Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer

Purpose: We evaluated the association between molecular subtypes of advanced gastric cancer (AGC) and the efficacy of standard chemotherapy or immune checkpoint inhibitors. Experimental Design: Patients with AGC who received systemic chemotherapy from October 2015 to July 2018 with available molecular features were analyzed. We investigated the efficacy of standard first- (fluoropyrimidine + platinum ± trastuzumab) and second-line (taxanes ± ramucirumab) chemotherapy, and subsequent anti–PD-1 therapy in patients with four molecular subtypes: MMR-D (mismatch repair deficient), EBV+, HER2+, and all negative. Results: 410 patients were analyzed: MMR-D 5.9%, EBV+ 4.1%, HER2+ 13.7%, and all negative 76.3%. In 285 patients who received standard first-line chemotherapy, the median progression-free survival (PFS) times were 4.2, 6.0, 7.5, and 7.6 months and the objective response rates (ORR) were 31%, 62%, 60%, and 49% in MMR-D, EBV+, HER2+, and all-negative subtypes, respectively. Multivariate analysis showed shorter PFS in MMR-D versus all-negative patients [HR, 1.97; 95% CIs, 1.09–3.53; P = 0.022]. In second-line setting, there were no significant differences in efficacy. In 110 patients who received anti–PD-1 therapy, median PFS times were 13.0, 3.7, 1.6, and 1.9 months and the ORRs were 58%, 33%, 7%, and 13%, respectively. Twelve patients with MMR-D received subsequent anti–PD-1 therapy and showed longer PFS compared with that in 10 (83%) patients who received earlier-line chemotherapy. Conclusions: MMR-D might result in shorter PFS with first-line chemotherapy for AGC. Subsequent anti–PD-1 therapy achieved higher ORR and longer PFS than prior chemotherapy in most patients with MMR-D, supporting the earlier use of immune checkpoint inhibitors.
Selection through Individualized Review: A Report on Phase IV of the Admissions Models Project.

The College Board is a not-for-profit membership association whose mission is to connect students to college success and opportunity. Founded in 1900, the association is composed of more than 4,500 schools, colleges, universities, and other educational organizations. Each year, the College Board serves over three million students and their parents, 23,000 high schools, and 3,500 colleges through major programs and services in college admissions, guidance, assessment, financial aid, enrollment, and teaching and learning. Among its best-known programs are the SAT ® , the PSAT/NMSQT ® , and the Advanced Placement Program ® (AP ®). The College Board is committed to the principles of excellence and equity, and that commitment is embodied in all of its programs, services, activities, and concerns.
Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer’s disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 μM Aβ1-42 and 50 μM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.
A new approach to both high safety and high performance of lithium-ion batteries

We present a new battery with high safety and performance, overcoming the materials-based conflict of reactivity versus stability. We present a novel concept to achieve high performance and high safety simultaneously by passivating a Li-ion cell and then self-heating before use. By adding a small amount of triallyl phosphate in conventional electrolytes, we show that resistances of the passivated cells can increase by ~5×, thereby ensuring high safety and thermal stability. High power before battery operation is delivered by self-heating to an elevated temperature such as 60°C within tens of seconds. The present approach of building a resistive cell with highly stable materials and then delivering high power on demand through rapid thermal stimulation leads to a revolutionary route to high safety when batteries are not in use and high battery performance upon operation.
Image-Based Phenotyping of Flowering Intensity in Cool-Season Crops

