NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

A novel tryptanthrin-based "on-off-on" probe for sequential sensing Cu2+/S2- in water samples.

Copper ions (Cu2+) and sulfide (S2-) play essential roles in many physiologies and pathologic processes. Herein, a new "on-off-on" tryptanthrin-based probe TR-1 (TR-1) has been designed and synthesized in a facile and economical way. TR-1 exhibited highly selective and sensitive response to Cu2+ without any interference over 14 competitive metal ions and the detection limit downs to 24 nM, which is far below the Chinese standard of fishery water quality (157 nM). The 'in situ' prepared complex TR-1 + Cu2+ could also be applied to detect S2- with the detection limit of 62 nM. Further, TR-1 was potentially applied for the analysis of copper ions in water samples.

Does the Cognitive Change Index Predict Future Cognitive and Clinical Decline? Longitudinal Analysis in a Demographically Diverse Cohort.

Background: The Cognitive Change Index (CCI) is a widely-used measure of self-perceived cognitive ability and change. Unfortunately, it is unclear if the CCI predicts future cognitive and clinical decline. Objective: We evaluated baseline CCI to predict transition from normal cognition to cognitive impairment in nondemented older adults and in predementia groups including, subjective cognitive decline, motoric cognitive risk syndrome, and mild cognitive impairment. Different versions of the CCI were assessed to uncover any differential risk sensitivity. We also examined the effect of ethnicity/race on CCI. Methods: Einstein Aging Study participants (N = 322, Mage = 77.57±4.96, % female=67.1, Meducation = 15.06±3.54, % non-Hispanic white = 46.3) completed an expanded 40-item CCI version (CCI-40) and neuropsychological evaluation (including Clinical Dementia Rating Scale [CDR], Montreal Cognitive Assessment, and Craft Story) at baseline and annual follow-up (Mfollow - up=3.4 years). CCI-40 includes the original 20 items (CCI-20) and the first 12 memory items (CCI-12). Linear mixed effects models (LME) and generalized LME assessed the association of CCI total scores at baseline with rate of decline in neuropsychological tests and CDR. Results: In the overall sample and across predementia groups, the CCI was associated with rate of change in log odds on CDR, with higher CCI at baseline predicting faster increase in the odds of being impaired on CDR. The predictive validity of the CCI broadly held across versions (CCI-12, 20, 40) and ethnic/racial groups (non-Hispanic black and white). Conclusions: Self-perception of cognitive change on the CCI is a useful marker of dementia risk in demographically/clinically diverse nondemented samples. All CCI versions successfully predicted decline.

Molecular recognition and binding between human plasminogen Kringle 5 and α-chain of human complement component C3b by frontal chromatography and dynamics simulation.

The binding and molecular recognition between α-chain of human complement C3b (α-chain of C3b) and human plasminogen Kringle 5 (Kringle 5) were studied and explored by frontal chromatography and dynamics simulation in the combination of bio-specific technologies. The specific interaction between the α-chain of C3b and Kringle 5 was initially confirmed by ligand blot and ELISA (Kd = 4.243×10-6 L/mol). Furthermore, the binding determination conducted via frontal chromatography showed that the presence of a single binding site between them, with the binding constant of 2.98 × 105 L/mol. Then the molecular recognition by dynamics simulation and molecular docking showed that there were 9 and 13 amino acid residues respective in the Kringle 5 and α-chain of C3b directly implicated in the binding and the main stabilizing forces were electrostatic force (-55.99 ± 11.82 kcal/mol) and Van der Waals forces (-42.70 ± 3.45 kcal/mol). Additionally, a loop structure (65-71) in Kringle 5 underwent a conformational change from a random structure to an α-helix and a loop structure (417-425) in α-chain of C3b was closer to the molecular center, both of them were more conducive to the binding between them. Meanwhile, the involvement of the lysine binding site of Kringle 5 played an important role in the binding process. In addition, the erythrocyte-antibody complement rosette assay substantiated that the presence of Kringle 5 hindered the transportation of α-chain of C3b to antigen-antibody complex in a dose-dependent manner. These findings collectively indicated that the α-chain of C3b is very likely a receptor protein for Kringle 5, which provides a methodology for other similar investigations and valuable insights into expansion of the pharmacological effects and potential application of Kringle 5 in immune-related diseases.

Synthesis and Antifungal Properties of 1,2,4-Triazole Schiff Base Agents Based on a 3D-QSAR Model.

