tbuckley/cabot-search huggingface dataset:
Magnetic Resonance Imaging in Studies of Perifocal Zone of Brain Gliomas (a Literature Review)
Authors: N. E. Zakharova, A. I. Batalov, E. L. Pogosbekyan, S. A. Goryaynov, L. M. Fadeeva, A. E. Bykanov, A. N. Tyurina, I. V. Chekhonin, S. A. Galstyan, I. N. Pronin, D. Yu. Usachev
Journal: Radiology - Practice (2023)

This review provides insight into application of modern MRI modalities including diffusion kurtosis imaging in assessment of perifocal glioma zone. Differentiation of “pure” perifocal vasogenic edema from edema infiltrated by glioma cells, as well as identification of peritumoral intact (on conventional MRI) brain matter infiltration make it possible to determine glial tumor borders more accurately. Analysis of diffusion and perfusion quantitative MR data allow determining glioma borders in areas with unaltered blood-brain barrier. There is a growing possibility to develop a personalized navigation algorithm for surgical removal of the tumor, followed by the determination of an individual plan for radiation and chemotherapy, as well as prediction of disease outcomes.
Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
Authors: Mingze Du, Kangze Liu, Huinan Lai, Jin Qian, Liya Ai, Jiying Zhang, Jun Yin, Dong Jiang
Journal: Bioactive Materials (2024)

Meniscus injury is one of the most common sports injuries within the knee joint, which is also a crucial pathogenic factor for osteoarthritis (OA). The current meniscus substitution products are far from able to restore meniscal biofunctions due to the inability to reconstruct the gradient heterogeneity of natural meniscus from biological and biomechanical perspectives. Here, inspired by the topology self-induced effect and native meniscus microstructure, we present an innovative tissue-engineered meniscus (TEM) with a unique gradient-sized diamond-pored microstructure (GSDP-TEM) through dual-stage temperature control 3D-printing system based on the mechanical/biocompatibility compatible high Mw poly(ε-caprolactone) (PCL). Biologically, the unique gradient microtopology allows the seeded mesenchymal stem cells with spatially heterogeneous differentiation, triggering gradient transition of the extracellular matrix (ECM) from the inside out. Biomechanically, GSDP-TEM presents excellent circumferential tensile modulus and load transmission ability similar to the natural meniscus. After implantation in rabbit knee, GSDP-TEM induces the regeneration of biomimetic heterogeneous neomeniscus and efficiently alleviates joint degeneration. This study provides an innovative strategy for functional meniscus reconstruction. Topological self-induced cell differentiation and biomechanical property also provides a simple and effective solution for other complex heterogeneous structure reconstructions in the human body and possesses high clinical translational potential.
Bio-responsive Au-miR-183 inhibitor enhances immunotherapy in hepatocellular carcinoma by inducing immunogenic cell death
Authors: Liang Yin, Yu Wei, Ya Liu, Xianwei Mo, Jintong Song, Weijuan Cai
Journal: Journal of Controlled Release (2024)

The treatment of advanced hepatocellular carcinoma (HCC) is limited, and immunotherapy is the current research focus of multi-disciplinary collaborative comprehensive treatment of HCC. Herein, we constructed a bio-responsive Au-miR-183 inhibitor (Au@miR-183i) delivery system targeting liver cancer stem cells (LCSCs), and adopted the strategy of combining αPD-L1 immunotherapy. The multifunctional Au@miR-183i nanocomplexes (NCs), which self-assemble based on the tumor microenvironment, consume NADPH and H2O2, leading to redox homeostasis disturbance, ROS accumulation, regulation of the LCSC niche, and induction of stemness regression. Moreover, self-assembled Au@miR-183i NCs specifically target the delivery of miR-183i to LCSCs, triggering the immunogenic cell death (ICD) effect, promoting the maturation of dendritic cells, inducing infiltration of CD8+ T cells, and facilitating the transformation of 'cold' tumors into 'hot' tumors. More importantly, consistent with the results in vitro, Au@miR-183i NCs demonstrated effective tumor targeting and strong ICD induction in vivo, assisted in enhancing αPD-L1 immunotherapy, and activated a robust systemic anti-tumor immune response in tumor-bearing mouse models. Overall, we provide a simple and universal therapeutic strategy by constructing a multifunctional bio-responsive Au@miR-183i NCs delivery system with LCSC targeting capability. Furthermore, nanocomplex-based ICD inducers have great promise in enhancing anti-tumor immunity and the PD-1/PD-L1 blocking efficacy in HCC, which provides a theoretical basis for effectively eliminating LCSCs and achieving a high-efficiency synergistic treatment strategy for HCC.
Comparison of 18F-AlF-NOTA-PRGD2 and 18F-FDG PET/CT Imaging in a Case of Primary Uveal Melanoma
Authors: Xue Zhu, Donghui Pan, Zhengwei Zhang, Ke Wang, Wenjun Zou
Journal: Clinical Nuclear Medicine (2024)

