tbuckley/cabot-search huggingface dataset:
Deep Learning Model to Diagnose Cardiac Amyloidosis from Hematoxylin/Eosin-Stained Myocardial Tissue
Authors: Takeshi Tohyama, Takeshi Iwasaki, Masataka Ikeda, Masato Katsuki, Tatsuya Watanabe, Kayo Misumi, Keisuke Shinohara, Takeo Fujino, Toru Hashimoto, Shouji Matsushima, Tomomi Ide, Junji Kishimoto, Koji Todaka, Yoshinao Oda, Kohtaro Abe
Journal:  (2024)

Abstract Aims Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue. Methods and results This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses. A deep learning model was developed to output the probabilities of cardiac amyloidosis for all the small patches cutout from each myocardial specimen. The developed model highlighted the area in the stained images as highly suspicious, corresponding to where Dylon staining marked amyloid deposition, and discriminated the patches in the evaluation dataset with an area under the curve of 0.965. Provided that the diagnostic criterion for cardiac amyloidosis was defined as a median probability of cardiac amyloidosis &amp;gt;50% in all patches, the model achieved perfect performance in discriminating patients with cardiac amyloidosis from those without it, with an area under the curve of 1.0. Conclusion A deep learning model was developed to diagnose cardiac amyloidosis from HE-stained myocardial tissue accurately. Although further prospective validation of this model using HE-stained myocardial tissues from multiple centres is needed, it may help minimize the risk of missing cardiac amyloidosis and maximize the utility of histological diagnosis in clinical practice.
Advances in 4D Bioprinting: The Next Frontier in Regenerative Medicine and Tissue Engineering Applications
Authors: Sareh Abolhassani, Roya fattahi, Farzaneh Safshekan, Jamileh Saremi, Elham Hasanzadeh
Journal: Advanced Healthcare Materials (2024)

4D bioprinting is a critical advancement in tissue engineering and regenerative medicine (TERM), enabling the creation of structures that dynamically respond to environmental stimuli over time. This review investigates various fabrication techniques and responsive materials that are central to these fields. It underscores the integration of multi-material and biocomposite approaches in 4D bioprinting, which is crucial for fabricating complex and functional constructs with heterogeneous properties. Using 4D bioprinting techniques enhances the mimicry of natural tissue characteristics, offering tailored responses and improved integration with biological systems. Furthermore, this study highlights the synergy between 4D bioprinting and tissue engineering and demonstrates the technology's potential for developing tissues and organs. In regenerative medicine, 4D bioprinting's applications extend to creating smart implants and advanced drug delivery systems that adapt to the body's changes, promoting healing and tissue regeneration. Finally, the challenges and future directions of 4D bioprinting are also explored and emphasize its transformative impact on biomedical engineering and the future of healthcare.
Right ventricular stroke work index from echocardiography in patients with pulmonary arterial hypertension—the role in short-term follow-up assessment
Authors: Raluca Jumatate, Anna Werther-Evaldsson, Annika Ingvarsson, Göran Rådegran, Carl Cronstedt Meurling, Ellen Ostenfeld
Journal:  (2024)

Right ventricular (RV) failure causes high mortality in patients with pulmonary arterial hypertension (PAH). RV stroke work index (RVSWi) poses as a potential predictor of outcome. We evaluated how RVSWi by echocardiography (ECHO) or right heart catheterization (RHC) is altered following PAH treatment and if RVSWi is an indicator of outcome in PAH.
Ultrasensitive Detection of FEN1 Activity for Cancer Diagnosis Using a CRISPR/Cas13a‐Based Triple Cascade Amplification System
Authors: Xia Cheng, Wenchen Zhao, Daixi Chen, Dandan Ren, Tianwei Qian, Xinyi Xia, Xiaohong Wang, Qijun Li, Jianjun Yang, Yan Gu, Peng Zhang, Kun Yin, Ping Yu, Wenpei Dong
Journal: Advanced Healthcare Materials (2024)

