Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Overcome the Limitation of Phenome-Wide Association Studies (PheWAS): Extension of PheWAS to Efficient and Robust Large-Scale ICD Codes Analysis.

The Phenome-wide association studies (PheWAS) have become widely used for efficient, high-throughput evaluation of relationship between a genetic factor and a large number of disease phenotypes, typically extracted from a DNA biobank linked with electronic medical records (EMR). Phecodes, billing code-derived disease case-control status, are usually used as outcome variables in PheWAS and logistic regression has been the standard choice of analysis method. Since the clinical diagnoses in EMR are often inaccurate with errors which can lead to biases in the odds ratio estimates, much effort has been put to accurately define the cases and controls to ensure an accurate analysis. Specifically in order to correctly classify controls in the population, an exclusion criteria list for each Phecode was manually compiled to obtain unbiased odds ratios. However, the accuracy of the list cannot be guaranteed without extensive data curation process. The costly curation process limits the efficiency of large-scale analyses that take full advantage of all structured phenotypic information available in EMR. Here, we proposed to estimate relative risks (RR) instead. We first demonstrated the desired nature of RR that overcomes the inaccuracy in the controls via theoretical formula. With simulation and real data application, we further confirmed that RR is unbiased without compiling exclusion criteria lists. With RR as estimates, we are able to efficiently extend PheWAS to a larger-scale, phenome construction agnostic analysis of phenotypes, using ICD 9/10 codes, which preserve much more disease-related clinical information than Phecodes.

Cost-effectiveness of medication therapy management among Medicare population and across racial/ethnic groups.

BACKGROUND: Inappropriate medication utilization among older adults is a pressing concern in the United States, owing to its high prevalence and the consequential detrimental impact it engenders. The adverse effects stemming from the inappropriate use of medication may be unequally borne by racial/ethnic minority populations, calling for greater efforts towards promoting equity in healthcare. The study objective was to assess the cost-effectiveness of Medication Therapy Management (MTM) services among Medicare beneficiaries and across racial/ethnic groups. METHODS: Medicare administrative data from 2016 to 2017 linked to Area Health Resources Files were used to analyze Medicare fee-for-service patients aged 65 or above with continuous Parts A/B/D coverage. The intervention group included new MTM enrollees in 2017; the control group referred to patients who met the general MTM eligible criteria but did not enroll in 2016 or 2017. The 2 groups were matched using a propensity score method. Effectiveness was evaluated as the proportion of appropriate medication utilization based on performance measures developed by the Pharmacy Quality Alliance. Costs were computed as total healthcare costs from Medicare perspective. A multivariable net benefit regressions with a classic linear model and Bayesian analysis were utilized. Net benefit was calculated based on willingness-to-pay thresholds at various multiples of the gross domestic product in 2017. Three-way interaction terms among dummy variables for MTM enrollment, 2017, and racial/ethnic minority groups were incorporated in a difference-in-differences study design. RESULTS: After adjusting for patient characteristics, the findings indicate that MTM receipt was associated with incremental net benefit among each race and ethnicity. For instance, the net benefit of MTM among the non-Hispanic White patients was $2498 (95% confidence interval = $1609, $3386) at a willingness-to-pay value of $59,908. The study found no significant difference in net benefits for MTM services between minority and White patients. CONCLUSION: The study provides evidence that MTM is a cost-effective tool for managing medication utilization among the Medicare population. However, MTM may not be cost-effective in reducing racial/ethnic disparities in medication utilization in the short term. Further research is needed to understand the long-term cost-effectiveness of MTM on racial/ethnic disparities.

Ethylene-responsive VviERF003 modulates glycosylated monoterpenoid synthesis by upregulating VviGT14 in grapes.

Terpenoids are important contributors to the aroma of grapes and wines. Grapes contain terpenoids in both volatile free form and non-volatile glycosidic form, with the latter being more abundant. Glycosylated terpenoids are deemed as latent aromatic potentials for their essential role in adding to the flowery and fruity bouquet of wines. However, the transcriptional regulatory mechanism underlying glycosylated terpenoid biosynthesis remains poorly understood. Our prior study identified an AP2/ERF transcription factor, VviERF003, through DNA pull-down screening using the promoter of terpenoid glycosyltransferase VviGT14 gene. This study demonstrated that both genes were co-expressed and synchronized with the accumulation of glycosylated monoterpenoids during grape maturation. VviERF003 can bind to the VviGT14 promoter and promote its activity according to yeast one-hybrid and dual-luciferase assays. VviERF003 upregulated VviGT14 expression in vivo, leading to increased production of glycosylated monoterpenoids based on the evidence from overexpression or RNA interference in leaves, berry skins, and calli of grapes, as well as tomato fruits. Additionally, VviERF003 and VviGT14 expressions and glycosylated monoterpenoid levels were induced by ethylene in grapes. The findings suggest that VviERF003 is ethylene-responsive and stimulates glycosylated monoterpenoid biosynthesis through upregulating VviGT14 expression.