Abstract Uveal melanoma is the most common intraocular malignancy in adults with a high rate of metastasis and mortality. This study presented the PET/CT imaging of 18 F-AlF-NOTA-PRGD2 and 18 F-FDG in a patient with primary uveal melanoma. In addition to fundus photograph and ophthalmic ultrasonography, both 18 F-AlF-NOTA-PRGD2 and 18 F-FDG PET/CT imaging showed increased radioactive uptake in the lesions within the scan area. The tumoral lesions presented significantly higher uptake of 18 F-AlF-NOTA-PRGD2 compared with that of 18 F-FDG.
Histological Typing in Patients With Cardiac Amyloidosis
Authors: Esther Gonzalez-Lopez, Ellen D. McPhail, Clara Salas-Anton, Fernando Dominguez, Morie A. Gertz, Angela Dispenzieri, Surendra Dasari, Paolo Milani, Laura Verga, Martha Grogan, Giovanni Palladini, Pablo Garcia-Pavia
Journal: Journal of the American College of Cardiology (2024)

Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most frequent forms of cardiac amyloidosis: immunoglobulin light chain amyloidosis and transthyretin (ATTR) amyloidosis. Nevertheless, initiation of specific therapies requires recognition of cardiac amyloidosis and appropriate characterization of the amyloid type. Although noninvasive diagnosis is possible for ATTR cardiac amyloidosis, histological demonstration and typing of amyloid deposits is still required for a substantial number of patients with ATTR and in all patients with light chain amyloidosis and other rarer forms of cardiac amyloidosis. Amyloid histological typing can be performed using different techniques: mass spectrometry, immunohistochemistry, and immunoelectron microscopy. This review describes which patients require histological confirmation of cardiac amyloidosis along with when and how to type amyloid deposits in histologic specimens. Furthermore, it covers the characteristics and limitations of the different typing methods that are available in clinical practice.
Discovering skin-rejuvenating matrikines: a new frontier in basic and applied dermatology
Authors: Ubaldo Armato, Ilaria Dal Prà
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Discovering skin-rejuvenating matrikines - a basic and applied Dermatology new frontier Get access Ubaldo Armato, Ubaldo Armato Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona Medical School, 8 Strada Le Grazie, Verona, Italy Correspondence: Ubaldo Armato, Email:uarmato@gmail.com https://orcid.org/0000-0002-7804-6143 Search for other works by this author on: Oxford Academic Google Scholar Ilaria Dal Prà Ilaria Dal Prà Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona Medical School, 8 Strada Le Grazie, Verona, Italy https://orcid.org/0000-0001-5523-4910 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae100, https://doi.org/10.1093/bjd/ljae100 Published: 12 March 2024 Article history Received: 04 March 2024 Accepted: 08 March 2024 Published: 12 March 2024
The clinical benefits of sodium–glucose cotransporter type 2 inhibitors in people with gout
Authors: Chio Yokose, Natalie McCormick, Abhishek Abhishek, Nicola Dalbeth, Tristan Pascart, Frédéric Lioté, Angelo Gaffo, John FitzGerald, Robert Terkeltaub, Meghan E Sise, James L Januzzi, Deborah J Wexler, Hyon K Choi
Journal: Nature Reviews Rheumatology (2024)
Involuntary closures of for-profit care homes in England by the Care Quality Commission
Authors: Anders Bach-Mortensen, Benjamin Goodair, Michelle Degli Esposti
Journal: The Lancet Healthy Longevity (2024)

