tbuckley/cabot-search huggingface dataset:
Unraveling dynamic immunological landscapes in intracerebral hemorrhage: insights from single‐cell and spatial transcriptomic profiling
Authors: Lingui Gu, Hualin Chen, Mingjiang Sun, Yihao Chen, Qinglei Shi, Jianbo Chang, Junji Wei, Wenbin Ma, Xinjie Bao, Renzhi Wang
Journal: MedComm (2024)

Abstract Intracerebral hemorrhage (ICH) poses a formidable challenge in stroke management, with limited therapeutic options, particularly in the realm of immune‐targeted interventions. Clinical trials targeting immune responses post‐ICH have encountered setbacks, potentially attributable to the substantial cellular heterogeneity and intricate intercellular networks within the brain. Here, we present a pioneering investigation utilizing single‐cell RNA sequencing and spatial transcriptome profiling at hyperacute (1 h), acute (24 h), and subacute (7 days) intervals post‐ICH, aimed at unraveling the dynamic immunological landscape and spatial distributions within the cerebral tissue. Our comprehensive analysis revealed distinct cell differentiation patterns among myeloid and lymphocyte populations, along with delineated spatial distributions across various brain regions. Notably, we identified a subset of lymphocytes characterized by the expression of Spp1 and Lyz2, termed macrophage‐associated lymphocytes, which exhibited close interactions with myeloid cells. Specifically, we observed prominent interactions between Lgmn+Macro‐T cells and microglia through the spp1–cd44 pathway during the acute phase post‐ICH in the choroid plexus. These findings represent a significant advancement in our understanding of immune cell dynamics at single‐cell resolution across distinct post‐ICH time points, thereby laying the groundwork for exploring critical temporal windows and informing the development of targeted therapeutic strategies.
Remodeling tumor‐associated macrophage for anti‐cancer effects by rational design of irreversible inhibition of mitogen‐activated protein kinase‐activated protein kinase 2
Authors: Danyi Wang, Deqiao Sun, Xiaoyan Wang, Xia Peng, Yinchun Ji, Lu Tang, Qichang He, Danqi Chen, Ye Yang, Xuan Zhou, Bing Xiong, Jing Ai
Journal: MedComm (2024)

Abstract Mitogen‐activated protein kinase‐activated protein kinase 2 (MK2) emerges as a pivotal target in developing anti‐cancer therapies. The limitations of ATP‐competitive inhibitors, due to insufficient potency and selectivity, underscore the urgent need for a covalent irreversible MK2 inhibitor. Our initial analyses of The Cancer Genome Atlas database revealed MK2's overexpression across various cancer types, especially those characterized by inflammation, linking it to poor prognosis and highlighting its significance. Investigating MK2's kinase domain led to the identification of a unique cysteine residue, enabling the creation of targeted covalent inhibitors. Compound 11 was developed, demonstrating robust MK2 inhibition (IC 50 = 2.3 nM) and high selectivity. It binds irreversibly to MK2, achieving prolonged signal suppression and reducing pathological inflammatory cytokines in macrophages. Furthermore, compound 11 or MK2 knockdown can inhibit the tumor‐promoting macrophage M2 phenotype in vitro and in vivo. In macrophage‐rich tumor model, compound 11 notably slowed growth in a dose‐dependent manner. These findings support MK2 as a promising anticancer target, especially relevant in cancers fueled by inflammation or dominated by macrophages, and provide compound 11 serving as an invaluable chemical tool for exploring MK2's functions.
Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models
Authors: Zhongkai Ma, Zhiyong Guo, Zhangfan Ding, Chang Cao, Jialu He, Heyi Tang, Yufei Hua, Jiawei Hong, Qiang Shen, Grace Paka Lubamba, Xiaoyi Wang, Zheng Yang, Guiquan Zhu, Chunjie Li
Journal: International Journal of Oral Science (2024)

