bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjunctive metformin for antipsychotic-induced dyslipidemia: a meta-analysis of randomized, double-blind, placebo-controlled trials
Authors: Jiang Wen-Long , Cai Dong-Bin , Yin Fei , Zhang Ling , Zhao Xi-Wu , He Jie , Ng Chee H. , Ungvari Gabor S. , Sim Kang , Hu Mei-Ling , Zheng Wei , Xiang Yu-Tao 
Published: April 2020

AbstractAntipsychotic-induced dyslipidemia could increase the risk of cardiovascular diseases. This is a meta-analysis of randomized double-blind placebo-controlled trials to examine the efficacy and safety of adjunctive metformin for dyslipidemia induced by antipsychotics in schizophrenia. The standardized mean differences (SMDs) and risk ratios (RRs) with their 95% confidence intervals (CIs) were calculated using the random-effects model with the RevMan 5.3 version software. The primary outcome was the change of serum lipid level. Twelve studies with 1215 schizophrenia patients (592 in metformin group and 623 in placebo group) were included and analyzed. Adjunctive metformin was significantly superior to placebo with regards to low density lipoprotein cholesterol (LDL-C) [SMD: −0.37 (95%CI:−0.69, −0.05),P = 0.02;I2 = 78%], total cholesterol [SMD: −0.47 (95%CI:−0.66, −0.29),P < 0.00001;I2 = 49%], triglyceride [SMD: −0.33 (95%CI:−0.45, −0.20),P < 0.00001;I2 = 0%], and high density lipoprotein cholesterol [SMD: 0.29 (95%CI:0.02, 0.57),P = 0.03;I2 = 69%]. The superiority of metformin in improving LDL-C level disappeared in a sensitivity analysis and 80% (8/10) of subgroup analyses. Metformin was significantly superior to placebo with regards to decrease in body weight, body mass index, glycated hemoglobin A1c, fasting insulin, and homeostasis model assessment-insulin resistance (P = 0.002–0.01), but not regarding changes in waist circumference, waist-to-hip rate, leptin, fasting glucose, and blood pressure (P = 0.07–0.33). The rates of discontinuation due to any reason [RR: 0.97 (95%CI: 0.66, 1.43),P = 0.89;I2 = 0%] was similar between the two groups. Adjunctive metformin could be useful to improve total cholesterol and triglyceride levels, but it was not effective in improving LDL-C level in schizophrenia.
Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
Authors: Lewis Charles P. , Port John D. , Blacker Caren J. , Sonmez A. Irem , Seewoo Bhedita J. , Leffler Jarrod M. , Frye Mark A. , Croarkin Paul E. 
Published: April 2020

AbstractThe anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy (1H-MRS) at 3 T, utilizing a 2-dimensionalJ-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluid-corrected ACC metabolite concentrations were compared between healthy control (HC,n = 16), depressed without SI (Dep/SI−,n = 13), and depressed with SI (Dep/SI+,n = 11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and theN-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI− and Dep/SI+ adolescents. Dep/SI+ adolescents had higher Glx than Dep/SI− participants (padj = 0.012) and had lower NAA/Glx than both Dep/SI− (padj = 0.002) and HC adolescents (padj = 0.039). There were significant relationships between SI intensity and Glx (pFDR = 0.026), SI severity and NAA/Glx (pFDR = 0.012), and SI intensity and NAA/Glx (pFDR = 0.004). ACC Glx and NAA/Glx discriminated Dep/SI− from Dep/SI+ participants. Uncoupled NAA−glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior.
On the diagnostic and neurobiological origins of bipolar disorder
Authors: Charney Alexander W. , Mullins Niamh , Park You Jeong , Xu Jonathan 
Published: April 2020

