keyword
https://read.qxmd.com/read/38547453/fibrinogen-levels-and-clot-properties-identify-patients-that-benefit-from-catheter-directed-thrombolysis-after-dvt
#1
JOURNAL ARTICLE
Aaron F J Iding, Ghadir Alkarithi, Hugo Ten Cate, Robert A S Ariëns, Arina J Ten Cate-Hoek
Ultrasound-accelerated catheter-directed thrombolysis (UA-CDT) to improve patency after deep vein thrombosis (DVT) has not conclusively been shown to prevent post-thrombotic syndrome (PTS) but might benefit patients who are unlikely to obtain patency with standard treatment. We hypothesized that these patients could be selected based on their fibrin clot properties. To study this, patients with acute iliofemoral DVT from the CAVA trial had blood samples taken at inclusion. Fibrin clot properties in plasma were determined by turbidimetric clotting (lag time and maximal turbidity) and lysis assays (time to 50% lysis and lysis rate), permeation assay (Ks), and confocal microscopy (fiber density), as well as levels of fibrin clot modifiers fibrinogen and C-reactive protein (CRP)...
March 28, 2024: Blood Advances
https://read.qxmd.com/read/38547445/synthesis-antimicrobial-and-in-silico-studies-of-c5-o-substituted-cytidine-derivatives-cinnamoylation-leads-to-improvement-of-antimicrobial-activity
#2
JOURNAL ARTICLE
Tahmida Sultana Bhuiyan, Mohamed A Said, Md Z H Bulbul, Sumeer Ahmed, Ajmal R Bhat, Mohammed Chalkha, Sarkar M A Kawsar
Nucleoside derivatives are important therapeutic drugs that have drawn significant attention recently. In this study, cytidine ( 1 ) was first exposed to react with cinnamoyl chloride in N , N -dimethylformamide, and trimethylamine to obtain 5'- O -(cinnamoyl)cytidine, which was further treated with several acylating agents to obtain a series of 2',3'-di- O -acyl derivatives. The chemical structures of the synthesized compounds were established through spectral, analytical, and physicochemical techniques. In vitro antimicrobial efficacy was evaluated, and the antimicrobial effect was greater than that of the precursor compound; in particular, compound 3 exhibited the most promising activity...
March 28, 2024: Nucleosides, Nucleotides & Nucleic Acids
https://read.qxmd.com/read/38547254/a-clinically-attenuated-double-mutant-of-porcine-reproductive-and-respiratory-syndrome-virus-2-that-does-not-prompt-overexpression-of-proinflammatory-cytokines-during-co-infection-with-a-secondary-pathogen
#3
JOURNAL ARTICLE
Chia-Ming Su, Jineui Kim, Junyu Tang, Yu Fan Hung, Federico A Zuckermann, Robert Husmann, Patrick Roady, Jiyoun Kim, Young-Min Lee, Dongwan Yoo
Porcine reproductive and respiratory syndrome virus (PRRSV) is known to suppress the type I interferon (IFNs-α/β) response during infection. PRRSV also activates the NF-κB signaling pathway, leading to the production of proinflammatory cytokines during infection. In swine farms, co-infections of PRRSV and other secondary bacterial pathogens are common and exacerbate the production of proinflammatory cytokines, contributing to the porcine respiratory disease complex (PRDC) which is clinically a severe disease...
March 28, 2024: PLoS Pathogens
https://read.qxmd.com/read/38547209/prozone-masks-elevated-sars-cov-2-antibody-level-measurements
#4
JOURNAL ARTICLE
Micaela N Sandoval, Samuel P McClellan, Stephen J Pont, Jessica A Ross, Michael D Swartz, Mark A Silberman, Eric Boerwinkle
We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high antibody concentration disrupts the immune complex formation, resulting in a spuriously low reported result. Following participant inquiries, we observed anomalously low measurement of SARS-CoV-2 spike protein antibody levels using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay from participants in the Texas Coronavirus Antibody Research survey (Texas CARES), an ongoing prospective, longitudinal antibody surveillance program...