Based on our previous research, a 3D-QSAR model (q2=0.51, ONC=5, r2=0.982, F=271.887, SEE=0.052) was established to predict the inhibitory effects of triazole Schiff base compounds on Fusarium graminearum, and its predictive ability was also confirmed through the statistical parameters. According to the results of the model design, 30 compounds with superior bioactivity compared to the template molecule 4 were obtained. Seven of these compounds (DES2-6, DES9-10) with improved biological activity and readily available raw materials were successfully synthesized. Their structures were confirmed through HRMS, NMR, and single crystal X-ray diffraction analysis (DES-5). The bioactivity of the final products was investigated through an in vitro antifungal assay. There was little difference in the EC50 values between the experimental and predicted values of the model, demonstrating the reliability of the model. Especially, DES-3 (EC50=9.915 mg/L) and DES-5 (EC50=9.384 mg/L) exhibited better inhibitory effects on Fusarium graminearum compared to the standard drug (SD) triadimenol (EC50=10.820 mg/L). These compounds could serve as potential new fungicides for future research. The interaction between the final products and isocitrate lyase (ICL) was investigated through molecular docking. Compounds with R groups that have a higher electron-donating capacity were found to be biologically active.

"Cognitive" Criteria in Older Adults With Slow Gait Speed: Implications for Motoric Cognitive Risk Syndrome.

BACKGROUND: Motoric cognitive risk syndrome (MCR) is a predementia condition that combines slow gait speed and subjective cognitive concerns (SCC). The SCC criterion is presently unstandardized, possibly limiting risk detection. We sought to (a) characterize SCC practices through MCR literature review; (b) investigate the ability of SCC in slow gait individuals in predicting the likelihood of cognitive impairment in a demographically diverse sample of community-dwelling, nondemented older adults. METHODS: First, we comprehensively reviewed the MCR literature, extracting information regarding SCC measures, items, sources, and cognitive domain. Next, Einstein Aging Study (EAS) participants (N = 278, Mage = 77.22 ±â€…4.74, %female = 67, Meducation = 15 ±â€…3.61, %non-Hispanic White = 46.3) completed gait, Clinical Dementia Rating Scale (CDR), and SCC assessment at baseline and annual follow-up (Mfollow-up = 3.5). Forty-two participants met slow gait criteria at baseline. Generalized linear mixed-effects models examined baseline SCC to predict cognitive impairment on CDR over follow-up. RESULTS: We reviewed all published MCR studies (N = 106) and documented ambiguity in SCC criteria, with a prevalent approach being use of a single self-reported memory item. In EAS, high SCC endorsement on a comprehensive, validated screen significantly affected the rate of cognitive impairment (CDR; ßinteraction = 0.039, p = .018) in slow gait individuals. CONCLUSIONS: An assessment approach that queries across numerous SCC domains was found to predict future decline in clinical dementia status in slow gait older adults. Current SCC practices in MCR, which tend to utilize a single-memory item, may not be the optimal approach. We discuss the implications of SCC criteria validation and standardization to enhance early dementia detection in MCR.

Natural products fragment-based design and synthesis of a novel pentacyclic ring system as potential MAPK inhibitor.

The synthesis of compounds based on fragments derived from natural products (NPs) serves as a source of inspiration for the design of pseudo-natural products (PNPs), to identify bioactive molecules that exhibit similar characteristics to NPs. These novel molecular scaffolds exhibit previously unexplored biological activities as well. This study reports the development and synthesis of a novel pentacyclic ring system, the indole-pyrimidine-quinoline (IPQ) scaffold. The design of this scaffold was based on the structural characteristics of four natural products, namely tryptanthrin, luotonin A, rutaecarpine, and camptothecin. Several successive steps accomplished the effective synthesis of the IPQ scaffold. The constituent components of the pentacycle, containing the indole, quinazolinone, pyrimidone, and quinoline units, possess significant biological significance. Compound 1a demonstrated noteworthy anti-tumor activity efficacy against A549 cell lines among the tested compounds. The compound 1a was observed to elicit cell cycle arrest in both the G2/M and S phases, as well as trigger apoptosis in A549 cells. These effects were attributed to its ability to modulate the activation of mitochondrial-related mitogen-activated protein kinase (MAPK) signaling pathways.

Examining the role of participant and study partner report in widely-used classification approaches of mild cognitive impairment in demographically-diverse community dwelling individuals: results from the Einstein aging study.

