Rashba valleys and quantum Hall states in few-layer black arsenic.

Exciting phenomena may emerge in non-centrosymmetric two-dimensional electronic systems when spin-orbit coupling (SOC)1 interplays dynamically with Coulomb interactions2,3, band topology4,5 and external modulating forces6-8. Here we report synergetic effects between SOC and the Stark effect in centrosymmetric few-layer black arsenic, which manifest as particle-hole asymmetric Rashba valley formation and exotic quantum Hall states that are reversibly controlled by electrostatic gating. The unusual findings are rooted in the puckering square lattice of black arsenic, in which heavy 4p orbitals form a Brillouin zone-centred Γ valley with pz symmetry, coexisting with doubly degenerate D valleys of px origin near the time-reversal-invariant momenta of the X points. When a perpendicular electric field breaks the structure inversion symmetry, strong Rashba SOC is activated for the px bands, which produces spin-valley-flavoured D± valleys paired by time-reversal symmetry, whereas Rashba splitting of the Γ valley is constrained by the pz symmetry. Intriguingly, the giant Stark effect shows the same px-orbital selectiveness, collectively shifting the valence band maximum of the D± Rashba valleys to exceed the Γ Rashba top. Such an orchestrating effect allows us to realize gate-tunable Rashba valley manipulations for two-dimensional hole gases, hallmarked by unconventional even-to-odd transitions in quantum Hall states due to the formation of a flavour-dependent Landau level spectrum. For two-dimensional electron gases, the quantization of the Γ Rashba valley is characterized by peculiar density-dependent transitions in the band topology from trivial parabolic pockets to helical Dirac fermions.

Bright light treatment counteracts stress-induced sleep alterations in mice, via a visual circuit related to the rostromedial tegmental nucleus.

Light in the environment greatly impacts a variety of brain functions, including sleep. Clinical evidence suggests that bright light treatment has a beneficial effect on stress-related diseases. Although stress can alter sleep patterns, the effect of bright light treatment on stress-induced sleep alterations and the underlying mechanism are poorly understood. Here, we show that bright light treatment reduces the increase in nonrapid eye movement (NREM) sleep induced by chronic stress through a di-synaptic visual circuit consisting of the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), lateral habenula (LHb), and rostromedial tegmental nucleus (RMTg). Specifically, chronic stress causes a marked increase in NREM sleep duration and a complementary decrease in wakefulness time in mice. Specific activation of RMTg-projecting LHb neurons or activation of RMTg neurons receiving direct LHb inputs mimics the effects of chronic stress on sleep patterns, while inhibition of RMTg-projecting LHb neurons or RMTg neurons receiving direct LHb inputs reduces the NREM sleep-promoting effects of chronic stress. Importantly, we demonstrate that bright light treatment reduces the NREM sleep-promoting effects of chronic stress through the vLGN/IGL-LHb-RMTg pathway. Together, our results provide a circuit mechanism underlying the effects of bright light treatment on sleep alterations induced by chronic stress.

Shortcut barcoding and early pooling for scalable multiplex single-cell reduced-representation CpG methylation sequencing at single nucleotide resolution.

DNA methylation is essential for a wide variety of biological processes, yet the development of a highly efficient and robust technology remains a challenge for routine single-cell analysis. We developed a multiplex scalable single-cell reduced representation bisulfite sequencing (msRRBS) technology. It allows cell-specific barcoded DNA fragments of individual cells to be pooled before bisulfite conversion, free of enzymatic modification or physical capture of the DNA ends, and achieves read mapping rates of 62.5 ± 3.9%, covering 60.0 ± 1.4% of CpG islands and 71.6 ± 1.6% of promoters in K562 cells. Its reproducibility is shown in duplicates of bulk cells with close to perfect correlation (R = 0.97-0.99). At a low 1 Mb of clean reads, msRRBS provides highly consistent coverage of CpG islands and promoters, outperforming the conventional methods with orders of magnitude reduction in cost. Here, we use this method to characterize the distinct methylation patterns and cellular heterogeneity of six cell lines, plus leukemia and hepatocellular carcinoma models. Taking 4 h of hands-on time, msRRBS offers a unique, highly efficient approach for dissecting methylation heterogeneity in a variety of multicellular systems.

