tbuckley/cabot-search huggingface dataset:
Aging of the eye: Lessons from cataracts and age-related macular degeneration
Authors: Ales Cvekl, Jan Vijg
Journal: Ageing Research Reviews (2024)

Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand the effects of the aging process on these diseases, including the genetic, molecular, and cellular mechanisms that underlie the increased risk of disease over the lifetime. Understanding of the aging eye increases general knowledge of the cellular physiology impacted by aging processes at various biological extremes. Two major diseases, age-related cataract and age-related macular degeneration (AMD) are caused by dysfunction of the lens and retina, respectively. Lens transparency and light refraction are mediated by lens fiber cells lacking nuclei and other organelles, which provides a unique opportunity to study a single aging hallmark, i.e., loss of proteostasis, within an environment of limited metabolism. In AMD, local dysfunction of the photoreceptors/retinal pigmented epithelium/Bruch's membrane/choriocapillaris complex in the macula leads to the loss of photoreceptors and eventually loss of central vision, and is driven by nearly all the hallmarks of aging and shares features with Alzheimer's disease, Parkinson's disease, cardiovascular disease, and diabetes. The aging eye can function as a model for studying basic mechanisms of aging and, vice versa, well-defined hallmarks of aging can be used as tools to understand age-related eye disease.
Human DNA-dependent protein kinase catalytic subunit deficiency: A comprehensive review and update
Authors: Jihane Adelon, Hassan Abolhassani, Saliha Esenboga, Fanny Fouyssac, Deniz Cagdas, Ilhan Tezcan, Barıs Kuskonmaz, Duygu Cetinkaya, Felipe Suarez, Seyed Alireza Mahdaviani, Samira Plassart, Anne-Laure Mathieu, Nicole Fabien, Christophe Malcus, Florence Morfin-Sherpa, Geneviève Billaud, Maud Tusseau, Sarah Benezech, Thierry Walzer, Jean-Pierre De Villartay, Yves Bertrand, Alexandre Belot
Journal: Journal of Allergy and Clinical Immunology (2024)
Vitamins and fatty acids against chemotherapy-induced intestinal mucositis
Authors: Alexandra Alcorta, Laura López-Gómez, Raffaele Capasso, Raquel Abalo
Journal: Pharmacology & Therapeutics (2024)

Chemotherapy has allowed an increase in cancer survivorship, but it causes important adverse effects. Mucositis affecting the gastrointestinal tract is one of the main problems acutely caused by many antineoplastic drugs, such as 5-fluorouracil or methotrexate. Mucositis may cause pain, diarrhea, anorexia, weight loss, systemic infections and even death. This narrative review focuses on intestinal mucositis and the role that some nutraceuticals, namely vitamins (both lipid- and water-soluble) as well as fatty acids (FAs) and lipid-based products, can have in it. In preclinical (cell cultures, animal models) and/or human studies, vitamins A, D, E, B2, B9 and C, omega-3 long-chain FAs (eicosapentaenoic, docosahexaenoic, conjugated linoleic acid), short-chain FAs (mainly butyrate), medium-chain FAs (capric acid), and different lipid-based products (emu oil, extra-virgin olive oil, lipid replacement therapy), enriched in beneficial FAs and natural antioxidants, were shown to exert beneficial effects (both preventative and palliative) against chemotherapy-induced intestinal mucositis. Although the exact mechanisms of action involved in these effects are not yet well known, our review highlights the interest of investigating on diet and nutrition to implement scientifically robust strategies to improve protection of cancer patients against chemotherapy-induced adverse effects.
Induction of steatosis in primary human hepatocytes recapitulates key pathophysiological aspects of metabolic dysfunction-associated steatotic liver disease
Authors: Yun Kwon, Pascal Gottmann, Surui Wang, Joel Tissink, Karsten Motzler, Revathi Sekar, Wiebke Albrecht, Cristina Cadenas, Jan G. Hengstler, Annette Schürmann, Anja Zeigerer
Journal: Journal of Hepatology (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Owing to limited available treatment options, novel pre-clinical models for target selection and drug validation are warranted. We have established and extensively characterized a primary human steatotic hepatocyte in vitro model system that could guide the development of treatment strategies for MASLD.
Strategies for intravesical drug delivery: From bladder physiological barriers and potential transport mechanisms
Authors: Zheng-an Li, Kai-chao Wen, Ji-heng Liu, Chuan Zhang, Feng Zhang, Feng-qian Li
Journal: Acta Pharmaceutica Sinica B (2024)

