tbuckley/cabot-search huggingface dataset:
New-generation advanced PROTACs as potential therapeutic agents in cancer therapy
Authors: Chao Wang, Yujing Zhang, Wujun Chen, Yudong Wu, Dongming Xing
Journal: Molecular Cancer (2024)

Abstract Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit the endogenous E3 ubiquitin ligases to facilitate degradation of the proteins of interest (POIs) through the ubiquitin–proteasome system (UPS) in a cyclic catalytic manner. Despite recent endeavors to advance the utilization of PROTACs in clinical settings, the majority of PROTACs fail to progress beyond the preclinical phase of drug development. There are multiple factors impeding the market entry of PROTACs, with the insufficiently precise degradation of favorable POIs standing out as one of the most formidable obstacles. Recently, there has been exploration of new-generation advanced PROTACs, including small-molecule PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, to improve the in vivo efficacy of PROTACs. These improved PROTACs possess the capability to mitigate undesirable physicochemical characteristics inherent in traditional PROTACs, thereby enhancing their targetability and reducing off-target side effects. The new-generation of advanced PROTACs will mark a pivotal turning point in the realm of targeted protein degradation. In this comprehensive review, we have meticulously summarized the state-of-the-art advancements achieved by these cutting-edge PROTACs, elucidated their underlying design principles, deliberated upon the prevailing challenges encountered, and provided an insightful outlook on future prospects within this burgeoning field.
Erratum to “EASL Clinical Practice Guidelines on acute-on-chronic liver failure” [J Hepatol 79 (2023) 461–491]
Authors: Richard Moreau, Marta Tonon, Aleksander Krag, Paolo Angeli, Marina Berenguer, Annalisa Berzigotti, Javier Fernandez, Claire Francoz, Thierry Gustot, Rajiv Jalan, Maria Papp, Jonel Trebicka
Journal: Journal of Hepatology (2024)

It has come to our attention that an error was introduced during the production of this manuscript. In the Venn diagram the colours of the circles for 'GI haemorrhage with shock' and 'Severe alcohol-related hepatitis' were reversed. The corrected figure is provided below. The authors and the editorial office apologize for any inconvenience caused.
Biomaterials-enabled electrical stimulation for tissue healing and regeneration
Authors: Han-Sem Kim, Tanza Baby, Jung-Hwan Lee, Ueon Sang Shin, Hae-Won Kim
Journal: Med-X (2024)

Abstract The electrical microenvironment is considered a pivotal determinant in various pathophysiological processes, including tissue homeostasis and wound healing. Consequently, extensive research endeavors have been directed toward applying electricity to cells and tissues through external force devices or biomaterial-based platforms. In addition to in situ electroconductive matrices, a new class of electroactive biomaterials responsive to stimuli has emerged as a focal point of interest. These electroactive materials, in response to intrinsic biochemical (e.g., glucose) or external physical stimuli (e.g., light, magnetism, stress), hold significant potential for cell stimulation and tissue regeneration. In this communication, we underscore this distinct category of electroactive biomaterials, discussing the currently developed biomaterial platforms and their biological roles in stimulating cells and tissues during the healing and regeneration process. We also critically evaluate the inherent limitations and challenges of these biomaterials while offering forward-looking insights into their promise for future clinical translations. Graphical Abstract
Safety and Efficacy of 177Lu-DOTATATE in Children and Young Adult Population
Authors: Piyush Aggarwal, Swayamjeet Satapathy, Ashwani Sood, Harmandeep Singh, Bhagwant Rai Mittal, Sadhna Lal, Rajesh Gupta, Chandan Krushna Das, Thakur Deen Yadav, Rama Walia
Journal: Clinical Nuclear Medicine (2024)

This single-center retrospective study explores the safety and efficacy of 177 Lu-DOTATATE in children and young adult population with metastatic/inoperable neuroendocrine tumors (NETs).
The wild side of grape genomics
Authors: Dario Cantu, Mélanie Massonnet, Noé Cochetel
Journal: Trends in Genetics (2024)

