tbuckley/cabot-search huggingface dataset:
Hippophae Rhamnoides‐derived Phytomedicine Nano‐System Modulates Bax/Fas Pathways to Reduce Proliferation in Triple‐Negative Breast Cancer
Authors: Jabeen Farheen, M. Zubair Iqbal, Asim Mushtaq, Yike Hou, Xiangdong Kong
Journal: Advanced Healthcare Materials (2024)

Triple-negative breast cancer (TNBC) is the most common primary tumor of the breast with limited effectual drug availability. Therefore, the aim of the study is to develop an innovative phyto-nanomedicine (PNM) to cure TNBC with the least genotoxicity. Hereinafter, the sea buckthorn' extracted polyphenols (SBP), combine with metformin (MET), are synthesized as a novel PNM to evaluate its anti-tumor properties, effectiveness, and mechanism of action in TNBC in vitro and in vivo models. The SBP exhibits 16 new kinds of polyphenols that are been reported earlier which regulated cell development, proliferation, and programmed cell death (PCD) effectively. SBP-MET PNM inhibits MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%) cell proliferation but does not affect L929 normal murine cell development and successfully induce PCD (73.19%) in MDA-MB-231 cells. Mechanistically, in vivo SBP-MET proteome expression profiling reveals upregulation of proapoptotic Bax protein and activation of Fas signaling pathways convince downstream Daxx and FADD proteins, which further triggers Caspase-3 that prompts apoptosis in human TNBC cells by cleaving PARP-1 protein. Current findings establish innovative highly biocompatible phyto-nanomedicine that has significant potential to inhibit TNBC cell growth and induce regulated cell death (RCD) in vivo model, thereby opening a new arena for TNBC therapy.
Cardiovascular Management of Aortopathy in Children: A Scientific Statement From the American Heart Association
Authors: Shaine A. Morris, Jonathan N. Flyer, Anji T. Yetman, Emilio Quezada, Elizabeth S. Cappella, Harry C. Dietz, Dianna M. Milewicz, Maral Ouzounian, Christina M. Rigelsky, Seda Tierney, Ronald V. Lacro
Journal: Circulation (2024)

Aortopathy encompasses a spectrum of conditions predisposing to dilation, aneurysm, dissection, or rupture of the aorta and other blood vessels. Aortopathy is diagnosed commonly in children, from infancy through adolescence, primarily affecting the thoracic aorta, with variable involvement of the peripheral vasculature. Pathogeneses include connective tissue disorders, smooth muscle contraction disorders, and congenital heart disease, including bicuspid aortic valve, among others. The American Heart Association has published guidelines for diagnosis and management of thoracic aortic disease. However, these guidelines are predominantly focused on adults and cannot be applied adeptly to growing children with emerging features, growth and developmental changes, including puberty, and different risk profiles compared with adults. Management to reduce risk of progressive aortic dilation and dissection or rupture in children is complex and involves genetic testing, cardiovascular imaging, medical therapy, lifestyle modifications, and surgical guidance that differ in many ways from adult management. Pediatric practice varies widely, likely because aortopathy is pathogenically heterogeneous, including genetic and nongenetic conditions, and there is limited published evidence to guide care in children. To optimize care and reduce variation in management, experts in pediatric aortopathy convened to generate this scientific statement regarding the cardiovascular care of children with aortopathy. Available evidence and expert consensus were combined to create this scientific statement. The most common causes of pediatric aortopathy are reviewed. This document provides a general framework for cardiovascular management of aortopathy in children, while allowing for modification based on the personal and familial characteristics of each child and family.
Exercise and training in sickle cell disease: Safety, potential benefits, and recommendations
Authors: Philippe Connes, Emeric Stauffer, Robert I. Liem, Elie Nader
Journal: American Journal of Hematology (2024)

Abstract Sickle cell disease (SCD) is a genetic disorder characterized by complex pathophysiological mechanisms leading to vaso‐occlusive crisis, chronic pain, chronic hemolytic anemia, and vascular complications, which require considerations for exercise and physical activity. This review aims to elucidate the safety, potential benefits, and recommendations regarding exercise and training in individuals with SCD. SCD patients are characterized by decreased exercise capacity and tolerance. Acute intense exercise may be accompanied by biological changes (acidosis, increased oxidative stress, and dehydration) that could increase the risk of red blood cell sickling and acute clinical complications. However, recent findings suggest that controlled exercise training is safe and well tolerated by SCD patients and could confer benefits in disease management. Regular endurance exercises of submaximal intensity or exercise interventions incorporating resistance training have been shown to improve cardiorespiratory and muscle function in SCD, which may improve quality of life. Recommendations for exercise prescription in SCD should be based on accurate clinical and functional evaluations, taking into account disease phenotype and cardiorespiratory status at rest and in response to exercise. Exercise programs should include gradual progression, incorporating adequate warm‐up, cool‐down, and hydration strategies. Exercise training represents promising therapeutic strategy in the management of SCD. It is now time to move through the investigation of long‐term biological, physiological, and clinical effects of regular physical activity in SCD patients.
Treating acute encephalitis
Authors: Kiran T. Thakur, Camille Legouy, Romain Sonneville
Journal: Intensive Care Medicine (2024)

