ABSTRACT
OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.
Subject(s)
Biomarkers, Tumor , Creatinine , Cytokines , Immune Checkpoint Inhibitors , Neoplasms , Humans , Male , Female , Neoplasms/drug therapy , Neoplasms/blood , Middle Aged , Aged , Cytokines/blood , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Creatinine/blood , Biomarkers, Tumor/blood , Adult , Aged, 80 and over , B7-H1 Antigen/blood , Case-Control StudiesABSTRACT
BACKGROUND: Genomic variants of the disease are often discovered nowadays through population-based genome-wide association studies (GWAS). Identifying genomic variations potentially underlying a phenotype, such as hypertension, in an individual is important for designing personalized treatment; however, population-level models, such as GWAS, may not capture all the important, individualized factors well. In addition, GWAS typically requires a large sample size to detect the association of low-frequency genomic variants with sufficient power. Here, we report an individualized Bayesian inference (IBI) algorithm for estimating the genomic variants that influence complex traits, such as hypertension, at the level of an individual (e.g., a patient). By modeling at the level of the individual, IBI seeks to find genomic variants observed in the individual's genome that provide a strong explanation of the phenotype observed in this individual. RESULTS: We applied the IBI algorithm to the data from the Framingham Heart Study to explore the genomic influences of hypertension. Among the top-ranking variants identified by IBI and GWAS, there is a significant number of shared variants (intersection); the unique variants identified only by IBI tend to have relatively lower minor allele frequency than those identified by GWAS. In addition, IBI discovered more individualized and diverse variants that explain hypertension patients better than GWAS. Furthermore, IBI found several well-known low-frequency variants as well as genes related to blood pressure that GWAS missed in the same cohort. Finally, IBI identified top-ranked variants that predicted hypertension better than GWAS, according to the area under the ROC curve. CONCLUSIONS: The results support IBI as a promising approach for complementing GWAS, especially in detecting low-frequency genomic variants as well as learning personalized genomic variants of clinical traits and disease, such as the complex trait of hypertension, to help advance precision medicine.
Subject(s)
Genome-Wide Association Study , Hypertension , Humans , Genome-Wide Association Study/methods , Bayes Theorem , Polymorphism, Single Nucleotide , Phenotype , Hypertension/genetics , GenomicsABSTRACT
The Indiana Geriatrics Workforce Enhancement Program (GWEP) implemented a new longitudinal geriatrics curriculum for advanced practice registered nurse (APRN) and master of social work (MSW) learners to prepare them for interprofessional collaborative practice in the care of older adults. This paper reports program outcomes of a novel longitudinal interprofessional geriatrics curriculum involving immersive learning for these learners. Outcomes are described in terms of learner reaction, modification of attitudes/perceptions, acquisition of knowledge/skills, behavior change, impact on the organization, and impact on the patient or client using the Freeth/Kirkpatrick evaluation model. Program participation influenced graduates' knowledge of and their perceived ability to participate in team care and job selection in geriatric-focused positions.
Subject(s)
Advanced Practice Nursing , Geriatrics , Humans , Aged , Program Evaluation , Advanced Practice Nursing/education , Interprofessional Relations , Curriculum , Geriatrics/education , Social WorkABSTRACT
The objective of this study was to increase screening for falls and dementia by improving interprofessional (IP) providers' and staffs' knowledge and attitudes toward the care of older patients and team-based care. An intervention, including education about screening and an electronic health record (EHR) flowsheet, was rolled-out across eight Federally Qualified Health Centers (FQHC). Participants were 262 IP health providers who served 6670 patients ≥ age 65 > age 65 . An EHR flowsheet with two-item screeners for falls and dementia triggered automatically for patients ≥ age 65. Documentation of screening for falls and dementia was abstracted from the EHR for the year prior to and the year after the interventions began. Baseline screening rates for falls and dementia were flat; from the start of education intervention until EHR live date, screening rates increased significantly; after EHR live date, the screening rates continued increasing significantly. A combined education-system intervention can improve screening for falls and dementia in FQHC.
