Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Evaluation and Genetic Landscape of Children and Young Adults Referred for Assessment of Bronchiectasis

Bronchiectasis is the abnormal dilation of the airway which may be caused by various etiologies in children. Beyond the more recognized cause of bacterial and viral infections and primary immunodeficiencies, other genetic conditions such as cystic fibrosis and primary ciliary dyskinesia (PCD) can also contribute to the disease. Currently, there is still debate on whether genome sequencing (GS) or exome sequencing reanalysis (rES) would be beneficial if the initial targeted testing results returned negative. This study aims to provide a back-to-back comparison between rES and GS to explore the best integrated approach for the functional and genetics evaluation for patients referred for assessment of bronchiectasis. In phase 1, an initial 60 patients were analyzed by exome sequencing (ES) with one additional individual recruited later as an affected sibling for ES. Functional evaluation of the nasal nitric oxide test, transmission electron microscopy, and high-speed video microscopy were also conducted when possible. In phase 2, GS was performed on 30 selected cases with trio samples available. To provide a back-to-back comparison, two teams of genome analysts were alternatively allocated to GS or rES and were blinded to each other’s analysis. The time for bioinformatics, analysis, and diagnostic utility was recorded for evaluation. ES revealed five positive diagnoses (5/60, 8.3%) in phase 1, and four additional diagnoses were made by rES and GS (4/30, 13%) during phase 2. Subsequently, one additional positive diagnosis was identified in a sibling by ES and an overall diagnostic yield of 10/61 (16.4%) was reached. Among those patients with a clinical suspicion of PCD (n = 31/61), the diagnostic yield was 26% (n = 8/31). While GS did not increase the diagnostic yield, we showed that a variant of uncertain significance could only be detected by GS due to improved coverage over ES and hence is a potential benefit for GS in the future. We show that genetic testing is an essential component for the diagnosis of early-onset bronchiectasis and is most effective when used in combination with functional tools such as TEM or HSVM. Our comparison of rES vs. GS suggests that rES and GS are comparable in clinical diagnosis.
Survival outcomes analysis according to mismatch repair status in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy

Background The predictive role of mismatch repair (MMR) status for survival outcomes and sensitivity in neoadjuvant chemoradiotherapy settings for patients with locally advanced rectal cancer (LARC) has been inconclusive. Methods A retrospective cohort of patients with LARC treated with neoadjuvant chemoradiotherapy (nCRT) was recruited. After adjusting for baseline characteristics, we used propensity score matching to reduce the effect of potential confounding factors on MMR status. The primary analysis was based on overall survival as the more important endpoint. Results This study included 269 patients. Patients with defective MMR (dMMR) were younger (58.5% vs. 60.0%, p=0.0274) and had lower body mass indices (p=0.0091), higher differentiation grades (p=0.0889), and more advanced rectal cancers (clinical T4 or T4b, p=0.0851; M1, p=0.0055) than those with proficient MMR (pMMR). However, propensity score-matched patients with dMMR (p=0.0013) exhibited superior overall survival, even in the M1 subgroup. More importantly, patients with proficient MMR who undergo early pathological downstaging, especially lymph node pathological downstaging, can achieve a prognosis similar to that of patients with dMMR. Conclusion The clinical significance of this retrospective study mainly includes two points: (1) Data from our study confirmed that LARC patients with dMMR status had better overall survival rates after nCRT, even in the M1 subgroup. (2) Similar survival outcomes were observed in older and female patients with early lymph node pathological downstaging, regardless of dMMR or pMMR.
Application progress of plant-mediated RNAi in pest control

