Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluorofenidone Alleviates Renal Fibrosis by Inhibiting Necroptosis Through RIPK3/MLKL Pathway

Cell death and sterile inflammation are major mechanisms of renal fibrosis, which eventually develop into end-stage renal disease. “Necroptosis” is a type of caspase-independent regulated cell death, and sterile inflammatory response caused by tissue injury is strongly related to necrosis. Fluorofenidone (AKF-PD) is a novel compound shown to ameliorate renal fibrosis and associated inflammation. We investigated whether AKF-PD could alleviate renal fibrosis by inhibiting necroptosis. Unilateral ureteral obstruction (UUO) was used to induce renal tubulointerstitial fibrosis in C57BL/6J mice. AKF-PD (500 mg/kg) or necrostatin-1 (Nec-1; 1.65 mg/kg) was administered simultaneously for 3 and 7 days. Obstructed kidneys and serum were harvested after euthanasia. AKF-PD and Nec-1 ameliorated renal tubular damage, inflammatory-cell infiltration, and collagen deposition, and the expression of proinflammatory factors (interlukin-1β, tumor necrosis factor [TNF]-α) and chemokines (monocyte chemoattractant protein-1) decreased. AKF-PD or Nec-1 treatment protected renal tubular epithelial cells from necrosis and reduced the release of lactate dehydrogenase in serum. Simultaneously, production of receptor-interacting protein kinase (RIPK)3 and mixed lineage kinase domain-like protein (MLKL) was also reduced 3 and 7 days after UUO. AKF-PD and Nec-1 significantly decreased the percentage of cell necrosis, inhibiting the phosphorylation of MLKL and RIPK3 in TNF-α- and Z-VAD–stimulated human proximal tubular epithelial (HK-2) cells. In conclusion, AKF-PD and Nec-1 have effective anti-inflammatory and antifibrotic activity in UUO-induced renal tubulointerstitial fibrosis, potentially mediated by the RIPK3/MLKL pathway.
Machine Learning Approaches for Quantifying Margalefidinium Polykrikoides Bloom from Airborne Hyperspectral Imagery

ABSTRACT Shin, J.; Kim, S.M. , and Ryu, J.-H. , 2020. Machine learning approaches for quantifying Margalefinium polykrikoides bloom from airborne hyperspectral imagery. In: Jung, H. -S. ; Lee, S. ; Ryu, J.-H. , and Cui, T. (eds.), Advances in Geospatial Research of Coastal Environments. Journal of Coastal Research, Special Issue No. 102, pp. 202-207. Coconut Creek (Florida), ISSN 0749-0208. The ichthyotoxic mixotrophic dinoflagellate Margalefidinium polykrikoides is well known for killing fish in aquaculture cages via gill clogging at high cell abundance. In order to establish a countermeasure against M. polykrikoides blooms, it is essential to monitor and quantify the spatial abundance of red tide cells with high accuracy. In this study, machine-learning (ML) approaches were applied to investigate the spectral features of M. polykrikoides cell abundance on the south coast of Korea. Four ML models were developed to retrieve the M. polykrikoides cell abundance in optically complex waters from airborne hyperspectral imagery (HSI). The models included the feed-forward neural network (FFN), support vector machine (SVM), ensemble bagged tree (EBT), and Gaussian process regression (GPR). Paired data of in situ spectra and M. polykrikoides cell abundance were used to train and validate the ML models. The performances of ML models were evaluated using the linear regression value (R2) and root mean squared error (RMSE), considering the predicted cell abundances calculated from HSI and ground truth. The GPR model utilized the validation data and showed the best performance (R2 = 0.57 and RMSE = 659.18 cells mL-1). GPR was also able to estimate the cell abundance with over 3,000 cell mL-1, indicating viable results. Therefore, using GPR is suggested to obtain more accurate red tide cell abundance maps. Local-based ML models for red tide cell abundance retrieval from HSI data can support the monitoring and surveillance of red tide blooms on the south coast of Korea.
Resting-State Functional Connectivity of the Punishment Network Associated With Conformity

