bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning Actions From Natural Language Instructions Using an ON-World Embodied Cognitive Architecture
Authors: Giorgi Ioanna , Cangelosi Angelo , Masala Giovanni L.
Published: May 2021

Endowing robots with the ability to view the world the way humans do, to understand natural language and to learn novel semantic meanings when they are deployed in the physical world, is a compelling problem. Another significant aspect is linking language to action, in particular, utterances involving abstract words, in artificial agents. In this work, we propose a novel methodology, using a brain-inspired architecture, to model an appropriate mapping of language with the percept and internal motor representation in humanoid robots. This research presents the first robotic instantiation of a complex architecture based on the Baddeley's Working Memory (WM) model. Our proposed method grants a scalable knowledge representation of verbal and non-verbal signals in the cognitive architecture, which supports incremental open-ended learning. Human spoken utterances about the workspace and the task are combined with the internal knowledge map of the robot to achieve task accomplishment goals. We train the robot to understand instructions involving higher-order (abstract) linguistic concepts of developmental complexity, which cannot be directly hooked in the physical world and are not pre-defined in the robot's static self-representation. Our proposed interactive learning method grants flexible run-time acquisition of novel linguistic forms and real-world information, without training the cognitive model anew. Hence, the robot can adapt to new workspaces that include novel objects and task outcomes. We assess the potential of the proposed methodology in verification experiments with a humanoid robot. The obtained results suggest robust capabilities of the model to link language bi-directionally with the physical environment and solve a variety of manipulation tasks, starting with limited knowledge and gradually learning from the run-time interaction with the tutor, past the pre-trained stage.
Imaging Voltage in Complete Neuronal Networks Within Patterned Microislands Reveals Preferential Wiring of Excitatory Hippocampal Neurons
Authors: Walker Alison S. , Raliski Benjamin K. , Nguyen Dat Vinh , Zhang Patrick , Sanders Kate , Karbasi Kaveh , Miller Evan W.
Published: May 2021

Voltage imaging with fluorescent dyes affords the opportunity to map neuronal activity in both time and space. One limitation to imaging is the inability to image complete neuronal networks: some fraction of cells remains outside of the observation window. Here, we combine voltage imaging, post hoc immunocytochemistry, and patterned microisland hippocampal culture to provide imaging of complete neuronal ensembles. The patterned microislands completely fill the field of view of our high-speed (500 Hz) camera, enabling reconstruction of the spiking patterns of every single neuron in the network. Cultures raised on microislands are similar to neurons grown on coverslips, with parallel developmental trajectories and composition of inhibitory and excitatory cell types (CA1, CA3, and dentate granule cells, or DGC). We calculate the likelihood that action potential firing in one neuron triggers action potential firing in a downstream neuron in a spontaneously active network to construct a functional connection map of these neuronal ensembles. Importantly, this functional map indicates preferential connectivity between DGC and CA3 neurons and between CA3 and CA1 neurons, mimicking the neuronal circuitry of the intact hippocampus. We envision that patterned microislands, in combination with voltage imaging and methods to classify cell types, will be a powerful method for exploring neuronal function in both healthy and disease states. Additionally, because the entire neuronal network is sampled simultaneously, this strategy has the power to go further, revealing all functional connections between all cell types.
Autism Spectrum Disorder Risk Factor Met Regulates the Organization of Inhibitory Synapses
Authors: Jeckel Pauline , Kriebel Martin , Volkmer Hansjürgen
Published: May 2021

A common hypothesis explains autism spectrum disorder (ASD) as a neurodevelopmental disorder linked to excitatory/inhibitory (E/I) imbalance in neuronal network connectivity. Mutation of genes including Met and downstream signaling components, e.g., PTEN, Tsc2 and, Rheb are involved in the control of synapse formation and stabilization and were all considered as risk genes for ASD. While the impact of Met on glutamatergic synapses was widely appreciated, its contribution to the stability of inhibitory, GABAergic synapses is poorly understood. The stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin. Here, we show in vivo and in vitro that Met is necessary and sufficient for the stabilization of GABAergic synapses via induction of gephyrin clustering. Likewise, we provide evidence for Met-dependent gephyrin clustering via activation of mTOR. Our results support the notion that deficient GABAergic signaling represents a pathomechanism for ASD.
Phenotypic Plasticity Conferred by the Metastatic Microenvironment of the Brain Strengthens the Intracranial Tumorigenicity of Lung Tumor Cells
Authors: Wei Xu-Ge , Bi Ke-Wei , Li Bo
Published: May 2021

Lung cancer is the leading cause of cancer-related deaths and is the primary source of brain metastases. Despite great advances in the study of the genetics and etiology of lung cancer in previous decades, the identification of the factors and mechanisms underlying the brain metastasis of lung tumors is still an open question. In this study, the results of bioinformatic conjoint analysis revealed that the metastatic microenvironment in the brain conferred lung tumor cell phenotypic plasticity, characterized by neural cell-like and embryonic–stem cell-like features. Meanwhile, the metabolic phenotype of the educated tumor cells underwent transition characterized by oxygen-related metabolism. The results of the experiments demonstrated that the downregulation of HOXB9 weakened the tumorigenicity of lung tumor cells. Bioinformatic prediction analysis also determined that many cell cycle-associated factors were potentially transcribed by HOXB9. Collectively, the results of this study suggested that under the influence of the metastatic environment of the brain, lung tumor cells seemed to acquire phenotypic plasticity characterized by neural cell-like features, and this transition may be associated with the aberrant upregulation of HOXB9.
Investigating 18F-FDG PET/CT Parameters as Prognostic Markers for Differentiated Thyroid Cancer: A Systematic Review
Authors: Wang Hongxi , Dai Hongyuan , Li Qianrui , Shen Guohua , Shi Lei , Tian Rong
Published: May 2021

Aims: The aim of this study was to determine whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters might be prognostic markers for patients with differentiated thyroid carcinoma (DTC).