Zinc finger protein 280C contributes to colorectal tumorigenesis by maintaining epigenetic repression at H3K27me3-marked loci.

Dysregulated epigenetic and transcriptional programming due to abnormalities of transcription factors (TFs) contributes to and sustains the oncogenicity of cancer cells. Here, we unveiled the role of zinc finger protein 280C (ZNF280C), a known DNA damage response protein, as a tumorigenic TF in colorectal cancer (CRC), required for colitis-associated carcinogenesis and Apc deficiency­driven intestinal tumorigenesis in mice. Consistently, ZNF280C silencing in human CRC cells inhibited proliferation, clonogenicity, migration, xenograft growth, and liver metastasis. As a C2H2 (Cys2-His2) zinc finger-containing TF, ZNF280C occupied genomic intervals with both transcriptionally active and repressive states and coincided with CCCTC-binding factor (CTCF) and cohesin binding. Notably, ZNF280C was crucial for the repression program of trimethylation of histone H3 at lysine 27 (H3K27me3)-marked genes and the maintenance of both focal and broad H3K27me3 levels. Mechanistically, ZNF280C counteracted CTCF/cohesin activities and condensed the chromatin environment at the cis elements of certain tumor suppressor genes marked by H3K27me3, at least partially through recruiting the epigenetic repressor structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1). In clinical relevance, ZNF280C was highly expressed in primary CRCs and distant metastases, and a higher ZNF280C level independently predicted worse prognosis of CRC patients. Thus, our study uncovered a contributor with good prognostic value to CRC pathogenesis and also elucidated the essence of DNA-binding TFs in orchestrating the epigenetic programming of gene regulation.

Mimicking Tumor Metastasis Using a Transwell-Integrated Organoids-On-a-Chip Platform.

The mortality rate among cancer patients is primarily attributed to tumor metastasis. The evaluation of metastasis potential provides a powerful framework for personalized therapies. However, little work has so far been undertaken to precisely model tumor metastasis in vitro, hindering the development of preventive and therapeutic interventions. In this work, a tumor-metastasis-mimicked Transwell-integrated organoids-on-a-chip platform (TOP) for precisely evaluating tumor metastatic potential is developed. Unlike the conventional Transwell device for detecting cell migration, the engineered device facilitates the assessment of metastasis in patient-derived organoids (PDO). Furthermore, a novel Transwell chamber with a hexagon-shaped structure is developed to mimic the migration of tumor cells into surrounding tissues, allowing for the evaluation of tumor metastasis in a horizontal direction. As a proof-of-concept demonstration, tumor organoids and metastatic clusters are further evaluated at the protein, genetic, and phenotypic levels. In addition, preliminary drug screening is undertaken to highlight the potential for using the device to combat cancers. In summary, the tumor-metastasis-mimicked TOP offers unique capabilities for evaluating the metastasis potential of tumor organoids and contributes to the development of personalized cancer therapies.

Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters.

PURPOSE: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). METHODS: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T 1 $$ {\mathrm{T}}_1 $$ relaxation time ( T 1 , B $$ {\mathrm{T}}_{1,B} $$ ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T 1 , B $$ {\mathrm{T}}_{1,B} $$ values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. RESULTS: Simulated and phantom experiments showed a strong dependence on AMS and FA ( R 2 $$ {R}^2 $$ >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( R 2 $$ {R}^2 $$ >0.59) was observed which was reduced when calculating MBF with individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. CONCLUSION: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters.

TRIM29 acts as a potential senescence suppressor with epigenetic activation in nasopharyngeal carcinoma.

