Miracle-dz/UniFAR-FTUs huggingface dataset:
BioModels—15 years of sharing computational models in life science

Abstract Computational modelling has become increasingly common in life science research. To provide a platform to support universal sharing, easy accessibility and model reproducibility, BioModels (https://www.ebi.ac.uk/biomodels/), a repository for mathematical models, was established in 2005. The current BioModels platform allows submission of models encoded in diverse modelling formats, including SBML, CellML, PharmML, COMBINE archive, MATLAB, Mathematica, R, Python or C++. The models submitted to BioModels are curated to verify the computational representation of the biological process and the reproducibility of the simulation results in the reference publication. The curation also involves encoding models in standard formats and annotation with controlled vocabularies following MIRIAM (minimal information required in the annotation of biochemical models) guidelines. BioModels now accepts large-scale submission of auto-generated computational models. With gradual growth in content over 15 years, BioModels currently hosts about 2000 models from the published literature. With about 800 curated models, BioModels has become the world’s largest repository of curated models and emerged as the third most used data resource after PubMed and Google Scholar among the scientists who use modelling in their research. Thus, BioModels benefits modellers by providing access to reliable and semantically enriched curated models in standard formats that are easy to share, reproduce and reuse.
Life-threatening hypersensitivity pneumonitis secondary to e-cigarettes

We report a case of hypersensitivity pneumonitis (HP) in a young person secondary to vaping. He presented with a putative diagnosis of asthma and required extracorporeal membrane oxygenation because of intractable respiratory failure. He developed a critical illness and steroid myopathy and required prolonged rehabilitation. Our patient fulfils diagnostic criteria for HP secondary to e-cigarettes with a positive exposure history, deterioration after skin prick testing, specific serum IgM antibodies against the implicated liquid raising the possibility that the relevant antigen was present in that liquid and radiological and histopathological features compatible with acute HP. There are two learning points. The first is always to consider a reaction to e-cigarettes in someone presenting with an atypical respiratory illness. The second is that we consider e-cigarettes as ‘much safer than tobacco’ at our peril.
The Problem With p and Statistical Significance.

There is a problem with p. Specifically, there is a problem with the declaration of statistical significance when p ≤ . 05. Longer ago than recently, the American Statistical Society, among others, called for changing the way researchers report results, including not reporting p values without also providing context for understanding what those values mean and eliminating the claim of statistical significance from research papers. Recently, the American Statistical Society has become more insistent in the call for us to change not only language but practice, as well. There are many good reasons for this insistence, and in case you missed the discussion, please see the 43 articles published in The American Statistician in March 2019 for details. The editorial in that issue provides excellent detail about the problems with p values and statements of statistical significance (Wasserstein, Schirm, & Lazar, 2019). The editors also, helpfully, introduce some potential solutions to p-value use. These solutions, which are further detailed in the collected articles, include the use of minimal important effect size (Amrhein, Trafimow, & Greenland, 2019) and second-generation p value, which takes practical significance into account (Greevy, Welty, Blume, DuPont, & Smith, 2019). Other suggestions are available; most of us will need to work closely with statisticians to make sure we choose the most appropriate approach for our work. Briefly, because some of you have asked us what to do about reporting statistical results in papers submitted to NursingResearch,we support the recommendation ofWasserstein et al. (2019) to accept uncertainty and to be thoughtful, open, and modest in reporting your statistical results. More specifically and as Hayat (2010) noted almost a decade ago in this Journal, significance testing is a subjective procedure; tests of significance do not provide an objective measure of scientific evidence nor do p values have any clinicalmeaning. A specific p value depends on many factors, including statistical power, effect size, and sample size. Thus, when reporting a p value, a context for understanding the value needs to be included, such as confidence intervals, odds ratios, hazard ratios, or regression coefficients, all of which provide an estimate of the magnitude of an effect. Matthews (2019) suggests providing clarity to the width of the confidence interval as another way to contextualize p values. The Publication Manual of the American Psychological Association, which is used by this Journal for manuscript style, will publish a new edition
The worth of the uniform [uniform crossover]