AbstractPsychiatry is constructed around a taxonomy of several hundred diagnoses differentiated by nuances in the timing, co-occurrence, and severity of symptoms. Bipolar disorder (BD) is notable among these diagnoses for manic, depressive, and psychotic symptoms all being core features. Here, we trace current understanding of the neurobiological origins of BD and related diagnoses. To provide context, we begin by exploring the historical origins of psychiatric taxonomy. We then illustrate how key discoveries in pharmacology and neuroscience gave rise to a generation of neurobiological hypotheses about the origins of these disorders that facilitated therapeutic innovation but failed to explain disease pathogenesis. Lastly, we examine the extent to which genetics has succeeded in filling this void and contributing to the construction of an objective classification of psychiatric disturbance.
Emerging role of PTEN loss in evasion of the immune response to tumours
Authors: Vidotto Thiago , Melo Camila Morais , Castelli Erick , Koti Madhuri , dos Reis Rodolfo Borges , Squire Jeremy A. 
Published: April 2020

AbstractMutations inPTENactivate the phosphoinositide 3-kinase (PI3K) signalling network, leading to many of the characteristic phenotypic changes of cancer. However, the primary effects of this gene on oncogenesis through control of the PI3K–AKT–mammalian target of rapamycin (mTOR) pathway might not be the only avenue by which PTEN affects tumour progression. PTEN has been shown to regulate the antiviral interferon network and thus alter how cancer cells communicate with and are targeted by immune cells. An active, T cell-infiltrated microenvironment is critical for immunotherapy success, which is also influenced by mutations in DNA damage repair pathways and the overall mutational burden of the tumour. As PTEN has a role in the maintenance of genomic integrity, it is likely that a loss of PTEN affects the immune response at two different levels and might therefore be instrumental in mediating failed responses to immunotherapy. In this review, we summarise findings that demonstrate how the loss of PTEN function elicits specific changes in the immune response in several types of cancer. We also discuss ongoing clinical trials that illustrate the potential utility of PTEN as a predictive biomarker for immune checkpoint blockade therapies.
The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer
Authors: Zhang Jinrui , Liu Shuyan , Li Qiong , Shi Yulin , Wu Yueguang , Liu Fang , Wang Shanshan , Zaky Mohamed Y. , Yousuf Waleed , Sun Qianhui , Guo Dong , Wang Taishu , Zhang Yingqiu , Wang Yang , Li Man , Liu Han 
Published: April 2020

AbstractErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Although multiple HSP90 inhibitors have been demonstrated to effectively trigger ErbB2 degradation, none succeeded in the clinical evaluations. To develop novel ErbB2-targeting strategies, we investigated the endocytic degradation and reversible ubiquitylation of ErbB2 in breast cancer. In this study, we reveal that HSP90 inhibition leads to efficient ubiquitylation and endocytic degradation of ErbB2 through the canonical endo-lysosomal route. USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity. Accordingly, the USP2 inhibitor ML364 is capable of inducing ErbB2 ubiquitylation and accelerating its turnover. ML364 potentiates the pro-degradation effects of HSP90 inhibitors on ErbB2 and hence sensitizes ErbB2-positive breast cancer cells to HSP90 inhibition. The combination of USP2 and HSP90 inhibitors effectively restrains ErbB2-positive breast cancer xenograft growth in vivo. Based on these observations, we conclude that USP2 safeguards ErbB2 surface levels by antagonizing its ubiquitylation-mediated endocytic degradation, which can be exploited to design novel therapeutic strategies against ErbB2-driven malignancies as combinatorial treatment with HSP90 inhibitors.
Interplay of Calcium and Nitric Oxide in improvement of Growth and Arsenic-induced Toxicity in Mustard Seedlings
Authors: Singh Rachana , Parihar Parul , Prasad Sheo Mohan 
Published: April 2020

