α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

High-density genetic map construction and QTL mapping of a zigzag-shaped stem trait in tea plant (Camellia sinensis).

The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.

The relationship between medication beliefs, patient activation, and self-rated health in patients taking oral anticancer agents.

PURPOSE: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH. METHODS: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, lung, or prostate cancer. Patients completed a self-reported survey including items of SRH, Beliefs about Medicines Questionnaire (BMQ), and Patient Activation Measure (PAM-13). Descriptive statistics, bivariate correlation, hierarchical multiple linear regression, and mediation analysis were conducted. RESULTS: The results indicate that patients taking OAAs have ambivalent attitudes toward medication. Both medication necessity (r = - 0.27) and concerns (r = - 0.21) were negatively associated with SRH, while patient activation was positively associated with SRH (r = 0.38). Patient activation had a negative association with medication concerns (r = - 0.36) and fully mediated the relationship between medication concerns and SRH in patients taking OAAs (indirect effect = - 0.154, 95% confidence interval, - 0.276 to - 0.060). CONCLUSION: The findings highlight the significance of activating patients to better understand and manage their OAAs. It is crucial for oncology professionals to provide multifaceted interventions to promote patient activation with an effort to mitigate the negative impact of medication beliefs on patient-perceived health outcomes.

Oncology patients' willingness to report their medication safety concerns from home: a qualitative study.

PURPOSE: Oncology patients often struggle to manage their medications and related adverse events during transitions of care. They are expected to take an active role in self-monitoring and timely reporting of their medication safety events or concerns to clinicians. The purpose of this study was to explore the factors influencing oncology patients' willingness to report adverse events or concerns related to their medication after their transitions back home. METHODS: A qualitative interview study was conducted with adult patients with breast, prostate, lung, or colorectal cancer who experienced care transitions within the previous year. A semi-structured interview guide was developed to understand patients' perceptions of reporting mediation-related safety events or concerns from home. All interviews were conducted via phone calls, recorded, and transcribed for thematic data analysis. RESULTS: A total of 41 individuals participated in the interviews. Three main themes and six subthemes emerged, including patients' perceived relationship with clinicians (the quality of communication and trust in clinicians), perceived severity of adverse medication events (perceived severe vs. non-severe events), and patient activation in self-management (self-efficacy in self-management and engagement in monitoring health outcomes). CONCLUSION: The patient-clinician relationship significantly affects patients' reporting behaviors, which can potentially interact with other factors, including the severity of adverse events. It is important to engage oncology patients in medication safety self-reporting from home by enhancing health communication, understanding patients' perceptions of severe events, and promoting patient activation. By addressing these efforts, healthcare providers should adopt a more patient-centered approach to enhance the overall quality and safety of oncological care.

The Acceptance and Use of Digital Technologies for Self-Reporting Medication Safety Events After Care Transitions to Home in Patients With Cancer: Survey Study.

BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood. OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance. METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions. RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78). CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.

Bulked Segregant RNA-Seq Reveals Different Gene Expression Patterns and Mutant Genes Associated with the Zigzag Pattern of Tea Plants (Camellia sinensis).

The unique zigzag-patterned tea plant is a rare germplasm resource. However, the molecular mechanism behind the formation of zigzag stems remains unclear. To address this, a BC1 genetic population of tea plants with zigzag stems was studied using histological observation and bulked segregant RNA-seq. The analysis revealed 1494 differentially expressed genes (DEGs) between the upright and zigzag stem groups. These DEGs may regulate the transduction and biosynthesis of plant hormones, and the effects on the phenylpropane biosynthesis pathways may cause the accumulation of lignin. Tissue sections further supported this finding, showing differences in cell wall thickness between upright and curved stems, potentially due to lignin accumulation. Additionally, 262 single-nucleotide polymorphisms (SNPs) across 38 genes were identified as key SNPs, and 5 genes related to zigzag stems were identified through homologous gene function annotation. Mutations in these genes may impact auxin distribution and content, resulting in the asymmetric development of vascular bundles in curved stems. In summary, we identified the key genes associated with the tortuous phenotype by using BSR-seq on a BC1 population to minimize genetic background noise.

USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice.

BACKGROUND: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. METHODS: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms. RESULTS: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent. CONCLUSIONS: USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.

