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Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.
Objectives
This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.
Methods
We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.
Results
Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.
Conclusions
These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.
This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome.
Methods:
Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis.
Results:
Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock–Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock–Taussig-Thomas shunt group 1–3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results.
Conclusions:
Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.
The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
To analyse the natural course of infants with otitis media with effusion who failed universal newborn hearing screening and to explore the appropriate observation period.
Methods
This retrospective cohort analysis included infants with otitis media with effusion who failed universal newborn hearing screening every 3 months for 12 months.
Results
The average recovery time of the 155 infants was 7.08 ± 0.32 months after diagnosis. Multivariate Cox regression analysis confirmed that frequent reflux, maxillofacial deformities and initial hearing status were independent factors affecting recovery. Moreover, the cumulative recovery of most infants with mild hearing loss and infants with moderate hearing loss accompanied by frequent reflux was significantly higher at six months after diagnosis than at three months.
Conclusion
For most infants with mild hearing loss, as well as those with moderate hearing loss accompanied by frequent reflux, the observation period can be extended to six months after diagnosis.
Planting patterns have significant effects on rice growth. Nonetheless, little is known about differences in annual crop yield and resource utilization among mechanized rice planting patterns in a rice–wheat cropping system. Field experiments were conducted from 2014 to 2017 using three treatments: pot seedling transplanting for rice and row sowing for wheat (PST-RS), carpet seedling transplanting for rice and row sowing for wheat (CST-RS) and row sowing for both crops (RS-RS). The results showed that, compared with RS-RS, PST-RS and CST-RS prolonged annual crop growth duration by 25–26 and 13–15 days, increased effective accumulated temperature by 399 and 212°C days and increased cumulative solar radiation by 454 and 228 MJ/m2 because of the earlier sowing of rice by 28 and 16 days in PST-RS and CST-RS, respectively. Compared with RS-RS, the annual crop yield of PST-RS and CST-RS increased by 3.1–3.8 and 2.0–2.6 t/ha, respectively, because of the increase in the number of spikelets/kernels per hectare, aboveground biomass, mean leaf area index and grain–leaf ratio. In addition, temperature production efficiency, solar radiation production efficiency and solar radiation use efficiency were higher in PST-RS, followed by CST-RS and RS-RS. These results suggest that mechanized rice planting patterns such as PST-RS increase annual crop production in rice–wheat cropping systems by increasing yield and solar energy utilization.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at −15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (−15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.
Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors.
Methods:
DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined.
Results:
Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving.
Conclusions:
These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.
Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.
Background: Human induced pluripotent stem cell-derived neural stem cells (hiPS-NSCs) represent an exciting therapeutic approach for traumatically spinal cord injury (SCI). Unfortunately, most patients are the in chronic injury phase where a dense perilesional chondroitin sulfate proteoglycan (CSPG) scar significantly hinders regeneration. CSPG-degrading enzymes can enhance NSC-mediated recovery, however, nonspecific intrathecal administration causes off-target effects. We aimed to genetically engineer hiPS-NSCs to express a scar-degrading ENZYME into their local environment to enhance functional recovery. Methods: A bicistronic scar-degrading ENZYME and RFP reporter vector was non-virally integrated into hiPS-NSCs and monoclonalized. ENZYME activity was assessed by WST-1 and DMMB biochemical assays and an in vitro CSPG spot assay with hiPS-NSC-derived neurons. To assess in vivo efficacy, T-cell deficient rats (N=60) with chronic (8wk) C6-7 SCIs were randomized to receive (1)SMaRT cells, (2)hiPS-NSCs, (3)vehicle, or (4)sham surgery. Results: SMaRT cells retained key hiPS-NSC characteristics while stably expressing ENZYME. The expressed ENZYME could appropriately degrade in vitro and ex vivo CSPGs. While blinded neurobehavioural and immunohistochemical assessments are ongoing at 40wks post-injury, an interim analysis demonstrated human cells extending remarkably long (≥20,000µm) axons along host white matter tracts. Conclusions: This work provides exciting proof-of-concept data that genetically-engineered SMaRT cells can degrade CSPGs and human NSCs can extend long-distance processes in chronic SCI.
