Miracle-dz/UniFAR-FTUs huggingface dataset:
Latest RNA and DNA nanopore sequencing allows for rapid avian influenza profiling

Avian influenza virus (AIV) currently causes a panzootic with extensive mortality in wild birds, poultry, and wild mammals, thus posing a major threat to global health and underscoring the need for efficient monitoring of its distribution and evolution. Here, we utilized a well-defined AIV strain to systematically investigate AIV characterization through rapid, portable nanopore sequencing by (i) benchmarking the performance of fully portable RNA extraction and viral detection; (ii) comparing the latest DNA and RNA nanopore sequencing approaches for in-depth AIV profiling; and (iii) evaluating the performance of various computational pipelines for viral consensus sequence creation and phylogenetic analysis. Our results show that the latest RNA-specific nanopores can accurately genomically profile AIV from native RNA while additionally detecting RNA epigenetic modifications. We further identified an optimal laboratory and bioinformatic pipeline for reconstructing viral consensus genomes from nanopore sequencing data at various rarefaction thresholds, which we validated by application to real-world environmental samples for AIV monitoring in livestock. Author Summary We tested portable, rapid, and easy-to-use technology to obtain more information about the potentially zoonotic RNA virus avian influenza virus, or AIV. AIV has spread globally via the migratory paths of wild birds, and endangers domestic birds, mammals, and human populations given past evidence of infections of different animal species. We here used novel genomic technology that is based on nanopores to explore the genomes of the virus; we established optimized ways of creating the viral genome by comparing different laboratory and computational approaches and the performance of nanopores that either sequence the viral RNA directly or the converted DNA. We then applied the optimized protocol to dust samples which were collected from a duck farm in France during an AIV outbreak. We showed that we were able to use the resulting data to reconstruct the relationship between the virus responsible for the outbreak and previously detected AIV. Altogether, we showed how novel easy-to-use genomic technology can support the surveillance of potentially zoonotic pathogens by accurately recreating the viral genomes to better understand evolution and transmission of these pathogens.
A quantitative pipeline to assess secretion of human leptin coding variants reveals mechanisms underlying leptin deficiencies

The hormone leptin, primarily secreted by adipocytes, plays a crucial role in regulating whole-body energy homeostasis. Homozygous loss-of-function mutations in the leptin gene (LEP) cause hyperphagia and severe obesity, primarily through alterations in leptin’s affinity for its receptor or changes in serum leptin concentrations. Although serum concentrations are influenced by various factors (e.g., gene expression, protein synthesis, stability in the serum), proper delivery of leptin from its site of synthesis in the endoplasmic reticulum via the secretory pathway to the extracellular serum is a critical step. However, the regulatory mechanisms and specific machinery involved in this trafficking route, particularly in the context of human LEP mutations, remain largely unexplored. We have employed the Retention Using Selective Hooks (RUSH) system to elucidate the secretory pathway of leptin. We have refined this system into a medium-throughput assay for examining the pathophysiology of a range of obesity-associated LEP variants. Our results reveal that leptin follows the default secretory pathway, with no additional regulatory steps identified prior to secretion. Through screening of leptin variants, we identified three mutations that lead to proteasomal degradation of leptin and one mutant that significantly decreased leptin secretion, likely through aberrant disulfide bond formation. These observations have identified novel pathogenic effects of leptin variants, which can be informative for therapeutics and diagnostics. Finally, our novel quantitative screening platform can be adapted for other secreted proteins.
Automated model discovery for human cardiac tissue: Discovering the best model and parameters

