Lipophilic Pyrimethamine analogs with anti-toxoplasmosis activity.

Survival analysis of time-to-death for under-five children in Somalia: Application of AFT modeling approach.

A fuzzy deep learning approach for liver lesions detection and classification in big data context

Multidisciplinary tumor boards (MTBs) and survival Outcomes: Adherence to MTB recommendations in patients with lung cancer treated at two European cancer centers (AdThera-2).

Lightweight ensemble vision transformer framework for non-invasive survival prediction in glioblastoma

Primary mediastinal lymphoma is rare in dogs and literature exploring this disease is limited. Therefore, the aim of this study was to describe presentation, treatment and outcome in a large cohort of dogs with mediastinal lymphoma and explore prognostic factors including chemotherapy protocol. This retrospective multi-institute study included 70 dogs with primary mediastinal lymphoma treated with lomustine-based (LOP/LOPP) or anthracycline-based (CHOP/CEOP) chemotherapy. Most immunophenotyped cases were of T-cell lineage (95.6%). The majority were substage b (90%) and hypercalcaemia was noted in 69.1% of dogs. Clinical and objective response rates to chemotherapy were 92.7% and 97.9%, respectively, with 76.6% of dogs achieving a complete response. Median progression free survival (PFS) was 132 days (95% CI 83-181), and median overall survival time (OST) was 223 days (95% CI 175-271). The 6-month, 1-year, and 2-year survival rates were 55.7%, 22.9%, and 15.7%, respectively. On multivariable analysis, factors associated with longer PFS included hypercalcaemia (p = 0.041), chemotherapy-induced neutropenia (p = 0.014) and CD4+/CD8- immunophenotype (p = 0.004). Neutropenia at diagnosis was associated with shorter PFS (p = 0.015) and OST (p = 0.004). Other factors associated with shorter OST included granular morphology (p = 0.023) and CD4+/CD8+ immunophenotype (p = 0.004). Chemotherapy-induced neutropenia was associated with improved OST (p = 0.042). Differences in outcome between anthracycline- or lomustine-based chemotherapy protocols were not statistically significant. Overall, the prognosis for primary mediastinal lymphoma in dogs is poor to fair when treated with multi-agent chemotherapy. This is the second study associating hypercalcaemia with improved PFS in dogs with non-indolent T-cell lymphoma. Results also suggest prognostic significance of specific CD4/CD8 expression patterns.

New combination therapy of praziquantel and Lactobacillus plantarum for enhancing the treatment of clonorchiasis in mice.

Retrospective, single-center analysis of second allogeneic stem cell transplantation versus non-transplant regimens for acute myeloid leukemia patients with relapse after first transplantation.

Feline malignant mammary tumors are frequently aggressive and associated with poor clinical outcomes. Over the years, the prognostic value of various clinical and pathological parameters has been investigated, though findings are not always consensual. Histologically, feline malignant mammary tumors are heterogenous tumors, and a recent revision of the 1999 World Health Organization (WHO) classification of canine and feline mammary tumors may provide a more accurate picture of their biological behavior. This study aimed to analyze and compare the 1999 WHO classification and the 2019 updated surgical pathology classification in the same case series. Additionally, we seek to evaluate the prognostic value of several clinicopathological features, including both histological classification systems. Our findings revealed that the 2019 revised surgical pathology classification allowed for a greater stratification of feline mammary tumors (FMT) compared to the 1999 WHO classification system. Notably, longer survival times were observed in queens with ductal-associated carcinomas. Other clinicopathological features were associated with unfavorable clinical outcomes, namely presence of multiple synchronous malignant mammary tumors, larger tumor size, higher clinical stage, infiltrative tumor growth and lymphovascular invasion (p ≤ 0.05). Additionally, our findings suggest that the prognostic relevance of each parameter may vary according to the clinical endpoint, warranting careful consideration during clinical interpretation. DATA AVAILABILITY: The data presented in this study are available from the corresponding author upon reasonable request.

