Publications by authors named "Teng Teng"

49 Publications

Multi-omics analysis of the amygdala in a rat chronic unpredictable mild stress model of depression.

Neuroscience 2021 Apr 6. Epub 2021 Apr 6.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Physical Examination, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Major depressive disorder is a serious and complex mental illness, and multiple brain regions are involved in its pathogenesis. There is increasing evidence that the amygdala is involved in depression; however, the underlying molecular mechanisms remain unclear. In this study, we applied a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomic and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic to study changes in the amygdala in a chronic unpredictable mild stress (CUMS) rat model of depression. Differential analysis identified 42 metabolites and 171 proteins that were differentially expressed in the CUMS and control groups. Integrated analyses revealed two major changes in the amygdala of CUMS rats: (1) perturbations in amino acids and carbohydrate metabolism, transport-/catabolism-related proteins activity, and metabolic enzyme activity; (2) abnormal expression of synaptogenesis and oxidative phosphorylation-associated proteins.
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http://dx.doi.org/10.1016/j.neuroscience.2021.03.031DOI Listing
April 2021

Solution-Processed OLEDs Based on Thermally Activated Delayed Fluorescence Copper(I) Complexes with Intraligand Charge-Transfer Excited State.

Molecules 2021 Feb 20;26(4). Epub 2021 Feb 20.

College of Materials Science and Engineering, Shenzhen University, Shenzhen 518055, China.

A new series of tetrahedral heteroleptic copper(I) complexes exhibiting efficient thermally-activated delayed fluorescence (TADF) in green to orange electromagnetic spectral regions has been developed by using D-A type N^N ligand and P^P ligands. Their structures, electrochemical, photophysical, and electroluminescence properties have been characterized. The complexes exhibit high photoluminescence quantum yields (PLQYs) of up to 0.71 at room temperature in doped film and the lifetimes are in a wide range of 4.3-24.1 μs. Density functional theory (DFT) calculations on the complexes reveal the lowest-lying intraligand charge-transfer excited states that are localized on the N^N ligands. Solution-processed organic light emitting diodes (OLEDs) based on one of the new emitters show a maximum external quantum efficiency (EQE) of 7.96%.
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http://dx.doi.org/10.3390/molecules26041125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924317PMC
February 2021

Overlap of burnout-depression symptoms among Chinese neurology graduate students in a national cross-sectional study.

BMC Med Educ 2021 Feb 2;21(1):83. Epub 2021 Feb 2.

School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.

Background: The overlap of burnout and depression is a phenomenon that can effectively reflect the psychological state of a group. However, whether burnout is a type of depression is still debated in current research. The high incidence of burnout and depressive symptoms among medical students indicates that it is urgent to provide appropriate health services for them. However, the proportion of burnout and depression in the overlapping symptoms experienced by medical students, and the characteristics of the relative influencing factors, remain unclear. Therefore, we addressed these issues for neurology graduate students in China.

Methods: Using data from a cross-sectional survey of Chinese neurology graduate students, a diagnostic model was established according to their burnout and/or depression symptoms. Burnout was assessed by using the Maslach Burnout Inventory. Depression symptoms were assessed with a two-item depression screening tool for primary care evaluation of mental disorders. Univariate analyses with chi-squared tests were conducted to assess associations between variables. Multinomial logistic regression models were used to analyze the effects of multiple factors on dependent variables. The factors included demographic information and three medical-study related problems.

Results: In total, 32.2% of surveyed students evidenced overlapping burnout and depression symptoms. Students with depressive symptoms tended to be included in the burnout students' category. In the regression model, being unmarried, having children, and career choice regret were related to students who had only burnout, while the students with overlapping symptoms were affected by more factors such as family income, the consideration of dropping out once.

Conclusions: The symptoms and related factors of burnout and depression among Chinese neurology postgraduates have obvious overlap and show a significant trend. The occurrence of depressive symptoms among medical students is closely related to whether they are burned out. Students with only burnout were common, but students with only depressive symptoms were uncommon. Finally, burnout may be a pre-depression state.
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http://dx.doi.org/10.1186/s12909-021-02511-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851928PMC
February 2021

Treatment of depression in children and adolescents - Authors' reply.

Lancet Psychiatry 2021 02;8(2):97-98

Department of Neurology, Chongqing, China. Electronic address:

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http://dx.doi.org/10.1016/S2215-0366(20)30537-XDOI Listing
February 2021

Efficacy and acceptability of parent-only group cognitive behavioral intervention for treatment of anxiety disorder in children and adolescents: a meta-analysis of randomized controlled trials.

BMC Psychiatry 2021 Jan 11;21(1):29. Epub 2021 Jan 11.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Anxiety disorder is the most prevalent mental disorder among children and adolescents, causing significant psychosocial problems and physical health conditions. Cognitive behavioral therapy (CBT) is an effective treatment for anxiety disorder in children and adolescents. And parent-only CBT is an alternative treatment for childhood anxiety disorder, which includes psychologists and parents rather than children in the treatment. As a new type of CBT, parent-only CBT has some advantages. However, it remains unclear whether parent-only CBT interventions are effective for treating children and adolescents with anxiety disorder.

