Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding cell culture dynamics: a tool for defining protocol parameters for improved processes and efficient manufacturing using human embryonic stem cells

ABSTRACT Standardization is crucial when culturing cells including human embryonic stem cells (hESCs) which are valuable for therapy development and disease modeling. Inherent issues regarding reproducibility of protocols are problematic as they hinder translation to good manufacturing practice (GMP), thus reducing clinical efficacy and uptake. Pluripotent cultures require standardization to ensure that input material is consistent prior to differentiation, as inconsistency of input cells creates end-product variation. To improve protocols, developers first must understand the cells they are working with and their related culture dynamics. This innovative work highlights key conditions required for optimized and cost-effective bioprocesses compared to generic protocols typically implemented. This entailed investigating conditions affecting growth, metabolism, and phenotype dynamics to ensure cell quality is appropriate for use. Results revealed critical process parameters (CPPs) including feeding regime and seeding density impact critical quality attributes (CQAs) including specific metabolic rate (SMR) and specific growth rate (SGR). This implied that process understanding, and control is essential to maintain key cell characteristics, reduce process variation and retain CQAs. Examination of cell dynamics and CPPs permitted the formation of a defined protocol for culturing H9 hESCs. The authors recommend that H9 seeding densities of 20,000 cells/cm2, four-day cultures or three-day cultures following a recovery passage from cryopreservation and 100% medium exchange after 48 hours are optimal. These parameters gave ~SGR of 0.018 hour−1 ± 1.5x10−3 over three days and cell viabilities ≥95%±0.4, while producing cells which highly expressed pluripotent and proliferation markers, Oct3/4 (>99% positive) and Ki-67 (>99% positive). Graphical abstract
DMA thermal analysis of yacon tuberous roots

Abstract Specimens prepared from yacon roots in first two weeks after harvest were tested by dynamic mechanical analysis thermal analysis at temperatures between 30 and 90°C. No differences between different parts of roots were proved. There were indicated some differences in the test parameters that were caused by short time storage of the roots. One source of the differences was loss of water during the roots storage. The measured modulus increased during short time storage. Detailed study of changes of the modulus during the specimen dynamic mechanical analysis test provided information about different development of the storage and loss moduli during the specimen heating. The observed results can be caused by changes in cellular membranes observed earlier during vegetable heating, and by composition changes due to less stable components of yacon like inulin.
Optimization of Pretreatment Method for Alkylmercuries Speciation in Coal by High‐Performance Liquid Chromatography Coupled with UV‐Digestion Cold Vapor Atomic Fluorescence Spectrometry

Abstract Exhaustive extraction of analytes in their original chemical forms from samples with complex matrices is a pivotal step for speciation analysis. Herein we propose a pretreatment method for extracting and preconcentrating methylmercury and ethylmercury from coal samples by using KBr–H2SO4/CuSO4–C6H5CH3–Na2S2O3 system. The extraction conditions, including the volume of the organic phase and the extraction time, were optimized in detail. Speciation analysis of alkylmercuries was carried out by high‐performance liquid chromatography online coupled with UV‐digestion and cold vapor atomic fluorescence spectrometry. The detection limits were 0.6 ng mL−1 for methylmercury and 1 ng mL−1 for ethylmercury, respectively. The recoveries of methylmercury and ethylmercury spiked in a sample were 84% and 82%, respectively. The method was applied successfully to analysis of alkylmercuries in four coal samples collected from northeast China. The authors were invited to contribute this paper to a special issue of the journal entitled “Spectroscopy and Automation”. This special issue was organized by Miguel de la Guardia, Professor of Analytical Chemistry at Valencia University, Spain.
Bioinspired design and assembly of platelet reinforced polymer films with enhanced absorption properties

Bioinspired by the natural structural composites, we selectively synthesized CuS hexagonal nanoplatelets by a simple wet chemical method; and a novel approach was also developed to synthesize the brick–mortar structure CuS/PVDF nanocomposite films by self-assembly of CuS hexagonal platelets building blocks. The mechanics of the composites can increase by 50%, and the absorption peak also can reach −29.66 dB at 10.90 GHz with low filler content, the enhanced mechanism was also explained.
Protective role of vitamin D against oxidative stress in diabetic retinopathy

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus. There is much evidence showing that a high level of mitochondrial overproduction of reactive oxygen species in the diabetic retina contributes in modifying cellular signalling and leads to retinal cell damage and finally to the development of DR pathogenesis. In the last few decades, it has been reported that vitamin D is involved in DR pathogenesis. Vitamin D, traditionally known as an essential nutrient crucial in bone metabolism, has also been proven to be a very effective antioxidant. It has been demonstrated that it modulates the production of advanced glycosylated end products, as well as several pathways including protein kinase C, the polyol pathway leading to the reduction of free radical formation. It prevents the translocation of nuclear factor kappa B, preventing the inflammatory response, acting as an immunomodulator, and modulates autophagy and apoptosis. In this review, we explore the molecular mechanisms by which vitamin D protects the eye from oxidative stress, in order to evaluate whether vitamin D supplementation may be useful to mitigate the deleterious effects of free radicals in DR.
Safety, tolerability and pharmacokinetics of emodepside, a potential novel treatment for onchocerciasis (river blindness), in healthy male subjects

Emodepside is an anthelmintic, originally developed for veterinary use. We investigated in healthy subjects the safety, and pharmacokinetics of a liquid service formulation (LSF) and immediate release (IR) tablet of emodepside in 2 randomised, parallel‐group, placebo‐controlled, Phase I studies.
Stomatin-Mediated Inhibition of the Akt Signaling Axis Suppresses Tumor Growth

These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis. The growth and progression of cancers are crucially regulated by the tumor microenvironment where tumor cells and stromal cells are mutually associated. In this study, we found that stomatin expression was markedly upregulated by the interaction between prostate cancer cells and stromal cells. Stomatin suppressed cancer cell proliferation and enhanced apoptosis in vitro and inhibited xenograft tumor growth in vivo. Stomatin inhibited Akt activation, which is mediated by phosphoinositide-dependent protein kinase 1 (PDPK1). PDPK1 protein stability was maintained by its binding to HSP90. Stomatin interacted with PDPK1 and interfered with the PDPK1–HSP90 complex formation, resulting in decreased PDPK1 expression. Knockdown of stomatin in cancer cells elevated Akt activation and promoted cell increase by promoting the interaction between PDPK1 and HSP90. Clinically, stomatin expression levels were significantly decreased in human prostate cancer samples with high Gleason scores, and lower expression of stomatin was associated with higher recurrence of prostate cancer after the operation. Collectively, these findings demonstrate the tumor-suppressive effect of stromal-induced stomatin on cancer cells. Significance: These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis.
Treatment allocation strategies for umbrella trials in the presence of multiple biomarkers: A comparison of methods

Umbrella trials are an innovative trial design where different treatments are matched with subtypes of a disease, with the matching typically based on a set of biomarkers. Consequently, when patients can be positive for more than one biomarker, they may be eligible for multiple treatment arms. In practice, different approaches could be applied to allocate patients who are positive for multiple biomarkers to treatments. However, to date there has been little exploration of how these approaches compare statistically. We conduct a simulation study to compare five approaches to handling treatment allocation in the presence of multiple biomarkers – equal randomisation; randomisation with fixed probability of allocation to control; Bayesian adaptive randomisation (BAR); constrained randomisation; and hierarchy of biomarkers. We evaluate these approaches under different scenarios in the context of a hypothetical phase II biomarker‐guided umbrella trial. We define the pairings representing the pre‐trial expectations on efficacy as linked pairs, and the other biomarker‐treatment pairings as unlinked. The hierarchy and BAR approaches have the highest power to detect a treatment‐biomarker linked interaction. However, the hierarchy procedure performs poorly if the pre‐specified treatment‐biomarker pairings are incorrect. The BAR method allocates a higher proportion of patients who are positive for multiple biomarkers to promising treatments when an unlinked interaction is present. In most scenarios, the constrained randomisation approach best balances allocation to all treatment arms. Pre‐specification of an approach to deal with treatment allocation in the presence of multiple biomarkers is important, especially when overlapping subgroups are likely.
Tesamorelin improves fat quality independent of changes in fat quantity

Supplemental Digital Content is available in the text Objectives: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density. Design: Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. Methods: CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader. Results: Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (−91 HU both arms, P = 0.80) and SAT density (−94 HU tesamorelin, −95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5–7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3–4.7), P < 0.001] area change. Conclusion: In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group.
Proshchenkoite-(Y) from Russia - a new mineral species in the vicanite group: descriptive data and crystal structure

Abstract A REE-bearing fluorosilicate from the Tommot REE-Nb deposit in Yakutia, Russia, described without a name in 1966, is characterized here as a new species, proshchenkoite-(Y), of the vicanite group of borosilicates. Wavelength-dispersive electron probe analyses gave the following empirical formula: (Y3.70REE7.54Ca1.55Na1.16Mn0.77Th0.10Pb0.01)∑14.83(Fe2+0.83Mn0.15Ti0.02)∑1.00Ca1. 00 (P0.70Si0.26As0.04)∑1.00Si6. 05B3.20(O34.55F13.45)∑48. Boron was analysed with a nuclear microprobe method based on the nuclear reaction 11B(p,α)2α. The simplified formula is (Y,REE,Ca,Na,Mn)15 (Fe2+,Mn)Ca(P,Si)Si6B3O34F14. The mineral is trigonal, R3m, with a = 10.7527(7) Å, c = 27.4002(18) Å, V = 2743.6(6) Å3, Z = 3. The crystal structure was refined to R1 = 0.042 for 1819 observed reflections. Proshchenkoite-(Y) is isostructural with okanoganite-(Y), vicanite-(Ce) and hundholmenite-(Y), and the differences in site occupancies are discussed. The strongest six reflections of the X-ray powder-diffraction pattern [dobs in Å, (I), (hkl)] are: 4.441, (36), (202); 3.144, (77), (214); 3.028, (45), (009); 2.968, (100), (027); 1.782, (32), (330); and 1.713, (32), (1.2.14). The mineral is optically uniaxial (-) with ω 1.734(2) and ε 1.728(2). The Mohs hardness is about 5; density measured on material subject to incipient metamictization is 4.72 g/cm3, as compared to Dcalc = 4.955 g/cm3. The result of electron microprobe analyses of alleged okanoganite-(Y) from the type locality in Okanogan County, Washington, USA, is also presented. We find here also that P > Si at one of the sites, whereas the analytical data of Boiocchi et al. (2004) indicate Si > P. Consequently, the mineral we have analysed is the P analogue of okanoganite-(Y), another new species.
An eye-tracking and visual analogue scale attractiveness evaluation of black space between the maxillary central incisors

ABSTRACT Objective: To study the influence of black space between the maxillary central incisors on the aesthetic visual perception of the face, via eye-tracking and visual analogue scale (VAS). Methods: Black space between the central incisors was created, for both sexes, as follows: control, 1-mm black space, 2-mm black space and 3-mm black space. Ninety raters participated in this study, divided into three groups: 30 laypeople, 30 nonorthodontists, and 30 orthodontists. After the visual calibration of each observer, eight photographs were presented in the Ogama® software concomitant with the use of the hardware The Eye Tribe®. Ogama generated information depending on the eye-tracking of each rater, regarding the time until the first fixation, time of fixation, heatmap, scanpath, and total time of fixation, to evaluate the areas deemed to be of interest according to the raters. Later on, the VAS was used, where each rater evaluated the images in an album on a scale of zero to 10 points. Results: The eyes and mouth were the areas more often noticed by the raters according to the heatmaps, while no significant difference was observed in time until the first fixation between the three groups of raters (p> 0.05). However, regarding the time of fixation on the mouth, a significant difference was observed (p< 0.05) when comparing the three groups. Conclusion: Black space has a negative effect on the aesthetic perception of the face. The amount of attention on the mouth is correspondent to the size of the black space.
Late Gadolinium Enhancement Magnetic Resonance Imaging Evaluation of Post–Atrial Fibrillation Ablation Esophageal Thermal Injury Across the Spectrum of Severity

Background Esophageal thermal injury (ETI) is a byproduct of atrial fibrillation (AF) ablation using thermal sources. The most severe form of ETI is represented by atrioesophageal fistula, which has a high mortality rate. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows identification of ETI. Hence, we sought to evaluate the utility of LGE‐MRI as a method to identify ETI across the entire spectrum of severity. Methods and Results All AF radiofrequency ablations performed at the University of Utah between January 2009 and December 2017 were reviewed. Patients with LGE‐MRI within 24 hours following AF ablation as well as patients who had esophagogastroduodenoscopy in addition to LGE‐MRI were identified. An additional patient with atrioesophageal fistula who had AF ablation at a different institution and had MRI and esophagogastroduodenoscopy at the University of Utah was identified. A total of 1269 AF radiofrequency ablations were identified. ETI severity was classified on the basis of esophageal LGE pattern (none, 60.9%; mild, 27.5%; moderate, 9.9%; severe, 1.7%). ETI resolved in most patients who underwent repeat LGE‐MRI at 3 months. All patients with esophagogastroduodenoscopy‐confirmed ETI had moderate‐to‐severe LGE 24 hours after ablation MRI. Moderate‐to‐severe LGE had 100% sensitivity and 58.1% specificity in detecting ETI, and a negative predictive value of 100%. Atrioesophageal fistula was visualized by both computed tomography and LGE‐MRI in one patient. Conclusions LGE‐MRI is useful in detecting and characterizing ETI across the entire severity spectrum. LGE‐MRI exhibits an extremely high sensitivity and negative predictive value in screening for ETI after AF ablation.
Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)‐induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low‐level viremia HBV‐HCC receiving non‐curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low‐level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV‐HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non‐antiviral group). The definition of low‐level viremia was an HBV DNA level <2000 IU/ml. Kaplan‐Meier curves, log‐rank tests and Cox regression analysis were used for statistical analyses. The median follow‐up duration was 39 months (1–174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child‐Pugh (CP) class and α‐fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2‐year survival. On subgroup analysis, antiviral therapy improved short‐term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low‐level viremia, antiviral therapy yielded short‐term survival benefits, particularly in patients with early‐stage HCC.
Multiple clades of Husavirus in South America revealed by next generation sequencing

Husavirus (HuV) is an unclassified virus of the order Picornavirales that has already been identified worldwide in various locations. The genetic, epidemiological, and pathogenic characteristics are, however, little understood. In children with acute gastroenteritis, this study used next-generation sequencing to recognize unknown sources of viruses. In particular, 251 fecal samples obtained from individuals were sequenced in southern, northeastern, and northern Brazil. all samples were also analyzed using culture methods and parasitological tests to classify other enteric pathogens such as bacteria, parasites, and viruses. 1.9% of the samples tested positive for HuV, for a total of 5 positive children, with a mean age of 2 year, with three males and two females. Detailed molecular characterization of full genomes showed that Brazilian HuVs’ nucleotide divergence is less than 11%. The genetic gap between Brazilian sequences and the closest HuV reported previously, on the other hand, is 18%. The study showed that Brazilian sequences are closely related to the HuV defined in Viet Nam in 2013, further characterization based on phylogenetics. At least two divergent clades of HuV in South America were also seen in the phylogenetic study.
The effect of 4-h versus 6-h time restricted feeding on sleep quality, duration, insomnia severity and obstructive sleep apnea in adults with obesity

Background: Time restricted feeding (TRF) involves deliberately restricting the times during which energy is ingested. Preliminary findings suggest that 8–10-h TRF improves sleep. However, the effects of shorter TRF windows (4–6 h) on sleep, remain unknown. Aims: This study compared the effects of 4-h versus 6-h TRF on sleep quality, duration, insomnia severity and the risk of obstructive sleep apnea. Methods: Adults with obesity (n = 49) were randomized into one of three groups: 4-h TRF (eating only between 3 and 7 p.m.), 6-h TRF (eating only between 1 and 7 p.m.), or a control group (no meal timing restrictions) for 8 weeks. Results: After 8 weeks, body weight decreased (p < 0.001) similarly by 4-h TRF (–3.9 ± 0.4 kg) and 6-h TRF (–3.4 ± 0.4 kg), versus controls. Sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), did not change by 4-h TRF (baseline: 5.9 ± 0.7; week 8: 4.8 ± 0.6) or 6-h TRF (baseline: 6.4 ± 0.8; week 8: 5.3 ± 0.9), versus controls. Wake time, bedtime, sleep duration and sleep onset latency also remained unchanged. Insomnia severity did not change by 4-h TRF (baseline: 4.4 ± 1.0; week 8: 4.7 ± 0.9) or 6-h TRF (baseline: 8.3 ± 1.2; week 8: 5.5 ± 1.1), versus controls. Percent of participants reporting obstructive sleep apnea symptoms did not change by 4-h TRF (baseline: 44%; week 8: 25%) or 6-h TRF (baseline: 47%; week 8: 20%), versus controls. Conclusion: These findings suggest that 4- and 6-h TRF have no effect on sleep quality, duration, insomnia severity, or the risk of obstructive sleep apnea.
Raman Investigation of Photopolymerization Reactions of Single Optically Levitated Microparticles

Raman spectroscopy was used to investigate polymerization reactions in a single micrometer-sized monomer droplet. An Ar+ laser levitated the microparticles and simultaneously excited the Raman scattering. The polymerization reaction was initiated by exposing the monomer droplets to the UV radiation of a mercury arc excitation lamp. The Raman spectrum of the reacting particle was investigated on-line. The results demonstrate that the combination of the technique of optical levitation and Raman spectroscopy allows nondestructive in situ measurements of single particles and is therefore very useful for the study of fundamental processes.