Miracle-dz/UniFAR-FTUs huggingface dataset:
Economic Analysis of the Immunostimulant OM-85 for the Prevention of Paediatric Recurrent Upper Respiratory Tract Infections

Objective: To evaluate the cost of preventing recurrent upper respiratory tract infections (URTIs) with a non- specific immunostimulating agent (OM-85) in at-risk children. Methods: A cost consequence analysis was conducted considering three different perspectives: Community, National Health Service and patient. A pre-existing decisional model was used to compare prophylaxis with OM-85 and no prophylaxis. The clinical data was based on the weighted average of the results of nine randomized pla-cebo-controlled trials identified by a Cochrane literature review. Clinical events considered in the model were natural resolution of the infection, onset of complications (acute otitis media, sinusitis, others) and their evolu-tion. Direct and indirect costs incurred by patient, NHS and Community were structured in accordance with the most authoritative guidelines and implemented with current Italian prices and tariffs. Sensibility analyses were performed to evaluate the model robustness. Results: The immunostimulating agent OM-85 achieved savings for 40.30 euro/patient in the perspective of the National Health Service and for 182.99 euro/patient in the community’s perspective. Sensitivity analyses con-firmed the robustness of base scenario results. Conclusions: Non-specific immunotherapy with OM-85 reduces the incidence of URTIs in at-risk children to-gether with savings for the community and NHS.
Benefits of higher resistance‐training volume are related to ribosome biogenesis

For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross‐sectional area, strength and type II fibre‐type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Out of 34 participants, thirteen displayed clear benefit of MOD on muscle hypertrophy and sixteen showed clear benefit of MOD on muscle strength gains. This coincided with greater total RNA accumulation in the early phase of the training period, suggesting that ribosomal biogenesis regulates the dose–response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose‐dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis.
Noncanonical Mechanisms for Direct Bone Marrow Generating Ang II (Angiotensin II) Predominate in CD68 Positive Myeloid Lineage Cells

Supplemental Digital Content is available in the text. Bone marrow (BM) Ang II (angiotensin II) is a major participant in the regulation of hematopoiesis and immunity. The novel tissue substrate Ang-(1–12) [angiotensin-(1–12)] and its cleaving enzyme chymase are an essential source of Ang II production in cardiac tissue. We hypothesized this noncanonical chymase-mediated Ang II–producing mechanism exists in the BM tissue. Immunohistostaining and flow cytometry confirmed the presence of Ang-(1–12) immunoreaction in the BM of SD (Sprague Dawley) rats. Chymase-mediated Ang II–producing activity in BM was ≈1000-fold higher than ACE (angiotensin-converting enzyme)-mediated Ang II–producing activity (4531±137 and 4.2±0.3 fmol/min per mg, respectively; n=6; P<0.001) and 280-fold higher than chymase activity in the left ventricle of 16.3±1.7 fmol/min per mg (P<0.001). Adding a selective chymase inhibitor, TEI-F00806, eliminated almost all 125I-Ang II production. Flow cytometry demonstrated that delta median fluorescence intensity of chymase in cluster of differentiation 68 positive cells was significantly higher than that in cluster of differentiation 68 negative cells (1546±157 and 222±48 arbitrary units, respectively; P=0.0021). Cluster of differentiation 68 positive and side scatter low subsets, considered to be myeloid progenitors, express the highest chymase fluorescence intensity in rat BM. Chymase activity and cellular expression was similar in both male and female rats. In conclusion, myeloid lineage cells, especially myeloid progenitors, have an extraordinary Ang II–producing activity by chymase in the BM.
Relating mechanical properties of vertebral trabecular bones to osteoporosis

Abstract Osteoporosis is an osteometabolic disease, which promotes structural degradation of bone tissue and reduction of mineral density. We reported here a mechanical resistance assay from normal, osteopenic and osteoporotic trabecular vertebral bones of human cadavers. We performed a compressed test on ninety samples, evaluating Young’s modulus and X-ray microtomography to measure bone volume fraction and trabecular thickness. This experimental data are employed for computing the orthotropic macroscopic behavior of vertebral trabecular bones using known analytical formulae that were obtained by Galka et al. (Arch Mech 51: 335-355, 1999) via an asymptotic homogenization model. A geometrical model with a periodic orthogonal plate-like structure is applied. The properties of the bone-trabecular mass are considered linear, homogeneous and orthotropic. Average values for all technical or engineering elastic properties are computed for three important regions of the trabecular bones corresponding to thirty individuals classified as normal, osteopenic or osteoporotic by calcaneus ultrassometry. This study could be useful for a better understanding of the elastic behavior of trabecular bones in human vertebral bodies, allowing an estimation of bone answer under stress in different directions and the risk of fracture associated with osteoporosis. Highlights Describing the elastic behavior of trabecular bones in human vertebral bodies at the micro and macroscopic. Allow a better estimation of the stress in different directions and risk of fracture associated with osteoporosis. Model request a very low computational cost. Offer a better understand the global effective coefficients of samples of trabecular bone, from the model of a periodic unit cell, in the format orthogonal plate-like structure with homogeneous bone mass.
Associations between maternal depressive symptoms and risk for offspring early-life psychopathology: the role of genetic and non-genetic mechanisms

