Miracle-dz/UniFAR-FTUs huggingface dataset:
Downregulation of homeodomain protein Cut is essential for Drosophila follicle maturation and ovulation

ABSTRACT Proper development and maturation of a follicle is essential for successful ovulation and reproduction; however, the molecular mechanisms for follicle maturation, particularly for somatic follicle cell differentiation, are poorly understood. During Drosophila oogenesis, the somatic follicle cells encasing oocytes undergo two distinct well-established transitions: the mitotic to endocycle switch at stage 6/7 and the endocycle to gene amplification switch at stage10A/10B. Here, we identify a novel third follicle cell transition that occurs in the final stages of oogenesis (stage 13/14). This late follicle cell transition is characterized by upregulation of the transcription factor Hindsight (Hnt), and downregulation of the homeodomain transcription factor Cut and the zinc-finger transcription factor Tramtrack-69 (Ttk69). We demonstrate that inducing expression of Cut in stage 14 follicle cells is sufficient to inhibit follicle rupture and ovulation through its negative regulation of Hnt and promotion of Ttk69 expression. Our work illustrates the importance of the stage13/14 transition for follicle maturation and demonstrates the complex regulation required for somatic follicle cells to differentiate into a state primed for follicle rupture and ovulation. Summary: A pathway with a complex transcriptional network, including multiple conserved factors, is necessary for final maturation of Drosophila ovarian follicle cells, which is essential for ovulation.
The RBG-1–RBG-2 complex modulates autophagy activity by regulating lysosomal biogenesis and function in C. elegans

ABSTRACT Vici syndrome is a severe and progressive multisystem disease caused by mutations in the EPG5 gene. In patient tissues and animal models, loss of EPG5 function is associated with defective autophagy caused by accumulation of non-degradative autolysosomes, but very little is known about the mechanism underlying this cellular phenotype. Here, we demonstrate that loss of function of the RBG-1–RBG-2 complex ameliorates the autophagy defect in C. elegans epg-5 mutants. The suppression effect is independent of the complex's activity as a RAB-3 GAP and a RAB-18 GEF. Loss of rbg-1 activity promotes lysosomal biogenesis and function, and also suppresses the accumulation of non-functional autolysosomes in epg-5 mutants. The mobility of late endosome- and lysosome-associated RAB-7 is reduced in epg-5 mutants, and this defect is rescued by simultaneous loss of function of rbg-1. Expression of the GDP-bound form of RAB-7 also promotes lysosomal biogenesis and suppresses the autophagy defect in epg-5 mutants. Our study reveals that the RBG-1–RBG-2 complex acts by modulating the dynamics of membrane-associated RAB-7 to regulate lysosomal biogenesis, and provides insights into the pathogenesis of Vici syndrome. Highlighted Article: Loss of function of the RBG-1-RBG-2 complex promotes lysosomal biogenesis and function, and also ameliorates the autophagy defect caused by mutations in the Vici syndrome gene EPG5.
Compressive and Flexural Strengths of EVA-Modified Mortars for 3D Additive Construction

The compressive and flexural strengths of mortars modified with ethylene-vinyl acetate (EVA) were experimentally investigated for use in three-dimensional (3D) additive construction (3DAC). EVA powder, which is available in a premix type, was employed as an admixture. The test results for the cast specimens showed that, at a curing age of 28 days, the compressive strengths ranged from 32.92 MPa to 43.50 MPa, and the flexural strengths ranged from 12.73 MPa to 14.49 MPa. The compressive and flexural strengths of the printed specimens were relatively lower: 23% to 26% and 3% to 7%, respectively. The compressive strength also decreased and the flexural strength increased when the EVA/cement ratio was increased. The results of the experiment reveal that the EVA-modified mortar had a high rate of strength development early on, making the material advantageous for use in 3DAC. It was determined that the appropriate EVA/cement ratio ranged between 5% and 15%. However, the printed specimens exhibited lower compressive and flexural strengths than did the cast specimens, and the compressive strength decreased as the EVA content was increased. This study provides the compressive and flexural strengths of common EVA-modified mortars, important data for 3DAC applications.
Parallel ILU Preconditioning for Structured Grid Matrices