Since its popularization by Syswerda (1989), uniform crossover (UC) has become perhaps the most widely used crossover operator, despite the fact that arguments backing low-disruption operators are as old as the genetic algorithm (GA) itself. We question the usual arguments given in favor of UC, and argue that on problems with even a mild degree of difficulty, disruption is indeed harmful. We conduct experiments on a function which is a simple concatenation of several copies of a non-separable function, which makes it difficult for a simple hill climber. We find that in this setup, UC is outperformed by the standard 2-point crossover fitted with inversion. According to our experiments, on problems where applying a GA makes sense, UC appears to perform worse than the classic 2-point crossover fitted with inversion, and essentially the same as a simple copy-and-mutate operator.
Disparities in outcomes associated with rural-urban insurance status in China among inpatient women with stroke: a registry-based cohort study.

Background Despite a few studies have demonstrated sex differences in stroke care and outcomes, limited research has explored insurance-related disparities in outcomes, particularly among women stroke patients. The aim was to determine whether rural-urban health insurance status affect the stroke treatment, process of care, and 1-year clinical outcomes for inpatient ischemic stroke in women. Methods Women patients with acute ischemic stroke (AIS) covered by New Rural Cooperative Medical Scheme (NRCMS) and urban resident/employee-based basic medical insurance scheme (URBMI/UEBMI) were abstracted from the China National Stroke Registry II (CNSR II). Shared frailty model in the Cox model or generalized estimating equation with consideration of the hospital's cluster effect were used to assess the associations between rural-urban insurance status and quality of care during hospitalization and 1-year stroke outcomes including all-cause death, 1-year recurrence, and 1-year disability. Results A total of 5,707 women patients enrolled from 219 hospitals in CNSR II were analyzed. Compared with 2,880 women patients covered by URBMI/UEBMI, 2,827 women patients covered by NRCMS were younger (65.7 versus 68.9 years), less likely to have vascular risk factors, awareness and treatment of hypertension and dyslipidemia prior to stroke. Women covered by NRCMS were more likely to receive early antithrombotics, discharge antithrombotics, lipid-lowering drugs, but less likely to receive antihypertensive medication than those covered by URBMI/UEBMI. One-year all-cause mortality and stroke recurrence were both significantly higher in women patients with NRCMS than those with URBMI/UEBMI [adjusted hazard ratio (95% confidence interval): 1.40 (1.06-1.84) and 1.38 (1.04-1.83), separately]. Conclusions AIS women patients with rural-urban insurance status demonstrated remarkable differences in age, stroke risk factors, awareness and treatment, the process of care, and 1-year stroke recurrence and mortality. Healthcare policymakers need to focus their attention on these disparities and take proper steps to improve primary healthcare service in rural areas.
Quantifying shape and ecology in avian pedal claws: The relationship between the bony core and keratinous sheath

Abstract Terrestrial tetrapods use their claws to interact with their environments in a plethora of ways. Birds in particular have developed a diversity of claw shapes since they are often not bound to terrestrial locomotion and have heterogeneous body masses ranging several orders of magnitude. Numerous previous studies have hypothesized a connection between pedal claw shape and ecological mode in birds, yet have generated conflicting results, spanning from clear ecological groupings based on claw shape to a complete overlap of ecological modes. The majority of these studies have relied on traditional morphometric arc measurements of keratinous sheaths and have variably accounted for likely confounding factors such as body mass and phylogenetic relatedness. To better address the hypothesized relationship between ecology and claw shape in birds, we collected 580 radiographs allowing visualization of the bony core and keratinous sheath shape in 21 avian orders. Geometric morphometrics was used to quantify bony core and keratinous sheath shape and was compared to results using traditional arc measurements. Neither approach significantly separates bird claws into coarse ecological categories after integrating body size and phylogenetic relatedness; however, some separation between ecological groups is evident and we find a gradual shift from the claw shape of ground‐dwelling birds to those of predatory birds. Further, the bony claw core and keratinous sheath are significantly correlated, and the degree of functional integration does not differ across ecological groups. Therefore, it is likely possible to compare fossil bony cores with extant keratinous sheaths after applying corrections. Finally, traditional metrics and geometric morphometric shape are significantly, yet loosely correlated. Based on these results, future workers are encouraged to use geometric morphometric approaches to study claw geometry and account for confounding factors such as body size, phylogeny, and individual variation prior to predicting ecology in fossil taxa.
Multiple retrograde tracing methods compatible with 3DISCO clearing