Fear of punishment prompts individuals to conform. However, why some people are more inclined than others to conform despite being unaware of any obvious punishment remains unclear, which means the dispositional determinants of individual differences in conformity propensity are poorly understood. Here, we explored whether such individual differences might be explained by individuals’ stable neural markers to potential punishment. To do this, we first defined the punishment network (PN) by combining all potential brain regions involved in punishment processing. We subsequently used a voxel-based global brain connectivity (GBC) method based on resting-state functional connectivity (FC) to characterize the hubs in the PN, which reflected an ongoing readiness state (i.e., sensitivity) for potential punishment. Then, we used the within-network connectivity (WNC) of each voxel in the PN of 264 participants to explain their tendency to conform by using a conformity scale. We found that a stronger WNC in the right thalamus, left insula, postcentral gyrus, and dACC was associated with a stronger tendency to conform. Furthermore, the FC among the four hubs seemed to form a three-phase ascending pathway, contributing to conformity propensity at every phase. Thus, our results suggest that task-independent spontaneous connectivity in the PN could predispose individuals to conform.
The Mysteries of Capsaicin-Sensitive Afferents

A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as “capsaicin desensitization,” during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several “mysteries” remain unsolved to date, including the molecular underpinnings of “capsaicin desensitization,” and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms.
Abnormal Cingulum Bundle Induced by Type 2 Diabetes Mellitus: A Diffusion Tensor Tractography Study

Purpose: In Type 2 diabetes (T2DM), white matter (WM) pathology has been suggested to play an important role in the etiology of T2DM-related cognitive impairment. This study aims to investigate the integrity of the cingulum bundle (CB), a major WM tract, in T2DM patients using diffusion tensor tractography. Methods: Thirty-seven T2DM patients and 34 age-, sex- and education matched healthy controls were included and underwent diffusion tensor imaging. Tractography of bilateral CB tracts was performed and diffusion measurements were compared between the two groups. Next, brain regions with significant group differences on fractional anisotropy (FA) values were set as the region of interest (ROI), and the CB fibers that passed through were identified. Diffusion measures were extracted from these fibers to investigate their correlations with the cognitive performances and endocrine parameters. Results: T2DM patients exhibited decreased FA in bilateral CB, increased mean diffusion (MD) in the right CB, and decreased length in the left CB. Through voxel-wise comparison, the most prominent FA difference was identified in the posterior segment of the CB and the reconstructed tract was part of the retrosplenial component. Importantly, the diffusion measurements of the tract were significantly correlated with the impaired performance in executive functioning and elevated insulin resistance (IR) in the T2DM group, instead of the control group. Conclusions: The diffusion measurements in bilateral CB were altered in T2DM patients, which might reflect important neuropathologic changes in the fibers. Our study adds to knowledge about how the cingulum changes structurally along its entire length in T2DM and highlights the relationship between WM and cognitive performance. Besides, IR might be an important risk factor that warrants further exploration.
Young Adults With Higher Motives and Expectancies of Regular Cannabis Use Show Poorer Psychosocial Functioning

