Cerebral dominance representation of directed connectivity within and between left-right hemispheres and frontal-posterior lobes in mild cognitive impairment.

Electroencephalography can assess connectivity between brain hemispheres, potentially influencing cognitive functions. Much of the existing electroencephalography research primarily focuses on undirected connectivity, leaving uncertainties about directed connectivity alterations between left-right brain hemispheres or frontal-posterior lobes in mild cognitive impairment. We analyzed resting-state electroencephalography data from 34 mild cognitive impairment individuals and 23 normal controls using directed transfer function and graph theory for directed network analysis. Concerning the dominance within left-right hemispheres or frontal-posterior lobes, the mild cognitive impairment group exhibited decreased connectivity within the frontal compared with posterior brain regions in the delta and theta bands. Regarding the dominance between the brain hemispheres or lobes, the mild cognitive impairment group showed reduced connectivity from the posterior to the frontal regions versus the reverse direction in the same bands. Among all participants, the intra-lobe frontal-posterior dominance correlated positively with executive function in the delta and alpha bands. Inter-lobe dominance between frontal and posterior regions also positively correlated with executive function, attention, and language in the delta band. Additionally, interhemispheric dominance between the left and right hemispheres positively correlated with attention in delta and theta bands. These findings suggest altered cerebral dominance in mild cognitive impairment, potentially serving as electrophysiological markers for neurocognitive disorders.

A Stable and Scalable Digital Composite Neurocognitive Test for Early Dementia Screening Based on Machine Learning: Model Development and Validation Study.

BACKGROUND: Dementia has become a major public health concern due to its heavy disease burden. Mild cognitive impairment (MCI) is a transitional stage between healthy aging and dementia. Early identification of MCI is an essential step in dementia prevention. OBJECTIVE: Based on machine learning (ML) methods, this study aimed to develop and validate a stable and scalable panel of cognitive tests for the early detection of MCI and dementia based on the Chinese Neuropsychological Consensus Battery (CNCB) in the Chinese Neuropsychological Normative Project (CN-NORM) cohort. METHODS: CN-NORM was a nationwide, multicenter study conducted in China with 871 participants, including an MCI group (n=327, 37.5%), a dementia group (n=186, 21.4%), and a cognitively normal (CN) group (n=358, 41.1%). We used the following 4 algorithms to select candidate variables: the F-score according to the SelectKBest method, the area under the curve (AUC) from logistic regression (LR), P values from the logit method, and backward stepwise elimination. Different models were constructed after considering the administration duration and complexity of combinations of various tests. Receiver operating characteristic curve and AUC metrics were used to evaluate the discriminative ability of the models via stratified sampling cross-validation and LR and support vector classification (SVC) algorithms. This model was further validated in the Alzheimer's Disease Neuroimaging Initiative phase 3 (ADNI-3) cohort (N=743), which included 416 (56%) CN subjects, 237 (31.9%) patients with MCI, and 90 (12.1%) patients with dementia. RESULTS: Except for social cognition, all other domains in the CNCB differed between the MCI and CN groups (P<.008). In feature selection results regarding discrimination between the MCI and CN groups, the Hopkins Verbal Learning Test-5 minutes Recall had the best performance, with the highest mean AUC of up to 0.80 (SD 0.02) and an F-score of up to 258.70. The scalability of model 5 (Hopkins Verbal Learning Test-5 minutes Recall and Trail Making Test-B) was the lowest. Model 5 achieved a higher level of discrimination than the Hong Kong Brief Cognitive test score in distinguishing between the MCI and CN groups (P<.05). Model 5 also provided the highest sensitivity of up to 0.82 (range 0.72-0.92) and 0.83 (range 0.75-0.91) according to LR and SVC, respectively. This model yielded a similar robust discriminative performance in the ADNI-3 cohort regarding differentiation between the MCI and CN groups, with a mean AUC of up to 0.81 (SD 0) according to both LR and SVC algorithms. CONCLUSIONS: We developed a stable and scalable composite neurocognitive test based on ML that could differentiate not only between patients with MCI and controls but also between patients with different stages of cognitive impairment. This composite neurocognitive test is a feasible and practical digital biomarker that can potentially be used in large-scale cognitive screening and intervention studies.