Many scientific simulation codes represent physical systems by storing data at a set of discrete points. For example, a weather modeling software application may store data representing temperature, wind velocity, air pressure, humidity, etc. at a set of points in the atmosphere over a portion of the Earth’s surface. Similarly, Computational Fluid Dynamics (CFD) software stores data representing fluid velocity, pressure, etc. at discrete points in the domain of the particular problem being solved. In many simulations, this set of discrete points is a structured grid; i.e., a finite n-dimensional regular lattice. One of the most important steps in many scientific simulations is the solution of a system of linear equations, where the unknowns of the system correspond to data elements at each of the discrete points used to model the system. If the simulation is based on a structured grid, this linear system will often have a special structure itself, and this structure may lead to more efficient techniques for solving the system than can be used for general sparse linear systems. Scientific simulations most often use an iterative technique such as the Conjugate Gradient Method or GMRES for solving linear systems. It is well known that these iterative techniques converge much more quickly if a preconditioner is used. The ILU, or Incomplete LU Factorization, preconditioner is a good choice but it is not parallelizable is a straightforward way. This thesis examines techniques for parallelizing the application of the ILU preconditioner to linear systems arising from scientific simulations on structured grids. Various techniques are tested and timing results are recorded for different types and sizes of linear systems on structured grids. ii I dedicate this work to my wife, Teresa Lockhart Eisenlohr, and to the memory of my parents, Laurence and Sylvia Eisenlohr
Resilience and psychiatric symptoms as mediators between perceived stress and non-medical use of prescription drugs among college students

ABSTRACT Background: Due to the high prevalence of non-medical use of prescription drugs (NMUPD; i.e., use of these drugs without a doctor’s prescription) among college students, it is important to identify psychosocial factors relevant to NMUPD. Prior research shows a link between perceived stress, psychiatric symptoms and NMUPD. Resilience is an essential concept in adaptive coping that emphasizes that resilience protects people against stress. Substantial evidence shows the mediation effect of resilience on the relationship between stress, psychiatric symptoms, and substance use. However, scant literature has examined associations between resilience and NMUPD. Objectives: The current study explored the relationship among perceived stress, psychiatric symptoms, resilience, and NMUPD in college students. Methods: Online data were collected from 1,052 undergraduates (68.7% females) with an average age of 19.8 years in 2016 in Virginia, United States, using anonymous surveys assessing perceived stress, psychiatric symptoms (i.e., depression and social anxiety), resilience (i.e., tenacity, tolerance, acceptance, control, and spirituality), and past-three-month NMUPD (i.e., opioids, sedatives, anxiolytics, and stimulants). Structural equation modeling was employed for data analysis. Results: Resilience together with psychiatric symptoms completely mediated the effects of perceived stress on NMUPD. Resilience completely mediated the relationship between perceived stress and psychiatric symptoms. The goodness-of-fit indicators suggested a good fit of data (RMSEA = .04; CFI = .97; TLI = .96; WRMR = 1.37). Conclusions: Resilience appears to offer protection that can mitigate the effects of perceived stress and psychiatric symptoms on NMUPD. Future interventions related to NMUPD among college students should attend to resilience.
Ground reaction forces of overground galloping in ridden Thoroughbred racehorses

ABSTRACT The horse has evolved to gallop economically at high speed. Limb force increases with speed but direct measures of limb ground reaction forces (GRFs) at gallop are sparse. This study reports GRFs for multiple limbs, using force plates, across seven Thoroughbred racehorses during ridden galloping. The results show peak vertical GRF values of 13.6 N kg−1 (non-lead hindlimb), 12.3 N kg−1 (lead hindlimb), 14.0 N kg−1 (non-lead forelimb) and 13.6 N kg−1 (lead forelimb) at 11.4 m s−1 and recorded values are consistent with those predicted from duty factor. The distribution of body weight between the forelimbs and hindlimbs is approximated to 50:50, and is variable with speed, unlike the 60:40 commonly stated for cursorial quadrupeds in the literature. An even distribution of load on all limbs may help minimise accumulation of fatigue and assist in injury avoidance. Cranio-caudal force data concur with the observation that horses apply a net accelerative impulse with the hindlimbs and a net decelerative impulse with the forelimbs. Capturing GRFs enhances our knowledge on the mechanics of galloping in fast-moving species and provides insight into injury risk and factors limiting athletic performance. Summary: Forces experienced by the limbs of racehorses during galloping increase with speed, concomitant with predictions from duty factor, though show an approximate 50:50 front:back impulse distribution, suggesting symmetry may be beneficial for injury avoidance.
The joint effect of insomnia symptoms and lifestyle factors on risk of self-reported fibromyalgia in women: longitudinal data from the HUNT Study