BRAF D594A mutation defines a unique biological and immuno-modulatory subgroup associated with functional CD8+ T cell infiltration in colorectal cancer.

BACKGROUND: BRAF non-V600 mutation occupies a relatively small but critical subset in colorectal cancer (CRC). However, little is known about the biological functions and impacts of BRAF class III mutation in CRC. Here, we aim to explore how D594A mutation impacts on biological behaviors and immune related signatures in murine CRC cells. METHODS: BRAF V600E (class I), G469V (class II) and D594A (class III) mutant cell lines were established based on MC38 cells. The biological behaviors of cells were evaluated in respect of cell growth, cell proliferation, cell apoptosis, cell migration and invasion by the methods of colony-forming assay, CCK-8 assay, Annexin V/PI staining and transwell assay. The concentrations of soluble cytokines were detected by ELISA. The membrane expression of immuno-modulatory molecules and the pattern of tumor infiltrating lymphocyte were evaluated by flow cytometry. The molecular mechanism was explored by RNA sequencing. Immunohistochemistry (IHC) staining was used for the detection of CD8α in tumor tissues. qRT-PCR and western blot were performed to assess the mRNA and protein expression. Anti-PD-L1 treatment and cytokines neutralization experiments were conducted in in vivo models. RESULTS: D594A mutant cells displayed lower grade malignancy characteristics than V600E (class I) and G469V (class II) mutant cells. Meanwhile, D594A mutation led to evident immuno-modulatory features including upregulation of MHC Class I and PD-L1. In vivo experiments displayed that the frequency of infiltrated CD8+ T cells was significantly high within D594A mutant tumors, which may provide potential response to anti-PD-L1 therapy. RNA sequencing analysis showed that D594A mutation led to enhanced expression of ATF3 and THBS1, which thus facilitated CXCL9 and CXCL10 production upon IFN-γ treatment. In addition, CXCL9 or CXCL10 neutralization reduced the infiltration of CD8+ T cells into THBS1-overexpressing tumors. CONCLUSIONS: D594A mutant CRC exhibited lower aggressiveness and immune-activated phenotype. ATF3-THBS1-CXCL9/CXCL10 axis mediated functional CD8+ T cells infiltration into the microenvironment of D594A mutant CRC. Our present study is helpful to define this mutation in CRC and provide important insights in designing effective immunotherapeutic strategies in clinic.

Polysaccharides and glycolipids of Mycobacterium tuberculosis and their induced immune responses.

Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis (M. tuberculosis). The structures of polysaccharides and glycolipids at M. tuberculosis cell wall vary among different strains, which affect the physiology and pathogenesis of mycobacteria by activating or inhibiting innate and acquired immunity. Among them, some components such as lipomannan (LM) and lipoarabinomannan (LAM) activate innate immunity by recognizing some kinds of pattern recognition receptors (PRRs) like Toll-like receptors, while other components like mannose-capped lipoarabinomannan (ManLAM) could prevent innate immune responses by inhibiting the secretion of pro-inflammatory cytokines and maturation of phagosomes. In addition, many glycolipids can activate natural killer T (NKT) cells and CD1-restricted T cells to produce interferon-γ (IFN-γ). Furthermore, humoral immunity against cell wall components, such as antibodies against LAM, plays a role in immunity against M. tuberculosis infection. Cell wall polysaccharides and glycolipids of M. tuberculosis have potential applications as antigens and adjuvants for novel TB subunit vaccines.

USP38 regulates inflammatory cardiac remodeling after myocardial infarction.

