Association of Patient-Reported Social Needs with Emergency Department Visits and Hospitalizations Among Federally Qualified Health Center Patients.

BACKGROUND: Health care systems are increasingly screening for unmet social needs. The association between patient-reported social needs and health care utilization is not well understood. OBJECTIVE: To investigate the association between patient-reported social needs, measured by the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE), and inpatient and emergency department (ED) utilization. DESIGN: This cohort study analyzed merged 2017-2019 electronic health record (EHR) data across multiple health systems. PARTICIPANTS: Adult patients from a federally qualified health center (FQHC) in central North Carolina who completed PRAPARE as part of a primary care visit with behavioral health services. MAIN MEASURES: The count of up to 12 unmet social needs, aggregated as 0, 1, 2, or 3 + . Outcomes include the probability of an ED visit and hospitalization 12 months after PRAPARE assessment, modeled by logistic regressions controlling for age, sex, race, ethnicity, comorbidity burden, being uninsured, and prior utilization in the past 12 months. KEY RESULTS: The study population consisted of 1924 adults (38.7% male, 50.1% Black, 36.3% Hispanic, 55.9% unemployed, 68.2% of patients reported 1 + needs). Those with more needs were younger, more likely to be unemployed, and experienced greater comorbidity burden. 35.3% of patients had ED visit(s) and 36.3% had hospitalization(s) 1 year after PRAPARE assessment. In adjusted analysis, having 3 + needs was associated with a percentage point increase in the predicted probability of hospitalization (average marginal effect 0.06, SE 0.03, p < 0.05) compared with having 0 needs. Similarly, having 2 needs (0.07, SE 0.03, p < 0.05) or 3 + needs (0.06, SE 0.03, p < 0.05) was associated with increased probability of ED visits compared to 0 needs. CONCLUSIONS: Patient-reported social needs were common and associated with health care utilization patterns. Future research should identify interventions to address unmet social needs to improve health and avoid potentially preventable escalating medical intervention.

Socioeconomic disadvantage and long-term survival duration in out-of-hospital cardiac arrest patients: A population-based cohort study.

Background: Socioeconomic status (SES) is a well-established determinant of cardiovascular health. However, the relationship between SES and clinical outcomes in long-term out-of-hospital cardiac arrest (OHCA) is less well-understood. The Singapore Housing Index (SHI) is a validated building-level SES indicator. We investigated whether SES as measured by SHI is associated with long-term OHCA survival in Singapore. Methods: We conducted an open cohort study with linked data from the Singapore Pan-Asian Resuscitation Outcomes Study (PAROS), and the Singapore Registry of Births and Deaths (SRBD) from 2010 to 2020. We fitted generalized structural equation models, calculating hazard ratios (HRs) using a Weibull model. We constructed Kaplan-Meier survival curves and calculated the predicted marginal probability for each SHI category. Results: We included 659 cases. In both univariable and multivariable analyses, SHI did not have a significant association with survival. Indirect pathways of SHI mediated through covariates such as Emergency Medical Services (EMS) response time (HR of low-medium, high-medium and high SHI when compared to low SHI: 0.98 (0.88-1.10), 1.01 (0.93-1.11), 1.02 (0.93-1.12) respectively), and age of arrest (HR of low-medium, high-medium and high SHI when compared to low SHI: 1.02 (0.75-1.38), 1.08 (0.84-1.38), 1.18 (0.91-1.54) respectively) had no significant association with OHCA survival. There was no clear trend in the predicted marginal probability of survival among the different SHI categories. Conclusions: We did not find a significant association between SES and OHCA survival outcomes in residential areas in Singapore. Among other reasons, this could be due to affordable healthcare across different socioeconomic classes.

Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.

Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies.

Care sequences leading to the diagnosis of Alzheimer's disease and related dementias: An analysis of electronic health records.