Excessive sleep increased the risk of incidence of cognitive impairment among older Chinese adults: a cohort study based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

STUDY OBJECTIVES: Based on a cohort from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we aimed to evaluate the relationship between sleep duration and the incidence of cognitive impairment among older Chinese adults. METHODS: We conducted a prospective analysis based on 3692 participants from the CLHLS at baseline (in 2011), and as a 3-year follow-up (till 2014), 531 participants (14.4%) had cognitive impairment, which was defined as a Mini-Mental State Examination score <24. Sleep duration was classified into three groups: short (≤5 hours/day), normal (>5 but <10 hours), and long (≥10 hours/day). A logistic regression model was used to examine the association between baseline sleep duration and cognitive impairment after adjusting for sociodemographic data, living habits, and health conditions. RESULTS: Five hundred sixty-two participants (15.2%) were in the short-duration group, and 608 participants (16.5%) were in the long-duration group. After adjusting for multiple potential confounders, compared with normal sleep duration, long sleep duration was associated with the incidence of cognitive impairment (OR = 1.309, 95% CI: 1.019-1.683), especially among men (OR = 1.527, 95% CI: 1.041-2.240) and those having a primary and above education level (OR = 1.559, 95% CI: 1.029-2.361). No significant association was observed between short sleep duration and cognitive impairment (OR = 0.860, 95% CI: 0.646-1.145). CONCLUSIONS: Excessive sleep may increase the risk of cognitive impairment in older individuals. It may be a suggestive sign of early neurodegeneration and may be a useful clinical tool to identify those at a higher risk of progressing to cognitive impairment.

Efficacy and acceptability of a second dose of ecological executive skills training for children with ADHD: a randomized controlled study and follow-up.

To explore the efficacy and acceptability of a second dose of the 12-session ecological executive skills training (EEST) 1 year after the initial training in children with ADHD. A total of 97 children (aged 6-12) with ADHD who finished the first dose for about 1 year were recruited in the current study. 70 children who agreed to participate the second dose were randomized to the second dose or waitlist group. Both groups were followed up 1 year after the second dose. Executive function, core symptoms were assessed at the time of pre-intervention first dose, pre-intervention second dose, post-intervention second dose and follow-up 1 year after second dose (phase 0-3). For the immediate efficacy, the improvements in the second dose group were greater than the waitlist group on planning by Stockings of Cambridge and delay aversion by Cambridge gambling task (P = 0.02-0.04, η2 = 0.07-0.08). The parent rating of symptoms assessed by ADHD-RS-IV of the second dose group were also greater than the waitlist group rated by self-report. For long term efficacy, Linear mixed model indicated that there was significant time effect for both groups between phase 3 and phase 1, phase 1 and phase 0 on Behavior Rating Scales of Executive Function and ADHD-RS-IV (F = 2.849-21.560, P = 0.001-0.048). The compliance rate was 94.3% for the second dose group and 49% for waitlist group. A second dose of EEST program might bring further efficacy of EF and core symptoms for children with ADHD and it was well accepted.

Trajectories of cognitive function and their determinants in older people: 12 years of follow-up in the Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: Cognitive decline in advanced age is closely related to dementia. The trajectory of cognitive function in older Chinese is yet to be fully investigated. We aimed to investigate the trajectories of cognitive function in a nationally representative sample of older people living in China and to explore the potential determinants of these trajectories. METHODS: This study included 2,038 cognitively healthy persons aged 65-104 years at their first observation in the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2014. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 12 years and to investigate associations between baseline predictors of group membership and these trajectories. RESULTS: Three trajectories were identified according to the following types of changes in MMSE scores: slow decline (14.0%), rapid decline (4.5%), and stable function (81.5%). Older age, female gender, having no schooling, a low frequency of leisure activity, and a low baseline MMSE score were associated with the slow decline trajectory. Older age, body mass index (BMI) less than 18.5 kg/m2, and having more than one cardiovascular disease (CVD) were associated with the rapid decline trajectory. CONCLUSION: Three trajectories of cognitive function were identified in the older Chinese population. The identified determinants of these trajectories could be targeted for developing prevention and intervention strategies for dementia.

