tbuckley/cabot-search huggingface dataset:
Abstract A005: Enhanced DNA damage and disruption of repair by iodinated thymidine analogues with Tipiracil for clinical radiation sensitization
Authors: Scott Grindrod, Alfredo Velana, Tyvin Rich, Mira Jung, Dalong Pang, Anatoly Dritschilo
Journal: Cancer Research (2024)

Abstract IUdR incorporation into cellular DNA enhances radiation induced DNA damage and impairs repair pathways. IUdR has been explored as a clinical radiation sensitizer in Phase I and II clinical trials of sarcomas and gliomas, showing clinical activity. A major barrier to acceptance of this therapy has been the poor pharmacokinetic (PK) profile of IUdR which has a blood plasma half-life of less than 10 minutes. Continuous IV infusion of IUdR has been used to achieve clinically relevant DNA incorporation into tumor cells, but technical limitations of delivery and acute toxicities in rapidly proliferating normal tissues presented barriers to advancing this approach. To improve the PK profile of IUdR, a prodrug strategy has been employed leading to the development of ropidoxuridine (IPdR), which improved the PK profile, demonstrated oral bioavailability of the active metabolite IUdR, showed less normal tissue toxicity, and provided tumor radiation sensitization. IPdR plus XRT has been tested in Phase 0 and Phase 1 clinical trials and a phase II trial is proposed for glioblastoma treatment. We report here a second approach to improve the PK profile of orally administered IUdR by combining these iodinated thymidine analogs with the metabolism inhibitor, Tipiracil (TPI) which inhibits thymidine phosphorylase, the primary enzyme responsible for irreversible IUdR degradation, and is currently used in the FDA approved combination drug Lonsurf. Oral co-administration of IUdR and TPI in rats dramatically improved the PK profile of IUdR, increasing the half-life of the compound to 1.5 hours and boosting the maximum plasma concentration by approximately 8-fold. We studied the effects of Tipiracil on the metabolism of IUdR by varying the molecular ratio of IUdR/TPI from 2:1 up to a ratio of 10:1 and discovered that the plasma concentration of IUdR plateaued between a ratio of 5:1 and 10:1. This new combination therapy of IUdR/TPI yields a PK profile of IUdR that is relevant to clinical treatment in combination with RT and offers to expand potential clinical radiation sensitizer applications. Citation Format: Scott Grindrod, Alfredo Velana, Tyvin Rich, Mira Jung, Dalong Pang, Anatoly Dritschilo. Enhanced DNA damage and disruption of repair by iodinated thymidine analogues with Tipiracil for clinical radiation sensitization [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A005.
Recent progress on the development of bioinspired surfaces with high aspect ratio microarray structures: From fabrication to applications
Authors: Guang Liu, Jiajun Yang, Kaiteng Zhang, Hongting Wu, Haipeng Yan, Yu Yan, Yingdong Zheng, Qingxu Zhang, Dengke Chen, Liwen Zhang, Zehui Zhao, Pengfei Zhang, Guang Yang, Huawei Chen
Journal: Journal of Controlled Release (2024)
NMR-based metabolomic signature: An important tool for the diagnosis and study of pathogenesis of autoimmune hepatitis
Authors: Aikaterini Dimou, Kalliopi Zachou, Christina Kostara, Kalliopi Azariadis, George Giannoulis, Aggeliki Lyberopoulou, Eleni Bairaktari, George N. Dalekos
Journal: Hepatology (2024)

Metabolomics is used to predict, diagnose, and monitor metabolic disorders but altered metabolomic signatures have also been reported in diverse diseases, including autoimmune disorders. However, the metabolomic profile in autoimmune hepatitis (AIH) has not been investigated in depth. Therefore, we investigated the metabolomic signature of AIH and its significance as a diagnostic and pathogenetic tool.
Cerebrovascular Malformation Mimicking Recurrent Lymphoma on Dual Time-Point 18F-FDOPA PET
Authors: Sonya Youngju Park, Min Kyoung Lee, Eun Ji Han, Young-Woo Jeon
Journal: Clinical Nuclear Medicine (2024)

Abstract Although 18 F-FDG is the dominant radiotracer for PET imaging of hematological malignancies, radiolabeled amino acids have also been investigated to improve image quality in areas of high 18 F-FDG uptake such as the central nervous system. We present a case of a 57-year-old woman who underwent an 18 F-FDOPA scan for primary CNS lymphoma, which demonstrated an unexpected false-positive uptake in the right frontal lobe, due to a developmental venous anomaly.
Al18F-NOTA-Octreotide PET/CT and 18F-FDG PET/CT for Detecting Cerebellar Hemangioblastoma in a Patient With Von Hippel-Lindau Disease
Authors: Guozhu Hou, Xin Cheng, Yihebali Chi, Xuejuan Wang, Rong Zheng
Journal: Clinical Nuclear Medicine (2024)

Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.
Bio-integrated scaffold facilitates large bone regeneration dominated by endochondral ossification
Authors: Lili Sun, Haoyi Niu, Yuqiong Wu, Shiyan Dong, Xuefeng Li, Betty Y.S. Kim, Changsheng Liu, Yifan Ma, Wen Jiang, Yuan Yuan
Journal: Bioactive Materials (2024)

Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.
Corrigendum to “Cooperative STAT3-NFkB signaling modulates mitochondrial dysfunction and metabolic profiling in hepatocellular carcinoma” [Metabolism, Volume 152, March 2024, 155771]
Authors: Sharmeen Ishteyaque, Gurvinder Singh, Karan Singh Yadav, Smriti Verma, Rakesh Kumar Sharma, Sumati Sen, Anurag Kumar Srivastav, Kalyan Mitr, Amit Lahiri, Dnyaneshwar U. Bawankule, Srikanta Kumar Rath, Dinesh Kumar, Madhav Nilakanth Mugale
Journal: Metabolism (2024)
Human cardiosphere-derived cells with activated mitochondria for better myocardial regenerative therapy
Authors: Masahiro Shiraishi, Daisuke Sasaki, Mitsue Hibino, Atsuhito Takeda, Hideyoshi Harashima, Yuma Yamada
Journal: Journal of Controlled Release (2024)

Cell transplantation is a promising therapeutic strategy for myocardial regeneration therapy. To improve therapeutic effects, we developed a culture medium additive that enhances the mitochondrial function of cardiomyocytes for transplantation. A mitochondrial targeting drug delivery system (MITO-Porter system) was used to deliver mitochondrial activation molecules to mouse-derived cardiac progenitor cells. In this study, we investigated whether the mitochondrial function of human-derived myocardial precursor cells could be enhanced using MITO-Porter. Human cardiosphere-derived cells (CDCs) were isolated from myocardium which was excised during surgery for congenital heart disease. MITO-Porter was added to the cell culture medium to generate mitochondrial activated CDCs (human MITO cells). The human MITO cells were transplanted into myocardial ischemia-reperfusion model rat, and the effect was investigated. The transplanted human MITO cells improved the cardiac function and suppressed myocardial fibrosis compared to conventional cell transplantation methods. These effects were observed not only with myocardial administration but also by intravenous administration of human MITO cells. This study is the first study that assessed whether the mitochondrial delivery of functional compounds improved the outcome of human-derived myocardial cell transplantation therapy.
An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II
Authors: Sabyasachi Das, Fatlum Rruga, Annita Montepeloso, Agnese Dimartino, Silvia Spadini, Guillaume Corre, Janki Patel, Eleonora Cavalca, Francesca Ferro, Alessandra Gatti, Rita Milazzo, Anne Galy, Letterio S. Politi, Gian Paolo Rizzardi, Giuliana Vallanti, Valentina Poletti, Alessandra Biffi
Journal: Molecular Therapy (2024)
Artificial intelligence-driven virtual rehabilitation for people living in the community: A scoping review
Authors: Ali Abedi, Tracey J. F. Colella, Maureen Pakosh, Shehroz S. Khan
Journal: npj Digital Medicine (2024)

Abstract Virtual Rehabilitation (VRehab) is a promising approach to improving the physical and mental functioning of patients living in the community. The use of VRehab technology results in the generation of multi-modal datasets collected through various devices. This presents opportunities for the development of Artificial Intelligence (AI) techniques in VRehab, namely the measurement, detection, and prediction of various patients’ health outcomes. The objective of this scoping review was to explore the applications and effectiveness of incorporating AI into home-based VRehab programs. PubMed/MEDLINE, Embase, IEEE Xplore, Web of Science databases, and Google Scholar were searched from inception until June 2023 for studies that applied AI for the delivery of VRehab programs to the homes of adult patients. After screening 2172 unique titles and abstracts and 51 full-text studies, 13 studies were included in the review. A variety of AI algorithms were applied to analyze data collected from various sensors and make inferences about patients’ health outcomes, most involving evaluating patients’ exercise quality and providing feedback to patients. The AI algorithms used in the studies were mostly fuzzy rule-based methods, template matching, and deep neural networks. Despite the growing body of literature on the use of AI in VRehab, very few studies have examined its use in patients’ homes. Current research suggests that integrating AI with home-based VRehab can lead to improved rehabilitation outcomes for patients. However, further research is required to fully assess the effectiveness of various forms of AI-driven home-based VRehab, taking into account its unique challenges and using standardized metrics.
Transient induction of actin cytoskeletal remodeling associated with dedifferentiation, proliferation, and redifferentiation stimulates cardiac regeneration
Authors: Wenbin Fu, Qiao Liao, Yu Shi, Wujian Liu, Hongmei Ren, Chunmei Xu, Chunyu Zeng
Journal: Acta Pharmaceutica Sinica B (2024)