Abstract Background Although maternal depressive symptoms are robustly associated with offspring early-life psychopathology symptoms, it is not clear which potential mechanisms are at play. We aimed to estimate the relative importance of genetic transmission and direct environmental exposure in these associations on three occasions in early childhood. Methods Biometric modeling of maternal sisters and their offspring from the Norwegian Mother and Child Cohort Study. The analyzed sample comprised 22 316 mothers and 35 589 offspring. Mothers reported their own depressive symptoms using the Symptom checklist, and offspring's concurrent symptoms of psychopathology using the Child Behavior Checklist at 1.5, 3, and 5 years postpartum. Results Associations between maternal symptoms of depression and offspring emotional problems were predominantly explained by passive genetic transmission at 1.5 and 3 years postpartum. At age 5, associations were more due to direct environmental exposure. For offspring behavioral problems, there was no net increase in the importance of direct environmental exposure across occasions. Conclusions Associations between maternal depressive symptoms and offspring psychopathology symptoms remained after accounting for shared genes, consistent with a small, causal effect. For offspring emotional problems, this effect appeared to increase in importance over time. Our findings imply that treatment of maternal depressive symptoms could also benefit the offspring, and that genetic confounding should be considered in future studies of such mother–offspring associations.
Follicular lymphoma: 2020 update on diagnosis and management

Follicular lymphoma (FL) is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma is characterized by diffuse lymphadenopathy, bone marrow involvement, and splenomegaly. Extranodal involvement is less common. Cytopenias are relatively common but constitutional symptoms of fever, night sweats, and weight loss are uncommon in the absence of transformation to diffuse large B cell lymphoma.
In vitro evaluation of Labrador dog spermatozoa cryopreserved in Tris-citric acid-fructose buffer supplemented with different combinations of extracellular and intracellular cryoprotectants

Abstract Aim of this study was to compare different combinations of penetrating intracellular CPAs, i.e., glycerol (G), ethylene glycol (EG), propylene glycol (PG), dimethyl formamide (DM), and methyl acetamide (MA) and extracellular [egg yolk (EY), egg yolk plasma (EYP), low-density lipoproteins (LDL), and coconut water (CW)] in Tris-citric acid-fructose buffer (T) for Labrador dog semen cryopreservation. The study was conducted in two parts, first trial was conducted to assess optimum glycerol concentration (5–7%) in TEY and equilibration time (ET, 2–4 hrs) for Labrador dog semen cryopreservation. Secondly, compatibility of 15% TEY, 15% TEYP, 13% TLDL, and 25% TCW with G, DMF, MA, D + M, EG, and PG was evaluated for in vitro sperm function tests. Decline in sperm attributes, i.e., motility, viability, plasma membrane integrity (PMI), and acrosome integrity (AI)) was significantly (p < 0.05) less in 7% TEY-G and 4 h compared to other concentrations and ET at post-thaw. There was significantly (p < 0.05) less decline in sperm attributes in TEY-G, TEYP-G, TLDL-G, TLDL-D, TLDL-EG, and TCW-D extenders compared to other combinations at post-thaw. However, these parameters were significantly (p < 0.05) high in TEY-G and TEYP-G compared to TEYP-D, TLDL-G, TLDL-D, TLDL-EG, and TCW-D extenders at post-thaw. However, decline in motility, viability, PMI, and AI was identical in these seven extenders. This study concluded that glycerol at a concentration of 7% in TEY and 4 h ET were optimum for successful cryopreservation and besides TEY-G, other combinations of protectants may be an alternative for canine semen cryopreservation.
Roles of RIN and ethylene in tomato fruit ripening and ripening‐associated traits

Summary RIPENING INHIBITOR (RIN)‐deficient fruits generated by CRISPR/Cas9 initiated partial ripening at a similar time to wild‐type (WT) fruits but only 10% WT concentrations of carotenoids and ethylene (ET) were synthesized. RIN‐deficient fruit never ripened completely, even when supplied with exogenous ET. The low amount of endogenous ET that they did produce was sufficient to enable ripening initiation and this could be suppressed by the ET perception inhibitor 1‐MCP. The reduced ET production by RIN‐deficient tomatoes was due to an inability to induce autocatalytic system‐2 ET synthesis, a characteristic feature of climacteric ripening. Production of volatiles and transcripts of key volatile biosynthetic genes also were greatly reduced in the absence of RIN. By contrast, the initial extent and rates of softening in the absence of RIN were similar to WT fruits, although detailed analysis showed that the expression of some cell wall‐modifying enzymes was delayed and others increased in the absence of RIN. These results support a model where RIN and ET, via ERFs, are required for full expression of ripening genes. Ethylene initiates ripening of mature green fruit, upregulates RIN expression and other changes, including system‐2 ET production. RIN, ET and other factors are required for completion of the full fruit‐ripening programme.
Stimuli‐Responsive Hydrogels with Antibacterial Activity Assembled from Guanosine, Aminoglycoside, and a Bifunctional Anchor