Objectives To investigate the association between insomnia symptoms and risk of self-reported fibromyalgia in women, and to explore whether leisure time physical activity and body mass index (BMI) modify this association. Design Prospective cohort study. Setting We used longitudinal data from the Norwegian Nord-Trøndelag Health Study collected in 1995–1997 (baseline) and 2006–2008 (follow-up). Participants A total of 14 172 women who reported to be free from fibromyalgia at baseline. Primary outcome measures We estimated adjusted risk ratios (RRs) with 95% CI for self-reported fibromyalgia at follow-up associated with baseline insomnia symptoms, leisure time physical activity and BMI. Results Overall, 466 incident cases of fibromyalgia were reported during the follow-up period of approximately 11 years, corresponding to a crude absolute risk (AR) of 3.3%. Compared with women without insomnia symptoms (crude AR=2.8%), women who reported one, two or three symptoms had RRs of fibromyalgia of 1.39 (95% CI: 1.08 to 1.80), 1.86 (95% CI: 1.33 to 2.59) and 2.66 (95% CI: 1.75 to 4.06), respectively. Compared with highly physically active women without insomnia symptoms (crude AR=2.7%), women with one or more insomnia symptoms had a RR of fibromyalgia of 1.90 (95% CI: 1.30 to 2.79) if they reported low physical activity and a RR of 1.55 (95% CI: 1.12 to 2.13) if they reported high physical activity. We found no synergistic effect between insomnia symptoms and BMI on risk of fibromyalgia; however, overweight and obese women with one or more insomnia symptoms had RRs of 2.35 (95% CI: 1.73 to 3.21) and 2.18 (95% CI: 1.42 to 3.35) compared with the reference group of normal weight women without insomnia symptoms (crude AR=2.3%). Conclusions Insomnia symptoms are strongly and positively associated with risk of fibromyalgia in adult women. Leisure time physical activity may compensate for some of the adverse effect of insomnia symptoms on risk of fibromyalgia.
Predictive Factors of Recurrence in Patients with Differentiated Thyroid Carcinoma: A Retrospective Analysis on 579 Patients

Differentiated thyroid carcinoma (DTC) is usually associated with a favorable prognosis. Nevertheless, up to 30% of patients present a local or distant recurrence. The aim of this study was to assess the incidence of recurrence after surgery for DTC and to identify predictive factors of recurrence. We included in this retrospective study 579 consecutive patients who underwent thyroidectomy for DTC from 2011 to 2016 at our institution. We observed biochemical or structural recurrent disease in 36 (6.2%) patients; five-year disease-free survival was 94.1%. On univariate analysis, male sex, histotype, lymph node yield, lymph node metastasis, extrathyroidal invasion and multicentricity were associated with significantly higher risk of recurrence, while microcarcinoma was correlated with significantly lower risk of recurrence. On multivariate analysis, only lymph node metastases (OR 4.724, p = 0.012) and microcarcinoma (OR 0.328, p = 0.034) were detected as independent predictive factors of recurrence. Postoperative management should be individualized and commensurate with the risk of recurrence: Patients with high-risk carcinoma should undergo strict follow-up and aggressive treatment. Furthermore, assessment of the risk should be repeated over time, considering individual response to therapy.
Pd Nanocatalyst Adorned on Magnetic Chitosan@N-Heterocyclic Carbene: Eco-Compatible Suzuki Cross-Coupling Reaction

