Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Purpose: Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib. Materials and Methods: In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes. Results: A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. Conclusion Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

In a conventional two-dimensional (2D) culture method, cells are attached to the bottom of the culture dish and grow into a monolayer. These 2D culture methods are easy to handle, cost-effective, reproducible, and adaptable to growing many different types of cells. However, monolayer 2D cell culture conditions are far from those of natural tissue, indicating the need for a threedimensional (3D) culture system. Various methods, such as hanging drop, scaffolds, hydrogels, microfluid systems, and bioreactor systems, have been utilized for 3D cell culture. Recently, external physical stimulation-based 3D cell culture platforms, such as acoustic and magnetic forces, were introduced. Acoustic waves can establish acoustic radiation force, which can induce suspended objects to gather in the pressure node region and aggregate to form clusters. Magnetic targeting consists of two components, a magnetically responsive carrier and a magnetic field gradient source. In a magnetic-based 3D cell culture platform, cells are aggregated by changing the magnetic force. Magnetic fields can manipulate cells through two different methods: positive magnetophoresis and negative magnetophoresis. Positive magnetophoresis is a way of imparting magnetic properties to cells by labeling them with magnetic nanoparticles. Negative magnetophoresis is a label-free principle-based method. 3D cell structures, such as spheroids, 3D network structures, and cell sheets, have been successfully fabricated using this acoustic and magnetic stimuli-based 3D cell culture platform. Additionally, fabricated 3D cell structures showed enhanced cell behavior, such as differentiation potential and tissue regeneration. Therefore, physical stimuli-based 3D cell culture platforms could be promising tools for tissue engineering.

Korean Community Health Status Indicators (K-CHSI) is a model-based database containing annual data on health outcomes and determinants at the municipal level (si/gun/gu-level regions, including mid-sized cities, counties, and districts). K-CHSI’s health outcomes include overall mortality, disease incidence, prevalence rates, and self-reported health. Health determinants were measured in 5 domains: socio-demographic factors, health behaviors, social environment, physical environment, and the healthcare system. The data sources are 71 public databases, including Causes of Death Statistics, Cancer Registration Statistics, Community Health Survey, Population Census, and Census on Establishments and Statistics of Urban Plans. This dataset covers Korea’s 17 metropolitan cities and provinces, with data from approximately 250 municipal regions (si/gun/gu). The current version of the database (DB version 1.3) was built using 12 years of data from 2008 to 2019. All data included in K-CHSI may be downloaded via the Korea Community Health Survey site, with no login requirement (https://chs.kdca.go.kr/chs/recsRoom/dataBaseMain.do). K-CHSI covers extensive health outcomes and health determinants at the municipal level over a period of more than 10 years, which enables ecological and time-series analyses of the relationships among various health outcomes and related factors.

Purpose: This study investigated the impact of nurse practice environment and organizational justice on nurses’job satisfaction. Methods: We identified the factors between nursing work environment and organizational justice to job satisfaction for 189 nurses working at a general hospital in city C. Data were collected from June 1st to 15th, 2023, and analyzed using descriptive statistics, t-test, ANOVA, Pearson’s correlation coefficients, and multiple stepwise regression, using IBM/SPSS 27.0 for the Windows program. Results: The mean job satisfaction was 3.24±0.55 points on a 5-point scale. Multiple stepwise regression revealed that the factors affecting nurses’job satisfaction included nursing foundations for quality of care (β=.26, p=.005), staffing and resource adequacy (β=.40, p<.001), collegial nurse-physician relations (β=-.24, p=.007), and distributive justice(β =.27, p<.001).These variables explained 55.0% of job satisfaction. Conclusion The research findings indicate that higher job satisfaction is associated with a better nurse practice environment and positive perceptions of organization justice. These findings indicate that it is necessary to enhance the nurse practice environment and improve organizational justice to enhance job satisfaction among nurses.

Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by rigidity, intractable multifocal seizures, microcephaly, apnea, and bradycardia immediately after birth. RMFSL is related to a mutation in breast cancer 1-associated ataxia telangiectasia mutated activation-1 protein (BRAT1). We report a case of a female infant born to non-consanguineous Korean parents who developed hypertonia, dysmorphic features, progressive encephalopathy with refractory seizures at birth, and worsening intermittent apnea, leading to intubation and death at 137 days of age. The initial repeated electroencephalographic findings were normal; however, a pattern of focal seizures emerged at 35 days of life. Rapid trio whole-exome sequencing revealed heterozygous mutations c.1313_1314delAG p.(Gln438Argfs*51) and c.1276C>T p. (Gln426*) in BRAT1. After genetic counseling for pregnancy planning, a preimplantation genetic diagnosis for targeted BRAT1 mutations was successfully performed, and a healthy baby was born. To our knowledge, this is the first reported case of a Korean patient with compound heterozygous mutations in BRAT1. An early and accurate genetic diagnosis can help provide timely treatment to patients and indicate the need for reproductive counseling for parents for family planning.

Purpose: Fear of cancer recurrence (FCR) is a common psychological issue in breast cancer (BC) survivors during early survivorship but whether the same is true among long-term survivors has yet to be empirically evaluated. This study investigated FCR level, its associated factors, and impact on quality of life (QoL) in long-term BC survivors. Materials and Methods: Participants included women diagnosed with BC between 2004 and 2010 at two tertiary hospitals. Survey was conducted in 2020. The study measured FCR with the Fear of Cancer Recurrence Inventory and other patient-reported outcomes, including depression and cancer-related QoL. Logistic regression was used to identify factors associated with FCR, and structural equation modeling was conducted to explore the impact of FCR on other outcomes. Results: Of 333 participants, the mean age at diagnosis was 45.5, and 46% experienced FCR. Age at diagnosis ≤ 45 (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.51 to 4.60), shorter time since diagnosis (aOR, 1.75, 95% CI, 1.08 to 2.89), and having a history of recurrence (aOR, 2.56; 95% CI, 1.16 to 5.65) was associated with more FCR. FCR was significantly associated with an increased risk of depression (β=0.471, p < 0.001) and negatively impacted emotional functioning (β=–0.531, p < 0.001). In addition, a higher FCR level may impair overall health-related QoL in long-term BC survivors (β=–0.108, p=0.021). Conclusion Ten years after diagnosis, long-term BC survivors still experienced a high level of FCR. Further, the negative impact of FCR on QoL and increased depression risk require an FCR screening and appropriate interventions to enhance long-term BC survivors' QoL.