Abstract Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups ( P = 0.126), better intraoperative bleeding control ( P = 0.001), and a significant reduction in cognitive workload ( P &lt; 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.
Morphometrics and Phylogenomics of Coca (<i>Erythroxylum</i> spp.) Illuminate Its Reticulate Evolution, With Implications for Taxonomy
Authors: Natalia A S Przelomska, Rudy A Diaz, Fabio Andrés Ávila, Gustavo A Ballen, Rocío Cortés-B, Logan Kistler, Daniel H Chitwood, Martha Charitonidou, Susanne S Renner, Oscar A Pérez-Escobar, Alexandre Antonelli
Journal: Molecular Biology and Evolution (2024)

Abstract South American coca (Erythroxylum coca and E. novogranatense) has been a keystone crop for many Andean and Amazonian communities for at least 8,000 years. However, over the last half-century, global demand for its alkaloid cocaine has driven intensive agriculture of this plant and placed it in the center of armed conflict and deforestation. To monitor the changing landscape of coca plantations, the United Nations Office on Drugs and Crime collects annual data on their areas of cultivation. However, attempts to delineate areas in which different varieties are grown have failed due to limitations around identification. In the absence of flowers, identification relies on leaf morphology, yet the extent to which this is reflected in taxonomy is uncertain. Here, we analyze the consistency of the current naming system of coca and its four closest wild relatives (the “coca clade”), using morphometrics, phylogenomics, molecular clocks, and population genomics. We include name-bearing type specimens of coca's closest wild relatives E. gracilipes and E. cataractarum. Morphometrics of 342 digitized herbarium specimens show that leaf shape and size fail to reliably discriminate between species and varieties. However, the statistical analyses illuminate that rounder and more obovate leaves of certain varieties could be associated with the subtle domestication syndrome of coca. Our phylogenomic data indicate extensive gene flow involving E. gracilipes which, combined with morphometrics, supports E. gracilipes being retained as a single species. Establishing a robust evolutionary-taxonomic framework for the coca clade will facilitate the development of cost-effective genotyping methods to support reliable identification.
Analysing Wilson’s and Goldberger’s Central Terminals: Theoretical Redesign of a Novel Central Terminal for Precordial Leads
Authors: Alejandro Jesús Bermejo Valdés
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

This study delves into the foundational aspects of electrocardiographic (ECG) lead systems, specifically focusing on Einthoven’s Triangle and Wilson’s Central Terminal. We introduce the innovative concept of a Precordial Central Terminal, a strategic arrangement of thoracic electrodes that establishes two Einthoven’s triangles within the horizontal plane, in accordance with physical-mathematical principles. Furthermore, we meticulously scrutinize Goldberger’s contributions to the field of ECG, particularly augmented leads, which shed light on the development of our theory. Additionally, we propose the implementation of a novel standardized electrocardiograph, characterized by its use of exclusively “precordial” electrodes, yet capable of providing a comprehensive three-dimensional perspective of cardiac electrical activity. By amalgamating theoretical underpinnings with empirical experimentation, our study lays the groundwork for future investigations, including the experimental validation of our innovative Precordial Terminal. This validation holds the promise of yielding substantial advancements in the realm of clinical electrocardiography.
Total outflow graft thrombosis: From permanent circulatory support to temporary circulatory support by deactivating HeartMate 3™ and implanting Impella 5.5® in a high urgent bridge to transplant concept
Authors: SJ Bauer
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

X-ray shows a male patient with two left ventricular assist devices. Initial presentation was with intermittent low-flow-alarms.
Role of Nursing in the Early Detection and Prevention of Stent Thrombosis in Patients Undergoing Coronary Angioplasty
Authors: Lucía Ferrer Bañolas
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

