Patients with locally advanced rectal cancer (LARC) who undergo neoadjuvant chemoradiotherapy (NCRT) and subsequently experience early recurrence (ER) within two years post-surgery tend to have unfavorable prognoses. Therefore, the accurate prediction of ER in LARC is of paramount importance. This study aimed to develop and validate an explainable artificial intelligence (AI) model, based on the systemic inflammation-nutritional tumor biomarker index (SINTI) derived from routine blood biomarkers, to predict ER in patients with LARC. We conducted a multicenter retrospective analysis involving two distinct patient cohorts: Cohort A (n = 715; from February 2011 to September 2017) and Cohort B (n = 224; spanning June 2020 to June 2023). Feature selection was executed utilizing the least absolute shrinkage and selection operator (LASSO) regularization to construct SINTI, effectively addressing multicollinearity. Predictive modeling incorporated ten different machine learning architectures, with hyperparameter optimization achieved through a randomized search complemented by nested tenfold cross-validation. Model performance was thoroughly evaluated using multiple metrics, including the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), clinical utility curves, and calibration plots. The interpretability of the model was enhanced through SHAP value analysis, followed by its deployment as a clinical decision support web application. The study included 715 patients from Center One and 224 from Center Two, identifying six key biomarkers as the core components of the SINTI model. Multivariable analysis confirmed that SINTI, clinical N stage, clinical T stage, and tumor size are independent predictors of early recurrence. The XGBoost algorithm exhibited robust discrimination during training cohort cross-validation, achieving a mean AUC of 0.860 (SD ± 0.021) and demonstrating consistent performance across validation datasets, with an internal AUC of 0.842 and an external AUC of 0.840. SHAP value interpretation revealed monotonic relationships between predictor variables and recurrence risk, with SINTI accounting for 36.1% of the total predictive weight. For clinical implementation, we deployed the optimized model as a web-based decision support tool, which can be accessed at https://p7toqbsdfbhlahdrugj4ra.streamlit.app/ . This interpretable AI framework demonstrates the potential to bridge data-driven modeling and clinical decision support, offering a transparent, potentially deployable solution for post-NCRT recurrence risk prediction following further prospective validation.

Neuroblastoma (NBL) is a pediatric malignancy with poor prognosis in high-risk cases. This study explores the function of albumin conformation factor 1 (ACF1) in NBL progression and delves into the underpinning mechanism. Exome and transcriptome sequencing were applied to analyze ACF1 mutations/expression in NBL tissues versus controls. ACF1 was knocked down in NBL cell lines (KELLY, BE2C, N2a) for in vitro assays (viability, proliferation, migration, apoptosis, therapy sensitivity) or in vivo xenograft/metastasis models with radiation/cisplatin. Mechanisms were probed via RNA-sequencing, chromatin immunoprecipitation, luciferase assays, co-immunoprecipitation, and immunofluorescence assays. Expression patterns and the correlations between ACF1, GCLM, and NAA20 were detected in human NBL tissue microarrays. ACF1 mutations and elevated expression correlated with advanced tumor staging, high-risk factors, and unfavorable prognosis in NBL datasets and TMAs. ACF1 knockdown suppressed NBL cell proliferation, mobility, and in vivo tumor growth/metastasis, while enhancing cisplatin/radiation sensitivity and apoptosis. Mechanistically, ACF1 knockdown reduced GCLM transcription via decreased H3K27ac/H3K4me3/Myc at its promoter, elevating lipid peroxidation and lowering glutathione (GSH) levels. Lactate induced ACF1 lactylation and nuclear translocation, promoted by NAA20 interaction (enhanced by lactate). NAA20 knockdown phenocopied ACF1 effects, rescued by GCLM overexpression. NAA20 and GCLM were upregulated in NBL datasets/TMAs. This study suggests that the NAA20-mediated ACF1 lactylation drives GCLM-dependent GSH synthesis, promoting NBL cell growth and metastasis. Targeting this axis may improve therapy response.

Associations between borderline personality disorder symptomatology and major depressive disorder: Insights from a general population study.