Encephalitis is a severe condition presenting with a rapidly progressive encephalopathy triggered by brain inflammation, with varying combinations of fever, focal central nervous system (CNS) findings, new-onset seizures, cerebrospinal fluid (CSF) pleocytosis, often with associated neuroimaging and electroencephalography (EEG) abnormalities [1].It is associated with a myriad of etiologies, most commonly viral infections and autoimmune causes (Fig. 1).Other etiologies include less common infectious culprits (i.e.fungal, protozoan, and subacute bacterial causes), post-infectious, and immune-mediated causes in relation to systemic conditions [2].Immunocompromised patients, who represent an increasing proportion of the population, present additional challenges given their increased susceptibility to unusual pathogens and atypical clinical presentations.Despite a rapid and thorough evaluation, etiology remains unknown in 40-50% of encephalitis cases.
CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors
Authors: Lei Peng, Giacomo Sferruzza, Luojia Yang, Liqun Zhou, Sidi Chen
Journal: Cellular and Molecular Immunology (2024)

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a specific focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.
A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology
Authors: Priya Gupta, Marco Galimberti, Yue Liu, Sarah Beck, Aliza Wingo, Thomas Wingo, Keyrun Adhikari, Henry R Kranzler, Murray B Stein, Joel Gelernter, Daniel F Levey
Journal: Nature Human Behaviour (2024)

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The 'big five' personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses, including depression, anxiety and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Here, utilizing the Million Veteran Program cohort, we conducted a genome-wide association study in individuals of European and African ancestry. Adding other published data, we performed genome-wide association study meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 208, 14, 3, 2 and 7 independent genome-wide significant loci associated with neuroticism, extraversion, agreeableness, conscientiousness and openness, respectively. These findings represent 62 novel loci for neuroticism, as well as the first genome-wide significant loci discovered for agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety, while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.
IL-33 released during challenge phase regulates allergic asthma in an age-dependent way
Authors: Hangyu Liu, Min Wu, Qiangqiang Wang, Liuchuang Gao, Han Jiang, Ketai Shi, Yawen Lin, Junyi Zhou, Ju Huang, Shen Qu, Yuwei Zhang, Fang Zheng, Yafei Huang, Junyan Han
Journal: Cellular and Molecular Immunology (2024)
READv2: advanced and user-friendly detection of biological relatedness in archaeogenomics
Authors: Erkin Alaçamlı, Thijessen Naidoo, Merve N Güler, Ekin Sağlıcan, Şevval Aktürk, Igor Mapelli, Kıvılcım Başak Vural, Mehmet Somel, Helena Malmström, Torsten Günther
Journal: Genome biology (2024)

Abstract The advent of genome-wide ancient DNA analysis has revolutionized our understanding of prehistoric societies. However, studying biological relatedness in these groups requires tailored approaches due to the challenges of analyzing ancient DNA. READv2, an optimized Python3 implementation of the most widely used tool for this purpose, addresses these challenges while surpassing its predecessor in speed and accuracy. For sufficient amounts of data, it can classify up to third-degree relatedness and differentiate between the two types of first-degree relatedness, full siblings and parent-offspring. READv2 enables user-friendly, efficient, and nuanced analysis of biological relatedness, facilitating a deeper understanding of past social structures.
A base editor for the long-term restoration of auditory function in mice with recessive profound deafness
Authors: Chong Cui, Shengyi Wang, Daqi Wang, Jingjing Zhao, Bowei Huang, Biyun Zhu, Yuxin Chen, Honghai Tang, Yu Han, Cheng Ye, Dan Mu, Chengdong Zhang, Yuan Yang, Yihan Bao, Jun Lv, Shuang Han, Geng-Lin Li, Huawei Li, Yilai Shu
Journal: Nature Biomedical Engineering (2024)
ZBTB46 coordinates angiogenesis and immunity to control tumor outcome
Authors: Ashraf Ul Kabir, Carisa Zeng, Madhav Subramanian, Jun Wu, Minseo Kim, Karen Krchma, Xiaoli Wang, Carmen M. Halabi, Hua Pan, Samuel A. Wickline, Daved H. Fremont, Maxim N. Artyomov, Kyunghee Choi
Journal: Nature Immunology (2024)
The Bioactive Interface of Titanium Implant with Both Anti‐Oxidative Stress and Immunomodulatory Properties for Enhancing Osseointegration under Diabetic Condition
Authors: Jianshuang Wu, Maowen Chen, Yao Xiao, Huan Yang, Gaoyang Wang, Xiaohong Zhang, Liangliang Dai, Zhang Yuan
Journal: Advanced Healthcare Materials (2024)