Luteolin, apigenin, and chrysin inhibit lipotoxicity-induced NLRP3 inflammasome activation and autophagy damage in macrophages by suppressing endoplasmic reticulum stress.

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant and anti-inflammatory properties, but whether they inhibit lipotoxicity-mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages and Kupffer cells stimulated with 100 µM palmitate (PA) in the presence or absence of 20 µM of each flavone. PA increased p-PERK, p-IRE1α, p-JNK1/2, CHOP, and TXNIP as well as p62 and LC3-II expression and induced autophagic flux damage. Caspase-1 activation and IL-1ß release were also noted after 24 h of exposure to PA. In the presence of the PERK inhibitor GSK2656157, PA-induced CHOP and TXNIP expression and caspase-1 activation were mitigated. Compared with PA treatment alone, Bcl-2 coupled to beclin-1 was elevated and autophagy was reversed by the JNK inhibitor SP600125. With luteolin, apigenin, and chrysin treatment, PA-induced ROS production, ER stress, TXNIP expression, autophagic flux damage, and apoptosis were ameliorated. Moreover, TXNIP binding to NLRP3 and IL-1ß release in response to LPS/PA challenge were reduced. These results suggest that luteolin, apigenin, and chrysin protect hepatic macrophages against PA-induced NLRP3 inflammasome activation and autophagy damage by attenuating endoplasmic reticulum stress.

Associations of Matrix Metalloproteinase-8 Genotypes to Renal Cell Carcinoma in Taiwan.

BACKGROUND/AIM: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aimed to elucidate the role of MMP-8 genotypes in RCC susceptibility. MATERIALS AND METHODS: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, sex, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed. RESULTS: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, sex, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes. CONCLUSION: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC.

Cancer diagnosis and treatment in working-age adults: Implications for employment, health insurance coverage, and financial hardship in the United States.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship. They summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship and health insurance coverage, benefit design, and employee benefits, such as paid sick leave, among working-age adults with a history of cancer and compare them with estimates among working-age adults without a history of cancer from the most recently available years of the National Health Interview Survey (2019-2021). Then, the authors identify opportunities for addressing employment and health insurance coverage challenges at multiple levels, including federal, state, and local policies; employers; cancer care delivery organizations; and nonprofit organizations. These efforts, when informed by research to identify best practices, can potentially help mitigate the financial hardship associated with cancer.

Accumulative Assessment of Upper Extremity.

OBJECTIVE: The Fugl-Meyer assessment for upper extremity (FMA-UE) is a measure for assessing upper extremity motor function in patients with stroke. However, the considerable administration time of the assessment decreases its feasibility. This study aimed to develop an accumulative assessment system of upper extremity motor function (AAS-UE) based on the FMA-UE to improve administrative efficiency while retaining sufficient psychometric properties. METHODS: The study used secondary data from 3 previous studies having FMA-UE datasets, including 2 follow-up studies for subacute stroke individuals and 1 test-retest study for individuals with chronic stroke. The AAS-UE adopted deep learning algorithms to use patients' prior information (ie, the FMA-UE scores in previous assessments, time interval of adjacent assessments, and chronicity of stroke) to select a short and personalized item set for the following assessment items and reproduce their FMA-UE scores. RESULTS: Our data included a total of 682 patients after stroke. The AAS-UE administered 10 different items for each patient. The AAS-UE demonstrated good concurrent validity (r = 0.97-0.99 with the FMA-UE), high test-retest reliability (intra-class correlation coefficient = 0.96), low random measurement error (percentage of minimal detectable change = 15.6%), good group-level responsiveness (standardized response mean = 0.65-1.07), and good individual-level responsiveness (30.5%-53.2% of patients showed significant improvement). These psychometric properties were comparable to those of the FMA-UE. CONCLUSION: The AAS-UE uses an innovative assessment method which makes good use of patients' prior information to achieve administrative efficiency with good psychometric properties. IMPACT: This study demonstrates a new assessment method to improve administrative efficiency while retaining psychometric properties, especially individual-level responsiveness and random measurement error, by making good use of patients' basic information and medical records.

tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones.