Flap endonuclease 1 (FEN1) is closely associated with tumor progression and proliferation, making it a promising biomarker for cancer diagnosis. However, developing a sensitive, reliable, and user-friendly method for quantitative FEN1 detection remains technically challenging. In this study, an ultrasensitive FEN1 biosensor is established using a target-induced cleavage-ligation-transcription-activation cascade strategy (LTACas13a) to enhance the cleavage ability of CRISPR/Cas13a. The LTACas13a method has shown excellent performance in screening FEN1 inhibitors and detecting endogenous FEN1 activity in living cells, as well as in clinical biological samples such as human serum and tissue samples. Additionally, using a universal dumbbell probe derived from FEN1, a multiplex LTACas13a strategy is developed for detecting various DNA glycosylases, including formamidopyrimidine DNA glycosylase, uracil DNA glycosylase, and human alkyl adenine DNA glycosylase. This straightforward approach provides a reliable and effective diagnostic tool for early-stage cancer detection and offers significant opportunities for FEN1 biosensing and related drug discovery.
Current State of CT Enterography in Diagnostics and Surgical Tactics in Crohn’s Disease (Literature Review)
Authors: A. L. Aprosimov, D. A. Lezhnev, Yu. V. Kulezneva
Journal: Radiology - Practice (2024)

Aim. Analysis of literature on the use of computed tomography enterography with intravenous contrast enhancement (CTE) in the assessment of the involvement, activity and severity of the Crohn's disease (CD), and expected resection margins in case surgical treatment is necessary. Materials and Methods. The largest and the most cited studies, fundamental works and recommendations on the diagnosis and treatment of IBD, published in open access scientific databases, were selected for the literature review. Results. Epidemiology of Crohn's disease, diagnostic capabilities of CTE and their role in surgery planning for patients with complicated CD are considered. Conclusions. The complicated epidemiological situation with CD requires early diagnosis, increased effectiveness of treatment, and reduction in disability and mortality in patients with CD. CTE is an effective and widely available method for the diagnosis of CD and continues to develop. Further study of the CTE possibilities, precise selection of patients for surgical treatment and preoperative assessment of the resection volume remains an actual problem.
Ultrasound Diagnosis of Injuries to the Organs of the Scrotum during a Mine Blast Wound. Clinical Observation
Authors: E. I. Rossoshanskaya, V. N. Troyan
Journal: Radiology - Practice (2024)

During today's armed conflicts, there has been a tendency to the increased frequency of injuries to the scrotum, which account for about 10 % of all injuries to the genitourinary system. Inaccurate and untimely diagnosis of damage to this area leads to erroneous treatment tactics, which can subsequently cause persistent pain syndrome, erectile dysfunction, and also lead to an increase in the number of infertile men. The article discusses a clinical case of the use of ultrasound research in the diagnosis of damage to the scrotal organs in a patient with a mine blast wound (MBW). Objective. Using the example of a clinical case, demonstrate the capabilities of the ultrasound method in visualizing structural changes in the organs of the scrotum during MBW, describe the characteristic ultrasound signs of damage to the scrotum and its organs in this type of injury. Materials and methods. A clinical case of a victim with a mine blast wound to the scrotum is presented. The patient underwent ultrasound and CT with intravenous contrast. The results of radiological research methods were compared with data obtained during surgery. Results. An ultrasound examination of the victim revealed ruptures of the tunica albuginea of both testicles (in the left testicle with prominence of testicular tissue into the scrotal cavity), hematomas of both testicles, intravaginal hematomas, foreign bodies of the scrotum and penis. The data obtained from ultrasound were confirmed intraoperatively. Conclusion. Ultrasound scanning is a reliable method for diagnosing combat wounds of the scrotum, which allows you to accurately visualize such injuries as hematomas of the testicle and surrounding soft tissues, rupture of the tunica albuginea of the testicle, foreign bodies of the scrotum, determine the presence and direction of the wound channel, the degree of vascularization of damaged organs, thereby assess the severity of injuries and outline the correct plan for further treatment of the victim.
Subphenotypes of body composition and their association with cardiometabolic risk – Magnetic resonance imaging in a population-based sample
Authors: Elena Grune, Johanna Nattenmüller, Lena S Kiefer, Jürgen Machann, Annette Peters, Fabian Bamberg, Christopher L Schlett, Susanne Rospleszcz
Journal: Metabolism (2024)
CD36-mediated uptake of oxidized LDL induces double-negative regulatory T cell ferroptosis in metabolic dysfunction-associated steatotic liver disease
Authors: Yunxiong Wei, Yuan Jiang, Jingjing Zhu, Zihan Zhang, Mengyi Li, Shimeng Zheng, Xiyu Wang, Jie Sun, Changying Li, Wen Shi, Songlin Wang, Xinjuan Liu, Minjie Lin, Zhongtao Zhang, Dong Zhang, Guangyong Sun
Journal: Metabolism (2024)
Metformin treatment in hyperglycemic INOCA patients
Authors: Pasquale Mone, Fahimeh Varzideh, Antonio Rainone, Urna Kansakar, Stanislovas S Jankauskas, Luigi Salemme, Maria Chiara Brunese, Giuseppe Speziale, Tullio Tesorio, Gaetano Santulli
Journal: Cardiovascular Research (2024)

