The Global Incident Gastrointestinal Cancers Attributable to Suboptimal Diets From 1990 to 2018.

BACKGROUND & 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 6 GI cancers and their subtypes. A comparative risk assessment model was used to estimate the proportional attributable burden and attributable rate of GI cancers to suboptimal diets by using the corroborative association estimates. In addition, correlation assessments with the Sociodemographic Index were carried out. RESULTS: In 2018, 21.5% (95% uncertainty interval, 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%), whereas the absolute diet-attributable cases doubled from 580,862 (510,658-664,076) in 1990 to 1,039,877 (923,482-1,187,244) 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 nonstarchy vegetable intake. In addition, 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 < .001) between the Sociodemographic Index 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.

Sexual bother and sexual activity before and after kidney transplantation.

Among patients awaiting kidney transplantation (KT), sexual dysfunction is common due to end-stage kidney disease (ESKD) but may improve post-KT. Leveraging a two-center prospective study, 2,422 adult KT candidates and 490 adult KT recipients (5/2014-12/2023) were identified. Using the Kidney Disease Quality of Life Scale Short Form (KDQOL-SF), participants reported on the negative impact of sexual dysfunction due to ESKD (i.e., sexual bother) at KT evaluation, admission, and post-KT follow-ups. Using mixed effect logistic regression models, we estimated odds and trajectories for odds of sexual bother. At evaluation, 46.1% of male and 29.6% of female candidates reported sexual bother; 39.0% and 34.5%, respectively, had been sexually active in the past 4 weeks. At admission, 53.8% male and 27.0% female recipients reported sexual bother; 41.6% and 41.8%, respectively, had been sexually active in the past 4 weeks. The estimated prevalence of sexual bother decreased during the first 3 years post-KT (OR per year: 0.39, 95%CI: 0.25-0.60). Sexual activity increased and peaked 1-year post-KT. 3 years post-KT, 48.9% of male and 50.0% of female recipients were sexually active. Sexual bother is common pre-KT and improves post-KT, and sexual activity increases post-KT. Sexual health is important and should be considered during KT management.

Multiplex Expression Cassette Assembly: A flexible and versatile method for building complex genetic circuits in conventional vectors.

The manipulation of multiple transcription units for simultaneous and coordinated expression is not only key to building complex genetic circuits to accomplish diverse functions in synthetic biology, but is also important in crop breeding for significantly improved productivity and overall performance. However, building constructs with multiple independent transcription units for fine-tuned and coordinated regulation is complicated and time-consuming. Here, we introduce the Multiplex Expression Cassette Assembly (MECA) method, which modifies canonical vectors compatible with Golden Gate Assembly, and then uses them to produce multi-cassette constructs. By embedding the junction syntax in primers that are used to amplify functional elements, MECA is able to make complex constructs using only one intermediate vector and one destination vector via two rounds of one-pot Golden Gate assembly reactions, without the need for dedicated vectors and a coherent library of standardized modules. As a proof-of-concept, we modified eukaryotic and prokaryotic expression vectors to generate constructs for transient expression of green fluorescent protein and ß-glucuronidase in Nicotiana benthamiana, genome editing to block monoterpene metabolism in tomato glandular trichomes, production of betanin in tobacco and synthesis of ß-carotene in Escherichia coli. Additionally, we engineered the stable production of thymol and carvacrol, bioactive compounds from Lamiaceae family plants, in glandular trichomes of tobacco. These results demonstrate that MECA is a flexible, efficient and versatile method for building complex genetic circuits, which will not only play a critical role in plant synthetic biology, but also facilitate improving agronomic traits and pyramiding traits for the development of next-generation elite crops.

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.

Obesogenic Medication Use in End-Stage Kidney Disease and Association With Transplant Listing.

OBJECTIVES: Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing. METHODS: Using 2017-2020 USRDS and Medicare claims, patients were identified as taking obesogenic medications if prescribed anticonvulsants, antidepressants, antidiabetics, anti-inflammatories, antipsychotics, and/or antihypertensives known to cause weight gain for ≥30 days in their first hemodialysis year. Ordinal logistic and Cox regression with inverse probability of treatment weighting were used to quantify obesogenic medications' association with body mass index (BMI) and listing, respectively. RESULTS: Among 271 401 hemodialysis initiates, 63.5% took ≥1 obesogenic medication. For those in underweight, normal weight, overweight, and class I, II, and III categories, 54.3%, 58.4%, 63.1%, 66.5%, 68.6%, and 68.8% took ≥1, respectively. Number of obesogenic medications was associated with increased BMI; use of one was associated with 13% increased odds of higher BMI (aOR [adjusted odds ratio] 1.14; 95%CI: 1.13-1.16; p < 0.001), use of three was associated with a 55% increase (aOR 1.55; 95%CI: 1.53-1.57; p < 0.001). Any use was associated with 6% lower odds of transplant listing (aHR [adjusted hazard ratio] 0.94; 95%CI: 0.92-0.96; p < 0.001). Within each BMI category, obesogenic medication use was associated with lower listing likelihood. CONCLUSIONS: Obesogenic medication use is common in ESKD patients-particularly those with obesity-and is associated with lower listing likelihood. Whenever possible, non-obesogenic alternatives should be chosen for ESKD patients attempting weight loss to achieve transplant listing.

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.

Ethical risks in robot health education: A qualitative study.

BACKGROUND: As health education robots may potentially become a significant support force in nursing practice in the future, it is imperative to adhere to the European Union's concept of "Responsible Research and Innovation" (RRI) and deeply reflect on the ethical risks hidden in the process of intelligent robotic health education. AIM: This study explores the perceptions of professional nursing professionals regarding the potential ethical risks associated with the clinical practice of intelligent robotic health education. RESEARCH DESIGN: This study adopts a descriptive phenomenological approach, employing Colaizzi's seven-step method for data analysis. PARTICIPANTS AND RESEARCH CONTEXT: We conducted semi-structured interviews with 17 nursing professionals from tertiary comprehensive hospitals in China. ETHICAL CONSIDERATIONS: This study has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Provincial Second Chinese Medicine Hospital. FINDINGS: Nursing personnel, adhering to the principles of RRI and the concept of "person-centered" care, have critically reflected on the potential ethical risks inherent in robotic health education. This reflection has primarily identified six themes: (a) threats to human dignity, (b) concerns about patient safety, (c) apprehensions about privacy disclosure, (d) worries about implicit burdens, (e) concerns about responsibility attribution, and (f) expectations for social support. CONCLUSIONS: This study focuses on health education robots, which are perceived to have minimal ethical risks, and provides rich and detailed insights into the ethical risks associated with robotic health education. Even seemingly safe health education robots elicit significant concerns among professionals regarding their safety and ethics in clinical practice. As we move forward, it is essential to remain attentive to the potential negative impacts of robots and actively address them.

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.