tbuckley/cabot-search huggingface dataset:
NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression
Authors: Songyi Liu, Chunlin Lin, Xiang Lin, Penghang Lin, Ruofan He, Xiaoyu Pan, Yan Lin, Jianxin Ye, Guangwei Zhu
Journal: Cancer Research (2024)

Abstract Gastric cancer is an aggressive malignancy with poor patient outcomes. N-Acetyltransferase 10 (NAT10) is an acetyltransferase that has been reported to contribute to gastric cancer progression. In-depth investigation into the underlying molecular mechanisms driven by NAT10 could help identify therapeutic targets to improve gastric cancer treatment. In this study, we found that NAT10 forms condensates to regulate RNA dynamics and promote gastric cancer progression. In samples of patients with gastric cancer, elevated NAT10 expression correlated with an unfavorable prognosis, advanced disease stage, and metastasis. NAT10 enhanced the proliferation, migration, and invasion of gastric cancer cells; supported the growth of patient-derived organoids; and accelerated tumor development. A C-terminal intrinsically disordered region-mediated liquid–liquid phase separation of NAT10 and was essential for its tumor-promoting function in gastric cancer. Moreover, NAT10 interacted with the splicing factor serine/arginine-rich splicing factor 2 (SRSF2), leading to its acetylation and increased stability. Acetylated SRSF2 directly bound to the pre-mRNA of the m6A reader YTHDF1, resulting in enhanced YTHDF1 exon 4 skipping and upregulation of a short YTHDF1 transcript that could stimulate gastric cancer cell proliferation and migration. Furthermore, YTHDF1 exon 4 skipping correlated with NAT10 and SRSF2 expression and was associated with a more aggressive phenotype in samples of patients with gastric cancer. Together, this study uncovers the role of NAT10 liquid–liquid phase separation in modulating YTHDF1 splicing through SRSF2 acetylation to drive gastric cancer progression, providing insights into the oncogenic mechanism of NAT10. Significance: Phase separation of NAT10 enables acetylation of SRSF2 that enhances YTHDF1 exon 4 skipping, which is a tumor-promoting axis in gastric cancer that represents potential therapeutic targets and prognostic biomarkers.
Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer
Authors: Jianqiang Yang, Fanghui Chen, Liwei Lang, Fan Yang, Zhenzhen Fu, Juan Martinez, Amber Cho, Nabil F. Saba, Yong Teng
Journal: Cancer Research (2024)

Abstract Head and neck squamous cell carcinoma (HNSCC) is addicted to glutaminolysis. Targeting this metabolic dependency has emerged as a potential therapeutic approach for HNSCC. In this study, we conducted a bioinformatic analysis of The Cancer Genome Atlas HNSCC cohort that revealed a robust correlation between expression of MYC (encoding the protein c-Myc) and glutaminase 1 (GLS1), which catalyzes the first step in glutaminolysis. Intriguingly, disruption of GLS1 signaling in HNSCC cells by genetic depletion or CB-839 treatment resulted in a reduction in c-Myc protein stability via a ubiquitin-specific peptidase 1–dependent ubiquitin–proteasome pathway. On the other hand, c-Myc directly binds to the promoter region of GLS1 and upregulates its transcription. Notably, the GLS1–c-Myc pathway enhanced acetyl-coenzyme A carboxylase–dependent Slug acetylation, prompting cancer cell invasion and metastasis. Thus, the GLS1–c-Myc axis emerged as a positive feedback loop critical for driving the aggressiveness of HNSCC. Therapeutically, combining CB-839 with the c-Myc inhibitor MYCi975 strongly suppressed GLS1–c-Myc signaling, resulting in a superior antitumor effect compared with either single agent in an orthotopic mouse model of HNSCC. These findings hold promise for the development of effective therapies for patients with HNSCC, addressing an urgent need arising from the significant incidence and high metastatic rate of the disease. Significance: GLS1 and c-Myc form a positive feedback loop that promotes head and neck cancer metastasis and can be targeted as a promising therapeutic strategy for this disease.
Strategies to make human skin models based on cellular senescence for ageing research
Authors: Zinaida Shakel, Sofia A. Costa Lima, Salette Reis
Journal: Ageing Research Reviews (2024)

