Evaluating the Readability of Online Blood Cancer Education Materials Across Different Readability Measures

Introduction The National Institutes of Health and the American Medical Association recommend patient education materials (EMs) be at or below the sixth-grade reading level. The American Cancer Society, Leukemia & Lymphoma Society, and National Comprehensive Cancer Network have accurate blood cancer EMs. Methods One hundred one (101) blood cancer EMs from the above organizations were assessed using the following: Flesch Reading Ease Formula (FREF), Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), Simple Measure of Gobbledygook Index (SMOG), and the Coleman-Liau Index (CLI). Results Only 3.96% of patient EMs scored at or below the seventh-grade reading level in all modalities. Healthcare professional education materials (HPEMs) averaged around the college to graduate level. For leukemia and lymphoma patient EMs, there were significant differences for FKGL vs. SMOG, FKGL vs. GFI, FKGL vs. CLI, SMOG vs. CLI, and GFI vs. CLI. For HPEMs, there were significant differences for FKGL vs. GFI and GFI vs. CLI. Conclusion The majority of patient EMs were above the seventh-grade reading level. A lack of easily readable patient EMs could lead to a poor understanding of disease and, thus, adverse health outcomes. Overall, patient EMs should not replace physician counseling. Physicians must close the gaps in patients\u27 understanding throughout their cancer treatment

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis and Therapeutic Strategies

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy

Convolutional neural network for biomarker discovery for triple negative breast cancer with RNA sequencing data

Triple negative breast cancers (TNBCs) are tumors with a poor treatment response and prognosis. In this study, we propose a new approach, candidate extraction from convolutional neural network (CNN) elements (CECE), for discovery of biomarkers for TNBCs. We used the GSE96058 and GSE81538 datasets to build a CNN model to classify TNBCs and non-TNBCs and used the model to make TNBC predictions for two additional datasets, the cancer genome atlas (TCGA) breast cancer RNA sequencing data and the data from Fudan University Shanghai Cancer Center (FUSCC). Using correctly predicted TNBCs from the GSE96058 and TCGA datasets, we calculated saliency maps for these subjects and extracted the genes that the CNN model used to separate TNBCs from non-TNBCs. Among the TNBC signature patterns that the CNN models learned from the training data, we found a set of 21 genes that can classify TNBCs into two major classes, or CECE subtypes, with distinct overall survival rates (P = 0.0074). We replicated this subtype classification in the FUSCC dataset using the same 21 genes, and the two subtypes had similar differential overall survival rates (P = 0.0490). When all TNBCs were combined from the 3 datasets, the CECE II subtype had a hazard ratio of 1.94 (95% CI, 1.25–3.01; P = 0.0032). The results demonstrate that the spatial patterns learned by the CNN models can be utilized to discover interacting biomarkers otherwise unlikely to be identified by traditional approaches

Belzutifan, HIF-2α Inhibitor, and Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-of-Function Mutation

The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations

Evaluation Fucoidan Extracts From and in Combination With Anticancer Drugs in Human Cancer Orthotopic Mouse Models

Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 10 6 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV 3 -GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV 3 or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway

Translating Planetary Health Principles Into Sustainable Primary Care Services

Global anthropogenic environmental degradations such as climate change are increasingly recognized as critical public health issues, on which human beings should urgently act in order to preserve sustainable conditions of living on Earth. "Planetary Health" is a breakthrough concept and emerging research field based on the recognition of the interdependent relationships between living organisms-both human and non-human-and their ecosystems. In that regards, there have been numerous calls by healthcare professionals for a greater recognition and adoption of Planetary Health perspective. At the same time, current Western healthcare systems are facing their limits when it comes to providing affordable, equitable and sustainable healthcare services. Furthermore, while hospital-centrism remains the dominant model of Western health systems, primary care and public health continue to be largely undervalued by policy makers. While healthcare services will have to adapt to the sanitary impacts of environmental degradations, they should also ambition to accompany and accelerate the societal transformations required to re-inscribe the functioning of human societies within planetary boundaries. The entire health system requires profound transformations to achieve this, with obviously a key role for public health. But we argue that the first line of care represented by primary care might also have an important role to play, with its holistic, interdisciplinary, and longitudinal approach to patients, strongly grounded in their living environments and communities. This will require however to redefine the roles, activities and organization of primary care actors to better integrate socio-environmental determinants of health, strengthen interprofessional collaborations, including non-medical collaborations and more generally develop new, environmentally-centered models of care. Furthermore, a planetary health perspective translated in primary care will require the strengthening of synergies between institutions and actors in the field of health and sustainability

Human endotrophin as a driver of malignant tumor growth

We have previously reported that the carboxy-terminal proteolytic cleavage product of the COL6??3 chain that we refer to as ???endotrophin??? has potent effects on transformed mammary ductal epithelial cells in rodents. Endotrophin (ETP) is abundantly expressed in adipose tissue. It is a chemoattractant for macrophages, exerts effects on endothelial cells and through epithelial-mesenchymal transition (EMT) enhances progression of tumor cells. In a recombinant form, human endotrophin exerts similar effects on human macrophages and endothelial cells as its rodent counterpart. It enhances EMT in human breast cancer cells and upon overexpression in tumor cells, the cells become chemoresistant. Here, we report the identification of endotrophin from human plasma. It is circulating at higher levels in breast cancer patients. We have developed neutralizing monoclonal antibodies against human endotrophin and provide evidence for the effectiveness of these antibodies to curb tumor growth and enhance chemosensitivity in a nude mouse model carrying human tumor cell lesions. Combined, the data validate endotrophin as a viable target for anti-tumor therapy for human breast cancer and opens the possibility for further use of these new reagents for anti-fibrotic approaches in liver, kidney, bone marrow and adipose tissue

Size-Resolved Identification, Characterization, and Quantification of Primary Biological Organic Aerosol at a European Rural Site

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