A novel magnetic-functionalized-multi-walled carbon nanotubes@chitosan N-heterocyclic carbene-palladium (M-f-MWCNTs@chitosan-NHC-Pd) nanocatalyst is developed in two steps. The first step entails the fabrication of a three-component cross-linking of chitosan utilizing the Debus-Radziszewski imidazole approach. The second step comprised the covalent grafting of prepared cross-linked chitosan to the outer walls of magnetically functionalized MWCNTs (M-f-MWCNTs) followed by introducing PdCl2 to generate the m-f-MWCNTs@cross-linked chitosan with a novel NHC ligand. The repeated units of the amino group in the chitosan polymer chain provide the synthesis of several imidazole units which also increase the number of Pd linkers thus leading to higher catalyst efficiency. The evaluation of catalytic activity was examined in the expeditious synthesis of biaryl compounds using the Suzuki cross-coupling reaction of various aryl halides and aryl boronic acids; ensuing results show the general applicability of nanocatalyst with superior conversion reaction yields, high turnover frequencies (TOFs) and turnover numbers (TON). Meanwhile, nanocatalyst showed admirable potential in reusability tests, being recycled for five runs without losing significant activities under optimum reaction conditions. The successfully synthesis of catalyst and its characterization was confirmed using the Fourier transform infrared spectrometer (FT-IR), spectrometer transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photo-electron spectroscopy (XPS) and thermogravimetric analysis (TGA).
Anthocyanins and Their Metabolites as Therapeutic Agents for Neurodegenerative Disease

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), are characterized by the death of neurons within specific regions of the brain or spinal cord. While the etiology of many neurodegenerative diseases remains elusive, several factors are thought to contribute to the neurodegenerative process, such as oxidative and nitrosative stress, excitotoxicity, endoplasmic reticulum stress, protein aggregation, and neuroinflammation. These processes culminate in the death of vulnerable neuronal populations, which manifests symptomatically as cognitive and/or motor impairments. Until recently, most treatments for these disorders have targeted single aspects of disease pathology; however, this strategy has proved largely ineffective, and focus has now turned towards therapeutics which target multiple aspects underlying neurodegeneration. Anthocyanins are unique flavonoid compounds that have been shown to modulate several of the factors contributing to neuronal death, and interest in their use as therapeutics for neurodegeneration has grown in recent years. Additionally, due to observations that the bioavailability of anthocyanins is low relative to that of their metabolites, it has been proposed that anthocyanin metabolites may play a significant part in mediating the beneficial effects of an anthocyanin-rich diet. Thus, in this review, we will explore the evidence evaluating the neuroprotective and therapeutic potential of anthocyanins and their common metabolites for treating neurodegenerative diseases.
Novel Biomarkers for Personalized Cancer Immunotherapy

Cancer immunotherapy has emerged as a novel and effective treatment strategy for several types of cancer. Immune checkpoint inhibitors (ICIs) have recently demonstrated impressive clinical benefit in some advanced cancers. Nonetheless, in the majority of patients, the successful use of ICIs is limited by a low response rate, high treatment cost, and treatment-related toxicity. Therefore, it is necessary to identify predictive and prognostic biomarkers to select the patients who are most likely to benefit from, and respond well to, these therapies. In this review, we summarize the evidence for candidate biomarkers of response to cancer immunotherapy.
Organ Doses from CT Localizer Radiographs: Development, Validation, and Application of a Monte Carlo Estimation Technique.