Methods: In this study, we evaluated the efficacy (the mean change scores of the anxiety rating scale from baseline to post-treatment, standardized mean difference SMD) and acceptability (the proportion of patients in the treatment group who withdrew from treatment early for any reason, risk ratios RRs) of parent-only cognitive behavioral therapy (CBT) for children and adolescents with anxiety disorder. We searched electronic databases, including PubMed, Cochrane Library, Embase, Web of Science, ProQuest, and PsycINFO from inception to June 2019. We included randomized controlled trials (RCTs) comparing parent-only CBT either with waitlist (WL), or CBT with parents in children and adolescents with anxiety disorder.

Results: Finally, six RCTs with 407 participants were included in the meta-analyses. In terms of efficacy, pooled analyses indicated that parent-only CBT was significantly more effective than WL for reducing anxiety symptoms with SMD of - 0.72 (95% CI - 1.41 to - 0.03, p = 0.04), and more remission rate with RR of 4.33 (37.96% vs. 6.85, 95% CI 1.82 to 10.27, p = 0.0009) at post-treatment. And our analyses showed no evidence that parent-only CBT had significantly greater efficacy than CBT with parents with SMD of 0.21 (95% CI - 0.09 to 0.50, p = 0.17). Acceptability in the parent-only CBT group was not significantly different to the WL group with RR of 0.92 (95% CI 0.52 to 1.62, p = 0.77), and was significantly worse than in the CBT with parents group with RR of 1.93 (95% CI 1.05 to 3.57, p = 0.03).

Conclusions: Current evidence indicates that parent-only CBT can be an alternative and acceptable intervention for treating children and adolescents with anxiety disorder.
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http://dx.doi.org/10.1186/s12888-020-03021-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802251PMC
January 2021

Chronic unpredictable mild stress produces depressive-like behavior, hypercortisolemia, and metabolic dysfunction in adolescent cynomolgus monkeys.

Transl Psychiatry 2021 01 4;11(1). Epub 2021 Jan 4.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Adolescent depression is a common and serious mental disorder with unique characteristics that are distinct from adult depression. The adult non-human primate stress-induced model of depressive-like behavior is an excellent model for the study of mechanisms; however, an adolescent nonhuman primate model is still lacking. Ten male adolescent cynomolgus monkeys were divided into a chronic unpredictable mild stress (CUMS, n = 5) group and a control (CON, n = 5) group by age and weight-matched pairs. The CUMS group was exposed to multiple unpredictable mild stressors for five cycles over 55 days. At baseline, there were no differences between CUMS and CON groups. At endpoint, the CUMS group demonstrated significantly higher depressive-like behavior (huddle posture), and significantly lower locomotion compared with the CON group. Furthermore, depressive-like behavior increased from baseline to endpoint in the CUMS group, but not changed in the CON group. In the attempt for apple test, the CUMS group made significantly fewer attempts for the apple than the CON group. In the human intruder test, the CUMS group showed significantly higher anxiety-like behaviors in the stare phase than the CON group. Hair cortisol level was significantly higher in the CUMS group than the CON group at endpoint, and was also elevated from baseline to endpoint. Metabolic profiling of plasma at endpoint identified alterations in metabolite pathways which overlapped with those of adolescent depression patients. CUMS can induce depressive-like and anxiety-like behaviors, hypercortisolemia, and metabolic perturbations in adolescent cynomolgus monkeys. This is a promising model to study the mechanisms underlying adolescent depression.
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http://dx.doi.org/10.1038/s41398-020-01132-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791128PMC
January 2021

N-Acetyl-L-cysteine Promotes Growth and Expansion of Single Circulating Tumor Cells by Mitigating Cellular Stress Responses.

Mol Cancer Res 2021 Mar 10;19(3):441-450. Epub 2020 Dec 10.

Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California.

Circulating tumor cells (CTC) can be isolated via a minimally invasive blood draw and are considered a "liquid biopsy" of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small-molecule drug screen to identify compounds that can improve culture efficiency for single CTCs. We found that N-acetyl-L-cysteine (NAC) and other antioxidants can promote expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single-cell expansion. RNA-seq analysis of growing clones and nongrowing clones confirmed the effect by NAC, but also indicates that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with predominant senescent features. Despite the challenge in expanding all CTCs, NAC treatment led to establishment of single CTC clones that have similar tumorigenic features. IMPLICATIONS: Through a small molecule screen and validation study, we found that NAC could improve the success of expansion of single CTCs by mitigating the initial stress, with the potential to facilitate the investigation of functional heterogeneity in CTCs.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925378PMC
March 2021

Face-to-Face Orientation of Quasiplanar Donor and Acceptor Enables Highly Efficient Intramolecular Exciplex Fluorescence.

Angew Chem Int Ed Engl 2021 Feb 27;60(8):3994-3998. Epub 2020 Dec 27.

College of Materials Science and Engineering, Shenzhen University, Shenzhen, 518055, P. R. China.

Intramolecular through-space charge-transfer (TSCT) excited states have been exploited for developing thermally activated delayed fluorescence (TADF) emitters, but the tuning of excited state dynamics by conformational engineering remains sparse. Designed here is a series of TSCT emitters with precisely controlled alignment of the donor and acceptor segments. With increasing intramolecular π-π interactions, the radiative decay rate of the lowest singlet excited state (S ) progressively increased together with a suppression of nonradiative decay, leading to significantly enhanced photoluminescence quantum yields of up to 0.99 in doped thin films. A high-efficiency electroluminescence device, with a maximum external quantum efficiency (EQE) of 23.96 %, was achieved and maintains >20 % at a brightness of 1000 cd m . This work sheds light on the importance of conformation control for achieving high-efficiency intramolecular exciplex emitters.
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http://dx.doi.org/10.1002/anie.202013051DOI Listing
February 2021

Lighting Silver(I) Complexes for Solution-Processed Organic Light-Emitting Diodes and Biological Applications via Thermally Activated Delayed Fluorescence.

