Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 5.411
Filter
1.
Article in English | MEDLINE | ID: mdl-38992936

ABSTRACT

Cyclic peptides are an important class of molecules that gained significant attention in the field of drug discovery due to their unique pharmacological characteristics and enhanced proteolytic stability. Yet, gastrointestinal degradation remains a major hurdle in the discovery of orally bioavailable cyclic peptides. Soft spot identification (SSID) of the regions in the cyclic peptide sequence susceptible to amide hydrolysis by proteases is used in the discovery stage to guide medicinal chemistry design. SSID can be an arduous task, traditionally performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), often resulting in complex and time-consuming manual analysis, particularly when isomeric linear peptide metabolites chromatographically coelute. Here, we present an alternative orthogonal approach that entails a high-resolution ion mobility (HRIM) system based on Structures for Lossless Ion Manipulation (SLIM) technology interfaced with quadrupole time-of-flight (QTOF) mass spectrometry to address some of the challenges associated with SSID. Two strategies were used to resolve linear isomeric peptide metabolites: labeled and label-free, both utilizing the HRIM platform. The label-free strategy leverages negative polarity to ionize the isomers which achieves better separation of the gas phase ions in the ion mobility (IM) dimension as compared to positive polarity, which is a more conventional approach when studying proteins and peptides. The second approach uses an isotope-labeled dimethyl tag on the terminal amine group, acting as a "shift reagent" to influence the mobility of isomers in the positive mode. This method resulted in baseline separation for the isomers of interest and produced unique product ions in the fragmentation spectra for unambiguous soft spot identification. Both label-free and labeled strategies demonstrated the ability to solve the challenges associated with SSID for cyclic peptides.

2.
Forensic Sci Int ; 361: 112127, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38964051

ABSTRACT

The chemical recovery of a defaced serial number is a common forensic science practice, however it is not understood how proficient experts perform in correctly identifying recovered serial numbers. Understanding the accuracy of experts and how they compare to novices in character recognition can help to establish a baseline for this expertise. In this study an expert-novice comparison assessment was completed involving 118 test plates, each stamped with six randomised alphanumeric characters. The plates were defaced and chemically recovered before being viewed by multiple participants over six time intervals. A total of 3169 character inspections were completed. An assessment of confidence and error rates were calculated for both expert (trained) and novice (untrained) participants. Errors were counted when a participant interpreted a different character to that of the ground truth and believed the result was accurate for reporting. The results showed a similar (2.3 % and 2.4 %) error rate for the cohorts, however a statistical difference in confidence levels was recorded, demonstrating the more conservative nature of experts. This study aims to assist in validating practitioner interpretations, through addressing some forensic science criticisms, such as establishing error rates to routine scientific practices.

3.
Int J Paediatr Dent ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982581

ABSTRACT

BACKGROUND: Surgical intervention for tongue-tie, or ankyloglossia performed by paediatric dentists can alleviate symptoms and improve functional abilities in infants and children. Despite widespread practice, there are currently no established clinical guidelines or consistent approaches for pre- and post-operative care of children. AIM: The aim of this study was to explore approaches to pre- and post-operative care for children with ankyloglossia having frenum surgery. DESIGN: A scoping review of peer-reviewed articles in four electronic databases was conducted. Intervention studies that reported on pre- or post-operative regimens for infants, children and adolescents (0 to 18 years) with a diagnosis of tongue-tie or ankyloglossia, who had surgical intervention such as frenotomy or frenectomy, were included and quality assessments performed. RESULTS: Twenty-three studies were identified, with seven studies incorporating both pre- and post-operative care, and 16 studies focussing solely on post-operative care. Tongue exercises were commonly prescribed, and only three studies examined the relationship between post-operative care and recovery outcomes. Considerable variability existed in study design, prescribed care and outcome measures. CONCLUSION: There was substantial variability in pre- and post-operative care protocols, including dosage, frequency and duration of exercises and other care regimens for infants and children having frenum surgery. Further research is needed to determine the most effective course of pre- and post-operative care for children undergoing frenum surgery.

4.
Cells ; 13(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38994931

ABSTRACT

James German's work to establish the natural history and cancer risk associated with Bloom syndrome (BS) has had a strong influence on the generation of scientists and clinicians working to understand other RECQ deficiencies and heritable cancer predisposition syndromes. I summarize work by us and others below, inspired by James German's precedents with BS, to understand and compare BS with the other heritable RECQ deficiency syndromes with a focus on Werner syndrome (WS). What we know, unanswered questions and new opportunities are discussed, as are potential ways to treat or modify WS-associated disease mechanisms and pathways.


