Miracle-dz/UniFAR-FTUs huggingface dataset:
First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas

Pancreatic β-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic β-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [18F]FB(ePEG12)12-exendin-4 (18F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of 18F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of 18F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of 18F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. 18F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of 18F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). 18F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. 18F-Ex4 is promising for clinical PET imaging targeting pancreatic β cells.
Extrinsically Integrated Instructional Quizzes in Learning Games: An Educational Disaster or Not?

Instructional quizzes are frequently used in educational games. When they present correct answers after learners have responded, these quizzes can be used on their own for teaching new factual and conceptual knowledge (no additional learning materials are needed). In games, these quizzes are often unrelated to gameplay: gameplay can be viewed as a reward for answering quiz questions. This has been criticized in game-based learning literature as a “chocolate-covered-broccoli” approach. However, is it really a bad approach? Theories offer conflicting predictions concerning the instructional efficiency of in-game quizzes relative to bare quizzes (i.e., not embedded in games) and empirical literature is lacking. Here, we present a within-subject design study (N = 69), in which 10–12-year-olds learn from both an in-game quiz and a bare quiz and undergo immediate and 2–3 weeks delayed post-test on the quiz questions. A modest difference in learning outcomes favoring the bare quiz was found in the immediate post-tests (d = 0.46), but not in the 2–3 weeks delayed post-tests (d = 0.09). Children enjoyed the game more than the bare quiz (dz = 0.65) and 59 preferred the game in the free-choice period. The findings suggest that both a bare quiz and a quiz within a game have their place at the table for useful educational interventions: the bare quiz should be preferred in schooling contexts; whereas, the game in leisure time situations as a voluntary activity. In the latter case, it should be considered how the game and the quiz are integrated.
Setting Statistical Thresholds Is Useful to Define Truly Effective Conservation Interventions

Effective interventions are needed to solve conflicts between humans and predators over livestock killing, nuisance behavior, and attacks on pets and humans. Progress in quantification of evidence-based effectiveness and selection of the best interventions raises new questions, such as the existence of thresholds to identify truly effective interventions. Current classification of more and less effective interventions is subjective and statistically unjustified. This study describes a novel method to differentiate true and untrue effectiveness on a basis of false positive risk (FPR). I have collected 152 cases of applications of damage-reducing interventions from 102 scientific publications, 26 countries, 22 predator species, and 6 categories of interventions. The analysis has shown that the 95% confidence interval of the relative risk of predator-caused damage was 0.10–0.25 for true effectiveness (FPR < 0.05) and 0.35–0.56 for untrue effectiveness (FPR ≥ 0.05). This means that damage was reduced by 75–90% for truly effective interventions and by 44–65% for interventions of untrue effectiveness. Based on this, it was specified that truly effective interventions have the relative risk ≤ 0.25 (damage reduction ≥ 75%) and the effectiveness of interventions with the relative risk > 0.25 (damage reduction < 75%) is untrue. This threshold is statistically well-justified, stable, easy to remember, and practical to use in anti-predator interventions. More research is essential to know how this threshold holds true for other conservation interventions aiming to reduce negative outcomes (e.g., poaching rates) or increase positive outcomes (e.g., species richness).
Do Ballast Water Management Systems Reduce Phytoplankton Introductions to Canadian Waters?

Global coastal aquatic ecosystems are negatively impacted by the introduction of harmful aquatic species through the discharge of ships’ ballast water. To reduce discharges of harmful aquatic organisms and pathogens, such as toxic phytoplankton species, ships are now transitioning to the use of ballast water management systems (BWMS) instead of ballast water exchange (BWE). This study examines the abundance and diversity of phytoplankton in ballast water managed by BWMS (or a combination of both BWE + BWMS) in comparison to those in ballast water managed by BWE alone (collected from ships arriving to Canada’s Pacific coast in 2017–2018 and 2008, respectively). The abundance and diversity of phytoplankton species were also examined in relation to key variables such as ballast water salinity and ballast water age. Total abundance of phytoplankton was significantly lower in preserved samples managed by either a BWMS or BWE + BWMS compared to BWE alone. Abundances in preserved samples were higher than observed in fresh (unpreserved) samples at the time of collection, with all samples managed by a BWMS meeting international limits for the number of viable organisms ≥10 and <50 μm in minimum dimension (based on six 1-mL live counts). While there was no apparent influence of factors such as treatment type [e.g., ultraviolet (UV) or chlorine], presence of filtration, ballast water salinity, ballast water age, nor location of last ballast water uptake on phytoplankton abundances in preserved samples, power to detect differences may be limited by sample size. Ballast water managed by BWMS also tended to have lower abundances of harmful phytoplankton species, although the difference was not statistically significant – additional research into the community composition of live cells in fresh samples could be valuable to discriminate the risk associated with phytoplankton surviving ballast water treatment.
Understanding the Role of Gibberellic Acid and Paclobutrazol in Terminal Heat Stress Tolerance in Wheat

