Self-Management Using eHealth Technologies for Liver Transplant Recipients: Scoping Review.

BACKGROUND: Liver transplantation has become increasingly common as a last-resort treatment for end-stage liver diseases and liver cancer, with continually improving success rates and long-term survival rates. Nevertheless, liver transplant recipients face lifelong challenges in self-management, including immunosuppressant therapy, lifestyle adjustments, and navigating complex health care systems. eHealth technologies hold the potential to aid and optimize self-management outcomes, but their adoption has been slow in this population due to the complexity of post-liver transplant management. OBJECTIVE: This study aims to examine the use of eHealth technologies in supporting self-management for liver transplant recipients and identify their benefits and challenges to suggest areas for further research. METHODS: Following the Arksey and O'Malley methodology for scoping reviews, we conducted a systematic search of 5 electronic databases: PubMed, CINAHL, Embase, PsycINFO, and Web of Science. We included studies that (1) examined or implemented eHealth-based self-management, (2) included liver transplant recipients aged ≥18 years, and (3) were published in a peer-reviewed journal. We excluded studies that (1) were case reports, conference abstracts, editorials, or letters; (2) did not focus on the posttransplantation phase; (3) did not focus on self-management; and (4) did not incorporate the concept of eHealth or used technology solely for data collection. The quality of the selected eHealth interventions was evaluated using (1) the Template for Intervention Description and Replication guidelines and checklist and (2) the 5 core self-management skills identified by Lorig and Holman. RESULTS: Of 1461 articles, 15 (1.03%) studies were included in the final analysis. Our findings indicate that eHealth-based self-management strategies for adult liver transplant recipients primarily address lifestyle management, medication adherence, and remote monitoring, highlighting a notable gap in alcohol relapse interventions. The studies used diverse technologies, including mobile apps, videoconferencing, and telehealth platforms, but showed limited integration of decision-making or resource use skills essential for comprehensive self-management. The reviewed studies highlighted the potential of eHealth in enhancing individualized health care, but only a few included collaborative features such as 2-way communication or tailored goal setting. While adherence and feasibility were generally high in many interventions, their effectiveness varied due to diverse methodologies and outcome measures. CONCLUSIONS: This scoping review maps the current literature on eHealth-based self-management support for liver transplant recipients, assessing its potential and challenges. Future studies should focus on developing predictive models and personalized eHealth interventions rooted in patient-generated data, incorporating digital human-to-human interactions to effectively address the complex needs of liver transplant recipients. This review emphasizes the need for future eHealth self-management research to address the digital divide, especially with the aging liver transplant recipient population, and ensure more inclusive studies across diverse ethnicities and regions.

REXO5 promotes genomic integrity through regulating R-loop using its exonuclease activity.

Chronic myeloid leukemia (CML), caused by BCR::ABL1 fusion gene, is known to regulate disease progression by altering the expression of genes. However, the molecular mechanisms underlying these changes are largely unknown. In this study, we identified RNA Exonuclease 5 (REXO5/LOC81691) as a novel gene with elevated mRNA expression levels in chronic myeloid leukemia (CML) patients. Additionally, using the REXO5 knockout (KO) K562 cell lines, we revealed a novel role for REXO5 in the DNA damage response (DDR). Compared to wild-type (WT) cells, REXO5 KO cells showed an accumulation of R-loops and increased DNA damage. We demonstrated that REXO5 translocates to sites of DNA damage through its RNA recognition motif (RRM) and selectively binds to R loops. Interestingly, we identified that REXO5 regulates R-loop levels by degrading mRNA within R-loop using its exonuclease domain. REXO5 KO showed ATR-CHK1 activation. Collectively, we demonstrated that REXO5 plays a key role in the physiological control of R-loops using its exonuclease domain. These findings may provide novel insights into how REXO5 expression changes contribute to CML pathogenesis.

The needs for digital health and eHeath literacy of cancer patients, caregivers, and healthcare providers: A multicenter, descriptive correlational study.