Objective: The role of subjective cognitive concerns (SCC) as a diagnostic criterion for MCI remains uncertain and limits the development of a universally (or widely)-accepted MCI definition. The optimal MCI definition should define an at-risk state and accurately predict the development of incident dementia. Questions remain about operationalization of definitions of self- and informant-reported SCCs and their individual and joint associations with incident dementia. Methods: The present study included Einstein Aging Study participants who were non-Hispanic White or Black, free of dementia at enrollment, had follow-up, and completed neuropsychological tests and self-reported SCC at enrollment to determine MCI status. Informant-reported SCC at baseline were assessed via the CERAD clinical history questionnaire. Self-reported SCC were measured using the CERAD, items from the EAS Health Self-Assessment, and the single memory item from the Geriatric Depression Scale. Cox proportional hazards models examined the association of different operationalizations of SCC with Petersen and Jak/Bondi MCI definitions on the risk of dementia, further controlling for age, sex, education, and race/ethnicity. Time-dependent sensitivity and specificity at specific time points for each definition, and Youden's index were calculated as an accuracy measure. Cox proportional hazards models were also used to evaluate the associations of combinations of self- and informant-reported SCC with the risk of incident dementia. Results: 91% of the sample endorsed at least one SCC. Youden's index showed that not including SCC in either Jak/Bondi or Petersen classifications had the best balance between sensitivity and specificity across follow-up. A subset of individuals with informants, on average, had a lower proportion of non-Hispanic Blacks and 94% endorsed at least one self-reported SCC. Both informant-reported and self-reported SCC were significantly associated with incident dementia. Conclusion: Our findings suggest that the SCC criterion may not improve the predictive validity for dementia when included in widely-employed definitions of MCI. Consistent with some prior research, informant-reported SCC was more related to risk of incident dementia than self-reported SCC. Given that requiring informant report as a diagnostic criterion may unintentionally exclude health disparate groups, additional consideration is needed to determine how best to utilize informant-report in MCI diagnosis.

Trans-retro-peritoneal laparoscopic partial nephrectomy for posterior hilar tumor: technical feasibility and preliminary results.

Background: Urologists still encounter challenges when it comes to the surgical management of tumors located on the posterior lip and posterior renal hilar region. We propose a trans-retro-peritoneal (TRP) technique to address the difficulties associated with posterior hilar tumors during retroperitoneal laparoscopic partial nephrectomy (LPN). Its efficacy was evaluated in a retrospective case-control study. Methods: The patients with posterior hilar tumors (≤7 cm) that underwent retroperitoneal LPN were included. The TRP technique allowed the posterior hilar tumor completely visible by incising the ventral peritoneum and rotating kidney ventrally during retroperitoneal LPN, which was applied in 36 cases, while the conventional retroperitoneal LPN was performed in 22 cases. Perioperative data were analyzed to evaluate the efficacy of TRP-LPN. Results: In TRP-LPN group, the TRP technique was successfully performed in all the patients without converting to open surgery or radical nephrectomy. The warm ischemia time was significantly shorter in TRP-LPN group than conventional LPN group (20.3 vs. 28.5 min, P<0.001). Furthermore, the mean estimated blood loss in TRR-LPN group was significantly less than that in conventional LPN group (86.5 vs. 90.9 mL, P<0.05). The mean operation time and recovery time of gastrointestinal function were similar between two groups. No severe complications occurred, and no positive surgical margin was found. The rate of Trifecta achievement was 50.0% (18/36) and 31.8% (7/22) respectively for TRP-LPN and conventional LPN (P=0.175). After mean follow-up of 21 months, no recurrence or metastasis occurred in all cases. Conclusions: Our findings, as demonstrated by the Trifecta outcomes, support the feasibility and efficacy of TRP-LPN in managing posterior renal hilar tumors. This approach may be considered as an efficient option for surgical management of such tumors.

Physiological mechanism of sodium salicylate and folcisteine on alleviating salt stress in wheat seedlings.

