Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Control Balancing Cell Proliferation and Inflammation is Crucial for an Effective Immune Response to Malaria

Malaria has a complex pathology with varying manifestations and symptoms, effects on host tissues, and different degrees of severity and ultimate outcome, depending on the causative Plasmodium pathogen and host species. Previously, we compared the peripheral blood transcriptomes of two macaque species (Macaca mulatta and Macaca fascicularis) in response to acute primary infection by Plasmodium knowlesi. Although these two species are very closely related, the infection in M. mulatta is fatal, unless aggressively treated, whereas M. fascicularis develops a chronic, but tolerable infection in the blood. As a reason for this stark difference, our analysis suggests delayed pathogen detection in M. mulatta followed by extended inflammation that eventually overwhelms this monkey’s immune response. By contrast, the natural host M. fascicularis detects the pathogen earlier and controls the inflammation. Additionally, M. fascicularis limits cell proliferation pathways during the log phase of infection, presumably in an attempt to control inflammation. Subsequent cell proliferation suggests a cell-mediated adaptive immune response. Here, we focus on molecular mechanisms underlying the key differences in the host and parasite responses and their coordination. SICAvar Type 1 surface antigens are highly correlated with pattern recognition receptor signaling and important inflammatory genes for both hosts. Analysis of pathogen detection pathways reveals a similar signaling mechanism, but with important differences in the glutamate G-protein coupled receptor (GPCR) signaling pathway. Furthermore, differences in inflammasome assembly processes suggests an important role of S100 proteins in balancing inflammation and cell proliferation. Both differences point to the importance of Ca2+ homeostasis in inflammation. Additionally, the kynurenine-to-tryptophan ratio, a known inflammatory biomarker, emphasizes higher inflammation in M. mulatta during log phase. Transcriptomics-aided metabolic modeling provides a functional method for evaluating these changes and understanding downstream changes in NAD metabolism and aryl hydrocarbon receptor (AhR) signaling, with enhanced NAD metabolism in M. fascicularis and stronger AhR signaling in M. mulatta. AhR signaling controls important immune genes like IL6, IFNγ and IDO1. However, direct changes due to AhR signaling could not be established due to complicated regulatory feedback mechanisms associated with the AhR repressor (AhRR). A complete understanding of the exact dynamics of the immune response is difficult to achieve. Nonetheless, our comparative analysis provides clear suggestions of processes that underlie an effective immune response. Thus, our study identifies multiple points of intervention that are apparently responsible for a balanced and effective immune response and thereby paves the way toward future immune strategies for treating malaria.
Exploring Behavioral Patterns for Data-Driven Modeling of Learners' Individual Differences

Educational data mining research has demonstrated that the large volume of learning data collected by modern e-learning systems could be used to recognize student behavior patterns and group students into cohorts with similar behavior. However, few attempts have been done to connect and compare behavioral patterns with known dimensions of individual differences. To what extent learner behavior is defined by known individual differences? Which of them could be a better predictor of learner engagement and performance? Could we use behavior patterns to build a data-driven model of individual differences that could be more useful for predicting critical outcomes of the learning process than traditional models? Our paper attempts to answer these questions using a large volume of learner data collected in an online practice system. We apply a sequential pattern mining approach to build individual models of learner practice behavior and reveal latent student subgroups that exhibit considerably different practice behavior. Using these models we explored the connections between learner behavior and both, the incoming and outgoing parameters of the learning process. Among incoming parameters we examined traditionally collected individual differences such as self-esteem, gender, and knowledge monitoring skills. We also attempted to bridge the gap between cluster-based behavior pattern models and traditional scale-based models of individual differences by quantifying learner behavior on a latent data-driven scale. Our research shows that this data-driven model of individual differences performs significantly better than traditional models of individual differences in predicting important parameters of the learning process, such as performance and engagement.
Proteolysis-Targeting Chimera (PROTAC): Is the Technology Looking at the Treatment of Brain Tumors?

