Miracle-dz/UniFAR-FTUs huggingface dataset:
Age- and sex-dependent effects of metformin on neural precursor cells and cognitive recovery in a model of neonatal stroke

Metformin expands the neural precursor pool in adult females, but not males, and is correlated with cognitive recovery. Resident neural stem and progenitor cells, collectively termed neural precursor cells (NPCs), reside in a well-defined neurogenic niche in the subventricular zone (SVZ) and contribute to ongoing postnatal neurogenesis. It is well established that the NPC niche can alter the behavior of NPCs. NPC activation is a promising therapeutic strategy for brain repair. The drug metformin has been shown to activate neural stem cells, promote differentiation, and lead to functional motor recovery in a neonatal stroke model. We demonstrate that metformin-induced NPC expansion and functional recovery is sex hormone dependent. Metformin increases the size of the NPC pool in adult females, but not males, and promotes cognitive recovery in a model of brain injury in females, but not males. Our data demonstrate that metformin has age- and sex-dependent effects on NPCs that correlate with functional recovery, which has important implications for neural repair.
GPR124 facilitates pericyte polarization and migration by regulating the formation of filopodia during ischemic injury

Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. Methods: A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. Results: GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. Conclusion: Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.
Exercise, Mood, Self-Efficacy, and Social Support as Predictors of Depressive Symptoms in Older Adults: Direct and Interaction Effects

Background Depression is a chronic condition that affects up to 15% of older adults. The healthogenic effects of regular exercise are well established, but it is still unclear which exercise-related variables characterise the antidepressant effects of exercise. Thus, the purpose of this study was to examine the extent to which exercise-related variables (exercise behaviour, exercise-induced mood, exercise self-efficacy, and social support) can predict depressive symptoms in a cohort of community-dwelling older adults. Methods This study employed a cross-sectional analysis of questionnaire data from a sample of 586 community-dwelling older Australians aged 65 to 96 years old. Participants completed the Center for Epidemiologic Studies Depression Scale, modified CHAMPS Physical Activity Questionnaire for Older Adults, Four-Dimension Mood Scale, Self-Efficacy for Exercise Scale, and Social Provisions Scale – Short Form. Bivariate correlations were performed, and hierarchical multiple regression was subsequently used to test the regression model. Results Exercise behaviour, exercise-induced mood, exercise self-efficacy, and social support were all negatively associated with depressive symptoms (r = −0.20 to −0.56). When the variables were entered as predictors into the hierarchical multiple regression model, social support was the strongest predictor of depressive symptoms (β = −0.42), followed by exercise-induced mood (β = −0.23), and exercise self-efficacy (β = −0.07). Exercise behaviour did not explain any additional variance in depressive symptoms. A modest interaction effect was also observed between exercise-induced mood and social support. Conclusion These findings indicate that social support is the strongest predictor of depressive symptomology in community-dwelling older adults, particularly when combined with positive exercise-induced mood states. When addressing the needs of older adults at risk of depression, healthcare professionals should consider the implementation of exercise programmes that are likely to benefit older adults by improving mood, enhancing self-efficacy, and building social support.
Pregnancy outcome in women with early pregnancy bleeding in a tertiary health care facility in Southwestern, Nigeria

Background: Bleeding in early pregnancy is a common occurrence, but very little is known about the outcome of pregnancy complicated by bleeding during the early part of the gestation. This prompted me to explore these in a prospective cohort study over a period of 12 months. Objectives: The aim of this study is to determine the mode of presentation and the materno-fetal outcome in pregnancies complicated by early pregnancy bleeding and compare with a group without such complication. Materials and Methods: A total of 72 cases were observed and these patients were matched with a control group in maternal age in years (+2), parity and gestational ages in weeks. Thus, a total number of 144 patients were studied. Results: Pregnancy loses or abortions occurred in 12 patients (16.6%) in the study group compared with 3 patients (4.1%) in the control group (P < 0.05), 14 patients (19.4%) had preterm deliveries in the study group, compared with four patients (5.5%) in the control group (P < 0.05) and low birth weight was observed in 15 patients (20.83%) among the study group compared with 5 patients (6.94%) in the control group (P < 0.05). All the three outcome measures above had statistically significant differences when compared in between the two groups. These poor outcomes were observed among those who bled in the second trimester, those who had episodes of bleeding in both the first and the second trimesters or recurrent vaginal bleeding throughout the pregnancy. Conclusion: The outcome of this study showed that bleeding in early pregnancy, especially during the second trimester or recurrent bleeding in both the first and the second trimesters correlates with poor pregnancy outcomes.
Stereotactic Radiofrequency Ablation of Liver Tumors in Octogenarians