Subject(s)
Dementia , Geriatrics , Humans , Aged , Interprofessional Education , Geriatrics/education , Dementia/diagnosisABSTRACT
Health outcomes for complex older adults are enhanced by interprofessional collaboration. Funded by a Geriatrics Workforce Enhancement Program (GWEP), an interprofessional team of educators developed a short-term geriatrics experience, including four hours of pre-clinical education and 12-20 hours of immersion in team-based care for advanced learners in nursing (n = 70 APN), social work (n = 48 MSW), and medicine (n = 122 medical students). Content focused on five areas: medication management, dementia, depression, falls, and myths about aging. Learners completed pre/post surveys measuring knowledge of geriatrics, attitudes toward geriatric patients and team care, and post-surveys regarding perceptions of the overall clinical experience. Results showed significant improvement in knowledge and attitudes toward older adults and interprofessional (IP) team practice. Qualitative comments reflected increased empathy toward and enthusiasm for working with older adults, valuing IP teams, and a desire for geriatrics content earlier in their respective curricula.
Subject(s)
Geriatrics , Students, Medical , Aged , Curriculum , Geriatrics/education , Humans , Interprofessional Relations , Patient Care Team , WorkforceABSTRACT
Psychological theories of identity concealment locate the ultimate source of concealment decisions within the social environment, yet most studies have not explicitly assessed stigmatizing environments beyond the immediate situation. We advanced the identity-concealment literature by objectively measuring structural forms of stigma related to sexual orientation (e.g., social policies) at proximal and distal geographic levels. We linked these measures to a new, population-based data set of 502 gay and bisexual men (residing in 44 states and Washington, DC; 269 counties; and 354 cities) who completed survey items about stigma, including identity-concealment motivation. Among gay men, the association between structural stigma and concealment motivation was (a) observed across three levels (city, county, and state), (b) conditional on one's exposure at another geographic level (participants reported the least motivations to conceal their identity if they resided in both cities and states that were lowest in structural stigma), and (c) mediated by subjective perceptions of greater structural stigma.
Subject(s)
Motivation , Sexual and Gender Minorities , Female , Humans , Male , Sexual Behavior , Social Stigma , Surveys and QuestionnairesABSTRACT
BACKGROUND: Ineffective transitions of care continue to be a source of risk for patients. Although there has been widespread implementation of electronic medical record (EMR) systems, little is currently known about hospitalists' and primary care providers' (PCPs) direct communication preferences at discharge using messaging capabilities in a shared EMR system. OBJECTIVE: We examined how hospitalists and PCPs with a shared EMR prefer to directly communicate at the time of hospital discharge by identifying preferred modes, information prioritization, challenges, facilitators, and proposed solutions. DESIGN: A sequential, explanatory mixed methods study with surveys and semi-structured interviews. PARTICIPANTS: Thirty-eight academic hospitalists and 63 PCPs working in outpatient clinics in a single safety net hospital system with a shared EMR. MAIN APPROACH: Descriptive statistics were used to analyze survey responses. Interviews were analyzed using immersion/crystallization and a mixture of inductive and deductive thematic analysis. KEY RESULTS: PCPs preferred direct communication at discharge through a message within the EMR while hospitalists preferred a message within the EMR and email. Qualitative results identified key themes related to patient care and direct communication: value of direct communication, safety, social determinants of health, and clinical judgment. Both groups prioritized direct communication for high-risk medications, pending and follow-up studies, and high-risk patients that hospitalists were concerned about. Overall, both hospitalists and PCPs reported that ensuring patient safety, flagging patients with social challenges, and expressing concerns about patients based on clinical judgment were key communication priorities. CONCLUSIONS: Hospitalists and primary care providers report considerable overlap in preferences for direct communication at the time of hospital discharge through a shared EMR. Specifically, both groups reported similar concerns regarding patient safety and continuity during transitions. Direct messaging within the EMR could enable "closed loop" communication that helps ensure safe transitions of care for high-risk patients.
Subject(s)
Hospitalists , Physicians, Primary Care , Attitude of Health Personnel , Communication , Electronic Health Records , Humans , Patient Discharge , Patient TransferABSTRACT
The aim of this study was to confirm pharmacokinetic screening of multiple components in healthy Korean subjects after oral administration of Samso-eum and perform quantitation of active components in the human plasma. Thirteen potential bioactive components [puerarin (PRR), daidzin, nodakenin, ginsenoside Rb1, 18ß-glycyrrhetinic acid (18ß-GTA), 6-shogaol, naringin, glycyrrhizin, hesperidin, platycodin D, naringenin, hesperetin, and 6-gingerol] were screened based on literature. The results showed that three analytes (daidzin, naringenin, and hesperetin) were detected in trace amounts. In addition, PRR and 18ß-GTA were detected in human plasma after the oral administration of Samso-eum. In this study, a liquid chromatography-electrospray ionization-tandem mass spectrometry method was validated for the simultaneous determination of PRR and 18ß-GTA in human plasma. This was the first study to evaluate pharmacokinetics of PRR and 18ß-GTA after the usual oral dose of Samso-eum (30 g containing 102.48 mg PRR, 48.18 mg glycyrrhizin) in human subjects.
