tbuckley/cabot-search huggingface dataset:
Evaluation of Systolic Function of the Right Ventricle in Patients with Chronic Obstructive Pulmonary Disease: A Cross Sectional Study about 30 Cases
Authors: NGAIDE Aliou Alassane, GAYE Ngoné Diaba, SARR Simon Antoine, AW Fatou, DIOUM Momar
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Introduction: Chronic pulmonary heart is the main cardiovascular complication of chronic obstructive pulmonary disease. The aims of our study were to evaluate the right ventricular systolic function in patients with chronic obstructive pulmonary disease and to investigate the relationship between parameters of right ventricular function and pulmonary function testing data. Methodology: A multicenter cross-sectional study was conducted between January 2013 and July 2013 in cardiology and pulmonology department in Dakar. Was included all in or outpatient diagnosed for chronic obstructive pulmonary disease. Results: 30 patients were evaluated in this cohort. The mean age was 62.4 years. Male predominance was noted (sex ratio of 9). Right heart failure was found in 7 patients (23.3%) had. Right ventricule enlargement was noted in 12 patients (40%). Mean sPAP was 58.58 ± 23.59 mmHg. Pulmonary arterial hypertension was found in 16 (53.3%) patients. TAPSE was impaired in 7 patients (23.3%). Reduction of right ventricule fractional area change was present in 14 (46.6%) patients. S’ of the tricuspid annulus velocity was reduced in 11 (33%) patients. Parameters correlated with the severity of chronic obstructive pulmonary disease were: TAPSE (p= 0.0099), right ventricule fractional area change (p = 0.0095), S’ of the annular tricuspid (p= 0.0173) TEI index (p= 0.038) and Pulmonary arterial hypertension (p= 0,023). Conclusion: Evaluation of right ventricular systolic function in chronic obstructive pulmonary disease is fundamental and must use multiple parameters.
Abstract B014: CHD5 suppresses glioblastoma by inhibiting MYC
Authors: Xueqin Sherine Sun, Alea Mills
Journal: Cancer Research (2024)

Abstract Fundamentally, cancer is a disease caused by genetic and epigenetic alterations that converge to reprogram gene expression networks, leading to unrestrained proliferation. Glioblastoma (GBM) is the most prevalent and aggressive primary brain cancer, median survival being approximately one year and the 5-year survival rate being only 5%. Despite decades of effort, this devastating picture has not appreciably improved and effective therapies have been elusive for GBM patients. A better understanding of GBM biology is essential for developing more effective therapies. Although several genetic alterations have been implicated in gliomagenesis, driving genetic factors responsible for GBM are still obscure, and the interplay between genetic alterations and epigenetic dysregulation is largely undocumented during the gliomagenic process. Here, we show that CHD5 — a gene mapping to the 1p36 chromosomal region that is notoriously deleted in many cancers, is recurrently deleted in over 20% of GBM cases and is further downregulated through epigenetic means. To delineate how CHD5 loss promotes gliomagenesis, we established a glioma-prone mouse model harboring conditional alleles of Pten, Trp53, and Chd5. We developed an engineered mouse neural stem cell (NSCs)-based strategy to elicit glioma formation, as NSCs are the major cell-of-origin for GBM. We show that Chd5 loss significantly impairs NSCs differentiation while promoting proliferation, transformation, and gliomagenesis in vivo. Mechanistically, Chd5 forms a Chd3-containing but Chd4-independent NuRD complex that directly binds the Myc promoter and super enhancers to govern Myc expression in normal NSCs, with the Snf2 domain of Chd5 playing the most critical chromatin regulating role in the context of GBM. Chd5 loss triggers the remodeling of chromatin, enhances accessibility, and augments Myc expression, leading to the formation of highly aggressive glioma. Furthermore, reactivating CHD5 in human GBM xenograft models significantly extends survival. This work demonstrates the tumor suppressive role of CHD5 in gliomagenesis, providing therapeutic insights for cancers with 1p36 deletions. In parallel, this work presents a powerful strategy for rapidly interrogating gene function during gliomagenesis using engineering NSCs and highlights the generation of novel mouse models with classic clinical features of GBM, offering new approaches for elucidating GBM biology that can inform on therapeutic opportunities for treating patients with GBM. Citation Format: Xueqin Sherine Sun, Alea Mills. CHD5 suppresses glioblastoma by inhibiting MYC [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B014.
scAbsolute: measuring single-cell ploidy and replication status
Authors: Michael P Schneider, Amy E Cullen, Justina Pangonyte, Jason Skelton, Harvey Major, Elke Van Oudenhove, Maria J Garcia, Blas Chaves Urbano, Anna M Piskorz, James D Brenton, Geoff Macintyre, Florian Markowetz
Journal: Genome biology (2024)