Multistimuli‐responsive hydrogels with specific functions have attracted great interest for biomedical applications; however, these smart hydrogels usually require the presynthesis of macromolecular building blocks with multiple ligands and the integration of bioactive cargoes into the gels. Here, a multistimuli‐responsive hydrogel with potent antibacterial activity by a combination of supramolecular assembly and iminoboronate chemistry is reported. The hydrogel consists of all‐small‐molecule building blocks including aminoglycoside, guanosine, potassium ion, and a bifunctional anchor bearing both boronic acid and aldehyde groups. Guanosines form quadruplexes in the presence of potassium ions via supramolecular assembly, and the bifunctional anchor connects aminoglycosides, a class of potent antibiotics to cis‐diol groups on quadruplexes via dynamic iminoboronate chemistry, yielding a smart hydrogel containing abundant antibiotics. The hydrogel is sensitive to multistimuli such as heat, acids, oxidants, glucose and crown ether, which promote the release of antibiotics from the gels. Moreover, the prepared hydrogels show potent antibacterial activities both in vitro and in vivo. The results provide a new option to prepare antibacterial hydrogels with multistimuli responsiveness via facile chemistry using all‐small‐molecule building blocks.
Influence of Host Plant Species and Fertilization Regime on Larval Performance and Feeding Preference of the Redbacked Cutworm and the Pale Western Cutworm (Lepidoptera: Noctuidae)

Abstract The redbacked cutworm, Euxoa ochrogaster (Guenée), and the pale western cutworm, Agrotis orthogonia (Morrison), are generalist pests that cause sporadic economic damage to several annual crops in the Canadian Prairies. Early larval instars feed on foliage, whereas mature larvae eat into the stem and sever crop seedlings. Here, we evaluate the influence of annual crop species and host fertilization on the larval performance and feeding preference of both cutworm species. Performance is the ability of an insect to reach its maximum growth potential. The first set of experiments evaluated larval development and preference on canola (Brassica napus L. [Capparales: Brassicaeae]), field peas (Pisum sativa L. [Fabales: Fabaceae]), and spring wheat (Triticum aestivum L. [Cyperales: Poaceae]). The redbacked cutworm had higher performance on canola and peas, while the pale western cutworm had higher performance on wheat. In multiple-choice feeding experiments, the redbacked cutworm consumed more canola, whereas the pale western cutworm consumed more spring wheat. The third set of experiments evaluated larval development on fertilized and unfertilized seedlings of canola and spring wheat seedlings. When fed unfertilized seedlings, the redbacked cutworm had better performance on canola than spring wheat, whereas pale western cutworm had better performance on spring wheat than canola. Fertilizer application enhanced the performance of both cutworms regardless of the crop species. Despite their generalist feeding behavior, both cutworm species have a larval feeding preference for the host plant on which they achieve high performance. Canola-cereal cropping is a common crop rotation schedule in the region; however, this tactic will not negatively impact cutworm performance.
High-resolution 3D tractography of fibrous tissue based on polarization-sensitive optical coherence tomography

Fibrous tissues play important roles in many parts of the body. Their highly organized directional structure is essential in achieving their normal biomechanical and physiological functions. Disruption of the typical fiber organization in these tissues is often linked to pathological changes and disease progression. Tractography is a specialized imaging method that can reveal the detailed fiber architecture. Here, we review recent developments in high-resolution optical tractography using Jones matrix polarization-sensitive optical coherence tomography. We also illustrate the use of this new tractography technology for visualizing depth-resolved, three-dimensional fibrous structures and quantifying tissue damages in several major fibrous tissues. Impact statement Organized fiber structure plays an essential role in realizing normal biological functions in fibrous tissues. A thorough understanding of the structure–function relationship in these tissues is crucial for developing effective technology to diagnose and treat diseases. Tractography imaging is an effective tool in visualizing and quantifying fiber architecture in fibrous tissues. This review describes a recently developed tractography technology that has shown great promise for fast image of 3D fiber organization with microscopic details.
Deep learning of pharmacogenomics resources: moving towards precision oncology