Subject(s)
Chromatography, Liquid/methods , Drugs, Chinese Herbal , Glycyrrhetinic Acid/analogs & derivatives , Isoflavones/blood , Tandem Mass Spectrometry/methods , Administration, Oral , Adult , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacokinetics , Glycyrrhetinic Acid/blood , Glycyrrhetinic Acid/chemistry , Glycyrrhetinic Acid/pharmacokinetics , Humans , Isoflavones/chemistry , Isoflavones/pharmacokinetics , Limit of Detection , Linear Models , Male , Reproducibility of Results , Young AdultABSTRACT
The trehalose biosynthetic pathway is of great interest for the development of novel therapeutics because trehalose is an essential disaccharide in many pathogens but is neither required nor synthesized in mammalian hosts. As such, trehalose-6-phosphate phosphatase (TPP), a key enzyme in trehalose biosynthesis, is likely an attractive target for novel chemotherapeutics. Based on a survey of genomes from a panel of parasitic nematodes and bacterial organisms and by way of a structure-based amino acid sequence alignment, we derive the topological structure of monoenzyme TPPs and classify them into 3 groups. Comparison of the functional roles of amino acid residues located in the active site for TPPs belonging to different groups reveal nuanced variations. Because current literature on this enzyme family shows a tendency to infer functional roles for individual amino acid residues, we investigated the roles of the strictly conserved aspartate tetrad in TPPs of the nematode Brugia malayi by using a conservative mutation approach. In contrast to aspartate-213, the residue inferred to carry out the nucleophilic attack on the substrate, we found that aspartate-215 and aspartate-428 of BmTPP are involved in the chemistry steps of enzymatic hydrolysis of the substrate. Therefore, we suggest that homology-based inference of functionally important amino acids by sequence comparison for monoenzyme TPPs should only be carried out for each of the 3 groups.-Cross, M., Lepage, R., Rajan, S., Biberacher, S., Young, N. D., Kim, B.-N., Coster, M. J., Gasser, R. B., Kim, J.-S., Hofmann, A. Probing function and structure of trehalose-6-phosphate phosphatases from pathogenic organisms suggests distinct molecular groupings.
Subject(s)
Brugia malayi/enzymology , Conserved Sequence , Helminth Proteins/chemistry , Phosphoric Monoester Hydrolases/chemistry , Animals , Aspartic Acid/chemistry , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Catalytic Domain , Helminth Proteins/genetics , Helminth Proteins/metabolism , Mycobacterium/enzymology , Phosphoric Monoester Hydrolases/genetics , Phosphoric Monoester Hydrolases/metabolismABSTRACT
Object: Intercellular adhesion molecule 1 (ICAM-1) is an adhesive protein involved in inflammatory responses and endothelial dysfunction. ICAM-1 expression is upregulated in cerebrovascular tissue affected by stroke. We investigated whether serum soluble ICAM-1 (sICAM-1) levels are associated with cerebral microbleeds (CMBs) and risk of hemorrhagic transformation (HT).Methods: 148 patients with acute ischemic stroke were enrolled. Serum sICAM-1 levels were measured and compared between patients and healthy controls. Multivariate logistic regression analysis was performed to estimate the relationship between serum sICAM-1 levels and the HT risk.Results: Serum sICAM-1 levels were significantly higher in ischemic stroke patients compared with healthy controls (p < .001), and higher in patients with CMBs (n = 81) compared with patients without CMBs (n = 67) (p < .001). Patients with high sICAM-1 levels (≥250.5 ng/mL) were more likely to have hypertension, diabetes mellitus, previous stroke, and CMBs compared with patients with low sICAM-1 levels. In stroke patients with CMBs, higher serum sICAM-1 levels were independently associated with increased HT risk.Conclusion: Serum sICAM-1 levels are associated with presence of CMBs and increased risk of HT in ischemic stroke patients.