Introduction: stent thrombosis is one of the serious complications after coronary angioplasty. It can present with chest pain and electrocardiographic changes or even sudden death and is characterized by angiographic or postmortem evidence of a newly formed thrombus in a previously stented segment and can occur from intraprocedurally to years after implantation. There are several risk factors, both related to the lesion and the procedure, as well as adherence to antiplatelet therapy and personal history. The objective of this case is to present a care plan to detect and prevent stent thrombosis in patients undergoing coronary angioplasty. Material and methods: an assessment is made through the model of the 14 needs of Virginia Henderson and the care plan is prepared with its respective diagnoses (NANDA), objectives (NOC) and interventions (NIC) with the indicators of results and activities. It will be evaluated using the Likert scale. Results and conclusions: the following diagnoses stand out: decreased cardiac output, ineffective peripheral tissue perfusion and deficient knowledge. Nursing intervenes in the early detection of signs and symptoms that may point us towards stent thrombosis, observing any change immediately, and in its prevention, carrying out health education after angioplasty, highlighting the importance of antithrombotic treatment and in modifying modifiable risk factors.
Is bempedoic acid effective for secondary prevention of cardiovascular disease?
Authors: Nasser Mikhail
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

Bempedoic acid is a cholesterol-lowering drug approved for reduction of the risk of myocardial infarction (MI) and coronary revascularization in adults who are unable to take recommended statin therapy with established cardiovascular disease (CVD), or at high risk for a CVD event but without established CVD. However, reduction of CV events by bempedoic acid in patients with documented CVD is modest and not statistically significant. The CLEAR Outcomes trial is the largest randomized trial of bempedoic acid including 13,970 patients; 70% of whom had documented CVD (secondary prevention cohort), and 30% were considered high CV risk but without established CV disease (primary prevention cohort). The primary outcome of the CLEAR OUTCOMES trial was a composite of death from CV causes, nonfatal MI, nonfatal stroke, or coronary revascularization (MACE-4). After a median follow-up of 40.6 months, the incidence of CV event was significantly decreased in the bempedoic group versus the placebo group in the whole study population; hazard ratio (HR) 0.87; 95% CI, 0.79 to 0.96; P=0.004). However, this decrease in CV events was mainly driven by the reduction of MACE-4 in the primary prevention cohort; HR 0.68 (95% CI, 0.53 to 0.87), whereas the corresponding reduction in the secondary prevention cohort was more modest; HR 0.91 (95% CI 0.82 to 1.01), Pinteraction=0.03. Results of a post-hoc analysis of the CLEAR Outcomes trial suggested possible increase in all-cause mortality; risk ratio (RR) 1.15 and CV mortality RR 1.21 in the secondary prevention patients. Conversely, in the primary prevention group, there was decrease in all-cause mortality RR 0.70 and CV mortality RR 0.58. While the investigators of the CLEAR Outcomes trial published results of the primary prevention group separately, they did not report those results in the larger secondary group despite greater number of CV events. A randomized trial evaluating bempedoic acid in patients with documented CVD is required to clarify its efficacy and safety in this group of patients. Until such trial is available, the use of bempedoic acid is not recommended for secondary prevention of CV disease.
Red blood cell transfusions may have the stongest analgesic effect during acute painful crises in sickle cell diseases
Authors: Mehmet Rami Helvaci
Journal: Clinical Cardiology and Cardiovascular Interventions (2023)