Abstract Exploring the spatial relationship of various neuron pools in the spinal cord is crucial and difficult due to its complexity. The single-labelling tracing and sectioning were employed in previous studies exploring the distribution of spinal motor neuron pools, which could only delineate one single motor neuron pool in one specimen and could not achieve intact-tissue observation. Here, with combination of neuroanatomy tracing techniques and the optical clearing technique, we developed a multiple retrograde tracing method compatible with 3DISCO clearing. Fluoro-Gold, Fluoro-Ruby, Cholera Toxin Subunit B, Alexa Fluor 488 and 647 Conjugate were injected intramuscularly in hindlimbs of C57BL/6 adults. After labelling, the harvested spinal cords were optically cleared by 3DISCO method and imaged using confocal microscope. There were positive signals of all four tracers and four motor neurons pools targeting injected muscles were labelled. Three-dimension model of four motor neuron pools was successfully reconstructed based on tomography images showing the spatial relationship of different neuron pools. In conclusion, using this method, we first delineated the spatial relationship of four different motor neuron pools targeting four skeletal muscles in one spinal cord at the same time, which provide a holistic view of motor neuron pools in the spinal cord.
High tumour-associated macrophages infiltration is correlated with poor survival outcome in classical Hodgkin’s lymphoma

Background: Classical Hodgkin’s lymphoma (cHL) represents the majority of HLs with a relatively good prognosis. In 20% ofpatients, primary treatment fails. Prediction of treatment failure is critical. A gene signature of tumour associated macrophages(TAM) correlated with response to treatment as CD68 positive TAM was found to be associated with shortened survival. We aimto investigate the relation CD68+TAM infiltration to patients’ outcome. Patients and Methods: Pathological materials of 115 patients with cHL were used. Clinical characteristics of patients werecollected from the records. CD68 immunostaining was performed to determine the number of infiltrating TAM and subsequentlyfollowed by stratification of results. Results of CD68 immunostaining were statistically analysed to correlate the extent of CD68+TAM infiltration with clinicopathological characteristics, treatment outcome, and patients’ survival. Results: High CD68+TAM infiltration was observed in more patients of cHL (96/115 of patients = 83.5%). High CD68+TAMinfiltration was associated with extranodal presentation (p = .001), and higher stage (p = .022). No associations with otherclinicopathological parameters were found. High CD68+TAM infiltration was not found to be an independent predictor oftreatment outcome. High CD68+TAM infiltration correlated with disease free survival (DFS) (log-rank = 4.505, p = .034) but notwith disease specific survival (DSS) (log-rank = 1.371, p = .242). Conclusions: The results of our study support the adverse prognostic effect of high TAM in cHL. Technical standardisation ofCD68 immunostaining is required to establish TAM infiltration as a prognostic predictor. Also in vivo and in vitro cHL modelshave to be established for proper understanding of the role of CD68 in modulating the TAM in cHL.
Flexible and Highly Sensitive Strain Sensor Based on Laser-Induced Graphene Pattern Fabricated by 355 nm Pulsed Laser

A laser-induced-graphene (LIG) pattern fabricated using a 355 nm pulsed laser was applied to a strain sensor. Structural analysis and functional evaluation of the LIG strain sensor were performed by Raman spectroscopy, scanning electron microscopy (SEM) imaging, and electrical–mechanical coupled testing. The electrical characteristics of the sensor with respect to laser fluence and focal length were evaluated. The sensor responded sensitively to small deformations, had a high gauge factor of ~160, and underwent mechanical fracture at 30% tensile strain. In addition, we have applied the LIG sensor, which has high sensitivity, a simple manufacturing process, and good durability, to human finger motion monitoring.
Linear ubiquitin assembly complex regulates lung epithelial driven responses during influenza infection.

