hsa-miR-520a is derived from MIR520A located at 19q13.42 and has a significant part in the development of various disorders, including different types of cancers, recurrent pregnancy loss, cerebral ischemia/reperfusion injury, and sciatica. In relation to cancer, numerous studies have presented diverse findings regarding the function of this particular miRNA. To summarize, it has been observed to be down-regulated in pancreatic cancer, glioma, ovarian cancer, cervical cancer, uterine corpus endometrial carcinoma, lung cancer, and acute myeloid leukemia. The purpose of this review is to offer an inclusive overview of the role of has-miR-520a in these disorders, with a specific focus on its target mRNAs in each setting and the deregulated signaling pathways involved. Additionally, we aimed to summarize the implication of miR-520a as a prognostic factor in malignancies. Finally, we performed comprehensive in-silico analyses to uncover the biological roles of this miRNA and introducing innovative concepts for future research endeavors.

OBJECTIVE: This study aims to explore the relationship between apparent diffusion coefficient (ADC) and fractional-order calculus (FROC)-specific parameters with prognostic indicators and Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation status in rectal cancer.
METHODS: One hundred fifty-eight patients with rectal cancer were retrospectively enrolled. Histogram measurements of ADC, diffusion coefficient (D), intravoxel diffusion heterogeneity (β), and a microstructural quantity (μ) were estimated for the whole-tumor volume. The relationships between histogram measurements and prognostic indicators were evaluated. The efficacy of histogram measurements, both conducted singly and in conjunction, for evaluating different KRAS mutation statuses was also assessed. The performance of mean and median histogram measurements in evaluating various KRAS mutation statuses was assessed using Receiver Operating Characteristic (ROC) curve analysis. A p-value of less than 0.05 was considered statistically significant.
RESULTS: The histogram measurements of ADC, D, β, and μ differed significantly between well-moderately differentiated groups and poorly differentiated groups, T1-2 and T3-4 subgroups, lymph node metastasis (LNM)-negative and LNM-positive subgroups, extranodal extension (ENE)-negative and ENE-positive subgroups, tumor deposit (TD)-negative and TD-positive subgroups, and lymphovascular invasion (LVI)-negative and LVI-positive subgroups. The combination of Dmean, βmean, and μmean achieved the highest performance [The area under the ROC curve (AUC) = 0.904] in evaluating the KRAS mutation status.
CONCLUSIONS: When assessing parameters from the FROC model as potential biomarkers through histograms, they surpass traditional ADC values in distinguishing prognostic indicators and determining KRAS mutation status in rectal cancer.

(1) Currently, the survival prognosis for patients with relapsed and refractory acute myeloid leukemia (R/R AML) is extremely poor. Therefore, the exploration of novel drugs is imperative to enhance the prognosis of patients with R/R AML. The therapeutic efficacy and mechanism of Chidamide, a novel epigenetic regulatory drug, in the treatment of R/R AML remain unclear.
METHODS: The mechanism of action of Chidamide has been explored in various AML cell lines through various methods such as cell apoptosis, cell cycle analysis, high-throughput transcriptome sequencing, gene silencing, and xenograft models.
RESULTS: Here, we have discovered that chidamide potently induces apoptosis, G0/G1 phase arrest, and mitochondrial membrane potential depolarization in R/R AML cells, encompassing both primary cells and cell lines. Through RNA-seq analysis, we further revealed that chidamide epigenetically regulates the upregulation of differentiation-related pathways while suppressing those associated with cell replication and cell cycle progression. Notably, our screening identified NR4A3 as a key suppressor gene whose upregulation by chidamide leads to P21-dependent cell cycle arrest in the G0/G1 phase.
CONCLUSIONS: We have discovered a novel epigenetic regulatory mechanism of chidamide in the treatment of relapsed and refractory acute myeloid leukemia (R/R AML).