Background: The hardened red blood cells (RBC)-induced capillary endothelial damage, inflammation, edema, and fibrosis are initiated at birth, and terminate with disseminated tissue hypoxia, acute painful crises, multiorgan failures, and sudden death even at childhood in the sickle cell diseases (SCD). Methods: All cases with the SCD were included into the study. Results: We studied 222 males and 212 females with similar mean ages (30.8 vs 30.3 years, p&gt;0.05, respectively). Disseminated teeth losses (5.4% vs 1.4%, p&lt;0.001), ileus (7.2% vs 1.4%, p&lt;0.001), cirrhosis (8.1% vs 1.8%, p&lt;0.001), leg ulcers (19.8% vs 7.0%, p&lt;0.001), digital clubbing (14.8% vs 6.6%, p&lt;0.001), coronary heart disease (18.0% vs 13.2%, p&lt;0.05), chronic renal disease (9.9% vs 6.1%, p&lt;0.05), chronic obstructive pulmonary disease (25.2% vs 7.0%, p&lt;0.001), and stroke (12.1% vs 7.5%, p&lt;0.05) were all higher but not acute chest syndrome (2.7% vs 3.7%, p&gt;0.05) or pulmonary hypertension (12.6% vs 11.7%, p&gt;0.05) or deep venous thrombosis and/or varices and/or telangiectasias (9.0% vs 6.6%, p&gt;0.05) in males, significantly. Conclusion: Infections, medical or surgical emergencies, or emotional stress-induced increased basal metabolic rate aggravates the sickling and capillary endothelial inflammation and edema, and may terminate with disseminated tissue hypoxia, acute painful crises, multiorgan failures, and sudden deaths in the SCD. RBC support may have the stongest analgesic effect, and decrease the risk of multiorgan failures and sudden death by decreasing the density of causative hardened cells from the circulation during such severe crises.
IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β–mediated immune suppression and potentiate anti-tumor responses in glioblastoma
Authors: Andrew J Hou, Ryan M Shih, Benjamin R Uy, Amanda Shafer, ZeNan L Chang, Begonya Comin-Anduix, Miriam Guemes, Zoran Galic, Su Phyu, Hideho Okada, Katie B Grausam, Joshua J Breunig, Christine E Brown, David A Nathanson, Robert M Prins, Yvonne Y Chen
Journal: Neuro-Oncology (2024)

Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.
Correction: Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress
Authors: Ken Uekawa, Yorito Hattori, Sung Ji Ahn, James Seo, Nicole Casey, Antoine Anfray, Ping Zhou, Wenjie Luo, Josef Anrather, Laibaik Park, Costantino Iadecola
Journal: Molecular Neurodegeneration (2024)
Prospective feasibility study of a novel rigidizing stabilizing overtube in the resection of complex gastrointestinal polyps
Authors: Salmaan Jawaid, Ahmed F. Aboelezz, Gehad Daba, Mai Khalaf, Fares Ayoub, Noor Zabad, Michael Mercado, Tara Keihanian, Mohamed Othman
Journal: Endoscopy (2024)

Abstract Background A novel rigidizing overtube (ROT) was developed to facilitate endoscopic removal of complex gastrointestinal polyps. We aimed to prospectively evaluate the efficacy and safety of the device in the management of large gastrointestinal polyps. Methods A prospective, single-center study, conducted between May 2021 and April 2023, enrolled patients undergoing endoscopic resection of colon/duodenal polyps ≥25 mm. Primary outcomes were safety, technical success, and clinical success defined as the ability of ROT to facilitate endoscopic polyp removal without changing the initial resection method. Results 97 patients (98 polyps), with a mean polyp size of 33.2 mm (median 31.1), were evaluated. Technical and clinical success rates were 100% and 84%, respectively. Ileocecal valve location was the only predictor of clinical failure (P = 0.02). The mean time to reach the lesion was 7.2 minutes (95%CI 5–8), with overall resection and procedure times of 53.6 minutes (95%CI 48–61) and 88.9 minutes (95%CI 79–95), respectively. No device-related adverse events occurred. Lower technical (67%) and clinical (67%) success rates were seen for duodenal polyps (n = 6). Conclusion The novel ROT was safe, with high technical and clinical success during resection of complex colon polyps. Future studies will determine timing of implementation during routine endoscopic resection.
Safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication influenza vaccine alone or coadministered with an inactivated influenza vaccine (Fluzone High-Dose Quadrivalent) in adults aged 65–85 years in the USA: a multicentre, randomised, double-blind, double-dummy, phase 1b trial
Authors: Joseph Eiden, Carlos Fierro, Alexander White, Matthew Davis, Margaret Rhee, Mark Turner, Bryan Murray, Renee Herber, Roger Aitchison, David Marshall, Michael J Moser, Robert Belshe, Harry Greenberg, Kathleen Coelingh, Yoshihiro Kawaoka, Gabriele Neumann, Pamuk Bilsel
Journal: The Lancet Infectious Diseases (2024)
Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial
Authors: Paul Little, Jane Vennik, Kate Rumsby, Beth Stuart, Taeko Becque, Michael Moore, Nick Francis, Alastair D Hay, Theo Verheij, Katherine Bradbury, Kate Greenwell, Laura Dennison, Sian Holt, James Denison-Day, Ben Ainsworth, James Raftery, Tammy Thomas, Christopher C Butler, Samantha Richards-Hall, Deb Smith, Hazel Patel, Samantha Williams, Jane Barnett, Karen Middleton, Sascha Miller, Sophie Johnson, Jacqui Nuttall, Fran Webley, Tracey Sach, Lucy Yardley, Adam W A Geraghty
Journal: The Lancet Respiratory Medicine (2024)
Improving lesion volume measurements on digital mammograms
Authors: Nikita Moriakov, Jim Peters, Ritse Mann, Nico Karssemeijer, Jos van Dijck, Mireille Broeders, Jonas Teuwen
Journal: Medical Image Analysis (2024)

