Miracle-dz/UniFAR-FTUs huggingface dataset:
Homocysteine thiolactone contributes to the prognostic value of fibrin clot structure/function in coronary artery disease

Fibrin clot structure/function contributes to cardiovascular disease. We examined sulfur-containing metabolites as determinants of fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to outcomes in coronary artery disease (CAD) patients. Effects of B-vitamin/folate therapy on CLT and Absmax were studied. Plasma samples were collected from 1,952 CAD patients randomized in a 2 x 2 factorial design to (i) folic acid, vitamins B12, B6; (ii) folic acid, vitamin B12; (iii) vitamin B6; (iv) placebo for 3.8 years in the Western Norway B-Vitamin Intervention Trial. Clot lysis time (CLT) and maximum absorbance (Absmax) were determined using a validated turbidimetric assay. Acute myocardial infarction (AMI) and mortality were assessed during a 7-year follow-up. Data were analyzed using bivariate and multiple regression. Survival free of events was studied using Kaplan Mayer plots. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Baseline urinary homocysteine (uHcy)-thiolactone and plasma cysteine (Cys) were significantly associated with CLT while plasma total Hcy was significantly associated with Absmax, independently of fibrinogen, triglycerides, vitamin E, glomerular filtration rate, body mass index, age, sex plasma creatinine, CRP, HDL-C, ApoA1, and previous diseases. B-vitamins/folate did not affect CLT and Absmax. Kaplan-Meier analysis showed associations of increased baseline CLT and Absmax with worse outcomes. In Cox regression analysis, baseline CLT and Absmax (>cutoff) predicted AMI (CLT: HR 1.58, 95% CI 1.10–2.28; P = 0.013. Absmax: HR 3.22, CI 1.19–8.69; P = 0.021) and mortality (CLT: HR 2.54, 95% CI 1.40–4.63; P = 0.002. Absmax: 2.39, 95% CI 1.17–4.92; P = 0.017). After adjustments for other prognostic biomarkers these associations remained significant. Cys and uHcy-thiolactone, but not tHcy, were significant predictors of AMI in Cox regression models that included CLT. Conclusions uHcy-thiolactone and plasma Cys are novel determinants of CLT, an important predictor of adverse CAD outcomes. CLT and Absmax were not affected by B-vitamin/folate therapy, which could account for the lack of efficacy of such therapy in CAD. Trial registration: URL: http://clinicaltrials.gov. Identifier: NCT00354081.
RAPID COMMUNICATION: The stepped nature of lightning, and the upward connecting streamer

We present numerical results that provide an explanation of the finite steps of 20–50 m taken by lightning as it descends from the clouds, or as lightning rises from tall buildings towards the clouds. We also explain why positive streamers rise steadily from the ground to meet the descending lightning bolt at a distance of about 40 m above the ground, completing the discharge channel. Thus, the results define the limits of protection afforded by Franklin rods to buildings. Calculations for a 0.5 m positive point-plane gap show that the axial electric field of an ascending streamer has a remarkable structure comprised of a primary streamer head, followed by a secondary streamer head, and then a long plateau at a level greater than 30 kV cm −1 . This plateau in the electric field continues to elongate as the streamer propagates, maintaining the conductivity in the streamer channel. Once all the voltage is dropped along the channel plateau, streamer propagation must stop until heating modifies the channel properties. A limit is thus defined for the length of the streamer channel of around 20–50 m for typical lightning voltages. The step length must also reduce as the channel approaches the Earth, as observed, because of voltage dropped along the lengthening channel.
Measuring how motivation affects information quality assessment: A gamification approach