Human skin ageing is closely related to the ageing of the whole organism, and it's a continuous multisided process that is influenced not only by genetic and physiological factors but also by the cumulative impact of environmental factors. Currently, there is a scientific community need for developing skin models representing ageing processes to (i) enhance understanding on the mechanisms of ageing, (ii) discover new drugs for the treatment of age-related diseases, and (iii) develop effective dermo-cosmetics. Bioengineers worldwide are trying to reproduce skin ageing in the laboratory aiming to better comprehend and mitigate the senescence process. This review provides details on the main ageing molecular mechanisms and procedures to obtain in vitro aged skin models.
Microbiome and pancreatic cancer: time to think about chemotherapy
Authors: Juliana de Castilhos, Katharina Tillmanns, Jana Blessing, Arnelyn Laraño, Vadim Borisov, Christoph K. Stein-Thoeringer
Journal: Gut Microbes (2024)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by late diagnosis, rapid progression, and a high mortality rate. Its complex biology, characterized by a dense, stromal tumor environment with an immunosuppressive milieu, contributes to resistance against standard treatments like chemotherapy and radiation. This comprehensive review explores the dynamic role of the microbiome in modulating chemotherapy efficacy and outcomes in PDAC. It delves into the microbiome's impact on drug metabolism and resistance, and the interaction between microbial elements, drugs, and human biology. We also highlight the significance of specific bacterial species and microbial enzymes in influencing drug action and the immune response in the tumor microenvironment. Cutting-edge methodologies, including artificial intelligence, low-biomass microbiome analysis and patient-derived organoid models, are discussed, offering insights into the nuanced interactions between microbes and cancer cells. The potential of microbiome-based interventions as adjuncts to conventional PDAC treatments are discussed, paving the way for personalized therapy approaches. This review synthesizes recent research to provide an in-depth understanding of how the microbiome affects chemotherapy efficacy. It focuses on elucidating key mechanisms and identifying existing knowledge gaps. Addressing these gaps is crucial for enhancing personalized medicine and refining cancer treatment strategies, ultimately improving patient outcomes.
Generating multi-pathological and multi-modal images and labels for brain MRI
Authors: Virginia Fernandez, Walter Hugo Lopez Pinaya, Pedro Borges, Mark S. Graham, Petru-Daniel Tudosiu, Tom Vercauteren, M. Jorge Cardoso
Journal: Medical Image Analysis (2024)

The last few years have seen a boom in using generative models to augment real datasets, as synthetic data can effectively model real data distributions and provide privacy-preserving, shareable datasets that can be used to train deep learning models. However, most of these methods are 2D and provide synthetic datasets that come, at most, with categorical annotations. The generation of paired images and segmentation samples that can be used in downstream, supervised segmentation tasks remains fairly uncharted territory. This work proposes a two-stage generative model capable of producing 2D and 3D semantic label maps and corresponding multi-modal images. We use a latent diffusion model for label synthesis and a VAE-GAN for semantic image synthesis. Synthetic datasets provided by this model are shown to work in a wide variety of segmentation tasks, supporting small, real datasets or fully replacing them while maintaining good performance. We also demonstrate its ability to improve downstream performance on out-of-distribution data.
Nanotechnology-assisted intracellular delivery of antibody as a precision therapy approach for KRAS-driven tumors
Authors: Ana M. López-Estévez, Lucía Sanjurjo, Ángela Turrero, Iker Arriaga, Nicola G.A. Abrescia, Ana Poveda, Jesús Jiménez-Barbero, Anxo Vidal, Dolores Torres, María José Alonso
Journal: Journal of Controlled Release (2024)

The Kirsten Rat Sarcoma Virus (KRAS) oncoprotein, one of the most prevalent mutations in cancer, has been deemed undruggable for decades. The hypothesis of this work was that delivering anti-KRAS monoclonal antibody (mAb) at the intracellular level could effectively target the KRAS oncoprotein. To reach this goal, we designed and developed tLyP1-targeted palmitoyl hyaluronate (HAC16)-based nanoassemblies (HANAs) adapted for the association of bevacizumab as a model mAb. Selected candidates with adequate physicochemical properties (below 150 nm, neutral surface charge), and high drug loading capacity (>10%, w/w) were adapted to entrap the antiKRASG12V mAb. The resulting antiKRASG12V-loaded HANAs exhibited a bilayer composed of HAC16 polymer and phosphatidylcholine (PC) enclosing a hydrophilic core, as evidenced by cryogenic-transmission electron microscopy (cryo-TEM) and X-ray photoelectron spectroscopy (XPS). Selected prototypes were found to efficiently engage the target KRASG12V and, inhibit proliferation and colony formation in KRASG12V-mutated lung cancer cell lines. In vivo, a selected formulation exhibited a tumor growth reduction in a pancreatic tumor-bearing mouse model. In brief, this study offers evidence of the potential to use nanotechnology for developing anti-KRAS precision therapy and provides a rational framework for advancing mAb intracellular delivery against intracellular targets.
A systematic review of the impacts of remote patient monitoring (RPM) interventions on safety, adherence, quality-of-life and cost-related outcomes
Authors: Si Ying Tan, Jennifer Sumner, Yuchen Wang, Alexander Wenjun Yip
Journal: npj Digital Medicine (2024)