Inorg Chem 2020 Sep 26;59(17):12122-12131. Epub 2020 Aug 26.

Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518055, People's Republic of China.

Luminescent coinage metal complexes have shown promising applications as electroluminescent emitters, photocatalysts/photosensitizers, and bioimaging/theranostic agents, rendering them attractive alternatives to transition metal complexes based on iridium, ruthenium, and platinum that have extremely low earth abundance. In comparison to the widely studied Au(I) and Cu(I) complexes, Ag(I) complexes have seldom been explored in this field because of their inferior emission properties. Herein, we report a novel series of [Ag(N^N)(P^P)]PF complexes exhibiting highly efficient thermally activated delayed fluorescence by using easily accessible neutral diamine ligands and commercially available ancillary diphosphine chelates. The photoluminescence quantum yields (PLQYs) of the Ag(I) emitters are ≤0.62 in doped films. The high PLQY with a large delayed fluorescence ratio enabled the fabrication of solution-processed organic light-emitting diodes (OLEDs) with a high maximum external quantum efficiency of 8.76%, among the highest values for Ag(I) emitter-based OLEDs. With superior emission properties and an excited state lifetime in the microsecond regime, together with its potent cytotoxicity, the selected Ag(I) complex has been used for simultaneous cell imaging and anticancer treatment in human liver carcinoma HepG2 cells, revealing the potential of luminescent Ag(I) complexes for biological applications such as theranostics.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01054DOI Listing
September 2020

Optimization of AsCas12a for combinatorial genetic screens in human cells.

Nat Biotechnol 2021 01 13;39(1):94-104. Epub 2020 Jul 13.

Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Cas12a RNA-guided endonucleases are promising tools for multiplexed genetic perturbations because they can process multiple guide RNAs expressed as a single transcript, and subsequently cleave target DNA. However, their widespread adoption has lagged behind Cas9-based strategies due to low activity and the lack of a well-validated pooled screening toolkit. In the present study, we describe the optimization of enhanced Cas12a from Acidaminococcus (enAsCas12a) for pooled, combinatorial genetic screens in human cells. By assaying the activity of thousands of guides, we refine on-target design rules and develop a comprehensive set of off-target rules to predict and exclude promiscuous guides. We also identify 38 direct repeat variants that can substitute for the wild-type sequence. We validate our optimized AsCas12a toolkit by screening for synthetic lethalities in OVCAR8 and A375 cancer cells, discovering an interaction between MARCH5 and WSB2. Finally, we show that enAsCas12a delivers similar performance to Cas9 in genome-wide dropout screens but at greatly reduced library size, which will facilitate screens in challenging models.
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http://dx.doi.org/10.1038/s41587-020-0600-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854777PMC
January 2021

Genome-Wide Detection of CNVs and Association With Body Weight in Sheep Based on 600K SNP Arrays.

Front Genet 2020 9;11:558. Epub 2020 Jun 9.

State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China.

Copy number variations (CNVs) are important genomic structural variations and can give rise to significant phenotypic diversity. Herein, we used high-density 600K SNP arrays to detect CNVs in two synthetic lines of sheep (DS and SHH) and in Hu sheep (a local Chinese breed). A total of 919 CNV regions (CNVRs) were detected with a total length of 48.17 Mb, accounting for 1.96% of the sheep genome. These CNVRs consisted of 730 gains, 102 losses, and 87 complex CNVRs. These CNVRs were significantly enriched in the segmental duplication (SD) region. A CNVR-based cluster analysis of the three breeds revealed that the DS and SHH breeds share a close genetic relationship. Functional analysis revealed that some genes in these CNVRs were also significantly enriched in the olfactory transduction pathway (oas04740), including members of the OR gene family such as , , and . Using association analyses and previous gene annotations, we determined that a subset of identified genes was likely to be associated with body weight, including , , , , and . Together, these results offer valuable information that will guide future efforts to explore the genetic basis for body weight in sheep.
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http://dx.doi.org/10.3389/fgene.2020.00558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297042PMC
June 2020

Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis.

Lancet Psychiatry 2020 07;7(7):581-601

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Background: Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents.

Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841.

Findings: From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (-0·78, 95% CrI -1·55 to -0·01) and psychodynamic therapy (-1·14, -2·20 to -0·08), but not more effective than fluoxetine alone (-0·22, -0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from -1·73 to -0·51); and only interpersonal therapy was more effective than all psychological controls (-1·37 to -0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as "low" to "very low" in terms of confidence of evidence according to Confidence In Network Meta-Analysis.

Interpretation: Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis.

Funding: National Key Research and Development Program of China.
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http://dx.doi.org/10.1016/S2215-0366(20)30137-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303954PMC
July 2020

Most Orthopaedic Studies Using the National Inpatient Sample Fail to Adhere to Recommended Research Practices: A Systematic Review.