Clinical significance of prognostic nutritional index in predicting the efficacy in patients with B-cell lymphoma. / é¢„åŽè¥å »æŒ‡æ•°åœ¨Bç»†èƒžæ·‹å·´ç˜¤æ‚£è€ ä¸­çš„ç–—æ•ˆé¢„æµ‹ä»·å€¼.

OBJECTIVES: To investigate the clinical significance of prognostic nutritional index (PNI) in predicting the efficacy in patients with B-cell lymphoma. METHODS: The clinical data from 111 patients with B-cell lymphoma (B-cell lymphoma group), who were newly diagnosed in the Third Xiangya Hospital of Central South University from February 2013 to September 2018, were retrospectively analyzed. A total of 93 volunteers selected from the Health Management Center in the Third Xiangya Hospital were set as control, The PNI was compared between the 2 groups. The PNI cut-off value was determined by receiver operating characteristic (ROC) curve analysis. According to the PNI values of patients before chemotherapy, the patients were also divided into a high PNI group (≥43.5) and a low PNI group (<43.5). The correlation of baseline characteristics was evaluated. The correlation between changes in PNI levels and efficacy were evaluated before and after chemotherapy. RESULTS: The PNI value in the B-cell lymphoma group was significantly lower than that in the healthy control group (P<0.05). Lactate dehydrogenase (LDH), presence or absence of B symptoms, international prognostic index (IPI), Eastern Cooperative Oncology Group (ECOG) performance status, source of germinal center, and the efficacy between the high PNI group and the low PNI group were significantly different (all P<0.05). The mean PNI in the effective patients in the low PNI group was increased from 38.10 before chemotherapy to 42.66 after chemotherapy, with significant difference (t=-2.562, P<0.05). The PNI value in the ineffective patients in the high PNI group was decreased from 50.50 before chemotherapy to 41.45 after chemotherapy, with significant difference (t=3.044, P<0.05). CONCLUSIONS: The level of PNI in patients with B-cell lymphoma is significantly lower than that in healthy people, and it is related to the baseline characteristics of prognosis. The change of PNI level before and after chemotherapy can provide certain basis for efficacy evaluation.

Highly enantioselective kinetic resolution of axially chiral BINAM derivatives catalyzed by a Brønsted acid.

A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid-catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.

Preventive interventions for individuals at risk of developing bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to explore whether early interventions can reduce affective symptoms and have long-term benefits among individuals at risk of bipolar disorder (BD). METHODS: The PubMed, Embase, and Web of Science databases were searched. The primary outcome was continuous symptom scores before and after treatment. Random effects meta-analyses were conducted for each outcome arm studied and pooled mean difference estimates were calculated. RESULTS: The search identified 10 controlled studies involving 425 participants and 6 single-arm studies involving 90 participants. For controlled trials, meta-analysis showed that the interventions led to greater reduction in clinical global score than placebo (standardized mean differences (SMD) = -0.96, 95 % CI:-1.32, -0.60), and supported a long-term longitudinal effect for pharmacotherapy (SMD = -0.42, 95 % CI: -0.79, -0.05). For single-arm trials, both pharmacotherapy and psychotherapy showed efficacy for depressive symptoms, while pharmacotherapy only showed efficacy for hypomania symptoms (effect size (ES) = -9.16, 95 % CI:-11.29, -7.04). Discontinuation of pharmacotherapy due to adverse effects did not show a difference. LIMITATIONS: The primary limitations are the small number of RCTs and the influence of medication dosage. CONCLUSIONS: Based on the limited available data, early interventions show efficacy for individuals at risk of BD. Psychological therapy might be more beneficial for depressive symptoms and have long-term benefits for hypomania. Pharmacotherapy may be appropriate in situations of severe hypomanic symptoms and the poor functioning. Large, well-designed, double-blind -controlled trials are needed to make solid conclusions about the efficacy of early interventions.