Soil salinization substantially hampers the growth and development of wheat, potentially leading to plant death in severe cases, thus reducing grain yield and quality. This phenomenon poses a significant threat to food security in China. We investigated the effects of two exogenous plant growth regulators, sodium salicylate and folcisteine, on the wheat physiology and key characteristics under salt stress using hydroponics method. The results indicated that both regulators effectively mitigated the growth inhibition of wheat under salt stress. We assessed morphological and physiological indexes, including antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], peroxidase [POD]) and malondialdehyde (MDA) concentration in wheat after foliar application of sodium salicylate and folcisteine under salt stress. The findings revealed that sodium salicylate was more effective than folcisteine. However, folcisteine showed superior performance in reducing hydrogen peroxide (H2O2) content and superoxide anion (O2-) level compared to sodium salicylate. Simultaneously, Concurrent application of both regulators synergistically enhanced their efficacy, yielding the most favorable outcomes. In addition, this study noted that while the initial effects of these regulators were not pronounced, their sustained application significantly improved wheat growth in stressful condition and alleviated the detrimental impacts of salt stress. This approach could effectively guarantee the food security and production in China.

Epidemiology of Motoric Cognitive Risk Syndrome in the Kerala Einstein Study: Protocol for a Prospective Cohort Study.

BACKGROUND: The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. OBJECTIVE: The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. METHODS: KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. RESULTS: KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. CONCLUSIONS: KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49933.

Screening, characterization and specific binding mechanism of aptamers against human plasminogen Kringle 5.

Plasminogen Kringle 5 is one of the most potent cytokines identified to inhibit the proliferation and migration of vascular endothelial cells. Herein, six aptamer candidates that specifically bind to Kringle 5 were generated by the systematic evolution of ligands by exponential enrichment (SELEX). After 10 rounds of screening against Kringle 5, a highly enriched ssDNA pool was sequenced and the representative aptamers were subjected to binding assays to evaluate their affinity and specificity. The preferred aptamer KG-4, which demonstrated a low dissociation constant (Kd) of âˆ¼ 432 nM and excellent selectivity for Kringle 5. A conserved "motif" of eight bases located at the stem-loop intersection, common to the aptamer, was further confirmed as the recognition element for binding with Kringle 5. The bulge formed by the motif and depression on the lysine binding site of Kringle 5 were both located at the binding interface, and the "induced fit" between their structures played a central role in the recognition process. Kringle 5 interacts KG-4 primarily through enthalpy-driven van der Waals forces and hydrogen bond. The key nucleotides A34 and C35 at motif on KG-4 and the positively charged amino acids in the loop 1 and loop 4 regions on Kringle 5 play a major role in the interaction. Furthermore, KG-4 dose-dependently reduced the proliferation inhibition of vascular endothelial cells by Kringle 5 and had a blocking effect on the function of Kringle 5 in inhibiting migration and promoting apoptosis of vascular endothelial cells in vitro. This study put a new light on protein-aptamer binding mechanism and may provide insight into the treatment of ischemic diseases by target depletion of Kringle 5.

Visual-somatosensory integration (VSI) as a novel marker of Alzheimer's disease: A comprehensive overview of the VSI study.

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer's disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer's pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.

Tracking cognition with the T-MoCA in a racially/ethnically diverse older adult cohort.

Introduction: We investigated the utility of the Telephone-Montreal Cognitive Assessment (T-MoCA) to track cognition in a diverse sample from the Einstein Aging Study. Methods: Telephone and in-person MoCA data, collected annually, were used to evaluate longitudinal cognitive performance. Joint models of T-MoCA and in-person MoCA compared changes, variance, and test-retest reliability measured by intraclass correlation coefficient by racial/ethnic group. Results: There were no significant differences in baseline performance or longitudinal changes across three study waves for both MoCA formats. T-MoCA performance improved over waves 1-3 but declined afterward. Test-retest reliability was lower for the T-MoCA than for the in-person MoCA. In comparison with non-Hispanic Whites, non-Hispanic Blacks and Hispanics performed worse at baseline on both MoCA formats and showed lower correlations between T-MoCA and in-person versions. Conclusions: The T-MoCA provides valuable information on cognitive change, despite racial/ethnic disparities and practice effects. We discuss implications for health disparity populations. Highlights: We assessed the comparability of Telephone-Montreal Cognitive Assessment (T-MoCA) and in-person MoCA for tracking cognition.Changes within 3 years in T-MoCA were similar to that for the in-person MoCA.T-MoCA is subject to practice effects and shows difference in performance by race/ethnicity.Test-retest reliability of T-MoCA is lower than that for in-person MoCA.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Randomized Controlled Trial of Social Ballroom Dancing and Treadmill Walking: Preliminary Findings on Executive Function and Neuroplasticity From Dementia-at-Risk Older Adults.

