Miracle-dz/UniFAR-FTUs huggingface dataset:
Editorial: A Compendium of Recent Research on Stem Cell-Based Therapy for Covid-19

Department of Biotechnology, University of Alicante, Alicante, Spain, University of Pablo de Olavide, Seville, Spain, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain, Department of Physiology, Institute of Bioengineering-ISABIAL, University Miguel Hernández School of Medicine, Alicante, Spain, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China, School of Life Sciences, Shanghai University, Shanghai, China, International Society on Aging and Disease, Bryan, TX, United States, Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Rocío, University of Seville, CSIC, Seville, Spain, Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain, Pediatric Cardiology Unit, Virgen del Rocio University Hospital, Seville, Spain, Institute of Biomedicine of Seville, University Hospital of Virgen del Rocío, University of Seville, CSIC, Seville, Spain
The Bradykinin B2 Receptor Agonist (NG291) Causes Rapid Onset of Transient Blood–Brain Barrier Disruption Without Evidence of Early Brain Injury

Background: The blood–brain barrier (BBB) describes the brain’s highly specialized capillaries, which form a dynamic interface that maintains central nervous system (CNS) homeostasis. The BBB supports the CNS, in part, by preventing the entry of potentially harmful circulating molecules into the brain. However, this specialized function is challenging for the development of CNS therapeutics. Several strategies to facilitate drug delivery into the brain parenchyma via disruption of the BBB have been proposed. Bradykinin has proven effective in disrupting mechanisms across the blood–tumor barrier. Unfortunately, bradykinin has limited therapeutic value because of its short half-life and the undesirable biological activity elicited by its active metabolites. Objective: To evaluate NG291, a stable bradykinin analog, with selective agonist activity on the bradykinin-B2 receptor and its ability to disrupt the BBB transiently. Methods: Sprague Dawley rats and CD-1 mice were subjected to NG291 treatment (either 50 or 100 μg/kg, intravenously). Time and dose-dependent BBB disruption were evaluated by histological analysis of Evans blue (EB) extravasation. Transcellular and paracellular BBB leakage were assessed by infiltration of 99mTc-albumin (66.5 KDa) and 14C-sucrose (340 Da) radiolabeled probes into the brains of CD-1 mice treated with NG291. NG291 influence on P-glycoprotein (P-gp) efflux pump activity was evaluated by quantifying the brain accumulation of 3H-verapamil, a known P-gp substrate, in CD-1 mice. Results: NG291-mediated BBB disruption was localized, dose-dependent, and reversible as measured by EB extravasation. 99mTc-albumin leakage was significantly increased by 50 μg/kg of NG291, whereas 100 μg/kg of NG291 significantly augmented both 14C-sucrose and 99mTc-albumin leakage. NG291 enhanced P-gp efflux transporter activity and was unable to increase brain uptake of the P-gp substrate pralidoxime. NG291 did not evoke significant short-term neurotoxicity, as it did not increase brain water content, the number of Fluoro-Jade C positive cells, or astrocyte activation. Conclusion: Our findings strongly suggest that NG291 increases BBB permeability by two different mechanisms in a dose-dependent manner and increases P-gp efflux transport. This increased permeability may facilitate the penetration into the brain of therapeutic candidates that are not P-gp substrates.
Connections to the Deep: Deep Vertical Migrations, an Important Part of the Life Cycle of Apherusa glacialis, an Arctic Ice-Associated Amphipod

Arctic sea ice contains a substantial amount of living biota of which part is lost through melt and export out of the Arctic Ocean every year. It is unclear how populations can be maintained within the Arctic Ocean. A representative ice inhabitant, the amphipod Apherusa glacialis was previously assumed to spend its entire life in the sea ice habitat, hence being dependent on sea ice to complete its life cycle. However, several recent studies report pelagic occurrences and suggest that seasonal vertical migrations might be an adaptive life history trait enabling a viable population size in the Arctic Ocean. In this study we use a particle-tracking model to investigate to what extent vertical migration might affect the species’ retention in the Arctic Ocean and the sea ice habitat. The modeled trajectories of A. glacialis were calculated based on ice drift and ocean currents from a coupled ocean – sea ice model covering the Arctic Ocean. We test two scenarios: (1) trajectories of A. glacialis that stay attached to the ice or follow the surface currents if they melt out of the ice and (2) trajectories of A. glacialis that undertake a seasonal vertical migration to drift with the currents at depth for parts of the year. In the multi-year model simulations it is assumed that after an initial period of 2 years A. glacialis that are located outside sea-ice cover each spring will perish while those located within the ice-covered region will reproduce. The model results show that a seasonal vertical migration both increases the total number of individuals and leads to a population distribution within the Arctic Ocean more in line with previous findings than the results from the non-migrating A. glacialis. Our results support the hypothesis that a seasonal migration may be an adaptive life history strategy in this species.
Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study

