The global incident gastrointestinal cancers attributable to suboptimal diets from 1990 to 2018.

BACKGROUND AND AIMS: The contribution of suboptimal diets to gastrointestinal (GI) cancer incidence globally remains unquantified, and we aimed to evaluate it. METHODS: Comprehensive meta-analyses and rigorous evidence grading assessment identified the associations between suboptimal diets and six GI cancers and their subtypes. A comparative risk assessment model was employed to estimate the proportional attributable burden and attributable rate of GI cancers to suboptimal diets by using the corroborative association estimates. Additionally, correlation assessments with the Sociodemographic Index (SDI) were carried out. RESULTS: In 2018, 21.5% (95% Uncertainty Interval (UI): 19.1%, 24.5%) of incident GI cancer cases globally were attributable to suboptimal diets, maintaining a relatively stable proportion since 1990 (22.4% (19.7%, 25.6%)), while the absolute diet-attributable cases doubled from 581 thousands (511 thousands, 664 thousands) in 1990 to 1,040 thousands (923 thousands, 1,187 thousands) in 2018. Excessive processed meat consumption (5.9% (4.2%, 7.9%)), insufficient fruit intake (4.8% (3.8%, 5.9%)), and insufficient whole grain intake (3.6% (2.8%, 5.1%)) were the most significant dietary risk factors in 2018, a shift from 1990 when the third major concern was insufficient non-starchy vegetable intake. Additionally, Central and Eastern Europe, and Central Asia experienced the highest attributable burden across regions in both 1990 (31.6% (27.0%, 37.4%)) and 2018 (31.6% (27.3%, 36.5%)), and a positive correlation (P < .01) between the SDI and the attributable GI cancer incidence was observed. CONCLUSIONS: Although the proportional attributable GI incidence remains relatively stable, the doubling of absolute cases from 1990 to 2018, along with the discrepancies among urbanicity and countries/regions, informs dietary priorities and more targeted preventive measures.

Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Protists regulate microbially mediated organic carbon turnover in soil aggregates.

Soil protists, the major predator of bacteria and fungi, shape the taxonomic and functional structure of soil microbiome via trophic regulation. However, how trophic interactions between protists and their prey influence microbially mediated soil organic carbon turnover remains largely unknown. Here, we investigated the protistan communities and microbial trophic interactions across different aggregates-size fractions in agricultural soil with long-term fertilization regimes. Our results showed that aggregate sizes significantly influenced the protistan community and microbial hierarchical interactions. Bacterivores were the predominant protistan functional group and were more abundant in macroaggregates and silt + clay than in microaggregates, while omnivores showed an opposite distribution pattern. Furthermore, partial least square path modeling revealed positive impacts of omnivores on the C-decomposition genes and soil organic matter (SOM) contents, while bacterivores displayed negative impacts. Microbial trophic interactions were intensive in macroaggregates and silt + clay but were restricted in microaggregates, as indicated by the intensity of protistan-bacterial associations and network complexity and connectivity. Cercozoan taxa were consistently identified as the keystone species in SOM degradation-related ecological clusters in macroaggregates and silt + clay, indicating the critical roles of protists in SOM degradation by regulating bacterial and fungal taxa. Chemical fertilization had a positive effect on soil C sequestration through suppressing SOM degradation-related ecological clusters in macroaggregate and silt + clay. Conversely, the associations between the trophic interactions and SOM contents were decoupled in microaggregates, suggesting limited microbial contributions to SOM turnovers. Our study demonstrates the importance of protists-driven trophic interactions on soil C cycling in agricultural ecosystems.

PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy.

The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

Advance Care Planning (ACP) in Medicare Beneficiaries with Heart Failure.