This study aimed to assess the prognostic significance of pretreatment CT-based body composition markers in patients with Hepatocellular carcinoma (HCC) treated with radioembolization. Automated analysis of baseline CT scans was performed to retrospectively evaluate body composition (BCA) parameters in 198 patients from a prospective registry database, including skeletal muscle (SM) and bone (B) volumes. BCA parameters and ratios were dichotomized using a maximally selected log-rank approach. Kaplan-Meier and uni- (UVA) and multivariate (MVA) Cox-proportional-hazard ratio (HR) survival analyses were performed. The median survival time was 18.5 months. In UVA, lower BCLC stage, ≦ 70 years of age, normal serum albumin, non-elevated C-reactive protein, normal aspartate aminotransferase (ASAT), normal alkaline phosphatase, normal gamma-glutamyl transaminase (GGT), absence of portal vein thrombosis and various BCA parameters were statistically significant with the skeletal muscle to bone ratio (SM/B) demonstrating the strongest survival discrimination with a median survival of 23.6 months for high and 12.0 months for low SM/B (HR: 0.65, 95 %CI: 0.46-0.9; p = 0.0001). In MVA, SM/B, BCLC stage, ASAT, and GGT remained independently significant. Patients with higher SM/B ratios demonstrated a significantly higher disease control rate during the initial imaging follow-up after three months (74.4 % vs. 54.0 %, p = 0.017). These findings suggest that fully automated, CT-based measurement of BCA parameters - particularly the SM/B ratio - can serve as an independent prognostic factor for survival and disease control in patients with Hepatocellular carcinoma (HCC) undergoing radioembolization. This could potentially facilitate the identification of patients who would benefit most from this treatment.

Vascularization is a prerequisite for the invivo survival of tissue engineering constructs, especially large-scale ones. However, due to inadequate research on the underlying mechanisms of physiological angiogenesis in biomaterials, the ability of emerging biotechnologies to facilitate the clinical translation of regenerative medicine strategies is compromised. In contrast, systematic research on these relevant mechanisms can provide key theoretical insights for the development of novel engineering strategies. Taking subcutaneous implantation of a thin, unloaded porous scaffold as the experimental model, this study investigates the progression of its spontaneous physiological vascularization. The experimental results reveal that vascularization is driven by sprouting angiogenesis and subsequent splitting angiogenesis. Specifically, the scaffold is neovascularized by sprouting which is induced by pro-angiogenic factors in the avascular area. This is a spatial process in which a primary vascular network forms and expands from the superficial to the deep regions of the scaffold, and the neovascularization capacity determines the upper limit of the size of living tissue formed within the scaffold. Subsequently, the primary vascular network undergoes remodeling and hierarchical development through splitting, which depends on the response to hemodynamic stress. This is a progressive temporal process, and the developmental capacity of the primary vascular network determines the survival time of this living tissue. Based on this, we propose that engineering interventions be used to provide artificial microenvironmental support in regions and at stages beyond spontaneous vascularization capacity to induce sprouting or facilitate splitting. This way, physiological vascularization of large-scale scaffolds is expected to be achieved.

Feline chronic kidney disease (CKD) has highly variable patterns of progression. Objective methods to differentiate cats with stable and progressive CKD are lacking. This retrospective study aimed to determine a slope cutoff for reciprocal of creatinine (creatinine-1) vs time to objectively differentiate stable and progressive feline CKD, and identify risk factors for CKD progression within 3 months of CKD diagnosis. Euthyroid client-owned cats with azotaemic CKD (n = 321) were included in this study. CKD cats that demonstrated stable (<25% increase) plasma creatinine concentration for >365 days (n = 194) were identified and the reciprocal plot of plasma creatinine vs time (creatinine-1 plot) from these cats was used to determine a cutoff to differentiate stable from progressive CKD. Risk factors for progressive CKD, including response to 3 months of standard treatment, were explored by binary logistic regression. Variables associated with mortality were evaluated using Cox regression. A slope cutoff of -9.5×10-5L/μmol/month (-8.4×10-3dL/mg/month) for creatinine-1 plot distinguished stable (n = 231) vs progressive (n = 90) CKD cats. Baseline plasma log-transformed fibroblast growth factor-23 (ln[FGF-23]), albumin concentrations, advancing age, and slope of creatinine-1, phosphate and body weight within the first 84 days of CKD diagnosis were independent risk factors for progression. Progressive cats had shorter median survival time [95% CI] than non-progressive cats (287 [246-354] vs 894 [812-1052] days; P < 0.001). Overall, cats with stable and progressive CKD can be distinguished using slope of creatinine-1 plot. Risk factors identified may facilitate early detection of cats with progressive CKD.