Post-translational modifications, such as ubiquitylation, need to be tightly controlled to guarantee the accurate localization and activity of proteins. Ubiquitylation is a dynamic process primarily responsible for proteasome-mediated degradation of substrate proteins and crucial for both normal homeostasis and disease. Alterations in ubiquitylation lead to the upregulation of oncoproteins and/or downregulation of tumor suppressors, thus concurring in tumorigenesis. PROteolysis-TArgeting Chimera (PROTAC) is an innovative strategy that takes advantage by the cell’s own Ubiquitin-Proteasome System (UPS). Each PROTAC molecule is composed by a ligand that recruits the target protein of interest (POI), a ligand specific for an E3 ubiquitin ligase enzyme, and a linker that connects these units. Upon binding to the POI, the PROTAC recruits the E3 inducing ubiquitylation-dependent proteasome degradation of the POI. To date, PROTAC technology has entered in clinical trials for several human cancers. Here, we will discuss the advantages and limitations of PROTACs development and safety considerations for their clinical application. Furthermore, we will review the potential of PROTAC strategy as therapeutic option in brain tumor, focusing on glioblastoma.
Visual Search in Naturalistic Scenes Reveals Impaired Cognitive Processing Speed in Multiple Sclerosis

Background Standardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs. impaired information processing speed measured by the Symbol Digit Modalities Test (SDMT) differ in their visual search behavior during ecologically valid tasks reflecting everyday activities. Methods Forty-three patients with relapsing-remitting MS enrolled in an eye-tracking experiment consisting of a visual search task with naturalistic images. Patients were grouped into “impaired” and “unimpaired” according to their SDMT performance. Reaction time, accuracy and eye-tracking parameters were measured. Results The groups did not differ regarding age, gender, and visual acuity. Patients with impaired SDMT (cut-off SDMT-z-score < −1.5) performance needed more time to find and fixate the target (q = 0.006). They spent less time fixating the target (q = 0.042). Impaired patients had slower reaction times and were less accurate (both q = 0.0495) even after controlling for patients' upper extremity function. Exploratory analysis revealed that unimpaired patients had higher accuracy than impaired patients particularly when the announced target was in unexpected location (p = 0.037). Correlational analysis suggested that SDMT performance is inversely linked to the time to first fixation of the target only if the announced target was in its expected location (r = −0.498, p = 0.003 vs. r = −0.212, p = 0.229). Conclusion Dysfunctional visual search behavior may be one of the mechanisms translating cognitive deficits into difficulties in everyday tasks in MS patients. Our results suggest that cognitively impaired patients search their visual environment less efficiently and this is particularly evident when top-down processes have to be employed.
Effect of Primary Tumor Location on Second- or Later-Line Treatment With Anti-Epidermal Growth Factor Receptor Antibodies in Patients With Metastatic Colorectal Cancer: A Retrospective Multi-Center Study

Background Current guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC. Methods Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test. Results Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005). Conclusions To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.
Production of Hydroxymethylfurfural Derivatives From Furfural Derivatives via Hydroxymethylation

Hydroxymethylfurfural (HMF) derivatives such as 2,5-bis(hydroxymethyl)furan (BHMF) and furandicarboxylic acid (FDCA) are promising alternative of fossil-based diols and dicarboxylic acids for synthesis of polyesters such as polyethylene terephthalate (PET). However, high cost for preparing HMF from biomass discourages the commercialization of HMF-derived polyesters. Since producing furfural (FUR) from five-carbon sugars (e.g., xylose) via dehydration is an inexpensive and commercialized process, we herein reported a method to synthesize BHMF derivatives (5-(ethoxymethyl)furan-2-methanol (EMFM), 2,5-bis(hydroxymethyl)furan monoacetate (BHMFM) and 2,5-bis(hydroxymethyl)furan diacetate (BHMFD) from furfural derivatives, i.e., (2-(ethoxymethyl)furan (EMF) and furfuryl acetate (FA)). To avoid strong acid-induced side reactions (e.g., furan ring opening, condensation and carbonization), two reaction systems, i.e., a low-concentration HCl aqueous solution combined with formaldehyde and anhydrous acetic acid combined with paraformaldehyde, were found to be suitable for such a hydroxymethylation reaction and could lead to decent product yields. In order to improve the carbon utilization, condensed furanic byproducts were further converted into hydrocarbon fuels via a reported two-step hydrodeoxygenation (HDO) process. This study not only validates the possibility of synthesizing functional HMF derivatives (EMFM, BHMFM, and BHMFD) from commercially-available FUR derivatives (EMF and FA), but also provide a new way to transform condensed furanics to value-added hydrocarbon fuels.
Radiomic Analysis of Tumour Heterogeneity Using MRI in Head and Neck Cancer Following Chemoradiotherapy: A Feasibility Study