Adult social care services in England are struggling, and sometimes failing, to supply the quality of care deserved by the most vulnerable people in society. The Care Quality Commission (CQC) is responsible for protecting the recipients of this crucial public service. Their strongest enforcement is the ability to cancel the registration—the legal right to operate—of a health or social care provider. Using novel data from the CQC, we show that the proportion of care home closures due to CQC enforcements, relative to all closures, is increasing. Since 2011, 816 care homes (representing 19 918 registered beds) have been involuntarily closed by the CQC. Our results show that effectively all involuntary closures (804/816) occurred in for-profit care homes. This data emphasises the need for a comprehensive assessment of the impact of for-profit provision on the quality and sustainability of adult social care in England.
Micro‐Engineered Heart Tissues On‐Chip with Heterotypic Cell Composition Display Self‐Organization and Improved Cardiac Function
Authors: Carla Cofiño‐Fabres, Tom Boonen, José M. Rivera‐Arbeláez, Minke Rijpkema, Lisanne Blauw, Patrick C. N. Rensen, Verena Schwach, Marcelo C. Ribeiro, Robert Passier
Journal: Advanced Healthcare Materials (2024)

Advanced in vitro models that recapitulate the structural organization and function of the human heart are highly needed for accurate disease modeling, more predictable drug screening, and safety pharmacology. Conventional 3D Engineered Heart Tissues (EHTs) lack heterotypic cell complexity and culture under flow, whereas microfluidic Heart-on-Chip (HoC) models in general lack the 3D configuration and accurate contractile readouts. In this study, an innovative and user-friendly HoC model is developed to overcome these limitations, by culturing human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs), endothelial (ECs)- and smooth muscle cells (SMCs), together with human cardiac fibroblasts (FBs), underflow, leading to self-organized miniaturized micro-EHTs (µEHTs) with a CM-EC interface reminiscent of the physiological capillary lining. µEHTs cultured under flow display enhanced contractile performance and conduction velocity. In addition, the presence of the EC layer altered drug responses in µEHT contraction. This observation suggests a potential barrier-like function of ECs, which may affect the availability of drugs to the CMs. These cardiac models with increased physiological complexity, will pave the way to screen for therapeutic targets and predict drug efficacy.
Risk of Hepatocellular Carcinoma by Steatotic Liver Disease and Its Newly Proposed Subclassification
Authors: Byeong Geun Song, Aryoung Kim, Myung Ji Goh, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Dong Hyun Sinn
Journal: Liver Cancer (2024)

Introduction: Steatotic liver disease (SLD) is a new overarching term proposed to replace nonalcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease. Subclassification includes metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. This study aimed to investigate whether SLD and its subclassification could stratify hepatocellular carcinoma (HCC) risk. Methods: A cohort of 85,119 adults without viral hepatitis or heavy alcohol intake was analyzed for the risk of HCC according to SLD and its subclassification. The fibrosis-4 (FIB-4) index was used to estimate the degree of liver fibrosis. Results: During a median follow-up of 11.9 years, HCC was diagnosed in 123 individuals. The incidence rate of HCC per 1,000 person-years was higher in individuals with SLD than in those without SLD (0.197 vs. 0.071, p &lt; 0.001), with an adjusted hazard ratio of 2.02 (95% confidence interval: 1.40–2.92). The HCC incidence rate per 1,000 person-years was 0, 0.180, and 0.648 for cryptogenic SLD, MASLD, and MetALD, respectively. When participants with SLD was further stratified by the FIB-4 index, the HCC incidence rate per 1,000 person-years was 0.074 for SLD with FIB-4 &lt; 1.3 and 0.673 for SLD with FIB-4 ≥ 1.3. Of note, HCC risk was substantially high (HCC incidence rate: 1.847 per 1,000 person-years) for MetALD with FIB-4 ≥ 1.3. Conclusions: HCC risk was different by SLD and its subclassification. The utilization of SLD and its subclassification can aid in stratifying HCC risk and facilitate the identification of individuals requiring interventions to mitigate the risk of HCC.
ACSL4-mediated membrane phospholipid remodeling induces integrin β1 activation to facilitate triple-negative breast cancer metastasis
Authors: Yuxiang Qiu, Xing Wang, Yan Sun, Ting Jin, Rui Tang, Xinyue Zhou, Ming Xu, Yubi Gan, Rui Wang, Haojun Luo, Manran Liu, Xi Tang
Journal: Cancer Research (2024)