Subject(s)
Bloom Syndrome , RecQ Helicases , Werner Syndrome , Humans , RecQ Helicases/genetics , RecQ Helicases/metabolism , RecQ Helicases/deficiency , Bloom Syndrome/genetics , Werner Syndrome/genetics , History, 20th Century
5.
Support Care Cancer ; 32(8): 502, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985186

ABSTRACT

PURPOSE: Service referrals are required for cancer survivors to access specialist dietary and exercise support. Many system-level factors influence referral practices within the healthcare system. Hence, the aim of this study was to identify system-level factors and their interconnectedness, as well as strategies for optimising dietary and exercise referral practices in Australia. METHODS: A full-day workshop involving national multidisciplinary key stakeholders explored system-level factors impacting dietary and exercise referral practices. Facilitated group discussions using the nominal group technique identified barriers and facilitators to referral practices based on the six World Health Organisation (WHO) building blocks. The systems-thinking approach generated six cognitive maps, each representing a building block. A causal loop diagram was developed to visualise factors that influence referral practices. Additionally, each group identified their top five strategies by leveraging facilitators and addressing barriers relevant to their WHO building block. RESULTS: Twenty-seven stakeholders participated in the workshop, including consumers (n = 2), cancer specialists (n = 4), nursing (n = 6) and allied health professionals (n = 10), and researchers, representatives of peak bodies, not-for-profit organisations, and government agencies (n = 5). Common system-level factors impacting on referral practices included funding, accessibility, knowledge and education, workforce capacity, and infrastructure. Fifteen system-level strategies were identified to improve referral practices. CONCLUSION: This study identified system-level factors and strategies that can be applied to policy planning and practice in Australia.


Subject(s)
Cancer Survivors , Referral and Consultation , Humans , Cancer Survivors/psychology , Australia , Exercise , Neoplasms/therapy , Male , Female
6.
Article in English | MEDLINE | ID: mdl-38993651

ABSTRACT

In this study, we investigate the performance of advanced 2D acquisition geometries - Pentagon and T-shaped - in digital breast tomosynthesis (DBT) and compare them against the conventional 1D geometry. Unlike the conventional approach, our proposed 2D geometries also incorporate anterior projections away from the chest wall. Implemented on the Next-Generation Tomosynthesis (NGT) prototype developed by X-ray Physics Lab (XPL), UPenn, we utilized various phantoms to compare three geometries: a Defrise slab phantom with alternating plastic slabs to study low-frequency modulation; a Checkerboard breast phantom (a 2D adaptation of the Defrise phantom design) to study the ability to reconstruct the fine features of the checkerboard squares; and the 360° Star-pattern phantom to assess aliasing and compute the Fourier-spectral distortion (FSD) metric that assesses spectral leakage and the contrast transfer function. We find that both Pentagon and T-shaped scans provide greater modulation amplitude of the Defrise phantom slabs and better resolve the squares of the Checkerboard phantom against the conventional scan. Notably, the Pentagon geometry exhibited a significant reduction in aliasing of spatial frequencies oriented in the right-left (RL) medio-lateral direction, which was corroborated by a near complete elimination of spectral leakage in the FSD plot. Conversely T-shaped scan redistributes the aliasing between both posteroanterior (PA) and RL directions thus maintaining non-inferiority against the conventional scan which is predominantly affected by PA aliasing. The results of this study underscore the potential of incorporating advanced 2D geometries in DBT systems, offering marked improvements in imaging performance over the conventional 1D approach.

7.
Acta Crystallogr F Struct Biol Commun ; 80(Pt 7): 154-163, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38958188

ABSTRACT

The third complementary-determining regions of the heavy-chain (CDR3H) variable regions (VH) of some cattle antibodies are highly extended, consisting of 48 or more residues. These `ultralong' CDR3Hs form ß-ribbon stalks that protrude from the surface of the antibody with a disulfide cross-linked knob region at their apex that dominates antigen interactions over the other CDR loops. The structure of the Fab fragment of a naturally paired bovine ultralong antibody (D08), identified by single B-cell sequencing, has been determined to 1.6 Šresolution. By swapping the D08 native light chain with that of an unrelated antigen-unknown ultralong antibody, it is shown that interactions between the CDR3s of the variable domains potentially affect the fine positioning of the ultralong CDR3H; however, comparison with other crystallographic structures shows that crystalline packing is also a major contributor. It is concluded that, on balance, the exact positioning of ultralong CDR3H loops is most likely to be due to the constraints of crystal packing.