PURPOSE: Digital health is an indispensable tool, but its use depends on the eHealth literacy (eHL) of end-users. This study aimed to understand the need for digital health and eHL among cancer patients, caregivers, and healthcare providers and to identify differences in digital health needs related to the eHL of cancer patients. METHODS: A multicenter, descriptive correlational study was conducted and included a total of 209 patients, 150 caregivers and 150 healthcare providers. Digital health needs were identified, and eHL was measured using the Korean version of the eHealth Literacy Scale. Differences in digital health needs in relation to the eHL of patients were analyzed. RESULTS: The most necessary digital health functions among cancer patients and caregivers were 'information and education on symptom management after cancer treatment' and 'education on coping methods for each type of cancer' (87.1-94.0%). Healthcare providers reported the need for a digital health function for 'medication information' and assisting in 'medical appointments' (96.7-98.0%). The preferred types of digital health were telemonitoring, mobile services, and telemedicine by telephone (81.3-90.5%). The mean eHL score of the cancer patients was 28.84 ± 6.75. Differences existed in the need for digital health functions and preferences for digital health types between cancer patients with high and low eHL. CONCLUSIONS: Cancer patients and caregivers expressed strong needs for digital health that provide information and education about symptom management and coping with cancer. Digital health interventions for cancer care need to be developed to reflect the identified needs and preferences and eHL of end-users.

Prevalence of pathogenic variants and digenic disease in patients diagnosed with normosmic hypogonadotropic hypogonadism/Kallmann Syndrome.

BACKGROUND: Hypogonadotropic hypogonadism (HH) is due to impaired gonadotropin releasing hormone (GnRH) action resulting in absent puberty and infertility. At least 44 genes have been identified to possess genetic variants in 40-50% of nHH/KS, and 2-20% have presumed digenic disease, but not all variants have been characterized in vitro. HYPOTHESIS: The prevalence of pathogenic (P)/likely pathogenic (LP) variants in monogenic and digenic nHH/KS is lower than reported. DESIGN: Cross-sectional study. SETTING: University Research Laboratory. SUBJECTS: 158 patients with nHH/KS. METHODS: Exome sequencing (ES) was performed and variants were filtered for 44 known genes using Varsome and confirmed by Sanger Sequencing. MAIN OUTCOME MEASURES: P/LP variants in nHH/KS genes. RESULTS: ES resulted in >370,000 variants, from which variants in 44 genes were filtered. Thirty-one confirmed P/LP variants in 10 genes (ANOS1, CHD7, DUSP6, FGFR1, HS6ST1, KISS1, PROKR2, SEMA3A, SEMA3E, TACR3), sufficient to cause disease, were identified in 30/158 (19%) patients. Only 2/158 (1.2%) patients had digenic variant combinations: a male with hemizygous ANOS1 and heterozygous TACR3 variants and a male with heterozygous SEMA3A and SEMA3E variants. Two patients (1.2%) had compound heterozygous GNRHR (autosomal recessive) variants-one P and one variant of uncertain significance (VUS). Five patients (3.2%) had heterozygous P/LP variants in either GNRHR or TACR3 (both autosomal recessive), but no second variant. CONCLUSION: Our prevalence of P/LP variants in nHH/KS was 19%, and digenicity was observed in 1.2%. These findings are less than those previously reported, and probably represent a more accurate estimation since VUS are not included.

The combination of calreticulin-targeting L-ASNase and anti-PD-L1 antibody modulates the tumor immune microenvironment to synergistically enhance the antitumor efficacy of radiotherapy.