Chemoresistance in esophageal cancer (EC) continues to impose formidable clinical challenges, driving disease recurrence and adverse outcomes. While vesicle-associated membrane protein 7 (VAMP7), a SNARE family regulator, has emerged as an oncogenic participant in tumor evolution, its mechanistic role in EC chemoresistance remains uncharted. Clinico-pathological analyses reveal pronounced VAMP7 overexpression in EC specimens, correlating with unfavorable prognosis, metastatic dissemination, advanced tumor staging, and cisplatin-refractory phenotypes. Functional interrogation demonstrates that VAMP7 silencing attenuates malignant hallmarks-proliferation, migratory capacity, and epithelial-mesenchymal transition (EMT)-while potentiating apoptotic cascades. Mechanistically, VAMP7 exhibits robust positive correlation with ferroptosis regulators GPX4 and NRF2, establishing its role as a ferroptosis checkpoint inhibitor that sustains cisplatin resistance. Combinatorial VAMP7 depletion and cisplatin treatment synergistically diminished neoplastic viability through dual mechanisms: amplification of ferroptosis biomarkers (lipid peroxidation, iron dysregulation) and induction of mitochondrial ultrastructural derangements. Conversely, ectopic VAMP7 expression in resistant clones upregulated GPX4/NRF2 axis activity and reinstated chemotolerance. Therapeutically, co-administration of ferroptosis agonists (RSL3/Erastin) with cisplatin abrogated VAMP7-mediated resistance, evidenced by suppressed xenograft growth and amplified mitochondrial pathology in preclinical models. This work identifies VAMP7 as a novel ferroptosis-chemoresistance nexus in EC, offering a translational framework for overcoming cisplatin refractoriness through coordinated inhibition of VAMP7 signaling and ferroptosis potentiation.

Persistent controversy surrounds the identification of risk factors contributing to postoperative complications and unfavorable neurological prognoses following cranioplasty (CP) after decompressive craniectomy (DC). This study sought to assess these postoperative outcomes in individuals undergoing 3D titanium mesh CP due to traumatic brain injury (TBI) or hemorrhagic stroke, as well as to determine predictors linked to postoperative complications and suboptimal neurological recovery. A retrospective, single-center analysis was performed on patients undergoing 3D titanium mesh CP after DC. The primary outcome measure encompassed postoperative complications occurring within 12 months post-CP. The secondary endpoint involved the Glasgow Outcome Scale score assessed at 12 months following CP. We examined various parameters to identify predictors associated with postoperative complications and unfavorable neurological outcomes. A total of 118 male patients (66%) were included, with trauma accounting for DC in 123 cases (68%). The overall incidence of postoperative complications was 45%, while poor neurological outcomes were observed in 30% of cases. Intraoperative dural depression during CP was correlated with an increased likelihood of postoperative epidural effusion; a time interval exceeding three months between DC and CP was associated with a heightened risk of hydrocephalus; bilateral CP demonstrated an elevated risk of wound dehiscence and infection. For poor GOS outcomes, pre-DC GCS score and DC due to stroke were identified as contributing factors, though no association was found with surgical timing. Early 3D titanium mesh CP, performed within three months after DC in TBI or stroke patients, appears to be a safe procedure without an increased incidence of postoperative complications or poor neurological prognosis. Conversely, delayed CP exceeding three months post-DC may increase the hydrocephalus's likelihood. Patients experiencing intraoperative dural depression during CP should be closely monitored for the potential development of postoperative epidural effusion. Additionally, those undergoing bilateral CP are at greater risk for wound dehiscence and infection. Compared to individuals with TBI-induced DC, stroke patients undergoing CP tend to exhibit poorer neurological recovery.

Mechanistic insights into hypoxia-induced TCF7L2 upregulation and its oncogenic effects on colorectal cancer.

Biochemical fingerprinting of dried blood serum from chronic lymphocytic leukemia patients by Raman spectroscopy: Towards prognostic classification.