Subject(s)
Complementarity Determining Regions , Immunoglobulin Fab Fragments , Immunoglobulin Heavy Chains , Immunoglobulin Light Chains , Models, Molecular , Animals , Cattle , Immunoglobulin Heavy Chains/chemistry , Crystallography, X-Ray , Immunoglobulin Light Chains/chemistry , Immunoglobulin Light Chains/genetics , Complementarity Determining Regions/chemistry , Immunoglobulin Fab Fragments/chemistry , Amino Acid Sequence , Protein Conformation
8.
9.
Bio Protoc ; 14(6): e4962, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38841291

ABSTRACT

Nanobodies are recombinant antigen-specific single domain antibodies (VHHs) derived from the heavy chain-only subset of camelid immunoglobulins. Their small molecular size, facile expression, high affinity, and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. From our work in producing nanobodies to over sixty different proteins, we present a standardised workflow for nanobody discovery from llama immunisation, library building, panning, and small-scale expression for prioritisation of binding clones. In addition, we introduce our suites of mammalian and bacterial vectors, which can be used to functionalise selected nanobodies for various applications such as in imaging and purification. Key features • Standardise the process of building nanobody libraries and finding nanobody binders so that it can be repeated in any lab with reasonable equipment. • Introduce two suites of vectors to functionalise nanobodies for production in either bacterial or mammalian cells.

10.
Int J Mol Sci ; 25(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38928326

ABSTRACT

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.


Subject(s)
Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Pancreatitis , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/pathology , Pancreatitis/metabolism , Pancreatitis/genetics , Pancreatitis/pathology , Pancreatitis/diagnosis , Mice , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Humans , Prognosis , Gene Expression Regulation, Neoplastic , Disease Models, Animal , Cell Line, Tumor , Disease Progression
11.
Reprod Fertil Dev ; 362024 Jun.
Article in English | MEDLINE | ID: mdl-38894494

ABSTRACT

Context Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFß) during foetal development have been implicated in the predisposition to polycystic ovary syndrome (PCOS) in later life, aside from its genetic predisposition. In foetal ovarian fibroblasts, TGFß1 has been shown to regulate androgen signalling and seven genes located in loci associated with PCOS. Since PCOS exhibits a myriad of symptoms, it likely involves many different organs. Aims To identify the relationships between TGFß signalling molecules and PCOS candidate genes in different tissues associated with PCOS. Methods Using RNA sequencing data, we examined the expression patterns of TGFß signalling molecules in the human ovary, testis, heart, liver, kidney, brain tissue, and cerebellum from 4 to 20weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFß signalling molecules and PCOS candidate genes. Key results TGFß signalling molecules were dynamically expressed in most tissues prenatally and/or postnatally. FBN3 , a PCOS candidate gene involved in TGFß signalling, was expressed during foetal development in all tissues. The PCOS candidate genes HMGA2, YAP1 , and RAD50 correlated significantly (P TGFBR1 in six out of the seven tissues examined. Conclusions This study suggests that possible crosstalk occurs between genes in loci associated with PCOS and TGFß signalling molecules in multiple tissues, particularly during foetal development. Implications Thus, alteration in TGFß signalling during foetal development could affect many tissues contributing to the multiple phenotypes of PCOS in later life.


Subject(s)
Polycystic Ovary Syndrome , Signal Transduction , Transforming Growth Factor beta , Humans , Female , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/genetics , Adult , Ovary/metabolism , Fetus/metabolism , Male , Pregnancy , Gene Expression Regulation, Developmental , Testis/metabolism , Testis/embryology , Fibrillins
12.
J Bone Metab ; 31(2): 114-131, 2024 May.
Article in English | MEDLINE | ID: mdl-38886969

