Prognostic significance and value of further classification of lymphovascular invasion in invasive breast cancer: a retrospective observational study.

PURPOSE: To investigate the prognostic significance of lymphovascular invasion in invasive breast cancer and the value of using specific vascular endothelial markers to further classify lymphovascular invasion. METHODS: We collected 2124 patients with invasive breast cancer who were hospitalized at the First Hospital of Dalian Medical University from 2012 to 2020. Statistical methods were used to investigate the relationship between lymphovascular invasion and clinicopathological characteristics of breast cancer, and the correlation between lymphovascular invasion on overall survival (OS) and disease-free survival (DFS) of various categories of breast cancers. Immunohistochemical staining of breast cancer samples containing lymphovascular invasion using specific vascular endothelial markers D2-40 and CD34 was used to classify lymphovascular invasion and to investigate the relationship between lymphovascular invasion and breast cancer progression. RESULTS: There was a high correlation between lymphovascular invasion and T stage, N stage and nerve invasion. Survival analyses showed that patients with lymphovascular invasion, especially luminal B, triple-negative, and Her-2 overexpression breast cancer patients, had poorer OS and DFS prognosis, and that lymphovascular invasion was an independent prognostic factor affecting OS and DFS in breast cancer. The immunohistochemical staining results showed that positive D2-40 staining of lymphovascular invasion was linked to the N stage and localized recurrence of breast cancer. CONCLUSION: Lymphovascular invasion is associated with aggressive clinicopathological features and is an independent poor prognostic factor in invasive breast cancer. Breast cancer localized recurrence rate and lymph node metastases are influenced by lymphatic vessel invasion. Immunohistochemical techniques should be added to the routine diagnosis of lymphovascular invasion.

The olfactory working memory capacity paradigm: A more sensitive and robust method of assessing cognitive function in male 5XFAD mice.

The olfactory working memory capacity (OWMC) paradigm is able to detect cognitive deficits in 5XFAD mice (an animal model of Alzheimer's disease [TG]) as early as 3 months of age, while other behavioral paradigms detect cognitive deficits only at 4-5 months of age. Therefore, we aimed to demonstrate that the OWMC paradigm is more sensitive and consistent in the early detection of declines in cognitive function than other commonly used behavioral paradigms. The prefrontal cortex (PFC), retrosplenial cortex (RSC), subiculum (SUB), and amygdala (AMY) of 5XFAD mice were harvested and subjected to immunostaining to detect the expression of ß-amyloid (Aß). Additionally, we compared the performance of 3-month-old male 5XFAD mice on common behavioral paradigms for assessing cognitive function (i.e., the open field [OF] test, novel object recognition [NOR] test, novel object location [NOL] test, Y-maze, and Morris water maze [MWM]) with that on the OWMC task. In the testing phase of the OWMC task, we varied the delay periods to evaluate the working memory capacity (WMC) of wild-type (WT) mice. Significant amyloid plaque deposition was observed in the PFC, RSC, SUB, and AMY of 3-month-old male 5XFAD mice. However, aside from the OWMC task, the other behavioral tests failed to detect cognitive deficits in 5XFAD mice. Additionally, to demonstrate the efficacy of the OWMC task in assessing WMC, we varied the retention delay periods; we found that the WMC of WT mice decreased with longer delay periods. The OWMC task is a sensitive and robust behavioral assay for detecting changes in cognitive function.

Sex differences in cognitive function trajectories and their determinants in older adults: Evidence from the Chinese longitudinal healthy longevity survey.

OBJECTIVES: To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories. METHODS: The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008-2018 cohort. 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 10 years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes. RESULTS: Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9 h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline. CONCLUSIONS: The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low-income and developing countries.

Attenuated neural activity in processing decision-making feedback in uncertain conditions in patients with mild cognitive impairment.