Subject(s)
Brain Ischemia/blood , Brain Ischemia/etiology , Cerebral Hemorrhage/etiology , Intercellular Adhesion Molecule-1/metabolism , Stroke/etiology , Aged , Cerebral Hemorrhage/blood , Female , Humans , Male , Prospective Studies , Risk Factors , Stroke/blood , Up-Regulation/physiologyABSTRACT
Uric acid has neuroprotective effect on Parkinson's disease (PD) by inhibiting oxidative damage and neuronal cell death. Our previous study has shown that uric acid protected dopaminergic cell line damage through inhibiting accumulation of NF-E2-related factor 2 (Nrf2). This study aimed to investigate its in vivo neuroprotective effect. PD was induced by MPTP intraperitoneally injection for 7 d in male C57BL/6 mice. Mice were treated with either uric acid (intraperitoneally injection 250 mg/kg) or saline for a total of 13 d. We showed that uric acid improved behavioral performances and cognition of PD mice, increased TH-positive dopaminergic neurons and decreased GFAP-positive astrocytes in substantia nigra (SN). Uric acid increased mRNA and protein expressions of Nrf2 and three Nrf2-responsive genes, including γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC), heme oxygenase-1 (HO-1) and NQO1. Uric acid significantly increased superoxide dismutase (SOD), CAT, glutathione (GSH) levels and decreased malondialdehyde (MDA) level in SN regions of MPTP-treated mice. Uric acid inhibited the hippocampal expression of IL-1ß and decreased serum and hippocampus levels of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α). In conclusion, uric acid demonstrates neuroprotective properties for dopaminergic neurons in PD mice through modulation of neuroinflammation and oxidative stress.
Subject(s)
Antioxidant Response Elements/drug effects , NF-E2-Related Factor 2/metabolism , Neuroprotective Agents/pharmacology , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Uric Acid/pharmacology , Animals , Behavior, Animal/drug effects , Cognition/drug effects , Cytokines/blood , Cytokines/metabolism , Hippocampus/drug effects , Hippocampus/pathology , Hippocampus/physiopathology , Inflammation/drug therapy , Inflammation/pathology , MPTP Poisoning/drug therapy , MPTP Poisoning/physiopathology , MPTP Poisoning/psychology , Male , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Parkinson Disease/psychology , Signal Transduction/drug effectsABSTRACT
BACKGROUND: Rituximab is an effective therapy for pemphigus, although relapses are common. OBJECTIVE: To identify biomarkers to predict relapse of pemphigus following rituximab treatment. METHODS: In this retrospective cohort study, 62 patients with pemphigus treated with 99 rituximab cycles provided longitudinal clinical scoring and biomarker data, including levels of CD19+ B cells, CD4+ T cells, and desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) autoantibodies. An extended time-variant Kaplan-Meier estimator and extended Cox model were applied. RESULTS: Relapse was rare before B-cell repopulation. Univariate analysis revealed low CD4 count (<400 cells/µL) to predict relapse (P < .001). A positive result of testing for Dsg1 (>20 IU) was predictive of relapse among patients with mucocutaneous disease (hazard ratio, 6.40; P = .019); a positive result of testing for Dsg3 (>20 IU) was predictive in patients with mucocutaneous and mucosal disease (hazard ratio, 32.92; P < .001). Multivariable analysis revealed that every CD4 value increase of 200 decreases the hazard ratio for relapse by 35% (P = .029). A positive result of testing for Dsg1 increases the risk for relapse by a factor of 12.32 in patients with mucocutaneous disease (P = .001); positive result of testing for Dsg3 increases risk for relapse by 28.38 in patients with mucosal and mucocutaneous disease (P = .006). LIMITATIONS: Limitations include the retrospective design and inconsistent follow-up. CONCLUSION: Relapse is associated with B-cell repopulation, low CD4+ T -cell count, and positive result of testing for Dsg1 and Dsg3.
Subject(s)
Immunologic Factors/therapeutic use , Pemphigus/blood , Pemphigus/drug therapy , Rituximab/therapeutic use , Autoantibodies/blood , B-Lymphocytes , Biomarkers/blood , Cohort Studies , Desmoglein 1/blood , Desmoglein 3/blood , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Recurrence , Retrospective StudiesABSTRACT
Openness is the core concept of the Belt and Road initiative (BRI), which plays a significant role in promoting the sustainable economic development of countries along the BRI. This study uses the entropy method to measure openness based on six dimensions: trade, investment, finance, tourism, technology, and information. Simultaneously, a super-SBM model with undesired output is proposed to measure green economy efficiency (GEE). Using the panel data of 66 countries along the BRI from 2008 to 2019, we empirically examine the impact of openness on GEE. The results are as follows: (1) The openness level of countries along the BRI is generally increasing, but the relative differences between countries tend to widen. (2) Openness has a significant U-shaped nonlinear effect on GEE, and the conclusion is still valid after considering the robustness test; (3) The spatial econometric model shows that openness not only affects the GEE of the local country, but also has a spillover effect on neighboring countries. Therefore, we believe that BRI countries should strengthen policy communication, break down border barriers, actively promote the orderly flow and diffusion of openness elements, and pay attention to the quantity and quality of openness development, which is key to the high-quality construction of the BRI.