This randomized controlled trial (NCT03475316) examined the relative efficacy of 6 months of social ballroom dancing and treadmill walking on a composite executive function score, generated from digit symbol substitution test, flanker interference, and walking while talking tasks. Brain activation during functional magnetic resonance imaging (fMRI) versions of these executive function tasks were secondary outcomes. Twenty-five dementia-at-risk older adults (memory impairment screen score of ≥3 to ≤6 and/or an Alzheimer's disease-8 Dementia Screening Interview of ≥1) were randomized in June 2019 to March 2020-16 completed the intervention before study termination due to the COVID-19 (eight in each group). Composite executive function scores improved post-intervention in both groups, but there was no evidence for between-group differences. Social dancing, however, generated greater improvements on digit symbol substitution test than treadmill walking. No intervention-related differences were observed in brain activation-although less hippocampal atrophy (tertiary) was observed following social dancing than treadmill walking. These preliminary findings are promising but need to be confirmed in future large-scale and sufficiently powered randomized controlled trials.

Concordance Between Logical Memory and Craft Story 21 in Community-Dwelling Older Adults: The Role of Demographic Factors And Cognitive Status.

OBJECTIVE: Episodic memory loss, a hallmark symptom of Alzheimer's Disease, is frequently quantified by story memory performance. The National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDSNB) replaced Logical Memory with Craft Story 21 in UDSNB Version 3. The concordance between these story memory tasks is poorly characterized in demographically diverse older adults, possibly jeopardizing the integrity of longitudinal data in aging cohorts. METHOD: Einstein Aging Study participants (n = 298; Mage = 76.6; Meducation = 15; 66.4% women; 43.3% Non-Hispanic White) completed UDSNB measures, including Craft Story and Logical Memory. Classification as normal cognition (n = 206) or mild cognitive impairment (n = 90) was based on Jak/Bondi criteria. Analyses included correlations, linear regression, and equipercentile equating methods to characterize the relationship between Logical Memory and Craft Story. Multivariate linear mixed effects models explored the association of covariates and practice effects over follow-up, stratified by cognitive status and race/ethnicity. RESULTS: Immediate (r = 0.54) and delayed (r = 0.56) versions of Logical Memory and Craft Story were moderately correlated. Age, education, depression, and female sex were associated with Logical Memory, while age, education, cognitive status, and male sex were associated with Craft Story. Significant differential effects of sex on story memory were observed. CONCLUSIONS: We demonstrated that Logical Memory and Craft Story may be used largely interchangeably; however, memory may be enhanced for stories with a protagonist of the same sex as the participant. Craft Story was somewhat more associated with mild cognitive impairment in the overall sample, but especially in non-Hispanic Black participants. We discuss how results inform test selection considerations.

The effect of chronoradiotherapy on cervical cancer patients: A multicenter randomized controlled study.

Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

Inflammatory biomarkers and motoric cognitive risk syndrome: Multicohort survey.

Background: Inflammation may play a role in Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome comprised of slow gait and cognitive complaints. Our objective was to examine associations of inflammatory biomarkers with MCR. Methods: We examined association of interleukin-6 (IL-6) and C-reactive protein (CRP) with prevalent MCR using logistic regression in 3,101 older adults (52% female) from five cohorts (National Center for Geriatrics & Gerontology Study of Geriatric Syndromes [NCGG-SGS], Central Control of Mobility in Aging [CCMA], Tasmanian Study of Cognition and Gait [TASCOG], LonGenity, and Einstein Aging Study [EAS]). Associations were reported as odds ratios adjusted for sex, age, education, depressive symptoms, body mass index, and vascular diseases (aOR) with 95% confidence intervals (CI). Meta-analysis and analyses stratified by vascular disease were also done. Results: Although associations between higher (worse) CRP and IL-6 tertiles and MCR were only seen in three out of the five cohorts (EAS, TASCOG, and LonGenity), when a pooled meta-analysis was performed, a robust association was demonstrated. In meta-analysis, highest tertiles of IL-6 (aOR 1.57, 95%CI 1.01- 2.44) and CRP (aOR 1.65, 95%CI 1.09-2.48) was associated with MCR versus lowest tertiles in the pooled sample. Higher CRP was associated with MCR among those with vascular disease in TASCOG and LonGenity cohorts, and among those without vascular disease in EAS. Conclusions: IL-6 and CRP levels are associated with MCR in older adults, and this association varies by presence of vascular disease.