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Total:
30
results
Exome-wide association analysis identifies novel risk loci for alcohol-associated hepatitis
CONCLUSIONS: This study has identified two new genes of high effect size with a previously unknown contribution to ALD, and highlights both the overlap in etiology between liver diseases, and the unique origins of AH.
Gonococcal Mimitope Vaccine Candidate Forms a Beta-Hairpin Turn and Binds Hydrophobically to a Therapeutic Monoclonal Antibody
The spread of multidrug-resistant strains of Neisseria gonorrhoeae, the etiologic agent of gonorrhea, represents a global health emergency. Therefore, the development of a safe and effective vaccine against gonorrhea is urgently needed. In previous studies, murine monoclonal antibody (mAb) 2C7 was raised against gonococcal lipooligosaccharide (LOS). mAb 2C7 elicits complement-dependent bactericida...
Improving the assessment of risk factors relevant to potential carcinogenicity of gene therapies: a consensus paper
Regulators and industry are actively seeking improvements and alternatives to current models and approaches to evaluate potential carcinogenicity of gene therapies (GTs). A meeting of invited experts was organised by NC3Rs/UKEMS (London, March 2023) to discuss this topic. This paper describes the consensus reached amongst delegates on the definition of vector genotoxicity, sources of uncertainty, ...
Detection of pharmacolipidodynamic effects following the intravenous and oral administration of gefitinib to C57Bl/6JRj mice by rapid UHPLC-MS analysis of plasma
Omics-based biomarker technologies, including metabolic profiling (metabolomics/metabonomics) and lipidomics, are making a significant impact on disease understanding, drug development, and translational research. A wide range of patho-physiological processes involve lipids and monitoring changes in lipid abundance can give valuable insights into mechanisms of drug action, off target pharmacology ...
COVID-19 clinical trials: who is likely to participate and why?
Aim: To identify factors associated with willingness to participate in a COVID-19 clinical trial and reasons for and against participating. Materials & methods: We surveyed Massachusetts (MA, USA) residents online using the Dynata survey platform and via phone using random digit dialing between October and November 2021. Respondents were asked to imagine they were hospitalized with COVID-19 and in...
Conquering hypertension in Vietnam: 12- month follow up results from a cluster-randomised controlled trial
BACKGROUND: Approximately 20% of adults in Vietnam have hypertension, and management of this chronic condition remains challenging. This study aimed to assess the effectiveness of a multicomponent intervention in reducing blood pressure (BP) in adults with uncontrolled hypertension.
Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study
CONCLUSION: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.
Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsets
Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype and function of pathogenic T cells across the spectrum of severity requires investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRM) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, SJS/TEN and DRESS, an...
Sociodemographic and clinical indicators of children and young people with cerebral palsy and reported unmet social needs
AIM: To determine the frequency, type, clinical, and sociodemographic associations of unmet social needs in children with cerebral palsy (CP).
ASCB statement of commitment to diversity, equity, and inclusion
No abstract
Protein language models enable prediction of polyreactivity of monospecific, bispecific, and heavy-chain-only antibodies
CONCLUSION: To our knowledge, this represents the first application of PLMs to predict assay data on bispecifics and VHH-Fcs.
"Expected to happen": perspectives on post-release overdose from recently incarcerated people with opioid use disorder
CONCLUSIONS: The perspectives of people with lived experience are vital to understanding the disproportionate risks of overdose for those recently released from incarceration. Our results highlight the intersectional factors that produce and reproduce the post-release overdose risk environment, providing support for interventions across each domain of the Risk Environment Framework. By capturing p...
Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy
CONCLUSION: In the era of precision medicine, where emphasis on primary drug targets prevails, our research challenges this paradigm by showcasing a robust synergy underpinned by an off-target dependency. Further dissection of the intricate genetic dependencies that underlie synergy can pave the way to developing more effective combination strategies in gastric cancer therapy.
Paramedic-Assisted Community Evaluation After Discharge: The PACED Intervention
CONCLUSIONS AND IMPLICATIONS: This pilot study of an MIH transition care program was feasible with high protocol fidelity. It yields preliminary evidence demonstrating a decreased risk of rehospitalization in frail older adults.
Living a private lie: intersectional stigma, depression and suicidal thoughts for selected young key populations living with HIV in Zambia
CONCLUSION: Effectively addressing stigmas and poor mental health outcomes among young HIV-positive MSM and TGW will require adopting a socio-ecological approach that focuses on structural interventions, more trauma-informed and identity-supportive care for young people with HIV, as well as strengthening of authentic community-informed public health efforts.
To treat or not to treat: a comparative effectiveness analysis of oral anticoagulant outcomes among U.S. nursing home residents with atrial fibrillation
CONCLUSIONS: Our results support the benefits of treatment with OACs to prevent ischemic strokes and increase longevity, while highlighting the need to weigh apparent benefits against elevated risk for bleeding. Results were consistent with net favorability of DOACs versus warfarin.
Stem Cells in Bone Tissue Engineering: Progress, Promises and Challenges
Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pul...