For more than half a century, scientists have developed mathematical models to understand the behavior of the human heart. Today, we have dozens of heart tissue models to choose from, but selecting the best model is limited to expert professionals, prone to user bias, and vulnerable to human error. Here we take the human out of the loop and automate the process of model discovery. Towards this goal, we establish a novel incompressible orthotropic constitutive neural network to simultaneously discover both, model and parameters, that best explain human cardiac tissue. Notably, our network features 32 individual terms, 8 isotropic and 24 anisotropic, and fully autonomously selects the best model, out of more than 4 billion possible combinations of terms. We demonstrate that we can successfully train the network with triaxial shear and biaxial extension tests and systematically sparsify the parameter vector with L1-regularization. Strikingly, we robustly discover a four-term model that features a quadratic term in the second invariant I2, and exponential quadratic terms in the fourth and eighth invariants I4f, I4n, and I8fs. Importantly, our discovered model is interpretable by design and has parameters with well-defined physical units. We show that it outperforms popular existing myocardium models and generalizes well, from homogeneous laboratory tests to heterogeneous whole heart simulations. This is made possible by a new universal material subroutine that directly takes the discovered network weights as input. Automating the process of model discovery has the potential to democratize cardiac modeling, broaden participation in scientific discovery, and accelerate the development of innovative treatments for cardiovascular disease. Our source code, data, and examples are available at https://github.com/LivingMatterLab/CANN.
High-dimensional mass cytometry reveals stemness state heterogeneity in pancreatic ductal adenocarcinoma

Stem-like cancer cells harbour high self-renewal capacity, exhibit enhanced tumourigenicity and have been associated with therapy resistance, metastasis and tumour relapse. Therefore, understanding the molecular features of stem-like cells is critical for targeting them effectively and improving treatment outcomes for cancer patients. Several markers have been used to isolate and study the putative stem-like cells of pancreatic ductal adenocarcinoma (PDAC), but the patterns of marker co-expression and overlap between identified individual subpopulations are yet to be comprehensively studied. Here we developed a mass cytometry antibody panel for simultaneous analysis of 33 stemness-associated markers at single-cell resolution. High-dimensional mass cytometry analysis of PDAC cell lines revealed molecularly heterogeneous stemness states and highlighted the role of genotype in determining the cell line-specific stemness signature. Stemness marker expression lie along a continuum in PDAC cell lines and patient samples indicative of stepwise phenotypic transitions. We also identified a subset of PDAC cells co-expressing high levels of Musashi-2, DCLK1 and CXCR4, and harbouring basal-like and EMT transcriptional programmes associated with highly plastic phenotype. This multiplexed analysis uncovers nuance and complexities of the stemness state in the PDAC.
Disordered proteins interact with the chemical environment to tune their protective function during drying

The conformational ensemble and function of intrinsically disordered proteins (IDPs) are sensitive to their solution environment. The inherent malleability of disordered proteins combined with the exposure of their residues accounts for this sensitivity. One context in which IDPs play important roles that is concomitant with massive changes to the intracellular environment is during desiccation (extreme drying). The ability of organisms to survive desiccation has long been linked to the accumulation of high levels of cosolutes such as trehalose or sucrose as well as the enrichment of IDPs, such as late embryogenesis abundant (LEA) proteins or cytoplasmic abundant heat soluble (CAHS) proteins. Despite knowing that IDPs play important roles and are co-enriched alongside endogenous, species-specific cosolutes during desiccation, little is known mechanistically about how IDP-cosolute interactions influence desiccation tolerance. Here, we test the notion that the protective function of desiccation-related IDPs is enhanced through conformational changes induced by endogenous cosolutes. We find that desiccation-related IDPs derived from four different organisms spanning two LEA protein families and the CAHS protein family, synergize best with endogenous cosolutes during drying to promote desiccation protection. Yet the structural parameters of protective IDPs do not correlate with synergy for either CAHS or LEA proteins. We further demonstrate that for CAHS, but not LEA proteins, synergy is related to self-assembly and the formation of a gel. Our results demonstrate that functional synergy between IDPs and endogenous cosolutes is a convergent desiccation protection strategy seen among different IDP families and organisms, yet, the mechanisms underlying this synergy differ between IDP families.
A gnotobiotic mouse model with divergent equol-producing phenotype: potential for determining microbial-driven health impacts of soy isoflavone daidzein