ABSTRACT

BACKGROUND: There is considerable heterogeneity in findings and a lack of consensus regarding the interplay between osteoporosis and outcomes in patients with lumbar degenerative spine disease. Therefore, the purpose of this systematic review and meta-analysis was to gather and analyze existing data on the effect of osteoporosis on radiographic, surgical, and clinical outcomes following surgery for lumbar degenerative spinal disease. METHODS: A systematic review was performed to determine the effect of osteoporosis on the incidence of adverse outcomes after surgical intervention for lumbar degenerative spinal diseases. The approach focused on the radiographic outcomes, reoperation rates, and other medical and surgical complications. Subsequently, a meta-analysis was performed on the eligible studies. RESULTS: The results of the meta-analysis suggested that osteoporotic patients experienced increased rates of adjacent segment disease (ASD; p=0.015) and cage subsidence (p=0.001) while demonstrating lower reoperation rates than non-osteoporotic patients (7.4% vs. 13.1%; p=0.038). The systematic review also indicated that the length of stay, overall costs, rates of screw loosening, and rates of wound and other medical complications may increase in patients with a lower bone mineral density. Fusion rates, as well as patient-reported and clinical outcomes, did not differ significantly between osteoporotic and non-osteoporotic patients. CONCLUSIONS: Osteoporosis was associated with an increased risk of ASD, cage migration, and possibly postoperative screw loosening, as well as longer hospital stays, incurring higher costs and an increased likelihood of postoperative complications. However, a link was not established between osteoporosis and poor clinical outcomes.

13.
Open Biol ; 14(6): 230252, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38835241

ABSTRACT

The Omicron strains of SARS-CoV-2 pose a significant challenge to the development of effective antibody-based treatments as immune evasion has compromised most available immune therapeutics. Therefore, in the 'arms race' with the virus, there is a continuing need to identify new biologics for the prevention or treatment of SARS-CoV-2 infections. Here, we report the isolation of nanobodies that bind to the Omicron BA.1 spike protein by screening nanobody phage display libraries previously generated from llamas immunized with either the Wuhan or Beta spike proteins. The structure and binding properties of three of these nanobodies (A8, H6 and B5-5) have been characterized in detail providing insight into their binding epitopes on the Omicron spike protein. Trimeric versions of H6 and B5-5 neutralized the SARS-CoV-2 variant of concern BA.5 both in vitro and in the hamster model of COVID-19 following nasal administration. Thus, either alone or in combination could serve as starting points for the development of new anti-viral immunotherapeutics.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , SARS-CoV-2 , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus , SARS-CoV-2/immunology , Single-Domain Antibodies/immunology , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/chemistry , COVID-19/immunology , COVID-19/virology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Humans , Antibodies, Viral/immunology , Camelids, New World/immunology , Epitopes/immunology , Epitopes/chemistry , Cricetinae , Protein Binding , Models, Molecular
14.
bioRxiv ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38895454

ABSTRACT

Motion perception is considered a hyperacuity. The presence of a visual frame of reference to compute relative motion is necessary to achieve this sensitivity [Legge, Gordon E., and F. W. Campbell. "Displacement detection in human vision." Vision Research 21.2 (1981): 205-213.]. However, there is a special condition where humans are unable to accurately detect relative motion: images moving in a direction consistent with retinal slip where the motion is unnaturally amplified can, under some conditions, appear stable [Arathorn, David W., et al. "How the unstable eye sees a stable and moving world." Journal of Vision 13.10.22 (2013)]. In this study, we asked: Is world-fixed retinal image background content necessary for the visual system to compute the direction of eye motion to render in the percept images moving with amplified slip as stable? Or, are non-visual cues sufficient? Subjects adjusted the parameters of a stimulus moving in a random trajectory to match the perceived motion of images moving contingent to the retina. Experiments were done with and without retinal image background content. The perceived motion of stimuli moving with amplified retinal slip was suppressed in the presence of visual content; however, higher magnitudes of motion were perceived under conditions with no visual cues. Our results demonstrate that the presence of retinal image background content is essential for the visual system to compute its direction of motion. The visual content that might be thought to provide a strong frame of reference to detect amplified retinal slips, instead paradoxically drives the misperception of relative motion.

