Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical evaluation of asthma biomarkers in clinical practice

The advent of personalized medicine has revolutionized the whole approach to the management of asthma, representing the essential basis for future developments. The cornerstones of personalized medicine are the highest precision in diagnosis, individualized prediction of disease evolution, and patient-tailored treatment. To this aim, enormous efforts have been established to discover biomarkers able to predict patients' phenotypes according to clinical, functional, and bio-humoral traits. Biomarkers are objectively measured characteristics used as indicators of biological or pathogenic processes or clinical responses to specific therapeutic interventions. The diagnosis of type-2 asthma, prediction of response to type-2 targeted treatments, and evaluation of the risk of exacerbation and lung function impairment have been associated with biomarkers detectable either in peripheral blood or in airway samples. The surrogate nature of serum biomarkers, set up to be less invasive than sputum analysis or bronchial biopsies, has shown several limits concerning their clinical applicability. Routinely used biomarkers, like peripheral eosinophilia, total IgE, or exhaled nitric oxide, result, even when combined, to be not completely satisfactory in segregating different type-2 asthma phenotypes, particularly in the context of severe asthma where the choice among different biologics is compelling. Moreover, the type-2 low fraction of patients is not only an orphan of biological treatments but is at risk of being misdiagnosed due to the low negative predictive value of type-2 high biomarkers. Sputum inflammatory cell analysis, considered the highest specific biomarker in discriminating eosinophilic inflammation in asthma, and therefore elected as the gold standard in clinical trials and research models, demonstrated many limits in clinical applicability. Many factors may influence the measure of these biomarkers, such as corticosteroid intake, comorbidities, and environmental exposures or habits. Not least, biomarkers variability over time is a confounding factor leading to wrong clinical choices. In this narrative review, we try to explore many aspects concerning the role of routinely used biomarkers in asthma, applying a critical view over the “state of the art” and contemporarily offering an overview of the most recent evidence in this field.
Polygenic power calculator: Statistical power and polygenic prediction accuracy of genome-wide association studies of complex traits

Power calculation is a necessary step when planning genome-wide association studies (GWAS) to ensure meaningful findings. Statistical power of GWAS depends on the genetic architecture of phenotype, sample size, and study design. While several computer programs have been developed to perform power calculation for single SNP association testing, it might be more appropriate for GWAS power calculation to address the probability of detecting any number of associated SNPs. In this paper, we derive the statistical power distribution across causal SNPs under the assumption of a point-normal effect size distribution. We demonstrate how key outcome indices of GWAS are related to the genetic architecture (heritability and polygenicity) of the phenotype through the power distribution. We also provide a fast, flexible and interactive power calculation tool which generates predictions for key GWAS outcomes including the number of independent significant SNPs, the phenotypic variance explained by these SNPs, and the predictive accuracy of resulting polygenic scores. These results could also be used to explore the future behaviour of GWAS as sample sizes increase further. Moreover, we present results from simulation studies to validate our derivation and evaluate the agreement between our predictions and reported GWAS results.
Editorial: Frontiers in astronomy and space sciences: Rising stars

NASA Ames Research Center, Moffet Field, CA, United States, Space Research Institute (IKI), Russian Academy of Sciences, Moscow, Russia, Department of Physics and Astronomy, University of Missouri, Columbia, MO, United States, National Institute for Astrophysics, Astronomical Observatory of Padua, Padua, Italy, Department of Chemistry “Giacomo Ciamician”, University of Bologna, Bologna, Italy, Max-Planck-Institut für Sonnensystemforschung, Göttingen, Germany, National Center for Atmospheric Research, Boulder, CO, United States, Univ. Grenoble Alpes, CNRS, IPAG, Grenoble, France, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, United States
Adherence to Sars-CoV2 vaccination in hematological patients