Epigenetic alterations marked by DNA methylation are frequent events during the early development of nasopharyngeal carcinoma (NPC). We identified that TRIM29 is hypomethylated and overexpressed in NPC cell lines and tissues. TRIM29 silencing not only limited the growth of NPC cells in vitro and in vivo, but also induced cellular senescence, along with reactive oxygen species (ROS) accumulation. Mechanistically, we found that TRIM29 interacted with voltage-dependent anion-selective channel 1 (VDAC1) to activate mitophagy clearing up damaged mitochondria, which are the major source of ROS. In patients with NPC, high levels of TRIM29 expression are associated with an advanced clinical stage. Moreover, we detected hypomethylation of TRIM29 in patient nasopharyngeal swab DNA. Our findings indicate that TRIM29 depends on VDAC1 to induce mitophagy and prevents cellular senescence by decreasing ROS. Detection of aberrantly methylated TRIM29 in the nasopharyngeal swab DNA could be a promising strategy for the early detection of NPC.

Robust cardiac T 1 ρ $$ {\mathrm{T}}_{1_{\boldsymbol{\rho}}} $$ mapping at 3T using adiabatic spin-lock preparations.

PURPOSE: The aim of this study is to develop and optimize an adiabatic T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ ( T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ ) mapping method for robust quantification of spin-lock (SL) relaxation in the myocardium at 3T. METHODS: Adiabatic SL (aSL) preparations were optimized for resilience against B 0 $$ {\mathrm{B}}_0 $$ and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities using Bloch simulations. Optimized B 0 $$ {\mathrm{B}}_0 $$ -aSL, Bal-aSL and B 1 $$ {\mathrm{B}}_1 $$ -aSL modules, each compensating for different inhomogeneities, were first validated in phantom and human calf. Myocardial T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ mapping was performed using a single breath-hold cardiac-triggered bSSFP-based sequence. Then, optimized T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ preparations were compared to each other and to conventional SL-prepared T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ maps (RefSL) in phantoms to assess repeatability, and in 13 healthy subjects to investigate image quality, precision, reproducibility and intersubject variability. Finally, aSL and RefSL sequences were tested on six patients with known or suspected cardiovascular disease and compared with LGE, T 1 $$ {\mathrm{T}}_1 $$ , and ECV mapping. RESULTS: The highest T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ preparation efficiency was obtained in simulations for modules comprising 2 HS pulses of 30 ms each. In vivo T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ maps yielded significantly higher quality than RefSL maps. Average myocardial T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ values were 183.28 ± $$ \pm $$ 25.53 ms, compared with 38.21 ± $$ \pm $$ 14.37 ms RefSL-prepared T 1 ρ $$ {\mathrm{T}}_{1\uprho} $$ . T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ maps showed a significant improvement in precision (avg. 14.47 ± $$ \pm $$ 3.71% aSL, 37.61 ± $$ \pm $$ 19.42% RefSL, p < 0.01) and reproducibility (avg. 4.64 ± $$ \pm $$ 2.18% aSL, 47.39 ± $$ \pm $$ 12.06% RefSL, p < 0.0001), with decreased inter-subject variability (avg. 8.76 ± $$ \pm $$ 3.65% aSL, 51.90 ± $$ \pm $$ 15.27% RefSL, p < 0.0001). Among aSL preparations, B 0 $$ {\mathrm{B}}_0 $$ -aSL achieved the better inter-subject variability. In patients, B 1 $$ {\mathrm{B}}_1 $$ -aSL preparations showed the best artifact resilience among the adiabatic preparations. T 1 ρ , adiab $$ {\mathrm{T}}_{1\uprho, \mathrm{adiab}} $$ times show focal alteration colocalized with areas of hyper-enhancement in the LGE images. CONCLUSION: Adiabatic preparations enable robust in vivo quantification of myocardial SL relaxation times at 3T.

Distinct brain activity alterations of treatment for bipolar disorders with psychotherapy and drug therapy: activation likelihood estimation meta-analysis.