Influenza A virus (IAV) is among the most common causes of pneumonia related death worldwide. Pulmonary epithelial cells are the primary target for viral infection and replication and respond by releasing inflammatory mediators that recruit immune cells to mount the host response. Severe lung injury and death during IAV infection results from an exuberant host inflammatory response. The linear ubiquitin assembly complex (LUBAC), composed of SHARPIN, HOIL-1L and HOIP, is a critical regulator of NF-κB-dependent inflammation. Using mice with lung epithelial specific deletions of HOIL-1L or HOIP in a model of IAV infection, we provided evidence that, while a reduction in the inflammatory response was beneficial, ablation of the LUBAC-dependent lung epithelial-driven response worsened lung injury and increased mortality. Moreover, we described a mechanism for the upregulation of HOIL-1L in infected and non-infected cells triggered by the activation of type I interferon receptor and mediated by IRF1, which was maladaptive and contributed to hyper-inflammation. Thus, we propose that lung epithelial LUBAC acts as a molecular rheostat that could be selectively targeted to modulate the immune response in patients with severe IAV-induced pneumonia.
Profile of bile acid subspecies is similar in blood and follicular fluid of cattle

Abstract The composition of follicular fluid (FF) has an impact on the developmental capacity of the oocyte and the resulting embryo. FF is composed of blood plasma constituents which cross the blood follicular barrier and the secretory components of granulosa and theca cells. Moreover, it has been shown recently that follicular cells have the ability to synthesize bile acids (BAs). BAs are present in several fluids of mammals especially in bile, blood and urine. FF is an essential impacting factor on the oocyte quality and therefore resulting embryos. To achieve a better understanding of this subject, the presence and concentration of BAs were measured in fluid collected from bovine follicles, categorized according to their size, throughout two entire oestrus cycles and compared to those in blood and urine. The body fluids were collected during the same examination procedure and in total samples from four heifers were obtained. A broad spectrum of 11 BA derivatives was measured applying liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The simultaneous and direct quantification of BAs in different body fluids of cattle are reported. Within the follicular fluid, blood and urine, cholic acid and glycocholic acid are the dominant BA subspecies irrespective of the oestrus cycle stage. Moreover, BA concentrations in blood compared to those in the FF were similar. For the first time these results clearly highlight the presence of different BA subspecies in FF, blood and urine during the oestrus cycle in cattle.
Co-designing for Community Oversight

Collective feedback can support an individual's decision-making process. For instance, individuals often seek the advice of friends, family, and co-workers to help them make privacy decisions. However, current technologies often do not provide mechanisms for this type of collaborative interaction. To address this gap, we propose a novel model of Community Oversight for Privacy and Security ("CO-oPS"), which identifies mechanisms for users to interact with people they trust to help one another make digital privacy and security decisions. We apply our CO-oPS model in the context of mobile applications ("apps"). To interrogate and refine this model, we conducted participatory design sessions with 32 participants in small groups of 2-4 people who know one another, with the goal of designing a mobile app that facilitates collaborative privacy and security decision-making. We describe and reflect on the opportunities and challenges that arise from the unequal motivation and trust in seeking support and giving support within and beyond a community. Through this research, we contribute a novel framework for collaborative digital privacy and security decision-making and provide empirical evidence towards how researchers and designers might translate this framework into design-based features.
Systematic spatio-temporal mapping reveals divergent cell death pathways in three mouse models of hereditary retinal degeneration

