteoporosis.
Causes and consequences of reciprocal translocations on sex chromosomes

Under XY sex determination, the Y chromosome is only inherited via males, whereas the X chromosome is predominantly found in females. Thus, it is favourable when alleles with high male fitness become associated with the Y chromosome and when alleles with high female fitness become associated with the X chromosome. These favourable associations can be strengthened through linkage. Rearrangements, such as inversions and sex chromosome–autosome fusions, can increase linkage and thereby become favoured (Charlesworth, 2017). In a From the Cover article in this issue of Molecular Ecology, Toups, Rodrigues, Perrin, and Kirkpatrick (2019) present the first genomic analysis of a sex chromosome reciprocal translocation, a particularly dramatic chromosomal rearrangement that modifies linkage with the sex chromosome. As a result of reciprocal translocation, one studied population of the common frog (Rana temporaria, Figure 1) displays a remarkable sex‐determining system in which there are two physically unlinked sex chromosomes that are exclusively cotransmitted (Figure 2a).
Illumina Sequencing Reveals the First Near-Complete Genome Sequence of Ugandan Passiflora Virus

Here, we present the first near-complete genome of Ugandan Passiflora virus (UPV) sequenced from a symptomatic sample of KH7 passion fruit (Passiflora edulis Sims) variety. UPV had limited amino acid identity with other potyviruses known to cause passion fruit woodiness disease (PWD). ABSTRACT Here, we present the first near-complete genome of Ugandan Passiflora virus (UPV) sequenced from a symptomatic sample of KH7 passion fruit (Passiflora edulis Sims) variety. UPV had limited amino acid identity with other potyviruses known to cause passion fruit woodiness disease (PWD). The closest relationship (71.2% amino acid similarity) was with Bean common mosaic necrosis virus.
Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection.
Mutation of RNA Polymerase β Subunit (rpoB) Promotes hVISA-to-VISA Phenotypic Conversion of Strain Mu3

ABSTRACT The clinical vancomycin-intermediate Staphylococcus aureus (VISA) strain Mu50 carries two mutations in the vraSR and graRS two-component regulatory systems (TCRSs), namely, vraS(I5N) and graR(N197S) (hereinafter designated graR*). The clinical heterogeneously vancomycin-intermediate S. aureus (hVISA) strain Mu3 shares with Mu50 the mutation in vraS that encodes the VraS two-component histidine kinase. Previously, we showed that introduction of the plasmid pgraR*, carrying the mutated two-component response regulator graR*, converted the hVISA strain Mu3 into VISA (vancomycin MIC = 4 mg/liter). Subsequently, however, we found that the introduction of a single copy of graR* into the Mu3 chromosome by a gene replacement method did not confer on Mu3 the VISA phenotype. The gene-replaced strain Mu3graR* thus obtained remained hVISA (MIC ≤ 2 mg/liter), although a small increase in vancomycin MIC was observed compared to that of the parent strain Mu3. Reevaluation of the Mu3 and Mu50 genomes revealed the presence of another mutation responsible for the expression of the VISA phenotype in Mu50. Here, we demonstrate that in addition to the two regulator mutations, a third mutation found in the Mu50 rpoB gene, encoding the RNA polymerase β subunit, was required for Mu3 to achieve the level of vancomycin resistance of Mu50. The selection of strain Mu3graR* with rifampin gave rise to rpoB mutants with various levels of increased vancomycin resistance. Furthermore, 3 (33%) of 10 independently isolated VISA strains established from the heterogeneous subpopulations of Mu3graR* were found to possess rpoB mutations with or without an accompanying rifampin-resistance phenotype. The data indicate that a sizable proportion of the resistant hVISA cell subpopulations is composed of spontaneous rpoB mutants with various degrees of increased vancomycin resistance.
A Global and Local Enhanced Residual U-Net for Accurate Retinal Vessel Segmentation

Retinal vessel segmentation is a critical procedure towards the accurate visualization, diagnosis, early treatment, and surgery planning of ocular diseases. Recent deep learning-based approaches have achieved impressive performance in retinal vessel segmentation. However, they usually apply global image pre-processing and take the whole retinal images as input during network training, which have two drawbacks for accurate retinal vessel segmentation. First, these methods lack the utilization of the local patch information. Second, they overlook the geometric constraint that retina only occurs in a specific area within the whole image or the extracted patch. As a consequence, these global-based methods suffer in handling details, such as recognizing the small thin vessels, discriminating the optic disk, etc. To address these drawbacks, this study proposes a Global and Local enhanced residual U-nEt (GLUE) for accurate retinal vessel segmentation, which benefits from both the globally and locally enhanced information inside the retinal region. Experimental results on two benchmark datasets demonstrate the effectiveness of the proposed method, which consistently improves the segmentation accuracy over a conventional U-Net and achieves competitive performance compared to the state-of-the-art.
Long‐Term Treatment of Incadronate Disodium Accumulates Microdamage but Improves the Trabecular Bone Microarchitecture in Dog Vertebra