Prostate cancer (PCa) is a prevalent malignancy in males, triggered by multiple factors. This study aimed to identify PCa-specific key genes with clinical significance and clarify their roles in PCa progression. To screen PCa-specific key genes, a comprehensive analytical strategy was adopted by integrating weighted gene co-expression network analysis (WGCNA) for mining highly correlated important genes, Cox regression analysis for evaluating clinical relevance, and multiple machine learning techniques. Functional validation experiments were further conducted, including CCK-8 assay to assess cell proliferation, transwell assay, and wound healing assay to detect cell invasion and migration abilities after ANO5 overexpression in PCa cells. In addition, a model was constructed using machine learning to systematically clarify the role of ANO family genes in the occurrence of PCa. Anoctamin 5 (ANO5) was identified as a PCa-specific key gene through the integrated analytical approach. Clinical data analysis revealed that higher ANO5 expression was significantly correlated with favorable clinical status and longer survival time of PCa patients. Functional experiments confirmed this finding: the overexpression of ANO5 in PCa cells has an inhibitory effect on the behavior of tumor cells. Transwell and wound healing experiments further confirmed that ANO5 can inhibit the migration of PCa cells. ANO5 is a PCa-specific key gene that correlates with favorable clinical outcomes and regulates PCa cell invasion, suggesting its potential as a prognostic biomarker and therapeutic target. In comparison, the systematic exploration of ANO family genes enriches the understanding of PCa oncogenesis mechanisms.

Isocitrate dehydrogenase (IDH)-mutant low-grade and high-grade gliomas are primary brain cancers with slower growth rates and longer survival than IDH-wildtype counterparts. However, these tumors are fatal and because of the younger age of patients, result in significant morbidity and loss of productivity. Several management options are available at initial diagnosis for IDH-mutant gliomas (including close surveillance, surgery, radiation therapy, chemotherapy and/or targeted therapies either alone or in combination), however, there is limited data about optimal timing and sequencing. When considering treatment, the risks associated with uncontrolled disease should be weighed against potential treatment-associated toxicities given the expected long overall survival times for many patients. Preservation of cognition, neurological function and quality of life remain a priority. Treatment decisions should therefore be made in the context of a neuro-oncology multidisciplinary team, and incorporating the patient's wishes and expectations. The management of recurrent IDH-mutant glioma is not well defined. This expert position statement aims to provide an Australian perspective on the evidence base and available treatments for contemporaneous management of IDH-mutant glioma in adults.

The resectability of pancreatic cancer depends on the extent of vascular involvement. Left-sided pancreatic cancer (LPC) rarely invades major vessels but frequently involves adjacent organs. This study aimed to assess the prognostic significance of radiological adjacent organ invasion (RAOI) in resectable LPC. This study included 162 patients who underwent distal pancreatectomy for resectable LPC between 2002 and 2020. Radiological adjacent organ invasion was defined as contact of the primary tumor or a continuous soft tissue density to the adjacent organs (stomach, adrenal gland, colon, or liver) on computed tomography. Clinicopathological factors and survival outcomes were compared between the RAOI (+) (n = 17) and RAOI (-) (n = 145) groups. The RAOI (+) group had significantly higher CA19-9 levels (279 vs. 33 U/mL, p = 0.005), larger radiological tumor sizes (37 vs. 21 mm, p < 0.001), and more frequently positive peritoneal cytology results (41% vs. 8%, p = 0.002). Overall survival (OS) in the RAOI (+) group was significantly worse than that in the RAOI (-) group (median survival time [MST], 25.9 vs. 67.2 months, p < 0.001). Among patients with negative cytology results (n = 141), OS was still significantly worse in the RAOI (+) group (MST, 33.5 vs. 71.9 months, p = 0.001). Multivariate analysis revealed CA19-9 levels ≥37 U/mL and RAOI as independent risk factors for poor OS. Radiological adjacent organ invasion is an independent negative prognostic factor in resectable LPC and is associated with early systemic dissemination and worse survival outcomes. Radiological adjacent organ invasion (+) LPC may be considered a borderline resectable disease that requires intensive multimodal treatment strategies.