The implications of soy consumption on human health have been a subject of debate, largely due to the mixed evidence regarding its benefits and potential risks. The variability in responses to soy has been partly attributed to differences in the metabolism of soy isoflavones, compounds with structural similarities to estrogen. Approximately one-third of humans possess gut bacteria capable of converting soy isoflavone daidzein into equol, a metabolite produced exclusively by gut microbiota with significant estrogenic potency. In contrast, lab-raised rodents are efficient equol producers, except for those raised germ-free. This discrepancy raises concerns about the applicability of traditional rodent models to humans. Herein, we designed a gnotobiotic mouse model to differentiate between equol producers and non-producers by introducing synthetic bacterial communities with and without the capacity into female and male germ-free mice. These gnotobiotic mice display equol-producing phenotypes consistent with the capacity of the gut microbiota received. Our findings confirm the model’s efficacy in mimicking human equol production capacity, offering a promising tool for future studies to explore the relationship between endogenous equol production and health outcomes like cardiometabolic and fertility. This approach aims to refine dietary guidelines by considering individual microbiome differences.
Phosphorus Distribution in Delta Sediments: A Unique Data Set from Deer Creek Reservoir

Recently, Deer Creek Reservoir (DCR) underwent a large drawdown to support dam reconstruction. This event exposed sediments inundated by the reservoir, since dam completion in the early 1940s. This event allowed us to take sediment data samples and evaluate them for phosphorous (P) content. It is difficult for normal reservoir sediment studies to have sediment samples at high spatial resolution because of access. During the drawdown, we collected 91 samples on a grid 100 m in one direction and 200 m in the other. This grid defined an area of approximately 750,000 m2 (185 acre). We took both surface samples, and at some sites, vertical samples. We determined water soluble P for all the samples, and P in four other reservoirs or fractions for 19 samples. Results showed water soluble P in the range of 2.28 × 10−3 to 9.81 × 10−3, KCl-P from 2.53 × 10−3 to 1.10 × 10−2, NaOH-P from 5.30 × 10−2 to 4.60 × 10−1, HCl-P from 1.28 × 10−1 to 1.34, and residual (mostly organic) P from 8.23 × 10−1 to 3.23 mg/g. We provide this data set to the community to support and encourage research in this area. We hope this data set will be used and analyzed to support other research efforts.
Post-pandemic crime trends in England and Wales

This study of recorded crime trends in England & Wales spans three and a half years, that is, two covid pandemic years from March 2020 and 18 ‘post-pandemic’ months following cessation of covid restrictions. Observed crime rates were compared to expected (based on 5-year ARIMA models) and the ambient population (using Community Mobility Reports). It finds that, In Year 1, observed rates diverged dramatically from expected, waxing and waning generally in line with the movement restrictions of three national lockdowns. In Year 2, movement restrictions loosened and observed crime rates moved towards but mostly remained far from expected. In post-pandemic Year 3, people’s movement increased and observed crime rates continued towards expected. By mid-Year 4 many rates remained below expected levels, their mean monthly differences including: theft from person (− 22%); burglary (− 20%); vehicle crime (− 29%); violence & sexual offences (− 27%); robbery (− 16%) and; public order offences (− 21%). An exceptional increase in shoplifting achieved 20% above expected rates by August 2023. Methodological limitations and further research on shoplifting and other issues are discussed. The main conclusion is that crime trends generally followed ambient population movement and that enduring lifestyle changes in the post-pandemic period, notably increased work-from-home, account for continuing below-expected rates of many crime types.
The effects of self-administered acupressure on fasting blood sugar, glycosylated hemoglobin, and anxiety levels in prediabetic women