The timing and duration of flowering are key agronomic traits that are often associated with the ability of a variety to escape abiotic stress such as heat and drought. Flowering information is valuable in both plant breeding and agricultural production management. Visual assessment, the standard protocol used for phenotyping flowering, is a low-throughput and subjective method. In this study, we evaluated multiple imaging sensors (RGB and multiple multispectral cameras), image resolution (proximal/remote sensing at 1.6 to 30 m above ground level/AGL), and image processing (standard and unsupervised learning) techniques in monitoring flowering intensity of four cool-season crops (canola, camelina, chickpea, and pea) to enhance the accuracy and efficiency in quantifying flowering traits. The features (flower area, percentage of flower area with respect to canopy area) extracted from proximal (1.6–2.2 m AGL) RGB and multispectral (with near infrared, green and blue band) image data were strongly correlated (r up to 0.89) with visual rating scores, especially in pea and canola. The features extracted from unmanned aerial vehicle integrated RGB image data (15–30 m AGL) could also accurately detect and quantify large flowers of winter canola (r up to 0.84), spring canola (r up to 0.72), and pea (r up to 0.72), but not camelina or chickpea flowers. When standard image processing using thresholds and unsupervised machine learning such as k-means clustering were utilized for flower detection and feature extraction, the results were comparable. In general, for applicability of imaging for flower detection, it is recommended that the image data resolution (i.e., ground sampling distance) is at least 2–3 times smaller than that of the flower size. Overall, this study demonstrates the feasibility of utilizing imaging for monitoring flowering intensity in multiple varieties of evaluated crops.
Accumulation of Ascorbic Acid in Tomato Cell Culture: Influence of the Genotype, Source Explant and Time of In Vitro Cultivation

The production and commercialization of natural antioxidants is gaining increasing importance due to their wide range of biological effects and applications. In vitro cell culture is a valuable source of plant bioactive compounds, especially those highly dependent on environmental factors. Nonetheless, research on the accumulation in plant cultured cells of water-soluble antioxidant vitamins, such as the ascorbic acid (AsA), is very limited. Tomato fruits are a main dietary source of vitamin C and in this work, we explored the potential of in vitro cultured cells for AsA accumulation. Specifically, using a full factorial design, we examined the effect of the source explant, the time in tissue culture and the genetic difference present in two Introgression Line (IL7-3 and IL12-4) that harbor Quantitative Trait Loci (QTLs) for ascorbic acid in fruits. Moreover, we performed an expression analysis of genes involved in AsA metabolism to highlight the molecular mechanisms that can account for the difference between fruit explants and calli. Our work indicated that cultured tomato cells accumulate AsA well beyond the amount present in fruits and that the three factors under investigation and their interaction significantly influence AsA accumulation. The time in tissue culture is the main single factor and, different from the expectations for secondary metabolites, explants from unripe, mature green fruits provided the highest increase in AsA. Moreover, in controlled conditions the genetic differences between the ILs and the control genotype are less relevant for calli cultivated for longer time. Our work showed the potential of tomato cell culture to produce AsA and prompt further refinements towards its possible large-scale exploitation.
Assessment of intermediate (process) outcomes in the BARI 2D clinical trial

BARI 2D is a 2-by-2 factorial clinical trial identifying optimal therapies for patients with documented stable coronary artery disease and Type 2 Diabetes. Previous results of the BARI 2D study indicated that there was a non-significant association between the therapies and 5-year survival outcomes. Our study hypothesizes that several intermediate variables may exist whose trajectories of improving or worsening in response to treatments act against each other leading to the previous non-significant associations. Before randomization, the participants were stratified to two types of revascularization - PCI or CABG. Then each participant was randomized to receive one cardiac therapy (prompt revascularization plus intensive medicine or intensive medicine alone), and also one glycemic therapy (insulin-sensitization or insulin-provision). Five intermediate outcomes BMI, SBP, HDL, LDL and Hba1c were studied. Linear regression was conducted to assess the difference of each intermediate outcome between therapies at Year 1 and at Year 3. Also conducted was a comparison of the trajectories over time by therapies using longitudinal repeated measures mixed models. In 2368 patients (mean age 62.4 years), the improvement of the intermediate outcomes was generally notable over the first year, and then slowly diminished over time. At both Year 1 and 3, insulin-provision resulted in higher BMI and Hba1c, and lower HDL than insulin-sensitization, irrespective of the assigned cardiac therapy and revascularization stratum. Longitudinally, insulin-provision resulted in higher Hba1c, irrespective of the assigned cardiac therapy and revascularization stratum; and an interaction effect of the cardiac and glycemic therapies on BMI was found in CABG stratum. These results suggested that insulin-sensitization therapy is superior to insulin-provision therapy generally. In CABG stratum, the effect of cardiac therapy on BMI depends on the assignment of glycemic therapy. The public health significance of this study is that, though the cancelling-out hypotheses for these five intermediate variables may be overly optimistic, it involves a potentially illuminating perspective to explain the mechanisms through which the BARI 2D treatment therapies affect multiple intermediate outcomes. This in turn could also help inform and enhance the targeted adjuvant therapies, thus resulting in improved survival outcomes by better focusing on controlling the harmful intermediate variables.
A Bayesian spatial shared component model for identifying crime-general and crime-specific hotspots