BACKGROUND: Heart failure is a leading cause of death in the USA, contributing to high expenditures near the end of life. Evidence remains lacking on whether billed advance care planning changes patterns of end-of-life healthcare utilization among patients with heart failure. Large-scale claims evaluation assessing billed advance care planning and end-of-life hospitalizations among patients with heart failure can fill evidence gaps to inform health policy and clinical practice. OBJECTIVE: Assess the association between billed advance care planning delivered and Medicare beneficiaries with heart failure upon the type and quantity of healthcare utilization in the last 30 days of life. DESIGN: This retrospective cross-sectional cohort study used Medicare fee-for-service claims from 2016 to 2020. PARTICIPANTS: A total of 48,466 deceased patients diagnosed with heart failure on Medicare. MAIN MEASURES: Billed advance care planning services between the last 12 months and last 30 days of life will serve as the exposure. The outcomes are end-of-life healthcare utilization and total expenditure in inpatient, outpatient, hospice, skilled nursing facility, and home healthcare services. KEY RESULTS: In the final cohort of 48,466 patients (median [IQR] age, 83 [76-89] years; 24,838 [51.2%] women; median [IQR] Charlson Comorbidity Index score, 4 [2-5]), 4406 patients had an advance care planning encounter. Total end-of-life expenditure among patients with billed advance care planning encounters was 19% lower (95% CI, 0.77-0.84) compared to patients without. Patients with billed advance care planning encounters had 2.65 times higher odds (95% CI, 2.47-2.83) of end-of-life outpatient utilization with a 33% higher expected total outpatient expenditure (95% CI, 1.24-1.42) compared with patients without a billed advance care planning encounter. CONCLUSIONS: Billed advance care planning delivery to individuals with heart failure occurs infrequently. Prioritizing billed advance care planning delivery to these individuals may reduce total end-of-life expenditures and end-of-life inpatient expenditures through promoting use of outpatient end-of-life services, including home healthcare and hospice.

Components of Residential Neighborhood Deprivation and Their Impact on the Likelihood of Live-Donor and Preemptive Kidney Transplantation.

INTRODUCTION: Adults residing in deprived neighborhoods face various socioeconomic stressors, hindering their likelihood of receiving live-donor kidney transplantation (LDKT) and preemptive kidney transplantation (KT). We quantified the association between residential neighborhood deprivation index (NDI) and the likelihood of LDKT/preemptive KT, testing for a differential impact by race and ethnicity. METHODS: We studied 403 937 adults (age ≥ 18) KT candidates (national transplant registry; 2006-2021). NDI and its 10 components were averaged at the ZIP-code level. Cause-specific hazards models were used to quantify the adjusted hazard ratio (aHR) of LDKT and preemptive KT across tertiles of NDI and its 10 components. RESULTS: Candidates residing in high-deprivation neighborhoods were more likely to be female (40.1% vs. 36.2%) and Black (41.9% vs. 17.7%), and were less likely to receive both LDKT (aHR = 0.66, 95% confidence interval [CI]: 0.64-0.67) and preemptive KT (aHR = 0.60, 95% CI: 0.59-0.62) than those in low-deprivation neighborhoods. These associations differedby race and ethnicity (Black: aHRLDKT = 0.58, 95% CI: 0.55-0.62; aHRpreemptive KT = 0.68, 95% CI: 0.63-0.73; Pinteractions: LDKT < 0.001; Preemptive KT = 0.002). All deprivation components were associated with the likelihood of both LDKT and preemptive KT (except median home value): for example, higher median household income (LDKT: aHR = 1.08, 95% CI: 1.07-1.09; Preemptive KT: aHR = 1.10, 95% CI: 1.08-1.11) and educational attainments (≥high school [LDKT: aHR = 1.17, 95% CI: 1.15-1.18; Preemptive KT: aHR = 1.23, 95% CI: 1.21-1.25]). CONCLUSION: Residence in socioeconomically deprived neighborhoods is associated with a lower likelihood of LDKT and preemptive KT, differentially impacting minority candidates. Identifying and understanding which neighborhood-level socioeconomic status contributes to these racial disparities can be instrumental in tailoring interventions to achieve health equity in LDKT and preemptive KT.

Medical Distrust Among Kidney Transplant Candidates.

BACKGROUND: Medical distrust may hinder kidney transplantation (KT) access. Among KT candidates evaluated for waitlisting, we identified factors associated with high distrust levels and quantified their association with waitlisting. METHODS: Among 812 candidates (2018-2023), we assessed distrust using the Revised Health Care System Distrust Scale across composite, competence, and values subscales. We used linear regression to quantify the associations between candidate and neighborhood-level factors and distrust scores. We used Cox models to quantify the associations between distrust scores and waitlisting. RESULTS: At KT evaluation, candidates who were aged 35-49 years (difference = 1.97, 95% CI: 0.78-3.16), female (difference = 1.10, 95% CI: 0.23-1.97), and Black (difference = 1.47, 95% CI: 0.47-2.47) were more likely to report higher composite distrust score. For subscales, candidates aged 35-49 were more likely to have higher competence distrust score (difference = 1.14, 95% CI: 0.59-1.68) and values distrust score (difference = 0.83, 95% CI: 0.05-1.61). Race/ethnicity (Black, difference = 1.42, 95% CI: 0.76-2.07; Hispanic, difference = 1.52, 95% CI: 0.35-2.69) was only associated with higher values distrust scores. Female candidates reporting higher rescaled values distrust scores (each one point) had a lower chance of waitlisting (aHR = 0.78, 95% CI: 0.63-0.98), whereas this association was not observed among males. Similarly, among non-White candidates, each 1-point increase in both rescaled composite (aHR = 0.87, 95% CI: 0.77-0.99) and values (aHR = 0.82, 95% CI: 0.68-0.99) distrust scores was associated with a lower chance of waitlisting, while there was no association among White candidates. CONCLUSION: Female, younger, and non-White candidates reported higher distrust scores. Values distrust may contribute to the long-standing racial/ethnic and gender disparities in access to KT. Implementing tailored strategies to reduce distrust in transplant care may improve KT access for groups that experience persistent disparities.