Intravesical drug delivery (IDD), as a noninvasive, local pathway of administration, has great clinical significance for bladder diseases, especially bladder cancer. Despite the many advantages of IDD such as enhanced focal drug exposure and avoidance of systemic adverse drug reactions, the effectiveness of drug delivery is greatly challenged by the physiological barriers of the bladder. In this review, the routes and barriers encountered in IDD are first discussed, and attention is paid to the potential internal/mucosal retention and absorption-transport mechanisms of drugs. On this basis, the avoidance, overcoming and utilization of the "three barriers" is further emphasized, and current design and fabrication strategies for intravesical drug delivery systems (IDDSs) are described mainly from the perspectives of constructing drug reservoirs, enhancing permeability and targeting, with the hope of providing systematic understanding and inspirations for the research of novel IDDSs and their treatment of bladder diseases.
Dynamic Immunoediting by Macrophages in Homologous Recombination Deficiency-Stratified Pancreatic Ductal Adenocarcinoma
Authors: Wei-Feng Hong, Feng Zhang, Nan Wang, Jun-Ming Bi, Ding-Wen Zhang, Lu-Sheng Wei, Zhen-Tao Song, Gordon B Mills, Min-Min Chen, Xue-Xin Li, Shi-Suo Du, Min Yu
Journal: Drug Resistance Updates (2024)
Target fishing and mechanistic insights of the natural anticancer drug candidate chlorogenic acid
Authors: Qinghua Wang, Tingting Du, Zhihui Zhang, Qingyang Zhang, Jie Zhang, Wenbin Li, Jian-Dong Jiang, Xiaoguang Chen, Hai-Yu Hu
Journal: Acta Pharmaceutica Sinica B (2024)

Chlorogenic acid (CGA) is a natural product that effectively inhibits tumor growth, demonstrated in many preclinical models, and phase II clinical trials for patients with glioma. However, its direct proteomic targets and anticancer molecular mechanisms remain unknown. Herein, we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) was one of the main target proteins of CGA by using affinity-based protein profiling (AfBPP) chemical proteomic approach. We performed in-depth studies on ACAT1/CGA interactions
Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022
Authors: R.A. Freedman, H.M. Heiling, T. Li, D. Trapani, N. Tayob, K.L. Smith, R. Davis, A.M. Pereslete, M.K. DeMeo, C. Cotter, W.Y. Chen, H.A. Parsons, C.A. Santa-Maria, C. Van Poznak, B. Moy, A.M. Brufsky, M.E. Melisko, C.C. O’Sullivan, N. Ashai, Y. Rauf, J.R. Nangia, R.T. Burns, J. Savoie, A.C. Wolff, E.P. Winer, M.F. Rimawi, I.E. Krop, N.U. Lin
Journal: Annals of Oncology (2024)