Understanding the physiological mechanism of tolerance under stress conditions is an imperative aspect of the crop improvement programme. The role of plant hormones is well-established in abiotic stress tolerance. However, the information on the role of gibberellic acid (GA) in abiotic stress tolerance in late sown wheat is still not thoroughly explored. Thus, we aimed to investigate the role of endogenous GA3 level in stress tolerance in contrasting wheat cultivars, viz., temperature-tolerant (HD 2643 and DBW 14) and susceptible (HD 2189 and HD 2833) cultivars under timely and late sown conditions. We created the variation in endogenous GA3 level by exogenous spray of GA3 and its biosynthesis inhibitor paclobutrazol (PBZ). Tolerant genotypes had higher antioxidant enzyme activity, membrane stability, and photosynthesis rate, lower lipid peroxidase activity, and better growth and yield traits under late sown conditions attributed to H2O2 content. Application of PBZ escalated antioxidant enzymes activity and photosynthesis rate, and reduced the lipid peroxidation and ion leakage in stress, leading to improved thermotolerance. GA3 had a non-significant effect on antioxidant enzyme activity, lipid peroxidation, and membrane stability. However, GA3 application increased the test weight in HD 2643 and HD 2833 under timely and late sown conditions. GA3 upregulated GA biosynthesis and degradation pathway genes, and PBZ downregulated kaurene oxidase and GA2ox gene expression. GA3 also upregulated the expression of the cell expansins gene under both timely and late sown conditions. Exogenous GA3 did not increase thermotolerance but positively affected test weight and cell expansins gene expression. No direct relationship existed between endogenous GA3 content and stress tolerance traits, indicating that PBZ could have conferred thermotolerance through an alternative mechanism instead of inhibiting GA3biosynthesis.
Development of an Early Warning Model for Predicting the Death Risk of Coronavirus Disease 2019 Based on Data Immediately Available on Admission

Introduction: COVID-19 has overloaded worldwide medical facilities, leaving some potentially high-risk patients trapped in outpatient clinics without sufficient treatment. However, there is still a lack of a simple and effective tool to identify these patients early. Methods: A retrospective cohort study was conducted to develop an early warning model for predicting the death risk of COVID-19. Seventy-five percent of the cases were used to construct the prediction model, and the remaining 25% were used to verify the prediction model based on data immediately available on admission. Results: From March 1, 2020, to April 16, 2020, a total of 4,711 COVID-19 patients were included in our study. The average age was 63.37 ± 16.70 years, of which 1,148 (24.37%) died. Finally, age, SpO2, body temperature (T), and mean arterial pressure (MAP) were selected for constructing the model by univariate analysis, multivariate analysis, and a review of the literature. We used five common methods for constructing the model and finally found that the full model had the best specificity and higher accuracy. The area under the ROC curve (AUC), specificity, sensitivity, and accuracy of full model in train cohort were, respectively, 0.798 (0.779, 0.816), 0.804, 0.656, and 0.768, and in the validation cohort were, respectively, 0.783 (0.751, 0.815), 0.800, 0.616, and 0.755. Visualization tools of the prediction model included a nomogram and an online dynamic nomogram (https://wanghai.shinyapps.io/dynnomapp/). Conclusion: We developed a prediction model that might aid in the early identification of COVID-19 patients with a high probability of mortality on admission. However, further research is required to determine whether this tool can be applied for outpatient or home-based COVID-19 patients.
Effect of Environmental Stress on the Nutrient Stoichiometry of the Clonal Plant Phragmites australis in Inland Riparian Wetlands of Northwest China

Clonal plants play an important role in determining ecosystem properties such as community stability, species diversity and nutrient cycling. However, relatively little information is available about the stoichiometric characteristics of clonal plants and their drivers in inland riparian wetlands under strong environmental stress. In this manuscript, we studied the clonal plant Phragmites australis in an inland riparian wetland of Northwest China and compared its nutrient distribution and stoichiometry trade-offs as well as its responses to soil environmental factors in three different environments, namely, a wetland, a salt marsh, and a desert. We found that (1) P. australis could adapt to heterogeneous environments by changing its nutrient allocation strategies, as evidenced by the significant decrease in N and P concentrations, and significant increase in whole-plant C:P and N:P ratios from the wetland to the desert habitats. (2) P. australis adapted to stressful environments by changing its nutrient allocation patterns among different modules, showing a greater tendency to invest N and P in underground modules (rhizomes and roots) and an increase in the utilization efficiency of N and P in the leaves, and stems as environmental stress increased. (3) The C-N, C-P, and N:P-C in the whole plant and in each module showed significant anisotropic growth relationships in the three habitats (P < 0.05). (4) Soil water, pH and salt were the main factors limiting nutrient stoichiometry. The results of this study clarified the ecological adaptation mechanism of the clonal plant P. australis to heterogeneous environments and provided targeted protection strategies for inland riparian wetlands in Northwest China.
Molecular and Pathological Investigations of Selected Viral Neuropathogens in Rabies-Negative Brains of Cats and Dogs Revealed Neurotropism of Carnivore Protoparvovirus-1