Clin Orthop Relat Res 2020 12;478(12):2743-2748

T. L. Teng, Tufts University School of Medicine, Boston, MA, USA.

Background: The National Inpatient Sample (NIS) database is accessible, inexpensive, and increasingly used in orthopaedic research, but it has complex design features that require nuanced methodological considerations for appropriate use and interpretation. A recent study showed poor adherence to recommended research practices for the NIS across a broad spectrum of medical and surgical fields, but the degree and patterns of nonadherence among orthopaedic publications remain unclear.

Questions/purposes: In this study, we sought: (1) to quantify nonadherence to recommended research practices provided by the Agency for Healthcare Research and Quality (AHRQ) for using the NIS data in orthopaedic studies from 2016-2017; and, (2) to identify the most common nonadherence practices.

Methods: We evaluated all 136 manuscripts published across the 74 orthopaedic journals listed on Scimago Journal & Country Rank that used the NIS from January 2016 through December 2017. Of those studies, 2% (3 of 136) were excluded because NIS was not used for analysis. The studies were evaluated for adherence to seven recommended research practices by the AHRQ: (1) identifying observations as hospitalization events rather than unique patients; (2) not performing state-level analyses; (3) limiting hospital-level analyses to data from year 1988-2011; (4) not performing physician-level analyses; (5) avoiding the use of nonspecific secondary diagnosis codes to infer in-hospital events; (6) using survey-specific analysis methods that account for clustering, stratification, and weighting; and (7) accounting for data changes in trend analyses spanning major transition periods in the data set (1997-1998 and 2011-2012).

Results: Overall, 93% (124 of 133) of the studies did not adhere to one or more practices. For each of the research practices assessed, 80% (106 of 133) of the studies did not account for the clustering and stratification in survey design; 56% (75 of 133) implied records were unique patients rather than hospitalization events; 41% (54 of 133) inappropriately used secondary diagnosis codes to infer in-hospital events.

Conclusions: Nearly all manuscripts published in orthopaedic journals using the NIS database in 2016 and 2017 failed to adhere to recommended research practices. Future research quantifying variations in study results on the basis of adherence to recommended research practices would be of value.

Clinical Relevance: With the ubiquitous presence of large-database studies in orthopaedic journals, our work points to the importance of rigorous methodological appraisal when evaluating results, and encourages journals to require the use of the methodology checklists upon submission of such studies. More research is needed to determine whether deviations from recommended research practices actually lead to biased conclusions that affect patient care and policy-related decisions.
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http://dx.doi.org/10.1097/CORR.0000000000001355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899397PMC
December 2020

Dietary Copper Plays an Important Role in Maintaining Intestinal Barrier Integrity During Alcohol-Induced Liver Disease Through Regulation of the Intestinal HIF-1α Signaling Pathway and Oxidative Stress.

Front Physiol 2020 8;11:369. Epub 2020 May 8.

Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Hepatology Institute of Wenzhou Medical University, Wenzhou, China.

Impaired intestinal barrier function and oxidative stress injury play critical roles in the pathogenesis of alcoholic liver disease (ALD), and recent investigations have revealed a role for dietary copper in the liver and intestinal barrier function. Therefore, the current study investigates the mechanisms and role of dietary copper in alcohol induced liver diseases. C57BL/6 mice were used to create an alcoholic liver disease model with a Lieber-DeCarli diet containing 5% alcohol and were fed with different concentrations of dietary copper of adequate (6 ppm, CuA), marginal (1.5 ppm, CuM), or supplemental (20 ppm, CuS) amounts. Caco-2 cells were also exposed to ethanol and different concentrations of copper. Damages of the liver and intestine were evaluated by transaminases, histology staining, and protein and mRNA level, as well as cell proliferation, oxidative stress, and mitochondrial membrane potential. In animal experiments, the results indicate that an alcohol diet causes liver injury and disruption of intestinal barrier function as well as decreasing the expression of genes such as HIF-1α, occludin, SOD1, and GPX1. Supplemental dietary copper can revert these changes except for SOD1, but marginal dietary copper can worsen these changes. The cell experiments showed that proper copper supplementation can promote cell growth and reduce reactive oxygen species (ROS) production. In conclusion, supplemental dietary copper has beneficial effects on alcohol-induced intestine and liver injury, and marginal dietary copper shows detrimental effects on these parameters.
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http://dx.doi.org/10.3389/fphys.2020.00369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227433PMC
May 2020

An Early Fecal Microbiota Transfer Improves the Intestinal Conditions on Microflora and Immunoglobulin and Antimicrobial Peptides in Piglets.

J Agric Food Chem 2020 Apr 17;68(17):4830-4843. Epub 2020 Apr 17.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, China.

The goal of this study was to investigate the effects of early fecal microbial transfer (FMT) on the microflora of recipient piglets, where Yorkshire newborn piglets and Min sows (an indigenous pig breed in China) were used as the fecal recipients and donors, respectively, to reveal the changes in immunity and development-related functions of the intestinal mucosa driven by FMT. The recipient group was inoculated with fecal microbial fluids from days 1 to 10. On day 21, the relative abundance of the was reduced; the concentrations of immunoglobulin M (IgM) and immunoglobulin G (IgG) in the jejunal mucosa, and that of IgG in the ileal mucosa of the recipient group, were increased ( < 0.05). On day 40, the relative abundance of the s in the recipient group was increased, while that of was decreased. The concentrations of IgG and IgM in the ileal mucosa of the recipient group were increased. FMT protected the intestine by modulating the antimicrobial peptides of the intestinal mucosa ( < 0.05). The results of this study revealed that early FMT can improve the gut microbiota, intestinal mucosal immunity, and intestinal development-related functions of Yorkshire piglets.
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http://dx.doi.org/10.1021/acs.jafc.0c00545DOI Listing
April 2020

Dinuclear Zn Complexes Exhibiting Thermally Activated Delayed Fluorescence and Luminescence Polymorphism.

