tbuckley/cabot-search huggingface dataset:
Consensus of Chinese Experts on Neoadjuvant and Conversion Therapies for Hepatocellular Carcinoma: 2023 Update
Authors: Xinyu Bi, Haitao Zhao, Hong Zhao, Guangming Li, Xiaodong Wang, Bo Chen, Wen Zhang, Xu Che, Zhen Huang, Yue Han, Liming Jiang, Yongkun Sun, Zhengqiang Yang, Jianguo Zhou, Yefan Zhang, Zhenyu Zhu, Minshan Chen, Shuqun Cheng, Jianqiang Cai
Journal: Liver Cancer (2024)

Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multidisciplinary team, and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.
Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism
Authors: Doyel Ghosal, Nilotpal Majumder, Pratik Das, Shivani Chaudhary, Sovan Dey, Priya Banerjee, Preeti Tiwari, Piyali Das, Piyali Basak, Samit K Nandi, Sourabh Ghosh, Sachin Kumar
Journal: Advanced Healthcare Materials (2024)

Abstract In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi‐ion‐releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg‐Fib‐PLA‐nCMB). Developed sprayable Alg‐Fib‐PLA‐nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg‐Fib‐PLA‐nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.
Targeted Delivery of Circular Single‐Stranded DNA Encoding IL‐12 for the Treatment of Triple‐Negative Breast Cancer
Authors: Yijing Zhang, Xisen Cao, Guang Hu, Rui Ye, Li Zhang, Jie Song
Journal: Advanced Healthcare Materials (2024)

Abstract Interleukin‐12 (IL‐12) is a critical cytokine with notable anticancer properties, including enhancing T‐cell‐mediated cancer cell killing, and curbing tumor angiogenesis. To date, many approaches are evaluated to achieve in situ overexpression of IL‐12, minimizing leakage and the ensuing toxicity. Here, it is focused on circular single‐stranded DNA (Css DNA), a type of DNA characterized by its unique structure, which could be expressed in mammals. It is discovered that Css DNA can induce sustained luciferase expression for half a year by intramuscular injection and showed effective antitumor results by intratumoral injection. Motivated by these findings, a folate‐modified LNP system is now developed for the delivery of Css DNA expressing IL‐12 for the therapy of 4T1 triple‐negative breast cancer (TNBC). This delivery system effectively activates anti‐cancer immune responses, slows tumor growth, significantly prolongs survival in animal models, and prevents tumor recurrence. After 6 months of long‐term observation, the elevated level of IL‐12 is still detectable in the lymph nodes and serum of the cured mice. This study highlights the long‐term sustained expression capacity of Css DNA and its ability to inhibit recurrence, and the potential of tumor‐targeted LNPs for Css DNA‐based cancer therapy, providing a new insight into gene overexpression strategy.
VISION: An Individual Patient Data Meta-analysis of Randomised Trials Comparing Magnetic Resonance Imaging Targeted Biopsy with Standard Transrectal Ultrasound Guided Biopsy in the Detection of Prostate Cancer
Authors: Veeru Kasivisvanathan, Vinson Wai-Shun Chan, Keiran D. Clement, Brooke Levis, Alexander Ng, Aqua Asif, Masoom A. Haider, Mark Emberton, Gregory R. Pond, Ridhi Agarwal, Katie Scandrett, Yemisi Takwoingi, Laurence Klotz, Caroline M. Moore
Journal: European Urology (2024)