AbstractIn this study, Ca2+ mediated NO signalling was studied in response to metalloid (As) stress in Brassica seedlings. Arsenic toxicity strongly suppressed the growth (fresh weight, root and shoot length), photosynthetic pigments, Chl a fluorescence indices (Kinetic traits: Fv, Fm, Fv/Fo, Fm/Fo, ФPo or Fv/Fm, Ψo, ФEo, PIABS, Area and N and redox status (AsA/DHA and GSH/GSSG ratios) of the cell; whereas energy flux traits: ABS/RC, TRo/RC, ETo/RC and DIo/RC along with Fo, Fo/Fv, Fo/Fm, ФDo and Sm) were enhanced. Further, addition of EGTA (Ca2+ scavenger) and LaCl3 (plasma membrane Ca2+ channel blocker) to As + Ca; while c‒PTIO (NO scavenger) and l‒NAME (NO synthase inhibitor) to As + SNP treated seedlings, siezed recovery on above parameters caused due to Ca2+ and NO supplementation, respectively to As stressed seedlings thereby indicating their signalling behaviour. Further, to investigate the link between Ca2+ and NO, when c‒PTIO and l‒NAME individually as well as in combination were supplemented to As + Ca treated seedlings; a sharp inhibition in above mentioned traits was observed even in presence of Ca2+, thereby signifying that NO plays crucial role in Ca2+ mediated signalling. In addition, As accumulation, ROS and their indices, antioxidant system, NO accumulation and thiol compounds were also studied that showed varied results.
Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats
Authors: Lucero Claudia M. , Andrade David C. , Toledo Camilo , Díaz Hugo S. , Pereyra Katherin V. , Diaz-Jara Esteban , Schwarz Karla G. , Marcus Noah J. , Retamal Mauricio A. , Quintanilla Rodrigo A. , Del Rio Rodrigo 
Published: April 2020

AbstractAlterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-ShuntGap27or AV-ShuntScr) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8thweek, AV-ShuntGap27showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-ShuntGap27showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-ShuntScr. Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.
A density functional theory study of high-performance pre-lithiated MS2 (M = Mo, W, V) Monolayers as the Anode Material of Lithium Ion Batteries
Authors: Liu Tingfeng , Jin Zhong , Liu Dong-Xin , Du Chunmiao , Wang Lu , Lin Haiping , Li Youyong 
Published: April 2020

AbstractRecent experimental study shows that the pre-lithiated MoS2 monolayer exhibits an enhanced electrochemical performance, coulombic efficiency of which is 26% higher than the pristine MoS2 based anode. The underlying mechanism of such significant enhancement, however, has not yet been addressed. By means of density functional theory (DFT) calculations, we systematically investigated the adsorption and diffusion behavior of lithium (Li) atoms on the MS2 (M = Mo, W, V) monolayers. On the pre-lithiated MS2 monolayers, the adsorption energy of extra Li ions are not significantly changed, implying the feasibility of multilayer adsorption. Of importance, the Li diffusion barriers on pre-lithiated MS2 are negligibly small because of the charge accumulation between the diffusing Li ions and the pre-lithiating Li layer. Correspondingly, we report that the pre-lithiation should be a general treatment which can be employed on many transition-metal di-chalcogenides to improve their storage capacities and charge-discharge performance in Li ion batteries. In addition, we propose that the pre-lithiated VS2 may serve as an outstanding anode material in LIBs.
Effects of delayed intraventricular TLR7 agonist administration on long-term neurological outcome following asphyxia in the preterm fetal sheep
Authors: Cho Kenta H. T. , Zeng Nina , Anekal Praju V. , Xu Bing , Fraser Mhoyra 
Published: April 2020

