tbuckley/cabot-search huggingface dataset:
A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer
Authors: Feng Qi, Na Gao, Jia Li, Chenfei Zhou, Jinling Jiang, Bin Zhou, Liting Guo, Xiaohui Feng, Jun Ji, Qu Cai, Liu Yang, Rongjia Zhu, Xinyi Que, Junwei Wu, Wenqi Xi, Wenxing Qin, Jun Zhang
Journal: Molecular Cancer (2024)

The quest to understand the molecular mechanisms of tumour metastasis and identify pivotal biomarkers for cancer therapy is increasing in importance. Single-omics analyses, constrained by their focus on a single biological layer, cannot fully elucidate the complexities of tumour molecular profiles and can thus overlook crucial molecular targets. In response to this limitation, we developed a multiobjective recommendation system (RJH-Metastasis 1.0) anchored in a multiomics knowledge graph to integrate genome, transcriptome, and proteome data and corroborative literature evidence and then conducted comprehensive analyses of colorectal cancer with liver metastasis (CRCLM). A total of 25 key genes significantly associated with CRCLM were recommended by our system, and GNB1, GATAD2A, GBP2, MACROD1, and EIF5B were further highlighted. Specifically, GNB1 presented fewer mutations but elevated RNA transcription and protein expression in CRCLM patients. The role of GNB1 in promoting the malignant behaviours of colon cancer cells was demonstrated via in vitro and in vivo studies. Aberrant expression of GNB1 could be regulated by METTL1-driven m7G modification. METTL1 knockdown decreased m7G modification in the 3' UTR of GNB1, increasing its mRNA transcription and translation during liver metastasis. Furthermore, GNB1 induced the formation of an immunosuppressive microenvironment by promoting the CLEC2C-KLRB1 interaction between memory B cells and KLRB1+PD-1+CD8+ cells. GNB1 expression and the efficacy of PD-1 antibody-based treatment in CRCLM patients were significantly correlated. In summary, our recommendation system can be used for effective exploration of key molecules in colorectal cancer, among which GNB1 was identified as a critical CRCLM promoter and immunotherapy biomarker in colorectal cancer patients.
Humanized In Vivo Bone Tissue Engineering: In Vitro Preculture Conditions Control the Structural, Cellular, and Matrix Composition of Humanized Bone Organs
Authors: Agathe Bessot, Flavia Medeiros Savi, Jennifer Gunter, Jayanti Mendhi, Shahrouz Amini, David Waugh, Jacqui McGovern, Dietmar W. Hutmacher, Nathalie Bock
Journal: Advanced Healthcare Materials (2024)

Abstract Bone tissue engineering (BTE) has long sought to elucidate the key factors controlling human/humanized bone formation for regenerative medicine and disease modeling applications, yet with no definitive answers due to the high number and co‐dependency of parameters. This study aims to clarify the relative impacts of in vitro biomimetic ‘preculture composition’ and ‘preculture duration’ before in vivo implantation as key criteria for the optimization of BTE design. These parameters are directly related to in vitro osteogenic differentiation (OD) and mineralization and are being investigated across different osteoprogenitor‐loaded biomaterials, specifically fibrous calcium phosphate‐polycaprolactone (CaP‐mPCL) scaffolds and gelatin methacryloyl (GelMA) hydrogels. The results show that OD and mineralization levels prior to implantation, enhanced by a mineralization medium supplement to the osteogenic medium (OM), significantly improve ectopic BTE outcomes, regardless of the biomaterial type. Specifically, preculture conditions are pivotal in achieving more faithful mimicry of human bone structure, cellular and extracellular matrix composition and organization, and provide control over bone marrow composition. This work emphasizes the potential of using biomimetic culture compositions, specifically the addition of a mineralization medium as a cost‐effective and straightforward approach to enhance BTE outcomes, facilitating rapid development of bone models with superior quality and resemblance to native bone.
Drug‐Induced Differential Gene Expression Analysis on Nanoliter Droplet Microarrays: Enabling Tool for Functional Precision Oncology
Authors: Razan El Khaled EL Faraj, Shraddha Chakraborty, Meijun Zhou, Morgan Sobol, David Thiele, Lilly M Shatford‐Adams, Maximiano Correa Cassal, Anne‐Kristin Kaster, Sascha Dietrich, Pavel A. Levkin, Anna A. Popova
Journal: Advanced Healthcare Materials (2024)