The recent accumulation of cancer genomic data provides an opportunity to understand how a tumor's genomic characteristics can affect its responses to drugs. This field, called pharmacogenomics, is a key area in the development of precision oncology. Deep learning (DL) methodology has emerged as a powerful technique to characterize and learn from rapidly accumulating pharmacogenomics data. We introduce the fundamentals and typical model architectures of DL. We review the use of DL in classification of cancers and cancer subtypes (diagnosis and treatment stratification of patients), prediction of drug response and drug synergy for individual tumors (treatment prioritization for a patient), drug repositioning and discovery and the study of mechanism/mode of action of treatments. For each topic, we summarize current genomics and pharmacogenomics data resources such as pan-cancer genomics data for cancer cell lines (CCLs) and tumors, and systematic pharmacologic screens of CCLs. By revisiting the published literature, including our in-house analyses, we demonstrate the unprecedented capability of DL enabled by rapid accumulation of data resources to decipher complex drug response patterns, thus potentially improving cancer medicine. Overall, this review provides an in-depth summary of state-of-the-art DL methods and up-to-date pharmacogenomics resources and future opportunities and challenges to realize the goal of precision oncology.
Meta‐analysis of clinical trials with competing time‐to‐event endpoints

Recommendations for the analysis of competing risks in the context of randomized clinical trials are well established. Meta‐analysis of individual patient data (IPD) is the gold standard for synthesizing evidence for clinical interpretation based on multiple studies. Surprisingly, no formal guidelines have been yet proposed to conduct an IPD meta‐analysis with competing risk endpoints. To fill this gap, this work details (i) how to handle the heterogeneity between trials via a stratified regression model for competing risks and (ii) that the usual metrics of inconsistency to assess heterogeneity can readily be employed. Our proposal is illustrated by the re‐analysis of a recently published meta‐analysis in nasopharyngeal carcinoma, aiming at quantifying the benefit of the addition of chemotherapy to radiotherapy on each competing endpoint.
Antihypertensive Medication Adherence and Confirmation of True Refractory Hypertension

Refractory hypertension (RfHTN) is a phenotype of antihypertensive treatment failure defined as uncontrolled BP despite the use of effective doses of ≥5 antihypertensive medications including a long-acting thiazide-like diuretic (chlorthalidone) and a mineralocorticoid receptor antagonist. The degree of medication nonadherence is unknown among patients with RfHTN. In this prospective evaluation, 54 patients with apparent RfHTN were recruited from the University of Alabama at Birmingham Hypertension Clinic after having uncontrolled BP at 3 or more clinic visits. All patients’ BP was evaluated by automated office BP and 24-hour ambulatory BP monitoring (n=49). Antihypertensive medication adherence was determined by measuring 24-hour urine specimens for antihypertensive medications and their metabolites by high-performance liquid chromatography-tandem mass spectrometry (n=45). Of the 45 patients who completed 24-hour ambulatory BP monitoring, 40 (88.9%) had confirmed RfHTN based on an elevated automated office BP (≥130/80 mm Hg), mean 24-hour ABP (≥125/75 mm Hg), and mean awake (day-time) ABP (≥130/80 mm Hg). Out of the 40 fully evaluated patients with RfHTN, 16 (40.0%) were fully adherent with all prescribed medications. Eighteen (45.0%) patients were partially adherent and 6 (15.0%) had none of the prescribed agents detected in their urine. Of 18 patients who were partially adherent, 5 (12.5%) were adherent with at least 5 medications, including chlorthalidone and the mineralocorticoid receptor antagonist, consistent with true RfHTN. Of patients identified as having apparent RfHTN, 52.5% were adherent with at least 5 antihypertensive medications, including chlorthalidone and a mineralocorticoid receptor antagonist, confirming true RfTHN. These findings validate RfHTN as a rare, but true phenotype of antihypertensive treatment failure.
Traffic Sign Recognition & Detection using Transfer learning

Traffic sign recognition feature is widely employed in industry today by researchers working in artificial intelligence and machine learning fields targeted to create an autonomous driving assistance system. This will help the driver’s human eye and manoeuvring capabilities which can’t be presumed to be consistent for high accuracy for all weather condition challenges. As the limitation of the human eye perception on a road sign is upsetting the road safety. This research paper illustrates a novel approach for Traffic image classification using Deep learning model to distinguish the different classes of traffic signs only after applying Data augmentation offered by Keras deep learning library for shifting traffic signs images (5%,10%,15%) and applying Gaussian blur technique for blurring (3:3,5:5 & 7:7) images. This will help us re-create a dataset similar to images captured during bad climatic, foggy or windy conditions seen in Ireland or badly captured images due to fast moving cars with limitation in camera angles from roads. We will be introducing these pictures on a pre-trained transfer learning model VGG19 as it has better accuracy and operational speed to create a best fit model. Results of this research work can be used by automobile companies to create enhanced image capturing cameras and classification models to make better autonomous systems and safer roads.