Purpose Existing research on the measurability of information quality (IQ) has delivered poor results and demonstrated low inter-rater agreement measured by Intra-Class Correlation (ICC) in evaluating IQ dimensions. Low ICC could result in a questionable interpretation of IQ. The purpose of this paper is to analyse whether assessors’ motivation can facilitate ICC. Methodology To acquire the participants’ views of IQ, we designed a survey as a gamified process. Additionally, we selected Web study to reach a broader audience. We increased the validity of the research by including a diverse set of participants (i.e. individuals with different education, demographic and social backgrounds). Findings The study results indicate that motivation improved the ICC of IQ on average by 0.27, demonstrating an increase in measurability from poor (0.29) to moderate (0.56). The results reveal a positive correlation between motivation level and ICC, with a significant overall increase in ICC relative to previous studies. The research also identified trends in ICC for different dimensions of IQ with the best results achieved for completeness and accuracy. Practical implications The work has important practical implications for future IQ research and suggests valuable guidelines. The results of this study imply that considering raters’ motivation improves the measurability of IQ substantially. Originality Previous studies addressed ICC in IQ dimension evaluation. However, assessors’ motivation has been neglected. This study investigates the impact of assessors’ motivation on the measurability of IQ. Compared to the results in related work, the level of agreement achieved with the most motivated group of participants was superior.
Confidence Bounds for the General Linear Model.

Abstract : In this paper, for the general linear model Y = X beta + e, we consider the construction of confidence bounds about the entire regression line. To accomplish this we exploit a powerful theorem of Scheffe. A procedure often encountered is one in which a set of confidence intervals about E(y,x) or prediction intervals for future observations are determined and then the end points are connected in such a fashion as to describe an envelope. The belief is that what has been accomplished is precisely what Scheffe's theorem allows one to do. In addition, we present some extensions concerning confidence bounds about combinations of regression lines and suggest a useful application of these results. Specifically, we propose to use the confidence bounds about the difference of regression lines to make a quantitative assessment of when and where independent sets of data characterizing the same phenomena are in agreement or disagreement.
Structural basis for HflXr-mediated antibiotic resistance in Listeria monocytogenes

Abstract HflX is a ubiquitous bacterial GTPase that splits and recycles stressed ribosomes. In addition to HflX, Listeria monocytogenes contains a second HflX homolog, HflXr. Unlike HflX, HflXr confers resistance to macrolide and lincosamide antibiotics by an experimentally unexplored mechanism. Here, we have determined cryo-EM structures of L. monocytogenes HflXr-50S and HflX-50S complexes as well as L. monocytogenes 70S ribosomes in the presence and absence of the lincosamide lincomycin. While the overall geometry of HflXr on the 50S subunit is similar to that of HflX, a loop within the N-terminal domain of HflXr, which is two amino acids longer than in HflX, reaches deeper into the peptidyltransferase center. Moreover, unlike HflX, the binding of HflXr induces conformational changes within adjacent rRNA nucleotides that would be incompatible with drug binding. These findings suggest that HflXr confers resistance using an allosteric ribosome protection mechanism, rather than by simply splitting and recycling antibiotic-stalled ribosomes.
Reliability of Continuous Shear Wave Elastography in the Pathological Patellar Tendon

Patellar tendon injuries occur via various mechanisms such as overuse, or due to surgical graft harvest for anterior cruciate ligament reconstruction (ACLR). Quantified patellar tendon stiffness after injury may help guide clinical care. Continuous shear wave elastography (cSWE) allows for the assessment of viscosity and shear modulus in tendons. The reliability of the measure, however, has not been established in the patellar tendon. The purpose of this study was to investigate the interrater reliability, intrarater reliability, and between‐day stability of cSWE in both healthy and pathological patellar tendons.
Downregulated formyl peptide receptor 2 expression in the epileptogenic foci of patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) show persistent neuroinflammation, which promotes epileptogenesis and epilepsy progression, suggesting that endogenous resolution of inflammation is inadequate to relieve neuronal network hyperexcitability. To explore the potential roles of formyl peptide receptor 2 (FPR2), which is a key regulator of inflammation resolution, in epilepsy caused by FCDIIb and TSC, we examined the expression and cellular distribution of FPR2.
Characterizing attributes of innovation of technologies for healthcare: a systematic review