Abstract Drug‐induced differential gene expression analysis (DGEA) is essential for uncovering the molecular basis of cell phenotypic changes and understanding individual tumor responses to anticancer drugs. Performing high throughput DGEA is challenging due to the high cost and labor‐intensive multi‐step sample preparation protocols. In particular, performing drug‐induced DGEA on cancer cells derived from patient biopsies is even more challenging due to the scarcity of available cells. A novel, miniaturized, nanoliter‐scale method for drug‐induced DGEA is introduced, enabling high‐throughput and parallel analysis of patient‐derived cell drug responses, overcoming the limitations and laborious nature of traditional protocols. The method is based on the Droplet Microarray (DMA), a microscope glass slide with hydrophilic spots on a superhydrophobic background, facilitating droplet formation for cell testing. DMA allows microscopy‐based phenotypic analysis, cDNA extraction, and DGEA. The procedure includes cell lysis for mRNA isolation and cDNA conversion followed by droplet pooling for qPCR analysis. In this study, the drug‐induced DGEA protocol on the DMA platform is demonstrated using patient‐derived chronic lymphocytic leukemia (CLL) cells. This methodology is critical for DGEA with limited cell numbers and promise for applications in functional precision oncology. This method enables molecular profiling of patient‐derived samples after drug treatment, crucial for understanding individual tumor responses to anticancer drugs.
Cosmic‐Ray Radiation Effects on Ibuprofen Tablet Formulation Inside and Outside of the International Space Station
Authors: Quy Don Tran, Nigel Spooner, Sean Geoghehan, Shanjaye Raj Thavarajah, Shamaun Rahman, Nam Nghiep Tran, Philip Michael Williams, Sandra Martinez Jarquin, Dong‐Hyun Kim, Kenneth Davey, Jeff Buell, Mark Shumbera, Mark Gittleman, Twyman Clements, Jana Stoudemire, Ian Fisk, Volker Hessel
Journal: Advanced Healthcare Materials (2024)

In extreme environments people will have different needs for medicine(s), making it crucial to understand how such environments affect drug efficacy. Ibuprofen, commonly used in tablet formulation on Earth, could fail in space despite standard pharmaceutical packaging. We introduce the concept of 'space medicines', where solid-dosage forms protect the pharmaceutical from accelerated degradation in spaceflight. We simulate dose(s) in International Space Station (ISS) through radionuclide and photon experiments, and establish the impact of alpha, beta and gamma rays. We demonstrate that tablet formulation protects from impact of alpha and beta rays; however, gamma rays decompose ibuprofen even when 'masked'. We systematically analyse 19 tablet compositions inside and outside the ISS to determine the effect of compositional changes in the tablet matrix. We confirm that the iron oxide-shielded tablets show minimal degradation (〈10%) inside the ISS, compared to moderate reductions (〉10%) for other formulations, with one exception. The tablets exhibited significantly greater ibuprofen degradation (〉 30-50%) outside ISS, due to harsh conditions. Significantly, we found that flavour have shielding potential by scavenging free radicals. We conclude that ibuprofen efficacy is adversely affected in space, and these effects are expected to worsen on missions to deeper space destinations.
Time‐Responsive Activity of Engineered Bacteria for Local Sterilization and Biofilm Removal in Periodontitis
Authors: Yang Bai, Hao‐Lin Guo, Tingting Hua, Bowen Li, Guoqing Feng, Zijan Zhang, Yue Teng, Yuan Liu, Niansong Qian, Bin Zheng
Journal: Advanced Healthcare Materials (2024)

Abstract Periodontitis is a highly prevalent and common condition in people of all ages, however, existing drugs to treat periodontitis have difficulty penetrating complex biofilms. Here, we report a biofilm‐penetrating probiotic hybrid strategy for the treatment of periodontitis. It consists of therapeutic probiotics of E. coli Nissle 1917, which can produce antimicrobial peptides and hydrogen, and is coated with D‐amino acids that can penetrate biofilms. After the fusion of D‐amino acids with the biofilm, EcN entered the plaque biofilm and produced antimicrobial peptides to kill porphyromonas gingivalis and eliminate periodontitis under the action of hydrogen. The efficacy of EcN@DA‐D in biofilm penetration and treatment of periodontitis was demonstrated in a rat model of periodontitis. In addition, the clinical combination to construct a rat periodontitis model by using clinical tissue has a significant therapeutic effect. In conclusion, EcN@DA‐D offers a promising topical treatment for periodontitis without developing detectable pathogen resistance and side effects.
Synthetic Periodontal Guided Tissue Regeneration Membrane with Self‐Assembling Biphasic Structure and Temperature‐Sensitive Shape Maintenance
Authors: W. Benton Swanson, Seth M. Woodbury, Renan Dal‐Fabbro, Lindsey Douglas, Jackson Albright, Miranda Eberle, David Niemann, Jinping Xu, Marco C. Bottino, Yuji Mishina
Journal: Advanced Healthcare Materials (2024)

