Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping EQ5D utilities from forced vital capacity and diffusing capacity in fibrotic interstitial lung disease

Objectives Fibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in fibrotic ILDs. Methods EQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry. Results The OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities < 0.5) and in the external validation cohort. Conclusion We developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies.
Effects of 5‐year experimental warming in the Alpine belt on soil Archaea: Multi‐omics approaches and prospects

Abstract We currently lack a predictive understanding of how soil archaeal communities may respond to climate change, particularly in Alpine areas where warming is far exceeding the global average. Here, we characterized the abundance, structure, and function of total (by metagenomics) and active soil archaea (by metatranscriptomics) after 5‐year experimental field warming (+1°C) in Italian Alpine grasslands and snowbeds. Our multi‐omics approach unveiled an increasing abundance of Archaea during warming in snowbeds, which was negatively correlated with the abundance of fungi (by qPCR) and micronutrients (Ca and Mg), but positively correlated with soil water content. In the snowbeds transcripts, warming resulted in the enrichment of abundances of transcription and nucleotide biosynthesis. Our study provides novel insights into possible changes in soil Archaea composition and function in the climate change scenario.
Target‐capture probes for phylogenomics of the Caenogastropoda

Target‐capture approaches have facilitated a rapid growth in the field of phylogenomics but few probe sets exist for molluscs, an exceptionally rich phylum with unparalleled ecological and morphological diversity. We designed and tested the first universal probe set using Phyluce to capture ultraconserved elements (UCEs) and exon loci from the Subclass Caenogastropoda ‐ one of six major lineages of gastropods. The probe set consists of 29,441 probes designed to target 1142 UCE loci and 1933 exon loci (3075 total). In silico analyses of our probe set yielded an average of 2110 loci from genomes and 1389 loci from transcriptomes of diverse caenogastropods, from which an average of 1669 and 849 loci were retained respectively after screening to remove those that matched multiple contigs. Phylogenetic analyses of the loci extracted from transcriptomes produced well‐supported trees very similar to those published based on transcriptomic analyses. Phylogenetic relationships estimated from loci extracted from genomes recover similar phylogenetic relationships, and indicate that the loci targeted with this probe set are informative for resolving deep phylogenetic relationships. An in vitro analysis of the probe set with the Epitoniidae, a diverse caenogastropod family of uncertain affinity and with poorly resolved evolutionary relationships, recovered a total of 2850 loci. Although preliminary, the analysis of loci captured by our probe set for a small number of epitoniid taxa produced a well‐resolved tree indicating that this probe set is also able to resolve relationships at shallower hierarchical scales. Together, the in silico and in vitro analyses indicate that target‐capture enrichment with this probe set is a useful tool for reconstructing phylogenetic relationships across taxonomic levels and evolutionary time scales.
The Arf family GTPases: Regulation of vesicle biogenesis and beyond

The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less‐studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting‐edge technologies and in vivo functional studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis.
Site-Specifically Conjugated Single-Domain Antibody Successfully Identifies Glypican-3–Expressing Liver Cancer by Immuno-PET

Visual Abstract Primary liver cancer is the third leading cause of cancer-related deaths, and its incidence and mortality are increasing worldwide. Hepatocellular carcinoma (HCC) accounts for 80% of primary liver cancer cases. Glypican-3 (GPC3) is a heparan sulfate proteoglycan that histopathologically defines HCC and represents an attractive tumor-selective marker for radiopharmaceutical imaging and therapy for this disease. Single-domain antibodies are a promising scaffold for imaging because of their favorable pharmacokinetic properties, good tumor penetration, and renal clearance. Although conventional lysine-directed bioconjugation can be used to yield conjugates for radiolabeling full-length antibodies, this stochastic approach risks negatively affecting target binding of the smaller single-domain antibodies. To address this challenge, site-specific approaches have been explored. Here, we used conventional and sortase-based site-specific conjugation methods to engineer GPC3-specific human single-domain antibody (HN3) PET probes. Methods: Bifunctional deferoxamine (DFO) isothiocyanate was used to synthesize native HN3 (nHN3)-DFO. Site-specifically modified HN3 (ssHN3)-DFO was engineered using sortase-mediated conjugation of triglycine-DFO chelator and HN3 containing an LPETG C-terminal tag. Both conjugates were radiolabeled with 89Zr, and their binding affinity in vitro and target engagement of GPC3-positive (GPC3+) tumors in vivo were determined. Results: Both 89Zr-ssHN3 and 89Zr-nHN3 displayed nanomolar affinity for GPC3 in vitro. Biodistribution and PET/CT image analysis in mice bearing isogenic A431 and A431-GPC3+ xenografts, as well as in HepG2 liver cancer xenografts, showed that both conjugates specifically identify GPC3+ tumors. 89Zr-ssHN3 exhibited more favorable biodistribution and pharmacokinetic properties, including higher tumor uptake and lower liver accumulation. Comparative PET/CT studies on mice imaged with both 18F-FDG and 89Zr-ssHN3 showed more consistent tumor accumulation for the single-domain antibody conjugate, further establishing its potential for PET imaging. Conclusion: 89Zr-ssHN3 showed clear advantages in tumor uptake and tumor-to-liver signal ratio over the conventionally modified 89Zr-nHN3 in xenograft models. Our results establish the potential of HN3-based single-domain antibody probes for GPC3-directed PET imaging of liver cancers.
A review of the International Seabed Authority database DeepData from a biological perspective: challenges and opportunities in the UN Ocean Decade