AbstractIn the preterm brain, accumulating evidence suggests toll-like receptors (TLRs) are key mediators of the downstream inflammatory pathways triggered by hypoxia-ischemia (HI), which have the potential to exacerbate or ameliorate injury. Recently we demonstrated that central acute administration of the TLR7 agonist Gardiquimod (GDQ) confers neuroprotection in the preterm fetal sheep at 3 days post-asphyxial recovery. However, it is unknown whether GDQ can afford long-term protection. To address this, we examined the long-term effects of GDQ. Briefly, fetal sheep (0.7 gestation) received sham asphyxia or asphyxia induced by umbilical cord occlusion, and were studied for 7 days recovery. Intracerebroventricular (ICV) infusion of GDQ (total dose 3.34 mg) or vehicle was performed from 1–4 hours after asphyxia. GDQ was associated with a robust increase in concentration of tumor necrosis factor-(TNF)-α in the fetal plasma, and interleukin-(IL)-10 in both the fetal plasma and cerebrospinal fluid. GDQ did not significantly change the number of total and immature/mature oligodendrocytes within the periventricular and intragyral white matter. No changes were observed in astroglial and microglial numbers and proliferating cells in both white matter regions. GDQ increased neuronal survival in the CA4 region of the hippocampus, but was associated with exacerbated neuronal injury within the caudate nucleus. In conclusion, our data suggest delayed acute ICV administration of GDQ after severe HI in the developing brain may not support long-term neuroprotection.
Darier disease is associated with heart failure: a cross-sectional case-control and population based study
Authors: Bachar-Wikstrom Etty , Curman Philip , Ahanian Tara , Leong Ivone U. S. , Larsson Henrik , Cederlöf Martin , Wikstrom Jakob D. 
Published: April 2020

AbstractHuman data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in heart disease is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum Ca2+ ATPase isoform 2 (SERCA2), which causes calcium dyshomeostasis and ER stress. We hypothesized that DD patients would have an increased risk for common heart disease. We performed a cross-sectional case-control clinical study on 25 DD patients and 25 matched controls; and a population-based cohort study on 935 subjects with DD and matched comparison subjects. Main outcomes and measures were N-terminal pro-brain natriuretic peptide, ECG and heart diagnosis (myocardial infarction, heart failure and arrythmia). DD subjects showed normal clinical heart phenotype including heart failure markers and ECG. The risk for heart failure was 1.59 (1,16-2,19) times elevated in DD subjects, while no major differences were found in myocardial infarcation or arrhythmias. Risk for heart failure when corrected for cardivascular risk factors or alcohol misuse was 1.53 (1.11–2.11) and 1.58 (1,15–2,18) respectively. Notably, heart failure occurred several years earlier in DD patients as compared to controls. We conclude that DD patients show a disease specific increased risk of heart failure which should be taken into account in patient management. The observation also strenghtens the clinical evidence on the important role of SERCA2 in heart failure pathophysiology.
High temperatures alter cross-over distribution and induce male meiotic restitution in Arabidopsis thaliana
Authors: De Storme Nico , Geelen Danny 
Published: April 2020

AbstractPlant fertility is highly sensitive to elevated temperature. Here, we report that hot spells induce the formation of dyads and triads by disrupting the biogenesis or stability of the radial microtubule arrays (RMAs) at telophase II. Heat-induced meiotic restitution inArabidopsisis predominantly SDR-type (Second Division Restitution) indicating specific interference with RMAs formed between separated sister chromatids. In addition, elevated temperatures caused distinct deviations in cross-over formation in male meiosis. Synapsis at pachytene was impaired and the obligate cross-over per chromosome was discarded, resulting in partial univalency in meiosis I (MI). At diakinesis, interconnections between non-homologous chromosomes tied separate bivalents together, suggesting heat induces ectopic events of non-homologous recombination. Summarized, heat interferes with male meiotic cross-over designation and cell wall formation, providing a mechanistic basis for plant karyotype change and genome evolution under high temperature conditions.
Harnessing C/N balance of Chromochloris zofingiensis to overcome the potential conflict in microalgal production
Authors: Sun Han , Ren Yuanyuan , Mao Xuemei , Li Xiaojie , Zhang Huaiyuan , Lao Yongmin , Chen Feng 
Published: April 2020