BACKGROUNDS: Many studies suggest that both psychotherapy and drug therapy are effective in the treatment of bipolar disorders (BDs). However, the pathophysiology of both types of intervention has not been established definitively. METHODS: An activation likelihood estimation meta-analysis was performed to identify the distinct brain activity alterations between psychotherapy and drug therapy for the treatment of BDs. Articles were identified by searching databases including PubMed, Embase, Cochrane Library, and Web of Science databases. Eligible studies on BDs were published up until 10 June 2021. RESULTS: 21 studies were included and we conducted a meta-analysis for different therapies and imaging tasks. After receiving psychotherapy, BD patients showed increased activation in the inferior frontal gyrus (IFG) and superior temporal gyrus. While after taking drug therapy, BD patients displayed increased activation in the anterior cingulate cortex, medial frontal gyrus, IFG, and decreased activation in the posterior cingulate cortex. The regions of brain activity changes caused by psychotherapy were mostly focused on the frontal areas, while drug therapy mainly impacted on the limbic areas. Different type of tasks also affected brain regions which were activated. CONCLUSIONS: Our comprehensive meta-analysis indicates that these two treatments might have effect on BD in their own therapeutic modes. Psychotherapy might have a top-down effect, while drug therapy might have a bottom-up effect. This study may contribute to differential diagnosis of BDs and would be helpful to finding more accurate neuroimaging biomarkers for BD treatment.

MR Assessed Changes of Renal Sinus Fat in Response to Glucose Regulation in West European and South Asian Patients With Type 2 Diabetes.

BACKGROUND: Ethnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI-quantified renal sinus fat volume could be a potential biomarker to help investigate the changes of DKD risk in response to glucose regulation. PURPOSE: To evaluate whether the effect of glucose-lowering treatment on renal sinus fat volume differed in West Europeans (WE) compared to South Asians (SA), and whether ethnic-related difference exists regarding the effect of liraglutide on renal sinus fat. STUDY TYPE: Retrospective. POPULATION: Ninety-three patients with type 2 diabetes mellitus, including 47 WE (27 males) aged 59.3 ± 6.5 years, and 46 SA (19 males) aged 54.4 ± 9.8 years. FIELD STRENGTH/SEQUENCE: 3.0 T dual-echo fast gradient-echo pulse sequence using two-point Dixon technique with a phase-correction algorithm. ASSESSMENT: Changes of renal sinus fat volume were measured by a radiologist (LL) with 4-years' experience, and were compared between the two ethnic groups, together with glycemic level, metabolic risk factors and renal function. The effects of liraglutide were assessed. STATISTICAL TESTS: Normality of the data was visually evaluated by histograms and Q-Q plots. Within-group and between-group differences were analyzed using paired t-tests and analysis of covariance. Associations were analyzed by person's correlation and multiple linear regression models. RESULTS: Renal sinus fat decreased in SA patients (Δ% = -7.6% ± 14.8%), but increased in WE patients (Δ% = 5.0% ± 13.1%), with a significant difference between the two ethnic groups. In the WE group, the increase of sinus fat volume was significant in the placebo subgroup (Δ% = 6.8% ± 12.5%), in contrast to the nonsignificant increase in the liraglutide subgroup (Δ% = 3.0% ± 13.8%, P = 0.444). DATA CONCLUSION: Renal sinus fat accumulation responds differently to glucose regulation, showing a reduction in SA patients in contrast to a persistent accumulation in WE patients. A trend of less accumulation of sinus fat in WE patients receiving liraglutide has been observed. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 4.

Cardiovascular magnetic resonance for evaluation of cardiac involvement in COVID-19: recommendations by the Society for Cardiovascular Magnetic Resonance.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.

Impact of rhG-CSF on Clinical Efficacy and Immune Cell Subsets after Initial Induction Chemotherapy in AML.

BACKGROUND: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML. METHODS: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy. Next, rhG-CSF stimulation experi-ments on leukemia cell lines and primary leukemia blasts were performed in vitro. RESULTS: There was no statistical difference between control group and rhG-CSF therapy group in complete remission rate and relapse free survival. The duration of agranulocytosis was significantly shortened in rhG-CSF therapy group compared with control group. The percentage of circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) were significantly increased after the administration of rhG-CSF. Furthermore, it was found that rhG-CSF did not promote the proliferation of leukemia cell lines and primary leukemia blasts, but increased the proportion of M-MDSCs and Tregs in vitro. CONCLUSIONS: Administration of rhG-CSF after initial induction therapy of AML does not affect the clinical remission and relapse rate, but reduces the duration of agranulocytosis and increases the proportion of M-MDSCs and Tregs.