2024: PloS One
https://read.qxmd.com/read/38547055/the-muc1-hif-1%C3%AE-signaling-axis-regulates-pancreatic-cancer-pathogenesis-through-polyamine-metabolism-remodeling
#5
JOURNAL ARTICLE
Divya Murthy, Kuldeep S Attri, Voddu Suresh, Girish H Rajacharya, Carlos A Valenzuela, Ravi Thakur, Junzhang Zhao, Surendra K Shukla, Nina V Chaika, Drew LaBreck, Chinthalapally V Rao, Michael A Hollingsworth, Kamiya Mehla, Pankaj K Singh
Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 ( SAT1 ), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation...
April 2, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38546977/multiscale-computational-framework-for-the-liquid-liquid-phase-separation-of-intrinsically-disordered-proteins
#6
JOURNAL ARTICLE
Kalindu S Fernando, Ghodsiehsadat Jahanmir, Ilona C Unarta, Ying Chau
The reversible assembly of intrinsically disordered proteins (IDPs) to form membraneless organelles (MLOs) is a fundamental process involved in the spatiotemporal regulation in living cells. MLOs formed via liquid-liquid phase separation (LLPS) serve as molecule-enhancing hubs to regulate cell functions. Owing to the complexity and dynamic nature of the protein assembly via a network of weak inter- and intra-molecular interactions, it is challenging to describe and predict the LLPS behavior. We have developed a multiscale computational model for IDPs, using the fused in sarcoma (FUS) protein and its variants as illustrative examples...
March 28, 2024: Langmuir: the ACS Journal of Surfaces and Colloids
https://read.qxmd.com/read/38546930/understanding-the-genetic-and-non-genetic-interconnections-in-the-aetiology-of-isolated-congenital-heart-disease-an-updated-review-part-1
#7
REVIEW
Jyoti Maddhesiya, Bhagyalaxmi Mohapatra
PURPOSE OF REVIEW: Congenital heart disease (CHD) is the most frequently occurring birth defect. Majority of the earlier reviews focussed on the association of genetic factors with CHD. A few epidemiological studies provide convincing evidence for environmental factors in the causation of CHD. Although the multifactorial theory of gene-environment interaction is the prevailing explanation, explicit understanding of the biological mechanism(s) involved, remains obscure. Nonetheless, integration of all the information into one platform would enable us to better understand the collective risk implicated in CHD development...
March 28, 2024: Current Cardiology Reports
https://read.qxmd.com/read/38546874/acetylation-of-c-myc-at-lysine-148-protects-neurons-after-ischemia
#8
JOURNAL ARTICLE
V V Guzenko, S S Bachurin, V A Dzreyan, A M Khaitin, Y N Kalyuzhnaya, S V Demyanenko
This study focuses on understanding the role of c-Myc, a cancer-associated transcription factor, in the penumbra following ischemic stroke. While its involvement in cell death and survival is recognized, its post-translational modifications, particularly acetylation, remain understudied in ischemia models. Investigating these modifications could have significant clinical implications for controlling c-Myc activity in the central nervous system. Although previous studies on c-Myc acetylation have been limited to non-neuronal cells, our research examines its expression in perifocal cells during stroke recovery to explore regulatory mechanisms via acetylation...
March 28, 2024: Neuromolecular Medicine
https://read.qxmd.com/read/38546811/structure-based-multitargeted-docking-screening-pharmacokinetics-dft-and-dynamics-simulation-studies-reveal-mitoglitazone-as-a-potent-inhibitor-of-cellular-survival-and-stress-response-proteins-of-lung-cancer
#9
JOURNAL ARTICLE
Abdulkarim S Binshaya, Omar Saad Alkahtani, Fahad M Aldakheel, Ahmed Hjazi, Hassan H Almasoudi
Lung cancer is a disease in which lung cells grow abnormally and uncontrollably, and the cause of it is direct smoking, secondhand smoke, radon, asbestos, and certain chemicals. The worldwide leading cause of death is lung cancer, which is responsible for more than 1.8 million deaths yearly and is expected to rise to 2.2 million by 2030. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which accounts for about 80% and small cell lung cancer (SCLC), which is more aggressive than NSCLC and is often diagnosed later and accounts for 20% of cases...