Background SARS-CoV2 vaccination efficiently prevents severe COVID-19, although hematological patients, particularly under therapy, respond less well. Besides vaccine efficacy, adherence to vaccination is essential for ensuring adequate protection of this vulnerable population. Methods We evaluated the impact of a program aimed at maximizing patient adherence by comparing the rate of SARS-CoV2 vaccination of our hematological patients and a matched sample of the general population. Results Vaccination rates were 88.9% among 2,156 patients, aged 65.2 ± 15.8 years (M ± SD, range 19-86 years). Rates differed considerably with age, i.e. 84.2% between 18-64 years and 92.4% above 65 years (p<0.0001), but not with sex. In the general population, rates were 76.3% overall, 73.0% between 18-64 and 86.7% above 65 years, all significantly lower than among patients, overall (Standardized Incidence ratio (SIR) 1.17; 95%CI 1.12-1.22, p<0.0001) as well as among younger (SIR 1.15; 1.07-1.24, p<0.0001) or older (SIR 1.06; 1.00-1.13, p=0.046) people. Vaccination rates increased to 92.2% overall (SIR 1.21; 1.16-1.27, p<0.0001), 88.5% in younger (SIR 1.21; 1.13-1.30, p<0.0001) and 94.8% in older (SIR 1.09; 1.03-1.12, p=0.0043) patients, after excluding those with medical contraindications, and further to 95.6% overall (SIR 1.26; 1.20-1.32, p<0.0001), 93.8% in younger (SIR 1.29; 1.20-1.38, p<0.0001) and 96.9% in older (SIR 1.11; 1.05-1.18, p=0.0004) patients, after excluding those not seen in hematology in 2021. Conclusions Vaccination rates were significantly higher in hematological patients compared to the general population regardless of age, sex and municipality. Acceptance of Covid vaccines by hematological patients may be improved by targeted information campaigns carried out by trusted health care professionals.
In silico immunogenicity assessment for sequences containing unnatural amino acids: A method using existing in silico algorithm infrastructure and a vision for future enhancements

The in silico prediction of T cell epitopes within any peptide or biologic drug candidate serves as an important first step for assessing immunogenicity. T cell epitopes bind human leukocyte antigen (HLA) by a well-characterized interaction of amino acid side chains and pockets in the HLA molecule binding groove. Immunoinformatics tools, such as the EpiMatrix algorithm, have been developed to screen natural amino acid sequences for peptides that will bind HLA. In addition to commonly occurring in synthetic peptide impurities, unnatural amino acids (UAA) are also often incorporated into novel peptide therapeutics to improve properties of the drug product. To date, the HLA binding properties of peptides containing UAA are not accurately estimated by most algorithms. Both scenarios warrant the need for enhanced predictive tools. The authors developed an in silico method for modeling the impact of a given UAA on a peptide’s likelihood of binding to HLA and, by extension, its immunogenic potential. In silico assessment of immunogenic potential allows for risk-based selection of best candidate peptides in further confirmatory in vitro, ex vivo, and in vivo assays, thereby reducing the overall cost of immunogenicity evaluation. Examples demonstrating in silico immunogenicity prediction for product impurities that are commonly found in formulations of the generic peptides teriparatide and semaglutide are provided. Next, this article discusses how HLA binding studies can be used to estimate the binding potentials of commonly encountered UAA and “correct” in silico estimates of binding based on their naturally occurring counterparts. As demonstrated here, these in vitro binding studies are usually performed with known ligands which have been modified to contain UAA in HLA anchor positions. An example using D-amino acids in relative binding position 1 (P1) of the PADRE peptide is presented. As more HLA binding data become available, new predictive models allowing for the direct estimation of HLA binding for peptides containing UAA can be established.
Quantitative rheo-microscopy of soft matter