Radiotherapy (RT) triggers immunogenic cell death (ICD). L-ASNase, which catalyzes the conversion of asparagine (Asn), thereby depleting it, is used in the treatment of blood cancers. In previous work, we showed that CRT3LP and CRT4LP, PASylated L-ASNases conjugated to the calreticulin (CRT)-specific monobodies CRT3 and CRT4, increase the efficacy of ICD-inducing chemotherapy. Here, we assessed their efficacy in tumor-bearing mice treated with RT. Methods: Monobody binding was evaluated by in silico molecular docking analysis. The expression and cellular localization of ecto-CRT were assessed by confocal imaging and flow cytometry. The antitumor effect and the roles of CRT3LP and CRT4LP in irradiation (IR)-induced ICD in tumors were analyzed by ELISA, immunohistochemistry, and immune analysis methods. Results: Molecular docking analysis showed that CRT3 and CRT4 monobodies were stably bound to CRT. Exposure to 10 Gy IR decreased the viability of CT-26 and MC-38 tumor cells in a time-dependent manner until 72 h, and increased the expression of the ICD marker ecto-CRT (CRT exposed on the cell surface) and the immune checkpoint marker PD-L1 until 48 h. IR enhanced the cytotoxicity of CRT3LP and CRT4LP in CT-26 and MC-38 tumor cells, and increased reactive oxygen species (ROS) levels. In mice bearing CT-26 and MC-38 subcutaneous tumors treated with 6 Gy IR, Rluc8-conjugated CRT-specific monobodies (CRT3-Rluc8 and CRT4-Rluc8) specifically targeted tumor tissues, and CRT3LP and CRT4LP increased total ROS levels in tumor tissues, thereby enhancing the antitumor efficacy of RT. Tumor tissues from these mice showed increased mature dendritic, CD4+ T, and CD8+ T cells and pro-inflammatory cytokines (IFNγ and TNFα) and decreased regulatory T cells, and the expression of tumor cell proliferation markers (Ki67 and CD31) was downregulated. These data indicate that the combination of IR and CRT-targeting L-ASNases activated and reprogramed the immune system of the tumor microenvironment. Consistent with these data, an immune checkpoint inhibitor (anti-PD-L1 antibody) markedly increased the therapeutic efficacy of combined IR and CRT-targeting L-ASNases. Conclusion: CRT-specific L-ASNases are useful as additive drug candidates in tumors treated with RT, and combination treatment with anti-PD-L1 antibody increases their therapeutic efficacy.

Machine learning-derived model for predicting poor post-treatment quality of life in Korean cancer survivors.

PURPOSE: A substantial number of cancer survivors have poor quality of life (QOL) even after completing cancer treatment. Thus, in this study, we used machine learning (ML) to develop predictive models for poor QOL in post-treatment cancer survivors in South Korea. METHODS: This cross-sectional study used online survey data from 1,005 post-treatment cancer survivors in South Korea. The outcome variable was QOL, which was measured using the global QOL subscale of the European Organization of Cancer and Treatment for Cancer Quality of Life Questionnaire, where a global QOL score < 60.4 was defined as poor QOL. Three ML models (random forest (RF), support vector machine, and extreme gradient boosting) and three deep learning models were used to develop predictive models for poor QOL. Model performance regarding accuracy, area under the receiver operating characteristic curve, F1 score, precision, and recall was evaluated. The SHapely Additive exPlanation (SHAP) method was used to identify important features. RESULTS: Of the 1,005 participants, 65.1% had poor QOL. Among the six models, the RF model had the best performance (accuracy = 0.85, F1 = 0.90). The SHAP method revealed that survivorship concerns (e.g., distress, pain, and fatigue) were the most important factors that affected poor QOL. CONCLUSIONS: The ML-based prediction model developed to predict poor QOL in Korean post-treatment cancer survivors showed good accuracy. The ML model proposed in this study can be used to support clinical decision-making in identifying survivors at risk of poor QOL.

Pulmonary Artery Measurements as Postnatal Prognostic Tool in Right Congenital Diaphragmatic Hernia.

BACKGROUND: Right-sided congenital diaphragmatic hernia (RCDH) is a rare and often fatal congenital anomaly, primarily attributed to lung hypoplasia, which is associated with small branch pulmonary artery (PA). This study investigated whether postnatal PA measurements obtained through echocardiography are associated with mortality or the extracorporeal membrane oxygenation (ECMO) requirement in neonates with RCDH. METHODS: A retrospective study was conducted on neonates with RCDH born between 2008 and 2022. Echocardiography was performed on the day of birth. The diameter of the main PA (MPA) was measured at the maximal dimension, and the diameters of the left PA (LPA) and right PA (RPA) were measured at the bifurcation. The primary outcome was mortality or ECMO requirement. Parameters, including the LPA:MPA ratio, RPA:MPA ratio, Nakata index, McGoon ratio, and ejection fraction (EF), were analyzed and compared with the observed-to-expected lung-to-head ratio (o/e LHR), initial blood gas, and defect size as predictive values. RESULTS: Among 39 neonates with RCDH, 25 (64.1 %) survived without ECMO. The non-survivor or ECMO group exhibited lower o/e LHR, reduced EF, smaller LPA and RPA diameters, and larger MPA diameter than survivors. Lower LPA:MPA ratio, Nakata index, McGoon ratio, and higher initial PaCO2 were associated with adverse outcomes. Notably, the LPA:MPA ratio showed the highest predictive capability (area under the curve, 0.983; p < 0.001). CONCLUSION: The LPA:MPA ratio is a promising postnatal predictor of mortality or ECMO requirement in neonates with RCDH. Additionally, Nakata index, McGoon ratio, and initial PaCO2 are significantly correlated with outcomes. LEVEL OF EVIDENCE: This is a level III. TYPE OF STUDY: Prognostic study.