An integrated restricted mean survival time-based evaluation of efficacy, toxicity, and cost in first-line immunotherapy regimens for metastatic renal cell carcinoma.

Chemerin Promotes Oral Squamous Cell Carcinoma Progression via NLRP3-Mediated Pyroptosis and the GSDMD-N Pathway.

Allicin-based biomimetic nanoparticles of the erythrocyte membrane for the delivery of lumefantrine to enhance its antimalarial effect

Effective risk stratification is essential for guiding treatment decisions in patients with metastatic renal cell carcinoma (mRCC). The Meet-URO score is a novel prognostic model that integrates the IMDC criteria with neutrophil-to-lymphocyte ratio (NLR) and the presence of bone metastases. Developed in the immunotherapy era, it has demonstrated superior prognostic accuracy compared to IMDC score across various clinical settings and treatment strategies. Its validation in the context of first-line immune-based combinations has been awaited. External validation of Meet-URO was performed using a large retrospective real-world cohort of mRCC patients treated with first-line immune-based combinations. Secondary analyses included a comparison with the IMDC score for predicting overall survival (OS) and progression-free survival (PFS). Additionally, restricted mean survival time (RMST) was assessed. 1,418 patients were included in the analysis: 54% received ICI-ICI regimen (nivolumab plus ipilimumab), while 46% received ICI-TKI combination. At baseline, 52.5% of patients had an NLR ≥ 3.2, and 32% had bone metastases. After a median follow-up of 26.8 months, the median OS and median PFS were 34.7 and 11.3 months respectively. Meet-URO demonstrated effective prognostic stratification, identifying patient groups with markedly different outcomes (median OS 11.5-51.4 months; 3-year OS 26-66%; RMST 20.0-42.8 months). Compared to IMDC, Meet-URO showed a significantly better OS (c-index 0.675 vs. 0.643; Δc = 0.032, p < 0.001) and PFS (c-index 0.60 vs. 0.58; p < 0.001) prediction performance. : Meet-URO demonstrated robust prognostic accuracy. Its integration into routine clinical practice and use as a stratification factor in clinical trials may support more personalized treatment strategies and enhance clinical trial design.

Artificial ultraviolet radiation (UVR) from solarium use has been linked to melanoma in some studies, while others report lower overall mortality. Whether melanoma risk is due to solarium use itself or to associated behaviors indicating intermittent solar overexposure remains unclear. The Melanoma of Southern Sweden (MISS) cohort included ~ 29,000 women enrolled in 1990 and followed for up to 34 years. Solarium use and sun exposure habits were assessed at baseline and after 10 years. Participants were categorized as non-users, solarium users without, or with indicators of intermittent solar overexposure. Cox proportional hazards models estimated hazard ratios (HRs) for melanoma, all-cause mortality, and melanoma specific mortality. Sensitivity analyses, attributable risk, and restricted mean survival time (RMST) over 25 years were evaluated. Solarium use without indicators of solar overexposure was not associated with melanoma risk. Solarium users with overexposure indicators had a higher melanoma risk (HR 1.60, 95% CI 1.30-2.00). Both solarium user groups had ~ 18% lower all-cause mortality than non-users. Melanoma specific mortality did not differ between groups. Approximately one-third of melanomas among solarium users was attributable to solar overexposure. Over 25 years, solarium users had an RMST nearly 10 months longer than non-users. Melanoma risk among solarium users appears driven by intermittent solar overexposure rather than solarium use itself, while solarium use was associated with lower all-cause mortality. Our findings indicate that prevention efforts should focus on reducing intermittent UV overexposure behaviors.