In vivo Fate of Targeted Drug Delivery Carriers.

This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.

Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a "car" or under an "umbrella") plays an essential role in the drug's therapeutic effect. This paper aims to highlight the importance of the carrier's role, which is vital for developing new drugs and advancing basic research.

Using Concept Mapping to Identify Community Partners' and Researchers' Perceptions of Social Justice: A Path Toward Eliminating Chronic Disease Disparities.

Background: A social justice framework can be used to inform healthy equity-focused research, and operationalizing social justice can inform strategic planning for research and practice models. This study aimed to develop a working definition of social justice based on input from a diverse group of collaborators to better inform the work conducted within the Center for Research, Health, and Social Justice. Methods: A concept mapping study was conducted from March to May 2022. A prompt designed to elicit social justice themes was developed (phase 1). At a study website, participants brainstormed statements that represented their definition of social justice (phase 2). Participants then sorted statements based on similarity and rated statements on importance (phase 3). Multidimensional scaling and hierarchical cluster analysis were used to identify nonoverlapping thematic clusters of statements (phase 4). Models were reviewed for best fit, and clusters were assigned names based on theme (phase 5). Results: Participants (n = 49) generated 52 unique statements that were sorted into 5 clusters describing social justice themes. Clusters included (1) Empathy, Awareness, and Understanding (n = 11); (2) Education and Systems Change (n = 10); (3) Policy Design and Implementation (n = 9); (4) Equity and Leveling the Playing Field (n = 11); and (5) Access to Services and Fair Living Standard (n = 11). High mean cluster ratings ranging from 5.22 to 6.02 out of 7 indicated all clusters were rated as being very important aspects of social justice. Conclusions: These data can guide the restructuring of research ecosystems that help eliminate race- and place-based health disparities.

Competitive Risk Analysis of Prognosis in Older Adults with Sigmoid Colon Adenocarcinoma: A Population-Based Study.

BACKGROUND: The purpose of this study is to employ a competing risk model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify prognostic factors for elderly individuals with sigmoid colon adenocarcinoma (SCA) and compare them with the classic Cox proportional hazards model. METHODS: We extracted data from elderly patients diagnosed with SCA registered in the SEER database between 2010 and 2015. Univariate analysis was conducted using cumulative incidence functions and Gray's test, while multivariate analysis was performed using both the Fine-Gray and Cox proportional hazards models. RESULTS: Among the 10,712 eligible elderly patients diagnosed with SCA, 5595 individuals passed away: 2987 due to sigmoid colon adenocarcinoma and 2608 from other causes. The results of one-way Gray's test showed that age, race, marital status, AJCC stage, differentiation grade, tumor size, surgical status, liver metastasis status, lung metastasis status, brain metastasis status, radiotherapy status, and chemotherapy status all affected the prognosis of SCA (P < .05). Multivariate analysis showed that sex, age, race, marital status, and surgical status affected the prognosis of SCA (P < .05). Multifactorial Fine-Gray analysis revealed that key factors influencing the prognosis of SCA patients include age, race, marital status, AJCC stage, grade classification, surgical status, tumor size, liver metastasis, lung metastasis, and chemotherapy status (P < .05). CONCLUSION: Data from the SEER database were used to more accurately estimate CIFs for sigmoid colon adenocarcinoma-specific mortality and prognostic factors using competing risk models.

A weighted Jackknife approach utilizing linear model based-estimators for clustered data.

Small number of clusters combined with cluster level heterogeneity poses a great challenge for the data analysis. We have published a weighted Jackknife approach to address this issue applying weighted cluster means as the basic estimators. The current study proposes a new version of the weighted delete-one-cluster Jackknife analytic framework, which employs Ordinary Least Squares or Generalized Least Squares estimators as the fundamentals. Algorithms for computing estimated variances of the study estimators have also been derived. Wald test statistics can be further obtained, and the statistical comparison in the outcome means of two conditions is determined using the cluster permutation procedure. The simulation studies show that the proposed framework produces estimates with higher precision and improved power for statistical hypothesis testing compared to other methods.

Supportive care needs and associated factors among caregivers of patients with colorectal cancer: a cross-sectional study.