RNA interference (RNAi)-based biopesticides are novel biologic products, developed using RNAi principles. They are engineered to target genes of agricultural diseases, insects, and weeds, interfering with their target gene expression so as to hinder their growth and alleviate their damaging effects on crops. RNAi-based biopesticides are broadly classified into resistant plant-based plant-incorporated protectants (PIPs) and non-plant-incorporated protectants. PIP RNAi-based biopesticides are novel biopesticides that combine the advantages of RNAi and resistant transgenic crops. Such RNAi-based biopesticides are developed through nuclear or plastid transformation to breed resistant plants, i.e., dsRNA-expressing transgenic plants. The dsRNA of target genes is expressed in the plant cell, with pest and disease control being achieved through plant-target organism interactions. Here, we review the action mechanism and strategies of RNAi for pest management, the development of RNAi-based transgenic plant, and the current status and advantages of deploying these products for pest control, as well as the future research directions and problems in production and commercialization. Overall, this study aims to elucidate the current development status of RNAi-based biopesticides and provide guidelines for future research.
The quantum leap in therapeutics for advanced ALK+ non-small cell lung cancer and pursuit to cure with precision medicine

Since the discovery 15 years ago, we have seen a quantum leap in the treatment and survival for individuals diagnosed with ALK+ lung cancers. Unfortunately however, for most, the diagnosis is made in an incurable circumstance given the late presentation of symptoms. Through a revolutionary wave of therapeutics, individuals may remarkably live over a decade, however many fall short of this milestone, as the molecular profile of this disease is very heterogeneous, reflected in variable survival outcomes. Despite a significant improval in survival and quality of life with ALK-inhibitor monotherapies, now available across multiple-generations, drug resistance and disease relapse remains inevitable, and treatment is offered in an empiric, stepwise, non personalised biomarker informed fashion. A proposed future focus to treating ALK to improve the chronicity of this disease and even promote cure, is to deliver a personalised dynamic approach to care, with rational combinations of drugs in conjunction with local ablative therapies to prevent and constantly proactively alter clonal selection. Such an approach would be informed by precision imaging with MRI-brain and FDG-PETs sequentially, and by regular plasma sampling including for circulating tumour DNA sequencing with personalised therapeutic switches occurring prior to the emergence of radiological and clinical relapse. Such an approach to care will require a complete paradigm shift in the way we approach the treatment of advanced cancer, however evidence to date in ALK+ lung cancers, support this new frontier of investigation.
The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease

Foxa2, a member of the Forkhead box (Fox) family of transcription factors, plays an important role in the regulation of lung function and lung tissue homeostasis. FOXA2 expression is reduced in the lung and airways epithelium of asthmatic patients and in mice absence of Foxa2 from the lung epithelium contributes to airway inflammation and goblet cell hyperplasia. Here we demonstrate a novel role for Foxa2 in the regulation of T helper differentiation and investigate its impact on lung inflammation. Conditional deletion of Foxa2 from T-cells led to increased Th2 cytokine secretion and differentiation, but decreased Th1 differentiation and IFN-γ expression in vitro. Induction of mouse allergic airway inflammation resulted in more severe disease in the conditional Foxa2 knockout than in control mice, with increased cellular infiltration to the lung, characterized by the recruitment of eosinophils and basophils, increased mucus production and increased production of Th2 cytokines and serum IgE. Thus, these experiments suggest that Foxa2 expression in T-cells is required to protect against the Th2 inflammatory response in allergic airway inflammation and that Foxa2 is important in T-cells to maintain the balance of effector cell differentiation and function in the lung.
Galectin-3 inhibitor GB0139 protects against acute lung injury by inhibiting neutrophil recruitment and activation