Transcriptomic data of human adrenocortical NCI-H295R cells treated with cortisol biosynthesis inhibitors.

Adrenal corticosteroid biosynthesis dysregulation can give rise to various pathological conditions, such as Cushing's syndrome, a disorder characterized by the sustained and excessive production of cortisol. Despite the development of several classes of steroidogenesis inhibitors to treat human diseases associated with cortisol overproduction, their use is limited by insufficient efficacy, adverse effects, and/or tolerability. Recently, we identified a series of benzimidazolylurea derivatives, including the representative compound CJ28, as novel cortisol biosynthesis inhibitors [1]. They significantly inhibited both basal and stimulated production of cortisol in NCI-H295R cells, a human adrenocarcinoma cell line. The inhibitory effects were attributed to both attenuated steroidogenesis and de novo cholesterol biosynthesis. Here, we provide transcriptomic (RNA-seq) data from adrenal cell cultures in response to treatment with either CJ28 or metyrapone (MET), an inhibitor of 11ß-hydroxylase). Total RNA was extracted from the cells treated with vehicle (0.1% DMSO), CJ28 (30 µM), or MET (30 µM) for 24 h. Primary sequence data were acquired using paired-end sequencing on an Illumina NovaSeq 6000 platform. The raw RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database (GSE236435). This dataset is a useful resource for providing valuable information on the gene expression networks underlying adrenocortical steroidogenesis.

Osteogenic Activities of Trifolirhizin as a Bioactive Compound for the Differentiation of Osteogenic Cells.

Plant extracts are widely used as traditional medicines. Sophora flavescens Aiton-derived natural compounds exert various beneficial effects, such as anti-inflammatory, anticancer, antioxidant, and antiregenerative activities, through their bioactive compounds, including flavonoids and alkaloids. In the present study, we investigated the biological effects of an S. flavescens-derived flavonoid, trifolirhizin (trifol), on the stimulation of osteogenic processes during osteoblast differentiation. Trifol (>98% purity) was successfully isolated from the root of S. flavescens and characterized. Trifol did not exhibit cellular toxicity in osteogenic cells, but promoted alkaline phosphatase (ALP) staining and activity, with enhanced expression of the osteoblast differentiation markers, including Alp, ColI, and Bsp. Trifol induced nuclear runt-related transcription factor 2 (RUNX2) expression during the differentiation of osteogenic cells, and concomitantly stimulated the major osteogenic signaling proteins, including GSK3ß, ß-catenin, and Smad1/5/8. Among the mitogen-activated protein kinases (MAPKs), Trifol activated JNK, but not ERK1/2 and p38. Trifol also increased the osteoblast-mediated bone-forming phenotypes, including transmigration, F-actin polymerization, and mineral apposition, during osteoblast differentiation. Overall, trifol exhibits bioactive activities related to osteogenic processes via differentiation, migration, and mineralization. Collectively, these results suggest that trifol may serve as an effective phytomedicine for bone diseases such as osteoporosis.

Factors Associated with Poor Quality of Life in Breast Cancer Survivors: A 3-Year Follow-Up Study.