Background: Young adults regularly using cannabis represent a uniquely vulnerable yet heterogeneous cohort. Few studies have examined user profiles using cannabis use motives and expectations. The association between user profiles and psychosocial functioning among only regular users remains unexplored. This exploration is important to improve public education efforts and design tailor treatment approaches. Methods: Regular cannabis users (at least weekly; n = 329) completed an online survey via Amazon Mechanical Turk. The survey measured levels of cannabis use, other substance use, motives and expectations of cannabis use, symptoms of psychosis, depression, anxiety and stress, and reckless behavior such as getting high before work or driving under the influence of cannabis. Latent class analysis was performed using motives and expectations to identify data driven patterns of regular cannabis use. Classes were then used to investigate mental health and behavioral correlates of differences in motives and expectations. Results: A 2-class solution provided the best fit to the data; Class 1: Low Motives and Expectancies (n = 158) characterized by lower endorsement across all motivation and expectation variables, and Class 2: High Motives and Expectancies (n = 171) characterized by endorsing multiple motivations, and higher positive and negative expectations of cannabis use. Classes differed in a range of cannabis use variables; e.g., greater proportion of peer use in Class 2. The High Motives and Expectancies users reported higher symptoms of psychosis (positive and negative symptoms), depression, anxiety, and stress. A higher proportion met the criteria for a cannabis use disorder compared with Low Motives and Expectancies users. High Motives and Expectancies users reported higher mean problems with nicotine dependence and illicit drug use other than cannabis and were more likely to get high before work and drive under the influence of cannabis. Conclusions: There is heterogeneity among young regular cannabis users in their motivations and expectancies of use and associated psychosocial functioning. Understanding motives and expectancies can help segregate which users are at higher risk of worse functioning. These findings are timely when designing targeted assessment and treatment strategies, particularly as cannabis is further decriminalized and accessibility increases.
Effect of Different Levels of Energy Diet Restriction on Energy Balance, Leptin and CL Development, Vascularization, and Function in South American Camelids

The objective was to determine the effect of energy diet restriction on energy balance, systemic leptin and corpus luteum (CL) vascularization, development, and function in South American camelids. In experiment 1, adult llamas were randomly assigned to receive a diet of 70% of their maintenance energy requirements (MER) (Restricted group, n = 7) or fed ad libitum (Control group, n = 7) during 28 days. Body live weight (BLW) and body condition score (BCS) were recorded, blood samples were collected every 2 weeks to measure plasma leptin concentrations, and energy metabolites were quantified. In experiment 2, adult alpacas were randomly assigned to receive a diet of 40% MER for 21 days (Restricted group, n = 7) or fed ad libitum (Control group, n = 7). Then, ovulation was induced with gonadorelin acetate (day = 0), and trans-rectal ultrasonography (7.5 MHz) was performed using B and Doppler mode to record the diameter of the pre-ovulatory follicle, ovulation, CL diameter, and vascularization from Days 0 to 13. Blood samples were collected every 48 h from Days 1 to 13 to quantify plasma leptin and progesterone concentrations. In experiment 1, energy diet restriction of 70% MER did not affect plasma leptin concentration and metabolic parameters of the Restricted group. In experiment 2, the Restricted group had a lower BCS (p < 0.001), a smaller diameter of the CL on Days 5 and 7 (p < 0.05), and a smaller maximum diameter of the CL (10.2 ± 0.6 mm) than the Control group (12.1 ± 0.6 mm; p = 0.04). Low energy restriction of 70% MER for 28 days did not affect the energy balance of llamas (Experiment 1). Moderate energy restriction of 40% MER for 21 days negatively affected energy balance (BCS), and CL development but not its vascularization, leptin, and progesterone concentrations. These species must be submitted to longer periods or a higher level of energy restriction to impair ovarian function.
Effectiveness of a Physical Education Program on the Motor and Pre-literacy Skills of Preschoolers From the Training-To-Health Project: A Focus on Weight Status

Many studies reported a positive relationship between motor skills, cognitive functions, and school performance in school-age children; however, little is known in preschool children. The aim of the present study was to demonstrate the effectiveness of a physical education program (PEP) on locomotor, object control skills, and pre-literacy cognitive functions in a wide population of preschoolers and verify whether weight status could influence these abilities. In the context of the Training-to-Health Project, a sample of 1,029 preschoolers was recruited in kindergartens from the urban area of Palermo (Italy). Their gross motor and pre-literacy skills were tested before (PRE) and after (POST) following 16 weeks (2 h/week) of a PEP, which included ludic-motor activities aimed at developing body awareness and fundamental motor and perceptual-sensory skills. Analyses of variance (ANOVA) were performed to assess the skills before and after the intervention and to evaluate the effect of different categories of weight status on the examined variables. Regression analyses were conducted to confirm the hypothesized interrelationship between motor and pre-literacy skills in the considered sample. Both locomotor/object control and pre-literacy skills were significantly higher in children after the PEP (p < 0.05). We found 23% of overweight children and no significant difference between weight status classes in both PRE and POST PEP groups. In the POST group, higher locomotor and object control skills were mostly associated with better pre-literacy skills. This study shows that PEP was effective in improving both motor and pre-literacy skills in preschoolers independently from age and gender, while weight status did not affect these skills suggesting that this program can be administrated indifferently in children with different categories of weight status. Therefore, PEP could be a decisive education strategy to enhance motor and cognitive learning in preschool children and to achieve successful academic outcomes.
Efficacy and Safety of Indomethacin in Covid -19 patients