Direct observation of the microscopic material structure and dynamics during rheological shear tests is the goal of rheo-microscopy experiments. Microscopically, they shed light on the many mechanisms and processes that determine the mechanical properties at the macroscopic scale. Moreover, they permit for the determination of the actual deformation field, which is particularly relevant to assess shear banding or wall slip. While microscopic observation of the sample during mechanical probing is achieved by a variety of custom and commercial instruments, the possibility of performing quantitative rheology is not commonly available. Here, we describe a flexible rheo-microscopy setup that is built around a parallel-sliding-plate, stress-controlled shear cell, optimized to be mounted horizontally on a commercial microscope. Mechanically, soft materials with moduli ranging from few tens of Pa up to tens of kPa can be subjected to a variety of waveforms, ranging from standard step stress and oscillatory stress to more peculiar signals, such as triangular waves or any other signal of interest. Optically, the shear cell is designed to be compatible with different imaging methods (e.g. bright field or confocal microscopy). Most of the components of the shear cell are commercially available, and those that are not can be reproduced by a standard machine shop, easing the implementation of the rheo-microscopy setup in interested laboratories.
Recent progresses and challenges in aqueous lithium–air batteries relating to the solid electrolyte separator: A mini-review

The lithium–air (Li–air) battery utilizes infinite oxygen in the air to store or release energy through a semi-open cathode structure and bears an ultra-high theoretical energy density of more than 1,000 Wh/kg. Therefore, it has been denoted as the candidate for next-generation energy storage in versatile fields such as electric vehicles, telecommunications, and special power supply. Among all types of Li–air batteries, an aqueous Li–air battery bears the advantages of a high theoretical energy density of more than 1,700 Wh/kg and does not have the critical pure oxygen atmosphere issues in a non-aqueous lithium–air battery system, which is more promising for the actual application. To date, great achievements have been made in materials’ design and cell configurations, but critical challenges still remain in the field of the solid electrolyte separator, its related lithium stripping/plating at the lithium anode, and catholyte design. In this mini-review, we summarized recent progress related to the solid electrolyte in aqueous Li–air batteries focusing on both material and battery device development. Moreover, we proposed a discussion and unique outlook on improving solid electrolyte compatibility and battery performance, thus designing an aqueous Li–air battery with higher energy density and better cycle performance in the future.
Periodontitis induced by Porphyromonas gingivalis drives impaired glucose metabolism in mice

Periodontitis has been demonstrated to be bidirectionally associated with diabetes and has been recognized as a complication of diabetes. As a periodontal pathogen, Porphyromonas gingivalis is a possible pathogen linking periodontal disease and systemic diseases. It has also been found to be involved in the occurrence and development of diabetes. In this study, 6-week-old male C57BL/6 mice were orally administered the P. gingivalis strain ATCC381 for 22 weeks. Histological analysis of the gingival tissue and quantified analysis of alveolar bone loss were performed to evaluate periodontal destruction. Body weight, fasting glucose, glucose tolerance test (GTT), and insulin tolerance test (ITT) were used to evaluate glucose metabolism disorder. We then analyzed the expression profiles of inflammatory cytokines and chemokines in gingival tissue, the liver, and adipose tissue, as well as in serum. The results showed that mice in the P. gingivalis-administered group developed apparent gingival inflammation and more alveolar bone loss compared to the control group. After 22 weeks of P. gingivalis infection, significant differences were observed at 30 and 60 min for the GTT and at 15 min for the ITT. P. gingivalis-administered mice showed an increase in the mRNA expression levels of the pro-inflammatory cytokines (TNF-α, IL-6, IL-17, and IL-23) and chemokines (CCL2, CCL8, and CXCL10) in the gingiva and serum. The expression levels of the glucose metabolism-related genes were also changed in the liver and adipose tissue. Our results indicate that oral administration of P. gingivalis can induce changes in the inflammatory cytokines and chemokines in the gingiva and blood, can lead to alveolar bone loss and to inflammatory changes in the liver and adipose tissues, and can promote glucose metabolism disorder in mice.
Laminin-bound integrin α6β4 promotes non-small cell lung cancer progression via the activation of YAP/TAZ signaling pathway