The PRECISION and PRECISE trials compared magnetic resonance imaging targeted biopsy (MRI ± TB) with the standard transrectal ultrasound (TRUS) guided biopsy for the detection of clinically significant prostate cancer (csPCa). PRECISION demonstrated superiority of MRI ± TB over TRUS guided biopsy, while PRECISE demonstrated noninferiority. The VISION study is a planned individual patient data meta-analysis (IPDMA) comparing MRI ± TB with TRUS guided biopsy for csPCa diagnosis. MEDLINE, EMBASE, Web of Science, Cochrane Central of Registered Trials, and ClinicalTrials.gov were searched on the November 12, 2023 for randomised controlled trials of biopsy-naïve patients with a clinical suspicion of prostate cancer undergoing MRI or standard TRUS. Studies were included if its participants with suspicious MRI underwent targeted biopsy alone and those with nonsuspicious lesion avoided biopsy. The primary outcome is the proportion of men diagnosed with csPCa (Gleason ≥3 + 4). Two studies, PRECISION and PRECISE (953 patients), were included in the IPDMA. In the MRI ± TB arm, 32.2% of patients avoided biopsy due to nonsuspicious MRI. MRI ± TB detected 8.7 percentage points (36.3% vs 27.6%; 95% confidence interval [CI] 2.8–14.6, p = 0.004) more csPCa than TRUS biopsy and 12.3 percentage points (9.6% vs 21.9%; 95% CI 7.8–16.9, p < 0.001) less clinically insignificant prostate cancer (cisPCa; Gleason 3 + 3). The overall risk of bias for the included studies were found to be low after assessment using the QUADAS-2, QUADAS-C, and ROB 2.0 tools. The MRI ± TB pathway is superior to TRUS biopsy in detecting csPCa and avoiding the diagnosis of cisPCa. MRI should be included in the standard of care pathway for prostate cancer diagnosis.
A Novel Artificial Intelligence–powered Tool for Precise Risk Stratification of Prostate Cancer Progression in Patients with Clinical Intermediate Risk
Authors: Sujit S. Nair, Hassan Muhammad, Parag Jain, Chensu Xie, Ina Pavlova, Rachel Brody, Wei Huang, Maria Nakadar, Xiangfu Zhang, Hirak Basu, George Wilding, Rajat Roy, Dimple Chakravarty, Ashutosh K. Tewari
Journal: European Urology (2024)
Extracellular Vesicle-Packaged ACSL4 Induces Hepatocyte Senescence to Promote Hepatocellular Carcinoma Progression
Authors: Pei-pei Hou, Chong-ming Zheng, Si-hong Wu, Xi-xiao Liu, Guang-xin Xiang, Wei-yang Cai, Gang Chen, Yong-liang Lou
Journal: Cancer Research (2024)

Abstract Extracellular vesicles (EVs) derived from cancer cells are crucial mediators of intercellular communication during tumor progression. The cargo in tumor-derived EVs that facilitates the establishment of a tumor-supportive microenvironment could serve as a therapeutic target to improve cancer treatment. Here, we demonstrated that hepatocellular carcinoma (HCC) cells secreted the acyl-CoA synthetase ACSL4 in large extracellular vesicles (lEVs) to modulate tumor-microenvironment interactions that promote HCC progression. HCC-derived lEV ACSL4 increased the intracellular abundance of polyunsaturated fatty acid-containing lipids and remodeled the lipid profile to potentiate lipid peroxidation in peritumoral hepatocytes, resulting in hepatocyte senescence accompanied by the senescence-associated secretory phenotype (SASP). Depletion of senescent hepatocytes by senolytic treatment suppressed tumor progression. In HCC cells, SREBP2-mediated transcriptional activation upregulated ACSL4 expression, and Akt-mediated phosphorylation of ACSL4 induced its packaging into lEVs by augmenting its interaction with Annexin A2. This study identified the critical regulatory function of ACSL4 secreted from HCC cells in inducing lipid remodeling and senescence in hepatocytes to support HCC progression, suggesting that targeting lEV ACSL4 is a potential therapeutic strategy for HCC.
Neural Circuitries between the Brain and Peripheral Solid Tumors
Authors: Xiang Chen, Yuli Geng, Guanxin Wei, Danzeng He, Jialong Lv, Wenhao Wen, Fan Xiang, Kaixiong Tao, Chuanqing Wu
Journal: Cancer Research (2024)