Characteristics of Odor Identification and Hedonics and Their Association with Piriform Cortex-Based Resting-State Functional Connectivity in Amnestic Mild Cognitive Impairment.

BACKGROUND: Olfactory identification dysfunction (OID) might be an early sign of amnestic mild cognitive impairment (aMCI). However, odor hedonics, the ability to perceive odor pleasantness, is neglected. Also, the neural substrate of OID remains unclear. OBJECTIVE: To explore the characteristics of odor identification and hedonics in aMCI and examine the potential neural correlates of OID by analyzing olfactory functional connectivity (FC) patterns in MCI. METHODS: Forty-five controls and 83 aMCI patients were examined. The Chinese smell identification test was used to assess olfaction. Global cognition, memory, and social cognition were assessed. Resting-state functional networks associated with olfactory cortex seeds were compared between the cognitively normal (CN) and aMCI groups, as well as between aMCI subgroups by the degree of OID. RESULTS: Compared to controls, aMCI patients had a significant deficit in olfactory identification, mainly reflected in the identification of pleasant and neutral odors. aMCI patients also rated pleasant and neutral odors much lower than controls. A positive correlation between olfaction and social cognition was found in aMCI. The seed-based FC analysis found that aMCI patients had higher FC between the right orbitofrontal cortex and right frontal lobe/middle frontal gyrus than controls. Subgroup analysis showed that, compared to aMCI without OID, aMCI with severe OID had abnormal FC in the bilateral piriform region. CONCLUSION: Our results suggest that OID in aMCI primarily refers to the identification of pleasant and neutral odors. The FC alterations in bilateral orbitofrontal cortex and piriform cortices might contribute to the impairment in odor identification.

Team idiosyncratic deals and team breakthrough innovation: Based on the perspective of input-process-output model.

Purpose: As a new human resource management practice, idiosyncratic deals are personalized employment arrangements negotiated between employees and employers and intended to benefit them both. It plays an important role in attracting, retaining and motivating employees to promote breakthrough innovation. Based on the input-process-output (I-P-O) model, this paper examines the relationship between team idiosyncratic deals and team breakthrough innovation, the mediating role of team exploratory-exploitative knowledge sharing, and the moderating roles of team transactive memory systems and team cognitive flexibility. Participants and methods: In order to reduce the effects of common method biases and causal lag effect, this study is divided into three stages for data collection, with a time interval of 1 month. Eighty teams (406 employees) from six enterprises in Shanghai and Hangzhou were selected as samples, and the hypothesis test was carried out by hierarchical regression analysis, bootstrap, and Johnson-Neyman method. Results: The results show that higher team idiosyncratic deals are associated with higher team breakthrough innovation through higher team exploratory-exploitative knowledge sharing, and that team transactive memory systems and team cognitive flexibility positively moderate the mediating effect of team exploratory-exploitative knowledge sharing in the relationship between team idiosyncratic deals and team breakthrough innovation in the first stage and the second stage, respectively. Under the joint effect of high team transactive memory systems and high team cognitive flexibility, the mediating effect of team exploratory-exploitative knowledge sharing is stronger. Conclusion: The research results break through the previous research framework of social exchange theory, and I-P-O model to explore the influence mechanism of team idiosyncratic deals, in order to promote the sustainable growth of team breakthrough innovation through this non-standard work arrangement. It is hoped that this research can inspire modern enterprises to create team idiosyncratic deals for valuable teams engaged in breakthrough innovation, which are more conducive to give full play to their heterogeneous talents, and finally help enterprises break through the industry bottleneck and win the market competition.

Decision-Making Profiles and Their Associations with Cognitive Performance in Mild Cognitive Impairment.

