Miracle-dz/UniFAR-FTUs huggingface dataset:
Age Specificity in Explicit and Implicit Endorsement of Prescriptive Age Stereotypes

In this study, we investigated explicit and implicit endorsement of prescriptive age stereotypes. To achieve that, we captured endorsement of a wide range of prescriptive expectations targeting both younger (younger adults are expected to be ambitious, eager to learn, unconventional, respectful) and older (older adults are expected to stay active, to be generous, dignified, and wise) people. Younger (n = 58, 50% female, Mage = 26.07 years, SD = 3.01) and older adults (n = 75, 44% female, Mage = 66.69 years, SD = 4.63) participated in the study. We assessed implicit endorsement of prescriptive age stereotypes with the Propositional Evaluation Paradigm (PEP) and used a direct measure to assess explicit endorsement. In general, we found strong support for age-specificity in both explicit and implicit endorsement of prescriptive age stereotypes: Sentences ascribing expectations for young/old to the respective age group (e.g., “young should be ambitious”; “old should be wise”) were endorsed much more strongly than sentences in which expectations for young/old were ascribed to the other age group (e.g., “old should be ambitious”; “young should be wise”). Age group differences in the endorsement of prescriptive age stereotypes were found. Compared to younger participants, older participants showed stronger endorsement for prescriptive beliefs targeting both younger and older targets. Explicit and implicit endorsement of prescriptive age stereotypes did not correlate with one another, thus revealing they might assess independent belief systems with different predictive potential.
Preoperative Platelet Distribution Width Represents a Novel Prognostic Biomarker in Patients With Nonmetastatic Renal Cell Carcinoma: A Retrospective Clinical Analysis

Purpose The study aimed to explore the prognostic value of platelet distribution width (PDW) in patients with nonmetastatic renal cell carcinoma (RCC). Methods We retrospective analyzed 706 patents with nonmetastatic RCC from January 2015 to December 2017. Clinicopathologic data and platelet indices were collected and analyzed by univariable and multivariable cox proportional hazard model. Progression-free survival (PFS) was analyzed using the Kaplan–Meier curve. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were performed to evaluate the improvement of predictive accuracy. Results Patients were divided into low PDW (N = 241, PDW ≤11.7%), intermediate PDW (N = 232, 11.7%< PDW ≤15.6%), and high PDW (N = 233, PDW >15.6%) groups according to the tertiles. Patients with low PDW were associated with more symptoms at presentation, larger tumor size, higher AJCC tumor stage, and more sarcomatoid differentiation. Besides, patients with low PDW had significantly shorter PFS compared to intermediate PDW and high PDW groups. On the multivariable model, AJCC tumor stage, nuclear grade, and PDW (either continuous or categorical variables) were independent factors correlated with PFS. The NRI and IDI showed adding PDW to SSIGN score improves its predictive accuracy related to 2-, 3-, and 4-year PFS. Conclusions Low PDW was related to advanced clinicopathologic features and worse prognosis in patients with nonmetastatic RCC. Thus, PDW could serve as a novel biomarker for risk stratification in these patients when used pre-or postoperatively.
Green Turtles Highlight Connectivity Across a Regional Marine Protected Area Network in West Africa