Abstract The recent discovery of the pivotal role of central nervous system (CNS) in controlling tumor initiation and progression has opened a new field of research. Increasing evidence suggests a bidirectional interaction between the brain and tumors. The brain influences the biological behavior of tumor cells through complex neural networks involving the peripheral nervous system, the endocrine system, and the immune system, while tumors can establish local autonomic and sensory neural networks to transmit signals into the CNS, thereby affecting brain activity. This review aims to summarize the latest research in brain-tumor crosstalk, exploring neural circuitries between the brain and various peripheral solid tumors, analyzing the roles in tumor development and the related molecular mediators and pathological mechanisms, and highlighting the critical impact on the understanding of cancer biology. Enhanced understanding of reciprocal communication between the brain and tumors will establish a solid theoretical basis for further research and could open avenues for repurposing psychiatric interventions in cancer treatment.
Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926
Authors: Douglas M. Dahl, Joseph P. Rodgers, William U. Shipley, M. Dror Michaelson, Chin-Lee Wu, William Parker, Ashesh B. Jani, Fabio L. Cury, Richard S. Hudes, Jeff M. Michalski, Alan C. Hartford, Daniel Song, Deborah E. Citrin, Theodore G. Karrison, Howard M. Sandler, Felix Y. Feng, Jason A. Efstathiou
Journal: Journal of Clinical Oncology (2024)

PURPOSE To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG). PATIENTS AND METHODS Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety. RESULTS This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia. CONCLUSION Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.
Exposure-Response–Based Multiattribute Clinical Utility Score Framework to Facilitate Optimal Dose Selection for Oncology Drugs
Authors: Yiming Cheng, Shuyu Chu, Jie Pu, Min Chen, Kevin Hong, Paulo Maciag, Ivan Chan, Li Zhu, Akintunde Bello, Yan Li
Journal: Journal of Clinical Oncology (2024)

PURPOSE The advent of new therapeutic modalities highlighted deficiencies in the traditional maximum tolerated dose approach for oncology drug dose selection and prompted the Food and Drug Administration (FDA)'s Project Optimus initiative, which suggests that sponsors take a holistic approach, including efficacy, safety, and pharmacokinetic (PK) and pharmacodynamic data, in conjunction with integrated exposure-response (ER) analyses. However, this method comes with an inherent challenge of the collation of the multisource data. To address this issue, an ER-based clinical utility score (CUS) framework, combining benefit and risk into a single measurement, was developed. METHODS Model-predicted outcomes for each clinically relevant end point, informed by ER modeling, are converted to a CUS using a user-defined utility function. Thereafter, individual CUS is integrated into a single score with user-defined weighting for each end point. The user-defined weighting feature allows the user to incorporate expert knowledge/understanding into weighing the product's benefit versus risk profile. RESULTS To validate the framework, data were leveraged from over 50 oncology programs from 2019 to 2023 on the basis of FDA new drug application/biologics license application review packages and/or related literature studies. Five representative cases were selected for in-depth evaluation. Results showed that the optimal benefit-risk ratio (highest CUS) was consistently observed at PK exposures synonymous with recommended doses. A recurring theme across cases was a greater emphasis on safety over efficacy in oncology drug dose determination. CONCLUSION The ER-based CUS framework offers a strategic tool to navigate the complexities of dose selection in oncology programs. It serves as a pillar to the importance of integrative data analysis, aligning with the vision of Project Optimus, and demonstrates its potential in guiding dose optimization by balancing therapeutic benefits against risk.
How We Monitor Cardiac Health in Breast Cancer Survivors
Authors: Suparna C. Clasen, Meagan E. Miller
Journal: Journal of Clinical Oncology (2024)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.
Managing climate-change refugia to prevent extinctions
Authors: Gunnar Keppel, Diana Stralberg, Toni Lyn Morelli, Zoltán Bátori
Journal: Trends in Ecology & Evolution (2024)