The present study aimed to explore the potential neural correlates during feedback evaluation during decision-making under risk and ambiguity in MCI. Nineteen individuals with MCI and twenty age-matched HCs were enrolled. Decision-making performance under risk and ambiguity was examined with the modified game of dice task (GDT) and an Iowa gambling task (IGT). Using task-related EEG data, reward positivity (RewP) and feedback P3 (fb-P3) were used to characterize participants' motivation and allocation of cognitive resources. Also, response time and event-related oscillation (ERO) were used to evaluate information processing speed, and the potent of post-feedback information integration and behavioral modulation. MCI patients had lower RewP (p = 0.022) and fb-P3 (p = 0.045) amplitudes in the GDT than HCs. Moreover, the amount and valence of feedback modulated the RewP (p = 0.008; p = 0.017) and fb-P3 (p < 0.001; p < 0.001). In the IGT, in addition to the significantly reduced fb-P3 observed in MCI patients (p = 0.010), the amount and valence of feedback modulated the RewP (p = 0.002; p = 0.020). Furthermore, MCI patients took longer to make decisions (t = 2.15, p = 0.041). The ERO analysis revealed that delta power was reduced in MCI (GDT: p = 0.045; p = 0.011). The findings suggest that, during feedback evaluation when making risky and ambiguous decisions, motivation, allocation of cognitive resources, information processing and neuronal excitability were attenuated in MCI. It implies that neural activity related to decision making was compromised in MCI.

Incongruent gray matter atrophy and functional connectivity of striatal subregions in behavioral variant frontotemporal dementia.

Previous studies on the striatum demonstrated that it is involved in the regulation of cognitive function and psychiatric symptoms in patients with behavioral variant frontotemporal dementia (bvFTD). Multiple lines of evidence have shown that striatal subregions have their own functions. However, the results of the existing studies on striatal subregions are inconsistent and unclear. In this study, we found that structural imaging analysis revealed that the bvFTD patients had smaller volumes of striatal subregions than the controls. We found that the degree of atrophy varied across the striatal subregions. Additionally, the right striatal subregions were significantly more atrophic than the left in bvFTD. Functional imaging analysis revealed that bvFTD patients exhibited different changed patterns of resting-state functional connectivity (RSFC) when striatal subregions were selected as regions of interest (ROI). The RSFC extending range on the right ROIs was more significant than on the left in the same subregion. Interestingly, the RSFC of the subregions extending to the insula were consistent. In addition, the left dorsolateral putamen may be involved in executive function regulation. This suggests that incongruence in striatal subregions may be critical to the bvFTD characteristics.

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.

Factors associated with health-seeking for urinary incontinence in Hong Kong Chinese women: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: To explore levels of urinary incontinence (UI) knowledge among Hong Kong Chinese women and the factors affecting patients' help-seeking behavior. METHODS: Chinese women with age ≥ 40 years who attended General Out-patient Clinics between May 1 and June 30, 2022, were invited to complete the questionnaire. The questionnaire consisted of four sections: (1) demographic data, (2) knowledge of UI (UI quiz), (3) severity of UI (UDI-6) and impairment of quality of life (QOL) (IIQ-7), and (4) barriers to seeking medical help. Severity of UI, impairment of QOL, knowledge of UI, and sociodemographic characteristics were analyzed regarding their relationship with help-seeking behavior. RESULTS: Of 351 women, 53.2% had symptoms of UI but only 25.0% symptomatic patients had consulted a doctor. The UI quiz score was 6.82 ± 2.76 (total 14) and the highest incorrect item was "Urinary incontinence is the normal aging" (incorrect rate 86.3%). The most frequent barrier for help-seeking was "The symptoms are not severe and do not affect me." Logistic regression analysis showed that UDI-6 score (adjusted OR = 1.06, P < 0.0001) and UI quiz score (adjusted OR = 1.30, P = 0.001) were the independent impact factors of patient's help-seeking behavior. CONCLUSIONS: Hong Kong Chinese women's knowledge toward UI is not sufficient, and the consultation rate is low. Besides symptom severity, the knowledge level of UI is the other independent factor affecting patients' help-seeking behavior. Community education on UI may encourage women to seek early help.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Co-occurrence of depressive and anxious symptoms and their influence on self-rated health: a national representative survey among Chinese older adults.