Abstract There is an urgent need for high-quality biodiversity data in the context of rapid environmental change. Nowhere is this need more urgent than in the deep ocean, with the possibility of seabed mining moving from exploration to exploitation, but where vast knowledge gaps persist. Regions of the seabed beyond national jurisdiction, managed by the International Seabed Authority (ISA), are undergoing intensive mining exploration, including the Clarion–Clipperton Zone (CCZ) in the Central Pacific. In 2019, the ISA launched its database ‘DeepData’, publishing environmental (including biological) data. Here, we explore how DeepData could support biological research and environmental policy development in the CCZ (and wider ocean regions) and whether data are findable, accessible, interoperable and reusable (FAIR). Given the direct connection of DeepData with the regulator of a rapidly developing potential industry, this review is particularly timely. We found evidence of extensive duplication of datasets; an absence of unique record identifiers and significant taxonomic data–quality issues, compromising FAIRness of the data. The publication of DeepData records on the OBIS ISA node in 2021 has led to large-scale improvements in data quality and accessibility. However, limitations in the usage of identifiers and issues with taxonomic information were also evident in datasets published on the node, stemming from mismapping of data from the ISA environmental data template to the data standard Darwin Core prior to data harvesting by OBIS. While notable data-quality issues remain, these changes signal a rapid evolution for the database and significant movement towards integrating with global systems, through the usage of data standards and publication on the global data aggregator OBIS. This is exactly what has been needed for biological datasets held by the ISA. We provide recommendations for the future development of the database to support this evolution towards FAIR. Database URL https://data.isa. org.jm/isa/map
“I think I could have coped if I was sleeping better”: Sleep across the trajectory of caring for a family member with dementia

Dementia-related sleep changes can lead to disruptions among families living with dementia which can jeopardise carers’ wellbeing and ability to provide support. This research explores and represents the sleep of family caregivers across the trajectory of caring, before, during, and after the key period of their care recipient moving into residential care. The focus of this paper is viewing dementia caregiving as a trajectory, characterised by care needs which change over time. Semi-structured interviews were conducted with 20 carers whose family member with dementia had transitioned into residential care within the prior 2 years. Themes constructed from these interviews indicated that sleep was linked to earlier life course patterns as well as to significant moments of transition in the caregiving journey. As dementia progressed, carers’ sleep progressively worsened in relation to the less predictable nature of dementia-symptoms, difficulty maintaining routines, and constant responsibilities creating a state of high alert. Carers attempted to facilitate better sleep and wellbeing for their family member, often sacrificing their own self-care. Around the care transition period, some cares reported not realising how sleep deprived they were; for others the busy momentum continued. After the transition, many carers acknowledged that they were exhausted, although many had not realised this while providing home-based care. Post-transition, many carers reported ongoing sleep disruptions associated with poor sleep habits established whilst caring, insomnia or nightmares and grief. Carers were optimistic that their sleep would improve with time and many were enjoying sleeping according to their own preferences. The sleep experience of family carers is unique and includes tensions between their essential need for sleep and the experience of care as self-sacrifice. Findings have implications for timely support and interventions for families living with dementia.
Understanding the barriers and facilitators of COVID-19 vaccine hesitancy amongst healthcare workers and healthcare students worldwide: An umbrella review protocol

Healthcare workers (HCWs) and healthcare students are at increased risk of becoming infected with and being a vector of transmission of COVID-19. Vaccination efforts amongst this group of persons have been hampered in some countries by hesitancy to uptake the COVID-19 vaccine. The factors related to vaccine hesitancy have been reported in several systematic reviews. However, a comprehensive overview of barriers and facilitators of COVID-19 vaccine hesitancy is greatly needed to address effective interventions in this population. Understanding and designing effective strategies to promote vaccination among HCWs is pivotal to secure an appropriate and safe healthcare provision. The current protocol describes the methodology for an Umbrella Review that explores the barriers and facilitators of COVID-19 vaccine hesitancy for HCWs and healthcare students. The databases that will be searched are CINAHL, MedLine, Cochrane Library, PubMed, ProQuest, Web of Science, Science Direct, IBSS, Google Scholar, and Epistemonikos. Studies will be eligible for inclusion if they: (i) conducted a systematic review (with or without meta-analysis); (ii) included primary sources utilizing a quantitative methodology; (iii) investigated factors related to COVID-19 vaccine hesitancy; (iv) and included a sub/population of HCWs or healthcare students aged 18–65. The screening processes and data extraction will be conducted independently by two reviewers. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews and Research Syntheses will be used to assess the methodological quality of the included reviews. The degree to which the included reviews contain the same primary studies will also be assessed and reported. The outcomes of this review will have wide-reaching implications for the research area, healthcare systems and institutions, and governments worldwide.
Fusion of various optimisation based feature smoothing methods for wearable and non‐invasive blood glucose estimation

Abstract The traditional blood glucose estimation method requires to take the invasive measurements several times a day. Therefore, it has a high infection risk and the users are suffered from the pain. Moreover, the long term consumable cost is high. Recently, the wearable and non‐invasive blood glucose estimation approach has been proposed. However, due to the unreliability of the acquisition device, the presence of the noise and the variations of the acquisition environments, the obtained features and the reference blood glucose values are highly unreliable. Moreover, different subjects have different responses of the infrared light to the blood glucose. To address this issue, a polynomial fitting approach to smooth the obtained features or the reference blood glucose values has been proposed. In particular, the design of the coefficients in the polynomial is formulated as the various optimisation problems. First, the blood glucose values are estimated based on the individual optimisation approaches. Second, the absolute difference values between the estimated blood glucose values and the actual blood glucose values based on each optimisation approach are computed. Third, these absolute difference values for each optimisation approach are sorted in the ascending order. Fourth, for each sorted blood glucose value, the optimisation method corresponding to the minimum absolute difference value is selected. Fifth, the accumulate probability of each selected optimisation method is computed. If the accumulate probability of any selected optimisation method at a point is greater than a threshold value, then the accumulate probabilities of these three selected optimisation methods at that point are reset to zero. A range of the sorted blood glucose values are defined as that with the corresponding boundaries points being the previous reset point and this reset point. Hence, after performing the above procedures for all the sorted reference blood glucose values in the validation set, the regions of the sorted reference blood glucose values and the corresponding optimisation methods in these regions are determined. It is worth noting that the conventional lowpass denoising method was performed in the signal domain (either in the time domain or in the frequency domain), while the authors’ proposed method is performed in the feature space or the reference blood glucose space. Hence, the authors’ proposed method can further improve the reliability of the obtained feature values or the reference blood glucose values so as to improve the accuracy of the blood glucose estimation. Moreover, the individual modelling regression method has been employed here to suppress the effects of different users having different responses of the infrared light to the blood glucose values. The computer numerical simulation results show that the authors’ proposed method yields the mean absolute relative deviation (MARD) at 0.0930 and the percentage of the test data falling in the zone A of the Clarke error grid at 94.1176%.
Genome‐wide single nucleotide polymorphisms reveal recurrent waves of speciation in niche‐pockets, in Europe's most venomous snake

