Miracle-dz/UniFAR-FTUs huggingface dataset:
Elucidation of Agonist and Antagonist Dynamic Binding Patterns in ER-α by Integration of Molecular Docking, Molecular Dynamics Simulations and Quantum Mechanical Calculations

Estrogen receptor alpha (ERα) is a ligand-dependent transcriptional factor in the nuclear receptor superfamily. Many structures of ERα bound with agonists and antagonists have been determined. However, the dynamic binding patterns of agonists and antagonists in the binding site of ERα remains unclear. Therefore, we performed molecular docking, molecular dynamics (MD) simulations, and quantum mechanical calculations to elucidate agonist and antagonist dynamic binding patterns in ERα. 17β-estradiol (E2) and 4-hydroxytamoxifen (OHT) were docked in the ligand binding pockets of the agonist and antagonist bound ERα. The best complex conformations from molecular docking were subjected to 100 nanosecond MD simulations. Hierarchical clustering was conducted to group the structures in the trajectory from MD simulations. The representative structure from each cluster was selected to calculate the binding interaction energy value for elucidation of the dynamic binding patterns of agonists and antagonists in the binding site of ERα. The binding interaction energy analysis revealed that OHT binds ERα more tightly in the antagonist conformer, while E2 prefers the agonist conformer. The results may help identify ERα antagonists as drug candidates and facilitate risk assessment of chemicals through ER-mediated responses.
Development of a Method of Measuring β-D-Glucan and Its Use in Preemptive Therapy for Invasive Fungal Infections

Invasive fungal infections (IFIs) are serious infections that develop in conjunction with neutropenia after chemotherapy for acute leukemia or with hematopoietic stem cell transplantation. Conventionally, empirical antifungal therapy was recommended to treat IFIs for patient safety despite a lack of evidence of fungal infections. However, many studies have indicated that antifungals were not necessary for over half of patients, and several detriments of empirical therapy were noted, e.g., antifungals caused adverse reactions, an increase in drug-resistant fungi was a possibility, and medical costs soared. β-D-glucan (BDG) is a component of clinically important fungi such as Aspergillus and Candida. The G-test was developed in Japan as a way to measure BDG in serum using a coagulation factor from the blood of the horseshoe crab. Pre-emptive antifungal therapy based upon serodiagnosis with a BDG or galactomannan assay and CT imaging has been introduced. With pre-emptive antifungal therapy, the prognosis is equivalent to that with empirical therapy, and the dose of the antifungal has been successfully reduced. Measurement of BDG has been adopted widely as a method of diagnosing IFIs and is listed in the key guidelines for fungal infections and febrile neutropenia.
Correlation between caffeine contents of green coffee beans and altitudes of the coffee plants grown in southwest Ethiopia

Caffeine contents of 45 green coffee bean samples collected from coffee plants grown at different altitudes in Southwest Ethiopia was determined by UV-Vis spectrophotometry. The caffeine contents were found in the range of 0.62 - 1.2% (w/w). A moderate negative correlation (R = 0.5463) was found between the caffeine contents of green coffee beans and the altitudes at which the coffee plants were grown. The caffeine contents of 9 of the green coffee bean samples analyzed by high performance liquid chromatography (HPLC) provided comparable results in the range of 0.60−1.1% (w/w). Statistical analysis of data (t-test) indicated absence of significant differences between the caffeine contents obtained by the two methods. Nonetheless, HPLC method is precise, accurate and reliable in determining caffeine content in green coffee bean samples while the UV-Vis spectrophotometry is simple, rapid, precise and more economical. KEY WORDS : Green coffee beans, Caffeine, Correlation between caffeine content and altitude of coffee plant, UV-Vis spectrophotometry, High performance liquid chromatography, Ethiopia Bull. Chem. Soc. Ethiop. 2018 , 32(1), 13-25 DOI: https://dx.doi. org/10.4314/bcse.v32i1.2
Graphene-Based Nanocomposites: Synthesis, Mechanical Properties, and Characterizations