Calcium (Ca2+) dysregulation has been linked to neuronal cell death, including in hereditary retinal degeneration. Ca2+ dysregulation is thought to cause rod and cone photoreceptor cell death. Spatial and temporal heterogeneities in retinal disease models have hampered validation of this hypothesis. We examined the role of Ca2+ in photoreceptor degeneration, assessing the activation pattern of Ca2+-dependent calpain proteases, generating spatio-temporal maps of the entire retina in the cpfl1 mouse model for primary cone degeneration, and in the rd1 and rd10 models for primary rod degeneration. We used Gaussian process models to distinguish the temporal sequences of degenerative molecular processes from other variability sources. In the rd1 and rd10 models, spatio-temporal pattern of increased calpain activity matched the progression of primary rod degeneration. High calpain activity coincided with activation of the calpain-2 isoform but not with calpain-1, suggesting differential roles for both calpain isoforms. Primary rod loss was linked to upregulation of apoptosis-inducing factor (AIF), although only a minute fraction of cells showed activity of the apoptotic marker caspase-3. After primary rod degeneration concluded, caspase-3 activation appeared in cones, suggesting apoptosis as the dominant mechanism for secondary cone loss. Gaussian process models highlighted calpain activity as a key event during primary rod photoreceptor cell death. Our data suggests a causal link between Ca2+ dysregulation and primary, non-apoptotic degeneration of photoreceptors and a role for apoptosis in secondary degeneration of cones, highlighting the importance of the spatial and temporal location of key molecular events, which may guide the evaluation of new therapies.
An Empirical Study of the Spillover Effects of Workload on Patient Length of Stay

We use two years of inpatient data from 243 California hospitals to quantify the relationship between hospital-level workload and patient length of stay (LOS), and its “spillover” effects across patient types. Patients are categorized as medical or surgical, and the effects of same type patient workload (occupancy) on LOS are analyzed. The analysis is repeated with workload replaced by other type patient occupancy, providing a “spillover” effect. We find that the effects of inpatient workload on LOS spillover across patient types, which we theorize results from most inpatients, regardless of type, utilizing the same shared resources (e.g. pharmacy and laboratory). These spillover effects remain even while we find that the effects of workload vary at different time points during a patient’s stay: LOS increases as inpatient workload on the day of admission increases, while inpatient workload at the end of the stay has a Ushaped effect on LOS.
Relation of IGF-I with subclinical cardiovascular markers including intima-media thickness, left ventricular mass index and NT-proBNP.

OBJECTIVE Several studies revealed relations between low or high insulin-like growth factor I (IGF-I) levels and risk of cardiovascular diseases or mortality whereas the mechanisms behind these associations are still unknown. DESIGN The study aimed to explore relations between IGF-I and changes in surrogate markers of cardiovascular disease including carotid intima-media thickness (IMT), left ventricular mass index (LVMI) and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS Longitudinal data of the population-based cohort Study of Health in Pomerania (SHIP) were used. IMT was measured by ultrasonography and LVMI was determined based on echocardiography. IGF-I and IGF-binding protein-3 (IGFBP-3) levels were measured by chemiluminescent immunoassays and the IGF-I/IGFBP-3 ratio was calculated. Mixed linear regression models adjusted for known cardiovascular confounders were performed. RESULTS Statistical analyses demonstrated relations between low baseline IGF-I levels [beta for ΔIMT per standard deviation increase -0.044 (standard error 0.012)] or IGF-I/IGFBP-3 ratio [beta -0.045 (0.012)] and a long-term IMT increase. No associations between IGF-I, IGFBP-3 or IGF-I/IGFBP-3 ratio and changes in LVMI were detected. With respect to NT-proBNP sex-specific associations with IGF-I were found. In women, higher baseline IGF-I levels [beta for ΔNT-proBNP per standard deviation increase 5.92 (2.2)] or IGF-I/IGFBP-3 ratio [beta 4.48 (2.2)] were related to an increase in NT-proBNP levels. Among men, U-shaped relations of baseline levels of IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio with an increase in NT-proBNP were found. CONCLUSIONS The study detected significant relations between IGF-I and long-term changes in IMT and NT-proBNP but not LVMI. These findings argue for different effects of the IGF-I axis with respect to various cardiovascular entities.