Abstract Due to rapid technological advancements, remote patient monitoring (RPM) technology has gained traction in recent years. While the effects of specific RPM interventions are known, few published reviews examine RPM in the context of care transitions from an inpatient hospital setting to a home environment. In this systematic review, we addressed this gap by examining the impacts of RPM interventions on patient safety, adherence, clinical and quality of life outcomes and cost-related outcomes during care transition from inpatient care to a home setting. We searched five academic databases (PubMed, CINAHL, PsycINFO, Embase and SCOPUS), screened 2606 articles, and included 29 studies from 16 countries. These studies examined seven types of RPM interventions (communication tools, computer-based systems, smartphone applications, web portals, augmented clinical devices with monitoring capabilities, wearables and standard clinical tools for intermittent monitoring). RPM interventions demonstrated positive outcomes in patient safety and adherence. RPM interventions also improved patients’ mobility and functional statuses, but the impact on other clinical and quality-of-life measures, such as physical and mental health symptoms, remains inconclusive. In terms of cost-related outcomes, there was a clear downward trend in the risks of hospital admission/readmission, length of stay, number of outpatient visits and non-hospitalisation costs. Future research should explore whether incorporating intervention components with a strong human element alongside the deployment of technology enhances the effectiveness of RPM. The review highlights the need for more economic evaluations and implementation studies that shed light on the facilitators and barriers to adopting RPM interventions in different care settings.
Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses
Authors: Hua Sun, J. Morgan Knight, Yi-Dong Li, Faramarz Ashoori, Martin J. Citardi, William C. Yao, David B. Corry, Amber U. Luong
Journal: Journal of Allergy and Clinical Immunology (2024)
Pediatric T-cell lymphoblastic lymphoma but not leukemia harbor TRB::NOTCH1 fusions with unfavorable outcome
Authors: Marcel Te Vrugt, Janna Sophie Wessolowski, Gerrit Randau, Amelie Alfert, Stephanie Müller, Kenneth Scholten, Claudia Sopalla, Claudia Lanvers-Kaminsky, Marc Hotfilder, Finn Asmus Lamp, Christine Damm-Welk, Jette Luedersen, Gabriele Escherich, Udo zur Stadt, Lena Behrmann, Wilhelm Woessmann, Ilske Oschlies, Matteo Marzi, Martin Zimmermann, Birgit Burkhardt
Journal: Blood (2024)
CRIg+ macrophages deficiency enhanced inflammation damage in IBD due to gut extracellular vesicles containing microbial DNA
Authors: Shangshu Nie, Zhongchao Zhang, Yudong Ji, Qiang Ding, Jin Gong, Fang Xiao, Liping Chen, Dean Tian, Mei Liu, Zhenlong Luo
Journal: Gut Microbes (2024)

Gut microbiota-derived extracellular vesicles (mEVs) are reported to regulate inflammatory response by delivering bacterial products into host cells. The complement receptor of the immunoglobulin superfamily macrophages (CRIg+ Mφ) could clear invading bacteria and their derivatives. Here, we investigate the role of CRIg+ Mφ and the mechanism by which mEVs regulate intestinal inflammation. We found that it is exacerbated in IBD patients and colitis mice by mEVs' leakage from disturbed gut microbiota, enriching microbial DNA in the intestinal mucosa. CRIg+ Mφ significantly decrease in IBD patients, allowing the spread of mEVs into the mucosa. The microbial DNA within mEVs is the key trigger for inflammation and barrier function damage. The cGAS/STING pathway is crucial in mEVs-mediated inflammatory injury. Blocking cGAS/STING signaling effectively alleviates inflammation caused by mEVs leakage and CRIg+ Mφ deficiency. Microbial DNA-containing mEVs, along with CRIg+ Mφ deficiency, stimulate inflammation in IBD, with the cGAS/STING pathway playing a crucial role.
Drug interaction with Udp-Glucuronosyltransferase (UGT) enzymes is a predictor of drug-induced liver injury
Authors: AyoOluwa O. Olubamiwa, Tsung-Jen Liao, Jinwen Zhao, Patrice Dehanne, Catherine Noban, Yeliz Angin, Olivier Barberan, Minjun Chen
Journal: Hepatology (2024)