Abstract Objectives Characterizing and evaluating the holistic value of innovative healthcare technologies (e.g. treatments, services) constitutes a crucial goal to maximize limited resources. However, the characteristics of innovation have not been well identified. This review aims to describe the characteristics of healthcare innovation. Methods We performed a comprehensive systematic search using PubMed, Embase, PsycINFO, and Econlit from inception to July 2022. Articles were included if they described innovation or the characteristics of innovation of the technologies in healthcare. Characteristics or definitions of innovation directly or indirectly described as innovation were extracted from the included articles. Two independent reviewers then conceptualized the identified characteristics of innovation to generate innovation attributes in healthcare. Results In total, 103 articles were included in this review. Eight attributes describing innovation, i.e. novelty, step change, substantial benefits, an improvement over existing technologies, convenience and/or adherence, added value, acceptable cost, and uncounted benefits, were conceptualized. Most of the identified innovation attributes were based on the researchers’ perspective. Conclusions This study conceptualized innovation attributes in healthcare based on the characteristics of healthcare innovation as defined in the literature. Further research is warranted to obtain a complete understanding of the perspectives of researchers and other stakeholders, including patients, healthcare providers, healthcare payers, and the pharmaceutical industry, on recognizing innovation in healthcare. KEY POINTS This is the first systematic review to conceptualize attributes of healthcare innovation. We conceptualized eight attributes describing innovation, i.e. novelty, step change, substantial benefits, an improvement over existing technologies, convenience and/or adherence, added value, acceptable cost, and uncounted benefits based on the similar concept. In existing literature, patients’ and caregivers’ perspectives were less frequently found to describe the innovation attributes. Future research is needed to identify, measure, and value various stakeholders, including patients’ and caregivers’ perspectives on healthcare innovation.
In vitro vascularization of hydrogel-based tissue constructs via a combined approach of cell sheet engineering and dynamic perfusion cell culture

The bioengineering of artificial tissue constructs requires special attention to their fast vascularization to provide cells with sufficient nutrients and oxygen. We addressed the challenge of in vitro vascularization by employing a combined approach of cell sheet engineering, 3D printing, and cellular self-organization in dynamic maturation culture. A confluent cell sheet of human umbilical vein endothelial cells (HUVECs) was detached from a thermoresponsive cell culture substrate and transferred onto a 3D-printed, perfusable tubular scaffold using a custom-made cell sheet rolling device. Under indirect co-culture conditions with human dermal fibroblasts (HDFs), the cell sheet-covered vessel mimic embedded in a collagen gel together with additional singularized HUVECs started sprouting into the surrounding gel, while the suspended cells around the tube self-organized and formed a dense lumen-containing 3D vascular network throughout the gel. The HDFs cultured below the HUVEC-containing cell culture insert provided angiogenic support to the HUVECs via molecular crosstalk without competing for space with the HUVECs or inducing rapid collagen matrix remodeling. The resulting vascular network remained viable under these conditions throughout the 3 week cell culture period. This static indirect co-culture setup was further transferred to dynamic flow conditions, where the medium perfusion was enabled via two independently addressable perfusion circuits equipped with two different cell culture chambers, one hosting the HDFs and the other hosting the HUVEC-laden collagen gel. Using this system, we successfully connected the collagen-embedded HUVEC culture to a dynamic medium flow, and within 1 week of the dynamic cell culture, we detected angiogenic sprouting and dense microvascular network formation via HUVEC self-organization in the hydrogel. Our approach of combining a 3D-printed and cell sheet-covered vascular precursor that retained its sprouting capacity together with the self-assembling HUVECs in a dynamic perfusion culture resulted in a vascular-like 3D network, which is a critical step toward the long-term vascularization of bioengineered in vitro tissue constructs.
Crystal structure of an L‐type lectin domain from archaea