Objectives To evaluate interval changes in heterogeneity on diffusion-weighted apparent diffusion coefficient (ADC) maps and T1-weighted post-gadolinium (T1w post gad) MRI in head and neck carcinoma (HNSCC), with and without chemo-radiotherapy (CRT) response. Methods This prospective observational cohort study included 24 participants (20 men, age 62.9 ± 8.8 years) with stage III and IV HNSCC. The primary tumour (n = 23) and largest lymph node (n = 22) dimensions, histogram parameters and grey-level co-occurrence matrix (GLCM) parameters were measured on ADC maps and T1w post gad sequences, performed pretreatment and 6 and 12 weeks post CRT. The 2-year treatment response at primary and nodal sites was recorded. The Wilcoxon signed-rank test was used to compare interval changes in parameters after stratifying for treatment response and failure (p < 0.001 statistical significance). Results 23/23 primary tumours and 18/22 nodes responded to CRT at 2 years. Responding HNSCC demonstrated a significant interval change in ADC histogram parameters (kurtosis, coefficient of variation, entropy, energy for primary tumour; kurtosis for nodes) and T1w post gad GLCM (entropy and contrast in the primary tumour and nodes) by 6 weeks post CRT (p < 0.001). Lymph nodes with treatment failure did not demonstrate an interval alteration in heterogeneity parameters. Conclusions ADC maps and T1w post gad MRI demonstrate the evolution of heterogeneity parameters in successfully treated HNSCC by 6 weeks post CRT; however, this is not observed in lymph nodes failing treatment. Advances in Knowledge Early reduction in heterogeneity is demonstrated on MRI when HNSCC responds to CRT.
Self-Triggered Control of Multi-Agent Systems With External Disturbances

This paper investigates the consensus of multi-agent systems (MASs) by virtue of event-triggered mechanism. Considering the existence of external disturbances, we use a disturbance observer to estimate the disturbance signals and eliminate the corresponding effects by using estimators to compensate the input control terms. The self-triggered condition is designed and proved that there is no Zeno behavior. We show that the proposed disturbance observer can estimate the external disturbance signals well under the self-triggered condition. Finally, simulation examples are presented to verify the theoretical results.
Association Between Weight Gain From Young to Middle Adulthood and Metabolic Syndrome Across Different BMI Categories at Young Adulthood

Objectives We aimed to assess the dose–response association between weight gain from young to middle adulthood and odds of metabolic syndrome, across body mass index (BMI) categories at young adulthood. Methods Based on a national population-based screening project, middle-aged (35–64 years) participants who recalled weight at age 25 years and received standardized measurements were included. Multivariable adjusted restricted cubic splines and logistic regression models were applied. Results In total, 437,849 participants were included (62.1% women, 52.0 ± 7.6 years). Larger weight gains from young to middle adulthood were associated with higher odds of metabolic syndrome at middle adulthood, with odds of 2.01 (1.98–2.05), 1.93 (1.92–1.94), and 1.67 (1.64–1.7) per 5-kg weight gain across participants who were underweight, normal-weight, and overweight/obese at young adulthood, respectively. After further adjusting for current BMI, larger weight gains still correlated with higher odds of metabolic syndrome among underweight and normal-weight participants, while an inverted U-shaped association was observed in overweight/obese participants. Conclusions Weight maintenance from young to middle adulthood could be effective to mitigate metabolic syndrome burden, especially among underweight and normal-weight people. Historical weight gain confers varied information about metabolic syndrome risk independent of attained BMI across BMI categories at young adulthood.
Expression Patterns of Glycosylation Regulators Define Tumor Microenvironment and Immunotherapy in Gastric Cancer