Abstract Cancer cells often exhibit DNA copy number aberrations and can vary widely in their ploidy. Correct estimation of the ploidy of single-cell genomes is paramount for downstream analysis. Based only on single-cell DNA sequencing information, scAbsolute achieves accurate and unbiased measurement of single-cell ploidy and replication status, including whole-genome duplications. We demonstrate scAbsolute’s capabilities using experimental cell multiplets, a FUCCI cell cycle expression system, and a benchmark against state-of-the-art methods. scAbsolute provides a robust foundation for single-cell DNA sequencing analysis across different technologies and has the potential to enable improvements in a number of downstream analyses.
Three near-complete genome assemblies reveal substantial centromere dynamics from diploid to tetraploid in Brachypodium genus
Authors: Chuanye Chen, Siying Wu, Yishuang Sun, Jingwei Zhou, Yiqian Chen, Jing Zhang, James A Birchler, Fangpu Han, Ning Yang, Handong Su
Journal: Genome biology (2024)

Abstract Background Centromeres are critical for maintaining genomic stability in eukaryotes, and their turnover shapes genome architectures and drives karyotype evolution. However, the co-evolution of centromeres from different species in allopolyploids over millions of years remains largely unknown. Results Here, we generate three near-complete genome assemblies, a tetraploid Brachypodium hybridum and its two diploid ancestors, Brachypodium distachyon and Brachypodium stacei . We detect high degrees of sequence, structural, and epigenetic variations of centromeres at base-pair resolution between closely related Brachypodium genomes, indicating the appearance and accumulation of species-specific centromere repeats from a common origin during evolution. We also find that centromere homogenization is accompanied by local satellite repeats bursting and retrotransposon purging, and the frequency of retrotransposon invasions drives the degree of interspecies centromere diversification. We further investigate the dynamics of centromeres during alloploidization process, and find that dramatic genetics and epigenetics architecture variations are associated with the turnover of centromeres between homologous chromosomal pairs from diploid to tetraploid. Additionally, our pangenomes analysis reveals the ongoing variations of satellite repeats and stable evolutionary homeostasis within centromeres among individuals of each Brachypodium genome with different polyploidy levels. Conclusions Our results provide unprecedented information on the genomic, epigenomic, and functional diversity of highly repetitive DNA between closely related species and their allopolyploid genomes at both coarse and fine scale.
Abstract B043: Feasibility of a traceback approach to facilitate genetic testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) study
Authors: Larissa L. White, Yolanda K. Prado, Ana A. Reyes, Jamilyn M. Zepp, Jennifer Sawyer, Mahesh Maiyani, Rachel Zucker, Sarah Vertrees, Alan F. Rope, Sheila Weinmann, Mika Caruncho, Sandra Soo-Jin Lee, Nora B. Henrikson, Heather Spencer Feigelson, Jessica Ezzell Hunter
Journal: Cancer Research (2024)