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and a high propensity to metastasize. Lipid metabolism has emerged as a critical regulator of tumor progression and metastasis in other cancer types. Characterization of the lipid metabolic features of TNBC could provide important insights into the drivers of TNBC metastasis. Here, we showed that metastatic TNBC tumors harbor more unsaturated phospholipids, especially long-chain polyunsaturated fatty acids, at the sn-2 position of phosphatidylcholine and phosphatidylethanolamine compared with primary tumors. Metastatic TNBC tumors upregulated ACSL4, a long-chain polyunsaturated acyl-CoA synthetase that drives the preferential incorporation of polyunsaturated fatty acids into phospholipids, resulting in the alteration of membrane phospholipid composition and properties. Moreover, ACSL4-mediated phospholipid remodeling of the cell membrane induced lipid-raft localization and activation of integrin β1 in a CD47-dependent manner, which led to downstream focal adhesion kinase phosphorylation that promoted metastasis. Importantly, pharmacologic inhibition of ACSL4 suppressed tumor growth and metastasis and increased chemosensitivity in TNBC models in vivo. These findings indicate that ACSL4-mediated phospholipid remodeling enables TNBC metastasis and can be inhibited as a potential strategy to improve the efficacy of chemotherapy in TNBC.
SPARC stabilizes ApoE to induce cholesterol-dependent invasion and sorafenib resistance in hepatocellular carcinoma
Authors: Shan Wan, Quan-Yao He, Yun Yang, Feng Liu, Xue Zhang, Xin Guo, Hui Niu, Yi Wang, Yi-Xuan Liu, Wen-Long Ye, Xiu-Ming Li, Xue-Mei ZhuanSun, Pu Sun, Xiao-Shun He, Guang Hu, Kai Breuhahn, Hua Zhao, Guo-Qiang Wu, Hua Wu
Journal: Cancer Research (2024)

Abstract Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastases. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC (secreted protein acidic and rich in cysteine) was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K–AKT signaling and inducing epithelial–mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC. Significance: Intracellular SPARC boosts cholesterol availability to fuel invasion and drug resistance in hepatocellular carcinoma, providing a rational approach to improve the treatment of advanced liver cancer.
Whole-genome DNA methylation profiling of intrahepatic cholangiocarcinoma reveals prognostic subtypes with distinct biological drivers
Authors: Haotian Liao, Xing Chen, Haichuan Wang, Youpei Lin, Lu Chen, Kefei Yuan, Mingheng Liao, Hanyu Jiang, Jiajie Peng, Zhenru Wu, Jiwei Huang, Jiaxin Li, Yong Zeng
Journal: Cancer Research (2024)

Abstract Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. Although the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving the treatment of cancers. In this study, we conducted whole-genome bisulfite sequencing on 331 iCCAs integrated with genetic, transcriptomic, and proteomic analyses, demonstrating the existence of four DNA methylation subtypes of iCCAs (S1–S4) that exhibited unique postoperative clinical outcomes. The S1 group was an IDH1/2 mutation–specific subtype with moderate survival. The S2 subtype was characterized by the lowest methylation level and the highest mutational burden among the four subtypes and displayed upregulation of a gene-expression pattern associated with cell cycle/DNA replication. The S3 group was distinguished by high interpatient heterogeneity of tumor immunity, a gene-expression pattern associated with carbohydrate metabolism, and an enrichment of KRAS alterations. Patients with the S2 and S3 subtypes had the shortest survival among the four subtypes. Tumors in the S4 subtype, which had the best prognosis, showed global methylation levels comparable to normal controls, increased FGFR2 fusions/BAP1 mutations, and the highest copy-number variant burdens. Further integrative and functional analyses identified GBP4 demethylation, which is highly prevalent in the S2 and S3 groups, as an epigenetic oncogenic factor that regulates iCCA proliferation, migration, and invasion. Together, this study identifies prognostic methylome alterations and epigenetic drivers in iCCA. Significance: Characterization of the DNA methylome of intrahepatic cholangiocarcinoma integrated with genomic, transcriptomic, and proteomic analyses uncovers molecular mechanisms affected by genome-wide DNA methylation alterations, providing a resource for identifying potential therapeutic targets.
A histone methylation-MAPK signaling axis drives durable epithelial-mesenchymal transition in hypoxic pancreatic cancer
Authors: Brooke A. Brown, Paul J. Myers, Sara J. Adair, Jason R. Pitarresi, Shiv K. Sah-Teli, Logan A. Campbell, William S. Hart, Michelle C. Barbeau, Kelsey Leong, Nicholas Seyler, William Kane, Kyoung Eun Lee, Edward Stelow, Marieke Jones, M. Celeste Simon, Peppi Koivunen, Todd W. Bauer, Ben Z. Stanger, Matthew J. Lazzara
Journal: Cancer Research (2024)