Graphene-based nanocomposites possess excellent mechanical, electrical, thermal, optical, and chemical properties. These materials have potential applications in high-performance transistors, biomedical systems, sensors, and solar cells. This paper presents a critical review of the recent developments in graphene-based nanocomposite research, exploring synthesis methods, characterizations, mechanical properties, and thermal properties. Emphasis is placed on characterization techniques and mechanical properties with detailed examples from recent literature. The importance of characterization techniques including Raman spectroscopy, X-ray diffraction (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM) for the characterization of graphene flakes and their composites were thoroughly discussed. Finally, the effect of graphene even at very low loadings on the mechanical properties of the composite matrix was extensively reviewed.
A Direct Observation Video Method for Describing COVID-19 Transmission Factors on a Micro-Geographical Scale: Viral Transmission (VT)-Scan

The COVID-19 pandemic severely affected many aspects of human life. While most health agencies agree mask wearing and physical distancing reduce viral transmission, efforts to improve the assessment of these behaviors are lacking. This study aimed to develop a direct observation video method [Viral Transmission (VT)-Scan] for assessing COVID-19 transmission behaviors and related factors (e.g., environmental setting). A wearable video device (WVD) was used to obtain videos of outdoor, public areas. The videos were examined to extract relevant information. All outcomes displayed good to excellent intra- and inter-reliability with intra-class correlation coefficients ranging from 0.836 to 0.997. The majority of people had a mask (60.8%) but 22.1% of them wore it improperly, 45.4% were not physical distancing, and 27.6% were simultaneously mask and physical distancing non-compliant. Transmission behaviors varied by demographics with white, obese males least likely to be mask-compliant and white, obese females least likely to physical distance. Certain environments (e.g., crosswalks) were identified as “hot spots” where higher rates of adverse transmission behaviors occurred. This study introduces a reliable method for obtaining objective data on COVID-19 transmission behaviors and related factors which may be useful for agent-based modeling and policy formation.
Risk Score Model for Microvascular Invasion in Hepatocellular Carcinoma: The Role of Tumor Burden and Alpha-Fetoprotein

Simple Summary Microvascular invasion (MVI) is the most consistently reported risk factor for recurrence after curative treatment in hepatocellular carcinoma (HCC), but the preoperative prediction of MVI is still challenging. We retrospectively collected 1153 patients who underwent liver resection for HCC, and our multivariate analysis revealed preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We used both factors to build a risk score model that is easy to calculate and objective, with minimal user bias. The preoperative prediction of MVI can guide the treatment plan of HCC, including surgical planning, criteria for transplantation, and adjuvant or neoadjuvant therapy. Our risk score model is easily and widely applicable with moderate performance, which optimizes clinical practice and helps study design in the future. Abstract Microvascular invasion (MVI) is a significant risk factor for the recurrence of hepatocellular carcinoma, but it is a histological feature that needs to be confirmed after hepatectomy or liver transplantation. The preoperative prediction of MVI can optimize the treatment plan of HCC, but an easy and widely applicable model is still lacking. The aim of our study was to predict the risk of MVI using objective preoperative factors. We retrospectively collected 1153 patients who underwent liver resection for HCC, and MVI was found to be associated with significantly poor disease-free survival. The patients were randomly split in a 3:1 ratio into training (n = 864) and validation (n = 289) datasets. The multivariate analysis of the training dataset found preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We built a risk score model with cutoff points of TTV at 30, 60, and 300 cm3 and AFP at 160 and 2000 ng/mL, and the model stratified the risk of MVI into low risk (14.1%), intermediate risk (36.4%), and high risk (60.5%). The validation of the risk score model with the validation dataset showed moderate performance (the concordance statistic: 0.731). The model comprised simple and objective preoperative factors with good applicability, which can help to guide treatment plans for HCC and future study design.
Protein kinase N2 mediates flow-induced eNOS activation and vascular tone regulation.