OBJECTIVE: To assess prognostic significance of residual tumor at repeat transurethral resection (reTUR) in contemporary non-muscle-invasive bladder cancer (NMIBC) patients.
METHODS: Patients were identified retrospectively from eight referral centers in France, Italy and Spain. The cohort included consecutive patients with high or very-high risk NMIBC who underwent reTUR and subsequent adjuvant BCG therapy.
RESULTS: A total of 440 high-risk NMIBC patients were screened, 29 (6%) were upstaged ≥ T2 at reTUR and 411 were analyzed (T1 stage: n = 275, 67%). Residual tumor was found in 191 cases (46%). In patients with T1 tumor on initial TURBT, persistent T1 tumor was found in 18% of reTUR (n = 49/275). In patients with high-grade Ta tumor on initial TURBT, T1 tumor was found in 6% of reTUR (n = 9/136). In multivariable logistic regression analysis, we found no statistical association between the use of photodynamic diagnosis (PDD, p = 0.4) or type of resection (conventional vs. en bloc, p = 0.6) and the risk of residual tumor. The estimated 5-yr recurrence and progression-free survival were 56% and 94%, respectively. Residual tumor was significantly associated with a higher risk of recurrence (p < 0.001) but not progression (p = 0.11). Only residual T1 tumor was associated with a higher risk of progression (p < 0.001) with an estimated 5-yr progression-free survival rate of 76%.
CONCLUSIONS: ReTUR should remain a standard for T1 tumors, irrespective of the use of en bloc resection or PDD and could be safely omitted in high-grade Ta tumors. Persistent T1 tumor at reTUR should not exclude these patients from conservative management, and further studies are needed to explore the benefit of a third resection in this subgroup.

UNASSIGNED: Frailty is linked to an increased incidence of hepatic decompensation and mortality in cirrhosis. The aim of our study was to identify a novel scanographic score that predicts frailty and its impact in cirrhosis.
UNASSIGNED: This study included 51 patients with cirrhosis. We used the frailty scale risk assessment score to identify frail patients. The density and area of different muscles at L3 level were analyzed on computed tomography (CT) sections. The L3 skeletal muscle area adjusted to height and density ratio (L3-SMDHR) was defined as L3 muscle wall*height/density.
UNASSIGNED: The L3-SMHDR is significantly higher in frail patients and in patients with Child B/C scores. Frailty was correlated with L3-SMHDR. Frailty and L3- SMHDR were correlated with liver-related events (LRE). We set the most appropriate cut-offs of L3-SMHDR for both sensitivity and specificity by using the ROC: 5.4 for males and 4.7 for females. The AUROC score was 0.784 for male and 0.975 for female patients. The Kappa score between frailty and L3-SMHDR was 0.752, with a percentage of agreement of 87.5%, showing a substantial agreement. This ratio with the divided categories has a sensitivity of 100%, a specificity of 76%, a positive predictive value of 79.3% and a negative predictive value of 100%. Patients with high L3-SMHDR have significantly lower survival time and a higher incidence of LRE.
UNASSIGNED: The L3-SMHDR is a new index for identifying frailty in cirrhosis by using measurable and reproducible variables. It can be used as a prognostic factor for frailty in patients with cirrhosis.

As cutting-edge technologies applied for the study of body fluid molecular biomarkers are continuously evolving, clinical applications of these biomarkers improve. Diverse forms of circulating molecular biomarkers have been described, including cell-free DNA (cfDNA), circulating tumor cells (CTCs), and cell-free microRNAs (cfmiRs), although unresolved issues remain in their applicability, specificity, sensitivity, and reproducibility. Translational studies demonstrating the clinical utility and importance of cfmiRs in multiple cancers have significantly increased. This review aims to summarize the last 5 years of translational cancer research in the field of cfmiRs and their potential clinical applications to diagnosis, prognosis, and monitoring disease recurrence or treatment responses with a focus on solid tumors. PubMed was utilized for the literature search, following rigorous exclusion criteria for studies based on tumor types, patient sample size, and clinical applications. A total of 136 studies on cfmiRs in different solid tumors were identified and divided based on tumor types, organ sites, number of cfmiRs found, methodology, and types of biofluids analyzed. This comprehensive review emphasizes clinical applications of cfmiRs and summarizes underserved areas where more research and validations are needed.