The purpose of this study was to identify subgroups of quality of life (QOL) changes in breast cancer survivors (BCSs), and to determine factors associated with subgroups of consistently low or deteriorated QOL. We enrolled 101 women recently diagnosed with breast cancer in South Korea and asked them to complete a questionnaire at baseline (within 1 month of diagnosis), 1 year later (Year 1), 2 years later (Year 2), and 3 years later (Year 3). We assessed QOL using the global QOL subscale from the EORTC QLQ-C30. We defined low QOL as a global QOL score 10 points below the mean score of the general population. Based on low QOL as defined in this study, we identified subgroups of QOL changes over 3 years. We identified four subgroups of QOL changes: improved (47.4%), stable (30%), continuously low (8.8%), and deteriorated (13.8%), and considered the last two categories (22.6%) poor QOL. Logistic regression analyses demonstrated that significant determinants of poor QOL were insomnia at Year 1, fatigue and anxiety at Year 2, and fatigue, depression, and comorbidity at Year 3. In conclusion, persistent symptoms of insomnia, fatigue, anxiety, depression, and comorbidity are potential risk factors for poor QOL in BCSs.

Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia.

BACKGROUND: Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. METHODS: We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. RESULTS: We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3- patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. CONCLUSION: Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.

A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.

In a patient diagnosed with both Kallmann syndrome (KS) and intellectual disability (ID), who carried an apparently balanced translocation t(7;12)(q22;q24)dn, array comparative genomic hybridization (aCGH) disclosed a cryptic heterozygous 4.7 Mb deletion del(12)(p11.21p11.23), unrelated to the translocation breakpoint. This novel discovery prompted us to consider the possibility that the combination of KS and neurological disorder in this patient could be attributed to gene(s) within this specific deletion at 12p11.21-12p11.23, rather than disrupted or dysregulated genes at the translocation breakpoints. To further support this hypothesis, we expanded our study by screening five candidate genes at both breakpoints of the chromosomal translocation in a cohort of 48 KS patients. However, no mutations were found, thus reinforcing our supposition. In order to delve deeper into the characterization of the 12p11.21-12p11.23 region, we enlisted six additional patients with small copy number variations (CNVs) and analyzed eight individuals carrying small CNVs in this region from the DECIPHER database. Our investigation utilized a combination of complementary approaches. Firstly, we conducted a comprehensive phenotypic-genotypic comparison of reported CNV cases. Additionally, we reviewed knockout animal models that exhibit phenotypic similarities to human conditions. Moreover, we analyzed reported variants in candidate genes and explored their association with corresponding phenotypes. Lastly, we examined the interacting genes associated with these phenotypes to gain further insights. As a result, we identified a dozen candidate genes: TSPAN11 as a potential KS candidate gene, TM7SF3, STK38L, ARNTL2, ERGIC2, TMTC1, DENND5B, and ETFBKMT as candidate genes for the neurodevelopmental disorder, and INTS13, REP15, PPFIBP1, and FAR2 as candidate genes for KS with ID. Notably, the high-level expression pattern of these genes in relevant human tissues further supported their candidacy. Based on our findings, we propose that dosage alterations of these candidate genes may contribute to sexual and/or cognitive impairments observed in patients with KS and/or ID. However, the confirmation of their causal roles necessitates further identification of point mutations in these candidate genes through next-generation sequencing.

Xanol Promotes Apoptosis and Autophagy and Inhibits Necroptosis and Metastasis via the Inhibition of AKT Signaling in Human Oral Squamous Cell Carcinoma.

Angelica keiskei Koidzumi (A. keiskei) is used as a traditional medicine, anti-aging agent, and health food, as well as to restore vitality. Xanthoangelol (xanol), a prenylated chalcone, is the predominant constituent of A. keiskei. Oral squamous cell carcinoma (OSCC), the most common malignancy, has a high proliferation rate and frequent metastasis. However, it is unknown whether xanol has anti-OSCC effects on apoptosis, autophagy, and necroptosis. In the present study, we purified xanol from A. keiskei and demonstrated that it suppressed cell proliferation and induced cytotoxicity in human OSCC. Xanol triggered apoptotic cell death by regulating apoptotic machinery molecules but inhibited necroptotic cell death by dephosphorylating the necroptotic machinery molecules RIP1, RIP3, and MLKL in human OSCC. We also found that xanol inhibited the PI3K/AKT/mTOR/p70S6K pathway and induced autophagosome formation by enhancing beclin-1 and LC3 expression levels and reducing p62 expression levels. Furthermore, we showed that xanol prevented the metastatic phenotypes of human OSCC by inhibiting migration and invasion via the reduction of MMP13 and VEGF. Finally, we demonstrated that xanol exerted anticancer effects on tumorigenicity associated with its transformed properties. Taken together, these findings demonstrate the anticancer effects and biological mechanism of action of xanol as an effective phytomedicine for human OSCC.

