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Colorectal cancer is a major cause of cancer-related deaths worldwide. A third of colorectal cancers reside in the rectum. Many patients with rectal cancer present in the locally-advanced stage which needs multi-modality therapy usually starting with neoadjuvant chemo-radiotherapy followed by surgery and adjuvant systemic chemotherapy. Total neoadjuvant therapy, defined as the preoperative administration of both neoadjuvant chemoradiotherapy and systemic chemotherapy is also an evolving treatment that can be delivered if indications for preoperative chemotherapy exist. Identifying biomarkers to predict response to neoadjuvant therapy, can improve patient selection for a non-surgical, active surveillance approach. Circulating tumor DNA (ctDNA) can be detected in about 75% of patients with locally-advanced rectal cancer (LARC) at the baseline and in about 15–20% of patients in the post-neoadjuvant, or postoperative setting. ctDNA clearance rate after delivering neoadjuvant chemoradiotherapy, or integrating baseline ctDNA with other conventional markers of clinical response can be a promising marker to select and monitor patients on the “watch and wait” approach. In this article, we aimed to integrate the recent findings and provide a unique insight into the utilization of preoperative ctDNA to predict clinical response in patients with LARC. We also sought to highlight the potential areas for future research in this field. Further studies with a larger number of participants from diverse populations and settings are needed to increase external validity of such investigations and determine the role of ctDNA in guiding clinical decisions and management of patients with LARC.

The recent advancement of mRNA technology has opened new therapeutic avenues for treating hematologic malignancies, offering innovative approaches to enhance existing immunotherapies. This review examines the expanding role of in vitro transcribed (IVT)-mRNA-based platforms in hemato-oncology, focusing on key areas: monoclonal antibody production, bispecific antibody development, and CAR-T cell engineering. Unlike conventional biologics, mRNA allows for in vivo expression of therapeutic proteins, reducing manufacturing complexity and expanding access through scalable, cell-free synthesis. IVT-mRNA-encoded monoclonal and bispecific antibodies can overcome limitations such as short half-life and the need for continuous infusion, while enabling innovations like Fc silencing, protease-activated masking, and combinatorial immunotherapies. In CAR-T cell therapy, IVT-mRNA provides transient, safer alternatives to viral vector-based approaches and facilitates emerging strategies such as in vivo CAR programming and IVT-mRNA vaccine-like boosters. Despite these advantages, challenges remain, including delivery precision, durability of therapeutic effects, and limited clinical trial success. Beyond therapeutic mechanisms, the integration of bioinformatics and AI in IVT-mRNA design is accelerating the development of personalized and efficient cancer treatments. Overall, mRNA technology is redefining immunotherapy in hematology and holds the potential to broaden access to advanced treatments globally.

Extracellular matrix (ECM) remodeling in cancer provides an essential substructure for tumor progression. We utilized patient-derived scaffolds (PDS) to model tumor ECM changes and study their impact on cell behavior. PDS were obtained from breast tumor and normal healthy breast tissue by decellularizing surgically resected specimens. We used PDS to design a 3D culture of the breast cancer cell line MCF-7. We utilized bioinformatics pipeline to identify hub genes indicative of cell invasiveness, and assessed their expression using quantitative real-time PCR. Our decellularization protocol led to decellularization of tissues while preserving key ECM components. ECM components such as collagen, glycosaminoglycans, collagen IV, and vimentin were significantly overexpressed in tumor compared to normal PDS. In 3D cultures, cells cultured on normal PDS had significantly lower viability and proliferation. Moreover, cells cultured for 15 days on tumor PDS showed significant overexpression of hub genes, CAV1, CXCR4, CNN3, MYB, and TGFB1, and secreted higher levels of IL-6 (122.91 vs. 30.23 pg/10⁶ cells, P  < 0.05), all markers of an aggressive breast cancer phenotype. Breast cancer cells fail to acquire aggressive features when cultured in an ECM lacking tumor-specific alterations. This underscores the potential of therapeutic approaches targeting the mechanobiological properties of the tumor ECM.

Background Acute kidney injury is a complication of COVID-19 and is associated with severity. Despite no specific antiviral treatment strategy, lopinavir/ritonavir and remdesivir have been used. Data on the association between AKI and receiving antiviral agents with outcomes in hospitalized patients with COVID-19 is scarce. We aimed to determine the incidence of AKI and its outcomes in COVID-19 patients with and without antiviral medications. Methods We conducted a retrospective study on hospitalized adult patients with SARS-CoV-2 infection in a tertiary center. The primary endpoint was determining mortality, intensive care unit (ICU) admission, and length of hospitalization affected by AKI development using antiviral agents. The logistic regression method was used to explore the predictive effects of AKI and antiviral therapy on composite outcomes (i.e., mortality, ICU admission, and prolonged hospitalization) in four defined groups by AKI development/not and utilizing antivirals/not. We used IBM SPSS version 24.0 software for statistical analysis. Results Out of 833 COVID-19 patients who were included, 75 patients were treated with antiviral agents and developed AKI. There was a significant difference in the occurrence of AKI and using antiviral medications (p = 0.001). Also, the group using antiviral agents and the development of AKI had the highest rate of preexisting hypertension (p = 0.002). Of note, the group of patients who used antiviral agents and also developed AKI had the most remarkable association with our composite outcome (p<0.0001), especially ICU admission (OR = 15.22; 95% CI: 8.06-27.32). Conclusions The presence of AKI among COVID-19 patients treated with antiviral agents is linked to increased severity and mortality. Therefore, it is imperative to explore preventive measures for AKI development in patients receiving antiviral therapy. Larger-scale randomized controlled trials may be warranted to provide a more comprehensive understanding of these associations.