OBJECTIVES: The prevalence of the co-occurrence of depressive and anxious symptoms (CO) and their influence on perceived overall health were not clear in community dwelling Chinese older adults. The aims of the study were to investigate the prevalence of CO and to explore its influence on self-rated health (SRH). METHOD: This study included 12301 individuals aged ≥65 years from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a nationally representative survey of older adults in mainland China. Participants received face-to-face interviews and assessments of depressive symptoms and anxious symptoms via 10-item of the Center for Epidemiologic Studies Depression Scale (CES-D-10) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), respectively. SRH was measured by self-reported. A logistic regression model was used to examine the association between CO and SRH after adjusting for confounding variables. RESULTS: The average age was 83.4 (SD: 11.0) years and there were 6576 (53.5%) females. The age- and sex-standardized prevalence of depressive symptoms only (DSO) was 38.6%, anxious symptoms only (ASO) was 1.5%, and CO was 10.8%. Compared with those without depressive and anxious symptoms, the older adults with DSO or ASO were more likely to have significant influence on SRH. And particularly, CO was likely to produce the greatest decrement in the level of SRH. CONCLUSION: CO was not rare in Chinese older adults nationwide. The older adults having CO had increased risk for lower level of SRH than having DSO or ASO. More attention should be given to CO among the older adults.

Diminished activation of excitatory neurons in the prelimbic cortex leads to impaired working memory capacity in mice.

BACKGROUND: Working memory capacity impairment is an early sign of Alzheimer's disease, but the underlying mechanisms remain unclear. Clarifying how working memory capacity is affected will help us better understand the pathological mechanism of Alzheimer's disease. We used the olfactory working memory capacity paradigm to evaluate memory capacity in 3-month-old 5XFAD (an animal model of Alzheimer's disease) mice. Immunofluorescence staining of the prefrontal cortex was performed to detect the number of FOS-positive neurons, calmodulin-dependent protein kinase II-positive neurons, and glutamate decarboxylase-positive neurons in the prelimbic cortex and infralimbic cortex. A chemogenetic method was then used to modulate the inhibition and activation of excitatory neurons in the prelimbic cortex of wild-type and 5XFAD mice and to measure the memory capacity of mice. RESULTS: Working memory capacity was significantly diminished in 5XFAD mice compared to littermate wild-type mice. Neuronal activation of the prelimbic cortex, but not the infralimbic cortex, was attenuated in 5XFAD mice performing the olfactory working memory capacity task. Subsequently, the FOS-positive neurons were co-localized with both calmodulin-dependent protein kinase II-positive neurons and glutamate decarboxylase-positive neurons. The results showed that the activation of excitatory neurons in the prelimbic cortex was correlated with working memory capacity in mice. Our results further demonstrate that the chemogenetic inhibition of prelimbic cortex excitatory neurons resulted in reduced working memory capacity in wild-type mice, while the chemogenetic activation of prelimbic cortex excitatory neurons improved the working memory capacity of 5XFAD mice. CONCLUSION: The diminished activation of prelimbic cortex excitatory neurons in 5XFAD mice during task performance is associated with reduced working memory capacity, and activation modulation of excitatory neurons by chemogenetic methods can improve memory capacity impairment in 5XFAD mice. These findings may provide a new direction for exploring Alzheimer's disease therapeutic approaches.

[Factors influencing cognitive function among the older adults in Beijing].