Glycosylation (Glyc) is prevalently related to gastric cancer (GC) pathophysiology. However, studies on the relationship between glycosylation regulators and tumor microenvironment (TME) and immunotherapy of GC remain scarce. We extracted expression data of 1,956 patients with GC from eight cohorts and systematically characterized the glycosylation patterns of six marker genes into phenotype clusters using the unsupervised clustering method. Next, we constructed a Glyc. score to quantify the glycosylation index of each patient with GC. Finally, we analyzed the relationship between Glyc. score and clinical traits including molecular subtype, TME, and immunotherapy of GC. On the basis of prognostic glycosylation-related differentially expressed genes, we constructed the Glyc. score and divided the samples into the high– and low–Glyc. score groups. The high–Glyc. score group showed a poor prognosis and was validated in multiple cohorts. Functional enrichment analysis revealed that the high–Glyc. score group was enriched in metabolism-related pathways. Furthermore, the high–Glyc. score group was associated with the infiltration of immune cells. Importantly, the established Glyc. score would contribute to predicting the response to anti–PD-1/L1 immunotherapy. In conclusion, the Glyc. score is a potentially useful tool to predict the prognosis of GC. Comprehensive analysis of glycosylation may provide novel insights into the epigenetics of GC and improve treatment strategies.
μMatch: 3D Shape Correspondence for Biological Image Data

Modern microscopy technologies allow imaging biological objects in 3D over a wide range of spatial and temporal scales, opening the way for a quantitative assessment of morphology. However, establishing a correspondence between objects to be compared, a first necessary step of most shape analysis workflows, remains challenging for soft-tissue objects without striking features allowing them to be landmarked. To address this issue, we introduce the μMatch 3D shape correspondence pipeline. μMatch implements a state-of-the-art correspondence algorithm initially developed for computer graphics and packages it in a streamlined pipeline including tools to carry out all steps from input data pre-processing to classical shape analysis routines. Importantly, μMatch does not require any landmarks on the object surface and establishes correspondence in a fully automated manner. Our open-source method is implemented in Python and can be used to process collections of objects described as triangular meshes. We quantitatively assess the validity of μMatch relying on a well-known benchmark dataset and further demonstrate its reliability by reproducing published results previously obtained through manual landmarking.
A New Concept of Work Engagement Theory in Cognitive Engagement, Emotional Engagement, and Physical Engagement

The concept of work engagement (WE) has aroused the interest of many scholars. However, there has been limited academic research in examining how authentic leadership (AL) can influence WE, which consequently influences organizational citizenship behavior (OCB) and task performance (TP). In particular, this study divides WE into cognitive engagement, emotional engagement, and physical engagement to fully reflect the engagement theory. This study introduces three dimensions of WE and tests the theoretical model to validate cognitive engagement, emotional engagement, and physical engagement. Empirical testing using a survey of 151 employees of retail travel agencies in Taiwan revealed that the AL can influence cognitive engagement, emotional engagement, and physical engagement, and also OCB and TP. These analysis results can assist vendors to implement OCB and TP through WE and AL.
Grafting Watermelon Onto Pumpkin Increases Chilling Tolerance by Up Regulating Arginine Decarboxylase to Increase Putrescine Biosynthesis

Low temperature is a major environmental factor that severely impairs plant growth and productivity. Watermelon (Citrullus lanatus) is a chilling-sensitive crop. Grafting of watermelon onto pumpkin rootstock is an effective technique to increase the chilling tolerance of watermelon when exposure to short-time chilling stress. However, the mechanism by which pumpkin rootstock increases chilling tolerance remains poorly understood. Under 10°C/5°C (day/night) chilling stress treatment, pumpkin-grafted watermelon seedlings showed higher chilling tolerance than self-grafted watermelon plants with significantly reduced lipid peroxidation and chilling injury (CI) index. Physiological analysis revealed that pumpkin rootstock grafting led to the notable accumulation of putrescine in watermelon seedlings under chilling conditions. Pre-treat foliar with 1 mM D-arginine (inhibitor of arginine decarboxylase, ADC) increased the electrolyte leakage (EL) of pumpkin-grafted watermelon leaves under chilling stress. This result can be ascribed to the decrease in transcript levels of ADC, ornithine decarboxylase, spermidine synthase, and polyamine oxidase genes involved in the synthesis and metabolism of polyamines. Transcriptome analysis showed that pumpkin rootstock improved chilling tolerance in watermelon seedlings by regulating differential gene expression under chilling stress. Pumpkin-grafted seedling reduced the number and expression level of differential genes in watermelon scion under chilling stress. It specifically increased the up-regulated expression of ADC (Cla97C11G210580), a key gene in the polyamine metabolism pathway, and ultimately promoted the accumulation of putrescine. In conclusion, pumpkin rootstock grafting increased the chilling tolerance of watermelon through transcription adjustments, up regulating the expression level of ADC, and promoting the synthesis of putrescine, which ultimately improved the chilling tolerance of pumpkin-grafted watermelon plants.