Background: Identifying novel diagnostic biomarkers with stable structures, such as circulating circular RNAs (circRNAs) can improve the early detection and management of BC. Herein, we conducted this study to analyze the expression profile of four circRNAs, including circCSPP1 (hsa_circ_0001806), circNRIP1 (hsa_circ_0004771), circSMAD2 (hsa_circ_0000847), and circFOXP1 (hsa_circ_0008234) in BC. Methods:Tumor tissues and adjacent normal tissues were obtained from patients with sporadic breast cancer (BC). Divergent primers were designed to amplify the target transcripts using quantitative real-time PCR. The expression profiles of circRNAs were analyzed in tumor and adjacent normal tissues. Sanger sequencing was performed to confirm the back-splicing junctions of circRNAs. ROC curves were generated to assess the potential of the mentioned RNAs as diagnostic biomarkers. Results:We observed a significant upregulation of circCSPP1, circNRIP1, and circSMAD2 in tumor tissue compared to adjacent normal tissues. Among them, circCSPP1 was the most highly upregulated one in tumor samples from 39 patients. Expression of circCSPP1 was significantly higher in estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, human epidermal growth factor receptor-2 (HER2)-negative, and triple-negatives compared to ER-positive, PR-positive, HER2-positive, and non-triple-negative ones. Expression of circNRIP1 was also significantly elevated in the ER-negative and the triple-negative subgroups. These three circRNAs also displayed a desirable potential as diagnostic biomarkers. Conclusion:This is the first paper that reports the upregulation of circCSPP1 and circSMAD2 in BC and upregulation of circCSPP1 and circNRIP1 in the triple-negative subgroup. Our findings suggest that circCSPP1, circNRIP1, and circSMAD2 may serve as promising diagnostic biomarkers for BC. Identifying the downstream pathways regulated by these circRNAs could lead to the discovery of new therapeutic targets.

Background Although several studies are available regarding baseline Electrocardiographic (ECG) parameters and major and minor ECG abnormalities, there is considerable controversy regarding their age and gender differences in the literature. Methods Data from 7630 adults aged ≥ 35 from the Tehran Cohort Study registered between March 2016 and March 2019 were collected. Basic ECG parameters values and abnormalities related to arrhythmia, defined according to the American Heart Association definitions, were analyzed and compared between genders and four distinct age groups. The odds ratio of having any major ECG abnormality between men and women, stratified by age, was calculated. Results The average age was 53.6 (± 12.66), and women made up 54.2% ( n  = 4132) of subjects. The average heart rate (HR) was higher among women( p  < 0.0001), while the average values of QRS duration, P wave duration, and RR intervals were higher among men( p  < 0.0001). Major ECG abnormalities were observed in 2.9% of the study population (right bundle branch block, left bundle branch block, and Atrial Fibrillation were the most common) and were more prevalent among men compared to women but without statistical significance (3.1% vs. 2.7% p  = 0.188). Moreover, minor abnormalities were observed in 25.9% of the study population and again were more prevalent among men (36.4% vs. 17% p  < 0.001). The prevalence of major ECG abnormalities was significantly higher in participants older than 65. Conclusion Major and minor ECG abnormalities were roughly more prevalent in male subjects. In both genders, the odds of having major ECG abnormalities surge with an increase in age.

Background Radiation cystitis (RC) is a major complication of pelvic radiotherapy, leading to inflammation, vascular damage, and fibrosis. While mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise in regenerative medicine, their therapeutic effects on RC remain unclear. This study evaluates the efficacy of human umbilical cord MSC-EVs (huMSC-EVs) in mitigating Radiation-induced bladder damage. Methods Animal models of RC were established using 20 Gy pelvic irradiation. Forty-four female Sprague-Dawley rats were divided into four groups: negative control (NC, no radiation), positive control (PC, radiation only), local treatment (LT, huMSC-EVs injected into the bladder wall), and systemic treatment (ST, intravenous huMSC-EVs). Bladder function and compliance were assessed via metabolic cage and urodynamic studies (UDS) at 6 and 24 weeks. Histopathological changes and inflammatory cytokine levels were evaluated at multiple time points. Results Administration of huMSC-EVs significantly improved urinary frequency and hematuria. Histological analysis showed reduced urothelial disintegration and edema in the early phase, and improved urothelial integrity, reduced hyperplasia and vascular lesions, and restored bladder architecture in the late phase, in the treated groups. UDS demonstrated preserved bladder compliance and voiding efficiency in LT rats, with significantly higher voided volume ( p  < 0.01) and lower post-voiding residue ( p  < 0.05) compared to the PC group 24 weeks post-irradiation. Pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were markedly lowered and their levels were similar to the non-radiated NC group in LT-treated rats ( p  = 1.00, p  = 0.22, p  = 0.16), 24 weeks post-irradiation. Conclusions Local huMSC-EVs therapy effectively reduces RC-related bladder injury and preserves function, likely by modulating inflammatory response and epithelial regeneration. These findings highlight huMSC-EVs as a promising strategy to prevent chronic RC, warranting further clinical exploration.