Comparative efficacy and safety of Sofosbuvir/Velpatasvir and Danoprevir for the treatment of chronic hepatitis C: the real-world data in China.

BACKGROUND: Sofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV. PATIENTS AND METHODS: 178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study. RESULTS: DNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups. CONCLUSION: In this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.

Formaldehyde Exposure Racial Disparities in Southeast Texas.

Formaldehyde (HCHO) exposures during a full year were calculated for different race/ethnicity groups living in Southeast Texas using a chemical transport model tagged to track nine emission categories. Petroleum and industrial emissions were the largest anthropogenic sources of HCHO exposure in Southeast Texas, accounting for 44% of the total HCHO population exposure. Approximately 50% of the HCHO exposures associated with petroleum and industrial sources were directly emitted (primary), while the other 50% formed in the atmosphere (secondary) from precursor emissions of reactive compounds such as ethylene and propylene. Biogenic emissions also formed secondary HCHO that accounted for 11% of the total population-weighted exposure across the study domain. Off-road equipment contributed 3.7% to total population-weighted exposure in Houston, while natural gas combustion contributed 5% in Beaumont. Mobile sources accounted for 3.7% of the total HCHO population exposure, with less than 10% secondary contribution. Exposure disparity patterns changed with the location. Hispanic and Latino residents were exposed to HCHO concentrations +1.75% above average in Houston due to petroleum and industrial sources and natural gas sources. Black and African American residents in Beaumont were exposed to HCHO concentrations +7% above average due to petroleum and industrial sources, off-road equipment, and food cooking. Asian residents in Beaumont were exposed to HCHO concentrations that were +2.5% above average due to HCHO associated with petroleum and industrial sources, off-road vehicles, and food cooking. White residents were exposed to below average HCHO concentrations in all domains because their homes were located further from primary HCHO emission sources. Given the unique features of the exposure disparities in each region, tailored solutions should be developed by local stakeholders. Potential options to consider in the development of those solutions include modifying processes to reduce emissions, installing control equipment to capture emissions, or increasing the distance between industrial sources and residential neighborhoods.

The impact of surprise billing laws on emergency services.

Numerous states implemented laws to protect emergency patients from surprise out-of-network medical bills. We investigated the effects of the state laws on emergency clinician reimbursements, charges, network participation, and potential surprise billing episodes. We did not find consistent evidence of effects on prices or charges. However, the state laws resulted in increased network participation and a reduction in potential surprise billing episodes. Our results suggest that the federal No Surprises Act, which is similar to many of the state laws, is unlikely to lead to price increases, but may benefit patients through increased provider network participation and alignment.

Histone-modifying enzymes: Roles in odontogenesis and beyond.

OBJECTIVES: Odontogenesis, an intricate process initiated by epithelium-mesenchyme interaction, is meticulously regulated by a cascade of regulatory mechanisms. Epigenetic modifications, especially histone modification, have been found to exhibit spatiotemporal specificity during tooth development. However, the expression patterns and roles of enzymes associated with histone modifications have yet to be systematically explored in odontogenesis. This review aims to summarize the histone-modifying enzymes in odontogenesis and their regulation mechanism during tooth development and provide the potential theoretical basis for the clinical management and intervention of dental developmental diseases. SUBJECTS AND METHODS: This study conducted a systematic search across PubMed and Web of Science databases, utilizing the keywords "odontogenesis," "histone modification," and "enzyme" for pertinent articles. RESULTS: No doubt histone modification contributes extensively to odontogenesis regulation, and the disturbances in histone modifications can derange the odontogenesis process. CONCLUSION: Further studies are warranted to elucidate these roles and their potential downstream effects, positioning histone modifications as a pivotal focal point for unraveling the intricacies of tooth development and regeneration.