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a key role in tumor progression and response to therapy. The dense PDAC stroma causes hypovascularity, which leads to hypoxia. Here, we showed that hypoxia drives long-lasting epithelial-mesenchymal transition (EMT) in PDAC primarily through a positive-feedback histone methylation-MAPK signaling axis. Transformed cells preferentially underwent EMT in hypoxic tumor regions in multiple model systems. Hypoxia drove a cell autonomous EMT in PDAC cells, which, unlike EMT in response to growth factors, could last for weeks. Furthermore, hypoxia reduced histone demethylase KDM2A activity, suppressed PP2 family phosphatase expression, and activated MAPKs to post-translationally stabilize histone methyltransferase NSD2, leading to an H3K36me2-dependent EMT in which hypoxia-inducible factors played only a supporting role. Hypoxia-driven EMT could be antagonized in vivo by combinations of MAPK inhibitors. Collectively, these results suggest that hypoxia promotes durable EMT in PDAC by inducing a histone methylation-MAPK axis that can be effectively targeted with multidrug therapies, providing a potential strategy for overcoming chemoresistance.
Predicting Obstructive Sleep Apnea Based on Computed Tomography Scan Using Deep Learning Models
Authors: Jeong-Whun Kim, Kyungsu Lee, Hyun Jik Kim, Hae Chan Park, Jae Youn Hwang, Seok-Won Park, Hyoun-Joong Kong, Jin Youp Kim
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

The incidence of clinically undiagnosed obstructive sleep apnea (OSA) is high among the general population because of limited access to polysomnography. Computed tomography (CT) of craniofacial regions obtained for other purposes can be beneficial in predicting OSA and its severity.
A Self‐Assembled 3D Model Demonstrates How Stiffness Educates Tumor Cell Phenotypes and Therapy Resistance in Pancreatic Cancer
Authors: Ying Liu, Babatunde O. Okesola, David Osuna de la Peña, Weiqi Li, Meng‐Lay Lin, Sara Trabulo, Marianthi Tatari, Rita T. Lawlor, Aldo Scarpa, Wen Wang, Martin Knight, Daniela Loessner, Christopher Heeschen, Alvaro Mata, Oliver M. T. Pearce
Journal: Advanced Healthcare Materials (2024)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression and therapy resistance. To further the understanding of how stiffening of the tumor microenvironment (TME) contributes to aggressiveness, a three‐dimensional (3D) self‐assembling hydrogel disease model is developed based on peptide amphiphiles (PAs, PA‐E3Y ) designed to tailor stiffness. The model displays nanofibrous architectures reminiscent of native TME and enables the study of the invasive behavior of PDAC cells. Enhanced tuneability of stiffness is demonstrated by interacting thermally annealed aqueous solutions of PA‐E3Y (PA‐E3Y h ) with divalent cations to create hydrogels with mechanical properties and ultrastructure similar to native tumor ECM. It is shown that stiffening of PA‐E3Y h hydrogels to levels found in PDAC induces ECM deposition, promotes epithelial‐to‐mesenchymal transition (EMT), enriches CD133 + /CXCR4 + cancer stem cells (CSCs), and subsequently enhances drug resistance. The findings reveal how a stiff 3D environment renders PDAC cells more aggressive and therefore more faithfully recapitulates in vivo tumors.