The formation of new and functional cardiomyocytes requires a 3-step process: dedifferentiation, proliferation, and redifferentiation, but the critical genes required for efficient dedifferentiation, proliferation, and redifferentiation remain unknown. In our study, a circular trajectory using single-nucleus RNA sequencing of the pericentriolar material 1 positive (PCM1+) cardiomyocyte nuclei from hearts 1 and 3 days after surgery-induced myocardial infarction (MI) on postnatal Day 1 was reconstructed and demonstrated that actin remodeling contributed to the dedifferentiation, proliferation, and redifferentiation of cardiomyocytes after injury. We identified four top actin-remodeling regulators, namely Tmsb4x, Tmsb10, Dmd, and Ctnna3, which we collectively referred to as 2D2P. Transiently expressed changes of 2D2P, using a polycistronic non-integrating lentivirus driven by Tnnt2 (cardiac-specific troponin T) promoters (Tnnt2-2D2P-NIL), efficiently induced transiently proliferative activation and actin remodeling in postnatal Day 7 cardiomyocytes and adult hearts. Furthermore, the intramyocardial delivery of Tnnt2-2D2P-NIL resulted in a sustained improvement in cardiac function without ventricular dilatation, thickened septum, or fatal arrhythmia for at least 4 months. In conclusion, this study highlights the importance of actin remodeling in cardiac regeneration and provides a foundation for new gene-cocktail-therapy approaches to improve cardiac repair and treat heart failure using a novel transient and cardiomyocyte-specific viral construct.
A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy
Authors: Rui Freitas, Andreia Miranda, Dylan Ferreira, Marta Relvas-Santos, Flávia Castro, Eduardo Ferreira, Cristiana Gaiteiro, Janine Soares, Sofia Cotton, Martina Gonçalves, Mariana Eiras, Beatriz Santos, Carlos Palmeira, Margareta P. Correia, Maria José Oliveira, Bruno Sarmento, Andreia Peixoto, Lúcio Lara Santos, André M.N. Silva, José Alexandre Ferreira
Journal: Journal of Controlled Release (2024)
Aptamer-based therapy for fighting biofilm-associated infections
Authors: Ana Margarida Sousa, Débora Ferreira, Lígia Raquel Rodrigues, Maria Olívia Pereira
Journal: Journal of Controlled Release (2024)

Biofilms are key players in the pathogenesis of most of chronic infections associated with host tissue or fluids and indwelling medical devices. These chronic infections are hard to be treated due to the increased biofilms tolerance towards antibiotics in comparison to planktonic (or free living) cells. Despite the advanced understanding of their formation and physiology, biofilms continue to be a challenge and there is no standardized therapeutic approach in clinical practice to eradicate them. Aptamers offer distinctive properties, including excellent affinity, selectivity, stability, making them valuable tools for therapeutic purposes. This review explores the flexibility and designability of aptamers as antibiofilm drugs but, importantly, as targeting tools for diverse drug and delivery systems. It highlights specific examples of application of aptamers in biofilms of diverse species according to different modes of action including inhibition of motility and adhesion, blocking of quorum sensing molecules, and dispersal of biofilm-cells to planktonic state. Moreover, it discusses the limitations and challenges that impaired an increased success of the use of aptamers on biofilm management, as well as the opportunities related to aptamers modifications that can significantly expand their applicability on the biofilm field.
Combination therapy with imiquimod and 5-fluorouracil cream for the treatment of actinic keratoses, a prospective open-label nonrandomized uncontrolled pilot trial
Authors: Richard Maxwell Regester, Amy C. Cannella, Julianna Hirz, Brian Sayles, Stacie Schlange, Amy Rau, Harlan R. Sayles, Anthony J. Griess
Journal: Journal of the American Academy of Dermatology (2024)
Targeting RORγ inhibits the growth and metastasis of hepatocellular carcinoma
Authors: Qianqian Liu, Junhua Wang, Huizi Sun, Zhenhua Zhang, Hong Wang, Shuai Ma, Chenxi Zhang, Qianqian Wang, Guodi Cai, Jianwei Zheng, Yichu Nie, Peiqing Liu, Junjian Wang
Journal: Molecular Therapy (2024)
The Risks of Normalizing Parental Vaccine Hesitancy
Authors: David M Higgins, Sean T O'Leary
Journal: New England Journal of Medicine (2024)