Laminin is an extracellular matrix multidomain trimeric glycoprotein, that has a potential role in tumor progression. Here, we studied the effects of non-small cell lung cancer (NSCLC) cells interaction on laminin and explored the underlying mechanism of laminin associated NSCLC progression. Culture of A549 and NCI-1299 cells on 2D collagen gels (containing laminin) significantly promoted the proliferative and tumorigenic characteristics, as well as cell invasion of tumor cells in vitro. Consistently, comparing the clinical NSCLC tumor tissues, a poor overall survival was observed in patients with high laminin expression. Mechanistically, the expression of integrin α6β4 was required for the pro-tumor effects of laminin. Meanwhile, we showed that the downstream signaling of integrin α6β4, involved the focal adhesion kinase (FAK)/Yes-Associated Protein (YAP)/TAZ signaling pathway. The activation of FAK/YAP/TAZ signaling pathway induced by laminin was validated in tumor tissues from NSCLC patients. Suppression of integrin α6β4/FAK/YAP/TAZ signaling pathway efficiently suppressed the laminin-induced tumor growth, and strengthened the anticancer effects of chemotherapy, describing a novel target for NSCLC treatment.
Apoptosis-mediated anti-proliferative activity of Calligonum comosum against human breast cancer cells, and molecular docking of its major polyphenolics to Caspase-3

Due to poor diagnosis breast cancer in women has emerged as the most common cause of death disease in developing countries. Medicinal plants have been used for thousands of years and can be useful in healthcare, especially in developing countries. Ethanol extracts of leaves of fire bush or arta (Calligonum comosum; EECC), exhibited significant anticancer potencies against two breast cancer cell lines, MCF-7 and MDA 231. These in vitro effects of EECC indicated potential anticancer activities that were determined to be specific since minimal toxicity was recorded against MCF-12, a non-cancerous breast cell line used as a reference. EECC also induced cell cycle arrest in MCF-7 and MDA 231 as revealed by the increased proportions of sub-G1 cells. Fluorescence-activated cell sorter analysis (FACS), utilizing double staining by annexin V-FITC/propidium iodide, revealed that the observed cytotoxic effects were mediated via apoptosis and necrosis. FACS measurement of thegreater in fluorescence intensity, linked with oxidation of DCFH to DCF, revealed that apoptosis was attributable to production of free radicals. EECC-mediated apoptosis was further validated by observation of up-regulation in the “executioner” enzyme, caspase 3. The current findings reveal that EECC exhibits significant, selective cytotoxicity to breast cancer cells, that proceeds via the generation of ROS, which culminates in apoptosis. The anti-proliferative effects of EECC weres further verified by use of a structure-based, virtual screening between its major bioactive polyphenolic constituents and the apoptosis executioner marker enzyme, caspase-3. Based on their glide score values against the active site of caspase 3, some phyto-constituents present in EECC, such as DL-alpha-tocopherol and campesterol, exhibited distinctive, drug-like potential with no predicted toxicity to non-target cells. Taken together, the usefulness of natural phenolic and flavonoid compounds contained in Calligonum comosum were suggested to be potent anticancer agents.
POLARBEAR constraints on cosmic birefringence and primordial magnetic fields