ABSTRACT The spatial patterning of crime hotspots provides place-based information for the design, allocation, and implementation of crime prevention policies and programmes. However, most spatial hotspot identification methods are univariate, analyse a single crime type, and do not consider if hotspots are shared amongst multiple crime types. This study applies a Bayesian spatial shared component model to identify crime-general and crime-specific hotspots for violent crime and property crime at the small-area scale. The spatial shared component model jointly analyzes both violent crime and property crime and separates the area-specific risks of each crime type into one shared component, which captures the underlying crime-general spatial pattern common to both crime types, and one type-specific component, which captures the crime-specific spatial pattern that diverges from the shared pattern. Crime-general and crime-specific hotspots are classified based on the posterior probability estimates of the shared and type-specific components, respectively. Results show that the crime-general pattern explains approximately 81% of the total variation of violent crime and 70% of the total variation of property crime. Crime-general hotspots are found to be more frequent than crime-specific hotspots, and property crime-specific hotspots are more frequent than violent crime-specific hotspots. Crime-general and crime-specific hotspots are areas that may be targeted with comprehensive initiatives designed for multiple crime types or specialized initiatives designed for a single crime type, respectively.
Nanosecond pulsed electric fields induce the integrated stress response via reactive oxygen species-mediated heme-regulated inhibitor (HRI) activation

The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS.
Improvement of Mechanical and Self-Healing Properties for Polymethacrylate Derivatives Containing Maleimide Modified Graphene Oxide

In this paper, a self-healable nanocomposite based on the Diels-Alder reaction is developed. A graphene-based nanofiller is introduced to improve the self-healing efficiency, as well as the mechanical properties of the nanocomposite. Graphene oxide (GO) is modified with maleimide functional groups, and the maleimide-modified GO (mGO) enhanced the compatibility of the polymer matrix and nanofiller. The tensile strength of the nanocomposite containing 0.030 wt% mGO is improved by 172%, compared to that of a polymer film incorporating both furan-functionalized polymer and bismaleimide without any nanofiller. Moreover, maleimide groups of the surface on mGO participate in the Diels-Alder reaction, which improves the self-healing efficiency. The mechanical and self-healing properties are significantly improved by using a small amount of mGO.
Aqueous humour proteins and treatment outcomes of anti-VEGF therapy in neovascular age-related macular degeneration

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = −0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P < 0.001) and IL-10 (β coefficient = −0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = −0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.
The Effect of Waste Engine Oil and Waste Polyethylene on UV Aging Resistance of Asphalt

Waste engine oil (WEO) and waste polyethylene (WPE) are two common wastes, which are easy to pollute the environment. As the primary material in road construction, natural asphalt is a non-renewable energy source and asphalt is vulnerable to ultraviolet (UV) radiation during the service life. It results in degradation of asphalt pavement performance. In this paper, 2 wt % to 8 wt % of WEO and WPE were used to modify asphalts and the UV aging simulation experiment was carried out. The physical parameters of asphalts before the UV aging experiment show that the asphalt containing 4 wt % WPE and 6 wt % WEO mixture (4 wt % WPE + 6 wt % WEO) has similar physical properties with that of the matrix asphalt. Besides, gel permeation chromatography (GPC) verifies that the molecular weight distribution of the asphalt containing 4 wt % WPE + 6 wt % WEO is close to that of the matrix asphalt. The storage stability test shows that 4 wt % WPE + 6 wt % WEO has good compatibility with the matrix asphalt. The functional groups and micro-morphology of asphalts before and after the UV aging experiment were investigated by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). FTIR results display that 4 wt % WPE + 6 wt % WEO can effectively reduce the formation of carbonyl and sulfoxide functional groups. AFM shows that 4 wt % WPE + 6 wt % WEO can also retard the formation of a “bee-like” structure in asphalt after the UV aging experiment. Based on the above results, it can be concluded that WEO and WPE mixture can replace part of asphalt and improve the UV aging resistance of asphalt.
High-intensity resistance training in newly diagnosed sarcoidosis- an exploratory study of effects on lung function, muscle strength, fatigue, dyspnea, health-related quality of life and lung immune cells