Background To evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection. Methods This study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital. Results The median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973). Conclusion Gastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.
A compact and low-phase-noise Ka-band pHEMT-based VCO

A low phase-noise Ka-band monolithic voltage-controlled oscillator (VCO) designed using the negative resistance concept is reported. A circuit fabricated using the three-dimensional monolithic microwave integrated circuit technology exhibits a high integration level; its size is a record at just 0.5 mm/sup 2/. On-wafer measurements demonstrate a low phase noise of -102 dBc/Hz at a 1-MHz offset. The VCO delivers an output power of 11.8 dBm at the center frequency of 28.3 GHz. The frequency tuning range is more than 3.8 GHz. Dependence of the circuit performance on the bias conditions is also reported and suggests that an optimum phase-noise characteristic can be achieved when biasing the transistor to optimize its transconductance and noise figure.
What Contributes to the Development and Maintenance of School Refusal in Chinese Adolescents: A Qualitative Study

Objective: Although, there has been a growing number of studies on school refusal in Western cultures, the underlying factors that contribute to school refusal in Chinese adolescents remain unclear. This study aimed to better understand why Chinese adolescents refuse to go to school and to further interpret what they want to express through their school refusal behaviors. Methods: We performed a qualitative study using an interpretative phenomenological analysis. Twenty adolescents with school refusal experiences were recruited from the clinical psychology department of two mental health hospitals in Shanghai, China. They participated in semistructured, face-to-face in-depth interviews. The interviews were transcribed verbatim and analyzed according to the guidelines of interpretative phenomenological analysis. Findings: Five main superordinate themes emerged from data analysis: (a) competition-oriented social environment; (b) family living space dominated by conflicts; (c) personal living space lacking meaningful support; (d) conflict between the pros and cons of being labeled with a psychiatric diagnosis; and (e) reintegration in school life. Conclusions: Our analysis emphasized the complex interacting effects of the social environment, family interpersonal conflicts, personal psychological factors and mental health complaints on the development and maintenance of Chinese adolescents' school refusal. These factors contributed to school refusal at each level and influenced each other's effects on school refusal behaviors. Therefore, interventions for Chinese teenagers with school refusal may need to integrate strategies that inspire reorganization and changes in different ecosystems, such as strategies related to government policy, peer relationships, family systems and individual inner dynamics.
Effective university-industry technology transfer

This paper presents an investigation of university-industry technology transfer in robotics and intelligent systems in Canada. The objective of the investigation was to determine which mechanisms for technology transfer are most effective and how to bring about an increase in effective technology transfer. This study shows that the most effective methods for transmitting and exploiting knowledge in the field of robotics and intelligent systems involve accessing the knowledge source directly (as opposed to acquiring the knowledge produced), building relationships, and focusing the research effort on a particular application or need. Strategies for increasing effective technology transfer include: involving industry in applied research, increasing industry R&D investment, increasing funding for the most effective technology transfer mechanisms, and changing the university environment to facilitate, properly evaluate, and reward interaction with industry. <<ETX>>
Early Transcriptional Changes in Rabies Virus-Infected Neurons and Their Impact on Neuronal Functions