ObjectiveThis study examined the associations of visceral adiposity index (VAI), body roundness index (BRI), and lipid accumulation product (LAP) with the risk, severity, and prognosis of knee osteoarthritis (KOA). The aim was to evaluate the clinical utility of these novel adiposity indices for early screening and prognostic assessment of KOA.MethodsA total of 124 patients with clinically and radiographically confirmed KOA and 120 healthy individuals who underwent routine physical examinations during the same period were enrolled as the KOA and control groups, respectively. Baseline data were collected retrospectively from electronic medical records. KOA patients were further classified into mild, moderate, and severe subgroups based on K-L grading and were followed for 12months.ResultsCompared with controls, the KOA group had significantly higher BMI, TG, TC, LDL-C, VAI, BRI, and LAP, and lower HDL-C (p < 0.05). VAI, BRI, and LAP increased progressively with KOA severity (p < 0.05), showing positive correlations (r = 0.608, 0.489, 0.551, p < 0.001), and were confirmed as independent risk factors (p < 0.05). ROC analysis yielded AUCs of 0.775 (95% CI: 0.718-0.833; cutoff: 2.91) for VAI, 0.752 (95% CI: 0.692-0.813; cutoff: 5.21) for BRI, and 0.779 (95% CI: 0.722-0.836; cutoff: 48.58) for LAP, with a combined AUC of 0.880 (95% CI: 0.839-0.922). Survival time differed significantly across groups stratified by these cutoffs (VAI: χ2 = 4.238; BRI: χ2 = 3.956; LAP: χ2 = 6.043; all p < 0.05).ConclusionThis study concludes that VAI, BRI, and LAP are closely linked to KOA. Firstly, their levels are significantly raised in patients and show a positive correlation with disease severity, marking them as useful clinical indicators. Secondly, the combined detection of these indices provides superior predictive value for KOA and is associated with an unfavorable prognosis, suggesting their utility in comprehensive risk assessment.

Left ventricular diastolic function modifies clinical outcomes of mild mitral regurgitation.

Bundle branch block and pacemaker Rhythm as independent predictors of mortality in critically ill cardiac patients.

Gossypol, a natural polyphenolic compound derived from Gossypium species, has demonstrated broad anticancer activity; however, its clinical application is limited by poor pharmacokinetic properties and toxicity. This study employed an integrated computational pharmacology approach to evaluate gossypol and its derivatives, identify potential cancer-related target proteins, and elucidate their molecular interactions. ADMET profiling, cytotoxicity prediction, target identification, protein expression and prognostic analysis, and molecular docking were systematically performed. Several gossypol derivatives, particularly anhydrogossypol and gossypolone, exhibited improved drug-likeness, reduced predicted toxicity, favorable anticancer activity, and enhanced selectivity toward cancer cells compared with the parent compound. PASS-based target prediction consistently identified DNA-3-methyladenine glycosylase (MPG), a key enzyme in the base excision repair pathway, as a high-confidence molecular target. Clinical relevance analysis revealed that elevated MPG expressions were associated with unfavorable prognosis and were highly expressed across multiple cancer types, including colorectal, breast, and lung cancers. Molecular docking demonstrated strong binding affinities of selected derivatives within the MPG active site, involving conserved and functionally important residues such as TYR-127, TYR-165, CYS-167, and ARG-182. These findings suggest that gossypol derivatives may exert anticancer effects by modulating MPG-mediated DNA repair mechanisms. Overall, this study highlights MPG as a promising therapeutic target and supports further experimental investigation of optimized gossypol derivatives as potential anticancer agents.