OBJECTIVE: To explore the current status of cognitive function of the older adults in Beijing, and to analyze the factors affecting their cognitive function. METHODS: It was a cross-sectional study. A questionnaire survy was conducted in 2023 among the older adults in Beijing. The cognitive function of the older adults was assessed with the Hong Kong brief cognitive test (HKBC) scale, a simple cognitive assessment tool. Using SPSS 27.0 to perform the descriptive analysis and multiple linear regression analysis of factors, which affect cognitive function among the older adults. RESULTS: Totally 349 older adults were recruited, with the highest percentage of respondents aged 60-69 years (41.3%), of whom 58.7% were female, 88.0% of the respondents had a junior high school or above education level. Most of the older adults (68.8%) worked 35-48 h/week before they retired, and 14.0% of the older adults had a family history of dementia. After controlling age and gender, the linear regression analysis showed that marital status married (ß=0.501, 95%CI: 0.144-0.859) and 3-4 times physical activity per week (ß=0.617, 95%CI: 0.087-1.148) were protective factors of cognitive function in the older adults, and depressive symptoms were a risk factor (ß= -0.723, 95%CI: -1.198 to -0.247) of cognitive function for the older adults. CONCLUSION: In this study, the factors influencing cognitive function among the older adults was analyzed based on a life-cycle perspective. Lack of physical activity and depressive symptoms were risk factors for cognitive function among the older adults. It was suggested that strengthening physical activity, improving mental health of the older adults, as well as conducting preventive intervention in early stages of the life-cycle will be benefit for preventing and slowing cognitive decline in the older adults.

Decrease in naturally occurring antibodies against epitopes of Alzheimer's disease (AD) risk gene products is associated with cognitive decline in AD.

BACKGROUND: Naturally occurring antibodies (NAbs) are germline-encoded immunoglobulins that can bind to and clear out self-neo-epitopes as well as apoptotic and necrotic cells. However, NAbs pathological relevance in Alzheimer's disease (AD) is not well-understood. METHODS: Twenty-eight candidate proteins encoded by AD-associated genes were selected for this study based on a number of selection criteria, including preferential expression in the brain and B-lymphocyte cells. The levels of NAbs in plasma were analyzed according to their epitopes in age- and gender-matched cognitively normal subjects (CN, n = 56), subjects with mild cognitive impairment (MCI, n = 16) and subjects with AD (n = 56). We aimed to study the levels of their NAbs in plasma and their associations with cognitive decline in individuals with AD. RESULTS: Of the 28 antigens tested, 17 showed decreased NAbs in individuals with AD; in particular, NAb-TREM2 had an area under the ROC curve of 0.806, with the highest sensitivity (0.370) at 95% specificity among all 28 tests. Further protein-protein interaction networks and functional enrichment analysis suggested that target genes were enriched in AD-related pathological processes classified under "Alzheimer's disease", "neurodegenerative disease" and "amyloidosis". The "Alzheimer's disease" and "neurodegenerative disease" clusters, which converged on the initial "recognition" step of microglial phagocytosis, showed the best diagnostic performance for AD. CONCLUSIONS: This study suggests a decline in the function of the adaptive immune system in AD, and the levels of circulating NAbs are likely to serve as biomarkers for surveilling the progression of AD.

Multi-scale analysis provides insights into the roles of ureide permeases in wheat nitrogen use efficiency.

The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In planta, tissue ureide levels are controlled by the activity of enzymes of the purine degradation pathway and by ureide transporters called ureide permeases (UPS). Little is known about the physiological function of UPS proteins in crop plants, and especially in monocotyledon species. Here, we identified 13 TaUPS genes in the wheat (Triticum aestivum L.) genome. Phylogenetic and genome location analyses revealed a close relationship of wheat UPSs to orthologues in other grasses and a division into TaUPS1, TaUPS2.1, and TaUPS2.2 groups, each consisting of three homeologs, with a total of four tandem duplications. Expression, localization, and biochemical analyses resolved spatio-temporal expression patterns of TaUPS genes, transporter localization at the plasma membrane, and a role for TaUPS2.1 proteins in cellular import of ureides and phloem and seed loading. In addition, positive correlations between TaUPS1 and TaUPS2.1 transcripts and ureide levels were found. Together the data support that TaUPSs function in regulating ureide pools at source and sink, along with source-to-sink transport. Moreover, comparative studies between wheat cultivars grown at low and high N strengthened a role for TaUPS1 and TaUPS2.1 transporters in efficient N use and in controlling primary metabolism. Co-expression, protein-protein interaction, and haplotype analyses further support TaUPS involvement in N partitioning, N use efficiency, and domestication. Overall, this work provides a new understanding on UPS transporters in grasses as well as insights for breeding resilient wheat varieties with improved N use efficiency.