15.
Neurosurgery ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38899868

ABSTRACT

BACKGROUND AND OBJECTIVES: Surgical treatment for symptomatic thoracic disc herniations (TDH) involves invasive open surgical approaches with relatively high complication rates and prolonged hospital stays. Although advantages of full endoscopic spine surgery (FESS) are well-established in lumbar disc herniations, data are limited for the endoscopic treatment of TDH despite potential benefits regarding surgical invasiveness. The aim of this study was to provide a comprehensive evaluation of potential benefits of FESS for the treatment of TDH. METHODS: PubMed, MEDLINE, EMBASE, and Scopus were systematically searched for the term "thoracic disc herniation" up to March 2023 and study quality appraised with a subsequent meta-analysis. Primary outcomes were perioperative complications, need for instrumentation, and reoperations. Simultaneously, we performed a multicenter retrospective evaluation of outcomes in patients undergoing full endoscopic thoracic discectomy. RESULTS: We identified 3190 patients from 108 studies for the traditional thoracic discectomy meta-analysis. Pooled incidence rates of complications were 25% (95% CI 0.22-0.29) for perioperative complications and 7% (95% CI 0.05-0.09) for reoperation. In this cohort, 37% (95% CI 0.26-0.49) of patients underwent instrumentation. The pooled mean for estimated blood loss for traditional approaches was 570 mL (95% CI 477.3-664.1) and 7.0 days (95% CI 5.91-8.14) for length of stay. For FESS, 41 patients from multiple institutions were retrospectively reviewed, perioperative complications were reported in 4 patients (9.7%), 4 (9.7%) required revision surgery, and 6 (14.6%) required instrumentation. Median blood loss was 5 mL (IQR 5-10), and length of stay was 0.43 days (IQR 0-1.23). CONCLUSION: The results suggest that full endoscopic thoracic discectomy is a safe and effective treatment option for patients with symptomatic TDH. When compared with open surgical approaches, FESS dramatically diminishes invasiveness, the rate of complications, and need for prolonged hospitalizations. Full endoscopic spine surgery has the capacity to alter the standard of care for TDH treatment toward an elective outpatient surgery.

16.
Commun Biol ; 7(1): 777, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937535

ABSTRACT

The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging.


Subject(s)
Aging , Locus Coeruleus , Magnetic Resonance Imaging , Norepinephrine , Locus Coeruleus/diagnostic imaging , Locus Coeruleus/physiology , Locus Coeruleus/metabolism , Humans , Male , Aging/physiology , Magnetic Resonance Imaging/methods , Aged , Female , Adult , Norepinephrine/metabolism , Middle Aged , Young Adult
17.
Fitoterapia ; 177: 106075, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38897244

ABSTRACT

The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology. Extracts prepared from certain plant species native to Canadian prairie and montane cordillera ecosystems have previously been shown to have anti-mitotic activity on human cancer cell lines. In this study, we investigated the glacier lily, Erythronium grandiflorum (Liliaceae), in which the species was the most phylogenetically distant from Asteraceae and had anti-mitotic activity. When added to cell lines, E. grandiflorum extracts induced rounded cell morphology and arrested cells in the G2/M phase of the cell cycle. Of the cells that displayed a rounded phenotype, all were positive for phospho-histone H3 and contained a distorted mitotic spindle. This anti-mitotic activity was distinct from that of the compound colchicine, which has been previously isolated from the Liliaceae family. By biology-guided fractionation, we isolated the natural product (+)-6-tuliposide A and are the first to report its anti-mitotic activity. These results reveal a chemical motif in secondary metabolites and expand the range of Canadian prairie plants with anti-mitotic activity that can become new scientific tools or used in the development of anti-proliferative medicines.

18.
JMIR Form Res ; 8: e49562, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833288

ABSTRACT

BACKGROUND: During the pandemic, patients with dementia were identified as a vulnerable population. X (formerly Twitter) became an important source of information for people seeking updates on COVID-19, and, therefore, identifying posts (formerly tweets) relevant to dementia can be an important support for patients with dementia and their caregivers. However, mining and coding relevant posts can be daunting due to the sheer volume and high percentage of irrelevant posts. OBJECTIVE: The objective of this study was to automate the identification of posts relevant to dementia and COVID-19 using natural language processing and machine learning (ML) algorithms. METHODS: We used a combination of natural language processing and ML algorithms with manually annotated posts to identify posts relevant to dementia and COVID-19. We used 3 data sets containing more than 100,000 posts and assessed the capability of various algorithms in correctly identifying relevant posts. RESULTS: Our results showed that (pretrained) transfer learning algorithms outperformed traditional ML algorithms in identifying posts relevant to dementia and COVID-19. Among the algorithms tested, the transfer learning algorithm A Lite Bidirectional Encoder Representations from Transformers (ALBERT) achieved an accuracy of 82.92% and an area under the curve of 83.53%. ALBERT substantially outperformed the other algorithms tested, further emphasizing the superior performance of transfer learning algorithms in the classification of posts. CONCLUSIONS: Transfer learning algorithms such as ALBERT are highly effective in identifying topic-specific posts, even when trained with limited or adjacent data, highlighting their superiority over other ML algorithms and applicability to other studies involving analysis of social media posts. Such an automated approach reduces the workload of manual coding of posts and facilitates their analysis for researchers and policy makers to support patients with dementia and their caregivers and other vulnerable populations.