Highlight: Glioblastoma is the most prevalent and deadly primary malignant brain tumor. The prognosis for glioblastoma remains unfavorable because of detrimental prognostic factors. Appropriate and advanced treatment can help in improving the survival rate of patients with glioblastoma. ABSTRACT Introduction: Glioblastoma is one of the deadly malignant brain tumor associated with a highly unfavorable prognosis, making it one of the significant challenge for clinicas due to its unfavorable poor prognostic. Patients with glioblastomas may experience headaches, nausea, vomiting, loss of consciousness, seizure/convulsion, altered mental status, and focal neurological deficits. Chemotherapy, radiation, and surgical resection became standar therapeutic options for patient with glioblastoma. This advanced treatment is important for increasing the survival rate of patients. Objective: This study aimed to evaluate survival outcomes in patients with glioblastoma treated with temozolomide plus radiotherapy compared with radiotherapy alone Methods: This study followed PRISMA guidelines and used the PICO framework. The inclusion criteria encompassed a range of study designs, including randomized controlled trials (RCTs), quasi-experimental, observational, and case-control studies, that evaluated survival outcomes in glioblastoma patients treated with radiotherapy plus 6 cycles of adjuvant temozolomide versus radiotherapy alone. Exclusion criteria eliminated studies that were not relevant to the comparative treatment approach. Results: Following three stages of screening, six articles that were directly relevant to the systematic review were selected for full-text analysis. Overall, radiotherapy plus temozolomide had better outcomes than radiotherapy alone. Median overall survival (OS) ranged from 10 to 17.5 months in patients with radiotherapy plus temozolomide, compared with 8 to 14 months in those treated with radiotherapy alone. Median progression-free survival (PFS) ranged from 6 to 10.1 months in patients with radiotherapy plus temozolomide, and 3.8 treated with radiotherapy alone. Conclusion: Diagnosing NPH remains challenging due to the overlap of its cognitive impairment symptoms with other neurocognitive disorders. Furthermore treatment response vary widely, makin it difficult for clinicians to effectively manage NPH patients. Although early and prompt diagnosis is crucial for successful therapy, clinician still face significant challenge.

Non-small cell lung cancer (NSCLC), the most common subtype of lung cancer, presents major clinical challenges owing to its highly complex tumor microenvironment and substantial cellular heterogeneity. A comprehensive understanding of the immune landscape-particularly the phenotypic diversity and functional roles of macrophage subpopulations-is critical for identifying novel therapeutic targets and developing more effective treatment strategies. We constructed a comprehensive single-cell atlas of Stage I NSCLC using single-cell RNA sequencing (scRNA-seq) to characterize immune heterogeneity, with particular emphasis on macrophage subsets. Network pharmacology was employed to investigate the interactions between AHSA1 and bioactive compounds derived from the traditional Chinese medicine formulation Yu Ping Feng San (YPFS). To further evaluate these interactions, molecular docking simulations were performed to assess binding affinities and elucidate the potential regulatory effects on macrophage polarization. ScRNA-seq analysis revealed heterogeneous macrophage subtypes, each exhibiting distinct roles in tumor progression. AHSA1 was identified as a key regulator of macrophage polarization, with higher expression levels associated with unfavorable prognosis. Through network pharmacology and molecular docking, strong binding affinities were observed between AHSA1 and Yu Ping Feng San (YPFS)-derived compounds, including wogonin, kaempferol, and quercetin. Notably, quercetin displayed the highest binding affinity and exerted the strongest inhibitory effect on M2 macrophage polarization. These findings identify AHSA1 as a pivotal regulator of macrophage polarization in NSCLC and position quercetin as a promising macrophage-targeted therapeutic candidate. Furthermore, the results highlight the potential of Yu Ping Feng San (YPFS) as a complementary therapeutic strategy for NSCLC, offering a bridge between traditional Chinese medicine and modern oncology.

The priority of the Protection System is the restoration of children rights, including life and health. It is common for children to present with untreated oral health problems upon admission, which require significant efforts. This case describes a 7-year-old boy who was temporarily housed in a Social Assistance Center in Mexico, and attended his first dental consultation at a School of Dentistry. Regarding his dental history, the patient presented no evidence of prior dental care. Clinically, a mixed dentition was observed, including multiple non-restorable primary molars with unfavorable prognosis. The patient presented a negative and defiant behavior. A comprehensive treatment plan was implemented, including restorations, extractions, and space maintainers. After discharge, the proposed follow-up was every 3 months. The difficulty of caring for children and adolescents temporarily placed in the Protection System is evident. It is important to highlight the work done by the multidisciplinary team to identify cases and address previously unmet needs.