To assess the level of supportive care needs of caregivers of colorectal cancer patients and explore the related key influencing factors. Totaling 283 caregivers of patients with colorectal cancer were investigated in this study. Firstly, caregivers were invited to complete a set of questionnaires, including the general information questionnaire, the Supportive Care Needs Survey-Partners and the Caregivers of cancer patients, the Caregiver Preparedness Scale, the Benefit Finding Scale, and the Comprehensive Score for Financial Toxicity. Univariate and multivariate linear regression were performed to investigate the associated factors of supportive care needs. The caregivers of patients with colorectal cancer have a moderate level of needs, scored at 2.71 ± 0.42. Caregiver preparedness, benefit finding, and financial toxicity were significantly negatively associated with the supportive care needs of caregivers (r = - 0.555, P < 0.001; r = - 0.534, P < 0.001; and r = - 0.615, P < 0.001, respectively). Our multivariate regression analysis identified some factors that directly affected the supportive care needs of caregivers, including the duration of illness, tumor stage, the age and educational level of caregivers, caregiver preparedness, benefit finding, and financial toxicity (R2 = 0.574, F = 23.337, P < 0.001). Supportive care needs are common among caregivers of colorectal cancer patients. Higher caregiver preparedness, benefit finding, and financial toxicity tend to ease these needs. Healthcare workers should have an in-depth understanding of the needs of caregivers of colorectal cancer patients and actively provide targeted financial/informational/technical/emotional support to promote nursing skills and reduce caregivers' burdens.

Synthesis and performance evaluation of temperature and salt-resistant organic/inorganic composite copolymers.

Ordinary polymers have poor adaptability in high-temperature and high-salt reservoir environments due to their properties. Organic/inorganic composite copolymer microspheres have the advantages of both of them, which are expected to break through their applicability limitations in such oil reservoirs. Therefore, its preparation and performance have always been of great concern to researchers. In this paper, AM/AMPS/Si-St ternary copolymers were synthesized by precipitation polymerization; then modified nano-silica particles were added to synthesize AM/AMPS/Si-St/g-SiO2 organic/inorganic composite quaternary copolymers. FT-IR and SEM characterized the copolymers to confirm that they were prepared successfully. Experiments were carried out to investigate the concentration and ratio of monomers, which showed that the Weissenberg effect could be avoided. The number of polymer molecules could be stabilized under AM concentration of 12 wt%, AM/AMPS/Si-St ratio of 8:1:1, nano silica of 3.3% and the modification conditions of KH570:SiO2 = 1:1. The experiments of temperature and salt resistance of two copolymers were evaluated and compared were conducted by using viscosity and particle size as parameters. The results showed that quaternary copolymers could increase the viscosity retention rate by about 10% compared with ternary copolymers under high content of Na+ and Mg2+. When the two copolymers were placed at 150°C, the appearance and morphology of the terpolymer changed obviously. Through the SEM image of the quaternary copolymers, it could be seen that although the spherical shape of the microsphere had been gradually lost, no degradation occurred, and the stable time of the modified microspheres had been effectively extended.

Optimizing Edge Active Sites via Intrinsic In-Plane Iridium Deficiency in Layered Iridium Oxides for Oxygen Evolution Electrocatalysis.

Improving catalytic activity of surface iridium sites without compromising catalytic stability is the core task of designing more efficient electrocatalysts for oxygen evolution reaction (OER) in acid. This work presents phase transition of a bulk layered iridate Na2IrO3 in acid solution at room temperature, and subsequent exfoliation to produce 2D iridium oxide nanosheets with around 4 nm thickness. The nanosheets consist of OH-terminated, honeycomb-type layers of edge-sharing IrO6 octahedral framework with intrinsic in-plane iridium deficiency. The nanosheet material is among the most active Ir-based catalysts reported for acidic OER and gives an iridium mass activity improvement up to a factor of 16.5 over rutile IrO2 nanoparticles. The material also exhibits good catalytic and structural stability and retains the catalytic activity for more than 1300 h. The combined experimental and theoretical results demonstrate that edge Ir sites of the layer are active centers for OER, with structural hydroxyl groups participating in the catalytic cycle of OER via a non-traditional adsorbate evolution mechanism. The existence of intrinsic in-plane iridium deficiency is the key to building a unique local environment of edge active sites that have optimal surface oxygen adsorption properties and thereby high catalytic activity.

The influence of resourcefulness on the family functioning of young- and middle-aged lymphoma patients in China: a cross-sectional study.