Treatment options for human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases (BCBMs) remain limited. We previously reported central nervous system (CNS) activity for neratinib and neratinib-capecitabine. Preclinical data suggest that neratinib may overcome resistance to ado-trastuzumab emtansine (T-DM1) when given in combination. In Translational Breast Cancer Research Consortium (TBCRC) 022's cohort 4, we examined the efficacy of neratinib plus T-DM1 in patients with HER2-positive BCBM.
3D-printed Bone Regeneration Scaffolds Modulate Bone Metabolic Homeostasis through Vascularization for Osteoporotic Bone Defects
Authors: Caiping Yan, Pengrui Zhang, Qiwei Qin, Ke Jiang, Yue Luo, Chao Xiang, Jiangtao He, Lu Chen, Dianming Jiang, Wenguo Cui, Yuling Li
Journal: Biomaterials (2024)
Accuracy of dental implant placement using different dynamic navigation and robotic systems: an in vitro study
Authors: Zonghe Xu, Lin Zhou, Bin Han, Shuang Wu, Yanjun Xiao, Sihui Zhang, Jiang Chen, Jianbin Guo, Dong Wu
Journal: npj Digital Medicine (2024)

Abstract Computer-aided implant surgery has undergone continuous development in recent years. In this study, active and passive systems of dynamic navigation were divided into active dynamic navigation system group and passive dynamic navigation system group (ADG and PDG), respectively. Active, passive and semi-active implant robots were divided into active robot group, passive robot group and semi-active robot group (ARG, PRG and SRG), respectively. Each group placed two implants (FDI tooth positions 31 and 36) in a model 12 times. The accuracy of 216 implants in 108 models were analysed. The coronal deviations of ADG, PDG, ARG, PRG and SRG were 0.85 ± 0.17 mm, 1.05 ± 0.42 mm, 0.29 ± 0.15 mm, 0.40 ± 0.16 mm and 0.33 ± 0.14 mm, respectively. The apical deviations of the five groups were 1.11 ± 0.23 mm, 1.07 ± 0.38 mm, 0.29 ± 0.15 mm, 0.50 ± 0.19 mm and 0.36 ± 0.16 mm, respectively. The axial deviations of the five groups were 1.78 ± 0.73°, 1.99 ± 1.20°, 0.61 ± 0.25°, 1.04 ± 0.37° and 0.42 ± 0.18°, respectively. The coronal, apical and axial deviations of ADG were higher than those of ARG, PRG and SRG (all P &lt; 0.001). Similarly, the coronal, apical and axial deviations of PDG were higher than those of ARG, PRG, and SRG (all P &lt; 0.001). Dynamic and robotic computer-aided implant surgery may show good implant accuracy in vitro. However, the accuracy and stability of implant robots are higher than those of dynamic navigation systems.
Advances in nucleic acid-targeted therapies for cardiovascular disease prevention
Authors: Umidakhon Makhmudova, Elisabeth Steinhagen-Thiessen, Massimo Volpe, Ulf Landmesser
Journal: Cardiovascular Research (2024)

Abstract Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques. Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen (AGT) are produced. Current targets in lipid metabolism include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (ApoA), apolipoprotein C3 (ApoC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing low-density lipoprotein receptor deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production. This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.
Impact of epidermal growth factor receptor and mitogen-activated kinase inhibition on hair follicles (HFs): partial HF immune privilege collapse and excessive interleukin-33 secretion
Authors: Keitaro Fukuda
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Impact of EGFR and MEK inhibition on hair follicles: partial hair follicle immune privilege collapse and excessive IL-33 secretion Get access Keitaro Fukuda Keitaro Fukuda Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, JapanDepartment of Dermatology, Keio University School of Medicine, Tokyo, Japan Corresponding author: Email:keitaro.fukuda@riken.jp https://orcid.org/0000-0001-8847-0063 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae284, https://doi.org/10.1093/bjd/ljae284 Published: 06 July 2024 Article history Received: 01 July 2024 Revision received: 02 July 2024 Accepted: 04 July 2024 Published: 06 July 2024
Deep learning for multi-type infectious keratitis diagnosis: A nationwide, cross-sectional, multicenter study
Authors: Zhongwen Li, He Xie, Zhouqian Wang, Daoyuan Li, Kuan Chen, Xihang Zong, Wei Qiang, Feng Wen, Zhihong Deng, Limin Chen, Huiping Li, He Dong, Pengcheng Wu, Tao Sun, Yan Cheng, Yanning Yang, Jinsong Xue, Qinxiang Zheng, Jiewei Jiang, Wei Chen
Journal: npj Digital Medicine (2024)