Chemistry 2020 May 11;26(30):6887-6893. Epub 2020 May 11.

Shenzhen Key Laboratory of Polymer Science and Technology, College of Materials Science and Engineering, Shenzhen University, 1066 Xueyuan Blvd., Shenzhen, 518055, P.R. China.

Zn complexes exhibiting strong emission in the solid state remain scarce, and most of them exhibit only prompt fluorescence. Herein the synthesis, structures, and photoluminescence properties of two Zn complexes containing new donor-acceptor ligands is reported. The new Zn complexes have dinuclear structures in which each metal ion adopts a distorted square-pyramidal geometry. The Zn complexes show strong emission in the solid state with quantum yields up to 50 %. Variable-temperature transient photoluminescence studies revealed an emission mechanism involving prompt and thermally activated delayed fluorescence (TADF). DFT calculations showed well-separated HOMO and LUMO in the ground state and small excited singlet-triplet energy splitting, accounting for the TADF. The complexes also exhibit different emission colors in the as-synthesized powder state and in single crystals, that is, they exhibit luminescence polymorphism. The single-crystal emission is responsive to mechanical grinding and was characterized by powder XRD.
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http://dx.doi.org/10.1002/chem.202000572DOI Listing
May 2020

Aberrant cell segregation in the craniofacial primordium and the emergence of facial dysmorphology in craniofrontonasal syndrome.

PLoS Genet 2020 02 24;16(2):e1008300. Epub 2020 Feb 24.

Program in Craniofacial Biology, University of California San Francisco, San Francisco, California, United States of America.

Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder characterized by craniofacial, skeletal, and neurological anomalies and is caused by mutations in EFNB1. Heterozygous females are more severely affected by CFNS than hemizygous males, a phenomenon called cellular interference that results from EPHRIN-B1 mosaicism. In Efnb1 heterozygous mice, mosaicism for EPHRIN-B1 results in cell sorting and more severe phenotypes than Efnb1 hemizygous males, but how craniofacial dysmorphology arises from cell segregation is unknown and CFNS etiology therefore remains poorly understood. Here, we couple geometric morphometric techniques with temporal and spatial interrogation of embryonic cell segregation in mouse mutant models to elucidate mechanisms underlying CFNS pathogenesis. By generating EPHRIN-B1 mosaicism at different developmental timepoints and in specific cell populations, we find that EPHRIN-B1 regulates cell segregation independently in early neural development and later in craniofacial development, correlating with the emergence of quantitative differences in face shape. Whereas specific craniofacial shape changes are qualitatively similar in Efnb1 heterozygous and hemizygous mutant embryos, heterozygous embryos are quantitatively more severely affected, indicating that Efnb1 mosaicism exacerbates loss of function phenotypes rather than having a neomorphic effect. Notably, neural tissue-specific disruption of Efnb1 does not appear to contribute to CFNS craniofacial dysmorphology, but its disruption within neural crest cell-derived mesenchyme results in phenotypes very similar to widespread loss. EPHRIN-B1 can bind and signal with EPHB1, EPHB2, and EPHB3 receptor tyrosine kinases, but the signaling partner(s) relevant to CFNS are unknown. Geometric morphometric analysis of an allelic series of Ephb1; Ephb2; Ephb3 mutant embryos indicates that EPHB2 and EPHB3 are key receptors mediating Efnb1 hemizygous-like phenotypes, but the complete loss of EPHB1-3 does not fully recapitulate the severity of CFNS-like Efnb1 heterozygosity. Finally, by generating Efnb1+/Δ; Ephb1; Ephb2; Ephb3 quadruple knockout mice, we determine how modulating cumulative receptor activity influences cell segregation in craniofacial development and find that while EPHB2 and EPHB3 play an important role in craniofacial cell segregation, EPHB1 is more important for cell segregation in the brain; surprisingly, complete loss of EPHB1-EPHB3 does not completely abrogate cell segregation. Together, these data advance our understanding of the etiology and signaling interactions underlying CFNS dysmorphology.
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http://dx.doi.org/10.1371/journal.pgen.1008300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058351PMC
February 2020

Effects of Dietary Selenium Deficiency or Excess on Selenoprotein Gene Expression in the Spleen Tissue of Pigs.

Animals (Basel) 2019 Dec 11;9(12). Epub 2019 Dec 11.

Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.