BACKGROUND: Lymphoma has become 1 of the 10 most common cancers with increased prevalence in young- and middle-aged adults in China. This poses a tremendous burden on patients and their families and brings great challenges to maintaining the balance of family functioning in young- and middle-aged patients. OBJECTIVE: This cross-sectional study aimed to analyse the influence of resourcefulness on the family functioning of Chinese young- and middle-aged lymphoma patients. METHODS: A total of 172 Chinese young- and middle-aged patients with lymphoma were recruited from the oncology departments of two tertiary hospitals in Zhengzhou, Henan, China. They were invited to complete a survey that included a demographic questionnaire, the Resourcefulness Scale and the Chinese Version Family Adaptability and Cohesion Scale II. Multiple linear regression was used to analyse the related factors for family functioning. RESULTS: The multiple regression analysis revealed that the main influencing factors of family cohesion were resourcefulness (ß = 0.338, 95% CI (0.072, 0.173)), spouse caregiver (ß = 0.376, 95% CI (1.938, 10.395)), and cancer stage (ß = -0.274, 95% CI (-3.219, -1.047)). Resourcefulness (ß = 0.438, 95% CI (0.096, 0.181)), spouse caregiver (ß = 0.340, 95% CI (1.348, 8.363)), and family per capita monthly income (ß = 0.157, 95% CI (0.066, 2.243)) were the influencing factors of family adaptability. CONCLUSIONS: Healthcare professionals and family scholars should value young- and middle-aged lymphoma patients' family functioning throughout the cancer treatment process, and family interventions should be designed by healthcare providers based on patients' resourcefulness. Moreover, healthcare providers need to pay attention to the risk factors of patients' family cohesion and adaptability, such as low family per capita monthly income, and consider employing corresponding measures to help them.

Comparing the performance of 2 human papillomavirus assays for a new use indication: a real-world evidence-based evaluation in the United States.

BACKGROUND: The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media. OBJECTIVE: The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated. STUDY DESIGN: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods. RESULTS: The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%-1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98-1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%-100.0%) and 90.9% (95% confidence interval, 62.3%-98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66. CONCLUSION: The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt.

Family resilience in cancer treatment and key influencing factors: A systematic review.

OBJECTIVE: To identify the status quo and key influencing factors of family resilience in cancer treatment. METHODS: Eight electronic databases (PubMed, Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang Database, VIP Database) were searched from 2000 to 10 May 2023. Inclusion criteria were the following: (a) study subjects were cancer patients or their family caregivers, (b) family resilience was measured as a variable, (c) reported factors associated with family resilience, (d) employed either quantitative or mixed methods design, (e) written in English or Chinese, (f) published in peer-reviewed journals. All included studies were evaluated for quality using the Mixed Method Appraisal Tool. RESULTS: Thirty studies were included in the systematic review. According to our analysis, the family resilience of cancer patients could be influenced by various factors associated with six clusters: (a) demographic characteristics, (b) severe staging and treatment of cancer, (c) psychological and health statuses, (d) family, and (e) social environment. Meanwhile, several specific protective factors and risk factors of family resilience were also identified. CONCLUSION: Family resilience plays an important role in promoting positive adaptation in the face of adversity in families of cancer patients/caregivers. This study classifies related influencing factors by analyzing both protective factors and risk factors (and some controversial factors of family resilience). We found that longitudinal studies are needed to further verify the dynamic changes of family resilience, and future research should focus on understanding family resilience from the dual perspectives of cancer patients and their caregivers, to provide comprehensive information for health professionals, and facilitate the development of effective family resilience intervention programs.

Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

Background: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that can potentially be a safe and effective sedative in intensive care units. This study aims to assess whether remimazolam besylate is not inferior to propofol in maintaining mild-to-moderate sedation in critically ill patients receiving long-term mechanical ventilation. Methods and analysis: This is a multicenter, randomized, single-blind, propofol-controlled, non-inferiority study. Eligible patients are randomly assigned to receive remimazolam besylate or propofol in a 1:1 ratio to maintain a Richmond Agitation-Sedation Scale score between -3 and 0. When patients are under-sedated, rescue sedation of dexmedetomidine is added. The primary outcome is the percentage of time in the target sedation range. The secondary outcomes are hours free from the invasive ventilator in 7 days, successful extubation in 7 days, and weaning time, the length of intensive care unit stay, the length of hospital stay, and mortality in 28 days. Modified intention-to-treat and safety analysis is performed. Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT05555667.