HighlightsClimate-change refugia can support biodiversity by maintaining buffered conditions despite climate change and are a critical tool for the unfolding extinction crisis.Despite their capacity to protect biodiversity, climate-change refugia will be increasingly vulnerable to the impacts of multiple interacting stressors and may hence require management.Effective protection of biodiversity under climate change can be facilitated by managing or newly establishing climate-change refugia on the basis of multiple factors and processes that create them.Using four clear steps, appropriate actions to maintain climate-change refugia, ranging from minimal management to more extensive restoration efforts, can be determined.Identifying and managing climate-change refugia can reduce extinctions and contribute to landscapes that are holistically managed for biodiversity conservation under climate change.AbstractEarth is facing simultaneous biodiversity and climate crises. Climate-change refugia – areas that are relatively buffered from climate change – can help address both of these problems by maintaining biodiversity components when the surrounding landscape no longer can. However, this capacity to support biodiversity is often vulnerable to severe climate change and other stressors. Thus, management actions need to consider the complex and multidimensional nature of refugia. We outline an approach to understand refugia-promoting processes and to evaluate refugial capacity to determine suitable management actions. Our framework applies climate-change refugia as tools to facilitate resistance in modern conservation planning. Such refugia-focused management can reduce extinctions and maintain biodiversity under climate change.
Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles
Authors: Jennifer E. Huffman, Jayna Nicholas, Julie Hahn, Adam S. Heath, Laura M. Raffield, Lisa R. Yanek, Jennifer A. Brody, Florian Thibord, Laura Almasy, Traci M. Bartz, Lawrence F. Bielak, Russell P. Bowler, Germán D. Carrasquilla, Daniel I. Chasman, Ming-Huei Chen, David B. Emmert, Mohsen Ghanbari, Jeffrey Haessler, Jouke-Jan Hottenga, Marcus E. Kleber, Ngoc-Quynh Le, Jiwon Lee, Joshua P. Lewis, Ruifang Li-Gao, Jian'an Luan, Anni Malmberg, Massimo Mangino, Riccardo E. Marioni, Angel Martinez-Perez, Nathan Pankratz, Ozren Polasek, Anne Richmond, Benjamin A. T. Rodriguez, Jerome I. Rotter, Maristella Steri, Pierre Suchon, Stella Trompet, Stefan Weiss, Marjan Zare, Paul Auer, Michael H. Cho, Paraskevi Christofidou, Gail Davies, Eco de Geus, Jean-François Deleuze, Graciela E. Delgado, Lynette Ekunwe, Nauder Faraday, Martin Gögele, Andreas Greinacher, He Gao, Tom Howard, Peter K. Joshi, Tuomas O. Kilpeläinen, Jari Lahti, Allan Linneberg, Silvia Naitza, Raymond Noordam, Ferran Paüls-Vergés, Stephen S. Rich, Frits R. Rosendaal, Igor Rudan, Kathleen A. Ryan, Juan Carlos Souto, Frank J. A. van Rooij, Heming Wang, Wei Zhao, Lewis C. Becker, Andrew Beswick, Michael R. Brown, Brian E. Cade, Harry Campbell, Kelly Cho, James D. Crapo, Joanne E. Curran, Moniek P. M. de Maat, Margaret Doyle, Paul Elliott, James S. Floyd, Christian Fuchsberger, Niels Grarup, Xiuqing Guo, Sarah E. Harris, Lifang Hou, Ivana Kolcic, Charles Kooperberg, Cristina Menni, Matthias Nauck, Jeffrey R. O'Connell, Valeria Orrù, Bruce M. Psaty, Katri Räikkönen, Jennifer A. Smith, Jose Manuel Soria, David J. Stott, Astrid van Hylckama Vlieg, Hugh Watkins, Gonneke Willemsen, Peter W. F. Wilson, Yoav Ben-Shlomo, John Blangero, Dorret Boomsma, Simon R. Cox, Abbas Dehghan, Johan G. Eriksson, Edoardo Fiorillo, Myriam Fornage, Torben Hansen, Caroline Hayward, M. Arfan Ikram, J. Wouter Jukema, Sharon L. R. Kardia, Leslie A. Lange, Winfried März, Rasika A. Mathias, Braxton D. Mitchell, Dennis O. Mook-Kanamori, Pierre-Emmanuel Morange, Oluf Pedersen, Peter P. Pramstaller, Susan Redline, Alexander Reiner, Paul M. Ridker, Edwin K. Silverman, Tim D. Spector, Uwe Völker, Nicholas J. Wareham, James F. Wilson, Jie Yao, David-Alexandre Trégouët, Andrew D. Johnson, Alisa S. Wolberg, Paul S. de Vries, Maria Sabater-Lleal, Alanna C. Morrison, Nicholas L. Smith
Journal: Blood (2024)
Angiotensin-(1-9) Retro-Enantiomer Peptide With Cardioprotective Activity
Authors: Yvo Flores, Gerald Zapata-Torres, Agustín Nuñez, Douglas J. Matthies, Larissa Alemán, Carolina Hernández-Fuentes, Gina Sánchez, Eyleen Araya, Fanny Guzman, Zully Pedrozo, Salvador Guardiola, Mónica Varese, Ernest Giralt, Ivan Maslov, Mark Del Borgo, Robert E. Widdop, Silvana Valdebenito, Eliseo A. Eugenin, Mario Chiong, Joseph A. Hill, María Paz Ocaranza, Marcelo J. Kogan, Sergio Lavandero
Journal: Circulation (2024)
Dynamic compliance penis enlargement patch
Authors: Rui Zheng, Wenwen Zhong, Muyuan Chai, Xuetao Shi
Journal: Bioactive Materials (2024)