March 28, 2024: Medical Oncology
https://read.qxmd.com/read/38546619/neoadjuvant-intent-immunotherapy-in-advanced-resectable-cutaneous-squamous-cell-carcinoma
#10
JOURNAL ARTICLE
Emily Y Kim, Emily S Ruiz, Mia S DeSimone, Sophia Z Shalhout, Glenn J Hanna, David M Miller, Chrysalyne Schmults, Eleni M Rettig, Ruth K Foreman, Rosh Sethi, Manisha Thakuria, Ann W Silk
IMPORTANCE: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. OBJECTIVE: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts...
March 28, 2024: JAMA Otolaryngology—Head & Neck Surgery
https://read.qxmd.com/read/38546551/neoadjuvant-dual-checkpoint-inhibitors-vs-anti-pd1-therapy-in-high-risk-resectable-melanoma-a-pooled-analysis
#11
JOURNAL ARTICLE
Ankit Mangla, Chanmi Lee, Matthew M Mirsky, Margaret Wang, Luke D Rothermel, Richard Hoehn, Jeremy S Bordeaux, Bryan T Carrol, Jason Theuner, Shawn Li, Pingfu Fu, John M Kirkwood
IMPORTANCE: Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known. OBJECTIVE: To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM. DESIGN, SETTING, AND PARTICIPANTS: In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials...
March 28, 2024: JAMA Oncology
https://read.qxmd.com/read/38546337/neurophysiological-trajectories-in-alzheimer-s-disease-progression
#12
JOURNAL ARTICLE
Kiwamu Kudo, Kamalini G Ranasinghe, Hirofumi Morise, Faatimah Syed, Kensuke Sekihara, Katherine P Rankin, Bruce L Miller, Joel H Kramer, Gil D Rabinovici, Keith Vossel, Heidi E Kirsch, Srikantan S Nagarajan
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography...
March 28, 2024: ELife
https://read.qxmd.com/read/38546328/identifying-the-suite-of-genes-central-to-swimming-in-the-biocontrol-bacterium-pseudomonas-protegens-pf-5
#13
JOURNAL ARTICLE
B K Fabian, C Foster, A Asher, K A Hassan, I T Paulsen, S G Tetu
Swimming motility is a key bacterial trait, important to success in many niches. Biocontrol bacteria, such as Pseudomonas protegens Pf-5, are increasingly used in agriculture to control crop diseases, where motility is important for colonization of the plant rhizosphere. Swimming motility typically involves a suite of flagella and chemotaxis genes, but the specific gene set employed for both regulation and biogenesis can differ substantially between organisms. Here we used transposon-directed insertion site sequencing (TraDIS), a genome-wide approach, to identify 249 genes involved in P...
March 2024: Microbial Genomics
https://read.qxmd.com/read/38546300/aortic-thrombus-with-bilateral-renal-infarcts-a-case-report
#14
JOURNAL ARTICLE
Lev Libet
INTRODUCTION: The presence of a hypercoagulable state predisposes to venous and arterial thrombi. While the relationship between protein C and S deficiencies with venous thrombus formation is clear, the relationship to arterial thrombi formation is less common. Thromboembolic disease of the renal arteries may result in renal infarction. The development of simultaneous bilateral renal infarction is rare and can lead to significant morbidity and mortality. CASE REPORT: This is a case of a 48-year-old male with known protein C deficiency who presented to the emergency department with sudden onset abdominal pain...
February 2024: Clinical Practice and Cases in Emergency Medicine
https://read.qxmd.com/read/38546267/the-staphylococcus-aureus-regulatory-program-in-a-human-skin-like-environment
#15
JOURNAL ARTICLE
Flavia G Costa, Krista B Mills, Heidi A Crosby, Alexander R Horswill
UNLABELLED: Staphylococcus aureus is a Gram-positive pathogen responsible for the majority of skin and soft tissue infections (SSTIs). S. aureus colonizes the anterior nares of approximately 20%-30% of the population and transiently colonizes the skin, thereby increasing the risk of developing SSTIs and more serious infections. Current laboratory models that mimic the skin surface environment are expensive, require substantial infrastructure, and limit the scope of bacterial physiology studies under human skin conditions...