Rationale: Galectin-3 (Gal-3) drives fibrosis during chronic lung injury, however, its role in acute lung injury (ALI) remains unknown. Effective pharmacological therapies available for ALI are limited; identifying novel concepts in treatment is essential. GB0139 is a Gal-3 inhibitor currently under clinical investigation for the treatment of idiopathic pulmonary fibrosis. We investigate the role of Gal-3 in ALI and evaluate whether its inhibition with GB0139 offers a protective role. The effect of GB0139 on ALI was explored in vivo and in vitro. Methods: The pharmacokinetic profile of intra-tracheal (i.t.) GB0139 was investigated in C57BL/6 mice to support the daily dosing regimen. GB0139 (1–30 µg) was then assessed following acute i.t. lipopolysaccharide (LPS) and bleomycin administration. Histology, broncho-alveolar lavage fluid (BALf) analysis, and flow cytometric analysis of lung digests and BALf were performed. The impact of GB0139 on cell activation and apoptosis was determined in vitro using neutrophils and THP-1, A549 and Jurkat E6 cell lines. Results: GB0139 decreased inflammation severity via a reduction in neutrophil and macrophage recruitment and neutrophil activation. GB0139 reduced LPS-mediated increases in interleukin (IL)-6, tumor necrosis factor alpha (TNFα) and macrophage inflammatory protein-1-alpha. In vitro, GB0139 inhibited Gal-3-induced neutrophil activation, monocyte IL-8 secretion, T cell apoptosis and the upregulation of pro-inflammatory genes encoding for IL-8, TNFα, IL-6 in alveolar epithelial cells in response to mechanical stretch. Conclusion: These data indicate that Gal-3 adopts a pro-inflammatory role following the early stages of lung injury and supports the development of GB0139, as a potential treatment approach in ALI.
Hydrogen-induced metallicity of SrTiO3 (001) surfaces : A density functional theory study

The effect of atomic hydrogen adsorption on ${\text{TiO}}_{2}$-terminated and SrO-terminated ${\text{SrTiO}}_{3}$ (001) surfaces is studied using density functional theory calculations. Several adsorption coverages (1/12, 1/6, 1/3, 1/2, 2/3, and 1 monolayer) are considered. It is found that the hydrogen adsorption shows site selectivity and causes remarkable surface distortion. Surface metallicity induced by the hydrogen adsorption is observed and revealed to be caused by the electron donation from hydrogen to the surface. Our results suggest a mechanism of hydrogen-induced degradation and hydrogen-sensitive $I\text{\ensuremath{-}}V$ characteristics of ${\text{SrTiO}}_{3}$-based devices.
Optimization of the thermoelectric properties of Ba8Ga16Ge30

Polycrystalline Ba8Ga16Ge30 clathrates with a systematic variation in the Ga:Ge stoichiometry were prepared to investigate the thermoelectric properties as a function of carrier concentration. Their corresponding transport properties were evaluated to identify the optimal carrier concentration for high temperature thermoelectric performance. These polycrystalline specimens demonstrate thermoelectric properties comparable to those obtained in single-crystal Ba8Ga16Ge30, confirming that polycrystalline clathrates can be optimized for high temperature thermoelectric applications.
Contributions from weak-interaction channels to inclusive hadron spectra at TeV energies

At the FERMILAB TEVATRON and CERN LHC accelerators partonic processes reach such a high energy region, where the weak interactions could enter into consideration in the hadron yields through the opening of resonant W and Z exchange diagrams. We investigate these contributions to inclusive charged hadron production in p+p and p+{\bar p} reactions at a few TeV energies, and compare our results to existing CDF and CMS data. We perform a leading order perturbative QCD calculation and include electroweak channels to estimate the order of magnitude of charged hadron excess. The energy dependence of hadron production and the fine structure of transverse momentum distributions are investigated. As expected, in p+ {\bar p} collisions electroweak channels yield much larger contribution, than in p+p collisions. However, these types of contributions remains close to be negligible at the available accelerator energies.
Revolver Hollow Core Optical Fibers

Revolver optical fibers (RF) are special type of hollow-core optical fibers with negative curvature of the core-cladding boundary and with cladding that is formed by a one ring layer of capillaries. The physical mechanisms contributing to the waveguiding parameters of RFs are discussed. The optical properties and possible applications of RFs are reviewed. Special attention is paid to the mid-IR hydrogen Raman lasers that are based on RFs and generating in the wavelength region from 2.9 to 4.4 μm.
Special configurations of robot-arms via screw theory