Throughout the year, the Thai Red Cross Society (TRCS), Bangkok, Thailand, received more than 100 animals that died of suspected rabies due to neurological clinical signs. Concerning the role of viral infection in the brain in the outcome of neurological diseases in cats and dogs, a comprehensive study was conducted of 107 brain samples of cats and dogs submitted to the TRCS from August 2019 to August 2020. Selective molecular screening using conventional polymerase chain reaction (PCR) and reverse transcription PCR targeting nine viral pathogens was employed in addition to histopathological investigations. The results showed that carnivore protoparvovirus-1 (CPPV-1) was detected in 18.69% of the cats and dogs sampled (20/107). These results were found in young and old animals; the brain tissue did not show any pathological changes suggesting encephalitis or cerebellar hypoplasia. In addition, feline calicivirus, feline alphaherpesvirus-1, feline coronavirus, and canine distemper virus were also detected, providing a broader range of potential viral infections to consider in the clinical manifestation of neurological disorders in companion animals. The detection of all pathogens was confirmed by the localization of each viral antigen in various resident brain cells using immunohistochemistry. A unique L582S amino acid substitution of the non-structural protein 1 gene coding sequence, speculated to be associated with the neurotropism of CPPV-1 in cats and dogs, was not evident. In conclusion, this study revealed a noteworthy neurotropism of CPPV-1 in both cats and dogs without neurological lesions.
The Cognitive Connectome in Healthy Aging

Objectives: Cognitive aging has been extensively investigated using both univariate and multivariate analyses. Sophisticated multivariate approaches such as graph theory could potentially capture unknown complex associations between multiple cognitive variables. The aim of this study was to assess whether cognition is organized into a structure that could be called the “cognitive connectome,” and whether such connectome differs between age groups. Methods: A total of 334 cognitively unimpaired individuals were stratified into early-middle-age (37–50 years, n = 110), late-middle-age (51–64 years, n = 106), and elderly (65–78 years, n = 118) groups. We built cognitive networks from 47 cognitive variables for each age group using graph theory and compared the groups using different global and nodal graph measures. Results: We identified a cognitive connectome characterized by five modules: verbal memory, visual memory—visuospatial abilities, procedural memory, executive—premotor functions, and processing speed. The elderly group showed reduced transitivity and average strength as well as increased global efficiency compared with the early-middle-age group. The late-middle-age group showed reduced global and local efficiency and modularity compared with the early-middle-age group. Nodal analyses showed the important role of executive functions and processing speed in explaining the differences between age groups. Conclusions: We identified a cognitive connectome that is rather stable during aging in cognitively healthy individuals, with the observed differences highlighting the important role of executive functions and processing speed. We translated the connectome concept from the neuroimaging field to cognitive data, demonstrating its potential to advance our understanding of the complexity of cognitive aging.
Weekly Variations of Short-Duration Maximal Jumping Performance in Soccer Players: Exploring Relationships With Accumulated Training Load and Match Demands

Purpose: The aim of this study was 2-fold: (1) to analyze variations of short-duration maximal jumping performance in players exposed to a match and those who were not and (2) to analyze the relationships between changes in the short-duration maximal jumping performance and different accumulated training load and match demands measures. Methods: Twenty-four professional soccer players (age: 20.3 ± 1.7 years) were monitored daily for their training load and match demands over 6 weeks. In addition, they performed a weekly short-duration maximal jumping performance test (72 h after the last match). Results: Negative moderate correlations were found between percentage of change of countermovement jump (CMJ) height and Acummulated training load (ATL) of total distance (TD), high metabolic load (HML), accelerations (ACC), and decelerations (DEC) (r = −0.38, p = 0.004; r = −0.33, p = 0.013; r = −0.39, p = 0.003; and r = −0.30, p = 0.026). No correlations were found for match load (ML). TD, HML, ACC, and DCC (r = 0.27, r = 0.25, r = 0.31, and r = 0.22, respectively) were used to predict the percentage of change of CMJ height. Conclusion: Match participation has negative effects on CMJ performance. The ATL of HML, ACC, DCC, and TD have a significant influence on both CMJ measures changes. Also, the ATL values of those metrics are the best predictors of the percentage changes of CMJ performance.
Deciphering the Antibacterial Role of Peptide From Bacillus subtilis subsp. spizizenii Ba49 Against Staphylococcus aureus