BACKGROUND: It is crucial for older adults, especially those with mild cognitive impairment (MCI), to make profitable decisions routinely. However, the results regarding decision-making (DM) remain inconsistent. OBJECTIVE: The present study assessed DM profiles under uncertainty conditions in individuals with MCI and their associations with multi-domain cognitive performance. METHOD: Fifty-three patients with MCI and forty-two age-, gender-, and education level-matched healthy controls (HCs) were administered a comprehensive neuropsychological battery test. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT) were used to assess DM competence in conditions involving ambiguity and risk, respectively. In addition, Spearman's correlations were used to examine relationships between GDT and multi-domain cognitive performance. RESULT: The final capital (FC) and frequency of utilization of negative feedback (FUNF) and positive feedback (FUPF) in the GDT were lower in MCI patients than in HCs. In addition, the number of shifts between safe and risky alternatives was significantly different across groups. However, IGT performance was comparable across groups. In the MCI patients, risky DM performance was associated with language, whereas in HCs was correlated with memory and executive functions. Besides, in MCI, performance on IGT was significantly correlated with social cognition. CONCLUSION: Individuals with mild cognitive impairment have difficulty utilizing feedback to make optimal decisions under risky situations. The association between decision-making performance and cognitive function is divergent regarding situational uncertainty and individuals' cognitive status. In mild cognitive impairment and normal aging, decision-making under ambiguity needs further investigation.

Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group. Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences. Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group. Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.

TMSCFX2 (X = Cl, Br) as halofluorocarbene sources for the synthesis of halofluorocyclopropanes.

TMSCFX2 (X = Cl, Br; TMS = trimethylsilyl) have been developed as halofluorocarbene (CFX, X = Cl, Br) precursors for [2+1] cyclopropanation with alkenes. Structurally diverse halofluorocyclopropanes were obtained in good to excellent yields. It was found that the reactivity order of the three halofluorocarbene reagents (TMSCF2Br, TMSCFCl2, and TMSCFBr2) in halofluorocyclopropanation with 1,1-diphenylethylene can be very different under different reaction conditions.

Reduced social activities and networks, but not social support, are associated with cognitive decline among older chinese adults: A prospective study.

BACKGROUND: Social relationships consist of distinct dimensions. The literature on the effect of specific social relationship subdomains on cognitive function is limited. This large-scale, prospective cohort study examined the associations of social relationships with cognitive decline and further explored which subdomains of social relationships were predictive of cognitive decline among elderly Chinese individuals. METHODS: A total of 3314 older Chinese adults aged 65-110 years from the 2011-2012 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included. Cognitive decline was defined based on the Chinese version of the Mini-Mental State Examination (MMSE). Social relationships were divided into three subdomains: social activities, social networks, and social support. Linear and binary logistic regression analyses were conducted to assess the effect of social relationships and the social relationship subdomains on cognitive decline after adjusting for age, sex, education, residence, exercise, drinking, smoking, activities of daily living, chronic diseases, depression, and baseline cognitive function. RESULTS: Seven hundred and sixty-eight participants (23.17%) developed greater cognitive decline during the 3-year follow-up. The social relationships score was negatively associated with cognitive decline. Binary adjusted odds ratios showed that after potential covariates were controlled, social relationships, activities, and networks significantly reduced the risk of cognitive decline. When all social relationships variables were entered simultaneously with all covariates, the effect of social activities and networks on the risk of greater cognitive decline remained significant. However, we did not observe a significant association between social support and the risk of greater cognitive decline. CONCLUSION: Our findings suggest that social relationships and the subdomains of social activities and networks, but not social support, have a protective effect against greater cognitive decline in older adults. This implies that structural dimensions of social relationships might be more important than functional dimensions in preserving cognitive health among elderly Chinese individuals.

Apathy as a Risky Neuropsychiatric Syndrome of Progression From Normal Aging to Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis.