Abstract The poor implant‐osseointegration under diabetic condition remains a challenge to be addressed urgently. Studies have confirmed that the diabetic pathological microenvironment is accompanied by excessive oxidative stress, imbalanced immune homeostasis, and persistent chronic inflammation, which seriously impairs the osteogenic process. Herein, a multifunctional bioactive interface with both anti‐oxidative stress and immunomodulatory properties is constructed on titanium implants. Briefly, manganese dioxide nanosheets are coated onto mesoporous polydopamine nanoparticles loaded with carbon monoxide gas precursor, namely MnO 2 ‐CO@MPDA NPs, and then they are integrated on the titanium implant to obtain MCM‐Ti. In the simulated diabetic microenvironment, under the action of MnO 2 nanoenzymes, MCM‐Ti can effectively eliminate intracellular reactive oxygen species while alleviating hypoxic state. Interestingly, the microenvironment mediates the responsive release of CO gas, which effectively drives macrophages toward M2 polarization, thereby ameliorating inflammatory response. The potential mechanism is that CO gas up‐regulates the expression of heme oxygenase‐1, further activating the Notch/Hes1/Stat3 signaling pathway. Furthermore, the conditioned medium derived from macrophages on MCM‐Ti surface significantly enhances the osteogenic differentiation of BMSCs. In a type 2 diabetic rat model, MCM‐Ti implant effectively alleviates the accompanying inflammation and enhances the osseointegration through the synergistic effects of resisting oxidative stress and remodeling immune homeostasis.
Frequency and mental health consequences of microaggressions experienced in the day-to-day lives of transgender and gender diverse people
Authors: David Matthew Doyle, Dimitri Georgiev, Thomas O. G. Lewis, Manuela Barreto
Journal: International Journal of Transgender Health (2024)

Introduction Increasingly, it is apparent that in order to understand mental health and well-being, it is necessary to examine the ebb and flow of experiences and emotions across people's day-to-day lives. For transgender and gender diverse (TGD) people, daily life is sometimes punctured by experiences of minority stress (e.g. in the form of microaggressions).
Pyroptosis and the fight against lung cancer
Authors: Jiwei Wang, Huiling Su, Min Wang, Richard Ward, Su An, Tian‐Rui Xu
Journal: Medicinal Research Reviews (2024)

Pyroptosis, a newly characterized type of inflammatory programmed cell death (PCD), is usually triggered by multiple inflammasomes which can recognize different danger or damage-associated molecular patterns (DAMPs), leading to the activation of caspase-1 and the cleavage of gasdermin D (GSDMD). Gasdermin family pore-forming proteins are the executers of pyroptosis and are normally maintained in an inactive state through auto-inhibition. Upon caspases mediated cleavage of gasdermins, the pro-pyroptotic N-terminal fragment is released from the auto-inhibition of C-terminal fragment and oligomerizes, forming pores in the plasma membrane. This results in the secretion of interleukin (IL)-1β, IL-18, and high-mobility group box 1 (HMGB1), generating osmotic swelling and lysis. Current therapeutic approaches including chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy for lung cancer treatment efficiently force the cancer cells to undergo pyroptosis, which then generates local and systemic antitumor immunity. Thus, pyroptosis is recognized as a new therapeutic regimen for the treatment of lung cancer. In this review, we briefly describe the signaling pathways involved in pyroptosis, and endeavor to discuss the antitumor effects of pyroptosis and its potential application in lung cancer therapy, focusing on the contribution of pyroptosis to microenvironmental reprogramming and evocation of antitumor immune response.
Navigating the European Union Artificial Intelligence Act for Healthcare
Authors: Felix Busch, Jakob Nikolas Kather, Christian Johner, Marina Moser, Daniel Truhn, Lisa C. Adams, Keno K. Bressem
Journal: npj Digital Medicine (2024)

