tbuckley/cabot-search huggingface dataset:
Cardiac and perivascular myofibroblasts, matrifibrocytes, and immune fibrocytes in hypertension; commonalities and differences with other cardiovascular diseases
Authors: Keiichi Torimoto, Katherine Elliott, Yuki Nakayama, Hiromi Yanagisawa, Satoru Eguchi
Journal: Cardiovascular Research (2024)

Abstract Hypertension is a major cause of cardiovascular diseases such as myocardial infarction and stroke. Cardiovascular fibrosis occurs with hypertension and contributes to vascular resistance, aortic stiffness, and cardiac hypertrophy. However, the molecular mechanisms leading to fibroblast activation in hypertension remain largely unknown. There are two types of fibrosis: replacement fibrosis and reactive fibrosis. Replacement fibrosis occurs in response to the loss of viable tissue to form a scar. Reactive fibrosis occurs in response to an increase in mechanical and neurohormonal stress. Although both types of fibrosis are considered adaptive processes, they become maladaptive when the tissue loss is too large, or the stress persists. Myofibroblasts represent a subpopulation of activated fibroblasts that have gained contractile function to promote wound healing. Therefore, myofibroblasts are a critical cell type that promotes replacement fibrosis. Although myofibroblasts were recognized as the fibroblasts participating in reactive fibrosis, recent experimental evidence indicated there are distinct fibroblast populations in cardiovascular reactive fibrosis. Accordingly, we will discuss the updated definition of fibroblast subpopulations, the regulatory mechanisms, and their potential roles in cardiovascular pathophysiology utilizing new knowledge from various lineage tracing and single-cell RNA sequencing studies. Among the fibroblast subpopulations, we will highlight the novel roles of matrifibrocytes and immune fibrocytes in cardiovascular fibrosis including experimental models of hypertension, pressure overload, myocardial infarction, atherosclerosis, aortic aneurysm, and nephrosclerosis. Exploration into the molecular mechanisms involved in the differentiation and activation of those fibroblast subpopulations may lead to novel treatments for end-organ damage associated with hypertension and other cardiovascular diseases.
The <i>Helicobacter pylori cag</i> pathogenicity island as a determinant of gastric cancer risk
Authors: Sirena C. Tran, Kaeli N. Bryant, Timothy L. Cover
Journal: Gut Microbes (2024)

Helicobacter pylori strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the cag pathogenicity island (cag PAI). Colonization of the human stomach with cag PAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with cag PAI-negative strains. The cag PAI encodes a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS) that delivers CagA and non-protein substrates into host cells. Animal model experiments indicate that CagA and the Cag T4SS stimulate a gastric mucosal inflammatory response and contribute to the development of gastric cancer. In this review, we discuss recent studies defining structural and functional features of CagA and the Cag T4SS and mechanisms by which H. pylori strains containing the cag PAI promote the development of gastric cancer and peptic ulcer disease.
Myocardial Infarction and Cardiac Arrest During Acquisition of 18F-FDG PET/CT
Authors: Bilal M. Omery, Amitjeet S. Kalirao
Journal: Clinical Nuclear Medicine (2024)

Abstract An 83-year-old man with multiple myeloma and history of coronary artery disease and ischemic cardiomyopathy experienced cardiac arrest during the 18 F-FDG PET/CT examination. The patient had not yet been treated for multiple myeloma. The PET/CT demonstrated focal FDG uptake about the left anterior descending coronary artery. Diffuse intense FDG uptake in the liver and less than normal uptake in other organs of usual FDG distribution were also present, likely due to altered hemodynamics and heart failure in the setting of an acute coronary syndrome.
Unusual 131I Uptake Caused by Paronychia in a Patient With Papillary Thyroid Cancer
Authors: Jun Yang, Zhengzhou Pan, Xinhui Su
Journal: Clinical Nuclear Medicine (2024)