Background: Apathy has been suggested as a potential predictor of mild cognitive impairment (MCI) progression to dementia. Whether it might predict the transition from normal cognitive function to cognitive impairment has been less studied. The current study aimed to provide a comprehensive summary of the evidence on the association between apathy and the transition from normal cognitive function to cognitive impairment. Methods: We searched the PubMed, Embase, and Web of Science databases for longitudinal prospective cohort studies that evaluated apathy at baseline in the cognitively normal population and had cognitive impairment as the outcome. Random effects models were used, and heterogeneity was explored with stratification. The stability of the synthesized result was indicated using sensitivity analysis by excluding one study each time and recalculating the overall effect. Results: Ten studies comprising 26,195 participants were included. Apathy status was available for 22,101 participants. Apathy was present in 1,803 of 22,101 participants (8.16%). Follow-up ranged from 1 to 13 years. The combined odds ratio (OR) of cognitive impairment for patients with apathy was 2.07 (95% CI: 1.43-2.99; I2 = 86%), and the combined hazard ratio was 2.70 (95% CI: 1.38-5.27; I2 = 94%). The OR meta-analyses for different conversion outcomes were MCI (OR = 3.38, 95% CI: 1.57-7.28; I2 =71%), cognitive decline (OR = 1.27, 95% CI: 0.81-2.00; I2 = 64%) and dementia (OR = 2.12, 95% CI: 1.32-3.41; I2 = 86%). Subgroup analysis suggested that the association between apathy and cognitive impairment changed with age, depression adjustments, apathy measurement, and follow-up time. Conclusions: Apathy was associated with a greater than 2-fold increased risk of progression to cognitive impairment in the cognitively normal population. Future interventions targeting apathy management in the general population may reduce the risk of cognitive impairment.

Platelet maximum aggregation rate serves as a marker in diagnosis and prognosis in patients with sepsis.

BACKGROUND: Multiple organ failure complicated by coagulation dysfunction is an important cause of death in patients with sepsis. This study aimed to explore the clinical significance of platelet maximum aggregation rate (MAR) in patients with sepsis and explored the relationship between MAR and prognosis to support treatment decision-making. METHODS: Blood samples from patients with sepsis (diagnosed according to the 2016 international diagnostic criteria for sepsis 3.0) treated between Sep 2017 and Apr 2018 were assessed. Patients were excluded if they had any other condition or treatment that may have affected platelet function in the previous 2 weeks. A control group of healthy subjects attending the physical examination center in the same period was also included. The MAR was measured using a whole blood platelet function analyzer (PL-12) using a range of different inducers of platelet aggregation, and normal saline. MAR was assessed in the healthy and septic groups, and survivors and non-survivors were compared in the sepsis group 28 days after treatment. RESULTS: The MAR in the sepsis group was significantly lower than that seen in the healthy group (P<0.05 for all inducers). The MAR of patients with sepsis was negatively correlated with their Sequential Organ Failure Assessment (SOFA) scores. In the sepsis group, the MAR of non-survivors was significantly lower than that of the survivors (P<0.05 for all inducers). CONCLUSIONS: The platelet MAR was significantly decreased in patients with sepsis and in non-survivors. These data may support treatment decision-making in patients with sepsis.

lncRNA CCAT1/miR-490-3p/MAPK1/c-Myc positive feedback loop drives progression of acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a frequently diagnosed malignancy in adults. Long non-coding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) has been well known to play vital roles in multiple malignancies including AML. Unfortunately, the detailed mechanism of CCAT1 in AML progression remains obscure. In this study, we demonstrated that CCAT1 was up-regulated in AML samples while its target, miR-490-3p, was relatively down-regulated. CCAT1 markedly increased viability and metastasis of AML cells, while miR-490-3p had opposite effects. CCAT1 could specifically bind to miR-490-3p and reduce its expression and activity, and MAPK1 was a target gene of miR-490-3p. Overexpressed CCAT1 could induce MAPK1 expression and c-Myc reciprocally increased CCAT1 expression. Our data implied that miR-490-3p could be a novel therapeutic target for AML, and highlights the crucial role of CCAT1/miR-490-3p/MAPK1/c-Myc positive feedback loop in AML progression.

Association of Odor Identification Ability With Amyloid-ß and Tau Burden: A Systematic Review and Meta-Analysis.

