tbuckley/cabot-search huggingface dataset:
Complete spatially resolved gene expression is not necessary for identifying spatial domains
Authors: Senlin Lin, Yan Cui, Fangyuan Zhao, Zhidong Yang, Jiangning Song, Jianhua Yao, Yu Zhao, Bin-Zhi Qian, Yi Zhao, Zhiyuan Yuan
Journal: Cell Genomics (2024)

Spatially resolved transcriptomics (SRT) technologies have revolutionized the study of tissue organization. We introduce a graph convolutional network with an attention and positive emphasis mechanism, termed BINARY, relying exclusively on binarized SRT data to accurately delineate spatial domains. BINARY outperforms existing methods across various SRT data types while using significantly less input information. Our study suggests that precise gene expression quantification may not always be essential, inspiring further exploration of the broader applications of spatially resolved binarized gene expression data.
Long-wavelength traveling waves of vasomotion modulate the perfusion of cortex
Authors: Thomas Broggini, Jacob Duckworth, Xiang Ji, Rui Liu, Xinyue Xia, Philipp Mächler, Iftach Shaked, Leon Paul Munting, Satish Iyengar, Michael Kotlikoff, Susanne J. van Veluw, Massimo Vergassola, Gal Mishne, David Kleinfeld
Journal: Neuron (2024)
Vaccination with nanoparticles displaying gH/gL from Epstein-Barr virus elicits limited cross-protection against rhesus lymphocryptovirus
Authors: Kristina R. Edwards, Karina Schmidt, Leah J. Homad, Gargi M. Kher, Guoyue Xu, Kristen A. Rodrigues, Elana Ben-Akiva, Joe Abbott, Martin Prlic, Evan W. Newell, Stephen C. De Rosa, Darrell J. Irvine, Marie Pancera, Andrew T. McGuire
Journal: Cell Reports Medicine (2024)

Epstein-Barr virus (EBV) is associated with infectious mononucleosis, cancer, and multiple sclerosis. A vaccine that prevents infection and/or EBV-associated morbidity is an unmet need. The viral gH/gL glycoprotein complex is essential for infectivity, making it an attractive vaccine target. Here, we evaluate the immunogenicity of a gH/gL nanoparticle vaccine adjuvanted with the Sigma Adjuvant System (SAS) or a saponin/monophosphoryl lipid A nanoparticle (SMNP) in rhesus macaques. Formulation with SMNP elicits higher titers of neutralizing antibodies and more vaccine-specific CD4
SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire
Authors: Alison Tarke, Parham Ramezani-Rad, Tertuliano Alves Pereira Neto, Yeji Lee, Vanessa Silva-Moraes, Benjamin Goodwin, Nathaniel Bloom, Leila Siddiqui, Liliana Avalos, April Frazier, Zeli Zhang, Ricardo da Silva Antunes, Jennifer Dan, Shane Crotty, Alba Grifoni, Alessandro Sette
Journal: Cell Reports Medicine (2024)

Little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS2) vaccine breakthrough infections (BTIs) on the magnitude and breadth of the T cell repertoire after exposure to different variants. We studied samples from individuals who experienced symptomatic BTIs during Delta or Omicron waves. In the pre-BTI samples, 30% of the donors exhibited substantial immune memory against non-S (spike) SARS2 antigens, consistent with previous undiagnosed asymptomatic SARS2 infections. Following symptomatic BTI, we observed (1) enhanced S-specific CD4 and CD8 T cell responses in donors without previous asymptomatic infection, (2) expansion of CD4 and CD8 T cell responses to non-S targets (M, N, and nsps) independent of SARS2 variant, and (3) generation of novel epitopes recognizing variant-specific mutations. These variant-specific T cell responses accounted for 9%-15% of the total epitope repertoire. Overall, BTIs boost vaccine-induced immune responses by increasing the magnitude and by broadening the repertoire of T cell antigens and epitopes recognized.
FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis
Authors: Dan Su, Ruobing Wang, Guangyu Chen, Chen Ding, Yueze Liu, JInxin Tao, Yuanyang Wang, Jiangdong Qiu, Wenhao Luo, Guihu Weng, Yang Gang, Taiping Zhang
Journal: Cancer Research (2024)