A 33-year-old woman was referred for radioiodine 6 months after total thyroidectomy and neck dissection for papillary thyroid cancer. Posttherapy whole-body 131 I scintigraphy showed not only the known activity in the neck but also accumulated activity in both feet. SPECT/CT revealed focal uptake in bilateral great toenails. On further clinical evaluation and follow-up, the patient was diagnosed as paronychia of the great toenails.
Physician Estimates and Patient-Reported Health Status in Atrial Fibrillation
Authors: Nobuhiro Ikemura, Shun Kohsaka, Takehiro Kimura, Philip G. Jones, Yoshinori Katsumata, Kojiro Tanimoto, Ikuko Ueda, Seiji Takatsuki, Masaki Ieda, Paul S. Chan, John A. Spertus
Journal: JAMA Network Open (2024)

A primary objective in managing atrial fibrillation (AF) is to optimize patients' health status, which can be done only if physicians accurately quantify the outcomes associated with AF in patients' lives.
Spontaneous Breathing Trial Techniques for Extubating Adults and Children Who Are Critically Ill
Authors: Karen E. A. Burns, Jeena Khan, Vorakamol Phoophiboon, Vatsal Trivedi, J. Carolina Gomez-Builes, Benedetta Giammarioli, Kimberley Lewis, Dipayan Chaudhuri, Kairavi Desai, Jan O. Friedrich
Journal: JAMA Network Open (2024)

Considerable controversy exists regarding the best spontaneous breathing trial (SBT) technique to use.
Pluvicto-Induced 18F-PSMA PET Bone Flare
Authors: Xiaofei Wang, Daniel Martin, Thomas Hogan, Kenneth Veselicky
Journal: Clinical Nuclear Medicine (2024)

Abstract A 79-year-old man with a history of metastatic prostate cancer was initially treated with Eligard and switched to relugolix in 2021. The 2022 bone scan presented superscan and extensive osseous metastatic lesions; some had intense PSMA uptake on the initial PSMA PET scan without nodal or visceral metastatic lesions. We treated him with Pluvicto and relugolix. The intermediate PSMA scan demonstrated prominent bone marrow PSMA uptake. However, PSA decreased 58.5%. We hypothesized that the patient might have a bone flare. The final PSMA scan confirmed our hypothesis. Based on our knowledge, this is the first case of Pluvicto-induced bone flare.
Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer
Authors: R.S. Laskar, C. Qu, J.R. Huyghe, T. Harrison, R.B. Hayes, Y. Cao, P.T. Campbell, R. Steinfelder, F.R. Talukdar, H. Brenner, S. Ogino, S. Brendt, D.T. Bishop, D.D. Buchanan, A.T. Chan, M. Cotterchio, S.B. Gruber, A. Gsur, B. van Guelpen, M.A. Jenkins, T.O. Keku, B.M. Lynch, L. Le Marchand, R.M. Martin, K. McCarthy, V. Moreno, R. Pearlman, M. Song, K.K. Tsilidis, P. Vodička, M.O. Woods, K. Wu, L. Hsu, M.J. Gunter, U. Peters, N. Murphy
Journal: Annals of Oncology (2024)

The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.
Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance
Authors: Tomoka Gose, Ali Rasouli, Sepehr Dehghani-Ghahnaviyeh, Po-Chao Wen, Yao Wang, John Lynch, Yu Fukuda, Talha Shafi, Robert C. Ford, Emad Tajkhorshid, John D. Schuetz
Journal: Drug Resistance Updates (2024)
Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells
Authors: Weiwei Yi, Jinhua Zhang, Yingxin Huang, Qiang Zhan, Mi Zou, Xiang Cheng, Xuguang Zhang, Zhinan Yin, Si Tao, Hui Cheng, Fudi Wang, Jun Guo, Zhenyu Ju, Zhiyang Chen
Journal: Leukemia (2024)
Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus
Authors: T.C. Rodrigues, D.B. Figueiredo, V.M. Gonçalves, K. Kaneko, I.Y. Saleem, E.N. Miyaji
Journal: Journal of Controlled Release (2024)

Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4
A case-based narrative review of pregnancy-associated atypical hemolytic uremic syndrome/complement-mediated thrombotic microangiopathy
Authors: Michael Che, Sarah M. Moran, Richard J. Smith, Kevin Y.M. Ren, Graeme N. Smith, M. Khaled Shamseddin, Carmen Avila-Casado, Jocelyn S. Garland
Journal: Kidney International (2024)

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy (TMA), caused by uncontrolled activation of the alternative complement pathway in the setting of autoantibodies to or rare pathogenic genetic variants in complement proteins. Pregnancy may serve as a trigger and unmask aHUS/complement-mediated TMA [aHUS/CM-TMA] which has severe, life-threatening consequences. It can be difficult to diagnose aHUS/CM-TMA in pregnancy due to overlapping clinical features with other TMA syndromes including hypertensive disorders of pregnancy. However, the distinction among TMA etiologies in pregnancy is important as each syndrome has specific disease management and treatment. In this narrative review, we discuss two cases to illustrate the diagnostic challenges and evolving approach in the management of pregnancy-associated aHUS/CM-TMA. The first case involves a 30-year-old female presenting in the first trimester who was diagnosed with aHUS/CM-TMA and treated with eculizumab from 19 weeks gestation. Genetic testing revealed a likely pathogenic variant in CFI. She successfully delivered a healthy infant at 30 weeks gestation. In the second case, a 22-year-old female developed severe postpartum HELLP syndrome and required hemodialysis. Her condition improved with supportive management, yet investigations assessing for aHUS/CM-TMA remained abnormal 6 months postpartum consistent with persistent complement activation but negative genetic testing. Through detailed case discussion describing tests assessing for placental health, fetal anatomy, complement activation, autoantibodies to complement regulatory proteins, and genetic testing for aHUS/CM-TMA, we describe how these results aided in the clinical diagnosis of pregnancy-associated aHUS/CM-TMA and assisted in guiding patient management including the use of anti-complement therapy.
S-amlodipine induces liver inflammation and dysfunction through the alteration of intestinal microbiome in a rat model
Authors: Xinxin Liu, Hui Fang, Liuzhu Pan, Peng Zhang, Huai Lin, Huihui Gao, Chaolin Ye, Daqing Mao, Yi Luo
Journal: Gut Microbes (2024)

S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further
Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages
Authors: Zhen He, Hongyu Xie, Haoyang Xu, Jinjie Wu, Wanyi Zeng, Qilang He, Christian Jobin, Sanqing Jin, Ping Lan
Journal: Gut Microbes (2024)

The gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in
Activation-induced cytidine deaminase causes recurrent splicing mutations in diffuse large B-cell lymphoma
Authors: Maria S. Benitez-Cantos, Carlos Cano, Marta Cuadros, Pedro P. Medina
Journal: Molecular Cancer (2024)

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma. A major mutagenic process in DLBCL is aberrant somatic hypermutation (aSHM) by activation-induced cytidine deaminase (AID), which occurs preferentially at R C H/ T W sequence motifs proximal to transcription start sites. Splice sequences are highly conserved, rich in R C H/ T W motifs, and recurrently mutated in DLBCL. Therefore, we hypothesized that aSHM may cause recurrent splicing mutations in DLBCL. In a meta-cohort of &gt; 1,800 DLBCLs, we found that 77.5% of splicing mutations in 29 recurrently mutated genes followed aSHM patterns. In addition, in whole-genome sequencing (WGS) data from 153 DLBCLs, proximal mutations in splice sequences, especially in donors, were significantly enriched in R C H/ T W motifs ( p &lt; 0.01). We validated this enrichment in two additional DLBCL cohorts (N &gt; 2,000; p &lt; 0.0001) and confirmed its absence in 12 cancer types without aSHM (N &gt; 6,300). Comparing sequencing data from mouse models with and without AID activity showed that the splice donor sequences were the top genomic feature enriched in AID-induced mutations ( p &lt; 0.0001). Finally, we observed that most AID-related splice site mutations are clonal within a sample, indicating that aSHM may cause early loss-of-function events in lymphomagenesis. Overall, these findings support that AID causes an overrepresentation of clonal splicing mutations in DLBCL. Graphical Abstract
Risk models in myelofibrosis—the past, present, and future
Authors: Ayalew Tefferi, Alessandro M. Vannucchi
Journal: American Journal of Hematology (2024)