Abstract Periodontal disease poses significant challenges to the long‐term stability of oral health by destroying the supporting structures of teeth. Guided tissue regeneration techniques, particularly barrier membranes, enable local regeneration by providing an isolated, protected compartment for osseous wound healing while excluding epithelial tissue. Here, this study reports on a thermosensitive periodontal membrane (TSPM) technology designed to overcome the mechanical limitations of current membranes through a semi‐interpenetrating network of high molecular weight poly(L‐lactic acid) (PLLA) and in situ‐polymerized mesh of poly(ε‐caprolactone)diacrylate (PCL‐DA), and poly lactide‐co‐glycolide diacrylate (PLGA‐DA). An optimized composition allows facile reshaping at greater than 52 °C and rigid shape maintenance at physiological temperature. Its unique bilayer morphology is achieved through self‐assembly and thermally‐induced phase separation, resulting in distinct yet continuous smooth and nanofibrous compartments adequate for epithelial occlusion and regeneration. Incorporating PLGA‐DA enhances the membrane's hydrophilicity and degradation properties, facilitating a more rapid and controlled degradation and therapeutic delivery. This study demonstrates its ability to promote local regeneration by serving as a barrier membrane and simultaneously as a scaffolding matrix in a rat orthotopic periodontal defect model. The TSPM outperformed a clinically available material (Epi‐Guide) to facilitate robust alveolar bone and periodontal ligament regeneration at 4 and 8 weeks.
Alum-anchored IL-12 combined with cytotoxic chemotherapy and immune checkpoint blockade enhanced antitumor immune responses in head and neck cancer models
Authors: Kellsye P Fabian, Ginette Santiago-Sanchez, Michelle R Padget, Wiem Lassoued, Clint Tanner Allen, Sailaja Battula, Howard Kaufman, James W Hodge
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background First-line treatment with pembrolizumab plus chemotherapy in recurrent and metastatic head and neck squamous cell carcinomas (HNSCC) has improved survival. However, the overall response rate with this standard of care regimen (SOC) remains limited. Interleukin (IL)-12 is a potent cytokine that facilitates the crosstalk between innate and adaptive immunity, making it crucial in the antitumor response. Alum-anchored murine IL-12 (mANK-101) has been demonstrated to elicit robust antitumor responses in diverse syngeneic models, which were correlated with increased immune effector functions and prolonged local retention of IL-12. This study investigates the therapeutic benefit of combining mANK-101 with SOC in the MOC1 and MOC2 murine HNSCC tumor models. Methods MOC1 and MOC2 tumor-bearing C57BL/6 mice were administered with a single intratumoral injection of mANK-101 and weekly intraperitoneal injections of cisplatin and α-programmed death 1 (PD-1) for 3 weeks. For MOC1, flow cytometry and cytokine array were performed to assess the immune effector functions associated with the combinational treatment. Multiplex immunofluorescence was employed to characterize the influence of the treatment on the immune architecture in the tumors. RNA analysis was implemented for in-depth examination of the macrophage and effector populations. Results In the MOC1 and MOC2 models, combination therapy with mANK-101, cisplatin, and α-PD-1 resulted in superior tumor growth inhibition and resulted in the highest rate of tumor-free survival when compared with treatment cohorts that received mANK-101 monotherapy or SOC treatment with α-PD-1 plus cisplatin. Furthermore, the combination therapy protected against tumor re-growth on rechallenge and controlled the growth of distal tumors. The improved therapeutic effect was associated with increased CD8 + T-cell recruitment, increased CD8 + and CD4 + activity, and repolarization of the macrophage population from M2 to M1 at the tumor site. Elevated and prolonged interferon-γ expression is central to the antitumor activity mediated by the combination therapy. In addition, the combination therapy with mANK-101+cisplatin+α-PD-1 induced the formation of tertiary lymphoid structure-like immune aggregates in the peritumoral space. Conclusion The current findings provide a rationale for the combination of alum-tethered IL-12 with cisplatin and α-PD-1 for HNSCC.
<i>VHL</i>missense mutation delineate aggressive clear cell renal cell carcinoma subtype with favorable immunotherapeutic response
Authors: Ziyang Xu, Li Liu, Wenbin Jiang, Youqi Qiu, Boyu Zhang, Jiangting Cheng, Jiyan Luo, Jianming Guo, Jiejie Xu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background von Hippel-Lindau ( VHL ) harbors the highest mutational frequency in clear cell renal cell carcinoma (ccRCC). Although VHL mutational subtypes exert diverse impacts on the functionality of the VHL protein, the clinical significance of VHL mutational heterogeneity remains largely obscure. Methods This study included a total of 1331 patients with ccRCC from localized data sets, including our localized Zhongshan Hospital (ZSHS) cohort (n=1270) and Zhongshan immune checkpoint blockade cohort (n=61), as well as 525 patients with ccRCC from two publicly available data sets with matched clinical annotation and multidimensional data. According to the putative biological effect, we subclassified VHL mutation into VHL Trunc and VHL Miss . The association of VHL status with clinical outcomes, genomic, oncogenic and immunologic characteristics was further depicted. Results VHL Miss ccRCC was associated with reduced survival in the localized ZSHS and The Cancer Genome Atlas cohorts. Clinical benefit from immunotherapy was observed in VHL Miss patients in all immunotherapy cohorts. VHL Miss ccRCC exhibited hyper-activated cell cycle and nuclear factor kappa B (NF-κB) instead of canonical hypoxia inducible factor pathways, which might contribute to its proliferative morphology. Meanwhile, VHL Miss ccRCC featured an inflamed microenvironment with enriched tertiary lymphoid structures. Conclusions VHL Miss mutations delineate an aggressive ccRCC subtype with distinct clinical outcomes, likely attributed to its specific oncogenic, morphologic and immunologic features.
AKAP12 positive fibroblast determines immunosuppressive contexture and immunotherapy response in patients with TNBC by promoting macrophage M2 polarization
Authors: Zhenkun Liu, Siyuan Hu, Xinlei Zhao, Wenxin Xu, Feng Ju, Meiying Gu, Jialei Weng, Yabing Du
Journal: Journal for ImmunoTherapy of Cancer (2024)

Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with high aggressiveness and poor prognosis. Cancer-associated fibroblasts (CAFs) are major components of the TNBC microenvironment and play an important role in tumor progression and treatment responses. Our goal is to identify specific CAFs subpopulations contributing to TNBC development.
Targeting CD93 on monocytes revitalizes antitumor immunity by enhancing the function and infiltration of CD8<sup>+</sup>T cells
Authors: Da Jiang, Aiqi Huang, Bai-Xi Zhu, Jiangling Gong, Yong-Hao Ruan, Xing-Chen Liu, Limin Zheng, Yan Wu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Limited activation and infiltration of CD8
Germline DNA damage repair variants and prognosis of patients with high-risk or metastatic prostate cancer
Authors: Konrad H. Stopsack, Joseph Vijai, Michael Conry, Jacob E. Berchuck, Yelena Kemel, Samantha E. Vasselman, Dory A. Freeman, Gwo-Shu M. Lee, Diana Mandelker, David B. Solit, Michael J. Morris, Kathryn L. Penney, Wassim Abida, Kenneth Offit, Lorelei A. Mucci, Philip W. Kantoff, Mark M. Pomerantz
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis. Experimental Design: Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up. Pathogenic or likely pathogenic germline variants in 26 DNA repair genes were assessed in relation to metastasis-free survival in high-risk localized prostate cancer and to overall survival in metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC). Results: Among 3,525 patients initially diagnosed with nonmetastatic prostate cancer, 2,594 had high-risk localized prostate cancer, 429 had mCSPC, and 502 had mCRPC at inclusion. BRCA2 variant carriers did not have worse metastasis-free survival in high-risk localized prostate cancer [hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.69–1.46] or overall survival in mCSPC (HR, 0.46; 95% CI, 0.14–1.45) or mCRPC (HR, 0.60; 95% CI, 0.31–1.17) compared with noncarriers of DNA repair variants. Among 868 additional patients with de novo metastatic (M1) prostate cancer, BRCA2 variant carriers tended to have worse overall survival (HR, 1.59; 95% CI, 1.01–2.51). BRCA2 prognostic associations were not explained by radiation, PARP inhibitor, or platinum therapy. Results for other genes were limited in precision because variants were less common. Conclusions: Among patients with high-risk or metastatic prostate cancer who were initially diagnosed with and treated for nonmetastatic tumors, germline DNA repair variants in BRCA2 do not confer a substantially worse prognosis.
Spontaneous breathing trials should be adapted for each patient according to the critical illness. A new individualised approach: the GLOBAL WEAN study
Authors: Mathieu Capdevila, Yassir Aarab, Clement Monet, Audrey De Jong, Aurelie Vonarb, Julie Carr, Nicolas Molinari, Xavier Capdevila, Laurent Brochard, Samir Jaber
Journal: Intensive Care Medicine (2024)
Expanding phenotypic insights of palmoplantar keratodermas based on novel <i>FAM83G</i> variants
Authors: Marike W van Gisbergen, S Vanya J Rossel, Tom E J Theunissen, Renske Janssen, Tariraishe Kaseke, Jasper J van der Smagt, Peter M Steijlen, Maaike Vreeburg, Antoni H Gostynski, Michel van Geel
Journal: British Journal of Dermatology (2024)

