Nucleosides are pervasive building blocks that are found throughout nature and used extensively in medicinal chemistry and biotechnology. However, the preparation of base-modified analogues using conventional synthetic methodology poses challenges in scale-up and purification. In this work, an integrated approach involving structural analysis, screening and reaction optimization, is established to prepare 2'-deoxyribonucleoside analogues catalysed by the type II nucleoside 2'-deoxyribosyltransferase from (NDT-2).
View Article and Find Full Text PDFObjective: To describe the surgical technique for removal of hoof wall masses in horses under standing sedation (SS) and local anesthesia (LA), and to report complications and long-term outcome following surgery.
Study Design: Observational retrospective study.
Animals: Client-owned horses (n = 30).
Computational models of musculoskeletal systems are essential tools for understanding how muscles, tendons, bones, and actuation signals generate motion. In particular, the OpenSim family of models has facilitated a wide range of studies on diverse human motions, clinical studies of gait, and even non-human locomotion. However, biological structures with many joints, such as fingers, necks, tails, and spines, have been a longstanding challenge to the OpenSim modeling community, especially because these structures comprise numerous bones and are frequently actuated by extrinsic muscles that span multiple joints-often more than three-and act through a complex network of branching tendons.
View Article and Find Full Text PDFIntroduction: The mantra "time is brain" cannot be overstated for patients suffering from acute ischemic stroke. This is especially true for those with large vessel occlusions (LVOs) requiring transfer to an endovascular thrombectomy (EVT) capable center. We sought to evaluate the spoke hospital door in-door out (DIDO) times for patients transferred to our hub center for EVT.
View Article and Find Full Text PDFBackground: Machine learning (ML) approaches have become increasingly popular in predicting surgical outcomes. However, it is unknown whether they are superior to traditional statistical methods such as logistic regression (LR). This study aimed to perform a systematic review and meta-analysis to compare the performance of ML vs LR models in predicting postoperative outcomes for patients undergoing gastrointestinal (GI) surgery.
View Article and Find Full Text PDFBackground: Homelessness is a growing concern in the US, with 3.5 million people experiencing it annually and 600,000 on any given night. Homeless individuals face increased vulnerability to 30-day hospital readmissions and higher mortality rates, straining the healthcare system and exacerbating existing disparities.
View Article and Find Full Text PDFObjective: To examine how patients with rheumatoid arthritis (RA) perceive RA-related laboratory testing and the potential utility of a blood test to predict treatment response to a new RA medication.
Methods: ArthritisPower members with RA were invited to participate in a cross-sectional survey on reasons for laboratory testing plus a choice-based conjoint analysis exercise to determine how patients value different attributes of a biomarker-based test to predict treatment response.
Results: Most patients perceived that their doctors ordered laboratory tests to check for active inflammation (85.
Dural arteriovenous fistulas (DAVFs) are rare intracranial vascular malformations that present with a variety of clinical signs and symptoms. Among these, intracranial hemorrhage is a severe complication. A 72-year-old male presented with headache and pulsatile tinnitus.
View Article and Find Full Text PDFTumor necrosis factor-[Formula: see text] inhibitors (TNFi) have been a standard treatment in ulcerative colitis (UC) for nearly 20 years. However, insufficient response rate to TNFi therapies along with concerns around their immunogenicity and inconvenience of drug delivery through injections calls for development of UC drugs targeting alternative proteins. Here, we propose a multi-omic network biology method for prioritization of protein targets for UC treatment.
View Article and Find Full Text PDFJ Cerebrovasc Endovasc Neurosurg
September 2023
Anterior communicating artery aneurysms are the most common intracranial aneurysm and have a high risk of rupture which can lead to morbidity and mortality. Traditionally, intracranial aneurysms were treated by clipping with neurosurgical access. However, certain patients may prefer less invasive approaches or not represent open surgical candidates.
View Article and Find Full Text PDFA 2021 study described the development and validation of a blood-based precision medicine test called the molecular signature response classifier (MSRC) that uses 23 features to identify rheumatoid arthritis (RA) patients who are likely nonresponders to tumor necrosis factor-α inhibitor (TNFi) therapy. Both the gene expression features and clinical components (sex, body mass index, patient global assessment, and anti-cyclic citrullinated protein) included in the MSRC were statistically significant contributors to MSRC results. In response to continued inquiries on this topic, we write this letter to provide additional insights into the contribution of clinical components to the MSRC on the Network-004 validation cohort.