'Food doesn't control me anymore!' psychosocial experiences during dietary management in adults with inflammatory bowel disease: A qualitative study.

AIMS: To explore the psychosocial experiences during dietary management among Chinese adults with inflammatory bowel disease. DESIGN: Qualitative phenomenological design. METHODS: Eighteen adults diagnosed with inflammatory bowel disease for more than 6 months were recruited using purposive sampling from June to December 2023. Two trained researchers used van Manen's approach to analyse the data. RESULTS: The three themes with multiple subthemes emerged: facing the unknown: at a loss and aggrieved, trying to cope: uncertain and distressed, and growing in adaptation: relieved and transcendent. The first theme included unknown relapses, overlooking diet management and the absence of dietary rules. The second theme showed different coping situations, like complex dietary information and ever-closing worlds. The third theme explores how participants adapted to disease and their eating patterns. CONCLUSION: The psychosocial experiences during dietary management are complex. The accumulation of diet-related experience, acceptance of illness and social support facilitate patients in overcoming negative emotions and adhering to dietary management. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Nurses should provide tailored dietary guidance and appropriate psychological interventions to promote healthy eating in patients. IMPACT: This study may enhance healthcare professionals' understanding, particularly those in China, of the diet-related experiences among patients. REPORTING METHOD: The Consolidated Criteria for Reporting Qualitative Research checklist. PATIENT OR PUBLIC CONTRIBUTION: Participants contributed by sharing their first hand experiences.

Global bibliometric mapping of dental development research for the period 2012-2021.

BACKGROUND: Dental development is a complex long-term biological process, significant attention should be paid to the dental development and health of this critical time window in childhood for the oral health of the whole life cycle. AIM: This study aimed to conduct bibliometric studies on the scientific outputs of global dental development research by the CiteSpace software. DESIGN: The global scientific outputs about dental development between January 1, 2012, and December 31, 2021, retrieved from Web of Science Core Collection, CiteSpace, and Microsoft Excel were applied for this bibliometric study. RESULTS: A total of 3746 reviews and articles were obtained from the Web of Science core database for exploring the basic publication characteristics, hotspots, and frontiers of this research field. The results showed that dental development is gaining more researcher's attention over time. In terms of countries, the USA and China were the major contributors to this research area. At the institutional level, Sichuan University ranked first. Meanwhile, international cooperation across regions was quite active. The Journal of Dental Research has exerted a broad and far-reaching influence on dental development research in both publications and citations. James P Simmer, Jungwook Kim, Charles E Smith, and Jan CC Hu are among the most influential scholars in this field. Finally, the future hotspots were proposed, covering three directions: dental analysis, tooth development, and post-translational phosphorylation of histones. CONCLUSION: In the past decade, the field of dental development has developed rapidly, and the cooperation between scholars, institutions, and researchers has become increasingly close.

Removing Negative Impacts from Inevitable Nonreproducible and Nonspecific Antibody-Probe Interactions in Viral Serology.

Serological assays are indispensable tools in public health. Presently deployed serological assays, however, largely overlook research progress made in the last two decades that jeopardizes the conceptual foundation of these assays, i.e., antibody (Ab) specificity. Challenges to traditional understanding of Ab specificity include Ab polyspecificity and most recently nonreproducible Ab-probe interactions (NRIs). Here, using SARS-CoV-2 and four common livestock viruses as a test bed, we developed a new serological platform that integrates recent understanding about Ab specificity. We first demonstrate that the response rate (RR) from a large-sized serum pool (∼100) is not affected by NRIs or by nonspecific Ab-probe interactions (NSIs), so RR can be incorporated into the diagnostic probe selection process. We subsequently used multiple probes (configured as a "protein peptide hybrid microarray", PPHM) to generate a digital microarray index (DMI) and finally demonstrated that DMI-based analysis yields an extremely robust probabilistic trend that enables accurate diagnosis of viral infection that overcomes multiple negative impacts exerted by NSI/NRI. Thus, our study with SARS-CoV-2 confirms that the PPHM-RR-DMI platform enables very rapid development of serological assays that outperform traditional assays (for both sensitivity and specificity) and supports that the platform is extendable to other viruses.