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide, primarily due to its rapid progression. The current treatment options for PDAC are limited, and a better understanding of the underlying mechanisms responsible for PDAC progression is required to identify improved therapeutic strategies. In this study, we identified FBXO32 as an oncogenic driver in PDAC. FBXO32 was aberrantly upregulated in PDAC, and high FBXO32 expression was significantly associated with an unfavorable prognosis in patients with PDAC. FRG1 deficiency promoted FBXO32 upregulation in PDAC. FBXO32 promoted cell migration and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, FBXO32 directly interacted with eEF1A1 and promoted its polyubiquitination at the K273 site, leading to enhanced activity of eEF1A1 and increased protein synthesis in PDAC cells. Moreover, FBXO32-catalyzed eEF1A1 ubiquitination boosted the translation of ITGB5 mRNA and activated focal adhesion kinase (FAK) signaling, thereby facilitating focal adhesion assembly and driving PDAC progression. Importantly, interfering with the FBXO32-eEF1A1 axis or pharmaceutical inhibition of FAK by defactinib, an FDA-approved FAK inhibitor, substantially inhibited PDAC growth and metastasis driven by aberrantly activated FBXO32-eEF1A1 signaling. Overall, this study uncovers a mechanism by which PDAC cells rely on FBXO32-mediated eEF1A1 activation to drive progression and metastasis. FBXO32 may serve as a promising biomarker for selecting eligible patients with PDAC for treatment with defactinib. Significance: FBXO32 upregulation in pancreatic cancer induced by FRG1 deficiency increases eEF1A1 activity to promote ITGB5 translation and stimulate FAK signaling, driving cancer progression and sensitizing tumors to the FAK inhibitor defactinib.
Targeting Super-Enhancer-Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance
Authors: Yi Sui, Teng Wang, Yanqing Mei, Ying Zhu, Wenyan Jiang, Jiayi Shen, Siyuan Yan, Wenjie Lu, Kewen Zhao, Jialin Mo, Chaochen Wang, Yujie Tang
Journal: Cancer Research (2024)

Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional-targeted therapies represent a promising direction for developing improved anti-Hh therapies. In this study, we integrated epigenetic/transcriptional-targeted small-molecule library screening with CRISPR/Cas9 knockout library screening and identified CDK9 and CDK12, two transcription elongation regulators, as therapeutic targets for antagonizing aberrant Hh activation and overcoming SMOi resistance. Inhibition of CDK9 or CDK12 potently suppressed Hh signaling and tumor growth in various SMOi responsive or resistant Hh-driven tumor models. Systemic epigenomic profiling elucidated the Hh-driven super-enhancer (SE) landscape and identified IRS1, encoding a critical component and cytoplasmic adaptor protein of the insulin-like growth factor (IGF) pathway, as an oncogenic Hh-driven SE target gene and effective therapeutic target in Hh-driven tumor models. Collectively, this study identifies SE-driven transcriptional dependencies that represent promising therapeutic vulnerabilities for suppressing the Hh pathway and overcoming SMOi resistance. As CDK9 and IRS inhibitors have already entered human clinical trials for cancer treatment, these findings provide comprehensive preclinical support for developing trials for Hh-driven cancers. Significance: Dissecting transcriptional dependencies driven by super-enhancers uncovers therapeutic targets in Hedgehog-driven cancers and identifies strategies for overcoming resistance to smoothened inhibitors.
The potential of micro- and nanoplastics to exacerbate the health impacts and global burden of non-communicable diseases
Authors: Stefan Krause, Valerie Ouellet, Deonie Allen, Steven Allen, Kerry Moss, Holly A. Nel, Semira Manaseki-Holland, Iseult Lynch
Journal: Cell Reports Medicine (2024)

