Miracle-dz/UniFAR-FTUs huggingface dataset:
Surgical Antimicrobial Prophylaxis in Patients of Neonatal and Pediatric Age Subjected to Eye Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Ocular surgery encompasses a wide range of procedures, including surgery of the tear ducts, eyelid, cornea and conjunctiva, lens, ocular muscle, and vitreoretinal and iris surgery. Operations are also performed for the removal of tumors, repairs of ocular trauma and, finally, corneal transplantation. Antibiotic prophylaxis for the prevention of surgical site infections (SSIs) in ocular surgery is a complex field in which shared lines of action are absent. In light of the scarcity of shared evidence in the use of ocular antimicrobial prophylaxis for the pediatric population, this consensus document aims to provide clinicians with a series of recommendations on antimicrobial prophylaxis for patients of neonatal and pediatric age undergoing eye surgery. The following scenarios are considered: (1) intraocular surgery; (2) extraocular surgery; (3) ocular trauma; (4) ocular neoplasm; (5) ocular surface transplantations; (6) corneal grafts. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding clinical actions in the peri-operative environment in eye surgery. The application of uniform and shared protocols aims to improve surgical practice, through the standardization of procedures, with a consequent reduction of SSIs, also limiting the phenomenon of antimicrobial resistance.
The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature

Quercetin is a phenolic flavonol compound with established antioxidant, anti-inflammatory, and immuno-stimulant properties. Recent studies demonstrate the potential of quercetin against COVID-19. This article highlighted the prophylactic/therapeutic potential of quercetin against COVID-19 in view of its clinical studies, inventions, and patents. The literature for the subject matter was collected utilizing different databases, including PubMed, Sci-Finder, Espacenet, Patentscope, and USPTO. Clinical studies expose the potential of quercetin monotherapy, and also its combination therapy with other compounds, including zinc, vitamin C, curcumin, vitamin D3, masitinib, hydroxychloroquine, azithromycin, and ivermectin. The patent literature also examines claims that quercetin containing nutraceuticals, pharmaceuticals, and dietary supplements, alone or in combination with other drugs/compounds, including favipiravir, remdesivir, molnupiravir, navitoclax, dasatinib, disulfiram, rucaparib, tamarixin, iota-carrageenan, and various herbal extracts (aloe, poria, rosemary, and sphagnum) has potential for use against COVID-19. The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). The USFDA designated quercetin as a “Generally Recognized as Safe” substance for use in the food and beverage industries. It is also an inexpensive and readily available compound. These facts increase the possibility and foreseeability of making novel and economical drug combinations containing quercetin to prevent/treat COVID-19. Quercetin is an acidic compound and shows metabolic interaction with some antivirals, antibiotics, and anti-inflammatory agents. Therefore, the physicochemical and metabolic drug interactions between quercetin and the combined drugs/compounds must be better understood before developing new compositions.
BCTT_A_219436 251..258

Department of Breast Oncology, Moffitt McKinley Outpatient Center, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA Abstract: Hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2 negative) breast cancer accounts for over 70% of all breast cancers. There has been much advancement in the treatment of HR+/HER2 negative metastatic breast cancer (MBC), in particular the development of more tailored and targeted therapies. Recently, greater understanding of the role of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway in breast cancer has led to the development of PI3K inhibitors, which have proven to be effective in the treatment of HR+/HER2 negative MBC. In this review, we will discuss the role of the PI3K/AKT/mTOR pathway in breast cancer and therapies that have been developed to inhibit PI3K. We will discuss in detail the development of PI3K inhibitor alpelisib, indications for use in HR+/HER2 negative MBC, safety and tolerability and the future direction of this therapy in the treatment of breast cancer.
Holism and Reductionism in the Illness/Disease Debate