The crystal structures of an L‐type lectin domain from Methanocaldococcus jannaschii in apo and mannose‐bound forms have been determined. A thorough investigation of L‐type lectin domains from several organisms provides insight into the differences in these domains from different kingdoms of life. While the overall fold of the L‐type lectin domain is conserved, differences in the lengths of the carbohydrate‐binding loops and significant variations in the Mn2+‐binding site compared to the Ca2+‐binding site are observed. Furthermore, the sequence and phylogenetic analyses suggest that the archaeal L‐type lectin domain is evolutionarily closer to the plant legume lectins than to its bacterial or animal counterparts. This is the first report of the biochemical, structural, sequence, and phylogenetic analyses of an L‐type lectin domain from archaea and serves to enhance our understanding of the species‐specific differences and evolution of L‐type lectin domains.
Participatory peer research exploring the experience of learning during Covid-19 for allied health and healthcare science students

Introduction The teaching and learning experience of allied health and healthcare science students has altered because of the Covid-19 pandemic. Limited research has explored the experience on the future healthcare workforce using participatory research design. The aim of this study was to explore the impact of a global pandemic on the clinical and academic experiences of healthcare student using a co-production approach with student peer researchers. Methods A participatory research approach adopting online focus groups facilitated by students trained as peer researchers was adopted. First, second and final year students from occupational therapy, physiotherapy, podiatry, healthcare science, diagnostic radiography and imaging, radiotherapy and oncology, and speech and language therapy were recruited to six focus groups. Data generated through focus groups were analysed thematically using the DEPICT model to support a partnership approach. Results Twenty-three participants took part in six focus groups. The themes identified were: rapid changes to learning; living alongside Covid-19 and psychological impact. Students preferred blended learning approaches when available, as reduced peer interaction, studying and sleeping in the same space, and technology fatigue decreased motivation. Conclusion Due to rapid changes in learning and the stress, anxiety and isolation created by the pandemic, managing study, personal life and placement resulted in a gap in confidence in clinical skills development for students. Students took their professional identity seriously, engaged in behaviours to reduce transmission of Covid-19 and employed a range of coping strategies to protect wellbeing. A challenge with the move to online delivery was the absence of informal peer learning and students indicated that moving forward they would value a hybrid approach to delivery. Higher Education should capitalise on innovative learning experiences developed during the pandemic however it is important to research the impact this has on student skill acquisition and learning experience.
FRET‐FLIM to Determine Protein Interactions and Membrane Topology of Enzyme Complexes

Determining protein‐protein interactions is vital for gaining knowledge on cellular and metabolic processes including enzyme complexes and metabolons. Förster resonance energy transfer with fluorescence lifetime imaging microscopy (FRET‐FLIM) is an advanced imaging methodology that allows for the quantitative detection of protein‐protein interactions. In this method, proteins of interest for interaction studies are fused to different fluorophores such as enhanced green fluorescent protein (eGFP; donor molecule) and monomeric red fluorescent protein (mRFP; acceptor molecule). Energy transfer between the two fluorophore groups can only occur efficiently when the proteins of interest are in close physical proximity, around ≤10 nm, and therefore are most likely interacting. FRET‐FLIM measures the decrease in excited‐state lifetime of the donor fluorophore (eGFP) with and without the presence of the acceptor (mRFP) and can therefore give information on protein‐protein interactions and the membrane topology of the tested protein. Here we describe the production of fluorescent protein fusions for FRET‐FLIM analysis in tobacco leaf epidermal cells using Agrobacterium‐mediated plant transformation and a FRET‐FLIM data acquisition and analysis protocol in plant cells. These protocols are applicable and can be adapted for both membrane and soluble proteins in different cellular localizations. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.
Vaccinia virus BTB-Kelch proteins C2 and F3 inhibit NF-κB activation