Men are particularly sensitive to penis size, especially those with a deformed or injured penis. This can lead to a strong desire for penis enlargement surgery. Given the ethical sensitivities of the penis, penile implants need to be developed with both efficacy and safety. In this study, a polyvinyl alcohol (PVA) patch for penile enlargement prepared via cyclic freeze‒thaw cycles and alkaline treatment. The PVA hydrogels treated with 5 M NaOH had the best mechanical properties and stability. A negative Poisson's ratio structure is incorporated into the design of the enlargement patch, which allows it to conform well to the deformation of the penis. In rabbit models, the enlarged patches can effectively enlarge the penis without degradation or fibrosis while maintaining long-term stability
Versatile effects of galectin-1 protein-containing lipid bilayer coating for cardiovascular applications
Authors: Md Lemon Hasan, Ju Ro Lee, Khandoker Asiqur Rahaman, Dae Hyeok Yang, Yoon Ki Joung
Journal: Bioactive Materials (2024)

Modulating inflammatory cells in an implantation site leads to severe complications and still unsolved challenges for blood-contacting medical devices. Inspired by the role of galectin-1 (Gal-1) in selective functions on multiple cells and immunomodulatory processes, we prepared a biologically target-specific surface coated with the lipid bilayer containing Gal-1 (Gal-1-SLB) and investigate the proof of the biological effects. First, lipoamido-dPEG-acid was deposited on a gold-coated substrate to form a self-assembled monolayer and then conjugated dioleoylphosphatidylethanolamine (DOPE) onto that to produce a lower leaflet of the supported lipid bilayer (SLB) before fusing membrane-derived vesicles extracted from B16-F10 cells. The Gal-1-SLB showed the expected anti-fouling activity by revealing the resistance to protein adsorption and bacterial adhesion.
Low-Dose Iron and Early Development in Breastfed Infants
Authors: Hong-Kun Jiang, Wan-Lin Cui
Journal: JAMA Pediatrics (2024)

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