DILI frequently contributes to the attrition of new drug candidates and is a common cause for the withdrawal of approved drugs from the market. Although some noncytochrome P450 (non-CYP) metabolism enzymes have been implicated in DILI development, their association with DILI outcomes has not been systematically evaluated.
An update to terminology describing abnormal uterine bleeding in female athletes: facilitating cross-disciplinary health care
Authors: Chimsom T Oleka, Travis Anderson, Kathryn E Ackerman, Kirsty J Elliott-Sale, Emily Kraus, Ellen Casey, Trent Stellingwerff, Amber T Donaldson, Jonathan T Finnoff, Eric G Post, William M Adams
Journal: British Journal of Sports Medicine (2024)
Updating the paradigm of prophylactic abdominal drainage following Pancreatoduodenectomy (review article)
Authors: Zhenli Li, Yibing Zhang, Yuanzhi Ni, Liang Li, Lindi Xu, Yang Guo, Shuaishuai Zhu, Yufu Tang
Journal: International Journal of Surgery (2024)

Background: Prophylactic abdominal drainage (PAD) is considered a routine procedure after pancreatoduodenectomy (PD) to prevent and detect severe complications at an early stage. However, the drainage itself may cause adverse consequences. Thus, the optimal strategy of PAD after PD remains controversial. Methods: The present paper summarizes the latest research on the strategies of PAD following PD, mainly focusing on 1) the selective placement of PAD, 2) the optimal drainage types, 3) the early removal of drainage (EDR), and 4) novel strategies for PAD management. Results: Accurate stratifications based on the potential risk factors of clinically relevant-postoperative pancreatic fistula (CR-POPF) facilitates the selective placement of PAD and the implementation of EDR, with postoperative outcomes superior or similar to routine PAD placement. Both active and passive drainage methods are feasible in most patients after PD, with similar prognostic outcomes. Novel predictive models with accurate, dynamic, and individualized performance further guide the management of PAD and afford a better prognosis. Conclusions: Evidence-based risk stratification of CR-POPF aids in the management of PAD in patients undergoing PD. Novel dynamic and individualized PAD strategies might be the next hotspot in drain-relevant explorations.
Norepinephrine versus phenylephrine affects prethrombotic response in patients undergoing cesarean section under spinal anesthesia: a randomized, double-blind, controlled study
Authors: Wenhui Tao, Jinfeng Bao, Yufang Xie, Wei Ding, Yule Wu, Ye Zhang, Xianwen Hu
Journal: International Journal of Surgery (2024)

Venous thromboembolism (VTE) is one of the most common and serious complications of cesarean section in parturients. Norepinephrine (NE) has been shown to activate coagulation. The aim of this study was to compare the effect of a fixed-rate prophylactic norepinephrine infusion and a fixed-rate prophylactic phenylephrine（PHE） infusion under spinal anesthesia for caesarean section on the prethrombotic response.
Ozaki technique versus ross operation for complex aortic valve diseases in children: A retrospective cohort study
Authors: Guan-Xi Wang, Sen Zhang, Kai Ma, Kun-Jing Pang, Xu Wang, Ke-Ming Yang, Ben-Qing Zhang, Yang Yang, Shou-Jun Li
Journal: International Journal of Surgery (2024)