To evaluate the effects of dietary Se deficiency and excess on the mRNA levels of selenoproteins in pig spleen tissues, 20 healthy uncastrated boars (Duroc × Landrace × Yorkshire, 10 ± 0.72 kg) were randomly divided into four groups (5 pigs per group). The pigs were fed a Se deficient corn-soybean basal feed (Se content <0.03 mg/kg) or basal feed with added sodium selenite at 0.3, 1.0, or 3.0 mg Se/kg diet, respectively. The experiment lasted 16 weeks. The spleen tissue was collected to examine the mRNA expression levels of 24 selenoprotein genes at the end of the study. Compared with pigs in other groups, those fed with the 1.0 mg Se/kg diet had higher mRNA levels of glutathione peroxidase 1 (), glutathione peroxidase 2 (), deiodinase type II (), thioredoxin reductase 3 (), selenoprotein H (), selenoprotein N, 1 (), selenoprotein P1 (), and selenoprotein V () in the spleen (p < 0.05). Dietary Se deficiency resulted in lower mRNA levels of , , glutathione peroxidase 3 (), , thioredoxin reductase 2 (), , , selenoprotein I (), selenoprotein K (), selenoprotein M (), , and in the spleen than the other three groups. Dietary Se levels did not affect the mRNA levels of glutathione peroxidase 4 (), deiodinase type I (), deiodinase type III (3), selenophosphate synthetase 2 (), thioredoxin reductase 1 (), selenoprotein O (), selenoprotein S (s), selenoprotein W (), selenoprotein X () and selenoprotein 15 () in the spleen (p > 0.05). Dietary Se levels can affect the transcription levels of 14 selenoprotein genes in the spleen of pigs.
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http://dx.doi.org/10.3390/ani9121122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940954PMC
December 2019

microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation.

J Cell Mol Med 2020 01 6;24(2):1256-1267. Epub 2019 Dec 6.

Department of Infectious Diseases, Wenzhou Key Laboratory of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou, China.

Autoimmune hepatitis (AIH) is a chronic liver disease due to autoimmune system attacks hepatocytes and causes inflammation and fibrosis. Intracellular signalling and miRNA may play an important role in regulation of liver injury. This study aimed to investigate the potential roles of microRNA 143 in a murine AIH model and a hepatocyte injury model. Murine AIH model was induced by hepatic antigen S100, and hepatocyte injury model was induced by LPS. Mice and AML12 cells were separated into six groups with or without the treatment of miRNA-143. Inflammation and fibrosis as well as gene expression were examined by different cellular and molecular techniques. The model was successfully established with the elevation of ALT and AST as well as inflammatory and fibrotic markers. Infection or transfection of mir-143 in mice or hepatocytes significantly attenuated the development of alleviation of hepatocyte injury. Moreover, the study demonstrated phosphorylation of TAK1-mediated miRNA-143 regulation of hepatic inflammation and fibrosis as well as hepatocyte injury. Our studies demonstrated a significant role of miRNA-143 in attenuation of liver injury in AIH mice and hepatocytes. miRNA-143 regulates inflammation and fibrosis through its regulation of TAK1 phosphorylation, which warrants TAK1 as a target for the development of new therapeutic strategy of autoimmune hepatitis.
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http://dx.doi.org/10.1111/jcmm.14750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991639PMC
January 2020

Toxicity of glyphosate in feed for weanling piglets and the mechanism of glyphosate detoxification by the liver nuclear receptor CAR/PXR pathway.

J Hazard Mater 2020 04 16;387:121707. Epub 2019 Nov 16.

Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address:

Glyphosate (GLP), the most widely used and productive pesticide worldwide, which safety and reliability gradually become a social concern. It is important to explore the toxic of GLP on the limitation level by governments on piglets and the potential role of hepatic CAR/PXR and Keap1-Nrf2 pathways in low levels of glyphosate detoxification. Compared with the control group, the production performance and organ index of GLP group showed no significant change. However, the liver GLP residue of 40 mg/kg group was significantly higher than the control group. We also found that the activity of ALP increased linearly and DBIL content increased quadratically. Furthermore, GLP could significantly increase SOD and GSH-Px and decrease T-AOC and CAT activities and significantly increase MDA and HO contents (P < 0.05); however, the genes expression of Keap1/Nrf2 pathway was not affected. Gene expression of CAR/PXR pathway showed that GLP could significantly stimulate the expression of CAR, but it could not affect the expression of phase Ⅰ (CYP1A1, CYP1A2, CYP2E1, CYP2A19, CYP3A29), phase Ⅱ (UGT1A6, GSTA1, GSTA2) detoxification enzymes and transporters (MDR1, MRP2, P-gp). Our study showed that although 10-40 mg/kg GLP would inevitably cause some liver damage and dysfunction, it can self-alleviating the toxic effect of GLP.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121707DOI Listing
April 2020

Circulating Tumor Cells Exhibit Metastatic Tropism and Reveal Brain Metastasis Drivers.

Cancer Discov 2020 01 10;10(1):86-103. Epub 2019 Oct 10.

Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California.

Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTC) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide a unique patient biopsy resource to decipher the cellular subpopulations that initiate metastasis and their molecular properties. However, one crucial question is whether CTCs derived and expanded from patients recapitulate human metastatic disease in an animal model. Here, we show that CTC lines established from patients with breast cancer are capable of generating metastases in mice with a pattern recapitulating most major organs from corresponding patients. Genome-wide sequencing analyses of metastatic variants identified semaphorin 4D as a regulator of tumor cell transmigration through the blood-brain barrier and MYC as a crucial regulator for the adaptation of disseminated tumor cells to the activated brain microenvironment. These data provide the direct experimental evidence of the promising role of CTCs as a prognostic factor for site-specific metastasis. SIGNIFICANCE: Interests abound in gaining new knowledge of the physiopathology of brain metastasis. In a direct metastatic tropism analysis, we demonstrated that -cultured CTCs from 4 patients with breast cancer showed organotropism, revealing molecular features that allow a subset of CTCs to enter and grow in the brain..
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http://dx.doi.org/10.1158/2159-8290.CD-19-0384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954305PMC
January 2020

Poor Access to Breast Reconstruction: A Geographical Shortage of Plastic Surgeons Relative to Breast Surgeons in the United States.