Effects of digital self-management symptom interventions on symptom outcomes in adult cancer patients: A systematic review and meta-analysis.

PURPOSE: Digital self-management (SM) interventions targeting symptom relief have demonstrated positive as well as null outcomes, whereas no study has synthesized the effect of the interventions. In this study, we aimed to evaluate the effectiveness of digital SM symptom interventions on symptom outcomes in adult cancer patients. METHODS: A systematic review and meta-analysis based on the previous scoping review was conducted. Six databases (PubMed, CINAHL, Embase, the Cochrane Library, RISS [Korean], and KoreaMed [Korean]) were searched. Population was adult cancer patients. Intervention was SM interventions applying digital health tool targeting symptom management. Comparison was usual care, waitlist controls or active controls. The primary outcome was symptom burden, and the secondary outcomes were individual symptoms. RESULTS: Our meta-analysis of 32 randomized controlled trials (RCTs) including 7888 patients demonstrated that digital SM symptom interventions had a significant effect on reducing symptom burden (effect size [ES] = -0.230) and relieving pain (ES = -0.292), fatigue (ES = -0.417), anxiety (ES = -0.320), and depression (ES = -0.261). CONCLUSIONS: Digital SM interventions can improve symptom outcomes in adult cancer patients. Oncology nurses should be aware that digital SM interventions have demonstrated promising outcomes in cancer patient care.

Factors Associated With Quality of Life Among Posttreatment Cancer Survivors in Korea: A Meta-analysis.

BACKGROUND: Identification of factors associated with quality of life (QOL) among cancer survivors is crucial for identifying potential targets for intervention. OBJECTIVES: We aimed to provide evidence of factors associated with the QOL among posttreatment cancer survivors in Korea. METHODS: We performed a systematic literature search from January 2000 to September 2022 using PubMed, EMBASE, CINAHL, PsycINFO, and Korean databases (RISS, SCIENCEON). We evaluated study quality using the Joanna Briggs Institute Quality Appraisal Checklists for Analytical Cross-sectional Studies and performed statistical analysis using the R 3.0 software (R Foundation for Statistical Computing, Vienna, Austria) package. We analyzed the pooled effect sizes of potential QOL correlates by the random-effects model. RESULTS: This meta-analysis included 31 studies with 8934 participants. The pooled estimates were significantly large for economic status (r = -0.53); significantly medium for fatigue (r = -0.39), anxiety (r = -0.29), depression (r = -0.42), self-efficacy (r = 0.37), and social support (r = 0.30); and significantly small for education level (r = -0.18), job status (r = -0.09), cancer stage (r = -0.20), and time since diagnosis (r = -0.26). CONCLUSIONS: Low education level, having no job, low economic status, advanced cancer stage, short disease period, fatigue, anxiety, and depression were significantly associated with worse QOL, whereas self-efficacy and social support were significantly associated with better QOL. IMPLICATIONS FOR PRACTICE: The findings have potential implications for identifying "at-risk survivors" of deteriorated QOL and for suggesting powerful strategies (eg, enhancing self-efficacy or social support) for improving QOL.

[Complete Rupture of the Extensor Hallucis Longus Tendon with Accessory Slip Mimicking a Partial Rupture: A Case Report]. / 부분파열로 오인된 긴엄지발가락폄근의 주힘줄의 ì™„ì „íŒŒì—´ê³¼ 동반된 보조힘줄: 증례 ë³´ê³ .

The accessory tendon of the extensor hallucis longus is a common type of extensor hallucis longus variation. This is a case of a 38-year-old female patient who initially considered conservative treatment for a suspected partial rupture, but finally underwent surgery after being diagnosed with a complete rupture of the main tendon and accessory tendon medial to the main tendon on MRI scan.

Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis.