BACKGROUND: We examined the sequences of clinical care leading to diagnoses of Alzheimer's disease and related dementias (ADRD) using electronic health records from a large academic medical center. METHODS: We included patients aged 65+ with their first ADRD diagnoses from January 1, 2014 to December 31, 2019. Using state sequence analysis, care sequences were defined by the ordering of healthcare utilizations occurred in the 2 years before ADRD diagnosis. RESULTS: Of 3621 patients (median age 80), nearly half followed a care sequence of having one primary care visit close to their ADRD diagnosis. Additional care sequences included periodic (n = 322, 8.9%) and multiple (n = 416, 11.5%) outpatient visits to primary care and having one (n = 395, 10.9%), multiple (n = 469, 13.0%), or highly frequent (n = 357, 10.7%) outpatient visits to other specialties. Patients' sociodemographic traits contributed to the variability in care sequences. CONCLUSIONS: Several distinct patterns of care leading to ADRD diagnoses were identified. Integrated care models are needed to promote early identification of ADRD. HIGHLIGHTS: Dementia patients followed distinct care pathways prior to their dementia diagnoses. Key sociodemographic traits contributed to the variation in the sequences of care. Racial differences in the sequencing of care were also found, but only in women.

Anlotinib exerts an anti-T-cell acute lymphoblastic leukemia effect in vitro and in vivo.

BACKGROUND: Despite some progress having been made regarding the treatment of T-cell acute lymphoblastic leukemia (T-ALL), the prognosis of T-ALL, particularly adult T-ALL, is still poor. Identifying novel, effective anti-T-ALL drugs is of great significance. Anlotinib, an oral tyrosine kinase inhibitor currently utilized in the treatment of lung cancer, exhibited a promising anti-T-ALL effect. A comprehensive study should therefore be conducted to explore both the in vitro as well as in vivo mechanisms of the anti-T-ALL effects of anlotinib. METHODS: CCK8 assays and flow cytometry were employed to investigate the viability, cell cycle distribution, and apoptosis of T-ALL cell lines when treated with anlotinib. T-ALL xenograft mouse models were established to examine the in vivo antileukemic effects of anlotinib. Cellular and molecular analysis of T-ALL were conducted to define the underlying mechanisms. RESULTS: In vitro, anlotinib significantly inhibited the viability, induced G2/M phase arrest and apoptosis in T-ALL cell lines in a concentration-dependent pattern. In vivo, anlotinib also demonstrated a strong anti-tumor effect at doses that are well-tolerated. Interestingly, anlotinib could decrease the protein levels of the intracellular domains of NOTCH1 (ICN1) and c-Myc, two important targets for T-ALL. Mechanistically, anlotinib-induced c-Myc reduction was associated with proteasome-mediated degradation, while the ICN1 reduction was not due to protein degradation or transcriptional repression. CONCLUSIONS: The present study showed that anlotinib may be a promising anti-T-ALL candidate drug, and simultaneous reduction of the protein levels of both ICN1 and c-Myc may contribute to the anti-T-ALL efficacy of anlotinib.

Initiation of Antihypertensive Medication from Midlife on Incident Dementia: The Health and Retirement Study.

BACKGROUND: Hypertension has been identified as a risk factor of dementia, but most randomized trials did not show efficacy in reducing the risk of dementia. Midlife hypertension may be a target for intervention, but it is infeasible to conduct a trial initiating antihypertensive medication from midlife till dementia occurs late life. OBJECTIVE: We aimed to emulate a target trial to estimate the effectiveness of initiating antihypertensive medication from midlife on reducing incident dementia using observational data. METHODS: The Health and Retirement Study from 1996 to 2018 was used to emulate a target trial among non-institutional dementia-free subjects aged 45 to 65 years. Dementia status was determined using algorithm based on cognitive tests. Individuals were assigned to initiating antihypertensive medication or not, based on the self-reported use of antihypertensive medication at baseline in 1996. Observational analog of intention-to-treat and per-protocol effects were conducted. Pooled logistic regression models with inverse-probability of treatment and censoring weighting using logistic regression models were applied, and risk ratios (RRs) were calculated, with 200 bootstrapping conducted for the 95% confidence intervals (CIs). RESULTS: A total of 2,375 subjects were included in the analysis. After 22 years of follow-up, initiating antihypertensive medication reduced incident dementia by 22% (RR = 0.78, 95% CI: 0.63, 0.99). No significant reduction of incident dementia was observed with sustained use of antihypertensive medication. CONCLUSION: Initiating antihypertensive medication from midlife may be beneficial for reducing incident dementia in late life. Future studies are warranted to estimate the effectiveness using large samples with improved clinical measurements.

Association between perceived risk of Alzheimer's disease and related dementias and cognitive function among U.S. older adults.