Non-communicable diseases (NCD) constitute one of the highest burdens of disease globally and are associated with inflammatory responses in target organs. There is increasing evidence of significant human exposure to micro- and nanoplastics (MnPs). This review of environmental MnP exposure and health impacts indicates that MnP particles, directly and indirectly through their leachates, may exacerbate inflammation. Meanwhile, persistent inflammation associated with NCDs in gastrointestinal and respiratory systems potentially increases MnP uptake, thus influencing MnP access to distal organs. Consequently, a future increase in MnP exposure potentially augments the risk and severity of NCDs. There is a critical need for an integrated one-health approach to human health and environmental research for assessing the drivers of human MnP exposure and their bidirectional links with NCDs. Assessing these risks requires interdisciplinary efforts to identify and link drivers of environmental MnP exposure and organismal uptake to studies of impacted disease mechanisms and health outcomes.
Targeting MCL1-driven anti-apoptotic pathways overcomes blast progression after hypomethylating agent failure in chronic myelomonocytic leukemia
Authors: Guillermo Montalban-Bravo, Natthakan Thongon, Juan Jose Rodriguez-Sevilla, Feiyang Ma, Irene Ganan-Gomez, Hui Yang, Yi June Kim, Vera Adema, Bethany Wildeman, Tomoyuki Tanaka, Faezeh Darbaniyan, Gheath Al-Atrash, Karen Dwyer, Sanam Loghavi, Rashmi Kanagal-Shamanna, Xingzhi Song, Jianhua Zhang, Koichi Takahashi, Hagop Kantarjian, Guillermo Garcia-Manero, Simona Colla
Journal: Cell Reports Medicine (2024)

RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Here, using single-cell, multi-omics technologies, we seek to dissect the biological mechanisms underlying the initiation and progression of RAS pathway-mutated CMML. We identify that RAS pathway mutations induce transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs) and downstream monocytic populations in response to cell-intrinsic and -extrinsic inflammatory signaling that also impair the functions of immune cells. HSPCs expand at disease progression after therapy with HMA or the BCL2 inhibitor venetoclax and rely on the NF-κB pathway effector MCL1 to maintain survival. Our study has implications for the development of therapies to improve the survival of patients with RAS pathway-mutated CMML.
Hyperemesis gravidarum theories dispelled by recent research: a paradigm change for better care and outcomes
Authors: Marlena Schoenberg Fejzo
Journal: Trends in Molecular Medicine (2024)

Nausea and vomiting (NVP) affect most pregnant women. At the severe end of the clinical spectrum, hyperemesis gravidarum (HG) can be life-threatening. The condition is fraught with misconceptions that have slowed progress and left women undertreated. Herein, recent scientific advances are presented that dispel common myths associated with HG related to maternal/offspring outcomes, etiology, and evolution. There is now strong evidence that (i) HG is associated with poor outcomes, (ii) a common cause of NVP and HG has been identified, and (iii) NVP is likely a protective evolutionary mechanism that occurs throughout the animal kingdom but is no longer necessary for human survival. Therefore, it is encouraging that we are finally on the cusp of testing treatments that may put an end to unnecessary suffering.
lSelf‐assembling P38 Peptide Inhibitor Nanoparticles Ameliorate the Transition from Acute to Chronic Kidney Disease by Suppressing Ferroptosis
Authors: Wang Xin, Shuiqin Gong, Yin Chen, Mengying Yao, Shaozong Qin, Jing Chen, Aihong Zhang, Wenrui Yu, Siyan Zhou, Bo Zhang, Jun Gu, Jinghong Zhao, Yinghui Huang
Journal: Advanced Healthcare Materials (2024)