SUMMARY The Jacobian of serial robot-arms is examined, and the matrix of cofactors of a singular Jacobian is presented as a means of explaining the physical nature of special configurations. Because the columns of both these matrices are screw coordinates, screw theory is central to proper understanding. ‘Realistic’ robot-arms are seen to behave in ways that can be explained not by particularizing from a general formulation but rather by carefully interpreting the relevant special screw systems from the outset. Higher singularities (with more than one freedom-loss) are then touched upon.
Exploring the Influence of Executive Management Diversity on IT Governance

As all organizations are attaching more strategic importance to information technology (IT), IT governance has gained researchers’ interest. In fact, a large body of literature focuses on firm-specific or executive management attributes such as leadership as determinants of IT governance. However, it is still relevant to identify other factors influencing IT governance. Since executive management demographics and demographic diversity have an impact on strategic decisions, we explore the influence of executive management diversity on IT governance. Results suggest that IT governance for a high educational-high tenure diversity profile differs significantly from that for a low industry-moderate tenure diversity profile and a high industry-low tenure diversity profile. Furthermore, IT governance structures differ according to executive management diversity profile more than IT governance processes and relational mechanisms.
High energy and high voltage integrated photo-electrochemical double layer capacitor

A novel, monolithic harvesting–storage (HS) device composed of a dye-sensitized solar cell (DSSC)-based module and a high voltage supercapacitor with impressive discharge capacity after photocharging is herein proposed. Both the harvesting and the storage sections are fabricated onto conductive glass substrates, paving the way to a smart and easy integration in window facades for energy self-sustainable buildings. In addition, the HS device can also be integrated in portable electronics or drive remote, off-grid sensor networks requiring high power intermittent electrical energy. The harvesting photovoltaic section is constituted by a series of four DSSCs integrated in a single W-type module while the storage section consists of an activated carbon-based supercapacitor (SC) utilizing Pyr14TFSI ionic liquid as the electrolyte. The testing of the two separated sections as well as of the integrated system is reported here. In particular, the integration is evaluated through photo-charge and subsequent discharge protocols performed at different galvanostatic currents, showing that the SC handles photo-charges up to 2.45 V while delivering discharge capacities exceeding 1.8 mA h (0.1 mA h cm−2) upon 1 mA discharge current. To the best of our knowledge this is a never reported before, absolute record value, for stable and reliable integrated HS devices.
Synthesis and characterization of a polymeric magnetic hybrid material composed of iron oxide nanoparticles and polyvinyl butyral Síntesis y caracterización de un material polimérico híbrido magnético de nanopartículas de óxido de hierro en una matriz de polivinil butiral

A Polymeric Magnetic Hybrid Material (PMHM), consisting of iron-oxide nanoparticles synthesized in-situ in a Polymer Matrix of Polyvinyl Butyral (PVB), was developed in two stages. First, a precursor film hybrid material (Fe(II)-PVB) was obtained. In the second stage, Fe(II)-PVB was treated with H2O2 under alkaline conditions to obtain the PMHM. Characterization by XRD shows that the crystalline structure of iron oxide into PMHM corresponds to goethite, and to maghemite or magnetite phases. FTIR-spectroscopy reveal that the PVB-matrix preserves its chemical structure into the PMHM. HRTEM-images show that iron oxide nanoparticles (~5 nm) with sphere-like morphology are embedded into PVB-matrix; and diagrams of magnetization versus temperature, show that embedded nanoparticles have a superparamagnetic-like behavior. Finally, magnetorheological results show that mechanical properties of PMHM can be modified under the application of an external magnetic field, showing that it is a good alternative to carry out functions as actuator or sensor in electronic or mechatronic devices.
Decision making with the analytical hierarchy process (AHP) for materials and design selection in the POPE lawn mower manufacturing for minimizing environmental impacts