This study aimed to investigate the effect of long‐term suppression of bone resorption by bisphosphonate on the microstructure, accumulation of microdamage, and mechanical properties of trabecular bone. Twenty‐nine 1‐year‐old beagles (15 males, 14 females) were divided into three groups. The control group (CNT) was treated daily with vehicle, and the other two groups were treated with incadronate at a dose of 0.3 mg/kg/day (LOW) or 0.6 mg/kg/day (HIGH) orally for 3 years. After death, the second thoracic vertebra was scanned with microcomputed tomography (micro‐CT) and assigned to histomorphometric and microdamage measurements. The fourth lumbar vertebra was mechanically tested by compression. Incadronate concentration in bone was measured in the 11th thoracic vertebra. Micro‐CT analysis demonstrated a platelike trabecular structure and increased concave surface of trabeculae in the thoracic vertebra of incadronate‐treated groups. Three‐year incadronate treatment significantly suppressed trabecular activation rates by 56% in LOW and 67% in HIGH without impairment of mineralization, and increased microdamage accumulation in both incadronate‐treated groups. Trabecular bone volume was significantly increased in both LOW and HIGH groups, and vertebral strength was significantly increased in the HIGH group compared with the CNT group. However, intrinsic material properties such as normalized ultimate stress and normalized toughness were reduced in incadronate‐treated groups. Incadronate concentration in bone was dose‐dependent. This study suggests that long‐term suppression of bone remodeling increases microdamage accumulation, but this is not necessarily associated with vertebral fragility because of compensated increase of bone mass and improved microarchitecture.
Use of “unidentified bright objects” on MRI for diagnosis of neurofibromatosis 1 in children

Background: “Unidentified bright objects” (UBOs) have been observed as areas of increased T2-weighted signal intensity on MRI in 43% to 93% of children with neurofibromatosis 1 (NF1). Because of this high frequency and the fact that the NIH diagnostic criteria often do not permit diagnosis of NF1 in early childhood, UBOs have been proposed as an additional diagnostic criterion. Methods: The authors examined the sensitivity and specificity of UBOs for NF1 in 19 affected children and 19 age-matched controls. Eleven of the control patients had CNS pathology that might be classified as UBOs on MRI scan. The authors measured the agreement in recognition of UBOs between two pediatric neuroradiologists who independently examined the MRI studies of these patients. They also assessed the effect of adding UBOs to the NIH diagnostic criteria on ability to diagnose NF1 in young patients. Results: Sensitivity and specificity of UBOs for NF1 averaged 97% and 79%, respectively. Agreement between the two radiologists was 84% overall, but varied greatly from one brain region to another. Adding UBOs as a diagnostic criterion permitted the diagnosis of 30% of young patients with NF1 mutations who do not meet the existing NIH diagnostic criteria for NF1. The value of including UBOs is less in older patients because a larger proportion of them meet the existing diagnostic criteria. Conclusions: UBOs are difficult to identify with certainty and occur in children with suspected CNS disorders who do not have NF1, but they tend to occur in different brain regions. UBOs may be more useful for diagnosis of NF1 in young children if they can be defined precisely and if only the cerebellum, brainstem, and basal ganglia are considered.
Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia

Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (P<0.001), overall (P=0.002) and event-free survival (P<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (P=0.01) and event-free survival (P=0.002), and showed a trend for overall survival (P=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double CEBPA mutations, NPM1 mutations and FLT3-ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. clinicaltrials.gov Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202).
Bicuspid aortic valve with right‐sided aortic arch aneurysm and Kommerell's diverticulum

Bicuspid aortic valve (BAV) is a common congenital cardiac malformation, frequently combined with ascending aorta dilation. However, isolated abnormalities of the aortic arch are less frequent in BAV patients. Here, we present a rare case of BAV combined with right‐sided aortic arch aneurysm, aberrant left subclavian artery, and Kommerell's diverticulum, diagnosed by echocardiography and computed tomography angiography. The patient was followed‐up regularly because of the life‐threatening risks of aortic arch aneurysms.
A three‐wave longitudinal study of subcortical–cortical resting‐state connectivity in adolescence: Testing age‐ and puberty‐related changes

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward‐driven behavior. Although reward‐driven behavior is supported by subcortical‐medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting‐state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three‐wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self‐reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age‐related strengthening of subcortico‐subcortical and cortico‐cortical connectivity. Subcortical–cortical connectivity, such as, between the nucleus accumbens—frontal medial cortex, and the caudate—dorsal anterior cingulate cortex, however, weakened across age. Model‐based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical–cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.
Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits

Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer’s disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.