Hypertrophic cardiomyopathy (HCM) is a common heart disease in cats, characterized by regional or diffuse hypertrophy of the left ventricular walls, with an uncertain etiology and heterogenous natural history. Several types of rhythm disturbances are often associated with the disease. This study conducts a comprehensive review of the current literature, in order to evaluate the diagnostic and prognostic effectiveness of electrocardiography and Holter monitoring in the management of feline hypertrophic cardiomyopathy. The main subjects of discussion will include general information about HCM and its connection to arrhythmias. We will explore the rhythm disturbances documented in the current literature on Holter monitoring, as well as the techniques used for Holter monitoring. Additionally, the review will cover classical electrocardiography (ECG) and its diagnostic utility. Prognostic indicators and anti-arrhythmic therapy will also be discussed in detail. The findings highlight the importance of understanding arrhythmias in feline HCM for accurate diagnosis, risk assessment, and therapeutic intervention. ECG and Holter monitoring may offer valuable insights into managing feline HCM.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, the impact of CAF subpopulation trajectory differentiation on CRC remains unclear.
METHODS: In this study, we first explored the trajectory differences of CAFs subpopulations using bulk and integrated single-cell sequencing data, and then performed consensus clustering of CRC samples based on the trajectory differential genes of CAFs subpopulations. Subsequently, we analyzed the heterogeneity of CRC subtypes using bioinformatics. Finally, we constructed relevant prognostic signature using machine learning and validated them using spatial transcriptomic data.
RESULTS: Based on the differential genes of CAFs subpopulation trajectory differentiation, we identified two CRC subtypes (C1 and C2) in this study. Compared to C1, C2 exhibited worse prognosis, higher immune evasion microenvironment and high CAF characteristics. C1 was primarily associated with metabolism, while C2 was primarily associated with cell metastasis and immune regulation. By combining 101 combinations of 10 machine learning algorithms, we developed a High-CAF risk signatures (HCAFRS) based on the C2 characteristic gene. HCAFRS was an independent prognostic factor for CRC and, when combined with clinical parameters, significantly predicted the overall survival of CRC patients. HCAFRS was closely associated with epithelial-mesenchymal transition, angiogenesis, and hypoxia. Furthermore, the risk score of HCAFRS was mainly derived from CAFs and was validated in the spatial transcriptomic data.
CONCLUSIONS: In conclusion, HCAFRS has the potential to serve as a promising prognostic indicator for CRC, improving the quality of life for CRC patients.

Introduction Gastric cancer is a significant major global health concern, particularly prevalent in Asia. In recent years, a large number of new cases have been diagnosed worldwide, leading to a substantial number of deaths. The disease tends to present more aggressively in these cases, leading to debates about the prognosis and survival outcomes. Nonetheless, research has shown that survival rates improve significantly when the tumor is completely surgically resected. Materials and methods This retrospective study included patients between 16 and 45 years old, diagnosed with gastric cancer, with the support of the pathology department, who underwent surgery in the upper GI service, in the period from January 2006 to December 2012. Data collected encompassed variables such as gender, age, tumor size, type of surgery, overall survival, disease-free period, type and histological degree of the tumor, clinical stage of the cancer, and R0 resection (curative resection). All patients with a confirmed diagnosis of gastric cancer were included and treated with surgery and D1 limited dissection or extended D2 dissection. Patients who have received chemotherapy prior to surgical treatment and those who have been surgically treated outside the XXI Century National Medical Center were excluded. Results A total of 104 patients were included; the predominant histological type was diffuse adenocarcinoma accounting for 79.8% and 81.7% of the cases were histological grade 3. The most common clinical stage was IIIA in 41.3% of the cases. In 53.8% of the cases, we obtained an R0 resection. D2 lymphadenectomy was performed in 53.8% of the cases, with an overall survival rate of 82.69%. Significant prognostic factors for survival included T4 depth with an increase in risk for mortality (OR: 25.93; 95% CI: 6.41-53.54; p=0.001), lymph node status (OR: 14.76; 95% CI: 4.6-46.83; p<0.001), and size greater than 5 cm (OR: 1.8; 95% CI: 0.61-6.35; p<0.001). Conclusions Gastric cancer is more common in adults aged above 60 years old, but the incidence in young adults under 45 years old has been increasing. Although young gastric cancer patients present with more aggressive tumor behavior, these patients can have similar or even better overall survival compared to older patients, being 35% in some cases, especially in the resectable setting. Further research is still needed to fully characterize the unique biology and optimal management of gastric cancer in young adults.

BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort.
METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers.
RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively).
CONCLUSIONS: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.