Analysis of mRNA-miRNA interaction network reveals the role of CAFs-derived exosomes in the immune regulation of oral squamous cell carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) have significant tumor regulatory functions, and CAFs-derived exosomes (CAFs-Exo) released from CAFs play an important role in the progression of oral squamous cell carcinoma (OSCC). However, a lack of comprehensive molecular biological analysis leaves the regulatory mechanisms of CAFs-Exo in OSCC unclear. METHODS: We used platelet derived growth factor-BB (PDGF-BB) to induce the transformation of human oral mucosa fibroblast (hOMF) into CAFs, and extracted exosomes from the supernatant of CAFs and hOMF. We validated the effect of CAFs-Exo on tumor progression by exosomes co-culture with Cal-27 and tumor-forming in nude mice. The cellular and exosomal transcriptomes were sequenced, and immune regulatory genes were screened and validated using mRNA-miRNA interaction network analysis in combination with publicly available databases. RESULTS: The results showed that CAFs-Exo had a stronger ability to promote OSCC proliferation and was associated with immunosuppression. We discovered that the presence of immune-related genes in CAFs-Exo may regulate the expression of PIGR, CD81, UACA, and PTTG1IP in Cal-27 by analyzing CAFs-Exo sequencing data and publicly available TCGA data. This may account for the ability of CAFs-Exo to exert immunomodulation and promote OSCC proliferation. CONCLUSIONS: CAFs-Exo was found to be involved in tumor immune regulation through hsa-miR-139-5p, ACTR2 and EIF6, while PIGR, CD81, UACA and PTTG1IP may be potentially effective targets for the treatment of OSCC in the future.

A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.

AIMS: The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. METHODS: A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. RESULTS: After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. CONCLUSION: We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.

A hybrid model for tuberculosis forecasting based on empirical mode decomposition in China.

BACKGROUND: Pulmonary Tuberculosis is a major public health problem endangering people's health, a scientifically accurate predictive model is of great practical significance for the prevention and treatment of pulmonary tuberculosis. METHODS: The reported incidence data of pulmonary tuberculosis were from the National Public Health Science Data Center ( https://www.phsciencedata.cn/ ). The ARIMA, LSTM, EMD-SARIMA, EMD-LSTM, EMD-ARMA-LSTM models were established using the reported monthly incidence of tuberculosis reported in China from January 2008 to December 2018. The MSE, MAE, RMSE and MAPE were used to evaluate the performance of the models to determine the best model. RESULTS: Comparing decomposition-based single model with undecomposed single model, it was found that: when predicting the incidence trend in the next year, compared with SARIMA model, the MSE, MAE, RMSE and MAPE of EMD-SARIMA decreased by 39.3%, 19.0%, 22.1% and 19.8%, respectively. The MSE, MAE, RMSE and MAPE of EMD-LSTM were reduced by 40.5%, 12.8%, 22.9% and 12.7%, respectively, compared with the LSTM model; Comparing the decomposition-based hybrid model with the decomposition-based single model, it was found that: when predicting the incidence trend in the next year, compared with EMD-SARIMA model, the MSE, MAE, RMSE and MAPE of EMD-ARMA-LSTM model decreased by 21.7%, 10.6%, 11.5% and 11.2%, respectively. The MSE, MAE, RMSE and MAPE of EMD-ARMA-LSTM were reduced by 16.7%, 9.6%, 8.7% and 12.3%, respectively, compared with EMD-LSTM model. Furthermore, the performance of the model were consistent when predicting the incidence trend in the next 3 months, 6 months and 9 months. CONCLUSION: The prediction performance of the decomposition-based single model is better than that of the undecomposed single model, and the prediction performance of the combined model using the advantages of different models is better than that of the decomposition-based single model, so the EMD-ARMA-LSTM combination model can improve the prediction accuracy better than other models, which can provide a theoretical basis for predicting the epidemic trend of pulmonary tuberculosis and formulating prevention and control policies.

Microbial network and composition changes according to tobacco varieties and interferes differently in black shank disease defense.