Purpose: This study aimed to evaluate the efficacy and overall clinical outcome of patients over the age of 80 undergoing stereotactic radiofrequency ablation (SRFA) and to compare the results to a younger population with propensity score matching. Materials and Methods: Between 2006 and 2018 36 patients aged between 80 and 90 years underwent 46 SRFA sessions of 70 primary and secondary liver tumors. For comparison of treatment safety and efficacy 36 younger patients were selected with propensity score matching by the R package “MatchIt” in this retrospective, single-center study. Results: 68/70 tumors were successfully ablated at first ablation session (97% primary technical efficacy rate). Local tumor recurrence developed in 5 of 70 nodules (7.1%). The complication rate above Clavien-Dindo Grade III was 6.5% (3 of 46). The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 84.6, 50.5, and 37.9% for HCC patients and 87.5%, 52.5% at 1-, and 3-years for CRC patients. The disease-free survival (DFS) for HCC patients after SRFA was 79.1, 35.6, and 23.7%, at 1-, 3-, and 5- years, and 75%, 22.5% at 1-, and 3-years for CRC patients. There were no significant differences in terms of technical efficacy, local recurrences, major complications, OS and DFS compared to the control group. Conclusion: SRFA in octogenarians is a safe, feasible and useful option in the management of primary or metastatic liver tumors with no significant difference in outcomes compared to a younger control group.
Development of an Eye Model With a Physiological Blink Mechanism

Purpose To develop an eye model with a physiological blink mechanism. Methods All parts of the eye model were designed using computer-aided design software. The eyelid consisted of a unique 3D printed structure containing teeth to physically secure a flexible membrane. Both the eyeball and eyelid membrane were synthesized using polyvinyl alcohol (PVA). Four molecular weights of PVA (89–98, 85–124, 130, and 146–186 kDa) were tested at a range of concentrations between 5% and 30% weight/volume. The wettability and water content of these materials were compared with the bovine cornea and sclera. The model was connected to a microfluidic pump, which delivers artificial tear solution (ATS) to the eyelid. A corneal topographer was used to evaluate the tear break-up and tear film regeneration. Results The eyelid flexes and slides across the eyeball during each blink, which ensures direct contact between the two surfaces. When loaded with an ATS, this mechanism evenly spreads the solution over the eyeball to generate an artificial tear film. The artificial tear film in this eye model had a tear break-up time (TBUT) of 5.13 ± 0.09 seconds at 1.4 μL/min flow rate, 6 blinks/min, and <25% humidity. Conclusions This model simulates a physiological blink actuation and an artificial tear film layer. Future studies will examine variations in flow rates and ATS composition to simulate clinical values of TBUT. Translational Relevance The eye model could be used to study in vitro TBUT, tear deposition, and simple drug delivery.
First record of the New Guinea flatworm Platydemus manokwari (Platyhelminthes, Geoplanidae) as an alien species in Hong Kong Island, China

Abstract The New Guinea flatworm (Platydemus manokwari) caused extinction of the native land snails on several Pacific island in past decades, and therefore it has been listed among the top 100 of the world’s worst invasive alien species. Using morphological and molecular methods, New Guinea flatworms were discovered and identified for the first time in Hong Kong Island during a field investigation in July and August 2018. The flatworms were 32–60 mm long, 3–5 mm wide, and 1–2 mm thick. The dorsal side of the flatworm was dark brown with a thin yellow central line, and its ventral side appeared pale grey. To further verify this species, both 18S rDNA and mitochondrial cytochrome c oxidase subunit I gene (COX1) obtained from three specimens of P. manokwari were sequenced and analysed. While comparing these sequences with those previously deposited in GenBank, these 18S rDNA sequences shared 100% identity with the single available 18S rDNA sequence of P. manokwari; and the obtained COX1 sequences were identical to those of P. manokwari world genotype. Two native snails, Criptosoma imperator and Bradybaena similaris, have been found to be the prey of this predator during this investigation. Therefore, the invasive New Guinea flatworm certainly will cause a serious impact on the biodiversity of native snail populations, and an economic and environmental risk assessment for P. manokwari need to be completed in the near future in Hong Kong.
Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment

Targeting tumor angiogenesis pathway via VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, the combined application of siVEGF and chemotherapeutic agents for simultaneous targeting of tumor proliferation and angiogenesis has been a research hotspot to explore a promising NSCLC therapy regimen. Methods: We designed, for the first time, a rational therapy strategy via intelligently co-delivering siVEGF and chemotherapeutics etoposide (ETO) by multi-functional nanoparticles (NPs) directed against the orthotopic NSCLC. These NPs consisted of cationic liposomes loaded with siVEGF and ETO and then coated with versatile polymer PEGylated histidine-grafted chitosan-lipoic acid (PHCL). We then comprehensively evaluated the anti-angiogenic and anti-proliferation efficiency in the in vitro tumor cell model and in bioluminescent orthotopic lung tumor bearing mice model. Results: The NPs co-delivering siVEGF and ETO exhibited tailor-made surface charge reversal features in mimicking tumor extracellular environment with improved internal tumor penetration capacity and higher cellular internalization. Furthermore, these NPs with flexible particles size triggered by intracellular acidic environment and redox environment showed pinpointed and sharp intracellular cargo release guaranteeing adequate active drug concentration in tumor cells. Enhanced VEGF gene expression silencing efficacy and improved tumor cell anti-proliferation effect were demonstrated in vitro. In addition, the PHCL layer improved the stability of these NPs in neutral environment allowing enhanced orthotopic lung tumor targeting efficiency in vivo. The combined therapy by siVEGF and ETO co-delivered NPs for orthotopic NSCLC simultaneously inhibited tumor proliferation and tumor angiogenesis resulting in more significant suppression of tumor growth and metastasis than monotherapy. Conclusion: Combined application of siVEGF and ETO by the multi-functional NPs with excellent and on-demand properties exhibited the desired antitumor effect on the orthotopic lung tumor. Our work has significant potential in promoting combined anti-angiogenesis therapy and chemotherapy regimen for clinical NSCLC treatment.
Distribution and Restoration of Serotonin-Immunoreactive Paraneuronal Cells During Caudal Fin Regeneration in Zebrafish

Aquatic vertebrates possess diverse types of sensory cells in their skin to detect stimuli in the water. In the adult zebrafish, a common model organism, the presence of such cells in fins has only rarely been studied. Here, we identified scattered serotonin (5-HT)-positive cells in the epidermis of the caudal fin. These cells were distinct from keratinocytes as revealed by their low immunoreactivity for cytokeratin and desmosome markers. Instead, they were detected by Calretinin (Calbindin-2) and Synaptic vesicle glycoprotein 2 (SV2) antibodies, indicating a calcium-regulated neurosecretory activity. Consistently, electron microscopy revealed abundant secretory organelles in desmosome-negative cells in the fin epidermis. Based on the markers, 5-HT, Calretinin and SV2, we referred to these cells as HCS-cells. We found that HCS-cells were spread throughout the entire caudal fin at an average density of 140 cells per mm2 on each fin surface. These cells were strongly enriched at ray bifurcations in wild type fins, as well as in elongated fins of another longfin mutant fish. To determine whether hydrodynamics play a role in the distribution of HCS-cells, we used an interdisciplinary approach and performed kinematic analysis. Measurements of particle velocity with a fin model revealed differences in fluid velocities between bifurcated rods and adjacent non-bifurcated regions. Therefore the accumulation of HCS-cells near bone bifurcations may be a biological adaptation for sensing of water parameters. The significance of this HCS-cell pattern is reinforced by the fact, that it is reestablished in the regenerated fin after amputation. Regeneration of HCS-cells was not impaired by the chemical inhibition of serotonin synthesis, suggesting that this neurotransmitter is not essential for the restorative process. In conclusion, our study identified a specific population of solitary paraneurons in the zebrafish fin, whose distribution correlates with fluid dynamics.
Effects of Early Language Deprivation on Brain Connectivity: Language Pathways in Deaf Native and Late First-Language Learners of American Sign Language

Previous research has identified ventral and dorsal white matter tracts as being crucial for language processing; their maturation correlates with increased language processing capacity. Unknown is whether the growth or maintenance of these language-relevant pathways is shaped by language experience in early life. To investigate the effects of early language deprivation and the sensory-motor modality of language on white matter tracts, we examined the white matter connectivity of language-relevant pathways in congenitally deaf people with or without early access to language. We acquired diffusion tensor imaging (DTI) data from two groups of individuals who experienced language from birth, twelve deaf native signers of American Sign Language, and twelve hearing L2 signers of ASL (native English speakers), and from three, well-studied individual cases who experienced minimal language during childhood. The results indicate that the sensory-motor modality of early language experience does not affect the white matter microstructure between crucial language regions. Both groups with early language experience, deaf and hearing, show leftward laterality in the two language-related tracts. However, all three cases with early language deprivation showed altered white matter microstructure, especially in the left dorsal arcuate fasciculus (AF) pathway.
Students' Adoption and Learning Outcomes in a MOOC-based Flipped Course