Networks of marine protected areas (MPAs) are invaluable for the protection of species with high dispersal capacity, yet connectivity within networks is poorly understood. We demonstrate the connectivity within the regional MPA network in West Africa (RAMPAO), mediated by the largest green turtle population in the eastern Atlantic Ocean. We equipped with satellite tags 45 female green turtles nesting in the Bijagós Archipelago, Guinea-Bissau, and tracked them during internesting, migration, and foraging to quantify the degree of coverage the RAMPAO network provides during each of these critical periods. During the internesting period, turtles were largely concentrated around the nesting islands, with a mean of 94.8% (SD 0.1%, range: 46% - 100%, n = 40 turtles) of tracking positions falling within MPA limits. Among the 35 turtles successfully tracked into the foraging period, we identified variable migratory strategies, with 12 turtles remaining near-resident at distances of 40-90 km from breeding sites, 10 turtles migrating 300-400 km to The Gambia and Senegal, and 13 turtles traveling >1000 km to northern Mauritania. Of the 35 foraging turtles, 26 used MPAs, with a mean of 78.0% (SD 34.8%, range: 3.7% - 100%) of their tracking positions falling within the limits of RAMPAO MPAs, across Guinea-Bissau, Senegal and Mauritania. Migration corridors with high concentrations of passing turtles were mostly located nearshore, and 21% of these high passage areas fell within the MPA network. Overall, we found that this population connects five RAMPAO MPAs, yet some foraging sites (e.g., in the Bijagós) and important migration areas (e.g., Cap-Vert peninsula) described here are currently unprotected. These results are relevant to any considerations of MPA extension or establishment within the regional network, which would contribute towards meeting the Convention on Biological Diversity targets for national marine protected area estate coverage. By documenting biological connectivity across RAMPAO, this study represents an important example of the relevance of international protected area networks for green turtle conservation and for wider conservation action at a regional scale.
Absorption, Metabolism, and Excretion of ACT-1004-1239, a First-In-Class CXCR7 Antagonist: In Vitro, Preclinical, and Clinical Data

ACT-1004-1239 is a potent, selective, first-in-class CXCR7 antagonist, which shows a favorable preclinical and clinical profile. Here we report the metabolites and the metabolic pathways of ACT-1004-1239 identified using results from in vitro and in vivo studies. Two complementary in vitro studies (incubation with human liver microsomes in the absence/presence of cytochrome P450- [CYP] specific chemical inhibitors and incubation with recombinant CYPs) were conducted to identify CYPs involved in ACT-1004-1239 metabolism. For the in vivo investigations, a microtracer approach was integrated in the first-in-human study to assess mass balance and absorption, distribution, metabolism, and excretion (ADME) characteristics of ACT-1004-1239. Six healthy male subjects received orally 100 mg non-radioactive ACT-1004-1239 together with 1 μCi 14C-ACT-1004-1239. Plasma, urine, and feces samples were collected up to 240 h post-dose and 14C-drug-related material was measured with accelerator mass spectrometry. This technique was also used to construct radiochromatograms of pooled human samples. Metabolite structure elucidation of human-relevant metabolites was performed using high performance liquid chromatography coupled with high resolution mass spectrometry and facilitated by the use of rat samples. CYP3A4 was identified as the major CYP catalyzing the formation of M1 in vitro. In humans, the cumulative recovery from urine and feces was 84.1% of the dose with the majority being eliminated via the feces (69.6%) and the rest via the urine (14.5%). In human plasma, two major circulating metabolites were identified, i.e., M1 and M23. Elimination via M1 was the only elimination pathway that contributed to ≥25% of ACT-1004-1239 elimination. M1 was identified as a secondary amine metabolite following oxidative N-dealkylation of the parent. M23 was identified as a difluorophenyl isoxazole carboxylic acid metabolite following central amide bond hydrolysis of the parent. Other metabolites observed in humans were A1, A2, and A3. Metabolite A1 was identified as an analog of M1 after oxidative defluorination, whereas both, A2 and A3, were identified as a reduced analog of M1 and parent, respectively, after addition of two hydrogen atoms at the isoxazole ring. In conclusion, CYP3A4 contributes to a relevant extent to ACT-1004-1239 disposition and two major circulating metabolites were observed in humans. Clinical Trial Registration: (https://clinicaltrials.gov/ct2/show/NCT03869320) ClinicalTrials.gov Identifier NCT03869320.
Identification of Potential Biomarkers and Small Molecule Drugs for Cutaneous Melanoma Using Integrated Bioinformatic Analysis