Abstract Background Indomethacin, a well-known non-steroidal anti-inflammatory drug (NSAID), has in addition broad spectrum anti-viral activity in the laboratory including on SARS-Cov-2 virus. This trial is to observe the likelihood of efficacy and safety of Indomethacin in treating RT-PCR positive Covid patients Materials and Methods The study was done in two groups. In the first group of the study, where mild and moderate patients were involved, Propensity Score Matching was used as a methodology to compare Indomethacin and paracetamol based treatments in addition to the standard protocol for treating covid-19 patients. Blood chemistry was collected before and after the treatment. The patients were monitored every day for clinical parameters. In this part, a patient developing hypoxia was the end point. In the second group, severe patients admitted with hypoxia were treated with Indomethacin in addition to Remdesivir, and the end point was the requirement of mechanical ventilation/admission to ICU. Results It was observed that patients treated with Indomethacin had a reduction in the number of days to become afebrile, reduction in cough and myalgia by half compared to the paracetamol set. Only one out of 72 patients in the Indomethacin arm of the first group required supplementary oxygen while 28 of the 72 patients required supplementary oxygen in the paracetamol arm. No one in the second group deteriorated enough to require mechanical ventilation. There wea no evidence of adverse reaction to indomethacin or deterioration of renal or liver function. Conclusion Indomethacin, along with standard care, seems to provide faster symptomatic relief and prevent progression of pneumonia in Covid-19 patients. It should be considered to replace paracetamol when there is no contraindication for its use.
Prognostic Importance of the Preoperative Naples Prognostic Score for Patients With Adenocarcinoma of the Esophagogastric Junction

Background The naples prognostic score (NPS) is established according to nutritional or inflammatory state, and it is identified as the new prognostic score for a variety of malignant tumors. However, its significance in cases suffering from adenocarcinoma of esophagogastric junction (AEJ) who receive surgery remains unclear so far. Methods In this study, patients receiving surgery without preoperative therapy were examined between June 2007 and August 2017 in a retrospective way. Typically, the serum albumin level, total cholesterol level, neutrophil-to-lymphocyte ratio, together with the lymphocyte-to-monocyte ratio, was determined to calculate the NPS. The prognostic impact of NPS was evaluated using survival analyses. Time-dependent receiver operating characteristic curve (t-ROC) analysis was also carried out for comparing prognostic impacts of those scoring systems. Results Altogether 231 cases were enrolled in this study. A higher NPS showed positive correlation with perineural invasion. Upon multivariate analysis, NPS was identified to be the independent prognostic factor to predict overall survival (OS) along with relapse-free survival (RFS) (both P< 0.05), and an especially strong correlation was observed at advanced pTNM stages based on NPS system. As for subgroup analyses on adjuvant chemotherapy or surgery only, NPS still independently predicted the OS as well as RFS (both P< 0.05) in both groups. Furthermore, t-ROC analysis showed that NPS was more accurate than the systemic inflammation score in predicting OS and RFS. Conclusions The NPS represents the simple and useful rating system, which can independently predict the survival for AEJ cases undergoing surgery.
Synergetic Effect of rHDL and LXR Agonist on Reduction of Atherosclerosis in Mice