Risk models in myelofibrosis (MYSEC-PM) or primary myelofibrosis (IPSS, DIPSS, DIPSS+, MIPSS70, MIPSS70+, MIPSSv2, GIPSS). No conflicts of interest related to this editorial are declared. Data S1. Supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Iron restriction in sickle cell disease: When less is more
Authors: Oswaldo L. Castro, Lucia De Franceschi, Tomas Ganz, Julie Kanter, Gregory J. Kato, Sant‐Rayn Pasricha, Stefano Rivella, John C. Wood
Journal: American Journal of Hematology (2024)

Primum non nocere! Can iron deficiency, an abnormality that causes anemia, benefit people with sickle cell disease (SCD) who already have an anemia? The published literature we review appears to answer this question in the affirmative: basic science considerations, animal model experiments, and noncontrolled clinical observations all suggest a therapeutic potential of iron restriction in SCD. This is because SCD's clinical manifestations are ultimately attributable to the polymerization of hemoglobin S (HbS), a process strongly influenced by intracellular HbS concentration. Even small decrements in HbS concentration greatly reduce polymerization, and iron deficiency lowers erythrocyte hemoglobin concentration. Thus, iron deficiency could improve SCD by changing its clinical features to those of a more benign anemia (i.e., a condition with fewer or no vaso-occlusive events). We propose that well-designed clinical studies be implemented to definitively determine whether iron restriction is a safe and effective option in SCD. These investigations are particularly timely now that pharmacologic agents are being developed, which may directly reduce red cell hemoglobin concentrations without the need for phlebotomies to deplete total body iron.
Small cells – big issues: biological implications and preclinical advancements in small cell lung cancer
Authors: Anna Solta, Büsra Ernhofer, Kristiina Boettiger, Zsolt Megyesfalvi, Simon Heeke, Mir Alireza Hoda, Christian Lang, Clemens Aigner, Fred R. Hirsch, Karin Schelch, Balazs Döme
Journal: Molecular Cancer (2024)

Abstract Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain inflammatory characteristics. The role of the transcription regulator YAP1 in defining a unique SCLC subset remains to be established. Although preclinical analyses have described numerous subtype-specific characteristics and vulnerabilities, the so far non-existing clinical subtype distinction may be a contributor to negative clinical trial outcomes. This comprehensive review aims to provide a framework for the development of novel personalized therapeutic approaches by compiling the most recent discoveries achieved by preclinical SCLC research. We highlight the challenges faced due to limited access to patient material as well as the advances accomplished by implementing state-of-the-art models and methodologies.
The role of MicroRNAs as early biomarkers of asbestos-related lung cancer: A systematic review and meta-analysis
Authors: D. Mukhopadhyay, P. Cocco, S. Orrù, R. Cherchi, S. De Matteis
Journal: Pulmonology (2024)

Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM. To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis. MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale. From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132–3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197‑3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574–5p; no miRNA was found associated to LC prognosis. Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.
Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice
Authors: Sanne de Wit, Lotte Geerlings, Canxia Shi, Just Dronkers, Elisabeth M Schouten, Gillian Blancke, Vanessa Andries, Tess Yntema, Wouter C Meijers, Debby P Y Koonen, Lars Vereecke, Herman H W Silljé, Joseph-Pierre Aboumsallem, Rudolf A de Boer
Journal: Cardiovascular Research (2024)

Heart failure (HF) and cancer are the leading causes of death worldwide. Epidemiological studies revealed that HF patients are prone to develop cancer. Preclinical studies provided some insights into this connection, but the exact mechanisms remain elusive. In colorectal cancer (CRC), gut microbial dysbiosis is linked to cancer progression and recent studies have shown that HF patients display microbial dysbiosis. This current study focussed on the effects of HF-induced microbial dysbiosis on colonic tumour formation.