Attitudes towards dementia among Chinese adults aged 50 years and older: a comparative study of immigrants living in Melbourne and nonimmigrants living in Beijing.

OBJECTIVES: This study investigated attitudes towards dementia among Chinese immigrants aged 50 years and over living in Australia and compares these attitudes with those of individuals living in mainland China. It aimed to better understand what older Chinese adults think about dementia and to inform the development of tailored dementia-related services for this group of people. DESIGN: A qualitative design involving individual interviews was employed in this study. PARTICIPANTS: Forty-six participants were recruited: 21 in Melbourne and 25 in Beijing. All interviewees were born in mainland China, were community-dwelling, and did not have a dementia diagnosis. MEASUREMENTS: The tripartite model of attitudes was used to guide the semi-structured interview design and report the results. Thematic qualitative analysis was employed. RESULTS: In both groups, most participants held negative feelings, stigmatized views and negative stereotypes of dementia. However, most participants expressed a willingness to help individuals living with dementia. Regarding dementia care, nearly all participants preferred home care but thought formal care would become the mainstream form of care in the future. Fewer Melbourne participants expressed concerns regarding developing dementia, were interested in dementia, or perceived a need for dementia-related educational activities. Melbourne participants also reported more avoidant responses to dementia or individuals living with dementia. CONCLUSION: This study carefully compares attitudes towards dementia between older Chinese immigrants in Melbourne and older Chinese adults in Beijing. Similarities and differences were observed between these two groups. Dementia-related service providers should consider the sociocultural changes and migration-related barriers experienced by Chinese immigrants.

Develop and validate a novel online AIHI-nomogram to predict severe liver inflammation in patients with autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Assessment of liver inflammation plays a vital role in the management of patients with autoimmune hepatitis (AIH). We aimed to establish and validate a nomogram to predict severe liver inflammation in AIH patients. PATIENTS AND METHODS: AIH patients who underwent liver biopsy were included and randomly divided into a training set and a validation set. Independent predictors of severe liver inflammation were selected by the least absolute shrinkage and selection operator regression from the training set and used to conduct a nomogram. Receiver characteristic curves (ROC), calibration curves, and decision curve analysis (DCA) were adopted to evaluate the performance of nomogram. RESULTS: Of the 213 patients, female patients accounted for 83.1% and the median age was 53.0 years. The albumin, gamma-glutamyl transpeptidase, total bilirubin, red cell distribution width, prothrombin time, and platelets were independent predictors of severe inflammation. An online AIHI-nomogram was established and was available at https://ndth-zzy.shinyapps.io/AIHI-nomogram/. The calibration curve revealed that the AIHI-nomogram had a good agreement with actual observation in the training and validation sets. The area under the ROCs of AIHI-nomogram were 0.795 in the training set and 0.759 in the validation set, showing significantly better performance than alanine aminotransferase and immunoglobulin G in the training and validation sets, as well in AIH patients with normal ALT in the training set. DCA indicated that the AIHI-nomogram was clinically useful. CONCLUSIONS: This novel AIHI-nomogram provided an excellent prediction of severe liver inflammation in AIH patients and could be used for the better management of AIH.

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.

Potential synthetic lethality for breast cancer: A selective sirtuin 2 inhibitor combined with a multiple kinase inhibitor sorafenib.

Sorafenib is a clinically useful multiple kinase inhibitor for the treatment of kidney cancer, liver cancer and acute myelocytic leukemia, while it has shown weak efficacy in suppressing breast cancer. Since sirtuin2 (SIRT2) is an important epigenetic regulator and associated with several cancer types including breast cancer, development and evaluation of new SIRT2 inhibitors to probe their therapeutic potentials is currently desirable. A highly selective SIRT2 inhibitor named I was previously developed by us, which showed activity to inhibit non-small cell lung cancer cell lines in vitro. We herein report expanded screening of I and its structurally similar inactive compound II against other cancer cell lines, and found that I had a wide spectrum of anticancer activity while II had no such effects. The I-sorafenib combination treatment exerted obvious synergistic reduction on cell viability of MCF-7 cells. We observed that the combination treatment could suppress cell proliferation, survival and migration, arrest cell cycle at G0/G1 phase, and induce apoptosis in MCF-7 cells, when compared with the single treatment. In vivo studies revealed that the combination treatment showed stronger tumor growth inhibition (87%), comparing with I-(42.8%) or sorafenib-solely-treated groups (61.1%) in MCF-7 xenograft model. In conclusion, this work clearly revealed a potential synthetic lethality effect for I combined with sorafenib, and will probably offer a new strategy at least for breast cancer treatment.