PRC1.6 localizes on chromatin with the human silencing hub (HUSH) complex for promoter-specific silencing
An obligate step in the life cycle of HIV-1 and other retroviruses is the establishment of the provirus in target cell chromosomes. Transcriptional regulation of proviruses is complex, and understanding the mechanisms underlying this regulation has ramifications for fundamental biology, human health, and gene therapy implementation. The three core components of the Human Silencing Hub (HUSH) compl...
Impact of atropisomerism on a non-steroidal glucocorticoid receptor agonist
To investigate atropisomers of non-steroidal glucocorticoid receptor modulator GSK866, a virtual library of substituted benzoic acid analogues was enumerated. Compounds from this library were subjected to a torsion angle scan using Spartan'20 to calculate the torsion rotation energy barrier which identified compounds predicted to be stable as atropisomers. After synthesis of the library, analysis ...
A 12-year Retrospective Cohort Study of Point-of-care Ultrasound and Aortic Dissection Risk Score in Type A Aortic Dissection
CONCLUSION: Although POCUS provides rapid information in the diagnosis of type A AD, 14% of patients with images available for review had no findings on POCUS. Of the whole cohort, 12% had an ADRS = 0. Further studies are needed to identify an optimal diagnostic pathway for this catastrophic disease.
Comparative Efficacy of Flow Diverter Devices in the Treatment of Carotid Sidewall Intracranial Aneurysms: a Retrospective, Multicenter Study
CONCLUSION: All the first-generation devices achieved good clinical outcomes and retreatment rates in treating ICA sidewall aneurysms. Prospective studies are needed to explore the nuanced differences between these devices in the long term.
Ventricular Tachycardia and Hospital Readmission in Patients Discharged From the Hospital After an Acute Myocardial Infarction
CONCLUSIONS: Patients who develop late VT may experience a higher risk of 30-day rehospitalization following hospital discharge for AMI, especially among those with ST-segment-elevation AMI. Larger studies are needed to confirm our findings.
Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid
Conformational dynamics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S) mediate exposure of the binding site for the cellular receptor, angiotensin-converting enzyme 2 (ACE2). The N-terminal domain (NTD) of S binds terminal sialic acid (SA) moieties on the cell surface, but the functional role of this interaction in virus entry is unknown. Here, we report...
Structural basis of homodimerization of the JNK scaffold protein JIP2 and its heterodimerization with JIP1
The scaffold proteins JIP1 and JIP2 intervene in the c-Jun N-terminal kinase (JNK) pathway to mediate signaling specificity by coordinating the simultaneous assembly of multiple kinases. Using NMR, we demonstrate that JIP1 and JIP2 heterodimerize via their SH3 domains with the affinity of heterodimerization being comparable to homodimerization. We present the high-resolution crystal structure of t...
Biflavonoid Methylchamaejasmin and Khaya grandifoliola Extract Inhibit NLRP3 Inflammasome in THP-1 Cell Model of Neuroinflammation
Neuroinflammation is a common hallmark of Alzheimer's disease (AD), with NLRP3 inflammasome proven to be activated in microglia of AD patients' brains. In this study, a newly isolated biflavonoid (7,7'-di-O-methylchamaejasmin/M8) and a crude extract of the plant Khaya grandifoliola (KG) were investigated for their inhibitory effect on inflammasome activation. In preliminary experiments, M8 and KG ...
mRNA-specific readthrough of nonsense codons by antisense oligonucleotides (R-ASOs)
Nonsense mutations account for 10% of human genetic disorders, including cystic fibrosis, Alagille syndrome, and Duchenne muscular dystrophy. A nonsense mutation results in the expression of a truncated protein, and therapeutic strategies aim to restore full-length protein expression. Most strategies under development, including small-molecule aminoglycosides, suppressor tRNAs, or the targeted deg...
"For the first time…I am seriously fighting burnout": clinician experiences with a challenging electronic health record transition
CONCLUSION: Our findings provide relevant strategies to navigate future EHR transitions while supporting clinical teams.
Technical success and long-term experience of a novel radial guide-catheter shape: the JCLRAD
No abstract
X-ray Attenuating Vesicles with Neutrophil Extracellular Trap (NET) Specificity: Synthesis and Testing in a Model System
X-ray attenuating contrast agents for imaging thrombi directly during endovascular thrombectomy (EVT) are urgently needed for shortening the wait time for treatment and for reducing the chances of blood clot fragmentation. Neutrophil extracellular traps (NETs) are a product of an innate immune system response by which neutrophils release decondensed chromatin strands decorated with granule and cyt...
Towards a More Objective and High-throughput Spheroid Invasion Assay Quantification Method
Multicellular spheroids embedded in 3D hydrogels are prominent in vitro models for 3D cell invasion. Yet, quantification methods for spheroid cell invasion that are high-throughput, objective and accessible are still lacking. Variations in spheroid sizes and the shapes of the cells within render it difficult to objectively assess invasion extent. The goal of this work is to develop a high-throughp...
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