INTRODUCTION: The aim of the study was to assess factors associated with the perceived risk of developing Alzheimer's disease and related dementias (ADRD) and how the perceived risk of ADRD was related to cognitive function. METHODS: We conducted a retrospective cohort study using 5 waves of data from the Health and Retirement Study (2012-2022) that included adults aged 65 years or older with no previous diagnosis of ADRD at baseline. Cognitive function was measured at baseline and over time using a summary score that included immediate/delayed word recall, serial 7's test, objective naming test, backwards counting, recall of the current date, and naming the president/vice-president (range = 0-35). Perceived risk of developing ADRD was categorized at baseline as "definitely not" (0% probability), "unlikely" (1-49%), "uncertain" (50%), and "more than likely" (>50-100%). Additional baseline measures included participants' sociodemographic background, psychosocial resources, health behaviors, physiological status, and healthcare utilization. RESULTS: Of 1457 respondents (median age 74 [IQR = 69-80] and 59.8% women), individuals who perceived that they were "more than likely" to develop ADRD had more depressive symptoms and were more likely to be hospitalized in the past two years than individuals who indicated that it was "unlikely" they would develop ADRD. Alternatively, respondnets who perceived that they would "definitely not" develop ADRD were more likely to be non-Hispanic Black, less educated, and have lower income than individuals who indicated it was "unlikely" they would develop ADRD. Respondents who reported their risks of developing ADRD as "more than likely" (ß = -2.10, P < 0.001) and "definitely not" (ß = -1.50, P < 0.001) had the lowest levels of cognitive function; and the associations were explained in part by their socioeconomic, psychosocial, and health status. CONCLUSIONS: Perceived risk of developing ADRD is associated with cognitive function. The (dis)concordance between individuals' perceived risk of ADRD and their cognitive function has important implications for increasing public awareness and developing interventions to prevent ADRD.

Meta-Analysis of Variations in Association between APOE ɛ4 and Alzheimer's Disease and Related Dementias Across Hispanic Regions of Origin.

BACKGROUND: Emerging research has shown racial and ethnic variations in the magnitude of association between the apolipoprotein ɛ4 (APOE ɛ4) allele and the risk of developing Alzheimer's disease and related dementias (ADRD). Studies researching this association among Hispanic groups within and outside of the United States have produced inconsistent results. OBJECTIVE: To examine the association between the APOE ɛ4 allele and the risk of developing ADRD in global Hispanic populations from different ethnic regions of origin. METHODS: PubMed, Embase, Scopus, and PsycInfo were searched for studies relating to Hispanic/Latin American origin, APOE ɛ4, and ADRD. Odds ratios (OR) of ADRD risk for individuals with APOE ɛ4 versus those without APOE ɛ4 were extracted and calculated using random effects analysis. RESULTS: 20 eligible studies represented Caribbean Hispanic, Mexican, South American, Spanish, and Cuban groups. Overall, APOE ɛ4 was significantly associated with increased risk of ADRD (Odds Ratio [OR] 3.80, 95% CI: 2.38-6.07). The association was only significant in the South American (OR: 4.61, 95% CI: 2.74-7.75) subgroup. CONCLUSION: There was an association between APOE ɛ4 and increased ADRD risk for the South American subgroup. The strength of this association varied across Hispanic subgroups. Data is limited with more studies especially needed for adjusted analysis on Spanish, Central American, Cuban Hispanic, and Caribbean Hispanic groups. Results suggest additional environmental or genetic risk factors are associated with ethnic variations.

Ten-Year Cardiovascular Disease Risk Score and Cognitive Function Among Older Adults: The National Health and Nutrition Examination Survey 2011 to 2014.

Background The Framingham 10-year cardiovascular disease risk score, which is based on age, sex, smoking, total cholesterol, high-density lipoprotein-cholesterol, blood pressure, and diabetes, has been found to be associated with cognitive health, but these findings have not been validated in a representative sample in the United States. We aimed to examine the associations of Framingham risk score with cognitive function among older adults in a nationally representative sample, as well as by race or ethnicity, education, and family income. Methods and Results A total of 2254 older adults ≥60 years (57% female, 79% non-Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included in the final sample for analysis. All components of the Framingham risk score were obtained with questionnaire or measured in the laboratory. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test, and Animal Fluency Test. Multivariable linear regression models were used to assess the associations between Framingham risk score and test-specific and global cognition Z scores. Each incremental 5% in Framingham 10-year cardiovascular disease risk was associated with lower Z scores for Digit Symbol Substitution Test (ß=-0.06 [95% CI, -0.09 to -0.03]), delayed memory (ß=-0.05 [95% CI, -0.08 to -0.01]), immediate memory (ß=-0.07 [95% CI, -0.10 to -0.03]), and global cognition (ß=-0.05 [95% CI, -0.09 to -0.02]). Socioeconomic status, particularly race or ethnicity and monthly income levels, were strong effect measure modifiers of the associations. Conclusions Lower cardiovascular risk factors are associated with better cognitive function.