Lesion volume is an important predictor for prognosis in breast cancer. However, it is currently impossible to compute lesion volumes accurately from digital mammography data, which is the most popular and readily available imaging modality for breast cancer. We make a step towards a more accurate lesion volume measurement on digital mammograms by developing a model that allows to estimate lesion volumes on processed mammogram. Processed mammograms are the images routinely used by radiologists in clinical practice as well as in breast cancer screening and are available in medical centers. Processed mammograms are obtained from raw mammograms, which are the X-ray data coming directly from the scanner, by applying certain vendor-specific non-linear transformations. At the core of our volume estimation method is a physics-based algorithm for measuring lesion volumes on raw mammograms. We subsequently extend this algorithm to processed mammograms via a deep learning image-to-image translation model that produces synthetic raw mammograms from processed mammograms in a multi-vendor setting. We assess the reliability and validity of our method using a dataset of 1778 mammograms with an annotated mass. Firstly, we investigate the correlations between lesion volumes computed from mediolateral oblique and craniocaudal views, with a resulting Pearson correlation of 0.93 [95% confidence interval (CI) 0.92 – 0.93]. Secondly, we compare the resulting lesion volumes from true and synthetic raw data, with a resulting Pearson correlation of 0.998 [95%CI 0.998 – 0.998] . Finally, for a subset of 100 mammograms with a malignant mass and concurrent MRI examination available, we analyze the agreement between lesion volume on mammography and MRI, resulting in an intraclass correlation coefficient of 0.81 [95%CI 0.73 – 0.87] for consistency and 0.78 [95%CI 0.66 – 0.86] for absolute agreement. In conclusion, we developed an algorithm to measure mammographic lesion volume that reached excellent reliability and good validity, when using MRI as ground truth. The algorithm may play a role in lesion characterization and breast cancer prognostication on mammograms.
Extracellular Vesicle-Functionalized Bioactive Scaffolds for Bone Regeneration
Authors: Taozhao Yu, Irene Shuping Zhao, Hongguang Pan, Jianhua Yang, Huanan Wang, Yongqiang Deng, Yang Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2024)

The clinical need for effective bone regeneration in compromised conditions continues to drive demand for innovative solutions. Among emerging strategies, extracellular vesicles (EVs) have shown promise as an acellular approach for bone regeneration. However, their efficacy is hindered by rapid sequestration and clearance when administered via bolus injection. To address this challenge, EV-functionalized scaffolds have recently been proposed as an alternative delivery strategy to enhance EV retention and subsequent healing efficacy. This review aims to consolidate recent advancements in the development of EV-functionalized scaffolds for augmenting bone regeneration. It explores various sources of EVs and different strategies for integrating them into biomaterials. Furthermore, the mechanisms underlying their therapeutic effects in bone regeneration are elucidated. Current limitations in clinical translation and perspectives on the design of more efficient EVs for improved therapeutic efficacy are also presented. Overall, this review can provide inspiration for the development of novel EV-assisted grafts with superior bone regeneration potential.