March 28, 2024: MBio
https://read.qxmd.com/read/38546099/cardiac-glycosides-inhibit-early-and-late-vaccinia-virus-protein-expression
#16
JOURNAL ARTICLE
Jerzy Samolej, Ian J White, Blair L Strang, Jason Mercer
Cardiac glycosides (CGs) are natural steroid glycosides, which act as inhibitors of the cellular sodium-potassium ATPase pump. Although traditionally considered toxic to human cells, CGs are widely used as drugs for the treatment of cardiovascular-related medical conditions. More recently, CGs have been explored as potential anti-viral drugs and inhibit replication of a range of RNA and DNA viruses. Previously, a compound screen identified CGs that inhibited vaccinia virus (VACV) infection. However, no further investigation of the inhibitory potential of these compounds was performed, nor was there investigation of the stage(s) of the poxvirus lifecycle they impacted...
March 2024: Journal of General Virology
https://read.qxmd.com/read/38546043/loss-of-ube2s-causes-meiosis-i-arrest-with-normal-spindle-assembly-checkpoint-dynamics-in-mouse-oocytes
#17
JOURNAL ARTICLE
Si-Min Sun, Bing-Wang Zhao, Yuan-Yuan Li, Hong-Yang Liu, Yuan-Hong Xu, Xue-Mei Yang, Jia-Ni Guo, Ying-Chun Ouyang, Chang-Jiang Weng, Yi-Chun Guan, Qing-Yuan Sun, Zhen-Bo Wang
The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear...
March 15, 2024: Development
https://read.qxmd.com/read/38545789/knocking-out-sodium-glucose-linked-transporter-5-prevents-fructose-induced-renal-oxidative-stress-and-salt-sensitive-hypertension
#18
JOURNAL ARTICLE
Beau R Forester, Ronghao Zhang, Brett Schuhler, Autumn Brostek, Agustin Gonzalez-Vicente, Jeffrey L Garvin
BACKGROUND: A fructose high-salt (FHS) diet increases systolic blood pressure and Ang II (angiotensin II)-stimulated proximal tubule (PT) superoxide (O2 - ) production. These increases are prevented by scavenging O2 - or an Ang II type 1 receptor antagonist. SGLT4 (sodium glucose-linked cotransporters 4) and SGLT5 are implicated in PT fructose reabsorption, but their roles in fructose-induced hypertension are unclear. We hypothesized that PT fructose reabsorption by SGLT5 initiates a genetic program enhancing Ang II-stimulated oxidative stress in males and females, thereby causing fructose-induced salt-sensitive hypertension...
March 28, 2024: Hypertension
https://read.qxmd.com/read/38545784/evaluation-of-plasma-biomarkers-for-causal-association-with-peripheral-artery-disease
#19
JOURNAL ARTICLE
Pranav Sharma, Derek Klarin, Benjamin F Voight, Philip S Tsao, Michael G Levin, Scott M Damrauer
BACKGROUND: Hundreds of biomarkers for peripheral artery disease (PAD) have been reported in the literature; however, the observational nature of these studies limits causal inference due to the potential of reverse causality and residual confounding. We sought to evaluate the potential causal impact of putative PAD biomarkers identified in human observational studies through genetic causal inference methods. METHODS: Putative circulating PAD biomarkers were identified from human observational studies through a comprehensive literature search based on terms related to PAD using PubMed, Cochrane, and Embase...
March 28, 2024: Arteriosclerosis, Thrombosis, and Vascular Biology
https://read.qxmd.com/read/38545652/renal-vascular-control-during-normothermia-and-passive-heat-stress-in-healthy-younger-men-and-women
#20
JOURNAL ARTICLE
Jessica A Freemas, Morgan L Worley, Mikaela C Gabler, Hayden W Hess, Curtis S Goss, Tyler B Baker, Blair D Johnson, Christopher L Chapman, Zachary J Schlader
We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared to men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase), 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, core temperature was increased by ~0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at one-hour post-CPT, subjects ingested a whey protein shake (1...
March 28, 2024: American Journal of Physiology. Renal Physiology
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