In the last decades it has become clear that medicine must find some way to combine its scientific and humanistic sides. In other words, an adequate notion of medicine requires an integrative position that mediates between the analytic-reductionist and the normative-holistic tendencies we find therein. This is especially important as these different styles of reasoning separate “illness” (something perceived and managed by the whole individual in concert with their environment) and “disease” (a “mechanical failure” of a biological element within the body). While the demand for an integrative view has typically been motivated by ethical concerns, we claim that it is also motivated, perhaps even more fundamentally, by epistemological and methodological reasons. Evidence-based bio-medicine employs experimental and statistical techniques which eliminate important differences in the ways that conscious humans evaluate, live with, and react to disease and illness. However, it is precisely these experiences that underpin the concepts and norms of bio-medicine. Humanistic disciplines, on the other hand, have the resources to investigate these experiences in an intersubjectively testable way. Medicine, therefore, cannot afford to ignore its nature as a human science; it must be concerned not only with disease and illness, but also with the ways in which patients as persons respond to malady. Insofar as attitudes and expectations influence the criteria of illness and disease, they must be studied as part of the genuine subject matter of medicine as a human science. In general, we urge that this is a necessary step to overcome today's trend to split evidence-based and clinical medicine.
Improving Heterogeneous Forest Height Maps by Integrating GEDI-Based Forest Height Information in a Multi-Sensor Mapping Process

Forests are one of the key elements in ecological transition policies in Europe. Sustainable forest management is needed in order to optimise wood harvesting, while preserving carbon storage, biodiversity and other ecological functions. Forest managers and public bodies need improved and cost-effective forest monitoring tools. Research studies have been carried out to assess the use of optical and radar images for producing forest height or biomass maps. The main limitations are the quantity, quality and representativeness of the reference data for model training. The Global Ecosystem Dynamics Investigation (GEDI) mission (full waveform LiDAR on board the International Space Station) has provided an unprecedented number of forest canopy height samples from 2019. These samples could be used to improve reference datasets. This paper aims to present and validate a method for estimating forest dominant height from open access optical and radar satellite images (Sentinel-1, Sentinel-2 and ALOS-2 PALSAR-2), and then to assess the use of GEDI samples to replace field height measurements in model calibration. Our approach combines satellite image features and dominant height measurements, or GEDI metrics, in a Support Vector Machine regression algorithm, with a feature selection process. The method is tested on mixed uneven-aged broadleaved and coniferous forests in France. Using dominant height measurements for model training, the cross-validation shows 7.3 to 11.6% relative Root Mean Square Error (RMSE) depending on the forest class. When using GEDI height metrics instead of field measurements for model training, errors increase to 12.8–16.7% relative RMSE. This level of error remains satisfactory; the use of GEDI could allow the production of dominant height maps on large areas with better sample representativeness. Future work will focus on confirming these results on new study sites, improving the filtering and processing of GEDI data, and producing height maps at regional or national scale. The resulting maps will help forest managers and public bodies to optimise forest resource inventories, as well as allow scientists to integrate these cartographic data into climate models.
Optimisation of Airline Dynamic Multileg Capacity Control Problem considering Competition from High-Speed Rail

This paper develops an optimisation model to address the dynamic multileg capacity control problem for the airline, taking into account the competition from the high-speed rail (HSR). Conventional capacity control models assume that the passenger demand is independent and that airlines control capacity independently. The proposed model considers the semi-independent demand, i.e., a customer of certain fare class arrives and makes choices from available alternatives provided by both airline and HSR. If the customer’s ﬁrst option is rejected, their booking request will be diverted both horizontally to the other operator and vertically to parallel ﬂights within the same operator. Making use of this assumption, the customer’s second and third choices are captured. With this model, airlines can control the sales process to determine whether or not to accept an initial booking request or diverted booking request to maximise their revenue. The deterministic linear programming (DLP) method is proposed as a model solution, enabling the computation of partitioned allocation and the bid price of each product. The optimal capacity control strategy is then obtained based on bid price control. To validate the model, numerical experiments are conducted to simulate customers’ actual arrival and to show that the model is capable of producing better revenue, especially in the event that demand exceeds supply. Moreover, the demand diversion eﬀect brings more revenue for both airline and HSR, and this potential revenue source has been ignored by previous research studies.
Complex systems models of financial and systemic risk