An adjusted partial least squares regression framework to utilize additional exposure information in environmental mixture data analysis.

In a large-scale environmental health population study that is composed of subprojects, often different fractions of participants out of the total enrolled have measures of specific outcomes. It's conceptually reasonable to assume the association study would benefit from utilizing additional exposure information from those with a specific outcome not measured. Partial least squares regression is a practical approach to determine the exposure-outcome associations for mixture data. Like a typical regression approach, however, the partial least squares regression requires that each data observation must have both complete covariate and outcome for model fitting. In this paper, we propose novel adjustments to the general partial least squares regression to estimate and examine the association effects of individual environmental exposure to an outcome within a more complete context of the study population's environmental mixture exposures. The proposed framework takes advantage of the bilinear model structure. It allows information from all participants, with or without the outcome values, to contribute to the model fitting and the assessment of association effects. Using this proposed framework, incorporation of additional information will lead to smaller root mean square errors in the estimation of association effects, and improve the ability to assess the significance of the effects.

Impact of HPV testing in opportunistic cervical screening: Support for primary HPV screening in the United States.

Human papillomavirus (HPV) testing for cervical screening increases diagnosis of precancer and reduces the incidence of cervical cancer more than cytology alone. However, real-world evidence from diverse practice settings is lacking for the United States (U.S.) to support clinician adoption of primary HPV screening. Using a population-based registry, which captures all cervical cytology (with or without HPV testing) and all cervical biopsies, we conducted a real-world evidence study of screening in women aged 30 to 64 years across the entire state of New Mexico. Negative cytology was used to distinguish cotests from reflex HPV tests. A total of 264 198 cervical screening tests (with exclusions based on clinical history) were recorded as the first screening test between 2014 and 2017. Diagnoses of cervical intraepithelial neoplasia grades 2 or 3 or greater (CIN2+, CIN3+) from 2014 to 2019 were the main outcomes. Of cytology-negative screens, 165 595 (67.1%) were cotests and 4.8% of these led to biopsy within 2 years vs 3.2% in the cytology-only group. Among cytology-negative, HPV tested women, 347 of 398 (87.2%) CIN2+ cases were diagnosed in HPV-positive women, as were 147 of 164 (89.6%) CIN3+ cases. Only 29/921 (3.2%) CIN3+ and 67/1964 (3.4%) CIN2+ cases were diagnosed in HPV-negative, cytology-positive women with biopsies. Under U.S. opportunistic screening, across a diversity of health care delivery practices, and in a population suffering multiple disparities, we show adding HPV testing to cytology substantially increased the yield of CIN2+ and CIN3+. CIN3+ was rarely diagnosed in HPV-negative women with abnormal cytology, supporting U.S. primary HPV-only screening.

Unchanged PCNA and DNMT1 dynamics during replication in DNA ligase I-deficient cells but abnormal chromatin levels of non-replicative histone H1.

DNA ligase I (LigI), the predominant enzyme that joins Okazaki fragments, interacts with PCNA and Pol δ. LigI also interacts with UHRF1, linking Okazaki fragment joining with DNA maintenance methylation. Okazaki fragments can also be joined by a relatively poorly characterized DNA ligase IIIα (LigIIIα)-dependent backup pathway. Here we examined the effect of LigI-deficiency on proteins at the replication fork. Notably, LigI-deficiency did not alter the kinetics of association of the PCNA clamp, the leading strand polymerase Pol ε, DNA maintenance methylation proteins and core histones with newly synthesized DNA. While the absence of major changes in replication and methylation proteins is consistent with the similar proliferation rate and DNA methylation levels of the LIG1 null cells compared with the parental cells, the increased levels of LigIIIα/XRCC1 and Pol δ at the replication fork and in bulk chromatin indicate that there are subtle replication defects in the absence of LigI. Interestingly, the non-replicative histone H1 variant, H1.0, is enriched in the chromatin of LigI-deficient mouse CH12F3 and human 46BR.1G1 cells. This alteration was not corrected by expression of wild type LigI, suggesting that it is a relatively stable epigenetic change that may contribute to the immunodeficiencies linked with inherited LigI-deficiency syndrome.