MOOC-based flipped courses are a new educational trend that has been on the rise over the last few years. However, experimental studies providing empirical evidence about the effectiveness of these educational approaches are scarce. This paper presents the results of a quasi-experiment of a MOOC-based flipped course. The study was conducted on a mandatory third year course on Organizational Behavior in the School of Engineering at Pontificia Universidad Católica de Chile with 316 students organized into experimental and control groups. Both groups had the same teacher, shared the same content and the assessment plan, but the experimental group followed a Flipped Classroom methodology and the control group the traditional lecture methodology. The objective of this quasi-experiment is to compare the learning outcomes of each group and analyze the experimental group’s adoption of the initiative. The quasi-experiment lasted an entire semester, and the preliminary findings show that students who participated in the flipped course obtained statistically significantly better grades in the first course exam than students in the control group. Also, the interactions with the MOOC’s content in the experimental group show a regular behavior, suggesting that they adopted the class methodology well.
Effective Visualization of Time-Critical Notifications in Virtual Reality

Virtual Reality (VR) devices empower users to be fully immersed into a virtual environment. In an enclosed environment such as this, notifications indicating risks (e.g., risk of injury when bumping into walls) must be perceived as quickly and correctly as possible. Different to findings from previous work using displays to investigate fast response times, it seems that immersion into a virtual environment, width of field of view, and use of near-eye displays observed through lenses may all be factors having considerable impact on the perception of time-critical notifications. Therefore, we studied the effectiveness of five different visualization types (color, shape, size, text, number) in two different setups (room-scale, fixed-position) with 20 participants in VR. Our study consisted of a part in which we tested one notification and a part with multiple notifications showing up at the same time. We measured reaction time, correctness and subjective user evaluation. Our results show that visualization types can be organized by a consistent effectiveness ranking for different numbers of notification elements presented. Further, we offer promising recommendations regarding which visualization type is best for showing time-critical notifications in future VR applications.
User expectations towards machine translation: A case study

Neural machine translation (NMT) systems have emerged as powerful platforms for providing fluent translations in a variety of languages and domains. The wide-spread adoption of NMT has heightened the need for studying the results and impact of these systems. Although acceptance of machine translation has been analyzed, the expectations of users towards NMT have not received much attention yet. This paper investigates the expectations of novice translators enrolled on a postgraduate program in specialized translation. In addition, it examines the confirmation or disconfirmation of expectations towards machine translation (MT) output among this user group. A three-step mixed-method approach was applied: a quantitative questionnaire and two recurrent (pre-trial and post-trial) evaluations of raw MT outputs. The evaluations consisted of the identification and classification of errors in NMT output according to the Multidimensional Quality Metrics. The respondents expected the MT output to be of rather low quality, but the quality of NMT output was not as high as the participants expected. Compared to the expected frequency of error types in the MT output, the reported frequency differed significantly. This paper argues that the users’ experience and expectations have an impact on the use and evaluation of machine translation.
Antennal Morphology and Ultrastructure of Holotrichia parallela (Coleoptera: Scarabaeidae)

Abstract Antennal morphology and type and distribution of antennal sensilla of Holotrichia parallela (Motschulsky) (Coleoptera: Scarabaeidae) were determined using scanning electron microscopy and transmission electron microscopy. Holotrichia parallela antennae were a typical lamellate type, including a basal scape, a pedicel, a flagellum, and a lamellar club composed of the three terminal flagellomeres. The antennae of males were slightly longer than those of females. Twenty-two subtypes of sensilla were identified on the outer and inner surfaces of the lamellae in both sexes: three sensilla trichodea (TRS), three sensilla chaetica (CHS), four sensilla placodea (PLAS), two sensilla coeloconica (COS), six sensilla auricilica (AUS), one Böhm's bristle (BB), and three sensilla basiconica (BAS). TRS, CHS, and BB were distributed primarily on the outer surfaces of the antennae as mechanoreceptor sensilla, while PLAS, COS, AUS, and BAS were concentrated on the inner surfaces of the lamellae as chemoreceptors. PLAS and BAS were more abundant in males than in females, but females had more COS and AUS. PLAS were distributed along the lamellar periphery, while COS, BAS, and AUS were distributed in the center of the lamellae.