With broad genetic diversity and as a source of key agronomic traits, wild grape species (Vitis spp.) are crucial to enhance viticulture's climatic resilience and sustainability. This review discusses how recent breakthroughs in the genome assembly and analysis of wild grape species have led to discoveries on grape evolution, from wild species' adaptation to environmental stress to grape domestication. We detail how diploid chromosome-scale genomes from wild Vitis spp. have enabled the identification of candidate disease-resistance and flower sex determination genes and the creation of the first Vitis graph-based pangenome. Finally, we explore how wild grape genomics can impact grape research and viticulture, including aspects such as data sharing, the development of functional genomics tools, and the acceleration of genetic improvement.
CLINICAL PROGNOSTIC FACTORS FOR OLDER PEOPLE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nicola Veronese, Anna Fazzari, Maria Armata, Angela Parisi, Alessandra Parrinello, Valentina Petralia, Carlo Saccaro, Miriam Vesco, Federica Tagliaferri, Veronica Andrea Fittipaldo, Jacopo Demurtas, Lee Smith, Ligia J. Dominguez, Alberto Pilotto, Mario Barbagallo
Journal: Ageing Research Reviews (2024)

To explore the accuracy and precision of prognostic tools used in older people in predicting mortality, hospitalization, and nursing home admission across different settings and timings.
Growing up with juvenile vulvar lichen sclerosus, the experiences and care needs of adult women with lichen sclerosus since childhood: a qualitative exploration
Authors: Beth Morrel, H Janneke Kampherbeek, Marianne J ten Kate-Booij, Irene A M van der Avoort, Colette L M van Hees, Kiki M G J Wigny, Curt W Burger, Suzanne G M A Pasmans, Marjolein Lugtenberg
Journal: British Journal of Dermatology (2024)

Abstract Background Vulvar lichen sclerosus (VLS) is a chronic remitting condition that affects the genital skin of females of all ages. Although qualitative studies have been conducted that have focused on women with VLS in mid-life or beyond, less is known about the experiences of individuals with VLS from childhood or adolescence onward. Objectives To gain an understanding of the experiences of women with a history of juvenile VLS (JVLS) with regard to the impact of the disease on their personal lives, and their experiences and needs regarding care and guidance. Methods A qualitative study was conducted consisting of 27 in-depth face-to-face interviews with adult women with a histologically confirmed history of JVLS, striving for maximum variation and saturation. Interviews were audio recorded and transcribed verbatim. A thorough thematic content analysis was performed. Results Three main themes were identified. Theme 1 was named ‘Varying impact of living with JVLS’: women experienced diverse emotional and physical impacts, from shame and denial to complete acceptance, from restrictions in daily functioning to no limitations; they felt hindered by their own lack of knowledge about JVLS and generally expressed positivity in sharing their experiences with people close to them. Theme 2 was entitled ‘Finding one’s way in care and guidance’: while navigating care and guidance, women often felt hindered by knowledge gaps among healthcare professionals (HCPs), lack of continuity in care and guidance, lack of life phase-adjusted and future-oriented information provision, inadequate guidance around life events and insufficient monitoring of determinants of treatment adherence. Theme 3 was named ‘Need for patient-tailored care involving appropriate and compassionate care and guidance’: patients stressed the need for age-appropriate and life phase-adjusted information, guidance around life events and compassionate contact with knowledgeable HCPs aware of the determinants of treatment adherence and influencing factors. Conclusions Age-appropriate, life phase-adjusted, individually tailored care for women diagnosed with VLS in childhood or adolescence is needed. Care and guidance from childhood onward should encompass a standard of care adapted to the individual as their needs change over time. This involves taking interpersonal differences into account, including differences in support network and coping strategies. These findings demonstrate the need to improve awareness and knowledge about JVLS/VLS among HCPs, especially primary care providers, and among the general public.
Unraveling the hypoxic puzzle: LncRNA LUCAT1 drives glioblastoma in cooperation with HIF1⍺
Authors: Ying Zhang, Kadie Hudson, Roger Abounader
Journal: Neuro-Oncology (2024)