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Purpose: To highlight the knowledge structure and evolutionary trends in research on autophagy in lung cancer. Methods: Research publications on autophagy in lung cancer were retrieved from the Web of Science Core Collection database. VOSviewer and CiteSpace data analysis software were used for the bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords related to this field. Results: From 2013 to 2022, research on autophagy in lung cancer developed rapidly, showing rising trends in annual publications and citations. China (1,986 papers; 48,913 citations), Shandong University (77 publications; 1,460 citations), and Wei Zhang (20 publications; 342 citations) were the most productive and influential country, institution, and author, respectively. The journal with the most publications and citations on autophagy in lung cancer was the International Journal of Molecular Sciences (93 publications; 3,948 citations). An analysis of keyword co-occurrence showed that related research topics were divided into five clusters: 1) Mechanisms influencing autophagy in lung cancer and the role of autophagy in lung cancer; 2) Effect of autophagy on the biological behavior of lung cancer; 3) Regulatory mechanisms of 2 cell death processes: autophagy and apoptosis in lung cancer cells; 4) Role of autophagy in lung cancer treatment and drug resistance; and 5) Role of autophagy-related genes in the occurrence and development of lung cancer. Cell proliferation, migration, epithelial-mesenchymal transition, and tumor microenvironment were the latest high-frequency keywords that represented promising future research directions. Conclusion: This is the first comprehensive study describing the knowledge structure and emerging frontiers of research on autophagy in lung cancer from 2013 to 2022 by means of a bibliometric analysis. The study points to promising future research directions focusing on in-depth autophagy mechanisms, clinical applications, and potential therapeutic strategies, providing a valuable reference for researchers in the field. Systematic Review Registration: [https://systematicreview.gov/], identifier [registration number].
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BACKGROUND: Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials. However, the research hotspots and trends in the application of nanomaterials in gastric cancer (GC) remain obscure. AIM: To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC. METHODS: Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study. VOSviewer and CiteSpace were used for bibliometric and visualization analyses. RESULTS: From 2000 to 2022, the application of nanomaterials in GC developed rapidly. The keyword co-occurrence analysis showed that the related research topics were divided into three clusters: (1) The application of nanomaterials in GC treatment; (2) The application and toxicity of nanomaterials in GC diagnosis; and (3) The effects of nanomaterials on the biological behavior of GC cells. Complexes, silver nanoparticles, and green synthesis are the latest high-frequency keywords that represent promising future research directions. CONCLUSION: The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.
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Purpose: To highlight the trends and frontiers of RNA methylation in cancer over the past 10 years. Methods: Research publications on RNA methylation in cancer were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and Bibliometrix were used to conduct bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords relevant to this field. Results: From 2014 to 2023, research on RNA methylation in cancer has developed rapidly, with an overall increase in the number of publications and citations. China (4320 papers, 115056citations), Sun Yat Sen University (274 papers, 15698 citations), and Zhang, Wei (48 papers, 893 citations) are respectively the countries, institutions, and authors with the highest number of published papers and citations. Frontiers in Oncology (182 papers, 2524 citations) and Molecular Cancer (69 papers, 9224 citations) are the journals with the highest number of published papers and citations in this field, respectively. Co-occurrence analysis of keywords indicates that the research topics can be divided into five clusters: Cluster one: The Role of RNA Methylation in Tumor Heterogeneity, Therapeutic Response, and Prognosis; Cluster two: The Role of Noncoding RNA in RNA Methylation and Tumors; Cluster three: Potential Therapeutic Targets of RNA Methylation in Tumors; Cluster four: The role of RNA methylation in tumor progression and metastasis: A case study of hepatocellular carcinoma and gastric cancer; Cluster five: Regulation mechanisms of m6A methylation in leukemia cell differentiation and tumorigenesis. Conclusion: This is the first comprehensive study using bibliometrics to analyze the trends and frontiers of RNA methylation in cancer over the past 10 years, pointing out promising research directions for the future and providing valuable references for researchers in this field.