An increase in antibiotic resistance has led to escalating the need for the development of alternate therapy. Antimicrobial peptides (AMPs) are at the forefront of replacing conventional antibiotics, showing slower development of drug resistance, antibiofilm activity, and the ability to modulate the host immune response. The ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens that jeopardize most conventional antibiotics are known to be involved in severe respiratory tract, bloodstream, urinary tract, soft tissue, and skin infections. Among them, S. aureus is an insidious microbe and developed resistance against conventional antibiotics. In the present study, an AMP (named as peptide-Ba49) isolated from Bacillus subtilis subsp. spizizenii strain from Allium cepa (the common onion) exhibited strong antibacterial efficacy against S. aureus ATCC 25923. The mode of action of this peptide-Ba49 on S. aureus was deciphered through various sensitive probes, i.e., DiSC3 (5) and H2DCFDA, suggesting the peptide-Ba49 to be acting upon through change in membrane potential and by triggering the production of reactive oxygen species (ROS). This induced disruption of the cell membrane was further supported by morphological studies using scanning electron microscopy (SEM). Investigations on a possible post-antibiotic effect (PAE) of peptide-Ba49 showed prolonged PAE against S. aureus. Furthermore, the peptide-Ba49 prevented the formation of S. aureus biofilm at low concentration and showed its potential to degrade the mature biofilm of S. aureus. The peptide-Ba49 also exhibited intracellular killing potential against S. aureus ATCC 25923 in the macrophage cells, and moreover, peptide-Ba49 was found to bolster the fibroblast cell migration in the scratch assay at low concentration, exhibiting a wound healing efficacy of this peptide. These studies demonstrated that peptide-Ba49 isolated from the strain B. subtilis subsp. spizizenii could be a therapeutic candidate to combat the pathogenic S. aureus infections.
Genome-Wide SNP Discovery and Population Genetic Analysis of Mesocentrotus nudus in China Seas

Mesocentrotus nudus is an important commercially aquatic species because of its high edible and medicinal values. However, wild stocks have dramatically decreased in recent decades. Understanding the population structure and genetic diversity can provide vital information for genetic conservation and improvement. In the present study, the genotyping-by-sequencing (GBS) approach was adopted to identify the genome-wide single-nucleotide polymorphisms (SNPs) from a collection of 80 individuals consisting of five geographical populations (16 individuals from each population), covering the natural habitats of M. nudus in China seas. An average of 0.96-Gb clean reads per sample were sequenced, and a total of 51,738 biallelic SNPs were identified. Based on these SNPs, diversity index analysis showed that all populations have a similar pattern with positive Fis (0.136) and low Ne (724.3). Low genetic differentiation and high genetic connectivity among five geographical populations were detected by pairwise Fst, principal component analysis (PCA), admixture, and phylogenetic analysis. Besides, two YWL individuals originating from an isolated ancestor may imply that there is a genetically differentiated population in the adjacent sea. Overall, the results showed that GBS is an effective method to detect genome-wide SNPs for M. nudus and suggested that the protective measures and the investigation with larger spatial scale and sample size for M. nudus should be carried out in the future.
Utilizing Intraoperative Navigated 3D Color Doppler Ultrasound in Glioma Surgery

Background In glioma surgery, the patient’s outcome is dramatically influenced by the extent of resection and residual tumor volume. To facilitate safe resection, neuronavigational systems are routinely used. However, due to brain shift, accuracy decreases with the course of the surgery. Intraoperative ultrasound has proved to provide excellent live imaging, which may be integrated into the navigational procedure. Here we describe the visualization of vascular landmarks and their shift during tumor resection using intraoperative navigated 3D color Doppler ultrasound (3D iUS color Doppler). Methods Six patients suffering from glial tumors located in the temporal lobe were included in this study. Intraoperative computed tomography was used for registration. Datasets of 3D iUS color Doppler were generated before dural opening and after tumor resection, and the vascular tree was segmented manually. In each dataset, one to four landmarks were identified, compared to the preoperative MRI, and the Euclidean distance was calculated. Results Pre-resectional mean Euclidean distance of the marked points was 4.1 ± 1.3 mm (mean ± SD), ranging from 2.6 to 6.0 mm. Post-resectional mean Euclidean distance was 4.7. ± 1.0 mm, ranging from 2.9 to 6.0 mm. Conclusion 3D iUS color Doppler allows estimation of brain shift intraoperatively, thus increasing patient safety. Future implementation of the reconstructed vessel tree into the navigational setup might allow navigational updating with further consecutive increasement of accuracy.