The primary purpose of this thesis is to develop mathematical models and tools that aid the understanding of financial systemic risk, by analysing and applying techniques from complexity science. Large systemic risks that arise in financial asset markets have proved that they can emerge virtually without warning, and create large financial and social costs. I argue that herd behaviour in asset markets is a source of such systemic risk. In this thesis, I present a new mathematical model of cascades on a stochastic pulse-coupled network, in the presence of binary opposing influences, and analyse it as both a mean field dynamical system, and probabilistically. I demonstrate that a critical coupling parameter exists separating a quiescent regime, from a volatile synchronous regime consisting of large cascades. Second, as an application to systemic risk, I develop a new model of a stylised financial market, using only minimal assumptions, and demonstrate how this replicates important empirical features of financial asset returns, such as long-memory volatility patterns, without recourse to strategy switching or stochastic volatility. Numerical evidence is presented that suggests this minimal market model self-organises to a critical regime, assuming only mild plausible optimising behaviour on the part of the agent. Lastly, I consider some implications for policy scenarios in light of my findings.
Detection of Cellular Senescence in Human Primary Melanocytes and Malignant Melanoma Cells In Vitro

Detection and quantification of senescent cells remain difficult due to variable phenotypes and the absence of highly specific and reliable biomarkers. It is therefore widely accepted to use a combination of multiple markers and cellular characteristics to define senescent cells in vitro. The exact choice of these markers is a subject of ongoing discussion and usually depends on objective reasons such as cell type and treatment conditions, as well as subjective considerations including feasibility and personal experience. This study aims to provide a comprehensive comparison of biomarkers and cellular characteristics used to detect senescence in melanocytic systems. Each marker was assessed in primary human melanocytes that overexpress mutant BRAFV600E, as it is commonly found in melanocytic nevi, and melanoma cells after treatment with the chemotherapeutic agent etoposide. The combined use of these two experimental settings is thought to allow profound conclusions on the choice of senescence biomarkers when working with melanocytic systems. Further, this study supports the development of standardized senescence detection and quantification by providing a comparative analysis that might also be helpful for other cell types and experimental conditions.
α-Linolenic Acid Suppresses Proliferation and Invasion in Osteosarcoma Cells via Inhibiting Fatty Acid Synthase

Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic acid is an omega-3 essential fatty acid and it possesses various biological activities. The present study was designed to reveal the effects of α-linolenic acid on osteosarcoma and to reveal whether the mechanism of α-linolenic acid in anticancer activity may be related to FASN inhibition. The cytotoxicity of α-linolenic acid was assessed in osteosarcoma MG63, 143B, and U2OS cells. Cell viability was detected by the MTT assay. The protein expression level was detected by western blotting. Flow cytometry, Annexin V/propidium iodide dual staining, and Hoechst 33258 staining were performed to assess the apoptotic effects. Wound healing assay was applied to detect the inhibitory effect of α-linolenic acid on osteosarcoma cells migration. The results showed that α-linolenic acid downregulated FASN expression. α-Linolenic acid inhibited osteosarcoma cell proliferation and migration in a dose-dependent manner. In addition, α-linolenic acid regulated endoplasmic reticulum transmembrane receptors and signal protein expression in osteosarcoma cells. The findings of the present study suggested that α-linolenic acid suppresses osteosarcoma cell proliferation and metastasis by inhibiting FASN expression, which provides a basis as a potential target for osteosarcoma treatment.
Path Attenuation and Source Characteristics during the 2019 Sichuan Changning Earthquake Sequence in China