Abstract Current guidelines state that genetic testing is clinically indicated for all individuals diagnosed with ovarian cancer (OC). Individuals with a prior diagnosis of OC who have not received genetic testing represent missed opportunities to identify individuals and their families with inherited variants that put them at a higher risk for cancer. The Genetic Risk Analysis in Ovarian Cancer (GRACE) study aims to address this significant healthcare gap using a “traceback testing” approach to identify individuals with a prior diagnosis of OC and to offer genetic risk information to them and their family members. Tumor registry data at two integrated health care systems (Kaiser Permanente Northwest and Colorado) identified cases of OC diagnosed 1998-2020 with no prior genetic testing or testing limited to BRCA1/2. The study aimed to provide genetic risk information to OC survivors as well as family members of patients who were deceased by leveraging stored pathology specimens for germline testing. Comprehensive genetic testing using a panel of 60 cancer risk genes was offered; genetic testing of the familial variant was offered to first- and second-degree relatives if a pathogenic or likely pathogenic variant was detected. A total of 317 eligible OC survivors were identified from tumor registry and medical record review; 79 (25%) consented for testing. Sixteen (21%) were found to carry a pathogenic or likely pathogenic variant in a cancer risk gene. Genes with pathogenic variants included BRCA1/2, BARD1, PMS2, DICER1, MUTYH, APC, and SDHB. Of 73 relatives eligible for cascade testing, 24 consented (≈ 33% uptake) and 9 were found to carry the familial variant. The uptake of testing by OC survivors and their relatives reflects a strong interest in genetic risk information. However, practical barriers must be addressed to provide genetic risk information to relatives of individuals who are deceased. The GRACE study can inform broad implementation of future traceback programs, providing information to prevent and mitigate the burden of ovarian and other hereditary cancers. Citation Format: Larissa L. White, Yolanda K. Prado, Ana A. Reyes, Jamilyn M. Zepp, Jennifer Sawyer, Mahesh Maiyani, Rachel Zucker, Sarah Vertrees, Alan F. Rope, Sheila Weinmann, Mika Caruncho, Sandra Soo-Jin Lee, Nora B. Henrikson, Heather Spencer Feigelson, Jessica Ezzell Hunter. Feasibility of a traceback approach to facilitate genetic testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) study [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B043.
Venoarterial extracorporeal membrane oxygenation in immunocompromised patients with cardiogenic shock: a cohort study and propensity-weighted analysis
Authors: Quentin Moyon, Félicien Triboulet, Jean Reuter, Guillaume Lebreton, Amandine Dorget, Marylou Para, Juliette Chommeloux, Jules Stern, Marc Pineton de Chambrun, Guillaume Hékimian, Charles-Edouard Luyt, Alain Combes, Romain Sonneville, Matthieu Schmidt
Journal: Intensive Care Medicine (2024)
Classes and predictors of reversal in male patients with congenital hypogonadotropic hypogonadism: a cross-sectional study of six international referral centres
Authors: Andrew A Dwyer, Isabella R McDonald, Biagio Cangiano, Luca Giovanelli, Luigi Maione, Leticia F G Silveira, Taneli Raivio, Ana Claudia Latronico, Jacques Young, Richard Quinton, Marco Bonomi, Luca Persani, Stephanie B Seminara, Christopher S Lee
Journal: The Lancet Diabetes & Endocrinology (2024)
Abstract A053: Understanding geospatial relationships in ovarian cancer risk
Authors: Victoria Wang, Jaime Hart, Kevin Elias
Journal: Cancer Research (2024)