Journal Article Accepted manuscript Unraveling the hypoxic puzzle: LncRNA LUCAT1 drives glioblastoma in cooperation with HIF1⍺ Get access Ying Zhang, Ying Zhang Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Kadie Hudson, Kadie Hudson Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger Abounader Roger Abounader Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA, USADepartment of Neurology, University of Virginia, Charlottesville, VA, USAUniversity of Virginia Comprehensive Cancer Center, University of Virginia, Charlottesville, VA, USA Correspondence to Roger Abounader, University of Virginia, 21 Hospital Drive, Room 4819, Charlottesville, VA 22908, USA. Email: ra6u@virginia.edu; Phone: 1-434-982-6634 https://orcid.org/0000-0003-4075-9460 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae096, https://doi.org/10.1093/neuonc/noae096 Published: 21 May 2024 Article history Received: 01 May 2024 Published: 21 May 2024
Consensus Review on Strategies to Improve Delivery Across the BBB Including Focused Ultrasound
Authors: Keaton Piper, Jay I Kumar, Joseph Domino, Chad Tuchek, Michael A Vogelbaum
Journal: Neuro-Oncology (2024)

Abstract Drug delivery to the central nervous system (CNS) has been a major challenge for CNS tumors due to the impermeability of the blood-brain barrier (BBB). There has been a multitude of techniques aimed at overcoming the BBB obstacle aimed at utilizing natural transport mechanisms or bypassing the BBB which we review here. Another approach that has generated recent interest in the recently published literature is to use new technologies (Laser Interstitial Thermal Therapy, LITT; or Low-Intensity Focused Ultrasound, LIFU) to temporarily increase BBB permeability. This review overviews the advantages, disadvantages, and major advances of each method. LIFU has been a major area of research to allow for chemotherapeutics to cross the BBB which has a particular emphasis in this review. While most of the advances remain in animal studies, there are an increasing number of translational clinical trials that will have results in the next few years.
European Society of Intensive Care Medicine clinical practice guideline on fluid therapy in adult critically ill patients. Part 1: the choice of resuscitation fluids
Authors: Yaseen M Arabi, Emilie Belley-Cote, Andrea Carsetti, Daniel De Backer, Katia Donadello, Nicole P Juffermans, Naomi Hammond, Jon Henrik Laake, Dawei Liu, Kathryn Maitland, Antonio Messina, Morten Hylander Møller, Daniele Poole, Rob Mac Sweeney, Jean-Louis Vincent, Fernando G Zampieri, Fayez AlShamsi
Journal: Intensive Care Medicine (2024)
US Public Health Preparedness and Response to Highly Pathogenic Avian Influenza A(H5N1) Viruses
Authors: Noah Kojima, Amelia Blumberg, Rachel Radcliffe, Brendan Flannery, Timothy M. Uyeki
Journal: JAMA (2024)

US public health preparedness and response to highly pathogenic avian influenza A(H5N1) viruses are assessed in this survey study conducted by the CDC.
Hydrogen Attenuates Cognitive Impairment in Rat Models of Vascular Dementia by Inhibiting Oxidative Stress and NLRP3 Inflammasome Activation
Authors: Congwen Yang, Yuxuan He, Shuang Ren, Yiqin Ding, Xinru Liu, Xue Li, Hao Sun, Dezhi Jiao, Haolin Zhang, Yingshuai Wang, Lin Sun
Journal: Advanced Healthcare Materials (2024)

Vascular dementia (VaD) is the second most common form of dementia worldwide. Oxidative stress and neuroinflammation are important factors contributing to cognitive dysfunction in patients with VaD. The antioxidant and anti-inflammatory properties of hydrogen are increasingly being utilized in neurological disorders, but conventional hydrogen delivery has the disadvantage of inefficiency. Therefore, magnesium silicide nanosheets (MSNs) are used to release hydrogen in vivo in larger quantities and for longer periods of time to explore the appropriate dosage and regimen. In this study, it is observed that hydrogen improved learning and working memory in VaD rats in the Morris water maze and Y-maze, which elicits improved cognitive function. Nissl staining of neurons shows that hydrogen treatment significantly improves edema in neuronal cells. The expression and activation of reactive oxygen species (ROS), Thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), caspase-1, and IL-1β in the hippocampus are measured via ELISA, Western blotting, real-time qPCR, and immunofluorescence. The results show that oxidative stress indicators and inflammasome-related factors are significantly decreased after 7dMSN treatment. Therefore, it is concluded that hydrogen can ameliorate neurological damage and cognitive dysfunction in VaD rats by inhibiting ROS/NLRP3/IL-1β-related oxidative stress and inflammation.
Generalization—a key challenge for responsible AI in patient-facing clinical applications
Authors: Lea Goetz, Nabeel Seedat, Robert Vandersluis, Mihaela van der Schaar
Journal: npj Digital Medicine (2024)