ABSTRACT Background: High-intensity resistance training is unexplored in untreated patients with newly diagnosed sarcoidosis. Objectives: To evaluate the effects of high-intensity resistance training on lung function, muscle strength, fatigue, dyspnea, health-related impairments, and lung immune cells. Methods: Eleven untreated patients with newly diagnosed sarcoidosis performed high-intensity resistance training at an intensity of 80% of 1 Repetition Maximum (RM) twice a week and daily inspiratory muscle training at regular intensity for 12 weeks. Assessment with spirometry, chest X-ray, questionnaires, and BAL (bronchoalveolar lavage) cells was performed before and in close adjacent to completed training. A final third assessment except bronchoscopy was performed at an average 5 months after the training period. Results: The training was well tolerated and muscular strength increased significantly while fatigue, dyspnea, and health-related impairments decreased, though not significantly in all measures. Mean percentage of lung lymphocytes decreased (p = 0.006). Conclusions: High-intensity resistance training and inspiratory muscle training at regular intensity in patients with newly diagnosed sarcoidosis led to improvements in muscular strength without adverse events and seems to be a non-invasive attractive way to improve fatigue, dyspnea, and quality of life. Analysis of lung immune cells possibly indicated a decreased inflammatory activity. These results provide a basis for larger randomized trials.
Ileal and total tract digestibility and nitrogen utilisation in blue fox (Vulpes lagopus) fed low-protein diets supplemented with DL-methionine and L-histidine

ABSTRACT To formulate low-protein diets for blue foxes with sufficient amounts of amino acids (AA), AA digestibility and AA requirements of the animals are crucial information. Therefore, a digestibility and nitrogen (N) balance trial was conducted with 20 blue foxes to determine the macronutrient and AA digestibility and N utilisation in low-protein diets supplemented with DL-methionine (Met) and L-histidine (His). In addition, plasma urea and plasma AA were measured. The diets were designated as P24 (control), P20, P20M, P16M and P16MH and contained energy from digestible crude protein (DCP) at 24%, 20% or 16% of total dietary metabolisable energy (ME). The 20% protein level was fed with or without Met and the 16% protein level was fed with Met and with or without His. The apparent total-tract digestibility (ATTD) of crude protein linearly decreased with decreasing dietary protein level. The ATTD of dry matter, organic matter and crude carbohydrates increased when wheat starch was added as a replacement for protein. The apparent ileal digestibility (AID) and ATTD methods were compared to determine the AA digestibility. The decreasing dietary protein supply decreased the ATTD of most of the AA: threonine, tryptophan (Trp), valine, alanine (Ala), aspartic acid (Asp), glutamic acid, glycine (Gly), proline (Pro), serine (Ser) and total AA. The AID of the AA was constant between diets. Diverging AA showed higher or lower digestibility when determined in the AID or ATTD methods. Isoleucine, lysine, Met, Ala and tyrosine showed higher levels of AID. Arginine, His, cysteine (Cys), Trp, Asp, Gly, Pro and Ser showed higher levels of ATTD, which may reflect the net loss of these AA in the large intestine. Met and His supplementation improved the ATTD and AID of the AA in question, respectively, but did not affect the other variables examined. N retention did not differ between diets and renal N excretion decreased with decreasing protein level; thus N utilisation improved. It was concluded that the protein supply and AA composition in low-protein diets with supplemented Met were adequate for adult blue foxes, since the lower protein supply improved N utilisation and did not affect N retention. However, His supplementation failed to reach the designed level and therefore showed no clear results.