Accumulating evidence highlights p38 as a crucial factor highly activated during the process of acute kidney injury (AKI), but the application of p38 inhibitor in AKI is quite limited due to the low efficiency and poor kidney-targeting ability. Herein, a novel self-assembling peptide nanoparticle with specific p38-inhibiting activity is constructed, which linked mitogen-activated protein kinase kinase 3b (MKK3b), the functional domain of p38, with the cell-penetrating TAT sequence, ultimately self-assembling into TAT-MKK3b nanoparticles (TMNPs) through tyrosinase oxidation. Subsequent in vitro and in vivo studies demonstrated that TMNPs preferably accumulated in the renal tubular epithelial cells (RTECs) through forming protein coronas by binding to albumin, and strongly improved the reduced renal function of ischemia-reperfusion injury (IRI)-induced AKI and its transition to chronic kidney disease (CKD). Mechanically, TMNPs inhibited ferroptosis via its solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis-inducing capacity and synergistic potent antioxidant property in AKI. The findings indicated that the multifunctional TMNPs exhibited renal targeting, ROS-scavenging, and ferroptosis-mitigating capabilities, which may serve as a promising therapeutic agent for the treatment of AKI and its progression to CKD.
Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in DSRCTs
Authors: Clémence Henon, Julien Vibert, Thomas Eychenne, Nadège Gruel, Léo Colmet-Daage, Carine Ngo, Marlène Garrido, Nicolas Dorvault, Maria Eugenia Marques Da Costa, Virginie Marty, Nicolas Signolle, Antonin Marchais, Noé Herbel, Asuka Kawai-Kawachi, Madison Lenormand, Clémence Astier, Roman Chabanon, Benjamin Verret, Rastislav Bahleda, Axel Le Cesne, Fatima Mechta-Grigoriou, Matthieu Faron, Charles Honoré, Olivier Delattre, Joshua J. Waterfall, Sarah Watson, Sophie Postel-Vinay
Journal: Cell Reports Medicine (2024)
Polymer Bioelectronics: A Solution for Both Stimulating and Recording Electrodes
Authors: Estelle A. Cuttaz, Zachary K. Bailey, Christopher A. R. Chapman, Josef A. Goding, Rylie A. Green
Journal: Advanced Healthcare Materials (2024)

The advent of closed-loop bionics has created a demand for electrode materials that are ideal for both stimulating and recording applications. The growing complexity and diminishing size of implantable devices for neural interfaces have moved beyond what can be achieved with conventional metallic electrode materials. Polymeric electrode materials are a recent development based on polymer composites of organic conductors such as conductive polymers. These materials present exciting new opportunities in the design and fabrication of next-generation electrode arrays which can overcome the electrochemical and mechanical limitations of conventional electrode materials. This review will examine the recent developments in polymeric electrode materials, their application as stimulating and recording electrodes in bionic devices, and their impact on the development of soft, conformal, and high-density neural interfaces.
Exploring the effect on primary endpoints in trials testing targeted therapy interventions for rheumatoid arthritis: a meta-epidemiological study on the appropriate use of a core outcome set
Authors: Philip Rask Lage-Hansen, Nikoletta Svendsen, Jamie Kirkham, Sabrina Mai Nielsen, Kirstine Amris, Maarten de Wit, Maarten Boers, Torkell Ellingsen, Robin Christensen
Journal: Annals of the Rheumatic Diseases (2024)

To explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA).
Comprehensive evaluation of a multicenter real-world study: Neoadjuvant immunochemotherapy in locally advanced gastric cancer
Authors: Kexun Li, Simiao Lu, Xuefeng Leng, Lin Peng
Journal: International Journal of Surgery (2024)

Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (Sichuan Cancer Hospital) Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China (Sichuan Cancer Hospital), 55 Section 4, South Renmin Road, Chengdu, Chengdu 610041, China. Tel: +8618908178797; fax: +86-028-85420156. E-mail address: [email protected] (L. Peng). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Commentary on “Prognostic factors for acute vertebrobasilar artery occlusion-reperfusion: a multicenter retrospective cohort study”
Authors: Jinping Zhang, Haitao Li, Zunlu Zhang, Mingzhe Hu, Bingchen Li
Journal: International Journal of Surgery (2024)

Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250014, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author Address: Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250014, China. E-mail address: [email protected] (J. Zhang). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Applications of generative AI in peer review process: friend or foe?
Authors: Haiyang Wu, Zaijie Sun, Qiang Guo, Cheng Li
Journal: International Journal of Surgery (2024)

aDepartment of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China bDepartment of Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China cDepartment of Orthopaedic Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China dDepartment of Orthopedics, Baodi Clinical College of Tianjin Medical University eDepartment of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China fCenter for Musculoskeletal Surgery (CMSC), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University of Berlin, Berlin Institute of Health, Berlin, Germany Haiyang Wu, Zaijie Sun, and Qiang Guo contributed equally to this study. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: The First Affiliated Hospital of Zhengzhou University Durham, NC UNITED STATES. E-mail address: [email protected] (H. Wu). *Corresponding author. Address: E-mail address: [email protected] (C. Li). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
The impact of omentoplasty on the reduction of overall complications in liver surgery: an analysis using prediction interval
Authors: Jiajun Chen, Jiao Huang, Xinyi Li
Journal: International Journal of Surgery (2024)

aStomatological Hospital of Chongqing Medical University, Chongqing 401147, China bChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China cChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author Address: College of Stomatology, Chongqing Medical University, 426#Songshibei Road, Yubei District, Chongqing, Post: 401147, P.R. China. E-mail address: [email protected] (X. Li). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Letter to the editor: A commentary on ‘Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study’
Authors: Yiqi Huang, Yiming Jin, Feng Jin, Sanmeizi Xie
Journal: International Journal of Surgery (2024)

aDepartment of Nephrology, Shaoxing Second Hospital, Shaoxing, Zhejiang, 312000, China bIntensive Care Unit, Shaoxing Second Hospital, Shaoxing, Zhejiang, 312000, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Intensive Care Unit, Shaoxing Second Hospital, Shaoxing, Zhejiang, 312000, China; E-mail address: [email protected] (S. Xie). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Transcutaneous electrical acupoint stimulation reduces postoperative patients’ length of stay and hospitalization costs: A systematic review and meta-analysis
Authors: Yilong Liu, Jiefu Fan, Xiaoqing Zhang, Wenping Xu, Zhiwen Shi, Jiarong Cai, Peiqin Wang
Journal: International Journal of Surgery (2024)

Objective: To study the effects of transcutaneous electrical acupoint stimulation (TEAS) on length of stay (LOS) and hospitalization costs in postoperative inpatients. Methods: Two researchers collectively searched PubMed, Embase, Cochrane Library, China Network Knowledge Infrastructure and Wanfang Database. The search time was set from the beginning to April 25, 2023, to identify randomized controlled trials articles that met the criteria. Statistical analyses were performed using the Stata software (version 16.0). The risk of bias was assessed using the Cochrane risk-of-bias tool, and publication bias was evaluated using a funnel plot and Egger’s test. The quality of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Thirty-four randomized controlled trials were included. The main results showed that TEAS reduced hospitalization costs (standardized mean difference (SMD)=−1.92; 95% confidence interval (CI) −3.40, −0.43), LOS (SMD=−1.00; 95% CI −1.30, −0.70) and postoperative LOS (SMD=−0.70; 95% CI −0.91, −0.49) in postoperative patients. Subgroup analyses further revealed that TEAS was effective in reducing both the overall and postoperative LOS in patients undergoing multiple surgical procedures. It is worth noting that the observed heterogeneity in the results may be attributed to variations in surgical procedures, stimulation frequencies, and stimulation points utilized in different trials. Conclusions: TEAS can help postoperative patients reduce their LOS and hospitalization cost. However, considering the bias identified and heterogeneity, the results of this review should be interpreted with caution.