Abstract The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves &gt; 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment.
Listening to animal behavior to understand changing ecosystems
Authors: William K. Oestreich, Ruth Y. Oliver, Melissa S. Chapman, Madeline C. Go, Megan F. McKenna
Journal: Trends in Ecology & Evolution (2024)

Interpreting sound gives powerful insight into the health of ecosystems. Beyond detecting the presence of wildlife, bioacoustic signals can reveal their behavior. However, behavioral bioacoustic information is underused because identifying the function and context of animals' sounds remains challenging. A growing acoustic toolbox is allowing researchers to begin decoding bioacoustic signals by linking individual and population-level sensing. Yet, studies integrating acoustic tools for behavioral insight across levels of biological organization remain scarce. We aim to catalyze the emerging field of behavioral bioacoustics by synthesizing recent successes and rising analytical, logistical, and ethical challenges. Because behavior typically represents animals' first response to environmental change, we posit that behavioral bioacoustics will provide theoretical and applied insights into animals' adaptations to global change.
Coverage with evidence development program on stereotactic body radiotherapy in Belgium (2013–2019): a nationwide registry-based prospective study
Authors: Yolande Lievens, Sharon Janssens, Maarten Lambrecht, Hilde Engels, Xavier Geets, Nicolas Jansen, Luigi Moretti, Vincent Remouchamps, Sander Roosens, Karin Stellamans, Dirk Verellen, Caroline Weltens, Reinhilde Weytjens, Nancy Van Damme
Journal: The Lancet Regional Health - Europe (2024)

Although stereotactic body radiotherapy (SBRT) was progressively adopted in clinical practice in Belgium, a reimbursement request in 2011 was not granted because of remaining clinical and economic uncertainty. A coverage with evidence development (CED) program on SBRT started in 2013, with the aim to assess clinical and technical patterns-of-care in Belgium and monitor survival per indication, in view of supporting inclusion in the reimbursement system.
Re: Vipul Patel, Jacques Marescaux, Marcio Covas Moschovas. The Humanitarian Impact of Telesurgery and Remote Surgery in Global Medicine. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.04.029
Authors: Chang-Kun Mao, Tao Zhang, Jun-Ting Li
Journal: European Urology (2024)
Reply to Chang-Kun Mao, Tao Zhang, and Jun-Ting Li’s Letter to the Editor re: Vipul Patel, Jacques Marescaux, Marcio Covas Moschovas. The Humanitarian Impact of Telesurgery and Remote Surgery in Global Medicine. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.04.029
Authors: Marcio Covas Moschovas, Vipul Patel
Journal: European Urology (2024)
Obesity-induced chronic low-grade inflammation in adipose tissue: A pathway to Alzheimer’s disease
Authors: Zhai Weijie, Zhao Meng, Wei Chunxiao, Meng Lingjie, Zhao Anguo, Zhang Yan, Cui Xinran, Xu Yanjiao, Sun Li
Journal: Ageing Research Reviews (2024)

Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, and insulin resistance (IR), which contribute substantially to the development of AD and subsequent morbidity and mortality. Adipose tissue (AT) is a highly dynamic organ composed of a diverse array of cell types, which can be classified based on their anatomic localization or cellular composition. The expansion and remodeling of AT in the context of obesity involves immunometabolic and functional shifts steered by the intertwined actions of multiple immune cells and cytokine signaling within AT, which contribute to the development of metabolic disorders, IR, and systemic markers of chronic low-grade inflammation. Chronic low-grade inflammation, a prolonged, low-dose stimulation by specific immunogens that can progress from localized sites and affect multiple organs throughout the body, leads to neurodystrophy, increased apoptosis, and disruption of homeostasis, manifesting as brain atrophy and AD-related pathology. In this review, we sought to elucidate the mechanisms by which AT contributes to the onset and progression of AD in obesity through the mediation of chronic low-grade inflammation, particularly focusing on the roles of adipokines and AT-resident immune cells.
Pharmacological interventions for intraplaque neovascularization in atherosclerosis
Authors: Azizah Ugusman, Nur Syahidah Nor Hisam, Nur Syakirah Othman, Nur Najmi Mohamad Anuar, Adila A. Hamid, Jaya Kumar, Maisarah Md Razmi, Amilia Aminuddin
Journal: Pharmacology & Therapeutics (2024)
Pan-cancer Analysis Reveals m6A Variation and Cell-specific Regulatory Network in Different Cancer Types
Authors: Yao Lin, Jingyi Li, Shuaiyi Liang, Yaxin Chen, Yueqi Li, Yixian Cun, Lei Tian, Yuanli Zhou, Yitong Chen, Jiemei Chu, Hubin Chen, Qiang Luo, Ruili Zheng, Gang Wang, Hao Liang, Ping Cui, Sanqi An
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract As the most abundant messenger RNA (mRNA) modification, N6-methyladenosine (m6A) plays a crucial role in RNA fate, impacting cellular and physiological processes in various tumor types. However, our understanding of the role of the m6A methylome in tumor heterogeneity remains limited. Herein, we collected and analyzed m6A methylomes across nine human tissues from 97 m6A sequencing (m6A-seq) and RNA sequencing (RNA-seq) samples. Our findings demonstrate that m6A exhibits different heterogeneity in most tumor tissues compared to normal tissues, which contributes to the diverse clinical outcomes in different cancer types. We also found that the cancer type-specific m6A level regulated the expression of different cancer-related genes in distinct cancer types. Utilizing a novel and reliable method called “m6A-express”, we predicted m6A-regulated genes and revealed that cancer type-specific m6A-regulated genes contributed to the prognosis, tumor origin, and infiltration level of immune cells in diverse patient populations. Furthermore, we identified cell-specific m6A regulators that regulate cancer-specific m6A and constructed a regulatory network. Experimental validation was performed, confirming that the cell-specific m6A regulator CAPRIN1 controls the m6A level of TP53. Overall, our work reveals the clinical relevance of m6A in various tumor tissues and explains how such heterogeneity is established. These results further suggest the potential of m6A in cancer precision medicine for patients with different cancer types.
Physical Activity for Hypertensives
Authors: M. Abdelbaki
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

Hypertension and sport, far from being mutually exclusive, are complementary. However, the right type of sport (preferably those involving endurance exercise) should be judiciously recommended for the right hypertensive (rather mild hypertensives without left ventricular hypertrophy). As far as possible, the hypertensive subject should be discouraged from taking part in competitive and/or high-level sports. Physical activity needs to be an integral part of prescribers' therapeutic decisions, and in particular of the dietary hygiene rules (weight loss, elimination of tobacco, reduction in fat intake) that need to be indicated to all hypertensives, whether or not they are sportsmen or women at the time of diagnosis of hypertension.
Acute Coronary Syndrome and Essential Thrombocytemia: a Case Report
Authors: M. Abdelbaki
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

Essential thrombocythemia is a myeloproliferative syndrome that rarely complicates myocardial infarction. We report the observation of a 32-year-old man with no particular history admitted to the cardiology department for an acute coronary syndrome without ST-segment elevation from V3-V6 with elevated troponin. Subsequent coronary angiography revealed a thrombosis of the IVA between IVA 2 and IVA 3, with slight recurrence in the right network. The blood count showed an isolated thrombocytosis of 600,000/mm3. The evolution was favorable under BASIC treatment and hydrea-based treatment of hyperplaquettosis.