Within the Balkan Peninsula, topographic and climatic agents have promoted biodiversity and shaped the speciation history of many ectotherms. Here, we targeted an iconic European reptile, the nose‐horned viper species‐complex (Vipera ammodytes), and explored its spatial and temporal evolution. We (i) utilized genome‐wide single nucleotide polymorphisms to infer genetic structure and build a time‐calibrated species‐tree, and (ii) applied species distribution modelling with niche‐divergence tests among major phylogenomic clades. Geographically structured genetic diversity was found. Cycles of recurrent isolation and expansion during glacial–interglacial periods led to allopatric speciation and to secondary contacts and formation of multiple hybrid zones throughout the Balkan Peninsula. Deep divergence is still detected among populations separated by old and imminent biogeographical barriers (Pindos Mountain Range, the Cyclades islands, etc.), but in most cases speciation is incomplete. At the other end of the speciation continuum, we recognize two well‐differentiated lineages, currently lacking any evidence of gene flow; one is distributed in the Northwestern Balkans and the other in the Southeastern Balkans, further expanding into Asia. Despite their split 5 million years ago, there is no evidence of ecological divergence, as speciation probably occurred in niche‐pockets of analogous environments. These two lineages probably represent different species, while V. transcaucasiana does not merit species status. By comparing the genomic phylogenies to an updated mitochondrial one, we propose an evolutionary scenario that resolves all mitonuclear conflicts, according to which the history of the V. ammodytes species‐complex was shaped by complex processes, including a major event of introgressive hybridization with asymmetric mitochondrial capture.
Asymmetry of cross-correlations between intra-day and overnight volatilities

We point out a stunning time asymmetry in the short-time cross-correlations between intra-day and overnight volatilities (absolute values of log-returns of stock prices). While overnight volatility is significantly (and positively) correlated with the intra-day volatility during the following day (allowing thus non-trivial predictions), it is much less correlated with the intra-day volatility during the preceding day. While the effect is not unexpected in view of previous observations, its robustness and extreme simplicity are remarkable.
Characterization of multi-DAA resistance using a novel hepatitis C virus genotype 3a infectious culture system

Background and Aims: The high HCV infection cure rates achieved with direct-acting antiviral (DAA) treatments could be compromised in the future by the emergence of antiviral resistance. Thus, it is essential to understand the viral determinants that influence DAA resistance, which is most prevalent in genotype 3. We aimed at studying how resistance to protease-, NS5A-, and NS5B-inhibitors influences the activities of glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir in cell culture, and how the HCV genome adapts to selective pressure by successive rounds of treatment failure. Approach and Results: A previously developed in vivo infectious cDNA clone of strain S52 (genotype 3a) was adapted to efficiently replicate and propagate in human hepatoma cells (Huh7.5) using 31 adaptive substitutions. DAA escape experiments resulted in the selection of S52 variants with decreased drug susceptibility (resistance), which was linked to the emergence of known resistance-associated substitutions (RASs). NS5A-inhibitor resistance was sufficient to promote treatment failure with double-DAA but not triple-DAA regimens. Enhanced viral fitness associated with the selection of sofosbuvir resistance accelerated escape from DAAs. After serial DAA treatment failure, HCV genetic evolution led to a complex genome-wide network of substitutions, some of which coevolved with known RASs. Conclusions: Baseline NS5A-RAS can compromise the efficacy of double-DAA pangenotypic regimens for HCV genotype 3, and enhanced viral fitness can accelerate treatment failure. Persistence of RASs after successive treatment failure is facilitated by the remarkable evolutionary capacity and plasticity of the HCV genome. Proof-of-concept for the potential development of multi-DAA resistance is shown.
Low-Reynolds-Number Airfoils

The airfoil section is the quintessence of a wing or lifting surface and, as such, occupies a central position in any design discipline relating to fluid mechanics, from animal flight through marine propellers to aircraft. The proper functioning of the airfoil is the prerequisite to the satisfactory performance of the lifting surface itself, and thus the airfoil is of fundamental technical importance. Transcending functional considerations, the physical shape of the airfQil-teardrop-like or paisley motif-like-seems to have some univer­ sal aesthetic appeal. As a consequence, the development and selection of airfoils has exercised an almost mystical fascination on designers. Since the early work of Eiffel and 10ukowsky at the turn of the century, fluid dynamicists have recognized the importance of the airfoil shape and have developed a bewildering plethora of airfoil designs and families, many with almost magical claims of efficaciousness. But the ideal shape of an airfoil depends profoundly upon the size and speed of the wing of which it is the core. This dependence is called scale effect. In the thirties, the significance of scale effect was first recognized. This relates to the phenomenon that an airfoil that has most excellent qualities on an insect or bird may not exhibit these advantages when scaled up for an airplane wing, and vice versa. Different sizes of airfoils require different shapes. This scale effect is characterized by the chord Reynolds number, R, defined by R = Vc/v, where V is the flight speed, c is the chord, and v is the kinematic viscosity of the fluid in which the airfoil is operating. The Reynolds number quantifies the relative importance of the inertial (fluid momentum) effects on the airfoil behavior, compared