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

CONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy.

PURPOSE: Although checkpoint inhibitors have improved first-line treatment for non-small cell lung cancer (NSCLC), a therapeutic need remains for patients whose disease does not respond or who experience disease progression after anti-PD-L1/PD-1 immunotherapy. CONTACT-01 (ClinicalTrials.gov identifier: NCT04471428) evaluated atezolizumab plus cabozantinib versus docetaxel in patients with metastatic NSCLC who developed disease progression after concurrent or sequential treatment with anti-PD-L1/PD-1 and platinum-containing chemotherapy. METHODS: This multicenter, open-label, phase III trial randomly assigned patients 1:1 to atezolizumab 1,200 mg intravenously once every 3 weeks (q3w) plus cabozantinib 40 mg orally once daily or docetaxel 75 mg/m2 intravenously once every 3 weeks. The primary end point was overall survival (OS). RESULTS: One hundred eighty-six patients were assigned atezolizumab plus cabozantinib, and 180 docetaxel. Minimum OS follow-up was 10.9 months. Median OS was 10.7 months (95% CI, 8.8 to 12.3) with atezolizumab plus cabozantinib and 10.5 months (95% CI, 8.6 to 13.0) with docetaxel (stratified hazard ratio [HR], 0.88 [95% CI, 0.68 to 1.16]; P = .3668). Median progression-free survival was 4.6 months (95% CI, 4.1 to 5.6) and 4.0 months (95% CI, 3.1 to 4.4), respectively (stratified HR, 0.74 [95% CI, 0.59 to 0.92]). Serious adverse events (AEs) occurred in 71 (38.4%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 3/4 treatment-related AEs occurred in 73 (39.5%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 5 AEs occurred in 14 (7.6%) and 10 (6.0%) patients in the atezolizumab plus cabozantinib and docetaxel arms, respectively (treatment-related in four [2.2%] and one [0.6%], respectively). CONCLUSION: Atezolizumab plus cabozantinib after disease progression following anti-PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy for metastatic NSCLC did not improve OS compared with docetaxel. Safety was consistent with known profiles of these agents.

In-Clinic vs. Online Recruitment of Women with a History of Cervical Intraepithelial Neoplasia or Cervical Cancer to a Smoking Cessation Trial: A Post-hoc Comparison of Participant Characteristics, Study Retention, and Cessation Outcomes.

INTRODUCTION: Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. METHODS: Participants were recruited from clinics within a university-based NCI-designated cancer center (n=87) and online nationally via Facebook (n=115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. RESULTS: Participants recruited online (vs. in-clinic) had higher educational attainment (p=.01) and health literacy (p=.003). They were more likely to have CIN vs. cancer, to be further from the time of diagnosis, and to have completed active treatment (p values<.001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1)=11.41, p<.001). There were no recruitment differences in self-reported (p=.90) or biochemically confirmed smoking abstinence (p=.18). CONCLUSIONS: Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (i.e., more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors to smoking cessation trials. IMPLICATIONS: People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN vs. cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12-months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group.

Volumetric brain MRI signatures of heart failure with preserved ejection fraction in the setting of dementia.

Heart failure with preserved ejection fraction (HFpEF) is an important, emerging risk factor for dementia, but it is not clear whether HFpEF contributes to a specific pattern of neuroanatomical changes in dementia. A major challenge to studying this is the relative paucity of datasets of patients with dementia, with/without HFpEF, and relevant neuroimaging. We sought to demonstrate the feasibility of using modern data mining tools to create and analyze clinical imaging datasets and identify the neuroanatomical signature of HFpEF-associated dementia. We leveraged the bioinformatics tools at Vanderbilt University Medical Center to identify patients with a diagnosis of dementia with and without comorbid HFpEF using the electronic health record. We identified high resolution, clinically-acquired neuroimaging data on 30 dementia patients with HFpEF (age 76.9 ± 8.12 years, 61% female) as well as 301 age- and sex-matched patients with dementia but without HFpEF to serve as comparators (age 76.2 ± 8.52 years, 60% female). We used automated image processing pipelines to parcellate the brain into 132 structures and quantify their volume. We found six regions with significant atrophy associated with HFpEF: accumbens area, amygdala, posterior insula, anterior orbital gyrus, angular gyrus, and cerebellar white matter. There were no regions with atrophy inversely associated with HFpEF. Patients with dementia and HFpEF have a distinct neuroimaging signature compared to patients with dementia only. Five of the six regions identified in are in the temporo-parietal region of the brain. Future studies should investigate mechanisms of injury associated with cerebrovascular disease leading to subsequent brain atrophy.