Audio Interview Interview with David Higgins on public confidence in the value of childhood vaccines and the importance of combating misinformation about vaccination. 6m 28s Download AbstractMost parents in the United States don't hesitate to have their children receive routine childhood vaccines. Suggesting otherwise is potentially harmful.
AI-derived epicardial fat measurements improve cardiovascular risk prediction from myocardial perfusion imaging
Authors: Robert J. H. Miller, Aakash Shanbhag, Aditya Killekar, Mark Lemley, Bryan Bednarski, Serge D. Van Kriekinge, Paul B. Kavanagh, Attila Feher, Edward J. Miller, Andrew J. Einstein, Terrence D. Ruddy, Joanna X. Liang, Valerie Builoff, Daniel S. Berman, Damini Dey, Piotr J. Slomka
Journal: npj Digital Medicine (2024)

Abstract Epicardial adipose tissue (EAT) volume and attenuation are associated with cardiovascular risk, but manual annotation is time-consuming. We evaluated whether automated deep learning-based EAT measurements from ungated computed tomography (CT) are associated with death or myocardial infarction (MI). We included 8781 patients from 4 sites without known coronary artery disease who underwent hybrid myocardial perfusion imaging. Of those, 500 patients from one site were used for model training and validation, with the remaining patients held out for testing ( n = 3511 internal testing, n = 4770 external testing). We modified an existing deep learning model to first identify the cardiac silhouette, then automatically segment EAT based on attenuation thresholds. Deep learning EAT measurements were obtained in &lt;2 s compared to 15 min for expert annotations. There was excellent agreement between EAT attenuation (Spearman correlation 0.90 internal, 0.82 external) and volume (Spearman correlation 0.90 internal, 0.91 external) by deep learning and expert segmentation in all 3 sites (Spearman correlation 0.90–0.98). During median follow-up of 2.7 years (IQR 1.6–4.9), 565 patients experienced death or MI. Elevated EAT volume and attenuation were independently associated with an increased risk of death or MI after adjustment for relevant confounders. Deep learning can automatically measure EAT volume and attenuation from low-dose, ungated CT with excellent correlation with expert annotations, but in a fraction of the time. EAT measurements offer additional prognostic insights within the context of hybrid perfusion imaging.
Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer
Authors: Praful Ravi, Dory Freeman, Jonathan Thomas, Arvind Ravi, Charlene Mantia, Bradley A McGregor, Jacob E Berchuck, Ilana Epstein, Petra Budde, Behnaz Ahangarian Abhari, Elena Rupieper, Jana Gajewski, Ann-Sophie Schubert, Annika L Kilian, Manuel Bräutigam, Hans-Dieter Zucht, Guru Sonpavde
Journal: Journal for ImmunoTherapy of Cancer (2024)

Comprehensive profiling of autoantibodies (AAbs) in metastatic urothelial cancer (mUC) has not been performed to date. This may aid in diagnosis of UC, uncover novel therapeutic targets in this disease as well as identify associations between AAbs and response and toxicity to systemic therapies. We used serum from patients with mUC collected prior to and after systemic therapy (immune checkpoint inhibitor (ICI) or platinum-based chemotherapy (PBC)) at Dana-Farber Cancer Institute. 38 age-matched and sex-matched healthy controls (HCs) from healthy blood donors were also evaluated. The SeroTag immuno-oncology discovery array (Oncimmune) was used, with quantification of the AAb reactivity toward 1132 antigens. Bound AAbs were detected using an anti-immunoglobulin G-specific detection antibody conjugated to the fluorescent reporter dye phycoerythrin. The AAb reactivity was reported as the median fluorescence intensity for each color and sample using a Luminex FlexMAP3D analyzer. Clinical outcomes of interest included radiographic response and development of immune-related adverse events (irAEs). Significance analysis of microarray was used to compare mUC versus HC and radiographic response. Associations with irAE were evaluated using a logistic regression model. P<0.05 was considered statistically significant. 66 patients were included with a median age of 68 years; 54 patients (82%) received ICI and 12 patients (18%) received PBC. Compared with HCs, AAbs against the cancer/testis antigens (CTAG1B, CTAG2, MAGEB18), HSPA1A, TP53, KRAS, and FGFR3 were significantly elevated in patients with mUC. AAbs against BRCA2, TP53, and CTNBB1 were associated with response, and those against BICD2 and UACA were associated with resistance to ICI therapy. AAbs against MITF, CDH3, and KDM4A were associated with development of irAEs in patient who received an ICI. A higher variance in pre-to-post treatment fold change in AAb levels was seen in patients treated with ICI versus PBC and was associated with response to ICI. This is the first report of comprehensive AAb profiling of patients with mUC and identified key AAbs that were elevated in patients with mUC versus HCs as well as AAbs associated with therapeutic response to ICI. These findings are hypothesis generating and further mechanistic studies evaluating humoral immunity in UC are required.