Relevance. Severe intestinal diseases, which include Crohn's disease and ulcerative colitis, are characterized by a chronic recurrent course, a high rate of complications, an unfavorable prognosis, prolonged drug therapy and manifestations in the oral cavity, such as a high level of carious process, non-carious lesions of the second group (increased abrasion, wedge-shaped defects, enamel erosions), gingivitis, periodontitis, plentiful plaque on the tongue and mucosal trauma. These features create difficulties in conducting high-quality professional hygiene, requiring maximum atraumatism and accuracy from the dentist. Objective. To select personal oral hygiene products and develop recommendations for using magnification techniques during professional oral hygiene procedures in patients with chronic intestinal diseases (Crohn’s disease). Methodology. In the presented clinical case, a patient with Crohn’s disease in an exacerbation stage was treated with a protocol for professional hygiene using a combined approach with three optical systems. This approach allowed effective removal of subgingival deposits without traumatizing or causing painful stretching of the sensitive oral mucosa. Simultaneously, individual hygiene was adjusted using a tongue scraper and moisturizing and anti-inflammatory agents. Results. Following the treatment, a significant improvement in hygiene indices was observed (OHI-S = 0.5, WTC = 2), with no bleeding on probing (SBI index = 0), no dry mucous membranes, or inflammation in the periodontal tissues. Conclusions. The developed recommendations for the use of optical systems are key for conducting effective, gentle professional hygiene procedures in patients with Crohn’s disease. They provide significant visual control and minimal trauma to the oral mucosa.

Inflammatory breast cancer (IBC) is a rare and highly aggressive form of breast cancer with an increased propensity to metastasize to distant organs including the brain. Higher serum levels of the calcium-binding proteins S100A8/A9, particularly of S100A9, have emerged as a clinically and biologically significant factor in aggressive breast cancers that are associated with poorer prognosis, tumor progression, and resistance to therapy. However, its contribution in IBC specifically remains undefined. Here, we investigated whether serum levels of S100A8/A9 predict outcomes in patients with IBC. Serum S100A8/A9 levels were measured in a cohort of 304 IBC patients using ELISA assay. S100A8/A9 levels were categorized by their third quartile value (S100A8/A9-low ≤ 3 rd quartile; S100A8/A9-high > 3 rd quartile). Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed with Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression models. The cumulative incidence of any metastases and the cumulative incidence of brain metastases were analyzed using Aalen-Johansen method, Gray test, and Fine-Gray models. The median follow-up time was 64 months. Forty-six percent of patients had estrogen receptor (ER)-negative tumors, 61.3% were stage III-IV, 77% high grade, 16.8% received adjuvant chemotherapy and 53.6% received adjuvant radiation. On univariate analysis, S100A8/A9 levels, disease stage, ER status, PR status, HER2 status, adjuvant chemotherapy, and adjuvant radiation therapy were significantly associated with OS and BCSS. Patients with high S100A8/A9 serum levels had poor OS ( P =0.01) and BCSS ( P =0.007) and had a higher risk of developing brain metastasis ( P =0.01) but not other metastasis. On multivariate analysis, high S100A8/A9 serum levels were independently associated with reduced OS (hazard ratio [HR]=1.7, 95% CI 1.1 to 2.6, P =0.01), reduced BCSS (HR=1.8, 95% CI 1.2 to 2.8, P =0.006), and increased cumulative incidence of developing brain metastasis (subdistribution hazard ratio (sHR)=1.8, 95% CI 1.1 to 3.0, P =0.03). In patients with IBC, high serum levels of S100A8/A9 are an independent prognostic factor for brain metastasis and poor clinical outcomes. These findings support the potential of S100A8/A9 as predictive biomarker for identifying increased risk of brain metastasis and unfavorable prognosis in patients with IBC.

The Maternal Embryonic Leucine Zipper Kinase (MELK) gene is a member of the Snf1/AMPK serine/threonine kinase family. MELK has recently attracted considerable interest in cancer biology due to its aberrant overexpression in various malignancies, including glioma, breast, lung, colorectal, gastric, and hematological cancers. It has been shown that higher MELK levels are often correlated with unfavorable prognosis, aggressive tumor manifestations, resistance to treatment, and stem-like tumor morphologies. In this review we aim to summarize the current understanding of MELK biology, including its functions in cell cycle regulation, apoptosis, oncogenic signaling pathways, and tumor stemness. We also discuss the therapeutic potential, limitations, and controversy of MELK inhibitors, and implications in cancer diagnosis and treatment. MELK may not be a universal driver oncogene; nonetheless, it is consistently linked to aggressive disease, underscoring its potential as a prognostic biomarker and a candidate for therapeutic co-targeting in combination treatments.