Journal Article Accepted manuscript Metformin treatment in hyperglycemic INOCA patients Get access Pasquale Mone, Pasquale Mone Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York City, NY, USAUniversity of Molise, Campobasso, ItalyCasa di Cura "Montevergine", Mercogliano (Avellino), Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Fahimeh Varzideh, Fahimeh Varzideh Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York City, NY, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonio Rainone, Antonio Rainone Casa di Cura "Montevergine", Mercogliano (Avellino), Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Urna Kansakar, Urna Kansakar Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York City, NY, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Stanislovas S Jankauskas, Stanislovas S Jankauskas Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York City, NY, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Luigi Salemme, Luigi Salemme Casa di Cura "Montevergine", Mercogliano (Avellino), Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria Chiara Brunese, Maria Chiara Brunese University of Molise, Campobasso, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Giuseppe Speziale, Giuseppe Speziale GVM Care & Research, Department of Cardiovascular Surgery, Anthea Hospital, Bari, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Tullio Tesorio, Tullio Tesorio Casa di Cura "Montevergine", Mercogliano (Avellino), Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Gaetano Santulli Gaetano Santulli Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, New York City, NY, USAUniversity of Naples "Federico II", ItalyDepartment of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York City, NY, USA Address Correspondence to: Gaetano Santulli, MD, PhD, FAHA, [email protected], Albert Einstein College of Medicine, New York City, NY, USA https://orcid.org/0000-0001-7231-375X Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvae269, https://doi.org/10.1093/cvr/cvae269 Published: 30 December 2024 Article history Received: 05 September 2024 Revision received: 03 November 2024 Accepted: 30 December 2024 Published: 30 December 2024
Acetylation-ubiquitination crosstalk of DJ-1 mediates microcalcification formation in diabetic plaques via collagen-matrix vesicles interaction
Authors: Zhen Sun, Lihua Li, Yao Wu, Lili Zhang, Guangyao Zang, Yongjiang Qian, Haipeng Yao, Xiang Mao, Zhongqun Wang
Journal: Cardiovascular Research (2024)