Abstract To examine the geographic distribution of ovarian cancer cases in the New England area and identify potential case clusters. Methods: This was a case-control study utilizing 1580 ovarian cancer patients from a single healthcare system (MGB). Using electronic health record (EHR) review, patient primary addresses were geocoded. To account for spatial distribution confounded by access to the MGB health system, 1750 patients from the MGB biobank system were geocoded as controls. Generalized additive models were used to determine the spatial patterning of cases and controls, controlled for age and race. Geospatial analysis was performed using ArcGIS software and R. Results: 3325 patients (1576 ovarian cancer patients, 1749 biobank controls) were successfully geocoded. Distribution of ovarian cancer cases and biobank patient controls were similar (average nearest neighbor distance 6337m vs 5623 m). Among the cohort of patients in New England (defined as MA, ME, NH, VT, RI, CT), there were 1476 ovarian cancer patients and 1663 biobank control patients. Use of a generalized additive model demonstrated higher incidence of ovarian cancer in Western CT, western MA, VT, and southern ME. These data are similar to SEER reported county-level incidence of late-stage ovarian cancer. Conclusions: Understanding the geospatial distribution of ovarian cancer cases can highlight potential clusters of higher incidences of disease. Causal relationships have yet to be established and require future investigation, but these data suggest spatially patterned exposures are worth examination. Citation Format: Victoria Wang, Jaime Hart, Kevin Elias. Understanding geospatial relationships in ovarian cancer risk [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A053.
Apoptotic extracellular vesicles restore homeostasis of the articular microenvironment for the treatment of rheumatoid arthritis
Authors: Xian Li, Shichun Li, Xiaoling Fu, Yingjun Wang
Journal: Bioactive Materials (2024)

Rheumatoid arthritis (RA) is a severe autoimmune disease with symptoms including synovial inflammation, cartilage erosion, and bone loss in RA lesions, which eventually lead to joint deformity and function loss. Most current treatments fail to achieve satisfying therapeutic outcomes with some adverse effects. Extracellular vesicles derived from apoptotic cells (apoEVs) have emerged as important mediators in intercellular communication regulating diverse physiological and pathological processes. In this study, we investigated the therapeutic efficacy of macrophage-derived and osteoclast-derived apoEVs (Mφ-apoEVs and OC-apoEVs) on RA. The
Mucoadhesive liposomal delivery system synergizing anti-inflammation and anti-oxidation for enhanced treatment against dry eye disease
Authors: Kexin Huang, Rong Guo, Haoyuan Luo, Houqin Liu, Dong Chen, Tao Deng, Jiaxin Li, Jiao He, Zhuping Xu, Man Li, Qin He
Journal: Journal of Controlled Release (2024)
Systemic delivery of proteins using novel peptides via the sublingual route
Authors: Jiamin Wu, Natalie Jones, Lukas Hohenwarter, Feng Zhao, Vanessa Chan, Zheng Tan, Tiffany Carlaw, Tessa Morin, Jing Li, Tejinder Kaur, Lucas J. Andrew, Colin J.D. Ross, Sarah Hedtrich, Shyh-Dar Li
Journal: Journal of Controlled Release (2024)
Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade
Authors: Saeid Moghassemi, Arezoo Dadashzadeh, Maria João Sousa, Hanne Vlieghe, Jie Yang, Cecibel María León-Félix, Christiani A. Amorim
Journal: Bioactive Materials (2024)

Small extracellular vesicles (sEVs) are known to be secreted by a vast majority of cells. These sEVs, specifically exosomes, induce specific cell-to-cell interactions and can activate signaling pathways in recipient cells through fusion or interaction. These nanovesicles possess several desirable properties, making them ideal for regenerative medicine and nanomedicine applications. These properties include exceptional stability, biocompatibility, wide biodistribution, and minimal immunogenicity. However, the practical utilization of sEVs, particularly in clinical settings and at a large scale, is hindered by the expensive procedures required for their isolation, limited circulation lifetime, and suboptimal targeting capacity. Despite these challenges, sEVs have demonstrated a remarkable ability to accommodate various cargoes and have found extensive applications in the biomedical sciences. To overcome the limitations of sEVs and broaden their potential applications, researchers should strive to deepen their understanding of current isolation, loading, and characterization techniques. Additionally, acquiring fundamental knowledge about sEVs origins and employing state-of-the-art methodologies in nanomedicine and regenerative medicine can expand the sEVs research scope. This review provides a comprehensive overview of state-of-the-art exosome-based strategies in diverse nanomedicine domains, encompassing cancer therapy, immunotherapy, and biomarker applications. Furthermore, we emphasize the immense potential of exosomes in regenerative medicine.
Neoadjuvant Peptide Receptor Radionuclide Therapy in a Rare Case of Pediatric Primary Hepatic Gastrinoma
Authors: Sougata Mahato, Piyush Aggarwal, Chennakeshava Thunga, Ashwani Sood, Ravi P. Kanojia, Ritambhra Nada, Sadhna B. Lal
Journal: Clinical Nuclear Medicine (2024)