19.
Ann Thorac Surg ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878949

ABSTRACT

BACKGROUND: The utility of operating room extubation (ORE) after cardiac surgery over fast-track extubation (FTE) within 6 hours remains contested. We hypothesized ORE would be associated with equivalent rates of morbidity and mortality, relative to FTE. METHODS: Patients undergoing nonemergent cardiac surgery were identified in The Society of Thoracic Surgeons Adult Cardiac Surgery Database between July 2017 and December 2022. Only procedures with The Society of Thoracic Surgeons risk models were included. Risk-adjusted outcomes of ORE and FTE were compared by observed-to-expected ratios with 95% CIs aggregated over all procedure types, and ORE vs FTE adjusted odds ratios (ORs) specific to each procedure type using multivariable logistic regression. Analyzed outcomes were operative mortality, prolonged length of stay, composite reoperation for bleeding and reintubation, and composite morbidity and mortality. RESULTS: The study population of 669,099 patients across 1069 hospitals included 36,298 ORE patients in 296 hospitals. Risk-adjusted analyses found that ORE was associated with statistically similar or better results across each of the 4 outcomes and procedure subtypes. Notably, rates of postoperative mortality were significantly lower in ORE patients undergoing coronary artery bypass grafting (OR, 0.54; 95% CI, 0.46-0.65), aortic valve replacement (OR, 0.43; 95% CI, 0.24-0.77), and mitral valve replacement (OR, 0.48; 95% CI, 0.26-0.89). CONCLUSIONS: Extubation in the OR was safe and effective in a selected patient population and may be associated with superior outcomes in coronary artery bypass, aortic valve replacement, and mitral valve replacement. These national data appear to confirm institutional experiences regarding the potential benefit of OR extubation. Further refinement of optimal populations may justify randomized investigation.

20.
JTCVS Tech ; 24: 66-75, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38835591

ABSTRACT

Objective: Mitral valve repair is the gold standard for treatment of mitral regurgitation, but the optimal technique remains debated. By using a regional collaborative, we sought to determine the change in repair technique over time. Methods: We identified all patients undergoing isolated mitral valve repair from 2012 to 2022 for degenerative mitral disease. Those with endocarditis, transcatheter repair, or tricuspid intervention were excluded. Continuous variables were analyzed via Wilcoxon rank sum, and categorical variables were analyzed via chi-square testing. Results: We identified 1653 patients who underwent mitral valve repair, with 875 (59.2%) undergoing a no resection repair. Over the last decade, there was no significant trend in the proportion of repair techniques across the region (P = .96). Those undergoing no resection repairs were more likely to have undergone prior cardiac surgery (5.0% vs 2.2%, P = .002) or minimally invasive approaches (61.4% vs 24.7%, P < .001) with similar predicted risk of mortality (median 0.6% vs 0.6%, P = .75). Intraoperatively, no resection repairs were associated with longer bypass times (140 [117-167] minutes vs 122 [91-159] minutes, P < .001). Operative mortality was similar between both groups (1.1% vs 1.0%, P = .82), as were other postoperative outcomes. Anterior leaflet prolapse (odds ratio, 11.16 [6.34-19.65], P < .001) and minimally invasive approach (odds ratio, 6.40 [5.06-8.10], P < .001) were most predictive of no resection repair. Conclusions: Despite minor differences in operative times, statewide over the past decade there remains a diverse mix of both classic "resect" and newer "respect" strategies with comparable short-term outcomes and no major timewise trends. These data may suggest that both approaches are equivocal.

SELECTION OF CITATIONS
SEARCH DETAIL
...