Author(s): Ade, PAR; Arnold, K; Atlas, M; Baccigalupi, C; Barron, D; Boettger, D; Borrill, J; Chapman, S; Chinone, Y; Cukierman, A; Dobbs, M; Ducout, A; Dunner, R; Elleflot, T; Errard, J; Fabbian, G; Feeney, S; Feng, C; Gilbert, A; Goeckner-Wald, N; Groh, J; Hall, G; Halverson, NW; Hasegawa, M; Hattori, K; Hazumi, M; Hill, C; Holzapfel, WL; Hori, Y; Howe, L; Inoue, Y; Jaehnig, GC; Jaffe, AH; Jeong, O; Katayama, N; Kaufman, JP; Keating, B; Kermish, Z; Keskitalo, R; Kisner, T; Kusaka, A; Le Jeune, M; Lee, AT; Leitch, EM; Leon, D; Li, Y; Linder, E; Lowry, L; Matsuda, F; Matsumura, T; Miller, N; Montgomery, J; Myers, MJ; Navaroli, M; Nishino, H; Okamura, T; Paar, H; Peloton, J; Pogosian, L; Poletti, D; Puglisi, G; Raum, C; Rebeiz, G; Reichardt, CL; Richards, PL; Ross, C; Rotermund, KM; Schenck, DE; Sherwin, BD; Shimon, M; Shirley, I; Siritanasak, P; Smecher, G; Stebor, N; Steinbach, B; Suzuki, A; Suzuki, JI; Tajima, O; Takakura, S; Tikhomirov, A; Tomaru, T; Whitehorn, N; Wilson, B; Yadav, A; Zahn, A | Abstract: © 2015 American Physical Society. We constrain anisotropic cosmic birefringence using four-point correlations of even-parity E-mode and odd-parity B-mode polarization in the cosmic microwave background measurements made by the POLARization of the Background Radiation (POLARBEAR) experiment in its first season of observations. We find that the anisotropic cosmic birefringence signal from any parity-violating processes is consistent with zero. The Faraday rotation from anisotropic cosmic birefringence can be compared with the equivalent quantity generated by primordial magnetic fields if they existed. The POLARBEAR nondetection translates into a 95% confidence level (C.L.) upper limit of 93 nanogauss (nG) on the amplitude of an equivalent primordial magnetic field inclusive of systematic uncertainties. This four-point correlation constraint on Faraday rotation is about 15 times tighter than the upper limit of 1380 nG inferred from constraining the contribution of Faraday rotation to two-point correlations of B-modes measured by Planck in 2015. Metric perturbations sourced by primordial magnetic fields would also contribute to the B-mode power spectrum. Using the POLARBEAR measurements of the B-mode power spectrum (two-point correlation), we set a 95% C.L. upper limit of 3.9 nG on primordial magnetic fields assuming a flat prior on the field amplitude. This limit is comparable to what was found in the Planck 2015 two-point correlation analysis with both temperature and polarization. We perform a set of systematic error tests and find no evidence for contamination. This work marks the first time that anisotropic cosmic birefringence or primordial magnetic fields have been constrained from the ground at subdegree scales.
An Online Experiment of a Price-Based Re-Rank Algorithm

Recommender Systems were created to support users in situations of information overload. However, users are consciously or unconsciously influenced by many factors in their decision making. In this paper, we focused our attention on the influence of price in user decision-making in the context of online hotel search and booking. First, we analyzed a historical dataset from a meta-search booking platform to evaluate the influence of different factors on user click behavior. Then, we performed an online A/B test on the same meta-search booking platform, in which we compared the current policy with a price-based re-rank policy. Our experiments suggested that, although in offline observations properties with lower prices tended to have a higher Click-Through Rate, in an online context a price-based re-rank was only sufficient to achieve an improvement in Click-Through Rate for the first position on the recommended list.
Efficacy and safety of acupuncture in the treatment of foot drop in post-stroke: A protocol for systematic review and meta-analysis

Background: Foot drop is a common complication in post-stroke. Patients with foot drop are at high risk for falls and fall-related injuries. Accordingly, it can reduce independence and quality of life in patients. Clinical studies have confirmed that acupuncture is effective in treating foot drop in post-stroke. However, there is a lack of systematic review exploring the efficacy and safety of acupuncture treatment. This study aims to assess the efficacy and safety of acupuncture in the treatment of foot drop in poststroke from the results of randomized controlled trials. Methods: We will search articles in 8 electronic databases including the Cochrane Central Register of Controlled Trials, the Web of Science, PubMed, Embase, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Data Database, and the Chinese Scientific Journal Database for RCTs of acupuncture treated foot drop in post-stroke from their inception to 10 August 2022. We will analyze the data meeting the inclusion criteria with the RevMan V.5. 4 software. Two authors will assess the quality of the study with the Cochrane collaborative risk bias tool. We will evaluate the certainty of the estimated evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Data analysis will be performed using STATA 16.0. Results: This study will review and evaluate the available evidence for the treatment of foot drop in post-stroke using acupuncture. Conclusion subsections: This study will determine the efficacy and safety of acupuncture applied to post-stroke individuals with foot drop.