Background: Several studies have investigated the effects of acupressure in patients with known diabetes. However, no studies have investigated the effects of acupressure on women with prediabetes. Objectives : The present study aimed to investigate the effects of self-administered acupressure on fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), and anxiety levels in prediabetic women. Methods: This randomized controlled trial was carried out on 50 women with prediabetes who referred to the Diabetes Clinic of Mazandaran University of Medical Sciences, Sari, Iran, from September 4, 2021, to February 20, 2023. Participants were randomly assigned to two groups of 25 to receive either metformin and self-administered acupressure or metformin and sham point pressure. FBS, HbA1c, and anxiety levels were measured in both groups before and 12 weeks after the intervention. All patients also received routine training. Data were analyzed using chi-square test and Fisher's exact test, independent samples t-test and analysis of covariance (ANCOVA). Results: The two groups did not differ significantly in their mean baseline FBS and HbA1c values. However, the mean baseline anxiety was significantly higher in the control group ( P =0.009). After the intervention, the mean FBS, HbA1c, and anxiety were significantly lower in the intervention group (P<0.001) . After controlling for the effect of baseline anxiety scores using ANCOVA, we found that the intervention was effective in reducing mean anxiety (P<0.001) . Conclusion: Self-administered acupressure reduced FBS, HbA1c, and anxiety levels in prediabetic women. Therefore, it is recommended that nurses and physicians train prediabetic patients to use self-administered acupressure to manage their anxiety and prediabetic symptoms.
OBSERVATION-BASED PEDESTRIAN SCENARIO EXTRACTION FOR VIRTUAL TESTING

An overall reduction of pedestrian-vehicle collisions is expected with the market penetration of Advanced Driver Assistant System (ADAS) and autonomous driving (AD) functions. The performance of ADAS is commonly evaluated through virtual scenario-based testing. Hence, scenario catalogs that represent realistic pedestrian-vehicle interactions are needed. This study shows an approach to automatically extract pedestrian-vehicle scenarios at a selected road intersection, which was observed with a dual-lens stationary observation system. A deep learning-based visual perception pipeline was implemented to reconstruct road user trajectories via state-of-the-art object detection, visual multi-object tracking and object re-identification models. These models were trained and fine-tuned on a manually annotated, diverse dataset, randomly sampled from recordings over multiple weeks. All models were evaluated using common performance metrics. Additionally, localization precision of reconstructed trajectories was assessed using georeferenced ground truth measurements conducted at the intersection. The visual perception pipeline was applied on selected video data and extracted trajectories converted according to the openSCENARIO standard, including a virtual representation of the selected road intersection. The compiled scenarios were further simulated with the openPASS framework. The results show that pedestrians and vehicles were tracked with high accuracy (Multiple Object Tracking Accuracy > 83.2%) and trajectories were reconstructed with a mean deviation
Homogenization of weakly coercive integral functionals in three-dimensional linear elasticity

— This paper deals with the homogenization through Γ-convergence of weakly coercive integral energies, with the oscillating density L(x/ε)∇v:∇v, in three-dimensional elasticity. The energies are weakly coercive in the sense where the classical functional coercivity satisfied by the periodic tensor L: ∫ R3 L(y)∇v:∇v dy > Λ(L) ∫ R3 |∇v| dy, for any smooth function v with compact support in R3, with Λ(L) > 0, is replaced by the relaxed condition Λ(L) > 0. We prove that the homogenized tensor L0 remains strongly elliptic, or equivalently Λ(L0) > 0, for any tensor L = L(y1) satisfying the pointwise inequality: L(y)M :M + D:Cof(M) > 0, a.e. y ∈ R, ∀M ∈ R3×3, adding a quadratic null-Lagrangian for some matrix D ∈ R3×3, and assuming the periodic functional coercivity Λper(L) > 0 (using smooth test functions v with periodic gradients). However, we derive rigorously the loss of strong ellipticity for the homogenized tensor, which is based on a Γ-convergence result under the sole assumption Λ(L) > 0, and on a rank-two lamination. Résumé (Homogénéisation de fonctionnelles intégrales faiblement coercives en élasticité linéaire tridimensionnelle) Dans cet article on étudie la Γ-convergence d’énergies intégrales faiblement coercives, de densité oscillante L(x/ε)∇v:∇v, en élasticité tridimensionnelle. Les énergies sont faiblement coercives du fait que la coercivité fonctionnelle classique satisfaite par le tenseur périodique L : ∫ R3 L(y)∇v:∇v dy > Λ(L) ∫ R3 |∇v| dy, pour toute fonction régulière v à support compact dans R3, avec Λ(L) > 0, est remplacée par la condition relaxée Λ(L) > 0. On montre que le tenseur homogénéisé L0 reste fortement elliptique ou, de manière équivalente, Λ(L0) > 0, pour tout tenseur L = L(y1) vérifiant l’inégalité ponctuelle : L(y)M :M + D:Cof(M) > 0, p.p. y ∈ R, ∀M ∈ R3×3, par l’addition d’un lagrangien nul pour une matrice D ∈ R3×3 donnée, et en supposant la coercivité fonctionnelle périodique Λper(L) > 0 (obtenue avec des fonctions test v de gradient périodique). Cependant, on obtient une perte d’ellipticité du tenseur homogénéisé, fondée sur un résultat de Γ-convergence sous la seule hypothèse Λ(L) > 0, et sur une lamination de rang 2. Mathematical subject classification (2010). — 35B27, 74B05, 74Q15.
Prosthodendri-Morphological and molecular characteristics of Paralecithodendrium longiforme (Digenea: Lecithodendriidae) adults and cercariae from Chinese pipistrelle bats and viviparid snails in Thailand