BACKGROUND: The inflammatory response and subsequent ventricular remodeling are key factors contributing to ventricular arrhythmias (VAs) after myocardial infarction (MI). Ubiquitin-specific protease 38 (USP38) is a member of the USP family, but the impact of USP38 in arrhythmia substrate generation after MI remains unclear. This study aimed to determine the role of USP38 in post-MI VAs and its underlying mechanisms. METHODS AND RESULTS: Surgical left descending coronary artery ligation was used to construct MI models. Morphological, biochemical, histological, and electrophysiological studies and molecular analyses were performed after MI on days 3 and 28. We found that the USP38 expression was remarkably increased after MI. Cardiac-conditional USP38 knockout (USP38-CKO) reduces the expression of the inflammatory marker CD68 as well as the inflammatory factors TNF-α and IL-1ß after MI, thereby alleviating advanced cardiac fibrosis, electrical remodeling, ion channel remodeling, and susceptibility to VAs. In contrast, cardiac-specific USP38 overexpression (USP38-TG) showed a significant opposite effect, exacerbating the early inflammatory response and cardiac remodeling after MI. Mechanistically, USP38 knockout inhibited activation of the TAK1/NF-κB signaling pathway after MI, whereas USP38 overexpression enhanced activation of the TAK1/NF-κB signaling pathway after MI. CONCLUSIONS: Our study confirms that USP38-CKO attenuates the inflammatory response, improves ventricular remodeling after myocardial infarction, and reduces susceptibility to malignant VA by inhibiting the activation of the TAK1/NF-κB pathway, with USP38-TG playing an opposing role. These results suggest that USP38 may be an important target for the treatment of cardiac remodeling and arrhythmias after MI.

Case report of avascular necrosis of the glans penis after PAE embolization.

BACKGROUND: Prostate artery embolization (PAE) is a relatively safe and effective alternative method for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. The adverse events caused by PAE are primarily mild, including urinary tract infection, acute urinary retention, dysuria, fever, etc. Severe complications, such as nontarget organ embolism syndrome or penile glans ischemic necrosis, are rare. Here, we report a case of severe ischemic necrosis of the glans penis after PAE and review the literature. CASE PRESENTATION: An 86-year-old male patient was admitted to the hospital due to progressive dysuria with gross hematuria. The patient underwent placement of a three-way urinary catheter to facilitate continuous bladder flushing, hemostasis, and rehydration. After admission, his hemoglobin decreased to 89 g/L. After an examination, the diagnosis was benign prostatic hyperplasia with bleeding. During communication with the patient regarding treatment, he requested prostate artery embolization due to his advanced age and concomitant disease status. He underwent bilateral prostate artery embolization under local anesthesia. His urine gradually turned clear. However, on the 6th day after embolization, the glans gradually showed ischemic changes. On the 10th day, there was partial necrosis and blackening of the glans. The glans completely healed, and the patient was able to urinate smoothly on the 60th day after local cleaning and debridement, the administration of pain relief, anti-inflammatory and anti-infection agents, and external application of burn ointment. CONCLUSION: Penile glans ischemic necrosis after PAE is rare. The symptoms include pain, congestion, swelling, and cyanosis in the glans.

Use of Electronic Communication with Clinicians Among Cancer Survivors: Health Information National Trend Survey in 2019 and 2020.

Purpose: To describe cancer survivors' use of electronic communication (e-communication) with clinicians and identify factors associated with their use, including the COVID-19 pandemic. Methods: Secondary analysis included cancer survivors (N = 1,482) from the combined Health Information National Trends Survey HINTS 5 Cycle 3 and Cycle 4. Survivors' use of e-communication was defined by at least one of four e-communication use behaviors in the past 12 months. Bivariate analysis and logistic regression were conducted to examine factors associated with e-communication use. All analyses considered the complex survey design using the jackknife replication method. Results: The prevalence of e-communication use was 64% among cancer survivors. The overall e-communication use slightly increased after the start of the COVID-19 pandemic (63% vs. 64%, p = 0.79). Older adults (≥65 years old) were less likely to use e-communication (odds ratio [OR] = 0.55; 95% confidence interval [CI], 0.36-0.86); survivors who were white (OR = 2.30; 95% CI, 1.36-3.86), living in a metro area (OR = 2.47; 95% CI, 1.44-4.27), diagnosed with breast cancer (OR = 2.03; 95% CI, 1.06-3.88), seeking cancer-related information previously (OR = 2.89; 95% CI, 1.83-4.58), or having a regular health care provider (OR = 2.07,; 95% CI, 1.10-3.88) were more likely to use e-communication. The start of the COVID-19 pandemic was marginally associated with the increased e-communication use (p = 0.053) when other variables were controlled. Conclusion: This nationally representative survey analysis has identified disparities in e-communication use among cancer survivors and revealed the potential increase in e-communication use under the impact of the COVID-19 pandemic. Additional support is clearly warranted for those older, nonwhite, living in rural areas, or without a regular provider, to promote their e-communication use for the delivery of optimal and high-quality cancer care.