The European Union's recently adopted Artificial Intelligence (AI) Act is the first comprehensive legal framework specifically on AI. This is particularly important for the healthcare domain, as other existing harmonisation legislation, such as the Medical Device Regulation, do not explicitly cover medical AI applications. Given the far-reaching impact of this regulation on the medical AI sector, this commentary provides an overview of the key elements of the AI Act, with easy-to-follow references to the relevant chapters.
A Genomics England haplotype reference panel and imputation of UK Biobank
Authors: Sinan Shi, Simone Rubinacci, Sile Hu, Loukas Moutsianas, Alex Stuckey, Anna C. Need, Pier Francesco Palamara, Mark Caulfield, Jonathan Marchini, Simon Myers
Journal: Nature Genetics (2024)

We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r
Ketogenic diet reshapes cancer metabolism through lysine β-hydroxybutyrylation
Authors: Junhong Qin, Xinhe Huang, Shengsong Gou, Sitao Zhang, Yujie Gou, Qian Zhang, Hongyu Chen, Lin Sun, Miaomiao Chen, Dan Liu, Cheng Han, Min Tang, Zihao Feng, Shenghui Niu, Lin Zhao, Yingfeng Tu, Zexian Liu, Weimin Xuan, Lunzhi Dai, Da Jia, Yu Xue
Journal: Nature Metabolism (2024)
Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS
Authors: Yi Zhang, Junyu Shi, Jie Zhu, Xinxin Ding, Jianxu Wei, Xue Jiang, Yijie Yang, Xiaomeng Zhang, Yongzhuo Huang, Hongchang Lai
Journal: Acta Pharmaceutica Sinica B (2024)

Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (
Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism-related vascular thrombosis with microvascular injury and its consequences
Authors: Danyang Zhao, Chao Han, Elmina Mammadova-Bach, Kanako Watanabe-Kusunoki, Tamisa Seeko Bandeira Honda, Yihong Li, Chenyu Li, Qiubo Li, Hao Long, Lyuben Lyubenov, Chongxu Shi, Donato Santovito, Christian Weber, Peter Boor, Patrick Droste, Samir Parikh, John Shapiro, Letizia De Chiara, Giulia Carangelo, Paola Romagnani, Sven Klussmann, Kai Hoehlig, Axel Vater, Hans-Joachim Anders
Journal: Kidney International (2024)

Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate the consequences of CCE like that with systemic vasculitis. Cholesterol microcrystal injection into the kidney artery of wildtype mice initiated intra-kidney immunothrombosis within a few hours followed by a sudden drop of glomerular filtration rate and ischemic kidney necrosis after 24 hours. Genetic deficiency of either C3 or C5aR prevented immunothrombosis, glomerular filtration rate drop, and ischemic necrosis at 24 hours as did preemptive treatment with inhibitors of either C5a or C5aR. Delayed C5a blockade after crystal injection still resolved crystal clots and prevented all consequences. Thus, selective blockade of C5a or C5aR is sufficient to attenuate the consequences of established CCE and prospective inhibition in high-risk patients may be clinically feasible and safe.
Melanin‐Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age‐Related Macular Degeneration
Authors: Keke Huang, Haoyue Deng, Shuang Wang, Fuxiao Zhang, Ge Huang, Lu Wang, Jianyu Liu, Xuli Zhao, Hui Ren, Guang Yang, Zhiqing Lin
Journal: Advanced Healthcare Materials (2024)

Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis and subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age-related macular degeneration (dAMD), causing irreversible vision loss in the global elderly population. However, currently, no effective interventional treatment strategy exists in clinical practice. Herein, lesion site-targeted melanin-like nanoparticles, named ConA-MelNPs, are designed as a novel ferroptosis inhibitor for retinal degenerative diseases. ConA-MelNPs possessed chelating iron ion characteristics, alleviating severe mitochondrial damage caused by oxidative stress and protecting RPE cells from ferroptosis induced by sodium iodate (NaIO
Efficacy versus effectiveness: The <scp>HORIZON</scp> Pivotal Fracture Trial and its emulation in Claims Data
Authors: Elvira D'Andrea, Sebastian Schneeweiss, Jessica M. Franklin, Seoyoung C. Kim, Robert J. Glynn, Su Been Lee, Shirley V. Wang
Journal: Arthritis & Rheumatology (2024)

To evaluate the concordance of results between the HORIZON-Pivotal Fracture Trial (PFT) and a non-randomized database study designed to emulate the trial.