Cardiovascular Disease-Related Emergency Department Visits and Hospitalization among Women with Hypertensive Disorders of Pregnancy.

INTRODUCTION: The risk of developing cardiovascular disease is higher for women who had hypertensive disorders of pregnancy than for women without a history of hypertensive disorders of pregnancy. However, it is unknown whether the emergency department visits and hospitalization differ between women with a history of hypertensive disorders of pregnancy and women without hypertensive disorders of pregnancy. The objective of this study was to characterize and compare cardiovascular disease-related emergency department visits, hospitalization rates, and diagnoses in women with a history of hypertensive disorders of pregnancy with those in women without. METHODS: This study included participants from the California Teachers Study (N=58,718) with a history of pregnancy and data from 1995 through 2020. Incidence of cardiovascular disease-related emergency department visits and hospitalizations based on linkages with hospital records were modeled using multivariable negative binomial regression. Data were analyzed in 2022. RESULTS: A total of 5% of the women had a history of hypertensive disorders of pregnancy (5.4%, 95% CI=5.2%, 5.6). A total of 31% of women had 1 or more cardiovascular disease-related emergency department visits (30.9%), and 30.1% had 1 or more hospitalizations. The incidence of cardiovascular disease-related emergency department visits (adjusted incident rate ratio=8.96, p<0.001) and hospitalizations (adjusted incident rate ratio=8.88, p<0.001) were significantly higher for women with hypertensive disorders of pregnancy than for those without, adjusting for other related characteristics of the women. CONCLUSIONS: History of hypertensive disorders of pregnancy is associated with higher cardiovascular disease-related emergency department visits and hospitalizations. These findings underscore the potential burden on women and the healthcare system of managing complications associated with hypertensive disorders of pregnancy. Evaluating and managing cardiovascular disease risk factors in women with a history of hypertensive disorders of pregnancy is necessary to avoid cardiovascular disease-related emergency department visits and hospitalizations in this group.

The forkhead box protein P3 gene rs3761548 promoter polymorphism confers a genetic contribution to the risk of preeclampsia: A systematic review and meta-analysis.

Various studies have investigated the risk of preeclampsia with the forkhead box protein P3 (FOXP3) gene rs2232365 and rs3761548 polymorphisms. However, the results remained contradictory. A comprehensive literature search was conducted using the Cochrane Library, PubMed, and Web of Science (up to Oct 11, 2021). Meta-analysis was carried out in the R language environment for statistical computing and graphics. A fixed-effect or random-effects model was used according to the statistical significance of heterogeneity among included studies. The pooled odds ratios and corresponding 95% confidence intervals were calculated to estimate the strength of the effect. For the rs2232365 polymorphism, statistical significance was detected neither in the overall population nor among the East Asian and West Asian subgroups. However, for rs3761548, the summarized statistics revealed a significant association between the C allele carriage and preeclampsia risk in the homozygote, heterozygote, and dominant models. The further stratified analysis found this effect might be specific to West-South Asian ethnic subgroups. To sum up, this meta-analysis showed that the FOXP3 rs3761548 polymorphism was significantly associated with preeclampsia susceptibility, and it had a deleterious effect especially in the West-South Asian population. In contrast, rs2232365 may serve as neither a protective nor a risk factor for preeclampsia onset.

Cognitive behavioural therapy and medication for treatment of adolescent depression: a network meta-analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) and medication are widely accepted and useful interventions for individuals with depression. However, a gap remains in our current understanding of how CBT directly benefits adolescents with depression. AIMS: The purpose of this study was to examine the short- and long-term effectiveness of CBT only, CBT+Medication, or Medication alone in reducing the duration of major depressive episodes, lessening internalizing and externalizing symptoms and improving global functioning. METHODS: Data were extracted from 14 unique studies with a total of 35 comparisons. Network meta-analysis was conducted and p-scores, a measure of the extent of certainty that one treatment is better than another, were used to rank treatments. RESULTS: There was no significant difference between any two treatments for depression, nor internalizing or externalizing symptoms. For global functioning, CBT had significantly greater effect at the longest follow-up than CBT+Medication. CBT+Medication had the highest p-score for depression, short- and long-term effects, and internalizing and externalizing symptoms long-term effects. No indication of publication bias was found. CONCLUSIONS: Neither modality, CBT nor medication, is superior for treating adolescent depression. However, CBT was superior in improving global functioning, which is essential for meeting developmental goals.