Predictors for quality of life in older adults: network analysis on cognitive and neuropsychiatric symptoms.

BACKGROUND: Quality of life (QoL) of older adults has become a pivotal concern of the public and health system. Previous studies found that both cognitive decline and neuropsychiatric symptoms (NPS) can affect QoL in older adults. However, it remains unclear how these symptoms are related to each other and impact on QoL. Our aim is to investigate the complex network relationship between cognitive and NPS symptoms in older adults, and to further explore their association with QoL. METHODS: A cross-sectional study was conducted in a sample of 389 older individuals with complaints of memory decline. The instruments included the Neuropsychiatric Inventory, the Mini Mental State Examination, and the 36-item Short Form Health Survey. Data was analyzed using network analysis and mediation analysis. RESULTS: We found that attention and agitation were the variables with the highest centrality in cognitive and NPS symptoms, respectively. In an exploratory mediation analysis, agitation was significantly associated with poor attention (ß = -0.214, P < 0.001) and reduced QoL (ß = -0.137, P = 0.005). The indirect effect of agitation on the QoL through attention was significant (95% confidence interval (CI) [-0.119, -0.035]). Furthermore, attention served as a mediator between agitation and QoL, accounting for 35.09% of the total effect. CONCLUSIONS: By elucidating the NPS-cognition-QoL relationship, the current study provides insights for developing rehabilitation programs among older adults to ensure their QoL.

Myocardial extracellular volume fraction quantification based on T1 mapping at 3 T: quality optimization by contour-based registration and segmental analysis.

BACKGROUND: Myocardial extracellular volume fraction (ECV) assessment can be affected by various technical and subject-related factors. PURPOSE: To evaluate the role of contour-based registration in quantification of ECV and investigate normal segment-based myocardial ECV values at 3T. MATERIAL AND METHODS: Pre- and post-contrast T1 mapping images of the left ventricular basal, mid-cavity, and apical slices were obtained in 26 healthy volunteers. ECV maps were generated using motion correction with and without contour-based registration. The image quality of all ECV maps was evaluated by a 4-point scale. Slices were dichotomized according to the occurrence of misregistration in the source data. Contour-registered ECVs and standard ECVs were compared within each subgroup using analysis of variance for repeated measurements and generalized linear mixed models. RESULTS: In all three slices, higher quality of ECV maps were found using contour-registered method than using standard method. Standard ECVs were statistically different from contour-registered ECVs in global (26.8% ± 2.8% vs. 25.8% ± 2.4%; P = 0.001), mid-cavity (25.4% ± 3.1% vs. 24.3% ± 2.5%; P = 0.016), and apical slices (28.7% ± 4.1% vs. 27.2% ± 3.4%; P = 0.010). In the misregistration subgroups, contour-registered ECVs were lower with smaller SDs (basal: 25.2% ± 1.8% vs. 26.7% ± 2.6%; P = 0.038; mid-cavity: 24.4% ± 2.3% vs. 26.8% ± 3.1%; P = 0.012; apical: 27.5% ± 3.6% vs. 29.7% ± 4.5%; P = 0.016). Apical (27.2% ± 3.4%) and basal-septal ECVs (25.6% ± 2.6%) were statistically higher than mid-cavity ECV (24.3% ± 2.5%; both P < 0.001). CONCLUSION: Contour-based registration can optimize image quality and improve the precision of ECV quantification in cases demonstrating ventricular misregistration among source images.

Development and Validation of a Knowledge Scale About the Behavioral and Psychological Symptoms of Dementia (KS-BPSD) Among Chinese Formal Caregivers.