Studies of schizophrenia at drug-naive state and on antipsychotic medication have reported a number of regions of gray-matter (GM) abnormalities but the reports have been inconsistent. The aim of this study was to conduct multimodal meta-analysis to compare the cross-sectional voxel-based morphometry studies of brain GM in antipsychotic-naive first-episode schizophrenia (AN-FES) and those with antipsychotic treatment within 1 year (AT-FES) to determine the similarities and differences in these groups. We conducted two separate meta-analyses containing 24 studies with a sample size of 801 patients and 957 healthy controls. A multimodal meta-analysis method was used to compare the findings between AN-FES and AT-FES. Meta-regression analyses were done to determine the influence of different variables including age, duration of illness, and positive and negative symptom scores. Finally, jack-knife analyses were done to test the robustness of the results. AN-FES and AT-FES showed common patterns of GM abnormalities in frontal (gyrus rectus), superior temporal, left hippocampal and insular cortex. GM in the left supramarginal gyrus and left middle temporal gyrus were found to be increased in AN-FES but decreased in AT-FES, whereas left median cingulate/paracingulate gyri and right hippocampus GM was decreased in AN-FES but increased in AT-FES. Findings suggest that both AN-FES and AT-FES share frontal, temporal and insular regions as common anatomical regions to be affected indicating these to be the primary regions of GM abnormalities in both groups.
It has been demonstrated that microRNAs (miRNAs) play important roles in the control of melanogenesis and hair color in mammals. By comparing miRNA expression profiles between brown and white alpaca skin, we previously identified miR508-3p as a differentially expressed miRNA suggesting its potential role in melanogenesis and hair color formation. The present study was conducted to determine the role of miR508-3p in melanogenesis in alpaca melanocytes. In situ hybridization showed that miR508-3p is abundantly present in the cytoplasma of alpaca melanocytes. miR508-3p was predicted to target the gene encoding microphthalmia transcription factor (MITF) and a luciferase reporter assay indicated that miR508-3p regulates MITF expression by directly targeting its 3′UTR. Overexpression of miR508-3p in alpaca melanocytes down-regulated MITF expression both at the messenger RNA and protein level and resulted in decreased expression of key melanogenic genes including tyrosinase and tyrosinase-related protein 2. Overexpression of miR508-3p in melanocytes also resulted in decreased melanin production including total alkali-soluble melanogenesis, eumelanogenesis and pheomelanogenesis. Results support a functional role of miR508-3p in regulating melanogenesis in alpaca melanocytes by directly targeting MITF.
Multidrug-resistant Pseudomonas aeruginosa (MDRPA) infections are major threats to healthcare-associated infection control and the intrinsic molecular mechanisms of MDRPA are also unclear. We examined 348 isolates of P. aeruginosa, including 188 MDRPA and 160 non-MDRPA, obtained from five tertiary-care hospitals in Guangzhou, China. Significant correlations were found between gene/enzyme carriage and increased rates of antimicrobial resistance (P < 0·01). gyrA mutation, OprD loss and metallo-β-lactamase (MBL) presence were identified as crucial molecular risk factors for MDRPA acquisition by a combination of univariate logistic regression and a multifactor dimensionality reduction approach. The MDRPA rate was also elevated with the increase in positive numbers of those three determinants (P < 0·001). Thus, gyrA mutation, OprD loss and MBL presence may serve as predictors for early screening of MDRPA infections in clinical settings.
Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified.
Method
A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives.
Results
SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups.
Conclusions
The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.
Computational fluid dynamics solutions of the Reynolds Averaged Navier-Stokes equations have been used to numerically predict the thrust of a thermally choked ram accelerator in subdetonative velocity regime. Studies were focused on a projectile operating in a 38-mm-diameter ram accelerator tube loaded with premixed propellant gas; methane/oxygen/nitrogen at 5.15 MPa fill pressure. Simulations were carried out for a series of incoming velocities. The shear stress transport turbulence model (SST) and the eddy dissipation combustion model (EDM) with five-step reaction mechanism were used to simulate the fully turbulent reactive flow field around the projectile. The predicted projectile thrust-velocity agreed well with the experimental measurements, in addition, the CFD predicted pressure variation and magnitude along projectile axial direction also agreed well with the test data. The present investigation reveals some key features of the shock-wave system around the projectile, which are important in determining the characteristics of the thermally choked propulsive mode. These findings are useful in understanding the characteristics of high speed turbulent combustion process in the ram accelerator.