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.

Plateletcrit for predicting prognosis in patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloid.

BACKGROUND: Platelet index was reported to be used as a potential prognostic marker in patients with liver fibrosis. We aimed to explore the association between plateletcrit (PCT) and severity of hepatic sinusoidal obstruction syndrome (HSOS). METHODS: Seventy consecutive patients who diagnosed as HSOS by CT and medical history during January 2017-November 2021 were included. All patients were divided into two groups which confirmed as favorable prognosis and poor prognosis on the basis of Child-Turcotte-Pugh score system. The clinical manifestation and laboratory parameters of two groups were retrospectively selected. PCT was evaluated within two groups, and the diagnostic accuracy was evaluated by the area under the receiver operating characteristic curve. RESULTS: The significant difference between the two groups not only in diarrhea, abdominal pain, abdominal distention, urine volume, and skin ecchymosis (p < 0.005), but also in WBC count, NE count, PLT count, TBIL, and D-Dimer (p < 0.005) were found. The PCT level was significantly higher in HSOS patients with poor prognosis (0.169 ± 0.060) than favorable prognosis patients (0.110 ± 0.047). The area under the receiver operating characteristic curve of RDW in predicting poor prognosis was 0.781, with 67.70% sensitivity and 79.5%specificity. CONCLUSIONS: The PCT level was correlated positively with the poor prognosis in HSOS patients. PCT can be a promising indicator for predicting prognosis in HSOS.

Long Noncoding RNA Brain Cytoplasmic RNA 1 Induces Cisplatin-Resistance of Cervical Cancer Cells by Sponging MicroRNA-330-5p and Upregulating High-Mobility Group Box 3.

OBJECTIVES: The aim of the study was to find out the function of long noncoding RNA brain cytoplasmic RNA 1 (BCYRN1) in cisplatin (DDP)-resistance of cervical cancer (CC) cells. Design and Materials, Setting, Methods: BCYRN1 expression in CC and DDP-resistant cells was evaluated, with the association of BCYRN1 and prognosis analyzed. Then, DDP-resistant cells with BCYRN1 knockdown were established and the DDP-resistance of these cells was assessed. BCYRN1 subcellular localization was detected and confirmed. Besides, the binding relations of BCYRN1 and microRNA (miR)-330-5p and between miR-330-5p and high-mobility group box 3 (HMGB3) were examined and verified. Moreover, the role of miR-330-5p and HMGB3 in the mechanism of BCYRN1 modulating DDP-resistance of CC cells was detected. In addition, xenograft transplantation was conducted to confirm the effect of BCYRN1 in CC cell DDP-resistance. RESULTS: BCYRN1 was overexpressed in CC, which resulted in poor prognosis and DDP-resistance. BCYRN1 knockdown in DDP-resistant cells downregulated DDP-resistance. Mechanically, BCYRN1 sponged miR-330-5p to strengthen HMGB3 mRNA level. Besides, miR-330-5p underexpression or HMGB3 overexpression reversed the function of BCYRN1 knockdown in inhibiting DDP-resistance of CC cells. Eventually, BCYRN1 knockdown reduced the DDP-resistance of CC cells in vivo. LIMITATIONS: There are still some deficiencies in the research; for example, whether there are other miRs working as the downstream genes of BCYRN1 in the competing endogenous RNA interaction is not fully clarified, nor the other downstream mechanisms of miR-330-5p. Besides, the experimental findings and their application into practice need extensive validation. CONCLUSIONS: BCYRN1 knockdown could disrupt the DDP-resistance of CC cells through upregulating miR-330-5p to suppress HMGB3 mRNA level.