To give an insight into the path attenuation and source characteristics of the 2019 Sichuan Changning earthquake sequence, 99 strong-motion recordings at 33 stations were studied. The S-wave Fourier amplitude spectra were used to determine the path-attenuation function and key parameters of the seismic source characteristics of this sequence. The results show the following: (1) The geometric spreading effect presents hinged-trilinear characteristics, and the corresponding geometric spreading rates were −0.97, 0.29, and −0.73 with the crossover distances 90 km and 183 km. (2) The quality factor Q is correlated with frequency and expressed as 217 × f0.82 for the range from 0.1 to 10.0 Hz. (3) The seismic moment was inversely proportional to the cube of the corner frequency, and their product was 2.37 × 1016 N. m/s3. (4) The stress drop varied from 1.18 to 12.44 MPa. Both the attenuation effect and source parameters of this sequence are significantly different from those of the Lushan and the Wenchuan aftershock sequences in the Sichuan region of China.
Effect of Agricultural Crop Wastes as Partial Replacement of Cement in Concrete Production

The main goal of this review paper was to study the physical and chemical properties of agricultural crop wastes and their potentials to partially replace in production of mortar and concrete. Bamboo leaves’ ashes (BLA), banana leaves’ ashes (BNLA), corncob leaves’ ashes (CCA), groundnut ashes (GNA), rice husk ashes (RHA), and sugarcane bagasse ashes (SCBA) were selected to be reviewed. The chemical composition of these agricultural wastes revealed that the they are basically composed of alumino-siliceous materials conforming the requirement of pozzolanic materials. Compared with cement, they have finer particle size and higher surface area. The effect of partial replacement of cement by BLA, BNLA, CCA, GNA, RHA, and SCBA on the properties of fresh concrete (consistency, workability, and setting time), mechanical properties (compressive and tensile strength), microstructure (scanning electron microscopy, derivative thermogravimetry, and X-ray diffraction), and durability (ultrapulse velocity, water absorption, and sulphate attack) of concrete was recapped. The inclusion of BLA, CCA, RHA, and SCBA as partial replacement of cement reduced the workability of concrete due to their finer particle size. The mechanical performance of concrete showed enhancement with partial replacement of cement by BLA, RHA, and SCBA due to the involvement of amorphous silica in secondary reaction to produce densified tetrahedral gel. Consequently, uniform and denser morphology was formed, and durability was enhanced as densification of hydrated gel increased. In general, the review exposed that agricultural crop wastes satisfy pozzolanic material properties and have strong potential to replace cement up to 10% without compromising the performance of concrete.
Administration of Hookworm Excretory/Secretory Proteins Improves Glucose Tolerance in a Mouse Model of Type 2 Diabetes

Diabetes is recognised as the world’s fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insulin resistance, we treated mice fed on normal or diabetes-promoting diets with excretory/secretory products (ES) from the gastrointestinal helminth Nippostrongylus brasiliensis. We demonstrated that treatment with crude ES products from adult worms (AES) or infective third-stage larvae (L3ES) from N. brasiliensis improved glucose tolerance and attenuated body weight gain in mice fed on a high glycaemic index diet. N. brasiliensis ES administration to mice was associated with a type 2 immune response measured by increased eosinophils and IL-5 in peripheral tissues but not IL-4, and with a decrease in the level of IL-6 in adipose tissue and corresponding increase in IL-6 levels in the liver. Moreover, treatment with AES or L3ES was associated with significant changes in the community composition of the gut microbiota at the phylum and order levels. These data highlight a role for N. brasiliensis ES in modulating the immune response associated with T2D, and suggest that N. brasiliensis ES contain molecules with therapeutic potential for treating metabolic syndrome and T2D.
Responding Autoreactive T Cells Cell Stimulation Followed by Inactivation of Self-Immunoglobulin Causes Polyclonal B Disruption of T Cell Tolerance to