Existing Datasets to Study the Impact of Internal Migration on Caregiving Arrangements among Older Adults in China.

Massive rural-to-urban migration in China has a significant impact on informal caregiving arrangements among Chinese older adults. To stimulate research on the intersection of migration and caregiving, we conducted an inventory of longitudinal aging survey datasets from mainland China. Large publicly available datasets that included measures related to migration and caregiving were searched and reviewed for eligibility. Key characteristics of each dataset, including study design, sample size, and measures, were extracted. Seven eligible datasets were identified, and five included nationally representative samples. Measures for migration varied across datasets. Some datasets included information on the migration history of older adults, whereas others focused on the migration of adult children. Similarly, caregiving was measured using different questions in each dataset. Caregiving activities were assessed with regard to their type, source, and amount. High-quality datasets exist to support research on migration and caregiving arrangements among Chinese older adults.

The moderating effect of cognitive reserve on cognitive function in patients with Acute Ischemic Stroke.

Background: Recovery of cognitive function after stroke has inter-individual variability. The theory of cognitive reserve offers a potential explanation of the variability in cognitive function after stroke. Objective: This study aimed to investigate the moderating effect of cognitive reserve on the relationship between the stroke severity and cognitive function after stroke. Materials and methods: A total of 220 patients with Acute Ischemic Stroke (AIS) were recruited in 2021 from two stroke centers in Nanjing, China. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Cognitive Reserve Index questionnaire (CRIq) and validated Montreal Cognitive Assessment, Changsha Version (MoCA-CS) were used to assess cognitive reserve and cognitive function within 7 days after stroke onset, respectively. A series of multivariate linear regression models were applied to test the moderating effect of cognitive reserve. Results: Patients with a higher level of cognitive reserve had better cognitive function after stroke compared with those with a lower level of cognitive reserve (ß = 0.074, p = 0.003). The interaction of NIHSS and cognitive reserve was statistically significant (ß = -0.010, p = 0.045) after adjusting for some key covariates [e.g., age, marital status, Oxfordshire Community Stroke Project (OCSP) classification, Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, cerebral vascular stenosis, diabetes and atrial fibrillation]. Conclusion: Cognitive reserve may help to buffer the effect of stroke-related pathology on cognitive decline in Chinese acute stroke patients. Enhancing cognitive reserve in stroke patients may be one of the potential strategies for preventing vascular dementia.

Factors associated with racial differences in all-cause 30-day readmission in adults with cardiovascular disease: an observational study of a large healthcare system.

OBJECTIVE: To examine factors contributing to racial differences in 30-day readmission in patients with cardiovascular disease (CVD). DESIGN: Patients were enrolled from 1 January 2015 to 31 August 2017 and data were collected from electronic health records and a standardised interview administered prior to discharge. SETTING: Duke Heart Center in the Duke University Health System. PARTICIPANTS: Patients aged 18 and older admitted for the treatment of cardiovascular-related conditions (n=734). MAIN OUTCOME AND MEASURES: All-cause readmission within 30 days was the main outcome. Multivariate logistic regression models were used to examine whether and to what extent socioeconomic, psychosocial, behavioural and healthcare-related factors contributed to 30-day readmissions in Black and White CVD patients. RESULTS: The median age of patients was 66 years and 18.1% (n=133) were readmitted within 30 days after discharge. Black patients were more likely than White patients to be readmitted (OR 1.62; 95% CI 1.18 to 2.23) and the racial difference in readmissions was largely reduced after taking into account differences in a wide range of clinical and non-clinical factors (OR 1.37; 95% CI 0.98 to 1.91). In Black patients, readmission risks were especially high in those who were retired (OR 3.71; 95% CI 1.71 to 8.07), never married (OR 2.21; 95% CI 1.21 to 4.05), had difficulty accessing their routine care (OR 2.88; 95% CI 1.70 to 4.88) or had been hospitalised in the prior year (OR 1.97; 95% CI 1.16 to 3.37). In White patients, being widowed (OR 2.39; 95% CI 1.41 to 4.07) and reporting a higher number of depressive symptoms (OR 1.07; 95% CI 1.00 to 1.13) were the key factors associated with higher risks of readmission. CONCLUSIONS AND RELEVANCE: Black patients were more likely than White patients to be readmitted within 30 days after hospitalisation for CVD. The factors contributing to readmission differed by race and offer important clues for identifying patients at high risk of readmission and tailoring interventions to reduce these risks.

Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV­2 papain-like protease.

The coronavirus papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15 (ISG15), which enable it to participate in virus replication and host innate immune pathways. Therefore, PLpro is considered an attractive antiviral drug target. Here, we show that parthenolide, a germacrane sesquiterpene lactone, has SARS-CoV-2 PLpro inhibitory activity. Parthenolide covalently binds to Cys-191 or Cys-194 of the PLpro protein, but not the Cys-111 at the PLpro catalytic site. Mutation of Cys-191 or Cys-194 reduces the activity of PLpro. Molecular docking studies show that parthenolide may also form hydrogen bonds with Lys-192, Thr-193, and Gln-231. Furthermore, parthenolide inhibits the deISGylation but not the deubiquitinating activity of PLpro in vitro. These results reveal that parthenolide inhibits PLpro activity by allosteric regulation.

JOSD2 regulates PKM2 nuclear translocation and reduces acute myeloid leukemia progression.

Pyruvate kinase M2 (PKM2) plays an important role in the metabolism and proliferation of leukemia cells. Here, we show that deubiquitinase JOSD2, a novel tumor suppressor, blocks PKM2 nuclear localization by reducing its K433 acetylation in acute myeloid leukemia (AML). Firstly, we show that JOSD2 is significantly down-regulated in primary AML cells. Reconstitute of JOSD2 in AML cells significantly inhibit cell viability and induce cell apoptosis. Next, PKM2 is identified as a novel interaction protein of JOSD2 by mass spectrometry, co- immunoprecipitation and co-immunofluorescence in HL60 cells. However, JOSD2 does not affect PKM2 protein stability. We then found out that JOSD2 inhibits nuclear localization of PKM2 by reducing its K433 acetylation modification, accompanied by decreased downstream gene expression through non-glycolytic functions. Finally, JOSD2 decreases AML progression in vivo. Taken together, we propose that JOSD2 blocks PKM2 nuclear localization and reduces AML progression.

Caregiver burden and its associated factors among family caregivers of persons with dementia in Shanghai, China: a cross-sectional study.

OBJECTIVE: To assess the level of caregiver burden and factors associated with it among family caregivers of persons with dementia (PWD) living in communities of Shanghai, China. DESIGN: Cross-sectional study. SETTING: Communities in Hongkou District of Shanghai, China. PARTICIPANTS: A random sample of 109 older adults with dementia and their primary family caregivers. MAIN OUTCOME MEASURE: Caregiver burden measured by the Caregiver Burden Inventory (CBI), and the Caregivers' depressive symptom measured by the simplified Chinese version of Self-rating Depression Scale was the outcome variable of the study. The independent variables, including the cognitive function (measured by Montreal Cognitive Assessment (MoCA), sleep quality assessed by the Pittsburgh Sleep Quality Index, abilities of daily life assessed by the Activities of Daily Living Scale, and behavioural and psychological symptoms assessed by the Neuropsychiatric Inventory of PWDs, the community service utilisation (measured by the Community Service Utilisation Measurement), perceived social support (assessed by three questions), positive aspects of caregiving (PAC) (assessed by the PAC) of dementia caregivers, were analysed. Multivariate linear regression was employed to determine the factors related to caregiver burden. RESULTS: The average level of CBI was 65.92±16.74. The score of MoCA, PAC and perceived social support of caregivers were negatively associated with caregiver burden (ß=-0.84, p<0.001, ß=-3.61, p=0.03 and ß=-1.22, p=0.001, respectively). Community service utilisation was positively associated (ß=3.46, p<0.001) with caregiver burden. Perceived social support by the caregiver moderated the relationship between caregiver burden and caregivers' depression symptoms. CONCLUSION: Dementia caregivers experienced a high level of caregiver burden. The cognitive function of PWD, PAC, social support and community service utilisation were factors associated with caregiver burden. Strengthening social support, providing more high-quality home care services, promoting PAC are imperative to reduce caregiver burden.