Background: The associations between olfactory identification (OI) ability and the Alzheimer's disease biomarkers were not clear. Objective: This meta-analysis aimed to examine the associations between OI and Aß and tau burden. Methods: Electronic databases (PubMed, Embase, PsycINFO, and Google Scholar) were searched until June 2019 to identify studies that reported correlation coefficients or regression coefficients between OI and Aß or tau levels measured by positron emission tomography (PET) or cerebrospinal fluid (CSF). Pooled Pearson correlation coefficients were computed for the PET imaging and CSF biomarkers, with subgroup analysis for subjects classified into different groups. Results: Nine studies met the inclusion criteria. Of these, five studies (N = 494) involved Aß PET, one involved tau PET (N = 26), and four involved CSF Aß or tau (N = 345). OI was negatively associated with Aß PET in the mixed (r = -0.25, P = 0.008) and cognitively normal groups (r = -0.15, P = 0.004) but not in the mild cognitive impairment group. A similar association with CSF total tau in the mixed group was also observed. No association was found between OI and CSF phosphorylated tau or Aß42 in the subgroup analysis of the CSF biomarkers. Due to a lack of data, no pooled r value could be computed for the association between the OI and tau PET. Conclusion: The associations between OI ability and Aß and CSF tau burden in older adults are negligible. While current evidence does not support the association, further studies using PET tau imaging are warranted.

Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level.

Objectives: Investigation of the genetic basis of endophenotype and analysis the pathways with multiple genes of small effects might increase the understanding of the genetic basis of attention deficit hyperactivity disorder (ADHD). Here we aimed to explore the genetic basis of cognitive flexibility in ADHD at the single nucleotide polymorphism (SNP), gene and pathway levels. Methods: The trail-making test was used to test the cognitive flexibility of 788 ADHD patients. A genome-wide association analysis of cognitive flexibility was conducted for 644,166 SNPs. Results: The top SNP rs2049161 (P = 5.08e-7) involved gene DLGAP1 and the top gene CADPS2 in the gene-based analysis resulted in much literature evidence of associations with psychiatric disorders. Gene expression and network analysis showed their contribution to cognition function. The interval-enrichment analysis highlighted a potential contribution of 'adenylate cyclase activity' and ADCY2 to cognitive flexibility. Candidate pathway-based analysis for all SNPs found that glutamate system-, neurite outgrowth- and noradrenergic system-related pathways were significantly associated with cognitive flexibility (FDR <0.05), among which the neurite outgrowth pathway was also associated with ADHD symptoms. Conclusions: This study provides evidence for the genes and pathways associated with cognitive flexibility and facilitate the uncovering of the genetic basis of ADHD.

DLGAP1 and NMDA receptor-associated postsynaptic density protein genes influence executive function in attention deficit hyperactivity disorder.

Objective: To explore the association of DLGAP1 gene with executive function (EF) in attention deficit hyperactivity disorder (ADHD) children. Method: A total of 763 ADHD children and 140 healthy controls were enrolled. The difference of EF between ADHD and controls was analyzed using the analysis of covariance (ANCOVA), with IQ, sex, and age as covariates. Both the associations of SNPs with EF and three symptom traits of ADHD were conducted using an additive linear regression model by PLINK with the same covariates as ANCOVA. Results: Compared with controls, children with ADHD showed poorer cognitive flexibility and inhibition. Two SNPs (rs2049161, p-value = 5.08e-7, adjusted p-value = 1.63e-4, rs16946051, p-value = 5.18e-7, adjusted p-value = 1.66e-4) survived multiple tests in Trail Making Test. Both SNPs also showed association with TOH (rs2049161, p = 6.82e-4, rs16946051, p = 7.91e-4). Set-based analysis for gene DLGAP1 and its functional pathway DLGAP1-DLG4-NMDA showed they were associated with cognitive flexibility at both gene (p = .0057) and pathway level (p = .0321). Furthermore, the gene and pathway also showed association with ADHD symptom score. The associated SNPs and their LD proxies were related to the expression of DLGAP1 in medulla and frontal cortex. Conclusion: Children with ADHD showed deficit in EF, especially, cognitive flexibility and inhibition. DLGAP1 was associated with cognitive flexibility and plan, and the role of DLGAP1 might be implemented through the complex of DLGAP1-DLG4-NMDA.