OBJECTIVES: The current study aimed to develop a scale assessing knowledge about behavioral and psychological symptoms of dementia (KS-BPSD) among Chinese formal caregivers and to investigate its psychometric properties and factorial structure. METHODS: The scale was generated with a systematic development process, and 229 formal caregivers working at nursing homes were recruited to construct and assess the psychometric properties of the scale. The preliminary scale was reviewed by an expert panel and items were selected based on item discrimination, difficulty, and item-total correlation. RESULTS: The final KS-BPSD version consisted of 12 items, loaded into three factors (i.e., Disease Characteristics, Care and Risks, and Treatment Needs) following principal component analysis (PCA). The KS-BPSD showed good test-retest reliability, internal consistency, as well as construct and concurrent validity. CONCLUSIONS: The 12-item KS-BPSD was found to have high reliability and preliminary validity in assessing the level of knowledge about patient's BPSD among formal Chinese caregivers in nursing homes. CLINICAL IMPLICATIONS: KS-BPSD is a reliable tool to address the knowledge discrepancies and support needs among dementia caregivers, helping to develop and evaluate educational programs in the management of patient's BPSD.

How formal caregiver's BPSD knowledge influences positive aspects of caregiving: the mediating role of attitude and the moderating role of self-efficacy.

BACKGROUND: The current study investigated the relationship between behavioural and psychological symptoms of dementia (BPSD) knowledge and positive aspects of caregiving (PAC), in addition, how caregiving attitude and self-efficacy mediate or moderate this relationship. METHODS: Two hundred twenty-nine formal caregivers (51males and 178females) who has worked in nursing homes for more than a month were recruited.With a cross-sectional, face-to-face survey, structural questionnaires were implemented to evaluate formal caregiver's BPSD knowledge, attitude, self-efficacy and PAC.A 13-item self-developed questionnaire was used to assess caregiver's BPSD knowledge about disease characteristics, care and risks, and treatment needs. Dementia attitude, self-efficacy and positive aspects of caregiving were measured by dementia attitude scale, the General self-efficacy scale, and Chinese version of positive aspects of caregiving respectively. Model 5 in the PROCESS micro was employed in order to verify the mediating effect of attitude and the moderating effect of self-efficacy on the relationship between BPSD knowledge and PAC. RESULTS: The results showed that greater BPSD knowledge was associated with increased PAC, and this relationship was fully mediated by increased friendly attitude toward people with dementia. Moreover, direct effect was moderated by self-efficacy, and that only among those with high self-efficacy, the direct effect of BPSD knowledge was found on promoting PAC. CONCLUSIONS: By elucidating the knowledge-attitude-practice pathway in handling patient's BPSD, the current study extends existing literature and provides insights for developing psychoeducation programs among formal caregivers.

Mahjong Playing and Leisure Physical Activity Alleviate Cognitive Symptoms in Older Community Residents.

Leisure activities, particularly physically and cognitively stimulating leisure activities, mitigate cognitive decline. The present study aimed to examine the relationship between mahjong playing, leisure physical activity, and mild cognitive impairment (MCI). Older adults with and without MCI were recruited (n = 489, healthy group; and n = 187, MCI group). The regression results showed that years of mahjong playing (odds ratio = 0.595, 95% confidence interval [0.376, 0.961], p = .032) and physical activity (odds ratio = 0.572, 95% confidence interval [0.381, 0.849], p = .012) were associated with reduced odds of having MCI after adjusting for a series of covariates. Leisure physical activity and mahjong playing interacted with each other and produced combined effects on the odds of having MCI. Combined cognitive and physical interventions may produce larger benefits on cognition than either intervention alone.

Where does fear originate in the brain? A coordinate-based meta-analysis of explicit and implicit fear processing.