The POPE lawn mower has become one of the most important household machines. This is because many people are using lawn mowers every day to cut the grass in their home gardens, public parks or street verges to maintain a beautiful environment. However, this product has some negative impacts on the environment such as gases emissions and creation of solid or liquid waste. In addition, this product has some issues such as corrosion on the materials of some parts, and an inefficient and short life span. The impacts on the environment associated with POPE lawn mowers are a result of the materials and design used in the manufacturing process. Furthermore, the purpose of this chapter is to describe and analyses the POPE lawn mower components and propose how it can be improved by selection of new materials and designs used during the manufacturing process. The findings of this chapter project will propose some solutions to these issues by using the Analytic Hierarchy Process (AHP) to make decision which allows for a selection of new materials and designs for manufacturing the POPE lawn mower with less environmental impacts and greater efficiency. Finally, this research recommends that companies manufacturing the POPE lawn mower could improve the lawn mower by selecting new designs, materials and making changes to the energy consumption to make this product more efficient with less environmental impacts.
Taste Receptor Activation in Tracheal Brush Cells by Denatonium Modulates ENaC Channels via Ca2+, cAMP and ACh

Mucociliary clearance is a primary defence mechanism of the airways consisting of two components, ciliary beating and transepithelial ion transport (ISC). Specialised chemosensory cholinergic epithelial cells, named brush cells (BC), are involved in regulating various physiological and immunological processes. However, it remains unclear if BC influence ISC. In murine tracheae, denatonium, a taste receptor agonist, reduced basal ISC in a concentration-dependent manner (EC50 397 µM). The inhibition of bitter taste signalling components with gallein (Gβγ subunits), U73122 (phospholipase C), 2-APB (IP3-receptors) or with TPPO (Trpm5, transient receptor potential-melastatin 5 channel) reduced the denatonium effect. Supportively, the ISC was also diminished in Trpm5−/− mice. Mecamylamine (nicotinic acetylcholine receptor, nAChR, inhibitor) and amiloride (epithelial sodium channel, ENaC, antagonist) decreased the denatonium effect. Additionally, the inhibition of Gα subunits (pertussis toxin) reduced the denatonium effect, while an inhibition of phosphodiesterase (IBMX) increased and of adenylate cyclase (forskolin) reversed the denatonium effect. The cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh172 and the KCNQ1 potassium channel antagonist chromanol 293B both reduced the denatonium effect. Thus, denatonium reduces ISC via the canonical bitter taste signalling cascade leading to the Trpm5-dependent nAChR-mediated inhibition of ENaC as well as Gα signalling leading to a reduction in cAMP-dependent ISC. Therefore, BC activation contributes to the regulation of fluid homeostasis.
CONSEQUENCES OF SELECTION FOR POST-WEANING GROWTH ‎PERFORMANCE ON CARCASS AND TISSUE WEIGHT ‎DISTRIBUTION TRAITS IN RABBITS

-----------------------------------------------------------------------------------------------ABSTRACT This study aimed to investigate the consequences of selection for post-weaning growth performance on carcass and tissue weight distribution traits using selection indices in rabbits through the multi-trait animal model. The experimental material involved 218 New Zealand White (NZW) rabbits, the progeny of 24 bucks and 93 adult does. The aggregate genotype of weaning weight (WW), slaughter weight (SW), and average daily gain (DG) from weaning to slaughter were included. The same three traits were used with different combinations as a source of information. FLB and by -0.12 in TCB% and increase by 0.11 to 0.15% in LOB with fluctuated change in HLB by -0.09 to 0.07%). As compared with their unrestricted forms, the restricted indices I 8(HLM) and I 9(HLM) would entail an only a slight reduction in accuracy of selection (r TI = 0.76 and 0.72, respectively) with acceptable improvement in WW (+104.7 and 108.2gm, respectively) and SW (+119.8 and 108.1gm, respectively) with an unfavorable increase in HLB by 0.37 and 0.07%, respectively. Conclusively , Use of weaning weight (WW) and slaughter weight (SW) as sources of information (I 2 ) in the following index: (r TI = 0.83) would be recommended to maximize the post-weaning growth traits regardless of the deterioration in carcass tissue weight distribution. However, the following restricted index: would be a preferred choice to the breeder, taking into consideration the expected deterioration in carcass tissue weight distribution, for biological and rabbit meat consumer desires reasons.