Microcalcification increases the vulnerability of plaques and has become an important driver of acute cardiovascular events in diabetic patients. However, the regulatory mechanisms remain unclear. DJ-1, a multifunctional protein, may play a potential role in the development of diabetic complications. Therefore, this study aims to explore the relationship between DJ-1 and microcalcification in diabetic plaques and investigate the mechanisms. The regulatory relationship between DJ-1 and diabetic vascular microcalcification was determined in anterior tibial arteries from diabetic foot amputated patients, a diabetic apolipoprotein E-deficient (ApoE-/-) mouse model, and a vascular smooth muscle cell (VSMC) model. The ubiquitination and acetylation levels of DJ-1 were detected, and the acetylation-ubiquitination crosstalk was explored. Then, the regulatory effects of DJ-1 on receptor for advanced glycation end products (RAGE) were clarified. Further, the role of DJ-1 in collagen- matrix vesicles (MVs) interaction in diabetic microenvironment was observed. The collagen interacting surface protein of MVs was verified with proteomics and the biomimetic MVs model.In clinical samples, the number of microcalcification nodules in anterior tibial artery plaques was negatively correlated with DJ-1 expression. In diabetic ApoE-/- mice and VSMCs models, knocking down DJ-1 significantly increased the number of microcalcified nodules. N-acetyltransferase 10 (NAT10) was an acetyltransferase of DJ-1. NAT10 could crosstalk the ubiquitination of DJ-1 and enhance the ubiquitination of DJ-1 by E3 ubiquitin ligase tripartite motif-containing protein 32 (TRIM32). Besides, the knockdown of DJ-1 activated signal transducer and activator of transcription 1 (STAT1), and then STAT1 could bind to RAGE promoter, thus upregulating RAGE. Furthermore, the knockdown of DJ-1 significantly promoted collagen-MVs interaction in diabetic microenvironment. Milk fat globule epidermal growth factor 8 (MFGE8) may serve as a collagen-interacting protein. The coating of MFGE8 protein could increase the interaction between collagen and biomimetic MVs. In the diabetic microenvironment, DJ-1 was a protective factor for vascular microcalcification. NAT10- and TRIM32-mediated acetylation-ubiquitination crosstalk resulted in the degradation of DJ-1. The decrease of DJ-1 could activate DJ-1/STAT1/RAGE microcalcification signal. Further, under the stimulation of DJ-1-mediated microcalcification signal, VSMCs released MVs with high abundance of MFGE8. MFGE8 promoted collagen-MVs interaction and finally accelerated the formation of microcalcification.
Brainstem C1 neurons mediate heart failure decompensation and mortality during acute salt loading
Authors: Karla G Schwarz, Katherin V Pereyra, Esteban Díaz-Jara, Sinay C Vicencio, Rodrigo Del Rio
Journal: Cardiovascular Research (2024)

Abstract Aims Heart failure (HF) is an emerging epidemic worldwide. Despite advances in treatment, the morbidity and mortality rate of HF remain high, and the global prevalence continues to rise. Common clinical features of HF include cardiac sympathoexcitation, disordered breathing, and kidney dysfunction; kidney dysfunction strongly contributes to sodium retention and fluid overload, leading to poor outcomes of HF patients. We have previously shown that brainstem pre-sympathetic neurons (C1) from the rostral ventrolateral medulla (RVLM) play a key role in sympathetic regulation in experimental models of HF. However, the role of RVLM-C1 neurons during salt-loading in the context of HF is unknown. This study tests whether RVLM C1 neurons drive cardiorespiratory decompensation and ultimately lead to sudden death in HF rats. Methods and results Adult male Sprague–Dawley rats underwent arteriovenous shunt to induce HF with preserved ejection fraction (HFpEF). Two weeks after HFpEF induction, bilateral selective ablation of RVLM C1 neurons was performed using anti-dopamine β-hydroxylase-saporin toxin. Animals were then fed a high Na+ diet (3% Na+ in food and 2% Na+ in water) for 3 weeks to induce compensated-to-decompensated HF state transition. Echocardiography, cardiac autonomic function, breathing function, and survival were assessed during the progression of HF. Salt loading resulted in marked decompensation in HF rats, as evidenced by a significant decrease in survival rates (survival: 10% vs. 100% HFpEF + Na+ vs. HFpEF). Furthermore, HFpEF + Na+ animals showed a further increase in cardiac sympathetic drive and more severe disordered breathing, including higher hypoxia-related epochs (i.e. apnoeas/hypopnoeas), compared with HF. Ablation of RVLM C1 neurons partly reduced the excessive cardiac sympathoexcitation during salt loading in HF, improved the exaggerated disordered breathing in HFpEF+ Na+ rats, and reduced decompensation-linked mortality. We found that hypoxia, but not high sodium, was the major contributor to impaired calcium handling in isolated adult cardiomyocytes. Conclusion Our results strongly suggest that RVLM C1 neurons contribute to acute HF decompensation during salt loading by a mechanism encompassing further increases in sympathetic outflow and hypoxia-related breathing disorders. This mechanism may ultimately impact cardiac contractility through cardiomyocyte calcium mishandling, increasing morbidity and mortality.
Machine learning and clinician predictions of antibiotic resistance in Enterobacterales bloodstream infections
Authors: Kevin Yuan, Augustine Luk, Jia Wei, A Sarah Walker, Tingting Zhu, David W Eyre
Journal: Journal of Infection (2024)