A cDNA library from white alpaca (Vicugna pacos) skin was constructed using SMART technology to investigate the global gene expression profile in alpaca skin and identify genes associated with physiology of alpaca skin and pigmentation. A total of 5359 high-quality EST (expressed sequence tag) sequences were generated by sequencing random cDNA clones from the library. Clustering analysis of sequences revealed a total of 3504 unique sequences including 739 contigs (assembled from 2594 ESTs) and 2765 singletons. BLAST analysis against GenBank nr database resulted in 1287 significant hits (E-value < 10−10), of which 863 were annotated through gene ontology analysis. Transcripts for genes related to fleece quality, growth and coat color (e.g. collagen types I and III, troponin C2 and secreted protein acidic and rich in cysteine) were abundantly present in the library. Other genes, such as keratin family genes known to be involved in melanosome protein production, were also identified in the library. Members (KRT10, 14 and 15) of this gene family are evolutionarily conserved as revealed by a cross-species comparative analysis. This collection of ESTs provides a valuable resource for future research to understand the network of gene expression linked to physiology of alpaca skin and development of pigmentation.
The storage ring tune measurement system at the Advanced Photon Source (APS) consists of signal pickup and beam excitation drive striplines. Striplines currently installed in the APS storage ring are of a four-blade (inner conductor) design that serves as a beam diagnostic tool and for transverse and longitudinal tune measurements. A new two-blade stripline was designed for the transverse feedback system and to be used for horizontal beam excitation. In this paper, we discuss its mechanical design, assembly procedure, and construction.
Knockout tournaments are often used in sports (or experiments where preferences are registered by comparisons instead of measurements) to determine the champion of an event. A knockout tournament plan (KTP) for n players is a rooted binary tree with n leaves to be labeled by the n players. Each subtree of two leaves represents a match between the two players labeling the two leaves; the winner of the match then moves on to label the root of the subtree. While there are many KTPs to choose from for a given number of players, in the real world an almost balanced KTP is usually chosen. One reason could be the perception that a balanced KTP is “fair” to the players, in the sense that, given a random labeling of leaves by players, a stronger player has a better chance to win the tournament. Surprisingly, it has been shown that not all KTPs have this property, and it is difficult to prove this property for any general class of KTPs. So far the property has been shown to hold only for balanced KTPs. In this paper we extend it to some classes of almost balanced KTPs.
We consider the group testing problem for a set of independent items I = [I1,… In] where Ii, has probability pi, of being defective and probability qi = 1 – pi of being good. The problem is to classify all items as good or defective with a minimum expected number of group tests where a group test is a test on a subset S of I with two possible outcomes: either S is pure (contains no defective) or S is contaminated (contains at least one defective, with no information provided about which or how many). No polynomial-time algorithm is known for the group testing problem even for the special case pi = p for all i. Hence, any method that reduces the size of the problem is very helpful. In this paper, we give such a method by providing a simple condition to screen items that should be tested (only) individually. This condition leads to a necessary and sufficient condition for the individual testing algorithm to be optimal, generalizing a result of Unger [1] for the special case of identical pi.
A consecutive−k−out−of−n:F system is an n−vertex graph where the system fails if and only if some k consecutive vertices all fail. Assuming that the n vertices have, independently, the respective failure probabilities q1,…, qn, the problem is to find, subject to πqi = Q (a constant), a set of q1,…, qn so as to maximize the system reliability. In the case that the graph is a circle (or cycle), Chang and Hwang [1] conjectured that q1 =… = qn, = Q1/n is optimal if n and k are relatively prime. In this paper, it is shown that the conjecture is true for sufficiently small Q. It is also shown by counterexample that the conjecture is not true in general.