AIMS: The soil-borne oomycete pathogen Phytophthora parasitica can cause black shank disease in tobacco plants. The use of resistant varieties can be used to control black shank disease. The potential relationships of the composition of the rhizosphere microbiome to resistance to black shank disease are poorly understood. This work aims to compare the rhizosphere microbial community and network of the tobacco resistant variety HB202 with the susceptible variety XY3. METHODS AND RESULTS: Rhizospheric soils were collected from tobacco plants of HB202 and XY3 in the fields with same soil types and agricultural operations. The compositions of the rhizosphere microbial communities were revealed by Illumina sequencing of bacterial 16S rRNA genes and fungal spacer (ITS) sequences and analysed with molecular ecological network pipeline. The alpha diversity of fungal communities of the two varieties was significantly different. The structure and composition of bacterial and fungal communities in the resistant variety in the rhizosphere was different from the susceptible variety. Relative abundances of beneficial genera in the HB202 microbiota were higher than in the XY3. Conversely, the XY3 microbiota exhibited a higher abundance of deleterious genera compared to the HB202 microbiota. The resistant variety influences the topological properties and microbial interactions in the rhizosphere against the disease. The network of the HB202 was more complex and had higher connectivity compared to the XY3 network. CONCLUSIONS: The rhizosphere microbial communities and networks of two tobacco varieties are very different. These changes in the microbial communities and their interactions may play an important role in tobacco resistance to black shank disease.

Silica nanoparticles promote wheat growth by mediating hormones and sugar metabolism.

BACKGROUND: Silica nanoparticles (SiNPs) have been demonstrated to have beneficial effects on plant growth and development, especially under biotic and abiotic stresses. However, the mechanisms of SiNPs-mediated plant growth strengthening are still unclear, especially under field condition. In this study, we evaluated the effect of SiNPs on the growth and sugar and hormone metabolisms of wheat in the field. RESULTS: SiNPs increased tillers and elongated internodes by 66.7% and 27.4%, respectively, resulting in a larger biomass. SiNPs can increase the net photosynthetic rate by increasing total chlorophyll contents. We speculated that SiNPs can regulate the growth of leaves and stems, partly by regulating the metabolisms of plant hormones and soluble sugar. Specifically, SiNPs can increase auxin (IAA) and fructose contents, which can promote wheat growth directly or indirectly. Furthermore, SiNPs increased the expression levels of key pathway genes related to soluble sugars (SPS, SUS, and α-glucosidase), chlorophyll (CHLH, CAO, and POR), IAA (TIR1), and abscisic acid (ABA) (PYR/PYL, PP2C, SnRK2, and ABF), whereas the expression levels of genes related to CTKs (IPT) was decreased after SiNPs treatment. CONCLUSIONS: This study shows that SiNPs can promote wheat growth and provides a theoretical foundation for the application of SiNPs in field conditions.

Rural-urban disparities in preventive breast and cervical cancer screening among women with early-onset dementia.

BACKGROUND: The early onset of Alzheimer's disease and related dementias (ADRD) before age 65 can introduce life and health care complications. Preserving an early-onset ADRD patient's daily functioning longer and delaying declines in health from non-ADRD conditions become important preventive goals. This study examined the differences in utilization of preventive cancer screenings between patients with and without early-onset ADRD, and compared utilization of the screenings in rural versus urban areas among women with early-onset ADRD in the United States. METHODS: We conducted a cross-sectional study of women aged 40 to 64 years eligible for mammogram and cervical cancer screenings using commercial insurance claims from 2012 to 2018. We measured the use of biennial mammogram among women 50 to 64 years old, and the use of triennial Pap smear test among women 40 to 64 years old. We used inverse probability weighted logistic regressions to estimate the odds of receiving preventive cancer screenings by the presence of early-onset ADRD or cognitive impairments (CI). We used multivariable logistic regressions to estimate the odds of receiving preventive cancer screenings by rural or urban residence among women with early-onset ADRD/CI. RESULTS: Among 6,349,308 women in the breast cancer screening sample (mean [SD] age, 56.52 [4.03] years), 36,131 had early-onset ADRD/CI (mean [SD] age, 57.99 [3.98] years). Among 6,583,088 women in the cervical cancer screening sample (mean [SD] age, 52.37 [6.81] years), 30,919 had early-onset ADRD/CI (mean [SD] age, 55.79 [6.22] years). Having early-onset ADRD/CI was associated with lower utilization of mammogram (OR: 0.92, 95% CI: 0.90-0.95). No significant difference was observed in Pap smear screening (OR: 0.99, 95% CI: 0.96-1.02) between patients with and without early-onset ADRD/CI. Among patients with early-onset ADRD/CI, those in rural areas were less likely than those in urban areas to have mammograms (OR: 0.91, 95% CI: 0.85-0.97) and Pap smears (OR: 0.65, 95% CI: 0.61-0.71). CONCLUSIONS: The observed pattern of rural-urban differences in cancer screening in our study emphasizes the need for efforts to promote evidence-based, individualized decision-making processes in the early-onset ADRD population.