AIMS: Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. MATERIALS AND METHODS: Human liver samples obtained from subjects with/without NASH were analyzed. For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). RESULTS: Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. CONCLUSIONS: This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH through autophagy activation mediated by inhibition of hepatocellular glucose uptake and consequently decreased intracellular O-GlcNAcylation.

Identification of a novel class of cortisol biosynthesis inhibitors and its implications in a therapeutic strategy for hypercortisolism.

AIMS: Dysregulation of adrenocortical steroid (corticosteroids) biosynthesis leads to pathological conditions such as Cushing's syndrome. Although several classes of steroid biosynthesis inhibitors have been developed to treat cortisol overproduction, limitations such as insufficient efficacy, adverse effects, and/or tolerability still remain. The present study aimed to develop a new class of small molecules that inhibit cortisol production, and investigated their putative modes of action. MAIN METHODS: We screened an in-house chemical library with drug-like chemical scaffolds using human adrenocortical NCI-H295R cells. We then evaluated and validated the effects of the selected compounds at multiple regulatory steps of the adrenal steroidogenic pathway. Finally, genome-wide RNA expression analysis coupled with gene enrichment analysis was conducted to infer possible action mechanisms. KEY FINDINGS: A subset of benzimidazolylurea derivatives, including a representative compound (designated as CJ28), inhibited both basal and stimulated production of cortisol and related intermediate steroids. CJ28 attenuated the mRNA expression of multiple genes involved in steroidogenesis and cholesterol biosynthesis. Furthermore, CJ28 significantly attenuated de novo cholesterol biosynthesis, which contributed to its suppression of cortisol production. SIGNIFICANCE: We identified a novel chemical scaffold that exerts inhibitory effects on cortisol and cholesterol biosynthesis via coordinated transcriptional silencing of gene expression networks. Our findings also reveal an additional adrenal-directed pharmacological strategy for hypercortisolism involving a combination of inhibitors targeting steroidogenesis and de novo cholesterol biosynthesis.

[Primary Neuroendocrine Carcinoma of the Breast: A Case Report and Literature Review]. / ìœ ë°©ì—ì„œ 발생한 원발성 ì‹ ê²½ë‚´ë¶„ë¹„ì•”ì¢ : 증례 ë³´ê³ ì™€ ë¬¸í—Œê³ ì°°.

In general, neuroendocrine cancer develops in the digestive or respiratory tract, and when it is found in other organs, it is often due to metastasis. Primary neuroendocrine carcinoma of the breast occurs very rarely, and the exact clinical picture, radiological findings, treatment and prognosis are not well known. Furthermore, only a small number of literature reports have been published. Here, we report the imaging findings of primary neuroendocrine carcinoma in the breast of a 51-year-old female, along with a literature review.

Patient Empowerment in Cancer Care: A Scoping Review.

BACKGROUND: Patient empowerment is receiving increasing attention in cancer care, and its relevance has led to a growing body of literature. Empowerment-related evidence, however, has not been comprehensively reviewed. OBJECTIVE: The purpose of this scoping review was to summarize the available evidence on patient empowerment in cancer care. Specifically, we examined how patient empowerment has been defined and measured and what we have learned. METHODS: We searched 6 databases (MEDLINE, PubMed, CINAHL, EMBASE, Cochrane Library, and PsycINFO), adapting key search terms (eg, "neoplasm," "empowerment") to each. Extracted data included author, publication year, country of data collection, main study purpose, study design, sampling method, setting, cancer trajectory, definition of empowerment and its source, measurement of empowerment, correlates, intervention (if applicable), and major results. RESULTS: Of the 2987 articles we initially identified, we included 64 studies (18 quantitative, 9 qualitative, 9 psychometric validation, 8 mixed methods, 6 reviews, and 14 others). Across designs, randomized controlled trials were the most frequent. A comprehensive summary by study designs was provided. CONCLUSIONS: The review highlights the importance of defining the empowerment concept, which is generally vague. There is a paucity of research on examining the relationship between empowerment and its related concepts. More nonexperimental studies (eg, cross-sectional, longitudinal, case-control studies) are required. IMPLICATIONS FOR PRACTICE: Nurses are in an optimal position to engage in the process of empowerment, leading to its benefits. To achieve the best outcomes, nurses need to clarify the definition, select an appropriate measurement, and be trained in empowerment strategies.