PURPOSE The purpose of this study was to simulate and validate organ doses from different CT localizer radiograph geometries using Monte Carlo methods for a population of patients. METHODS A Monte Carlo method was developed to estimate organ doses from CT localizer radiographs using PENELOPE. The method was validated by comparing dosimetry estimates with measurements using an anthropomorphic phantom imbedded with thermoluminescent dosimeters (TLDs) scanned on a commercial CT system (Siemens SOMATOM Flash). The Monte Carlo simulation platform was then applied to conduct a population study with fifty-seven adult computational phantoms (XCAT). In the population study, clinically relevant chest localizer protocols were simulated with the x-ray tube in anterior-posterior (AP), right lateral, and PA positions. Mean organ doses and associated standard deviations (in mGy) were then estimated for all simulations. The obtained organ doses were studied as a function of patient chest diameter. Organ doses for breast and lung were compared across different views and represented as a percentage of organ doses from rotational CT scans. RESULTS The validation study showed an agreement between the Monte Carlo and physical TLD measurements with a maximum percent difference of 15.5% and a mean difference of 3.5% across all organs. The XCAT population study showed that breast dose from AP localizers was the highest with a mean value of 0.24 mGy across patients, while the lung dose was relatively consistent across different localizer geometries. The organ dose estimates were found to vary across the patient population, partially explained by the changes in the patient chest diameter. The average effective dose was 0.18 mGy for AP, 0.09 mGy for lateral, and 0.08 mGy for PA localizer. CONCLUSION A platform to estimate organ doses in CT localizer scans using Monte Carlo methods was implemented and validated based on comparison with physical dose measurements. The simulation platform was applied to a virtual patient population, where the localizer organ doses were found to range within 0.4-8.6% of corresponding organ doses for a typical CT scan, 0.2-3.3% of organ doses for a CT pulmonary angiography scan, and 1.1-20.8% of organ doses for a low dose lung cancer screening scan.
TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema

A long‐term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset.
Structure Elucidation and Toxicity Analysis of the Degradation Products of Deoxynivalenol by Gaseous Ozone

Fusarium Head Blight (FHB) or scab is a fungal disease of cereal grains. Wheat scab affects the yield and quality of wheat and produces mycotoxins such as deoxynivalenol (DON), which can seriously threaten human and animal health. In this study, gaseous ozone was used to degrade DON in wheat scab and the degradation products of ozonolysis were analyzed by ultra-performance liquid chromatography quadrupole-orbitrap mass spectrometry (UHPLC Q-Orbitrap). Toxicology analyses of the degradation products were also studied using structure-activity relationships. Ozone (8 mg L−1 concentration) was applied to 2 μg mL−1 of DON in ultrapure water, resulted in 95.68% degradation within 15 s. Ten ozonized products of DON in ultrapure water were analyzed and six main products (C15H18O7, C15H18O9, C15H22O9, C15H20O10, C15H18O8, and C15H20O9) were analyzed at varying concentrations of ozone and DON. Structural formulae were assigned to fragmentation products generated by MS2 and Mass Frontier® software. According to structure-activity relationship studies, the toxicities of the ozonized products were significantly decreased due to de-epoxidation and the attack of ozone at the C9-10 double bond in DON. Based on the results of the study above, we can find that gaseous ozone is an efficient and safe technology to degrade DON, and these results may provide a theoretical basis for the practical research of detoxifying DON in scabby wheat and other grains.
Merits of sponge-like PLGA microspheres as long-acting injectables of hydrophobic drug

Abstract Our study was initiated to challenge the preconception that nonporous PLGA microspheres with compact matrices should be used to develop long-acting depot injectables of hydrophobic drugs. A simple, new oil-in-water emulsion technique was utilized to produce porous PLGA microspheres with a sponge-like skeleton. Then, their applicability to developing sustained-release depots of hydrophobic drugs was explored in this study. As control, nonporous microspheres with a compact matrix were produced following a typical solvent evaporation process. Both microsphere manufacturing processes used non-halogenated isopropyl formate and progesterone as a dispersed solvent and a model hydrophobic drug, respectively. Various attempts were made to evaluate critical quality attributes of the porous microspheres and the nonporous ones. Surprisingly, the former displayed interesting features from the viewpoints of manufacturability and microsphere quality. For example, the spongy microspheres improved drug encapsulation efficiency and particle size uniformity, inhibited drug crystallization during microencapsulation, and minimized the residual solvent content in microspheres. Furthermore, the porous microspheres provided continual drug release kinetics without a lag time and much faster drug release than the non-porous microspheres did. In summary, the porous and sponge-like PLGA microspheres might find lucrative applications in developing sustained release dosage forms of hydrophobic drugs.