View Article and Find Full Text PDFBackground: The molecular signature response classifier (MSRC) predicts tumor necrosis factor-ɑ inhibitor (TNFi) non-response in rheumatoid arthritis. This study evaluates decision-making, validity, and utility of MSRC testing.
Methods: This comparative cohort study compared an MSRC-tested arm (N = 627) from the Study to Accelerate Information of Molecular Signatures (AIMS) with an external control arm (N = 2721) from US electronic health records.
Background: Acute pain after mastectomy is increased with concurrent breast reconstruction. One postulated advantage of prepectoral breast reconstruction is less postoperative pain; however, no comparisons to partial submuscular reconstruction have been made to date. Here, we examined the postoperative pain experienced between patients with prepectoral and subpectoral breast reconstruction after mastectomy.
View Article and Find Full Text PDFCult Med Psychiatry
December 2023
There is ample evidence that homelessness is associated with high rates of morbidity and mortality. Street Medicine seeks to eliminate these disparities by providing healthcare on the streets to people who are unsheltered. While extant research describes health disparities for the unsheltered and programmatic approaches to addressing housing instability, there are few published studies describing how healthcare providers build and maintain relationships with patients on the street.
View Article and Find Full Text PDFBoulder placement is a common method to restore degraded instream habitats by enhancing habitat complexity. This experimental study is the foremost attempt to systematically investigate the influence of rock-ramp boulder placement with varying boulder concentration and flow rate on habitat hydraulic complexity metrics, including the kinetic energy gradient and modified recirculation metrics. By adding boulders to a reach, the modified recirculation metric increased by one order of magnitude for all boulder concentrations.
View Article and Find Full Text PDFStiff-person syndrome is a well-recognised disease in humans, whilst cases of stiff-horse syndrome (SHS) have been rarely reported in the veterinary medicine literature. SHS is a progressive immunomediated disorder of the central nervous system leading to a disturbance of gamma amino butyric acid transmission at the neuromuscular junction in which antibodies are produced against the enzyme glutamic acid decarboxylase. A 6 year-old Irish Sport Horse was presented for investigation of involuntary violent contraction of hindlimb and back muscles triggered by stress.
View Article and Find Full Text PDFNPR1 is a master regulator of the defence transcriptome induced by the plant immune signal salicylic acid. Despite the important role of NPR1 in plant immunity, understanding of its regulatory mechanisms has been hindered by a lack of structural information. Here we report cryo-electron microscopy and crystal structures of Arabidopsis NPR1 and its complex with the transcription factor TGA3.
View Article and Find Full Text PDFBackground: A blood-based molecular signature response classifier (MSRC) predicts non-response to tumor necrosis factor-ɑ inhibitors (TNFi) in rheumatoid arthritis (RA).
Research Design And Methods: This is an interim analysis of data collected in the Study to Accelerate Information of Molecular Signatures (AIMS) in RA from patients who received the MSRC test between September 2020 and November 2021. Absolute changes in clinical disease activity index (CDAI) scores from baseline were evaluated at 12 weeks (n = 470) and 24 weeks (n = 274).
This cross-cohort study aimed to (1) determine a network-based molecular signature that predicts the likelihood of inadequate response to the tumor necrosis factor-ɑ inhibitor (TNFi) therapy, infliximab, in ulcerative colitis (UC) patients, and (2) address biomarker irreproducibility across different cohort studies. Whole-transcriptome microarray data were derived from biopsies of affected colon tissue from 2 cohorts of infliximab-treated UC patients (training N = 24 and validation N = 22). Response was defined as endoscopic and histologic healing at 4-6 weeks and 8 weeks, respectively.
View Article and Find Full Text PDFTo understand the experiences and perspectives of physiotherapy (PT) students, their clinical instructor, nurses, physicians, and patients with a role-emerging student clinical placement in an emergency department (ED) and to identify barriers and facilitators in implementing this placement model. We conducted qualitative semi-structured interviews with 6 PT students, 1 PT clinical instructor, 15 nurses, 12 physicians, and 17 patients. Five researchers independently coded the transcribed interviews and performed thematic analysis in an interpretive description tradition with frequent peer debriefing and reflexive discussions.
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