Ann Plast Surg 2019 04;82(4S Suppl 3):S256-S258

Department of Surgical Oncology, Avera Medical Group Comprehensive Breast Care, Sioux Falls, SD.

Background: Breast cancer surgery involves removal of cancer performed by a breast surgeon and reconstruction performed by a plastic surgeon. Historically, many women have not undergone breast reconstruction surgery (BRS), with current literature suggesting that geographic barriers may play a role. Our objective was to determine if there is a geographic shortage of plastic surgeons in the United States and to assess for trends in access to BRS for rural, suburban, and urban populations.

Methods: A database investigation of the 2018 membership for the American Society of Breast Surgeons and the American Society of Plastic Surgeons was performed. We searched for a breast surgeon's geographic presence by zip code and looked for the presence of a plastic surgeon within 10 and 20 miles. Zip codes were then categorized as urban, suburban, or rural. Within each population category, the average numbers of breast surgeons and plastic surgeons were quantified.

Results: Twenty-five percent of breast surgeon zip codes had no plastic surgeons located within 10 miles; 10% of breast surgeon zip codes had no plastic surgeon within 20 miles. There were on average 7.03 breast surgeons in each urbanized area. Suburban and rural areas had an average of 1.14 and 1.00 breast surgeons, respectively. There were on average 10.97 plastic surgeons per urbanized area. Suburban and rural areas had, on average, 0.23 and 0.06 plastic surgeons, respectively.

Conclusions: A national comparison of the geographical distribution between breast surgeons and plastic surgeons indicates a shortage of plastic surgeons, especially in rural and suburban areas.
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http://dx.doi.org/10.1097/SAP.0000000000001846DOI Listing
April 2019

Sensitivity to splicing modulation of BCL2 family genes defines cancer therapeutic strategies for splicing modulators.

Nat Commun 2019 01 11;10(1):137. Epub 2019 Jan 11.

H3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA, 02139, USA.

Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly recognized as a hallmark of cancer. Small molecule splicing modulators have been introduced into clinical trials to treat solid tumors or leukemia bearing recurrent spliceosome mutations. Nevertheless, further investigation of the molecular mechanisms that may enlighten therapeutic strategies for splicing modulators is highly desired. Here, using unbiased functional approaches, we report that the sensitivity to splicing modulation of the anti-apoptotic BCL2 family genes is a key mechanism underlying preferential cytotoxicity induced by the SF3b-targeting splicing modulator E7107. While BCL2A1, BCL2L2 and MCL1 are prone to splicing perturbation, BCL2L1 exhibits resistance to E7107-induced splicing modulation. Consequently, E7107 selectively induces apoptosis in BCL2A1-dependent melanoma cells and MCL1-dependent NSCLC cells. Furthermore, combination of BCLxL (BCL2L1-encoded) inhibitors and E7107 remarkably enhances cytotoxicity in cancer cells. These findings inform mechanism-based approaches to the future clinical development of splicing modulators in cancer treatment.
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http://dx.doi.org/10.1038/s41467-018-08150-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329755PMC
January 2019

Different Types and Acceptability of Psychotherapies for Acute Anxiety Disorders in Children and Adolescents: A Network Meta-analysis.

JAMA Psychiatry 2019 01;76(1):41-50

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Importance: Anxiety disorders are common in children and adolescents, and uncertainty remains regarding the optimal strategy of psychotherapies in this population.

Objective: To compare and rank the different types of psychotherapies and the different ways of delivering psychological treatments for anxiety disorders in children and adolescents.

Data Sources: PubMed, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ProQuest Dissertations, LILACS (Literatura Latino Americana em Ciências da Saúde), international trial registers, and US Food and Drug Administration reports were searched from inception to November 30, 2017.

Study Selection: Randomized clinical trials that compared any structured psychotherapy with another psychotherapy or a control condition for anxiety disorders in children and adolescents were selected.

Data Extraction And Synthesis: Four researchers independently performed data extraction and quality assessment. Pairwise meta-analyses and Bayesian network meta-analysis within the random-effects model were used to synthesize data.

Main Outcomes And Measures: Efficacy (change in anxiety symptoms) posttreatment and at follow-up, acceptability (all-cause discontinuation), and quality of life and functional improvement were measured. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results: A total of 101 unique trials including 6625 unique participants compared 11 different psychotherapies with 4 specific control conditions. The certainty of evidence was rated as low or very low for most comparisons. For efficacy, most psychotherapies were significantly more effective than the wait list condition posttreatment (standardized mean difference [SMD], -1.43 to -0.61) and at the longest follow-up (SMD, -1.84 to -1.64). However, only group cognitive behavioral therapy (CBT) was significantly more effective than the other psychotherapies and all control conditions posttreatment. For acceptability, bibliotherapy CBT had significantly more all-cause discontinuations than some psychotherapies and control conditions (range of odds ratios, 2.48-9.32). In terms of quality of life and functional improvement, CBT (delivered in different ways) was significantly beneficial compared with psychological placebo and the wait list condition (SMDs, 0.73 to 1.99).