Background: Cutaneous melanoma (CM) is a type of skin cancer with a high fatality rate, and its pathogenesis has not yet been fully elucidated. Methods: We obtained the gene expression datasets of CM through the Gene Expression Omnibus (GEO) database. Subsequently, robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between CM cases and normal skin controls. Gene functional annotation was performed to explore the potential function of the DEGs. We built the protein–protein interaction (PPI) network by the Interactive Gene database retrieval tool (STRING) and selected hub modules by Molecular Complexity Detection (MCODE). We furthered and validated our results using the TCGA-GTEX dataset. Finally, potential small molecule drugs were predicted by CMap database and verified by molecular docking method. Results: A total of 135 DEGs were obtained by RRA synthesis analysis. GMPR, EMP3, SLC45A2, PDZD2, NPY1R, DLG5 and ADH1B were screened as potential targets for CM. Furazolidone was screened as a potential small molecule drug for the treatment of CM, and its mechanism may be related to the inhibition of CM cell proliferation by acting on GMPR. Conclusion: We identified seven prognostic therapeutic targets associated with CM and furazolidone could be used as a potential drug for CM treatment, providing new prognostic markers, potential therapeutic targets and small molecule drugs for the treatment and prevention of CM.
Facial Stimulation Induces Long-Term Potentiation of Mossy Fiber-Granule Cell Synaptic Transmission via GluN2A-Containing N-Methyl-D-Aspartate Receptor/Nitric Oxide Cascade in the Mouse Cerebellum

Long-term synaptic plasticity in the cerebellar cortex is a possible mechanism for motor learning. Previous studies have demonstrated the induction of mossy fiber-granule cell (MF-GrC) synaptic plasticity under in vitro and in vivo conditions, but the mechanisms underlying sensory stimulation-evoked long-term synaptic plasticity of MF-GrC in living animals are unclear. In this study, we investigated the mechanism of long-term potentiation (LTP) of MF-GrC synaptic transmission in the cerebellum induced by train of facial stimulation at 20 Hz in urethane-anesthetized mice using electrophysiological recording, immunohistochemistry techniques, and pharmacological methods. Blockade of GABAA receptor activity and repetitive facial stimulation at 20 Hz (240 pulses) induced an LTP of MF-GrC synapses in the mouse cerebellar cortical folium Crus II, accompanied with a decrease in paired-pulse ratio (N2/N1). The facial stimulation-induced MF-GrC LTP was abolished by either an N-methyl-D-aspartate (NMDA) receptor blocker, i.e., D-APV, or a specific GluNR2A subunit-containing NMDA receptor antagonist, PEAQX, but was not prevented by selective GluNR2B or GluNR2C/D subunit-containing NMDA receptor blockers. Application of GNE-0723, a selective and brain-penetrant-positive allosteric modulator of GluN2A subunit-containing NMDA receptors, produced an LTP of N1, accompanied with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. Inhibition of nitric oxide synthesis (NOS) prevented the facial stimulation-induced MF-GrC LTP, while activation of NOS produced an LTP of N1, with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. In addition, GluN2A-containing NMDA receptor immunoreactivity was observed in the mouse cerebellar granular layer. These results indicate that facial stimulation at 20 Hz induced LTP of MF-GrC synaptic transmission via the GluN2A-containing NMDA receptor/nitric oxide cascade in mice. The results suggest that the sensory stimulation-evoked LTP of MF-GrC synaptic transmission in the granular layer may play a critical role in cerebellar adaptation to native mossy fiber excitatory inputs and motor learning behavior in living animals.
Branched PCL-Based Thermogelling Copolymers: Controlling Polymer Architecture to Tune Drug Release Profiles

Temperature-responsive hydrogels, or thermogels, are a unique class of biomaterials that show facile and spontaneous transition from solution to gel when warmed. Their high biocompatibility, and ease of formulation with both small molecule drugs and biologics have made these materials prime candidates as injectable gel depots for sustained local drug delivery. At present, controlling the kinetics and profile of drug release from thermogels is achieved mainly by varying the ratio of hydrophobic: hydrophilic composition and the polymer molecular weight. Herein, we introduce polymer branching as a hitherto-overlooked polymer design parameter that exhibits profound influences on the rate and profile of drug release. Through a family of amphiphilic thermogelling polymers with systematic variations in degree of branching, we demonstrate that more highly-branched polymers are able to pack less efficiently with each other during thermogel formation, with implications on their physical properties and stability towards gel erosion. This in turn resulted in faster rates of release for both encapsulated small molecule hydrophobic drug and protein. Our results demonstrate the possibility of exploiting polymer branching as a hitherto-overlooked design parameter for tailoring the kinetics and profile of drug release in injectable thermogel depots.
Human Face Perception Using Electroencephalography and Magnetoencephalography