Background: The Ozaki technique demonstrated promising results in adults, but few studies reported on pediatric patients with limited follow-up time. This study aimed to evaluate the mid-term results of Ozaki technique compared with Ross operation for complex aortic valve (AV) diseases in children. Materials and Methods: One hundred and seventeen children underwent either Ozaki (n = 64) or Ross (n = 53) operation from January 2017 to December 2023. The primary endpoint was incidence of moderate or severe regurgitation/stenosis (AR/AS) post procedure. Results: No significant difference was observed in age (6.5±3.4 vs. 7.9±4.3 years) and weight (25.9±15.5 vs. 31.0±25.9 kgs) at surgery. The Ozaki group had significantly more patients in heart failure (20.3% vs. 1.9%, P = 0.003) before surgery and more patients needed ECMO installation (6.3% vs. 0, P = 0.125) after surgery. The Ozaki group were in worse status with more patients occurred heart failure (20.3% vs. 1.9%, P = 0.003) before surgery and needed ECMO installation (6.3% vs. 0, P = 0.125) after surgery. During follow up (20.4±17.3 vs. 22.7±22.8 months, P = 0.526), five patients (7.8%) in Ozaki group but no patients in Ross group required reoperations. The incidence of moderate or severe AR (28.1% vs. 3.1%) and AS (31.3% vs. 5.7%) were significantly higher than Ross group. Multivariate analysis identified lower age [HR:1.282 (95%CI:1.075-1.529), P = 0.006] and ECMO installation [HR:0.126 (0.018-0.887), P = 0.037] to be risk factors for moderate or severe AR, and higher aortic transvalvular gradient before discharge was confirmed as the only risk factor for moderate or severe AS (≥36 mmHg) at follow up in Ozaki group. Conclusion: Ozaki technique may be used as a palliative procedure for complex AV diseases in children, but its’ mid-term results were not durable as Ross surgery, especially younger patients.
Retraction Note: MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex
Authors: M Konopleva, M Milella, P Ruvolo, J C Watts, M R Ricciardi, B Korchin, McQueen Teresa, William Bornmann, T Tsao, P Bergamo, D H Mak, W Chen, J McCubrey, A Tafuri, M Andreeff
Journal: Leukemia (2024)
The innate immune landscape of dMMR/MSI cancers predicts outcome of nivolumab treatment: results from the Drug Rediscovery Protocol
Authors: Laurien J. Zeverijn, Birgit S. Geurts, Thomas W. Battaglia, Jade M. van Berge Henegouwen, Gijs F. de Wit, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Paul Roepman, Wendy W.J. de Leng, Anne M.L. Jansen, Myriam Chalabi, Carla M.L. van Herpen, Lot A. Devriese, Frans L.G. Erdkamp, Mariette Labots, Maja J. A. de Jonge, Emile D. Kerver, Adriaan D. Bins, Lindsay V.M. Leek, Jessica C.L. Notohardjo, Alfonsus J.M. van den Eertwegh, Lodewyk F.A. Wessels, Henk M.W. Verheul, Hans Gelderblom, Joris van de Haar, Emile E. Voest
Journal: Clinical Cancer Research (2024)

The treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid mismatch repair deficiency/microsatellite-instable (dMMR/MSI) tumors, and in-depth biomarker analyses were performed to inform precision immunotherapy approaches.
Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy
Authors: Yazi Yang, Sen Qin, Mengyu Yang, Ting Wang, Ru Feng, Chunli Zhang, Enrun Zheng, Qinghua Li, Pengyu Xiang, Shangyong Ning, Xiaodong Xu, Xin Zuo, Shuai Zhang, Xiaoya Yun, Xuehong Zhou, Yue Wang, Lin He, Yongfeng Shang, Luyang Sun, Hui Liu
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The purpose of this study was to investigate the remodeling of the multiple myeloma microenvironment after B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor T (CAR-T) cell therapy. Experimental Design: We performed single-cell RNA sequencing on paired bone marrow specimens (n = 14) from seven patients with multiple myeloma before (i.e., baseline, “day −4”) and after (i.e., “day 28”) lymphodepleted BCMA CAR-T cell therapy. Results: Our analysis revealed heterogeneity in gene expression profiles among multiple myeloma cells, even those harboring the same cytogenetic abnormalities. The best overall responses of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells, enhanced CD8+ effector T-cell cytotoxic activity, and elevated type 1 conventional dendritic cell (DC) antigen presentation ability. DC re-clustering inferred intramedullary-originated type 3 conventional DCs with extramedullary migration. Cell–cell communication network analysis indicated that BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway–mediated immunosuppression and activates MIF pathway–mediated anti–multiple myeloma immunity. Conclusions: Our study sheds light on multiple myeloma microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.
Cryoablation does not significantly contribute to systemic effector immune responses in poorly immunogenic B16F10 melanoma model
Authors: Chakradhar Yakkala, Jesus Corria-Osorio, Lana Kandalaft, Alban Denys, Bhanu Koppolu, Rafael Duran
Journal: Clinical Cancer Research (2024)

Cryoablation is a minimally invasive procedure implemented to destroy solid tumors. It also results in the release of tumor antigens into the systemic circulation. Preclinical studies using immunogenic tumor models have shown that cryoablation evokes antitumor immune responses. The mechanisms by which cryoablation impacts immune responses in poorly immunogenic tumors have not been sufficiently explored.