This study aimed to describe the morphological and molecular characteristics of Para-lecithodendrium longiforme (Digenea: Lecithodendriidae) adults and cercariae isolated in Thailand. Adult flukes were isolated from the Chinese pipistrelle bat ( Hypsugo sp.), and cercariae were detected in the viviparid snail ( Filopaludina martensi martensi ) from Chi-ang Mai province. The morphological characteristics were observed and described us-ing conventional methods, and the molecular characteristics with internal transcribed spacer 2 (ITS2) and 28S rDNA gene sequences. The adult flukes were fusiform, 0.84– 0.98 mm in length, and 0.37–0.49 mm in width, and were distinguishable from other species by the presence of longitudinal uterine coils. The cercariae were nonvirgulate xi-phidiocercariae, with the oral sucker bigger than the acetabulum, the tail without fin fold, a body size of 117.5–138.3×48.3–52.2 µm, and a tail size of 100.7–103.7×15.0–18.9 µm. Molecular studies revealed that the adults and cercariae shared 99.3% (ITS2) and 99.6% (28S rDNA) homology with each other. They were phylogenetically close to P. longiforme with an identity of 94.5% for ITS2 and 98.7% for 28S rDNA. This study provides new information on the natural definitive host and first intermediate host of P. lon-giforme in Thailand. The discovery of its cercarial stage in Filopaludina snails highlights the importance of monitoring the associated second intermediate host and prevention and control of this potentially zoonotic trematode.
Effects of Percutaneous Closure of Patent Ductus Arteriosus in Effects of Percutaneous Closure of Patent Ductus Arteriosus in Infants Less than One Year of Age: A Systematic Review Infants Less than One Year of Age: A Systematic Review

Background: Patent ductus arteriosus (PDA) is the continuous opening of the ductus arteriosus in an infant’s heart after birth. This, when left untreated, can lead to numerous complications, including pulmonary hypertension as a result of the increased flow of blood into the lungs or even death. Historically, the first treatment option to correct PDA was surgery, opening up the chest cavity to close the duct; however, it has been seen to cause later neurodevelopmental impairments leading to further problems for the infant [1]. Therefore, clinicians searched for an alternative, leading to the use of percutaneous closure. Catheter-based PDA closure is increasingly performed during infancy (<1 year of age); however, the safety and feasibility of this intervention is currently not completely characterized in infants. Thus, the purpose of this study is to assess the safety and feasibility of percutaneous PDA closure in infants as reported in the available medical literature. Methods: We conducted a systematic review of all pertinent published data from January 1965 – December 2015. A total of 5 electronic databases were searched. Inclusion criteria were (1) peer review journal source; (2) patient age birth to 1 year; and (3) adequate assessment and reporting of adverse events (AEs) and other safety data. Results: Of 1060 articles identified, 949 were reviewed, but only 19 articles met inclusion criteria satisfactorily. Eighteen articles were case-control studies and one was a cohort study. No randomized controlled studies were identified. A tally of patients from all 19 included articles revealed 505 patients underwent a percutaneous procedure to close PDA. Among these, 480 (95%) were amenable to placement of PDA device/coil. Of these, 471 (93%) were reported to have attained complete PDA closure. In addition,