Vaccinia virus (VACV) encodes scores of proteins that suppress host innate immunity and many of these target intracellular signalling pathways leading to activation of inflammation. The transcription factor NF-κB plays a critical role in the host response to infection and is targeted by many viruses, including VACV that encodes 12 NF-κB inhibitors that interfere at different stages in this signalling pathway. Here we report that VACV proteins C2 and F3 are additional inhibitors of this pathway. C2 and F3 are BTB-Kelch proteins that are expressed early during infection, are non-essential for virus replication, but affect the outcome of infection in vivo. Using reporter gene assays, RT-qPCR analyses of endogenous gene expression, and ELISA, these BTB-Kelch proteins are shown here to diminish NF-κB activation by reducing translocation of p65 into the nucleus. C2 and F3 are the 13th and 14th NF-κB inhibitors encoded by VACV. Remarkably, in every case tested, these individual proteins affect virulence in vivo and therefore have non-redundant functions. Lastly, immunisation with a VACV strain lacking C2 induced a stronger CD8+ T cell response and better protection against virus challenge.
Cross-correlation of CMB Polarization Lensing with High-z Submillimeter Herschel-ATLAS Galaxies

We report a 4. 8σ measurement of the cross-correlation signal between the cosmic microwave background (CMB) lensing convergence reconstructed from measurements of the CMB polarization made by the Polarbear experiment and the infrared-selected galaxies of the Herschel-ATLAS survey. This is the first measurement of its kind. We infer a best-fit galaxy bias of , corresponding to a host halo mass of at an effective redshift of z ∼ 2 from the cross-correlation power spectrum. Residual uncertainties in the redshift distribution of the submillimeter galaxies are subdominant with respect to the statistical precision. We perform a suite of systematic tests, finding that instrumental and astrophysical contaminations are small compared to the statistical error. This cross-correlation measurement only relies on CMB polarization information that, differently from CMB temperature maps, is less contaminated by galactic and extragalactic foregrounds, providing a clearer view of the projected matter distribution. This result demonstrates the feasibility and robustness of this approach for future high-sensitivity CMB polarization experiments.
Checklist for Artificial Intelligence in Medical Imaging Reporting Adherence in Peer-Reviewed and Preprint Manuscripts With the Highest Altmetric Attention Scores: A Meta-Research Study

Purpose: To establish reporting adherence to the Checklist for Artificial Intelligence in Medical Imaging (CLAIM) in diagnostic accuracy AI studies with the highest Altmetric Attention Scores (AAS), and to compare completeness of reporting between peer-reviewed manuscripts and preprints. Methods: MEDLINE, EMBASE, arXiv, bioRxiv, and medRxiv were retrospectively searched for 100 diagnostic accuracy medical imaging AI studies in peer-reviewed journals and preprint platforms with the highest AAS since the release of CLAIM to June 24, 2021. Studies were evaluated for adherence to the 42-item CLAIM checklist with comparison between peer-reviewed manuscripts and preprints. The impact of additional factors was explored including body region, models on COVID-19 diagnosis and journal impact factor. Results: Median CLAIM adherence was 48% (20/42). The median CLAIM score of manuscripts published in peer-reviewed journals was higher than preprints, 57% (24/42) vs 40% (16/42), P < . 0001. Chest radiology was the body region with the least complete reporting (P = .0352), with manuscripts on COVID-19 less complete than others (43% vs 54%, P = .0002). For studies published in peer-reviewed journals with an impact factor, the CLAIM score correlated with impact factor, rho = 0.43, P = . 0040. Completeness of reporting based on CLAIM score had a positive correlation with a study’s AAS, rho = 0.68, P < . 0001. Conclusions: Overall reporting adherence to CLAIM is low in imaging diagnostic accuracy AI studies with the highest AAS, with preprints reporting fewer study details than peer-reviewed manuscripts. Improved CLAIM adherence could promote adoption of AI into clinical practice and facilitate investigators building upon prior works.