The face has a large amount of information that is useful for humans in social communication. Recently, non-invasive methods have been used to investigate human brain activity related to perception and cognition processes. Electroencephalography (EEG) and magnetoencephalography (MEG) have excellent temporal resolution and reasonably good spatial resolution. Therefore, they are useful to investigate time sequences of human brain activity related to the face perception process. In this review, we introduce our previous EEG and MEG studies of human face perception that demonstrated the following characteristics of face perception processing: (1) Event-related components in the temporal area related to the activity in the inferior temporal (IT) area, corresponding to the fusiform face area (FFA), are evoked approximately 180 msec after the presentation of a face. The activity in the IT area plays an important role in the detection processing of a face, and the contours of a face affect the activity in the IT areas. (2) Event-related components in the temporal area related to the superior temporal sulcus (STS) activity are larger when eyes are averted than when directly looking into the eyes. (3) The direction of features of a face affects the face perception processing in the right hemisphere. On the other hand, the matching of the direction between the contours and features of a face affects the processing in the left hemisphere. (4) Random dots blinking (RDB), which uses temporal changes in patterns of many small dots to present stimuli without a change in luminance during the presentation of a face, is a useful visual stimulus method to investigate the brain activity related to face perception processing in the IT area using EEG and MEG.
The Neuropeptide α-Calcitonin Gene-Related Peptide as the Mediator of Beneficial Effects of Exercise in the Cardiovascular System

Regular physical activity exerts cardiovascular protective effects in healthy individuals and those with chronic cardiovascular diseases. Exercise is accompanied by an increased plasma concentration of α-calcitonin gene-related peptide (αCGRP), a 37-amino acid peptide with vasodilatory effects and causative roles in migraine. Moreover, mouse models revealed that loss of αCGRP disrupts physiological adaptation of the cardiovascular system to exercise in normotension and aggravates cardiovascular impairment in primary chronic hypertension, both can be reversed by αCGRP administration. This suggests that αCGRP agonists could be a therapeutic option to mediate the cardiovascular protective effects of exercise in clinical setting where exercise is not possible or contraindicated. Of note, FDA has recently approved αCGRP antagonists for migraine prophylaxis therapy, however, the cardiovascular safety of long-term anti-CGRP therapy in individuals with cardiovascular diseases has yet to be established. Current evidence from preclinical models suggests that chronic αCGRP antagonism may abolish the cardiovascular protective effects of exercise in both normotension and chronic hypertension.
Improvement of Direct Interspecies Electron Transfer via Adding Conductive Materials in Anaerobic Digestion: Mechanisms, Performances, and Challenges

Anaerobic digestion is an effective and sustainable technology for resource utilization of organic wastes. Recently, adding conductive materials in anaerobic digestion to promote direct interspecies electron transfer (DIET) has become a hot topic, which enhances the syntrophic conversion of various organics to methane. This review comprehensively summarizes the recent findings of DIET mechanisms with different mediating ways. Meanwhile, the influence of DIET on anaerobic digestion performance and the underlying mechanisms of how DIET mediated by conductive materials influences the lag phase, methane production, and system stability are systematically explored. Furthermore, current challenges such as the unclear biological mechanisms, influences of non-DIET mechanisms, limitations of organic matters syntrophically oxidized by way of DIET, and problems in practical application of DIET mediated by conductive materials are discussed in detail. Finally, the future research directions for practical application of DIET are outlined.
Tolerance for Wolves in the United States