Recurrent abdominal pain poses a diagnostic challenge in the pediatric population. Functional and structural etiologies can contribute to this condition. The organic etiologies of recurrent abdominal pain are diagnoses of exclusions and considering them as the initial diagnosis could lead to mis‐ or delayed diagnosis with potentially several clinical consequences. Intermittent ureteropelvic junction obstruction (UPJO) is one of the structural etiologies of recurrent abdominal pain that could mimic the clinical presentation of functional etiologies. The absence of radiologic evidence of intermittent UPJO in the interval between the attack episodes makes it a diagnostic challenge, especially in the initial stages. This underscores the value of imaging evaluation during abdominal pain episodes or performing diuretic‐enhanced imaging modalities to capture the structural changes between the episodes. This study comprehensively discussed the diagnostic challenges associated with pediatric intermittent UPJO. We also present a known case of recurrent abdominal pain initially diagnosed as abdominal migraine, which was later reclassified as intermittent UPJO. Moreover, we reviewed the conventional diagnostic approaches in identifying the presence of structural etiologies in intermittent UPJO.

Background Revascularization in diabetic patients with coronary artery disease remains a challenge in cardiology practice. Although clinical trials have reported the mid-term superiority of coronary artery bypass grafting (CABG) surgery over percutaneous coronary intervention in these patients, little is known about the long-term outcomes of CABG in diabetic patients compared to non-diabetics, particularly in developing countries. Methods Between 2007 and 2016, we recruited all patients who underwent isolated CABG in a tertiary care cardiovascular center in a developing country. The patients were followed at 3–6 months and 12 months after surgery, and then annually. The study endpoints were 7-year all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). Results Of 23,873 patients (17,529 males, mean age 65.67 years) who underwent CABG, 9227 (38.65%) patients were diagnosed with diabetes. After adjustment for potential confounders, patients with diabetes experienced a 31% increase in MACCE seven years after surgery compared to the non-diabetic patients (HR = 1.31, 95% CI: 1.25–1.38, P-value < 0.0001). Meanwhile, diabetes contributes to a 52% increase in the risk of all-cause mortality after CABG (HR = 1.52, 95% CI: 1.42–1.61, P-value < 0.0001). Conclusions Our study showed a higher risk of all-cause mortality and MACCE at seven years in diabetic patients undergoing isolated CABG. The outcomes in the studied center in a developing country were comparable to western centers. The high incidence of adverse outcomes in the long term in diabetic patients implies that not only short-term but long-term measures should be taken to improve the CABG outcomes in this challenging patient population.

Background and Aims In the current study, we aimed to identify the association between major and minor electrocardiographic abnormalities and cardiovascular risk factors. Methods We used the Tehran cohort study baseline data, an ongoing multidisciplinary, longitudinal study designed to identify cardiovascular disease risk factors in the adult population of Tehran. The electrocardiograms (ECGs) of 7630 Iranian adults aged 35 years and above were analyzed. ECG abnormalities were categorized into major or minor groups based on their clinical importance. Results were obtained by multivariable logistic regression and are expressed as odds ratios (ORs). Results A total of 756 (9.9%) participants had major ECG abnormalities, while minor abnormalities were detected in 2526 (33.1%). Males comprised 45.8% of the total population, and 41.8% of them had minor abnormalities. Individuals with older age, diabetes (OR = 1.35; 95% CI: 1.11–1.64), and hypertension (OR = 2.21; 95% CI: 1.82–2.68) had an increased risk of major ECG abnormalities. In contrast, intermediate (OR = 0.69; 95% CI: 0.57–0.84) and high physical activity levels (OR = 0.66; 95% CI: 0.51–0.86) were associated with a lower prevalence of major abnormalities. Male sex, older age, hypertension, and current smoking were also associated with an increased prevalence of ECG abnormalities combined (major or minor). Conclusion Major and minor ECG abnormalities are linked with important cardiovascular risk factors such as diabetes and hypertension. Since these abnormalities have been associated with poor outcomes, screening patients with cardiovascular risk factors with an ECG may distinguish high‐risk individuals who require appropriate care and follow‐up.