Rabies is a zoonotic disease caused by rabies virus (RABV). As rabies advances, patients develop a variety of severe neurological symptoms that inevitably lead to coma and death. Unlike other neurotropic viruses that can induce symptoms of a similar range, RABV-infected post-mortem brains do not show significant signs of inflammation nor the structural damages on neurons. This suggests that the observed neurological symptoms possibly originate from dysfunctions of neurons. However, many aspects of neuronal dysfunctions in the context of RABV infection are only partially understood, and therefore require further investigation. In this study, we used differentiated neurons to characterize the RABV-induced transcriptomic changes at the early time-points of infection. We found that the genes modulated in response to the infection are particularly involved in cell cycle, gene expression, immune response, and neuronal function-associated processes. Comparing a wild-type RABV to a mutant virus harboring altered matrix proteins, we found that the RABV matrix protein plays an important role in the early down-regulation of host genes, of which a significant number is involved in neuronal functions. The kinetics of differentially expressed genes (DEGs) are also different between the wild type and mutant virus datasets. The number of modulated genes remained constant upon wild-type RABV infection up to 24 h post-infection, but dramatically increased in the mutant condition. This result suggests that the intact viral matrix protein is important to control the size of host gene modulation. We then examined the signaling pathways previously studied in relation to the innate immune responses against RABV, and found that these pathways contribute to the changes in neuronal function-associated processes. We further examined a set of regulated genes that could impact neuronal functions collectively, and demonstrated in calcium imaging that indeed the spontaneous activity of neurons is influenced by RABV infection. Overall, our findings suggest that neuronal function-associated genes are modulated by RABV early on, potentially through the viral matrix protein-interacting signaling molecules and their downstream pathways.
TAS2R16 Activation Suppresses LPS-Induced Cytokine Expression in Human Gingival Fibroblasts

Sustained and non-resolved inflammation is a characteristic of periodontitis. Upon acute inflammation, gingival fibroblasts release cytokines to recruit immune cells to counter environmental stimuli. The intricate regulation of pro-inflammatory signaling pathways, such as NF-κB, is necessary to maintain periodontal homeostasis. Nonetheless, how inflammation is resolved has not yet been elucidated. In this study, 22 subtypes of taste receptor family 2 (TAS2Rs), as well as the downstream machineries of Gα-gustducin and phospholipase C-β2 (PLCβ2), were identified in human gingival fibroblasts (HGFs). Various bitter agonists could induce an intensive cytosolic Ca2+ response in HGFs. More importantly, TAS2R16 was expressed at a relatively high level, and its agonist, salicin, showed robust Ca2+ evocative effects in HGFs. Activation of TAS2R16 signaling by salicin inhibited the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines, at least in part, by repressing LPS-induced intracellular cAMP elevation and NF-κB p65 nuclear translocation in HGFs. These findings indicate that TAS2Rs activation in HGFs may mediate endogenous pro-inflammation resolution by antagonizing NF-κB signaling, providing a novel paradigm and treatment target for the better management of periodontitis.
Multi-Process Action Control in Physical Activity: A Primer

The gap between the decision to engage in physical activity and subsequent behavioral enactment is considerable for many. Action control theories focus on this discordance in an attempt to improve the translation of intention into behavior. The purpose of this mini-review was to overview one of these approaches, the multi-process action control (M-PAC) framework, which has evolved from a collection of previous works. The main concepts and operational structure of M-PAC was overviewed followed by applications of the framework in physical activity, and concluded with unanswered questions, limitations, and possibilities for future research. In M-PAC, it is suggested that three layered processes (reflective, regulatory, reflexive) build upon each other from the formation of an intention to a sustained profile of physical activity action control. Intention-behavior discordance is because of strategic challenges in goal pursuit (differences in outcome vs. behavioral goals; balancing multiple behavioral goals) and automatic tendencies (approach-avoidance, conservation of energy expenditure). Regulatory processes (prospective and reactive tactics) are employed to hold the relationship between reflective processes and behavior concordant by countering these strategic challenges and automatic tendencies until the development of reflexive processes (habit, identity) begin to co-determine action control. Results from 29 observational and preliminary experimental studies generally support the proposed M-PAC framework. Future research is needed to explore the temporal dynamic between reflexive and regulatory constructs, and implement M-PAC interventions in different forms (e.g., mobile health), and at different levels of scale (clinical, group, population).
Configuration of the Volatile Aromatic Profile of Carob Powder Milled From Pods of Genetic Variants Harvested at Progressive Stages of Ripening From High and Low Altitudes