Perceived Participation in Decision-Making on Primary Surgery and Associated Factors Among Early Breast Cancer Patients: A Cross-sectional Study.

BACKGROUND: Breast cancer patients wish to participate in the treatment decision-making, but the perceived participation was inconsistent with the willingness, leading to poor patient outcomes. OBJECTIVE: The aims of this study were to explore the perceived participation in the primary surgery decision-making among Chinese patients with early-stage breast cancer (BCa) and to analyze the relationships of demographic and clinical factors, participation competence, self-efficacy, social support, and doctors' promotion of participation with the guidance of the capability, opportunity, motivation-behavior system (the COM-B system). METHODS: Paper surveys were used to collect data from 218 participants. The participation competence, self-efficacy, social support, and the doctor facilitation of involvement were evaluated to measure factors related to perceived participation among early-stage BCa. RESULTS: Perceived participation was low, and participants with a high level of participation competence, self-efficacy, and social support and who were employed and had a higher education level and higher family income perceived higher participation in primary surgery decision-making. CONCLUSIONS: Perceived participation was low and may be facilitated by patients' internal and external factors during the decision-making process. Health professionals should be aware that patient participation in decision-making is a type of self-care health behavior, and targeted decision support interventions should be provided to facilitate participation. IMPLICATIONS FOR PRACTICE: Patient-perceived participation may be evaluated from the perspective of self-care management behaviors among BCa patients. Nurse practitioners should emphasize their important roles in providing information, patient education, and psychological support to better contribute to the course of the treatment decision-making process for BCa patients who faced primary surgery.

Maternal comorbidity index and severe maternal morbidity among medicaid covered pregnant women in a US Southern rural state.

BACKGROUND: The rates of SMM have been steadily increasing in Arkansas, a southern rural state, which has the 5th highest maternal death rate among the US states. The aims of the study were to test the functionality of the Bateman index in association to SMM, in clustering the risks of pregnancies to SMM, and to study the predictability of SMM using the Bateman index. STUDY DESIGN: From the ANGELS database, 72,183 pregnancies covered by Medicaid in Arkansas between 2013 and 2016 were included in this study. The expanded CDC ICD-9/ICD-10 criteria were used to identify SMM. The Bateman comorbidity index was applied in quantifying the comorbidity burden for a pregnancy. Multivariable logistic regressions, KMeans method, and five widely used predictive models were applied respectively for each of the study aims. RESULTS: SMM prevalence remained persistently high among Arkansas women covered by Medicaid (195 per 10,000 deliveries) during the study period. Using the Bateman comorbidity index score, the study population was divided into four groups, with a monotonically increasing odds of SMM from a lower score group to a higher score group. The association between the index score and the occurrence of SMM is confirmed with statistical significance: relative to Bateman score falling in 0-1, adjusted Odds Ratios and 95% CIs are: 2.1 (1.78, 2.46) for score in 2-5; 5.08 (3.81, 6.79) for score in 6-9; and 8.53 (4.57, 15.92) for score ≥10. Noticeably, more than one-third of SMM cases were detected from the studied pregnancies that did not have any of the comorbid conditions identified. In the prediction analyses, we observed minimal predictability of SMM using the comorbidity index: the calculated c-statistics ranged between 62% and 67%; the Precision-Recall AUC values are <7% for internal validation and <9% for external validation procedures. CONCLUSIONS: The comorbidity index can be used in quantifying the risk of SMM and can help cluster the study population into risk tiers of SMM, especially in rural states where there are disproportionately higher rates of SMM; however, the predictive value of the comorbidity index for SMM is inappreciable.

Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

Background: We have previously shown that the long non-coding (lnc)RNA prostate cancer associated 3 (PCA3; formerly prostate cancer antigen 3) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene PRUNE2 (a homolog of the Drosophila prune gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the PCA3/PRUNE2 regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression. Methods: The reciprocal PCA3 and PRUNE2 gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497). We compared the tumor gene expression of PCA3 and PRUNE2 to their corresponding expression in the normal prostate. We also serially examined clinical/pathological variables including time to disease recurrence. Results: We consistently observed increased expression of PCA3 and decreased expression of PRUNE2 in prostate cancer compared with the adjacent normal prostate across all tumor grades and stages. However, there was no association between the relative gene expression levels of PCA3 or PRUNE2 and time to disease recurrence, independent of tumor grades and stages. Conclusions: We concluded that upregulation of the lncRNA PCA3 and targeted downregulation of the protein-coding PRUNE2 gene in prostate cancer could be early (rather than late) molecular events in the progression of human prostate tumorigenesis but are not associated with biochemical recurrence. Further studies of PCA3/PRUNE2 dysregulation are warranted. Funding: We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).