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Bisexual men are disproportionately affected by negative mental health outcomes compared to heterosexual and gay men. These disparities are related to the unique stressors that they experience, and emerging evidence suggests that their experiences of these stressors can be different depending on the gender of their partner. However, previous studies have largely focused on bisexual women and little is known about the role of partner gender in bisexual men's experiences and mental health. We examined the associations between relationship type and outness, stigma-related experiences, and mental health using data from Wave 1 of the National Study of Stigma and Sexual Health, a probability-based sample of 502 gay and bisexual men in the U.S. Analyses focused on the subset of 128 men who identified as bisexual (44.53% in relationships with women, 14.84% in relationships with men, 40.63% not in relationships). Bisexual men in relationships with men reported being more out than those in relationships with women and those who were not in relationships; furthermore, bisexual men in relationships with men reported more discrimination and family stress than those in relationships with women. Bisexual men who were not in relationships reported more anticipated and internalized stigma than those in relationships with men; additionally, bisexual men who were not in relationships reported more anticipated stigma and depression than those in relationships with women. Partner gender plays a role in bisexual men's stigma-related experiences and mental health, and efforts to improve bisexual men's health should attend to sexual orientation, relationship status, and partner gender.
ABSTRACT
Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.
Subject(s)
Antineoplastic Agents , Pancreatitis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Animals , Mice , Asparaginase/adverse effects , Retinoids/adverse effects , Vitamin A/therapeutic use , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Systems Analysis , Antineoplastic Agents/adverse effectsABSTRACT
INTRODUCTION: Sleep tracker data have not been utilized routinely in sleep-related disorders and their management. Sleep-related disorders are common in primary care practice and incorporating sleep tracker data may help in improving patient care. We conducted a pilot study to assess the feasibility of a sleep program using the Fitbit Charge 2™ device and SleepLife® application. The main aim of the study was to examine whether a program using a commercially available wearable sleep tracker device providing objective sleep data would improve communication in primary care settings between patients and their providers. Secondary aims included whether patient satisfaction with care would improve as result of the program. METHODS: A prospective, randomized, parallel group, observational pilot study was conducted in 20 primary care clinics in Indianapolis, IN from June 2018 to February 2019. Inclusion criteria included patients over the age of 18, have a diagnosis of insomnia identified by electronic medical record and/or a validated questionnaire, and were on a prescription sleep aid. The study was not specific to any sleep aid prescription, branded or generic, and was not designed to evaluate a drug or drug class. Each primary care clinic was randomized to either the SleepLife® intervention or the control arm. All patients were provided with a Fitbit Charge 2™ device. Only patients in the intervention arm were educated on how to use the SleepLife® application. Physicians in the intervention arm were set up with the SleepLife® portal on their computers. RESULTS: Forty-nine physicians and 75 patients were enrolled in the study. Patients had a mean age of 57 (SD 12.8) years and 61% were female. Mean age of physicians was 47 (SD 10.6) years. Patients showed high rates of involvement in the program with 83% completing all survey questions. Physician survey completion rate was 55%. Only one physician logged into the SleepLife portal to check their patients' sleep status. At the end of the 6-week intervention, patients' composite general satisfaction scores with sleep health management decreased significantly in the intervention arm when compared to controls (p = 0.03). Patients' satisfaction with communication also decreased significantly in the intervention group (p = 0.01). The sleep outcomes, which were calculated on the basis of study questionnaire answers, improved significantly in the intervention group as compared to the control group (p = 0.04). Physician communication satisfaction scores remained unchanged (p = 0.12). CONCLUSIONS: SleepLife® and its related physician portal can facilitate physician-patient communication, and it captures patient sleep outcomes including behaviors and habits. Patients were highly engaged with the program, while physicians did not demonstrate engagement. The study design and questionnaires do not specifically address the reasons behind the decreased patient satisfaction with care and communication, but it was perceived to be a result of physician non-responsiveness. Sleep quality scores on the other hand showed an improvement among SleepLife® users, suggesting that patients may have implemented good sleep practices on their own. Given that it was a feasibility study, and the sample size was small, we were not able to make major inferences regarding the difference between sleep disorder types. Additionally, we excluded patients with a history of alcohol use, substance abuse, or depression because of concerns that they may affect sleep independently. To promote the growth of technology in primary care, further research incorporating results from this study and physician engagement techniques should be included.