Carob powder is increasingly valued as a substitute for cocoa and as a flavor-enhancing component of processed foods. However, little is known about the impact of preharvest factors such as fruit maturity, genotype and altitude on its volatile organic compounds (VOCs) composition. The current study examined the VOCs composition of powder milled from pods of two genotypes cultivated at 15 and 510 m altitude and harvested at six progressive stages of maturity, ranging from fully developed immature green (RS1) to late ripe (RS6). Fifty-six VOCs categorized into acids, esters, aldehydes, ketones, alcohols, furans, and alkanes were identified through HS-SPME GC-MS analysis. Maturity was the most influential factor, followed by altitude and least by genotype. Aldehydes and alcohols correlated positively (r = 0.789; p < 0.001), both accumulated in immature carobs and decreased with progressive ripening, resulting in the attenuation of green grassy aroma. Conversely, acids increased with ripening and dominated the carob volatilome at full maturity, correlating negatively with aldehydes and alcohols (r = −0.835 and r = −0.950, respectively; p < 0.001). The most abundant VOC throughout ripening (17.3-57.7%) was isobutyric acid, responsible for the characteristic cheesy-acidic-buttery aroma of carob powder. The pleasurable aroma detected at the immature stages (RS2 and RS3) was traced to isobutyrate and methyl isobutyrate esters, rendering unripe green carob powder a potential admixture component for improving the aroma of novel food products. Lower altitude favored the accumulation of acids linked to less pleasant aroma, whereas isobutyric acid was more abundant at higher altitude. This constitutes a significant indication that higher altitude enhances the characteristic carob-like aroma and sensory quality of carob powder.
Novel Insights Into Gene Signatures and Their Correlation With Immune Infiltration of Peripheral Blood Mononuclear Cells in Behcet’s Disease

Background Behcet’s disease (BD) is a chronic inflammatory disease that involves systemic vasculitis and mainly manifests as oral and genital ulcers, uveitis, and skin damage as the first clinical symptoms, leading to gastrointestinal, aortic, or even neural deterioration. There is an urgent need for effective gene signatures for BD’s early diagnosis and elucidation of its underlying etiology. Methods We identified 82 differentially expressed genes (DEGs) in BD cases compared with healthy controls (HC) after combining two Gene Expression Omnibus datasets. We performed pathway analyses on these DEGs and constructed a gene co-expression network and its correlation with clinical traits. Hub genes were identified using a protein–protein interaction network. We manually selected CCL4 as a central hub gene, and gene-set enrichment and immune cell subset analyses were applied on patients in high- and low-CCL4 expression groups. Meanwhile, we validated the diagnostic value of hub genes in differentiating BD patients from HC in peripheral blood mononuclear cells using real-time PCR. Results Twelve hub genes were identified, and we validated the upregulation of CCL4 and the downregulation of NPY2R mRNA expression. Higher expression of CCL4 was accompanied by larger fractions of CD8 + T cells, natural killer cells, M1 macrophages, and activated mast cells. Receiver operator characteristic curves showed good discrimination between cases and controls based on the expression of these genes. Conclusion CCL4 and NPY2R could be diagnostic biomarkers for BD that reveal inflammatory status and predict vascular involvement in BD, respectively.
Statistical Evaluation of Mechanistic Water‐Quality Models

Current practice for the verification of water‐quality simulation models is to use a combination of modeler judgment and graphical analysis to assess the adequacy of a model. Statistical testing of goodness‐of‐fit is sometimes undertaken, but usually with a null hypothesis that does not allow distinction between acceptable fit and highly variable data. In this paper, statistical methods are proposed to augment, but not replace, this conventional approach with a quantitative expression of goodness‐of‐fit. Model verification is expressed as a problem in hypothesis testing that may be conducted using a variety of statistical methods. Guidance is provided on the appropriate structure of the null hypothesis so that good model fit is not confounded with highly variable predictions and observations. In addition, consequences and corrective measures associated with assumption violations are examined. The t‐test, the Wilcoxon test, regression analysis, and the Kolmogorov‐Smirnov test are extensively discussed, and.
Optimal Shoulder Abduction Angles during Baseball Pitching from Maximal Wrist Velocity and Minimal Kinetics Viewpoints

Baseball coaches train pitchers to keep their shoulder abduction at 90o during delivery, because this angle is believed to maximize ball speed and reduce the stress on the throwing arm. In fact, however, the shoulder abduction angle for some pitchers, including professional pitchers, deviates from 90o. There likely are reasons for such deviation. The purposes of this study, therefore, were to investigate the effects of shoulder abduction angle on ball velocity and on the injury-related joint kinetic variable, and to determine why the shoulder abduction angle varies among pitchers. Eleven professional pitchers were videotaped with two high-speed cameras. The resulting kinematic data were used to simulate several pitching motions by varying the shoulder abduction angle from the actual angle. Maximum wrist velocity was used as a reasonable approximation of ball velocity. Elbow varus torque was used as a kinetic variable. The square torque for the throwing arm and torque change for the throwing arm were used .