Formation of nitric oxide (NO) by the endothelial NO-synthase (eNOS) is a central process in the homeostatic regulation of vascular functions including blood pressure regulation and fluid shear stress exerted by the flowing blood is a main stimulus of eNOS activity. Previous work has identified several mechanosensing and -transducing processes in endothelial cells, which mediate this process and result in the stimulation of eNOS activity through phosphorylation of the enzyme via various kinases including AKT. How the initial mechanosensing and signaling processes are linked to eNOS phosphorylation is unclear. In human endothelial cells, we demonstrated that protein kinase N2 (PKN2), which is activated by flow through the mechanosensitive cation channel Piezo1 and Gq/G11-mediated signaling, as well as Ca2+ and PDK1, plays a pivotal role in this process. Active PKN2 promoted phosphorylation of human eNOS at serine 1177 and at a newly identified site, serine 1179. These phosphorylation events additively led to increased eNOS activity. PKN2-mediated eNOS phosphorylation at serine 1177 involved phosphorylation of AKT synergistically with mTORC2-mediated AKT phosphorylation while active PKN2 directly phosphorylated human eNOS at serine 1179. Mice with induced endothelium-specific deficiency of PKN2 showed strongly reduced flow-induced vasodilation and developed arterial hypertension accompanied by reduced eNOS activation. These results uncover a central mechanism that couples upstream mechanosignaling processes in endothelial cells to the regulation of eNOS-mediated NO formation, vascular tone and blood pressure.
Living Space and Job Prospects and Their Relationship with Subjective Well-Being during COVID-19 Confinement in Spain: The Mediator Role of Resilience

The objective of this study was to examine the relationships of participants’ home characteristics (living space) and job prospects after the coronavirus disease 2019 (COVID-19) pandemic to their subjective psychological well-being (SWB) (in terms of both affective and cognitive aspects). We also examined the role of participants’ resilience as a possible mediator in the relationships among the aforementioned variables. The sample comprised 474 Spanish adults who completed an online questionnaire between 14 and 24 April 2020, when COVID-19 confinement was very strict in Spain. We proposed a path analysis model including the described variables. The model presented a good fit (χ2 = 7.41, df = 5, p = 0.376, comparative fit index = 0.996, Tucker–Lewis index = 0.987; root mean square error of approximation = 0.032). The results indicated that living space and future job prospects predicted resilience, which, in turn, was related to SWB. Moreover, the bootstrapping results revealed a mediating effect of resilience that showed indirect relationships between living space and SWB and between job prospects and SWB. Our results underline the importance of environmental (living space) and job-related variables to predict SWB as well as the mediating role that resilience may play during the confinement period.
Is It Possible to Have Home E-Monitoring of Pulmonary Function in Our Patients with Duchenne Muscular Dystrophy in the COVID-19 Pandemic?—A One Center Pilot Study

Background: Duchenne muscular dystrophy (DMD) is the most common, progressive, irreversible muscular dystrophy. Pulmonary function is crucial for duration of life in this disease. Currently, the European Respiratory Society is focused on digital health, seeking innovations that will be realistic for digital respiratory medicine to support professionals and patients during the COVID-19 pandemic. Aims: The aim of this study was to investigate whether it is possible to monitor pulmonary function at home using an individual electronic spirometry system in boys with Duchenne muscular dystrophy. Materials and methods: In this observational, prospective study, conducted from March 2021 to June 2021, twenty boys with DMD (aged 8–16) were enrolled. The patients were recruited from the Rare Disease Centre, University Clinical Centre, of Gdańsk, Poland. Medical history and anthropometric data were collected, and spirometry (Jaeger, Germany) was performed in all patients at the start of the study. Each patient received an electronic individual spirometer (AioCare) and was asked to perform spirometry on their own every day, morning and evening, at home for a period of 4 weeks. The number of measurements, correctness of performing measurements, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF) were evaluated. Results: Finally, 14 out of 20 boys enrolled in the study with a mean age of 12.5 years (7 non-ambulatory) applied and received a home spirometer (AioCare). A total of 283 measurements were performed by all patients at home for 4 weeks. Half of the patients were able to perform measurements correctly. There were no significant differences between mean values of FVC, FE1, PEF between home and hospital spirometry (p > 0.05) expect PEF pv% (p < 0.00046). Patients with higher FEV1 (p = 0.0387) and lower BMI (p = 0.0494) were more likely to take home spirometer measurements. The mean general satisfaction rating of home-spirometry was 4.33/5 (SD 0.78), the mean intelligibility rating was 4.83/5 (SD 0.58). Reasons for irregular measurements were: forgetting (43%), lack of motivation (29%), difficulty (14%), lack of time (14%). Conclusion: Home electronic monitoring of pulmonary function in patients with DMD is possible to implement in daily routines at home. This protocol should be introduced as early as possible in patients 7–8 years old with good, preserved lung function. Patients accept this form of medical care but require more education about the benefits of e-monitoring. There is a need to implement a system to remind patients of the use of electronic medical devices at home, e.g., via SMS (short message service).
Molecular Dissection of the Gene OsGA2ox8 Conferring Osmotic Stress Tolerance in Rice