Mutation of the tumor suppressor gene TP53 promotes ovarian cancer progression and therapeutic resistance. Whether mutant p53 (mtp53) regulates alternative splicing and how this regulation can be exploited for cancer therapy remain unclear. Here, small nuclear ribonucleoprotein D2 polypeptide (SNRPD2) as a binding partner of mtp53 is identified. SNRPD2 is highly expressed in ovarian cancer and associated with an unfavorable prognosis. The overexpression of SNRPD2 promotes, whereas its depletion inhibits, the growth and migration of ovarian cancer cells. Mechanistically, mtp53 cooperates with SNRPD2 to facilitate the assembly of the Sm/SMN protein complex, an essential component of the spliceosome, modulating alternative splicing of pre-mRNAs. Specifically, the co-depletion of mtp53 and SNRPD2 reduces the level of OTUD3 oncogenic transcripts while increasing its tumor suppressor counterparts through an exon-skipping event. Moreover, therapeutic engineered exosomes are developed with their surfaces decorated with iRGD and their interiors loaded with siRNAs targeting mtp53 and SNRPD2. These exosomes effectively suppress the growth of ovarian cancer cells and enhance their sensitivity to chemotherapy in vivo. Collectively, this study uncovers that mtp53 and SNRPD2 cooperatively regulate alternative splicing to drive ovarian cancer progression, and co-targeting these two molecules via engineered exosomes represents a potential therapeutic strategy for ovarian cancer.

Bladder cancer is the most prevalent malignancy of the urinary tract, characterized by an unfavorable prognosis, elevated rates of recurrence, and a lack of targeted therapeutic approaches. In this research, we evaluated the efficacy of TAK-901, a specific inhibitor targeting Aurora kinase, and elucidate the anti-cancer mechanisms in bladder cancer. TAK-901 exhibited a dose-dependent inhibition of proliferation, colony formation, and migration, as well as induction of apoptosis in T24 and UMUC-3 cells. Additionally, bladder cancer cells undergo cell cycle arrest at the G2/M phase when exposed to TAK-901. Mechanistic studies revealed that the targeted inhibition of EGFR by TAK-901 impacted AKT and FOXO3a phosphorylation, leading to the activation of FOXO-dependent transcriptional activity, which subsequently triggered apoptotic pathways through inducing BIM expression. Furthermore, our study demonstrated that TAK-901 attenuated tumor growth in the UMUC-3-Luc xenograft model and significantly reduced Ki-67 expression in tumor tissues. Finally, we propose a novel treatment strategy involving the synergistic inhibition of bladder cancer cell growth by combining TAK-901 with Afatinib. Our research strongly suggests that Aurora A and Aurora B are promising epigenetic therapeutic targets in bladder cancer. Furthermore, TAK-901 can function as a targeted kinase inhibitor and EGFR inhibitor for the treatment of bladder cancer by activating the FOXO signaling pathway, which induces apoptosis in bladder cancer cells.

Advanced-stage and metastatic endometrial cancer (EC) are characterized by markedly poor survival outcomes, necessitating a deeper understanding of the mechanisms driving disease advancement. Tumor-associated macrophages (TAMs), particularly the M2 subtype, are instrumental in remodeling the tumor microenvironment and promoting EC proliferation, migration, and metastasis. However, the specific mediators responsible for TAM-driven EC progression remain inadequately elucidated. In this study, we investigated the role of the C-X-C motif chemokine ligand 1 (CXCL1) and its receptor, chemokine receptor 2 (CXCR2), in TAM-induced EC progression. CXCR2, as the primary receptor for CXCL1, activates the NF-κB signaling pathway upon binding, thereby mediating the epithelial-mesenchymal transition process in EC cells and enhancing metastatic potential. This mechanism can be effectively inhibited by silencing CXCR2 or by employing the NF-κB inhibitor BAY 11-7082. Neutralizing CXCL1 markedly diminished the proliferative and migratory burdens imposed by TAMs on EC in subcutaneous xenograft EC models. Additionally, in EC tissue samples, CXCL1 and CXCR2 expression, as well as the extent of macrophage infiltration, exhibited a significant positive relationship with disease progression, suggesting an unfavorable prognosis. In conclusion, targeting the CXCL1/CXCR2 axis is a potential therapeutic approach for EC treatment.