Screening of rosmarinic acid from Salvia miltiorrhizae acting on the novel target TRPC1 based on the 'homology modelling-virtual screening-molecular docking-affinity assay-activity evaluation' method.

CONTEXT: Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of 'thoracic obstruction'. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment. OBJECTIVE: This work screens the active component acting on TRPC1 from Salvia miltiorrhizae. MATERIALS AND METHODS: TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski's rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells. RESULTS: Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza. Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 µM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells. DISCUSSION AND CONCLUSIONS: We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae, and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.

The prognostic impact of myosteatosis on overall survival in gynecological cancer patients: A meta-analysis and trial sequential analysis.

Myosteatosis is a novel imaging biomarker for survival in gynecological cancer patients; however, the evidence is inconsistent. This meta-analysis aims to investigate the impact of myosteatosis on overall survival in the gynecological oncology setting. Three databases (PubMed, EMBASE and Web of Science) were systematically searched for relevant literature up to October 30, 2021. A random-effects model was used to evaluate the predictive effect of myosteatosis on overall survival in the gynecological cancer population. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. Trial sequential analysis was used to control the risk of random errors. Twelve studies with a total of 2519 patients were included. Myosteatosis was associated with a 50% increased mortality risk (HR 1.50, 95% CI 1.24-1.82, P < .001) in gynecological cancer patients. Subgroup analyses stratified by study design, statistical model, treatment, sample size and stage confirmed the predictive value of myosteatosis on survival. However, the prognostic ability of myosteatosis only was held in the American and European populations but lost in Asians. Additionally, myosteatosis was not associated with the increased mortality in endometrial and cervical cancers, except for ovarian cancers. Overall, myosteatosis is a powerful predictor of reduced overall survival in gynecological cancer patients.

A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally.

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity. To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named "PLGA-PEG-poly(I:C)" (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4+ T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1, IgG2c in serum, and sIgA in lung washings. Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses.

Tolerance to oral anticancer agent treatment in older adults with cancer: a secondary analysis of data from electronic health records and a pilot study of patient-reported outcomes.

BACKGROUND: More than 60% of cancer cases occur in older adults, and many are treated with oral anticancer agents. Yet, the treatment tolerability in older adults has not been fully understood due to their underrepresentation in oncology clinical trials, creating challenges for treatment decision-making and symptom management. The objective of this study was to investigate the tolerance of capecitabine, an example of oral chemotherapy, among older adults with cancer and explore factors associated with capecitabine-related side effects and treatment changes, to enhance supportive care. METHODS: A secondary analysis used combined data from electronic health records and a pilot study of patient-reported outcomes, with a total of 97 adult patients taking capecitabine during 2016-2017, including older adult patients aged 65 years or older (n = 43). The data extracted included patient socio-demographics, capecitabine information, side effects, and capecitabine treatment changes (dose reductions and dose interruptions). Bivariate correlations, negative binomial regression, and multiple linear regression were conducted for data analysis. RESULTS: Older adults were more likely to experience fatigue (86% vs. 51%, p = .001) and experienced more severe fatigue (ß = 0.44, p = 0.03) and hand-foot syndrome (HFS) (ß = 1.15, p = 0.004) than younger adults. The severity of fatigue and HFS were associated with the number of outpatient medications (ß = 0.06, p = 0.006) and the duration of treatment (ß = 0.50, p = 0.009), respectively. Correlations among side effects presented different patterns between younger and older adults. Although more older adults experienced dose reductions (21% vs. 13%) and dose interruptions (33% vs. 28%) than younger adults, the differences were not statistically different. Female sex, breast cancer diagnosis, capecitabine monotherapy, and severe HFS were found to be associated with dose reductions (p-values < 0.05). CONCLUSIONS: Older adults were less likely to tolerate capecitabine treatment and had different co-occurring side effects compared to younger adults. While dose reductions are common among older adults, age 65 years or older may not be an independent factor of treatment changes. Other socio-demographic and clinical factors may be more likely to be associated. Future studies can be conducted to further explore older adults' tolerance to a variety of oral anticancer agents to generate more evidence to support optimal treatment decision-making and symptom management.

Assessing Neonatal Intensive Care Unit Structures and Outcomes Before and During the COVID-19 Pandemic: Network Analysis Study.