Gastrinomas with predilection for the adult male population are located in the gastrinoma triangle (>90%). Primary hepatic gastrinoma especially in pediatric population is very rare. Peptide receptor radionuclide therapy has shown benefit in metastatic gastroenteropancreatic neuroendocrine tumors (NETs) with an increasing interest in expanding its role as neoadjuvant treatment modality to improve the surgical candidature in inoperable NETs. There is currently no literature supporting its role in the pediatric NET patients. We present a rare case of a young boy with primary hepatic gastrinoma where 177Lu-based peptide receptor radionuclide therapy in the neoadjuvant setting contributed to his final disease-free status.
Can 18F-FES PET Improve the Evaluation of 18F-FDG PET in Patients With Metastatic Invasive Lobular Carcinoma?
Authors: Cheng Liu, Guang Ma, Xiaoping Xu, Shaoli Song, Zhongyi Yang
Journal: Clinical Nuclear Medicine (2024)

Invasive lobular carcinoma (ILC) exhibits a low affinity for 18F-FDG. The estrogen receptor (ER) is commonly expressed in ILCs, suggesting a potential benefit of targeting with the ER probe 18F-FES in this patient population. The objective of this study was to evaluate the diagnostic performance of 18F-FES imaging in patients with metastatic ILC and compare it with that of 18F-FDG.
18F-FDG and 68Ga-PSMA PET/CT in Paratesticular Mesothelioma
Authors: Forough Kalantari, Gregor Schweighofer-Zwink, Gundula Rendl, Christian Pirich, Mohsen Beheshti
Journal: Clinical Nuclear Medicine (2024)

Abstract A 66-year-old man with local prostate adenocarcinoma underwent radical prostatectomy (Gleason score 3 + 4 = 7, pT2c) in 2016. Four years later, he presented with a hydrocele and cystic atypical change in the left scrotum and soft tissue in the left groin. Final histopathology revealed spermatic cord mesothelioma and left hemangiosis carcinomatosa. A bone biopsy of the sacrum revealed infiltrates of a prostatic adenocarcinoma with small cell neuroendocrine differentiation. Dual-tracer PET/CT imaging using 18 F-FDG and 68 Ga-PSMA was able to identify local recurrence of scrotal mesothelioma and differentiate metastases of prostate cancer from malignant mesothelioma.
FDG PET/CT Findings of a Small Cell Carcinoma of the Lung Presented as Diffuse Dermatomyositis
Authors: Xinyu Li, Bin Tian, Xia Bai
Journal: Clinical Nuclear Medicine (2024)

Patients with dermatomyositis are prone to have occult malignancy. A previously healthy 68-year-old man with dermatomyositis underwent FDG PET/CT to detect possible malignancy of unknown origin. The images showed not only diffuse increased activity in the muscle, which was related to the known dermatomyositis, but also intense activity in the anterior chest with foci of abnormal activity throughout the body. Pathology examination confirmed small cell carcinoma of the lung with widespread metastases.
Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis
Authors: Peng Hua, Ruifeng Liang, Suleixin Yang, Yanbei Tu, Meiwan Chen
Journal: Bioactive Materials (2024)

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.
Combination of disulfiram and Copper−Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer
Authors: Lijun Yang, Cancan Yao, Zhenning Su, Yihao Fang, Nil Kanatha Pandey, Eric Amador, Tian Diao, Guo Bao, Derong Cao, Xihua Chen, Xiangbo Xu, Bin He, Yufeng Zheng, Wei Chen
Journal: Bioactive Materials (2024)

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu