Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of self-microemulsifying drug delivery system for phospholipid complex of telmisartan using D-optimal mixture design

To improve the dissolution behavior of telmisartan (TMS), a poorly water-soluble angiotensin II receptor blocker, TMS-phospholipid complex (TPC) was prepared by solvent evaporation method and characterized by differential scanning calorimetry and powder X-ray diffractometry. The crystalline structure of TMS was transited into an amorphous state by TPC formation. The equilibrium solubility of TPC (1.3–6.1 mg/mL) in various vehicles was about 100 times higher than that of TMS (0.009–0.058 mg/mL). TPC-loaded self-microemulsifying drug delivery system (SMEDDS) formulation was optimized using the D-optimal mixture design with the composition of 14% Capryol 90 (oil; X1), 59.9% tween 80 (surfactant; X2), and 26.1% tetraglycol (cosurfactant; X3) as independent variables, which resulted in a droplet size of 22.17 nm (Y1), TMS solubilization of 4.06 mg/mL (Y2), and 99.4% drug release in 15 min (Y3) as response factors. The desirability function value was 0.854, indicating the reliability and accuracy of optimization; in addition, good agreement was found between the model prediction and experimental values of Y1, Y2, and Y3. Dissolution of raw TMS was poor and pH-dependent, where it had extremely low dissolution (< 1% for 2 h) in water, pH 4, and pH 6.8 media; however, it showed fast and high dissolution (> 90% in 5 min) in pH 1.2 medium. In contrast, the dissolution of the optimized TPC-loaded SMEDDS was pH-independent and reached over 90% within 5 min in all the media tested. Thus, we suggested that phospholipid complex formation and SMEDDS formulation using the experimental design method might be a promising approach to enhance the dissolution of poorly soluble drugs.
Microgravity‐induced hepatogenic differentiation of rBMSCs on board the SJ‐10 satellite

Bone marrow‐derived mesenchymal stem cells (BMSCs) are able to differentiate into functional hepatocytelike cells, which are expected to serve as a potential cell source in regenerative medicine, tissue engineering, and clinical treatment of liver injury. Little is known about whether and how space microgravity is able to direct the hepatogenic differentiation of BMSCs in the actual space microenvironment. In this study, we examined the effects of space microgravity on BMSC hepatogenic differentiation on board the SJ‐10 Recoverable Scientific Satellite. Rat BMSCs were cultured and induced in hepatogenic induction medium for 3 and 10 d in custom‐made space cell culture hardware. Cell growth was monitored periodically in orbit, and the fixed cells and collected supernatants were retrieved back to the Earth for further analyses. Data indicated that space microgravity improves the differentiating capability of the cells by up‐regulating hepatocyte‐specific albumin and cytokeratin 18. The resulting cells tended to be maturated, with an in‐orbit period of up to 10 d. In space, mechanosensitive molecules of β1‐integrin, β‐actin, α‐tubulin, and Ras homolog gene family member A presented enhanced expression, whereas those of cell‐surface glycoprotein CD44, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, vinculin, cell division control protein 42 homolog, and Rho‐associated coiled‐coil kinase yielded reduced expression. Also observed in space were the depolymerization of actin filaments and the accumulation of microtubules and vimentin through the altered expression and location of focal adhesion complexes, Rho guanosine 5′‐triphosphatases, as well as the enhanced exosome‐mediated mRNA transfer. This work furthers the understanding of the underlying mechanisms of space microgravity in directing hepatogenic differentiation of BMSCs. —Lii, D. , Sun, S. , Zhang, F. , Luo, C. , Zheng, L. , Wu, Y. , Li, N. , Zhang, C. , Wang, C. , Chen, Q. , Long, M. Microgravity‐induced hepatogenic differentiation of rBMSCs on board the SJ‐10 satellite. FASEB J. 33, 4273–4286 (2019). www.fasebj. org
Development and validation of a preoperative prediction model for colorectal cancer T-staging based on MDCT images and clinical information

Objectives This study aimed to establish and evaluate the efficacy of a prediction model for colorectal cancer T-staging. Results T-staging was positively correlated with the level of carcinoembryonic antigen (CEA), expression of carbohydrate antigen 19-9 (CA19-9), wall deformity, blurred outer edges, fat infiltration, infiltration into the surrounding tissue, tumor size and wall thickness. Age, location, enhancement rate and enhancement homogeneity were negatively correlated with T-staging. The predictive results of the model were consistent with the pathological gold standard, and the kappa value was 0.805. The total accuracy of staging improved from 51.04% to 86.98% with the proposed model. Materials and Methods The clinical, imaging and pathological data of 611 patients with colorectal cancer (419 patients in the training group and 192 patients in the validation group) were collected. A spearman correlation analysis was used to validate the relationship among these factors and pathological T-staging. A prediction model was trained with the random forest algorithm. T staging of the patients in the validation group was predicted by both prediction model and traditional method. The consistency, accuracy, sensitivity, specificity and area under the curve (AUC) were used to compare the efficacy of the two methods. Conclusions The newly established comprehensive model can improve the predictive efficiency of preoperative colorectal cancer T-staging.
Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria

Significance This study draws on the power of superresolution microscopy to investigate how metabolons behave near different subcellular components. We revealed an interdependent relationship among purinosomes, mitochondria, and microtubules. This further suggests a role for each in maximizing purine production in times of high intracellular demand. With the increasing number of reported metabolons, this study has uncovered a potential general strategy for how metabolons use subcellular networks to facilitate metabolic trade between themselves and other cellular organelles. To meet their purine demand, cells activate the de novo purine biosynthetic pathway and transiently cluster the pathway enzymes into metabolons called purinosomes. Recently, we have shown that purinosomes were spatially colocalized with mitochondria and microtubules, yet it remained unclear as to what drives these associations and whether a relationship between them exist. Here, we employed superresolution imaging methods to describe purinosome transit in the context of subcellular localization. Time-resolved imaging of purinosomes showed that these assemblies exhibit directed motion as they move along a microtubule toward mitochondria, where upon colocalization, a change in purinosome motion was observed. A majority of purinosomes colocalized with mitochondria were also deemed colocalized with microtubules. Nocodazole-dependent microtubule depolymerization resulted in a loss in the purinosome–mitochondria colocalization, suggesting that the association of purinosomes with mitochondria is facilitated by microtubule-directed transport, and thereby supporting our notion of an interdependency between these subcellular components in maximizing purine production through the de novo purine biosynthetic pathway.
Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3‐internal tandem duplication genotypes

The revised 2017 European LeukemiaNet (ELN) classification (ELN‐2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms‐like tyrosine kinase 3 (FLT3)–internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN‐2017 in comparison with ELN‐2010 in younger patients with AML has not been validated to date.
Clinical Rating Scales for Urinary Symptoms in Parkinson Disease: Critique and Recommendations

The prevalence of lower urinary tract symptoms (LUTS) is high in Parkinson's disease (PD). These problems negatively affect quality of life and include both storage and voiding problems. The International Parkinson and Movement Disorder Society established a task force to review clinical rating scales/questionnaires for the assessment of urinary symptoms in PD.
Moving table magnetic particle imaging: a stepwise approach preserving high spatio-temporal resolution

Abstract. Magnetic particle imaging (MPI) is a highly sensitive imaging method that enables the visualization of magnetic tracer materials with a temporal resolution of more than 46 volumes per second. In MPI, the size of the field of view (FoV) scales with the strengths of the applied magnetic fields. In clinical applications, those strengths are limited by peripheral nerve stimulation, specific absorption rates, and the requirement to acquire images of high spatial resolution. Therefore, the size of the FoV is usually a few cubic centimeters. To bypass this limitation, additional focus fields and/or external object movements can be applied. The latter approach is investigated. An object is moved through the scanner bore one step at a time, whereas the MPI scanner continuously acquires data from its static FoV. Using a 3-D phantom and dynamic 3-D in vivo data, it is shown that the data from such a moving table experiment can be jointly reconstructed after reordering the data with respect to the stepwise object shifts and heart beat phases.
Increased Vulnerability to Atrial Fibrillation Is Associated With Increased Susceptibility to Alternans in Old Sheep

Background Atrial fibrillation (AF) is common in the elderly, but rare in the young; however, the changes that occur with age that promote AF are not fully understood. Action potential (AP) alternans may be involved in the initiation of AF. Using a translationally relevant model, we investigated whether age‐associated atrial vulnerability to AF was associated with susceptibility to AP alternans. Methods and Results AF was induced in conscious young and old sheep using 50 Hz burst pacing. Old sheep were more vulnerable to AF. Monophasic and cellular APs were recorded from the right atrium in vivo and from myocytes isolated from the left and right atrial appendages. AP alternans occurred at lower stimulation frequencies in old sheep than young in vivo (old, 3.0±0.1 Hz; young, 3.3±0.1 Hz; P<0.05) and in isolated myocytes (old, 1.6±0.1 Hz; young, 2.0±0.1 Hz; P<0.05). Simultaneous recordings of [Ca2+]i and membrane potential in myocytes showed that alternans of APs and [Ca2+]i often occurred together. However, at low stimulation rates [Ca2+]i alternans could occur without AP alternans, whereas at high stimulation rates AP alternans could still be observed despite disabling Ca2+ cycling using thapsigargin. Conclusions We have shown, for the first time in a large mammalian model, that aging is associated with increased duration of AF and susceptibility to AP alternans. We suggest that instabilities in Ca2+ handling initiate alternans at low stimulation rates, but that AP restitution alone can sustain alternans at higher rates.
Non-invasive Amide Proton Transfer Imaging and ZOOM Diffusion-Weighted Imaging in Differentiating Benign and Malignant Thyroid Micronodules

Background: Pre-operative non-invasive differentiation of benign and malignant thyroid nodules is difficult for doctors. This study aims to determine whether amide proton transfer (APT) imaging and zonally oblique multi-slice (ZOOM) diffusion-weighted imaging (DWI) can provide increased accuracy in differentiating benign and malignant thyroid nodules. Methods: This retrospective study was approved by the institutional review board and included 60 thyroid nodules in 50 patients. All of the nodules were classified as malignant (n = 21) or benign (n = 39) based on pathology. It was meaningful to analyze the APT and apparent diffusion coefficient (ADC) values of the two groups by independent t-test to identify the benign and malignant thyroid nodules. The relationship between APT and ZOOM DWI was explored through Pearson correlation analysis. The diagnostic efficacy of APT and ZOOM DWI in determining if thyroid nodules were benign or malignant was compared using receiver operating characteristic (ROC) curve analysis. Results: The mean APTw value of the benign nodules was 2.99 ± 0.79, while that of the malignant nodules was 2.14 ± 0.73. Additionally, there was a significant difference in the APTw values of the two groups (P < 0.05). The mean ADC value of the benign nodules was 1.84 ± 0.41, and was significantly different from that of the malignant nodules, which was 1.21 ± 0.19 (P < 0.05). Scatter point and Pearson test showed a moderate positive correlation between the APT and ADC values (P < 0.05). The ROC curve showed that the area under the curve (AUC) value of ZOOM DWI (AUC = 0.937) was greater than that of APT (AUC = 0.783) (P = 0.028). Conclusion: APT and ZOOM DWI imaging improved the accuracy of distinguishing between benign and malignant thyroid nodules. ZOOM DWI is superior to APTw imaging (Z = 2.198, P < 0.05).
In vivo validation of cerebral near-infrared spectroscopy: a review

Abstract. We summarize the available in vivo validation of cerebral near-infrared spectroscopy (NIRS) oximetry to inform future in vivo validation strategies. In particular, to establish a way forward in the assessment of NIRS instrumentation for future randomized trials, a systematic literature search is performed. The records are screened and abstracts are assessed to select studies fulfilling our inclusion criteria. Twenty-two pediatric and 28 adult studies are analyzed after exclusion of three articles in each group. All studies compare regional cerebral tissue oxygenation measured by cerebral NIRS to invasive measurement of central or jugular venous oxygen saturation. In studies without Bland–Altman plots, we extracted data from scatter plots enabling estimation of mean difference (MD), standard deviation (SD), and limits of agreement (LOA). To assess the agreement between rStO2 (regional cerebral tissue oxygenation) estimated by NIRS and by blood samples, weighted averages of the MDs and SDs from each study are calculated. We found a fair agreement between the overall mean of cerebral tissue oxygenation and the mean of a reference value measured by co-oximetry whatever NIRS instrument or site of blood sampling used. Cerebral oxygenation overestimates the reference at low values, some instruments apparently more than others. Thus, a high degree of scatter and a lack of a good reference method complicate in vivo validation of NIRS. It is difficult to draw any firm conclusions despite the large number of studies, and the result of this review leaves us questioning if more of such validation studies of cerebral NIRS oximetry are really needed. Furthermore, the combination of lack of validation and poor repeatability is an important issue when designing a randomized clinical trial of implementing cerebral NIRS oximetry into clinical care.
Force analysis of shoulder joint muscles in the early phase of brain stroke.