We report two unrelated patients with new pathogenic variants in the FAM83G gene, supporting the causal link to previously identified families with recessive hereditary palmoplantar keratoderma. Although structural changes of the hairs are a key feature of FAM83G associated disease, a complete loss of the gene seen in one of the patients, shows normal hair and does not support this part of the clinical phenotype.
Basophils: Regulators of lung inflammation over space and time
Authors: Régis Joulia, Clare M. Lloyd
Journal: The Journal of Experimental Medicine (2024)

In this issue of JEM, Schuijs et al. (https://doi.org/10.1084/jem.20240103) highlight a novel role for basophils during allergic immune responses to house dust mites (HDM). They reveal that interleukin-33 (IL-33)-activated basophils facilitate the recruitment and extravasation of Th2 cells into the lungs during a specific time frame via their interactions with pulmonary endothelial cells.
Diabetes Care in the School Setting: A Statement of the American Diabetes Association
Authors: Fran Cogen, Henry Rodriguez, Christine A. March, Cynthia E. Muñoz, Jacqueline McManemin, Margaret Pellizzari, Janet Rodriguez, Leah Wycoff, Alan L. Yatvin, Torie Atkinson, Nuha A. ElSayed, Raveendhara R. Bannuru, Elizabeth J. Pekas, Crystal Woodward, Jennifer Sherman
Journal: Diabetes Care (2024)

Diabetes is a prevalent chronic disease in school-age children. To keep students with diabetes safe at school, support their long-term health, prevent complications, and ensure full participation in all school activities, proper monitoring of and response to glucose levels must be attended to throughout the school day and during all school-sponsored activities. Care coordination among the family, school, and diabetes health care professionals is critical. With proper planning, including the education and training of school staff, children and youth with diabetes can fully and safely participate in school. In this statement, we review the legal framework for diabetes care in schools, the core components of school-based diabetes care, the responsibilities of various stakeholders, and special circumstances.
Consensus Considerations and Good Practice Points for Use of Continuous Glucose Monitoring Systems in Hospital Settings
Authors: Julie L.V. Shaw, Raveendhara R. Bannuru, Lori Beach, Nuha A. ElSayed, Guido Freckmann, Anna K. Füzéry, Angela W.S. Fung, Jeremy Gilbert, Yun Huang, Nichole Korpi-Steiner, Samantha Logan, Rebecca Longo, Dylan MacKay, Lisa Maks, Stefan Pleus, Kendall Rogers, Jane Jeffrie Seley, Zachary Taxin, Fiona Thompson-Hutchison, Nicole V. Tolan, Nam K. Tran, Guillermo E. Umpierrez, Allison A. Venner
Journal: Diabetes Care (2024)

Continuous glucose monitoring (CGM) systems provide frequent glucose measurements in interstitial fluid and have been used widely in ambulatory settings for diabetes management. During the coronavirus disease 2019 (COVID-19) pandemic, regulators in the U.S. and Canada temporarily allowed for CGM systems to be used in hospitals with the aim of reducing health care professional COVID-19 exposure and limiting use of personal protective equipment. As such, studies on hospital CGM system use have been possible. With improved sensor accuracy, there is increased interest in CGM usage for diabetes management in hospitals. Laboratorians and health care professionals must determine how to integrate CGM usage into practice. The aim of this consensus guidance document is to provide an update on the application of CGM systems in hospital, with insights and opinions from laboratory medicine, endocrinology, and nursing.
Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn’s disease
Authors: Deborah Häcker, Kolja Siebert, Byron J Smith, Nikolai Köhler, Alessandra Riva, Aritra Mahapatra, Helena Heimes, Jiatong Nie, Amira Metwaly, Hannes Hölz, Quirin Manz, Federica De Zen, Jeannine Heetmeyer, Katharina Socas, Giang Le Thi, Chen Meng, Karin Kleigrewe, Josch K Pauling, Klaus Neuhaus, Markus List, Katherine S Pollard, Tobias Schwerd, Dirk Haller
Journal: Cell Host & Microbe (2024)