Generalization – the ability of AI systems to apply and/or extrapolate their knowledge to new data which might differ from the original training data – is a major challenge for the effective and responsible implementation of human-centric AI applications. Current debate in bioethics proposes selective prediction as a solution. Here we explore data-based reasons for generalization challenges and look at how selective predictions might be implemented technically, focusing on clinical AI applications in real-world healthcare settings.
Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation
Authors: Soon-Gook Hong, Julianne W Ashby, John P Kennelly, Meigan Wu, Michelle Steel, Eesha Chattopadhyay, Rob Foreman, Peter Tontonoz, Elizabeth J Tarling, Patric Turowski, Marcus Gallagher-Jones, Julia J Mack
Journal: Journal of Clinical Investigation (2024)

Endothelial cells (ECs) in the descending aorta are exposed to high laminar shear stress, and this supports an anti-inflammatory phenotype. High laminar shear stress also induces flow-aligned cell elongation and front-rear polarity, but whether these are required for the anti-inflammatory phenotype is unclear. Here, we showed that Caveolin-1-rich microdomains polarize to the downstream end of ECs that are exposed to continuous high laminar flow. These microdomains were characterized by high membrane rigidity, filamentous actin (F-actin), and raft-associated lipids. Transient receptor potential vanilloid-type 4 (TRPV4) ion channels were ubiquitously expressed on the plasma membrane but mediated localized Ca2+ entry only at these microdomains where they physically interacted with clustered Caveolin-1. These focal Ca2+ bursts activated endothelial nitric oxide synthase (eNOS) within the confines of these domains. Importantly, we found that signaling at these domains required both cell body elongation and sustained flow. Finally, TRPV4 signaling at these domains was necessary and sufficient to suppress inflammatory gene expression, and exogenous activation of TRPV4 channels ameliorated the inflammatory response to stimuli both in vitro and in vivo. Our work revealed a polarized mechanosensitive signaling hub in arterial ECs that dampens inflammatory gene expression and promotes cell resilience.
Assessment of Macrovascular Invasion in Advanced Hepatocellular Carcinoma: Clinical Implications and Treatment Outcomes with Systemic Therapy
Authors: Masanori Inoue, Sadahisa Ogasawara, Kazufumi Kobayashi, Tomomi Okubo, Norio Itokawa, Masamichi Obu, Kentaro Fujimoto, Hidemi Unozawa, Sae Yumita, Kisako Fujiwara, Miyuki Nakagawa, Hiroaki Kanzaki, Keisuke Koroki, Soichiro Kiyono, Masato Nakamura, Naoya Kanogawa, Takayuki Kondo, Shingo Nakamoto, Kengo Nagashima, Ei Itobayashi, Masanori Atsukawa, Yoshihiro Koma, Ryosaku Azemoto, Naoya Kato
Journal: Liver Cancer (2024)