Gibberellin 2-oxidase (GA2ox) plays an important role in the GA catabolic pathway and the molecular function of the OsGA2ox genes in plant abiotic stress tolerance remains largely unknown. In this study, we functionally characterized the rice gibberellin 2-oxidase 8 (OsGA2ox8) gene. The OsGA2ox8 protein was localized in the nucleus, cell membrane, and cytoplasm, and was induced in response to various abiotic stresses and phytohormones. The overexpression of OsGA2ox8 significantly enhanced the osmotic stress tolerance of transgenic rice plants by increasing the number of osmotic regulators and antioxidants. OsGA2ox8 was differentially expressed in the shoots and roots to cope with osmotic stress. The plants overexpressing OsGA2ox8 showed reduced lengths of shoots and roots at the seedling stage, but no difference in plant height at the heading stage was observed, which may be due to the interaction of OsGA2ox8 and OsGA20ox1, implying a complex feedback regulation between GA biosynthesis and metabolism in rice. Importantly, OsGA2ox8 was able to indirectly regulate several genes associated with the anthocyanin and flavonoid biosynthetic pathway and the jasmonic acid (JA) and abscisic acid (ABA) biosynthetic pathway, and overexpression of OsGA2ox8 activated JA signal transduction by inhibiting the expression of jasmonate ZIM domain-containing proteins. These results provide a basis for a future understanding of the networks and respective phenotypic effects associated with OsGA2ox8.
Greener Pretreatment Approaches for the Valorisation of Natural Fibre Biomass into Bioproducts

The utilization of lignocellulosic biomass in various applications has a promising potential as advanced technology progresses due to its renowned advantages as cheap and abundant feedstock. The main drawback in the utilization of this type of biomass is the essential requirement for the pretreatment process. The most common pretreatment process applied is chemical pretreatment. However, it is a non-eco-friendly process. Therefore, this review aims to bring into light several greener pretreatment processes as an alternative approach for the current chemical pretreatment. The main processes for each physical and biological pretreatment process are reviewed and highlighted. Additionally, recent advances in the effect of different non-chemical pretreatment approaches for the natural fibres are also critically discussed with a focus on bioproducts conversion.
High-Resolution Bioprinting of Recombinant Human Collagen Type III