High-density lipoproteins (HDLs) are unique in that they play an important role in the reverse cholesterol transport process. However, reconstituted HDL (rHDL) infusions have demonstrated limited beneficial effect in clinical practice. This is perhaps a consequence of the limited cholesterol efflux abilities of atheroma macrophages due to decreased expression of cholesterol transporters in advanced atheromas and following rHDL infusion treatment. Thus, we propose that a combination therapy of rHDL and a liver X receptor (LXR) agonist could maximize the therapeutic benefit of rHDL by upregulating ATP-binding cassette transporters A-1 (ABCA1) and ATP-binding cassette transporter G-1 (ABCG1), and enhancing cholesterol efflux to rHDL. In macrophages, rHDL downregulated the expression of ABCA1/G1 in a dose- and rHDL composition-dependent manner. Although LXR agonist, T0901317 (T1317), upregulated the expression of ABCA1 and ABCG1, the drug itself did not have any effect on cholesterol efflux (6.6 ± 0.5%) while the combination of rHDL and T1317 exhibited enhanced cholesterol efflux from [3H]-cholesterol loaded J774A.1 macrophages (23.3 ± 1.3%). Treatment with rHDL + T1317 significantly reduced the area of aortic plaque in ApoE−/− mice compared to PBS treated control animals (24.16 ± 1.42% vs. 31.59 ± 1.93%, p < 0.001), while neither rHDL nor T1317 treatment alone had a significant effect. Together, we show that rHDL paired with an LXR agonist can induce a synergetic effect in reducing atheroma burden. This synergy could lead to lower overall effective dose for both drugs, potentially overcoming the existing barriers in clinical development and renewing pharmaceutical interest in these two drug classes.
Target-Target Perceptual Similarity Within the Attentional Blink

Three experiments investigated the role of target-target perceptual similarity within the attentional blink (AB). Various geometric shapes were presented in a rapid serial visual presentation task. Targets could have 2, 1, or 0 shared features. Features included shape and size. The second target was presented after five or six different lags after the first target. The task was to detect both targets on each trial. Second-target report accuracy was increased by target-target similarity. This modulation was observed more for mixed-trial design as compared with blocked design. Results are discussed in terms of increased stability of working memory representations and reduced interference for second-target processing.
Cytokines in CAR T Cell–Associated Neurotoxicity

Chimeric antigen receptor (CAR) T cells provide new therapeutic options for patients with relapsed/refractory hematologic malignancies. However, neurotoxicity is a frequent, and potentially fatal, complication. The spectrum of manifestations ranges from delirium and language dysfunction to seizures, coma, and fatal cerebral edema. This novel syndrome has been designated immune effector cell–associated neurotoxicity syndrome (ICANS). In this review, we draw an arc from our current understanding of how systemic and potentially local cytokine release act on the CNS, toward possible preventive and therapeutic approaches. We systematically review reported correlations of secreted inflammatory mediators in the serum/plasma and cerebrospinal fluid with the risk of ICANS in patients receiving CAR T cell therapy. Possible pathophysiologic impacts on the CNS are covered in detail for the most promising candidate cytokines, including IL-1, IL-6, IL-15, and GM-CSF. To provide insight into possible final common pathways of CNS inflammation, we place ICANS into the context of other systemic inflammatory conditions that are associated with neurologic dysfunction, including sepsis-associated encephalopathy, cerebral malaria, thrombotic microangiopathy, CNS infections, and hepatic encephalopathy. We then review in detail what is known about systemic cytokine interaction with components of the neurovascular unit, including endothelial cells, pericytes, and astrocytes, and how microglia and neurons respond to systemic inflammatory challenges. Current therapeutic approaches, including corticosteroids and blockade of IL-1 and IL-6 signaling, are reviewed in the context of what is known about the role of cytokines in ICANS. Throughout, we point out gaps in knowledge and possible new approaches for the investigation of the mechanism, prevention, and treatment of ICANS.