Scavenger receptor (SR)-speciﬁc delivery by maleylation of a ubiquitous self-protein, Ig, to SR-bearing APCs results in self-limiting induction of autoimmune effects in vivo. Immunization with maleyl-Ig breaks T cell tolerance to self-Ig and causes hypergammaglobulinemia, with increases in spleen weight and cellularity. The majority of splenic B cells show an activated phenotype upon maleyl-Ig immunization, leading to large-scale conversion to a CD138 1 phenotype and to signiﬁcant increases in CD138-expressing splenic plasma cells. The polyclonal B cell activation, hypergammaglobulinemia, and autoreactive Ig-speciﬁc T cell responses decline over a 2-mo period postimmunization. Following adoptive transfer, T cells from maleyl-Ig-immune mice taken at 2 wk postimmunization can induce hypergammaglobulinemia in the recipients, but those taken at 10 wk postimmunization cannot. Hypergammaglobulinemia in the adoptive transfer recipients is also transient and is followed by an inability to respond to fresh maleyl-Ig immunization, suggesting that the autoreactive Ig-speciﬁc T cells are inactivated peripherally following disruption of tolerance. Thus, although autoreactive T cell responses to a ubiquitous self-Ag, Ig, are induced by SR-mediated delivery to professional APCs in vivo resulting in autoimmune pathophysiological effects, they are effectively and rapidly turned off by inactivation of these activated Ig-speciﬁc T cells in vivo. The Journal of Immunology, 2000, 164: 1713–1721.
Prediction des Conditions Sonores dans les Salles de Classe au Moyen des Carateristiques Physiques de l'environnement

A field study has been conducted in 50 classrooms from 6 primary schools in Montreal in order to identify physical characteristics that would predict speech intelligibility in classrooms. An empirical model founded on the evaluation of the signal-to-noise ratio in dBA and of the reverberation time at 1000 Hz has been used. Three variables have been identified as predictors of an optimal speech intelligibility in classrooms, namely the absence of ventilation noise, the enclosure of the rooms by complete partitions and the presence of acoustic tiles on the ceiling.
NANOMECHANICAL TESTING OF ICCGHAZ OF ARCTIC STEEL

An ever increasing demand for energy is forcing the oil industry to push technology forward, as new oil rich fields are discovered further North. The Arctic offers a harsh, cold climate, leading to new challenges within the field of materials technology. Offshore and onshore Arctic production demand strong, and tough materials, able to withstand temperatures down to −60 ◦C, in addition to extreme weather. As the temperature drops the risk for brittle material failure will increase. Understanding material deformation and governing mechanisms under such conditions can prevent material failure, while maintaining cost-efficiency. Application of nanomechanical testing methods has become increasingly important within materials research. Understanding material properties at the microand nano-level, has attracted significant interest. Most small-scale experiments have been conducted at room temperature, as this requires a less complex set-up. However, testing of Arctic steels requires low temperature smallscale experiments to obtain material performance in its field of operation. The scope of this thesis was to modify existing cryogenic experimental equipment. Characterization of regions in a weld simulated zone of a steel developed for use under Arctic conditions, was to be conducted. Additionally, establishing nanomechanical properties was desired. The approach was to machine micro-sized cantilevers and pillars, using a focused ion beam. The specimens were loaded, and compressed, at room temperature, and at approximately −80 ◦C. The in-house made and modified cryogenic set-up enabled highly accurate low temperature nanomechanical testing. A nanoindenter was utilized to map the hardness at the micro-level, obtaining the variations of hardness in the microstructure. This thesis yielded interesting results regarding hardness, nanomechanical material properties and testing methods. However, pushing the equipment beyond its specifications resulted in experimental data requiring compensation for several unforeseen effects. The critical stress intensity factors were calculated through the J-integral for both pure iron and steel cantilevers. Pillar compression to obtain the microstructure yield strength, was also conducted, all contributing to the characterization of the microstructure and nanomechanical properties of the steel.