The development of commercial collagen inks for extrusion-based bioprinting has increased the amount of research on pure collagen bioprinting, i.e., collagen inks not mixed with gelatin, alginate, or other more common biomaterial inks. New printing techniques have also improved the resolution achievable with pure collagen bioprinting. However, the resultant collagen constructs still appear too weak to replicate dense collagenous tissues, such as the cornea. This work aims to demonstrate the first reported case of bioprinted recombinant collagen films with suitable optical and mechanical properties for corneal tissue engineering. The printing technology used, aerosol jet® printing (AJP), is a high-resolution printing method normally used to deposit conductive inks for electronic printing. In this work, AJP was employed to deposit recombinant human collagen type III (RHCIII) in overlapping continuous lines of 60 µm to form thin layers. Layers were repeated up to 764 times to result in a construct that was considered a few hundred microns thick when swollen. Samples were subsequently neutralised and crosslinked using EDC:NHS crosslinking. Nanoindentation and absorbance measurements were conducted, and the results show that the AJP-deposited RHCIII samples possess suitable mechanical and optical properties for corneal tissue engineering: an average effective elastic modulus of 506 ± 173 kPa and transparency ≥87% at all visible wavelengths. Circular dichroism showed that there was some loss of helicity of the collagen due to aerosolisation. SDS-PAGE and pepsin digestion were used to show that while some collagen is degraded due to aerosolisation, it remains an inaccessible substrate for pepsin cleavage.
A Comparative Evaluation of Third-Generation Advanced High-Strength Steels for Automotive Forming and Crash Applications

While the third generation of advanced high-strength steels (3rd Gen AHSS) have increasingly gained attention for automotive lightweighting, it remains unclear to what extent the developed methodologies for the conventional dual-phase (DP) steels are applicable to this new class of steels. The present paper provides a comprehensive study on the constitutive, formability, tribology, and fracture behavior of three commercial 3rd Gen AHSS with an ultimate strength level ranging from 980 to 1180 MPa which are contrasted with two DP steels of the same strength levels and the 590R AHSS. The hardening response to large strain levels was determined experimentally using tensile and shear tests and then evaluated in 3D simulations of tensile tests. In general, the strain rate sensitivity of the two 3rd Gen 1180 AHSS was significantly different as one grade exhibited larger transformation-induced behavior. The in-plane formability of the three 1180 MPa steels was similar but with a stark contrast in the local formability whereas the opposite trend was observed for the 3rd Gen 980 and the DP980 steel. The forming limit curves could be accurately predicted using the experimentally measured hardening behavior and the deterministic modified Bressan–Williams through-thickness shear model or the linearized Modified Maximum Force Criterion. The resistance to sliding of the three 3rd Gen AHSS in the Twist Compression Test revealed a comparable coefficient of friction to the 590R except for the electro-galvanized 3rd Gen 1180 V1. An efficient experimental approach to fracture characterization for AHSS was developed that exploits tool contact and bending to obtain fracture strains on the surface of the specimen by suppressing necking. Miniature conical hole expansion, biaxial punch tests, and the VDA 238-100 bend test were performed to construct stress-state dependent fracture loci for use in forming and crash simulations. It is demonstrated that, the 3rd Gen 1180 V2 can potentially replace the DP980 steel in terms of both the global and local formability.
Multiplicity Eludes Peer Review: The Case of COVID-19 Research

Multiplicity arises when data analysis involves multiple simultaneous inferences, increasing the chance of spurious findings. It is a widespread problem frequently ignored by researchers. In this paper, we perform an exploratory analysis of the Web of Science database for COVID-19 observational studies. We examined 100 top-cited COVID-19 peer-reviewed articles based on p-values, including up to 7100 simultaneous tests, with 50% including >34 tests, and 20% > 100 tests. We found that the larger the number of tests performed, the larger the number of significant results (r = 0.87, p < 10−6). The number of p-values in the abstracts was not related to the number of p-values in the papers. However, the highly significant results (p < 0.001) in the abstracts were strongly correlated (r = 0.61, p < 10−6) with the number of p < 0.001 significances in the papers. Furthermore, the abstracts included a higher proportion of significant results (0.91 vs. 0.50), and 80% reported only significant results. Only one reviewed paper addressed multiplicity-induced type I error inflation, pointing to potentially spurious results bypassing the peer-review process. We conclude the need to pay special attention to the increased chance of false discoveries in observational studies, including non-replicated striking discoveries with a potentially large social impact. We propose some easy-to-implement measures to assess and limit the effects of multiplicity.