Macrovascular invasion (MVI) is a strong prognostic factor for advanced hepatocellular carcinoma (HCC). The current criteria for radiological assessment are unclear in evaluating the impact of MVI on systemic therapy. In this study, we standardized the assessment of MVI and validated its clinical relevance. Clinical data were collected from patients with advanced HCC and MVI who received first-line systemic therapy at four medical centers in Japan. First, we used MVI progressive disease (MVI-PD) to track MVI progression and Response Evaluation Criteria in Solid Tumors version 1.1 progressive disease (RECIST v1.1-PD) to evaluate tumor enlargement other than MVI and the appearance of new lesions. Next, we assessed the prognostic value of MVI-PD and RECIST v1.1-PD. Of the 207 advanced HCC patients with MVI, 189 received appropriate imaging evaluation. Forty (21.2%) patients had MVI-PD and RECIST v1.1-PD, 51 (27.0%) had prior MVI-PD, and 61 (32.3%) had prior RECIST v1.1-PD. In a landmark analysis, the prognosis of 163 patients who survived more than 3 months was analyzed based on the assessment of imaging response during the first 3 months. The median overall survival (OS) was 5.4 months in those who had MVI-PD and RECIST v1.1-PD, 7.4 months in those who had RECIST v1.1-PD only, 7.2 months in those who had MVI-PD only, and 19.7 months in patients who had neither (p < 0.001). The correlation coefficients between progression-free survival and OS in patients with appropriate imaging assessments were similar for MVI-PD (0.515) and RECIST v1.1-PD (0.498). Our findings demonstrate the link between MVI progression and poor OS in systemic therapy for advanced HCC, emphasizing the importance of an accurate method for assessing MVI progression.
Final results of RIGHT Choice: Ribociclib plus endocrine therapy vs combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2− advanced breast cancer
Authors: Yen-Shen Lu, Eznal Izwadi Bin Mohd Mahidin, Hamdy Azim, Yesim Eralp, Yoon Sim Yap, Seock-Ah Im, Julie Rihani, Erhan Gokmen, Ahmed El Bastawisy, Nuri Karadurmus, Yueh Ni Lim, Chun Sen Lim, Le Thanh Duc, Wei-Pang Chung, K. Govind Babu, Konstantin Penkov, James Bowles, Teresa Delgar Alfaro, Jiwen Wu, Melissa Gao, Khemaies Slimane, Nagi S. El Saghir, Adher Alsayed, Ahmed El Bastawisy, Ajay Gogia, Chaiyut Charoentum, Chanchal Goswami, Chien-Ting Liu, Chun Sen Lim, Elena Artamonova, Erhan Gokmen, Esat Namal, Eznal Izwadi Mohd Mahidin, Fadi Farhat, Flora Chong Li Tze, Gül Başaran, Hakan Harputluoglu, Hamdy Abdel Azim, Hikmat Abdelrazeq, Hesham ElGhazaly, K. Govind Babu, Konstantin Penkov, Le Thanh Duc, Ling-Ming Tseng, Liudmila Osmanova, Ludmila Zhukova, Meher Lakshmi Konatum, Mehmet Ali Nahit Şendur, Ming-Shen Dai, Mona Ayoubi, Nagi El-Saghir, Naiyarat Prasongsook, Napa Parinyanitikul, Nikita Volkov, Nuri Karadurmus, Patrapim Sunpaweravong, Peter Cher Siang Ang, Pei Jye Voon, Rabab Gaafar, Rasha Abdel Motagaly, Richard Khanyile, Sema Sezgin Goksu, Shin-Cheh Chen, Sudeep Gupta, Su Mien Lynette Ngo, Swee Hsia Choong, Terence Aik Huang Tan, Umut Demirci, Wei-Pang Chung, Wen-Son Hsieh, Yen-Shen Lu, Yesim Eralp, Yoon Sim Yap, Yuan-Ching Chang, Yueh Ni Lim
Journal: Journal of Clinical Oncology (2024)

A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).
Cost-effectiveness of the Baveno VI criteria compared to endoscopy for high-risk varices in patients with Child Pugh A cirrhosis
Authors: Elena Pizzo, Tuba Saygın Avşar, Juan G. Abraldes, Joan Genesca, Emmanuel A. Tsochatzis
Journal: Clinical Gastroenterology and Hepatology (2024)

Although upper gastrointestinal endoscopy (EGD) remains the gold standard for detecting varices in cirrhosis, the Baveno VI criteria proposed a combination of transient elastography and platelet count that could rule out high-risk varices, therefore sparing the need for an endoscopy, with significant potential cost savings. We performed a cost-effectiveness analysis of the Baveno VI criteria compared with EGD in the diagnosis of high-risk varices in cirrhosis.
TNIK’s emerging role in cancer, metabolism, and age-related diseases
Authors: Collin Y. Ewald, Fadi E. Pulous, Sarah Wing Yan Lok, Frank W. Pun, Alex Aliper, Feng Ren, Alex Zhavoronkov
Journal: Trends in Pharmacological Sciences (2024)

Traf2- and Nck-interacting kinase (TNIK) has emerged as a key regulator of pathological metabolic signaling in several diseases and is a promising drug target. Originally studied for its role in cell migration and proliferation, TNIK possesses several newly identified functions that drive the pathogenesis of multiple diseases. Specifically, we evaluate TNIK's newfound roles in cancer, metabolic disorders, and neuronal function. We emphasize the implications of TNIK signaling in metabolic signaling and evaluate the translational potential of these discoveries. We also highlight how TNIK's role in many biological processes converges upon several hallmarks of aging. We conclude by discussing the therapeutic landscape of TNIK-targeting drugs and the recent success of clinical trials targeting TNIK.