BACKGROUND: Health care organizations (HCOs) adopt strategies (eg. physical distancing) to protect clinicians and patients in intensive care units (ICUs) during the COVID-19 pandemic. Many care activities physically performed before the COVID-19 pandemic have transitioned to virtual systems during the pandemic. These transitions can interfere with collaboration structures in the ICU, which may impact clinical outcomes. Understanding the differences can help HCOs identify challenges when transitioning physical collaboration to the virtual setting in the post-COVID-19 era. OBJECTIVE: This study aims to leverage network analysis to determine the changes in neonatal ICU (NICU) collaboration structures from the pre- to the intra-COVID-19 era. METHODS: In this retrospective study, we applied network analysis to the utilization of electronic health records (EHRs) of 712 critically ill neonates (pre-COVID-19, n=386; intra-COVID-19, n=326, excluding those with COVID-19) admitted to the NICU of Vanderbilt University Medical Center between September 1, 2019, and June 30, 2020, to assess collaboration between clinicians. We characterized pre-COVID-19 as the period of September-December 2019 and intra-COVID-19 as the period of March-June 2020. These 2 groups were compared using patients' clinical characteristics, including age, sex, race, length of stay (LOS), and discharge dispositions. We leveraged the clinicians' actions committed to the patients' EHRs to measure clinician-clinician connections. We characterized a collaboration relationship (tie) between 2 clinicians as actioning EHRs of the same patient within the same day. On defining collaboration relationship, we built pre- and intra-COVID-19 networks. We used 3 sociometric measurements, including eigenvector centrality, eccentricity, and betweenness, to quantify a clinician's leadership, collaboration difficulty, and broad skill sets in a network, respectively. We assessed the extent to which the eigenvector centrality, eccentricity, and betweenness of clinicians in the 2 networks are statistically different, using Mann-Whitney U tests (95% CI). RESULTS: Collaboration difficulty increased from the pre- to intra-COVID-19 periods (median eccentricity: 3 vs 4; P<.001). Nurses had reduced leadership (median eigenvector centrality: 0.183 vs 0.087; P<.001), and neonatologists with broader skill sets cared for more patients in the NICU structure during the pandemic (median betweenness centrality: 0.0001 vs 0.005; P<.001). The pre- and intra-COVID-19 patient groups shared similar distributions in sex (~0 difference), race (4% difference in White, and 3% difference in African American), LOS (interquartile range difference in 1.5 days), and discharge dispositions (~0 difference in home, 2% difference in expired, and 2% difference in others). There were no significant differences in the patient demographics and outcomes between the 2 groups. CONCLUSIONS: Management of NICU-admitted patients typically requires multidisciplinary care teams. Understanding collaboration structures can provide fine-grained evidence to potentially refine or optimize existing teamwork in the NICU.

Acceptance and Use of Home-Based Electronic Symptom Self-Reporting Systems in Patients With Cancer: Systematic Review.

BACKGROUND: Electronic symptom self-reporting systems (e-SRS) have been shown to improve symptoms and survival in patients with cancer. However, patient engagement in using e-SRS for voluntary symptom self-reporting is less optimal. Multiple factors can potentially affect patients' acceptance and engagement in using home-based e-SRS. However, such factors have not been fully explored in cancer populations. OBJECTIVE: The aim of this study is to understand the acceptance and use of home-based e-SRS by patients with cancer and identify associated facilitators and barriers. METHODS: PubMed, CINAHL, Scopus, and PsycINFO (January 2010 to March 2020) were searched using a combination of Medical Subject Headings (MeSH) terms and keywords such as symptom self-reporting, electronic/technology, cancer, and their synonyms. Included studies focused on the use of home-based e-SRS by patients with cancer and their families. Studies on patients' use of e-SRS in clinical settings only were excluded. Of the 3740 papers retrieved, 33 were included in the final review. Factors associated with patient acceptance and use of e-SRS were extracted and synthesized. RESULTS: Most e-SRS were web based (22/33, 66%) or mobile app based (9/33, 27%). The e-SRS initial acceptance, represented by patient enrollment rates, ranged from 40% (22/55) to 100% (100/100). High e-SRS acceptance was rated by 69% (59/85) to 77.6% (337/434) of the patients after they used the system. The e-SRS use, measured by patients' response rates to questionnaires (ranging from 1596/3521, 45.33% to 92%) or system log-on rates (ranging from 4/12, 33% to 99/100, 99%), declined over time in general patterns. Few studies (n=7) reported e-SRS use beyond 6 months, with the response rates ranging from 62% (40/64) to 85.1% (541/636) and the log-on rates ranging from 63.6% (103/162) to 77% (49/64). The availability of compatible devices and technical support, interactive system features, information accessibility, privacy, questionnaire quality, patient physical/psychosocial status, and age were associated with patient acceptance and use of home-based e-SRS. CONCLUSIONS: Acceptance and use of home-based e-SRS by patients with cancer varied significantly across studies, as assessed by a variety of approaches. The lack of access to technology has remained a barrier to e-SRS adoption. Interactive system features and personalized questionnaires may increase patient engagement. More studies are needed to further understand patients' long-term use of home-based e-SRS behavior patterns to develop personalized interventions to support symptom self-management and self-reporting of patients with cancer for optimal health outcomes.