Improving compliance with swallowing exercise to decrease radiotherapy-related dysphagia in patients with head and neck cancer.

Objective: Dysphagia, one of the most common complications in head and neck cancer (HNC) treated with radiotherapy, can severely affect patients' quality of life. Currently, because no "gold standard" treatment exists, swallowing exercise remains the main rehabilitation strategy for dysphagia. However, patients' compliance with long-term swallowing exercise is only 40%, thus, greatly compromising outcomes. This article aims to analyze thefactors influencing swallowing exercise compliance in patients with HNC and explains strategies developed to date for improved rehabilitation outcomes. Methods: Research studies published between 2005 and 2022 were retrieved from seven databases: PubMed, Cochrane Library, Embase, CINAHL, CNKI, Wan Fang Database, and VIP Database, and 21 articles were shortlisted and systematically reviewed. Results: The swallowing exercise compliance in patients with HNC undergoing radiotherapy was affected by multiple factors, including socio-demographic factors, illness-associated factors, treatment-associated factors, and psychosocial factors. Regarding the interventions, current strategies mainly address psychosocial issues via developing various education programs. Conclusions: Different factors influencing swallowing exercise compliance are important and should be observed. Measures including developing multidisciplinary teams, applying innovative equipment, refining the intervention procedure, and applying systematic theory frameworks should be performed to achieve better outcomes of compliance interventions.

Cross-cultural applicability of eye-tracking in assessing attention to emotional faces in preschool-aged children.

Humans show an attention bias toward emotional versus neutral information, which is considered an adaptive pattern of information processing. Deviations from this pattern have been observed in children with socially withdrawn behaviors, with most research being conducted in controlled settings among children from urban areas. The goal of the current study was to examine the cross-cultural applicability of two eye-tracking-based measures in assessing attention biases and their relations to children's symptoms of socially withdrawn behaviors in two independent and diverse samples of preschool children. The cross-cultural comparison was conducted between the Navajo Birth Cohort study (NBCS), an indigenous cohort with relatively low socioeconomic status (SES), and the Illinois Kids Development study (IKIDS), a primarily Non-Hispanic White and high SES cohort. Children in both cohorts completed eye-tracking tasks with pictures of emotional faces, and mothers reported on children's symptoms of socially withdrawn behaviors. Results showed that general patterns of attention biases were mostly the same across samples, reflecting heightened attention toward emotional versus neutral faces. The differences across two samples mostly involved the magnitude of attention biases. NBCS children were slower to disengage from happy faces when these emotional faces were paired with neutral faces. Additionally, socially withdrawn children in the NBCS sample showed a pattern of attentional avoidance for emotional faces. The comparability of overall patterns of attention biases provides initial support for the cross-cultural applicability of the eye-tracking measures and demonstrates the robustness of these methods across clinical and community settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Characterizing Cancer and Work Disparities Using Electronic Health Records.

Advancements in cancer diagnosis and treatment have resulted in improvements in survivor outcomes; however, cancer survivors are more likely to experience adverse employment outcomes such as job loss, reduced working hours, and early retirement. The purpose of this study was to examine employment disparities among cancer survivors. Our study collected data from 29,136 cancer survivors (ages 18-65) between 2015 and 2021 using electronic health records (EHR) and linked to cancer registry data. Of those with employment information (n = 7296), differences in employment status were explored by race, ethnicity, sex, geography, marital status, education, age, and cancer site. Of the patients with employment status available, 61% were employed, 28% were not employed, 9% were disabled, 2% were retired. Logistic regression results revealed adjusted effects: a positive association between employment and marriage, while racial and ethnic minority adults, rurality, and certain age categories were less likely to be employed. Unadjusted results showed a positive association between employment and education. These results contribute to an emerging body of literature showing adverse employment outcomes for cancer survivors.