Intracranial aneurysm wall displacement depicted by amplified Flow predicts growth.

BACKGROUND: Abnormal intracranial aneurysm (IA) wall motion has been associated with IA growth and rupture. Recently, a new image processing algorithm called amplified Flow (aFlow) has been used to successfully track IA wall motion by combining the amplification of cine and four-dimensional (4D) Flow MRI. We sought to apply aFlow to assess wall motion as a potential marker of IA growth in a paired-wise analysis of patients with growing versus stable aneurysms. METHODS: In this retrospective case-control study, 10 patients with growing IAs and a matched cohort of 10 patients with stable IAs who had baseline 4D Flow MRI were included. The aFlow was used to amplify and extract IA wall displacements from 4D Flow MRI. The associations of aFlow parameters with commonly used risk factors and morphometric features were assessed using paired-wise univariate and multivariate analyses. RESULTS: aFlow quantitative results showed significantly (P=0.035) higher wall motion displacement depicted by mean±SD 90th% values of 2.34±0.72 in growing IAs versus 1.39±0.58 in stable IAs with an area under the curve of 0.85. There was also significantly (P<0.05) higher variability of wall deformation across IA geometry in growing versus stable IAs depicted by the dispersion variables including 121-150% larger standard deviation ([Formula: see text]) and 128-161% wider interquartile range [Formula: see text]. CONCLUSIONS: aFlow-derived quantitative assessment of IA wall motion showed greater wall motion and higher variability of wall deformation in growing versus stable IAs.

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions. Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing. Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023. Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD). Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323). Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

Examining the effects of binaural beat music on sleep quality, heart rate variability, and depression in older people with poor sleep quality in a long-term care institution: A randomized controlled trial.

OBJECTIVE: This study aimed to examine the effects of binaural beat music (BBM) on sleep quality, heart rate variability, and depression in older people with poor sleep quality in a long-term care institution. METHODS: A single-blind randomized controlled trial design was employed, and 64 older participants with poor sleep quality were recruited from a long-term care institution in Taiwan. Participants were randomized into the BBM group or control group and received 14 days of intervention. During the intervention period, participants in the experimental group listened to 20 min of Taiwanese Hokkien oldies embedded with BBM once in the morning and afternoon three times a week. Participants in the control group only listened to Taiwanese Hokkien oldies. Questionnaires and heart rate variability analysis were used to assess participants' sleep quality, heart rate variability, and depressive symptoms. RESULTS: Significant improvements were observed in sleep quality, along with an increase in heart rate variability means of heart rate and normal sinus beats, and a decrease in low-frequency normalized units and depression severity in the BBM group after the intervention. In the control group, effects on sleep quality were inconsistent, heart rate variability showed significant improvements in some autonomic nervous function regulation, and depression severity was significantly decreased. Furthermore, the BBM group showed a significant improvement in sleep quality and a significant reduction in sympathetic nervous activity compared with the control group. CONCLUSION: This study demonstrates that 14 days of BBM intervention, a non-invasive intervention, could improve sleep quality and depression in older people with poor sleep quality in long-term care institutions. Geriatr Gerontol Int 2024; 24: 297-304.

Longitudinal varying coefficient single-index model with censored covariates.

It is of interest to health policy research to estimate the population-averaged longitudinal medical cost trajectory from initial cancer diagnosis to death, and understand how the trajectory curve is affected by patient characteristics. This research question leads to a number of statistical challenges because the longitudinal cost data are often non-normally distributed with skewness, zero-inflation, and heteroscedasticity. The trajectory is nonlinear, and its length and shape depend on survival, which are subject to censoring. Modeling the association between multiple patient characteristics and nonlinear cost trajectory curves of varying lengths should take into consideration parsimony, flexibility, and interpretation. We propose a novel longitudinal varying coefficient single-index model. Multiple patient characteristics are summarized in a single-index, representing a patient's overall propensity for healthcare use. The effects of this index on various segments of the cost trajectory depend on both time and survival, which is flexibly modeled by a bivariate varying coefficient function. The model is estimated by generalized estimating equations with an extended marginal mean structure to accommodate censored survival time as a covariate. We established the pointwise confidence interval of the varying coefficient and a test for the covariate effect. The numerical performance was extensively studied in simulations. We applied the proposed methodology to medical cost data of prostate cancer patients from the Surveillance, Epidemiology, and End Results-Medicare-Linked Database.