Treatment with endoscopic transnasal resection of hypothalamic pilocytic astrocytomas: a single-center experience.

BACKGROUNDS: Pilocytic astrocytomas (PAs) are World Health Organization (WHO) grade I tumors, which are relatively common, and are benign lesions in children. PAs could originate from the cerebellum, optic pathways, and third ventricular/hypothalamic region. Traditional various transcranial routes are used for hypothalamic PAs (HPAs). However, there are few studies on hypothalamic PAs treated through the endoscopic endonasal approach (EEA). This study reports the preliminary experience of the investigators and results with HPAs via expanded EEAs. METHODS: All patients with HPAs, undergone EEA in our hospital from 2017 to 2019, were retrospectively reviewed. The demographic data, clinical symptoms, complications, skull base reconstruction, prognosis, and endocrinological data were all recorded and analyzed in detail. RESULTS: Finally, five female patients were enrolled. The average age of patients was 28.6 ± 14.0. All patients had complaints about their menstrual disorder. One patient had severe bilateral visual impairment. Furthermore, only one patient suffered from severe headache due to acute hydrocephalus, although there were four patients with headache or dizziness. Four cases achieved gross-total resection, and one patient achieved subtotal resection. Furthermore, there was visual improvement in one patient (case 5), and postoperative worsening of vision in one patient (case 4). However, only one patient had postoperative intracranial infection. None of the patients experienced a postoperative CSF leak, and in situ bone flap (ISBF) techniques were used for two cases for skull base repair. In particular, ISBF combined with free middle turbinate mucosal flap was used for case 5. After three years of follow-up, three patients are still alive, two patients had no neurological or visual symptoms, or tumor recurrence, and one patient had severe hypothalamic dysfunction. Unfortunately, one patient died of severe postoperative hypothalamus reaction, which presented with coma, high fever, diabetes insipidus, hypernatremia and intracranial infection. The other patient died of recurrent severe pancreatitis at one year after the operation. CONCLUSION: Although the data is still very limited and preliminary, EEA provides a direct approach to HPAs with acceptable prognosis in terms of tumor resection, endocrinological and visual outcomes. ISBF technique is safe and reliable for skull base reconstruction.

A Robust SMC-PHD Filter for Multi-Target Tracking with Unknown Heavy-Tailed Measurement Noise.

In multi-target tracking, the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter is a practical algorithm. Influenced by outliers under unknown heavy-tailed measurement noise, the SMC-PHD filter suffers severe performance degradation. In this paper, a robust SMC-PHD (RSMC-PHD) filter is proposed. In the proposed filter, Student-t distribution is introduced to describe the unknown heavy-tailed measurement noise where the degrees of freedom (DOF) and the scale matrix of the Student-t distribution are respectively modeled as a Gamma distribution and an inverse Wishart distribution. Furthermore, the variational Bayesian (VB) technique is employed to infer the unknown DOF and scale matrix parameters while the recursion estimation framework of the RSMC-PHD filter is derived. In addition, considering that the introduced Student- t distribution might lead to an overestimation of the target number, a strategy is applied to modify the updated weight of each particle. Simulation results demonstrate that the proposed filter is effective with unknown heavy-tailed measurement noise.