Conclusions And Relevance: Group CBT would be the more appropriate choice of psychotherapy for anxiety disorders in children and adolescents, based on these findings. Other types of psychotherapies and different ways of delivering psychological treatment can be alternative options. Further research is needed to explore specific anxiety disorders, disorder-specific psychotherapy, and moderators of treatment effect.

Trial Registration: PROSPERO Identifier: CRD42015016283.
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http://dx.doi.org/10.1001/jamapsychiatry.2018.3070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583467PMC
January 2019

A Novel Method of Emergency Situation Detection for a Brain-Controlled Vehicle by Combining EEG Signals With Surrounding Information.

IEEE Trans Neural Syst Rehabil Eng 2018 10 4;26(10):1926-1934. Epub 2018 Sep 4.

In this paper, to address the safety of brain-controlled vehicles under emergency situations, we propose a novel method of emergency situation detection by fusing driver electroencephalography (EEG) signals with surrounding information. We first build a novel EEG-based detection model of driver emergency braking intention. We then recognize emergency situations by fusing the result of the proposed EEG-based intention detection model with that of the obstacle detection model based on surrounding information. The real-time detection system of driver emergency braking intention is implemented on an embedded system, and the driver-and-hardware-in-the-loop-experiment of the proposed detection method of emergency situations is performed. Experimental results show that the proposed method can detect emergency situations with the system accuracy of 94.89%, false alarm rate of 0.05%, and response time of 540 ms. This paper has important values in the future development of brain-controlled vehicles, human-centric advanced driver assistant systems, and self-driving vehicles and opens a new avenue on how cognitive neuroscience may be applied to human-machine integration.
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http://dx.doi.org/10.1109/TNSRE.2018.2868486DOI Listing
October 2018

Inosine alleviates depression-like behavior and increases the activity of the ERK-CREB signaling in adolescent male rats.

Neuroreport 2018 09;29(14):1223-1229

Neurology, The First Affiliated Hospital of Chongqing Medical University.

Inosine, a major breakdown product of adenosine by the enzyme adenosine deaminase, binds to adenosine receptors and initiates intracellular signaling events. Adenosine and inosine have already been described as capable of modulating depression-like behavior in adult rodent model. In this study, we investigated the antidepressant-like effect of inosine, acutely administered (10 or 50 mg/kg, intraperitoneal), in postnatal day 28 male Sprague-Dawley rats. The effects of inosine were assessed using the forced swimming test and locomotor activity test. Changes in the extracellular signal-regulated kinases (ERK)-cyclic AMP response element binding protein (CREB) signaling pathway in the hippocampus and prefrontal cortex were examined by western blot analysis. The results showed that inosine had an antidepressant-like effect in the forced swimming test in adolescent rats without affecting locomotor activity. Furthermore, we found that inosine increased the activity of ERK and CREB in the hippocampus and prefrontal cortex. Inosine administered intraperitoneally may alleviate depression-like behaviors in adolescent rats, and the ERK-CREB signal system may be the target of the antidepressant action of inosine.
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http://dx.doi.org/10.1097/WNR.0000000000001101DOI Listing
September 2018

Efficacy and acceptability of psychological interventions for social anxiety disorder in children and adolescents: a meta-analysis of randomized controlled trials.

Eur Child Adolesc Psychiatry 2019 Jan 13;28(1):79-89. Epub 2018 Jul 13.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People's Republic of China.

Social anxiety disorder (SAD) is highly prevalent and persistent in children and adolescents. However, evidence for the efficacy and acceptability of psychological interventions for SAD in children and adolescents remains unclear. Seven electronic databases (PubMed, CENTRAL, Embase, Web of Science, PsycINFO, CINAHL, and ProQuest) were searched. Randomized controlled trials (RCTs) that compared psychological interventions for SAD with control conditions in children and adolescents were included. Primary outcomes were the efficacy (mean change in anxiety symptom scores) and acceptability (dropouts for all reasons). Secondary outcomes were remission, quality of life/functional improvement, and depressive symptoms measures. Seventeen RCTs were included in this meta-analysis. Psychological interventions (including cognitive behavioral therapy and behavioral therapy) were significantly more effective than control conditions, with a standardized mean difference (SMD) of - 1.13, and remission with a risk ratio (RR) of 8.99, the number needed to treat was 3.3. There was no statistically significant difference between psychological interventions and control conditions for all-cause dropouts (RR = 1.00). Psychological interventions were superior to control conditions in improving quality of life/functioning (SMD = 0.79) and reducing depressive symptoms (SMD = - 0.39). Given considerable heterogeneity of primary efficacy outcome, a series of subgroup analyses of different variables were conducted. Psychological interventions are probably efficacious in the treatment of SAD among children and adolescents, and may markedly improve quality of life and functioning in this population. However, this finding should be interpreted with caution because of the high heterogeneity of trials and low literature quality.
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http://dx.doi.org/10.1007/s00787-018-1189-xDOI Listing
January 2019

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types.

Cell Rep 2018 04;23(1):282-296.e4

H3 Biomedicine, Inc., 300 Technology Square, Cambridge, MA 02139, USA. Electronic address:

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis.
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http://dx.doi.org/10.1016/j.celrep.2018.01.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933844PMC
April 2018