PURPOSE Upper limb impairment in the early phase of brain stroke is one of the key problems in rehabilitation. An estimation of muscle force can be a helpful factor for functional improvement after a stroke. The primary goals of this study were to determine the muscles with the lowest force in the affected (A) and non-affected (non-A) upper limb. Moreover, the differences between men and women were compared and these values were correlated with age. METHODS One hundred (n = 35 female, n = 65 male) post-stroke pa- tients met the inclusion criteria. The mean age of the study participants was 66.1 years. Muscle force for external and internal rotators of shoulder was measured with handheld dynamometer. Moreover, the correlation coefficients for differences in muscular force with the patient's age were estimated. RESULTS Our study reports that the force of the (A) side in relation to the (non-A) was by 37% weaker. We observed about a 40% decrease in the force of the shoulder's external rotation (female - 42%; male - 41%) and shoulder's flexion (by 38% - female; 40% - male). Significant correlations between the muscle force and the age of post-stroke patients were also found. It was concluded that about 4 weeks after the first stroke in the patient's life, the external rotators are the most affected group of shoulder muscles. CONCLUSIONS Neither sex nor the side of the ischemic brain injury influence the muscle force, whereas age determines both muscle force and muscle force deficits. Older post-stroke patients demonstrate fewer deficits in muscle strength than younger ones.
Accessibility and Applicability of Currently Available e-Mental Health Programs for Depression for People With Poststroke Aphasia: Scoping Review

Background Depression affects approximately 60% of people with aphasia 1 year post stroke and is associated with disability, lower quality of life, and mortality. Web-delivered mental health (e-mental health) programs are effective, convenient, and cost-effective for the general population and thus are increasingly used in the management of depression. However, it is unknown if such services are applicable and communicatively accessible to people with poststroke aphasia. Objective The aim of this study was to identify freely available e-mental health programs for depression and determine their applicability and accessibility for people with poststroke aphasia. Methods A Web-based search was conducted to identify and review freely available e-mental health programs for depression. These programs were then evaluated in terms of their (1) general features via a general evaluation tool, (2) communicative accessibility for people with aphasia via an aphasia-specific communicative accessibility evaluation tool, and (3) empirical evidence for the general population and stroke survivors with and without aphasia. The program that met the most general evaluation criteria and aphasia-specific communicative accessibility evaluation criteria was then trialed by a small subgroup of people with poststroke aphasia. Results A total of 8 programs were identified. Of these, 4 had published evidence in support of their efficacy for use within the general population. However, no empirical evidence was identified that specifically supported any programs’ use for stroke survivors with or without aphasia. One evidence-based program scored at least 80% (16/19 and 16/20, respectively) on both the general and aphasia-specific communicative accessibility evaluation tools and was subject to a preliminary trial by 3 people with poststroke aphasia. During this trial, participants were either unable to independently use the program or gave it low usability scores on a post-trial satisfaction survey. On this basis, further evaluation was considered unwarranted. Conclusions Despite fulfilling majority of the general evaluation and aphasia-specific evaluation criteria, the highest rated program was still found to be unsuitable for people with poststroke aphasia. Thus, e-mental health programs require substantial redevelopment if they are likely to be useful to people with poststroke aphasia.
High-Fidelity Modelling Methodology of Light-Limited Photosynthetic Production in Microalgae

Reliable quantitative description of light-limited growth in microalgae is key to improving the design and operation of industrial production systems. This article shows how the capability to predict photosynthetic processes can benefit from a synergy between mathematical modelling and lab-scale experiments using systematic design of experiment techniques. A model of chlorophyll fluorescence developed by the authors [Nikolaou et al., J Biotechnol 194:91–99, 2015] is used as starting point, whereby the representation of non-photochemical-quenching (NPQ) process is refined for biological consistency. This model spans multiple time scales ranging from milliseconds to hours, thus calling for a combination of various experimental techniques in order to arrive at a sufficiently rich data set and determine statistically meaningful estimates for the model parameters. The methodology is demonstrated for the microalga Nannochloropsis gaditana by combining pulse amplitude modulation (PAM) fluorescence, photosynthesis rate and antenna size measurements. The results show that the calibrated model is capable of accurate quantitative predictions under a wide range of transient light conditions. Moreover, this work provides an experimental validation of the link between fluorescence and photosynthesis-irradiance (PI) curves which had been theoricized.
Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging

ABSTRACT Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW +10 reviewed advances in understanding of the critical changes in hypothalamic–pituitary–ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results STRAW +10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage −3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage −1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions STRAW +10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW +10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.
Thermal creep and the skyrmion Hall angle in driven skyrmion crystals

We numerically examine thermal effects on the skyrmion Hall angle for driven skyrmions interacting with quenched disorder. We identify a creep regime in which motion occurs via intermittent jumps between pinned and flowing states. Here the skyrmion Hall angle is zero since the skyrmions have time to relax into equilibrium positions in the pinning sites, eliminating the side-jump motion induced by the Magnus force. At higher drives we find a crossover to a viscous flow regime where the skyrmion Hall angle is finite and increases with increasing drive or temperature. Our results are in agreement with recent experiments which also show a regime of finite skyrmion velocity with zero skyrmion Hall angle crossing over to a viscous flow regime with a skyrmion Hall angle that increases with drive.