AbstractAccumulation of high-value products in microalgae is not conducive with rapid cell growth, which is the potential conflict in microalgal production. Overcoming such conflict faces numerous challenges in comprehensively understanding cell behavior and metabolism. Here, we show a fully integrated interaction between cell behavior, carbon partitioning, carbon availability and path rate of central carbon metabolism, and have practically overcome the production conflict of Chromochloris zofingiensis. We demonstrate that elevated carbon availability and active path rate of precursors are determinants for product biosynthesis, and the former exhibits a superior potential. As protein content reaches a threshold value to confer survival advantages, carbon availability becomes the major limiting factor for product biosynthesis and cell reproduction. Based on integrated interaction, regulating the C/N balance by feeding carbon source under excess light increases content of high-value products without inhibiting cell growth. Our findings provide a new orientation to achieve great productivity improvements in microalgal production.
Evidence that levels of nine essential metals in post-mortem human-Alzheimer’s-brain andex vivorat-brain tissues are unaffected by differences in post-mortem delay, age, disease staging, and brain bank location
Authors: Scholefield Melissa , Church Stephanie J , Xu Jingshu , Kassab Sarah , Gardiner Natalie J , Roncaroli Federico , Hooper Nigel M , Unwin Richard D , Cooper Garth J S 
Published: April 2020

AbstractStudies of neurodegenerative conditions such as Alzheimer’s disease (AD) using post mortem brain tissues have uncovered several perturbations in metals such as copper, iron, and zinc. However, studies of the effects of key, potentially confounding variables on these tissues are currently lacking. Moreover, human-brain tissues have limited availability, further enhancing the difficulty of matching potentially-significant variables including age, sex-matching, post-mortem delay (PMD), and neuropathological stage. This study aimed to investigate the effects of such factors and how they might influence metal concentrations in post-mortem brains. Cingulate gyrus from AD cases and matched controls was obtained from two brain banks, based in Auckland, New Zealand and Manchester, UK. Inductively-coupled plasma mass spectrometry (ICP-MS) was employed to measure levels of nine essential metals in brain tissues, and compared concentrations between cases and controls, and between cohorts, to analyse effects of age, sex, Braak stage, brain weight, and PMD. The same methods were used to investigate the effects of PMD under more controlled conditions using ex vivo healthy adult rat-brain tissue. Metal concentrations in human brain were found to be unmodified by differences in age, sex-matching, Braak stage, brain weight, and PMD between cohorts. Some metals were, however, found to vary significantly across different regions in rat brains. These results indicate that investigations of metal homeostasis in AD and other neurodegenerative conditions can be reliably performed using brain tissues without confounding by varying PMD, age, sex-matching, brain weight, and Braak stage. However, regions of study should be selected carefully.
Bacterial association and comparison between lung and intestine in rats
Authors: Liu Tian-hao , Zhang Chen-yang , Din Ahmad Ud , Li Ning , Wang Qian , Yu Jing-ze , Xu Zhen-yuan , Li Chen-xi , Zhang Xiao-mei , Yuan Jia-li , Chen Li-guo , Yang Zhong-shan 
Published: April 2020

AbstractThe association between lung and intestine has already been reported, but the differences in community structures or functions between lung and intestine bacteria yet need to explore. To explore the differences in community structures or functions, the lung tissues and fecal contents in rats were collected and analyzed through 16S rRNA sequencing. It was found that intestine bacteria was more abundant and diverse than lung bacteria. In intestine bacteria, Firmicutes and Bacteroides were identified as major phyla while Lactobacillus was among the most abundant genus. However, in lung the major identified phylum was Proteobacteria and genus Pseudomonas was most prominent genus. On the other hand, in contrast the lung bacteria was more concentrated in cytoskeleton and function in energy production and conversion. While, intestine bacteria were enriched in RNA processing, modification chromatin structure, dynamics and amino acid metabolism. The study provides the basis for understanding the relationships between lung and intestine bacteria.