Integrated Analysis of Transcriptome and Metabolome to Unveil Impact on Enhancing Grape Aroma Quality with Synthetic Auxin: Spotlight the Mediation of ABA in Crosstalk with Auxin.

It is widely accepted that prevéraison application of naphthaleneacetic acid (NAA) can delay the ripening of grapes and improve their quality. However, how NAA impacts grape aroma compound concentrations remains unclear. This study incorporated the analyses of aroma metabolome, phytohormones, and transcriptome of Vitis vinifera L. cv. Cabernet Sauvignon grapes cultivated in continental arid/semiarid regions of western China. The analyses demonstrated that NAA application increased ß-damascenone and 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN) in the harvested grapes by delaying véraison and upregulating VvPSY1 and VvCCD4b expressions. Additionally, NAA treatment decreased 2-isobutyl-3-methoxypyrazine (IBMP) at the same phenological stage. Notably, abscisic acid (ABA) levels increased in NAA-treated grapes during véraison, which triggered further changes in norisoprenoid metabolisms. The ABA-responsive factor VvABF2 was potentially involved in VvPSY1 positive modulation, while the auxin response factor VvARF10 may play a role in VvCCD4b upregulation and VvOMT2 downregulation during NAA induction. VvARF10 possibly acts as a crosstalk node between the ABA and auxin signaling pathways following NAA treatment in regulating aroma biosynthesis.

Laparoscopic hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: a systematic review and meta-analysis.

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH). METHODS: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals. RESULTS: Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival. CONCLUSIONS: HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.

Mechanistic insights into Qiteng Xiaozhuo Granules' regulation of autophagy for chronic glomerulonephritis treatment: Serum pharmacochemistry, network pharmacology, and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Qiteng Xiaozhuo Granules (QTXZG), a traditional Chinese medicine prescription, is widely acknowledged for its therapeutic efficacy and lack of discernible toxicity in clinical practice, substantiating its potential in the treatment of chronic glomerulonephritis (CGN). Nevertheless, the specific effectiveness and underlying mechanisms of QTXZG remain insufficiently explored. AIM OF THE STUDY: The purpose of this study was to explore the mechanism of the QTXZG in the treatment of CGN via targeting autophagy based on serum pharmacochemistry, network pharmacology, and experimental validation. METHODS: Serum samples from SD rats orally administered QTXZG were analyzed using UPLC-QE/MS to identify contained compounds. Network and functional enrichment analyses elucidated QTXZG's targets and biological mechanisms. Reliability was ensured through molecular docking, in vivo and in vitro experiments. RESULTS: After oral administration of QTXZG, 39 enriched compounds in serum samples collected 1 h later were identified as potential active agents, with 508 potential targets recognized as QTXZG-specific targets. Through integration of various databases, intersection analysis of QTXZG targets, CGN-related genes, and autophagy-related targets identified 10 core autophagy-related targets for QTXZG in CGN. GO and KEGG analyses emphasized their roles in autophagy, inflammation, and immune processes, particularly emphasizing the enrichment of the AMPK/mTOR signaling pathway. Molecular docking results demonstrated strong binding affinities between QTXZG's key compounds and the predicted core targets. In animal experiments, QTXZG was found to ameliorate renal tissue damage in CGN model mice, significantly reducing serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Importantly, both animal and cell experiments revealed QTXZG's ability to decrease excessive ROS and inflammatory factor release in mesangial cells. Furthermore, in vitro and in vivo experiments confirmed QTXZG's capacity to upregulate Beclin1 and LC3II/I expression, decrease p62 expression, and induce CGN autophagy through modulation of the AMPK/mTOR pathway. CONCLUSIONS: This study indicated that QTXZG can induce autophagy in CGN by affecting the AMPK/mTOR pathway, and induction of autophagy may be one of the possible mechanisms of QTXZG's anti-CGN.