Patients with Gram-negative bloodstream infections are at risk of serious adverse outcomes without active treatment, but identifying who has antimicrobial resistance (AMR) to target empirical treatment is challenging.
Aligning knowledge concepts to whole slide images for precise histopathology image analysis
Authors: Weiqin Zhao, Ziyu Guo, Yinshuang Fan, Yuming Jiang, Maximus C. F. Yeung, Lequan Yu
Journal: npj Digital Medicine (2024)

Due to the large size and lack of fine-grained annotation, Whole Slide Images (WSIs) analysis is commonly approached as a Multiple Instance Learning (MIL) problem. However, previous studies only learn from training data, posing a stark contrast to how human clinicians teach each other and reason about histopathologic entities and factors. Here, we present a novel knowledge concept-based MIL framework, named ConcepPath, to fill this gap. Specifically, ConcepPath utilizes GPT-4 to induce reliable disease-specific human expert concepts from medical literature and incorporate them with a group of purely learnable concepts to extract complementary knowledge from training data. In ConcepPath, WSIs are aligned to these linguistic knowledge concepts by utilizing the pathology vision-language model as the basic building component. In the application of lung cancer subtyping, breast cancer HER2 scoring, and gastric cancer immunotherapy-sensitive subtyping tasks, ConcepPath significantly outperformed previous SOTA methods, which lacked the guidance of human expert knowledge.
Chromatin-based memory as a self-stabilizing influence on cell identity
Authors: Charles C. Bell, Geoffrey J. Faulkner, Omer Gilan
Journal: Genome biology (2024)

Cell types are traditionally thought to be specified and stabilized by gene regulatory networks. Here, we explore how chromatin memory contributes to the specification and stabilization of cell states. Through pervasive, local, feedback loops, chromatin memory enables cell states that were initially unstable to become stable. Deeper appreciation of this self-stabilizing role for chromatin broadens our perspective of Waddington's epigenetic landscape from a static surface with islands of stability shaped by evolution, to a plasticine surface molded by experience. With implications for the evolution of cell types, stabilization of resistant states in cancer, and the widespread plasticity of complex life.
Resveratrol amplifies the anti-tumor effect of α-PD-1 by altering the intestinal microbiome and PGD2 content
Authors: Baohua Luo, Qingling An, Jingyu Lei, Dengxu Tan, Xiaoqiu Liu, Hui Li, Yong Zhao, Jing Qin, Caiqin Zhang, Yongbin Zhang, Changhong Shi
Journal: Gut Microbes (2024)

Patients with pancreatic cancer (PC) receive limited benefits from immune checkpoint inhibitors (ICIs) alone. Recent studies have indicated that the combination of intestinal microflora regulators and ICI may be an effective strategy for enhancing the response to tumor immunotherapy. Resveratrol has been shown to regulate both intestinal microbiota and the immune microenvironment; therefore, we speculated that resveratrol may enhance the immunotherapeutic effect of α-PD-1 on PC. We constructed a double-humanized mouse model with both a humanized immune system and PC to evaluate the efficacy of different doses of resveratrol combined with anti-PD-1 mAb therapy and analyze the characteristics of the tumor immune microenvironment after treatment. In addition, I6S sequencing was performed on mouse fecal samples, and metabolomic analyses were performed on plasma samples to understand the characteristics of the intestinal microbiome and metabolites to explore the potential mechanism of anti-tumor immunity mediated by combined immunotherapy. Results suggested that the combination of resveratrol with anti-PD-1 mAb promoted the infiltration and activation of CD8+ T cells in tumor tissues, thus effectively inhibiting PC growth. Attentively, the effect emphasized the combined effect, dose-dependent nature and the involvement of gut microbiome. Furthermore, metabonomics showed that the combination therapy significantly increased the abundance of the metabolite prostaglandin D2 (PGD2), which was most likely related to the increased abundance of Desulfovibrio fairfieldensis. Finally, we confirmed that PGD2 amplified anti-tumor effect of α-PD-1 by activating prostaglandin D receptor 1 (DP1) to promote CD8 infiltration in double humanized PC mice and subcutaneously transplanted KPC mice. Overall, our data revealed resveratrol has the potential to enhance the efficacy of α-PD-1 by regulating the gut microbiome and its metabolites, and PGD2 was an effective molecular mediating the infiltration of CD8+T cells into tumor tissue to amplify the anti-tumor effect of α-PD-1.