Processing of fear is of crucial importance for human survival and it can generally occur at explicit and implicit conditions. It is worth noting that explicit and implicit fear processing produces different behavioral and neurophysiological outcomes. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta-analysis to identify: (a) the "core" network of fear processing in healthy individuals; (b) common and specific neural activations associated with explicit and implicit processing of fear. Following PRISMA guidelines, a total of 92 fMRI and PET studies were included in the meta-analysis. The overall analysis show that the core fear network comprises the amygdala, pulvinar, and fronto-occipital regions. Both implicit and explicit fear processing activated amygdala, declive, fusiform gyrus, and middle frontal gyrus, suggesting that these two types of fear processing share a common neural substrate. Explicit fear processing elicited more activations at the pulvinar and parahippocampal gyrus, suggesting visual attention/orientation and contextual association play important roles during explicit fear processing. In contrast, implicit fear processing elicited more activations at the cerebellum-amygdala-cortical pathway, indicating an 'alarm' system underlying implicit fear processing. These findings have shed light on the neural mechanism underlying fear processing at different levels of awareness.

Identification of cardiovascular abnormalities by multiparametric magnetic resonance imaging in end-stage renal disease patients with preserved left ventricular ejection fraction.

OBJECTIVES: Our study aimed to evaluate myocardial strain and tissue characteristics by multiparametric cardiovascular magnetic resonance (CMR) imaging in end-stage renal disease (ESRD) patients on peritoneal dialysis with preserved left ventricular ejection fraction (LVEF). METHODS: ESRD patients on peritoneal dialysis with echocardiographic LVEF > 50% and age- and sex-matched healthy volunteers underwent multiparametric CMR at 3 T. LV function, LV myocardial native T1 and T2, and biventricular strain were measured and compared between the patients and controls. Associations of LV myocardial mass index (LVMI) with tissue characterization and strain were evaluated by multiple linear regression. RESULTS: A total of 65 subjects (42 healthy volunteers and 23 ESRD patients) were enrolled. ESRD group demonstrated larger LVMI, higher native T1 and T2 (1301.9 ± 30.6 ms, 44.6 ± 2.6 ms) than those of the control group (1255.8 ± 45.2 ms, 40.5 ± 1.6 ms; both p < 0.001). Decreased LV strain and increased right ventricular circumferential strain were observed in the ESRD group. In ESRD patients with normal diastolic function on echocardiography, native T1 and T2 values were higher than those of the control group (p = 0.006, p = 0.001). Increased LVMI was associated with increased native T1 (p = 0.001) and T2 value (p < 0.001) after adjusting for age and sex. Increased myocardial native T1 value was associated with reduced LV strain after adjusting age, sex, and LVMI. CONCLUSIONS: ESRD patients on peritoneal dialysis with preserved LVEF demonstrated higher myocardial mass, higher native T1 and T2 values, decreased LV strain, and increased RVGCS compared with healthy controls. Increased myocardial T1 and T2 were found in ESRD even when no systolic or diastolic dysfunction was detected by routine echocardiography. KEY POINTS: • Even with preserved LVEF and no known cardiovascular diseases, ESRD patients on peritoneal dialysis demonstrated elevated myocardial T1 and T2 values and decreased left ventricular strain. • Subclinical changes in myocardial tissue composition may exist in ESRD patients on peritoneal dialysis even when no systolic or diastolic dysfunction was detected by routine echocardiography based on ejection fraction, left atrium size, and tissue Doppler. • Right ventricular free wall strain could be enhanced in response to subclinical LV systolic dysfunction in ESRD patients on peritoneal dialysis with preserved LVEF at an early stage.

USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5.

The Krüppel-like factor 5 (KLF5) transcription factor is highly expressed in basal type breast cancer and promotes breast cancer cell proliferation, survival, migration, and tumorigenesis. KLF5 protein stability is regulated by ubiquitination. In this study, ubiquitin-specific protease 3 (USP3) was identified as a new KLF5 deubiquitinase by genome-wide siRNA library screening. We demonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination. USP3 knockdown inhibits breast cancer cell proliferation in vitro and tumorigenesis in vivo, which can be partially rescued by ectopic expression of KLF5. Furthermore, we observed a positive correlation between USP3 and KLF5 protein expression levels in human breast cancer samples. These findings suggest that USP3 is a new KLF5 deubiquitinase and that USP3 may represent a potential therapeutic target for breast cancer.