This study applies a psychological hazard-acceptance model to U.S. wolf conservation. Where most prior studies have focused on human populations most likely to interact with wolves (e.g., people who reside in wolves’ range), we sought to model tolerance among the general public throughout the United States, with representative samples from two regions with ongoing recovery efforts (i.e., the Northern Rocky Mountains and Western Great Lakes) as well as the rest of the country. As opposed to typical, attitudinal measures of tolerance (e.g., wildlife acceptance capacity) we sought to model supportive and oppositional behavior among the U.S. public as a function of perceptions of risk, benefit, and control, trust in the U.S. Fish and Wildlife Service, and affect toward wolves. At the national level, results predict a moderate amount of the variance for tolerant, stewardship behaviors (r2 = 0.22–0.25) and intolerant, oppositional behaviors to wolf conservation (r2 = 0.14–0.22). Most respondents (55%) did not intend to engage in either supportive or oppositional actions, and 23% indicated a preference for wolf populations to increase nationally. These preferences varied slightly by sample region when weighted to reflect regional demographics, with about one in three respondents in the Northern Rocky Mountains preferring for wolf populations to increase (32%), and slightly fewer saying the same in the Western Great Lakes region (30%) and rest of the United States (27%). We performed a post hoc logistic regression to identify factors that predisposed U.S. residents nationally to engage in any behavior toward wolves (tolerant or intolerant). This analysis suggested that the perceived importance of the wolf issue was most predictive of intentions to engage in behavior relevant to wolf conservation. Analyses indicate high levels of tolerance for wolves nationally, some support for their restoration, and only small minorities engaging in oppositional behavior. With the recent shift to individual state-level management, a more diverse policy matrix will increase the importance of understanding how human tolerance for wolves varies spatially (at the local level), and what factors drive tolerance at both the individual and group level.
Comparison of the Unfolded Protein Response in Cellobiose Utilization of Recombinant Angel- and W303-1A-Derived Yeast Expressing β-Glucosidase

The unfolded protein response (UPR) is one of the most important protein quality control mechanisms in cells. At least, three factors are predicted to activate the UPR in yeast cells during fermentation. Using UPRE-lacZ as a reporter, we constructed two indicator strains, KZ and WZ, based on Angel-derived K-a and W303-1A strains, respectively, and investigated their UPR response to tunicamycin, ethanol, and acetic acid. Then, four strains carrying plasmids BG-cwp2 and BG were obtained to realize the displaying and secretion of β-glucosidase, respectively. The results of cellobiose utilization assays indicated interactions between the UPR and the metabolic burden between the strain source, anchoring moiety, oxygen supply, and cellobiose concentration. Meanwhile, as expected, growth (OD600), β-glucosidase, and β-galactosidase activities were shown to have a positive inter-relationship, in which the values of the KZ-derived strains were far lower than those of the WZ-derived strains. Additionally, extra metabolic burden by displaying over secreting was also much more serious in strain KZ than in strain WZ. The maximum ethanol titer of the four strains (KZ (BG-cwp2), KZ (BG), WZ (BG-cwp2), and WZ (BG)) in oxygen-limited 10% cellobiose fermentation was 3.173, 5.307, 5.495, and 5.486% (v/v), respectively, and the acetic acid titer ranged from 0.038 to 0.060% (v/v). The corresponding maximum values of the ratio of β-galactosidase activity to that of the control were 3.30, 5.29, 6.45, and 8.72, respectively. Under aerobic conditions with 2% cellobiose, those values were 3.79, 4.97, 6.99, and 7.67, respectively. A comparison of the results implied that β-glucosidase expression durably induced the UPR, and the effect of ethanol and acetic acid depended on the titer produced. Further study is necessary to identify ethanol- or acid-specific target gene expression. Taken together, our results indicated that the host strain W303-1A is a better secretory protein producer, and the first step to modify strain K-a for cellulosic ethanol fermentation would be to relieve the bottleneck of UPR capacity. The results of the present study will help to identify candidate host strains and optimize expression and fermentation by quantifying UPR induction.