Methods: We searched for eligible articles in PubMed, EMBASE (Ovid), Cochrane Library, and ClinicalTrials.gov from inception to February 2021. We included studies addressing the association between 18F-FDG PET/CT parameters and clinical outcomes among patients with DTC. Quality assessment was performed using the Quality in Prognosis Studies (QUIPS) tool.

Results: A total of 25 studies including 2,954 patients (1,994 females, 67.5%) were included; 2,416 patients (81.8%) had papillary thyroid carcinoma (PTC), and the mean or median follow-up time ranged from 19.1 months to 17.1 years. Thirteen (52.0%) studies were assessed as “unclear” for the domain of study participation. The most common timing of PET/CT scans was after thyroidectomy (in 20 of 25 studies, 80%), especially in patients with an elevated thyroglobulin (Tg) and a negative radioiodine whole-body scan (WBS). The most common PET parameter was FDG uptake. Twelve of 17 (70.6%) and 12 of 12 (100%) studies showed an association between PET/CT parameters and disease progression and survival in patients with DTC, respectively.

Conclusion:18F-FDG PET/CT parameters alone or combined with other variables can serve as prognostic markers to identify DTC patients with poor outcomes, especially in the setting of an elevated Tg and a negative WBS. Future research is needed to confirm these findings and to examine the prognostic value of PET/CT parameters for DTC patients, considering the heterogeneity in PET/CT parameters, unclear information of patients, and PET/CT-adapted treatment modifications.
Clinical Relevance of ABCB1, ABCG2, and ABCC2 Gene Polymorphisms in Chronic Myeloid Leukemia Patients Treated With Nilotinib
Authors: Loscocco Federica , Visani Giuseppe , Ruzzo Annamaria , Bagaloni Irene , Fuligni Fabio , Galimberti Sara , Di Paolo Antonello , Stagno Fabio , Pregno Patrizia , Annunziata Mario , Gozzini Antonella , Barulli Sara , Gabucci Elisa , Magnani Mauro , Isidori Alessandro
Published: May 2021

Tyrosine kinase inhibitors (TKIs) have radically changed the outcome of chronic myeloid leukemia (CML) patients in the last 20 years. Moreover, the advent of second generation TKIs, namely nilotinib and dasatinib, have largely increased the number of CML patients achieving deep and sustained molecular responses. However, the possible mechanisms capable of influencing the maintenance of the long-term molecular response are not yet fully known and understood. In this light, polymorphisms in MDR-ABC transporters may influence the efficacy and safety of TKIs. In this study, we examined seven single nucleotide polymorphisms (SNPs) in four ABC transporter genes: ABCC1 rs212090 (5463T>A), ABCC2 rs3740066 (3972C>T), ABCC2 rs4148386 G>A, ABCC2 rs1885301 (1549G>A), ABCG2 rs2231137 (34G>A), ABCG2 rs2231142 G>C, ABCB1 rs1045642 (3435C>T), to determine their effect on the achievement and/or loss of molecular response in 90 CML patients treated with nilotinib. We found that ABCC2 rs3740066 CC and CT as well as the ABCB1 rs1045642 TT genotypes correlated with a higher probability to achieve MR3 in a shorter time (p=0.02, p=0.004, and p=0.01), whereas ABCG2 rs2231137 GG was associated with lower probability of MR3 achievement (p=0.005). Moreover, ABCC2 rs3740066 CC genotype, the ABCB1 rs1045642 CC and TT genotypes were positively correlated with MR4 achievement (p=0.02, p=0.007, and p=0.003). We then generated a predictive model incorporating the information of four genotypes, to evaluate the combined effect of the SNPs. The combination of SNPs present in the model affected the probability and the time to molecular response. This model had a high prognostic significance for both MR3 and MR4 (p=0.005 and p=0.008, respectively). Finally, we found ABCG2 rs2231142 GG genotype to be associated with a decrease risk of MR3 loss. In conclusion, MDR-transporters SNPs may significantly affect the achievement and loss of molecular response in CML patients treated with nilotinib.
Extracorporeal Shock Wave Lithotripsy and Combined Therapy in Children: Efficacy and Long-Term Results
Authors: Burgos Lucena Laura , Fernández Bautista Beatriz , Parente Hernández Alberto , Ortiz Rodríguez Ruben , Angulo Madero Jose María
Published: May 2021

Background: Extracorporeal shock wave lithotripsy (ESWL) is nowadays the first choice for the treatment of upper urinary tract stones smaller than 2 cm, considering its low complications and high success rate.

Aim: To present an update of the current situation of ESWL treatment and to analyse our series of patients and the efficacy of combined lithiasis treatment in different locations and sizes.

Patients and Method: Retrospective study including patients with urolithiasis treated with ESWL between 2007 and 2019. Collected data included: gender and age at treatment, presentation symptoms, imaging studies, stone location and size, complications and stone clearance. Success was defined as stone-free status or the presence of clinically insignificant residual fragments (<4 mm after 3 months follow-up). Patients with residual stones larger than 4 mm after 3 months were programmed for another ESWL session or received a combined sandwich therapy, followed by URS or percutaneous approach.

Results: Between 2007 and 2019, 37 patients presented a total of 41 lithiasis episodes that were treated with ESWL sessions. Median age at first procedure was 9 years old (1–17) and median follow-up time was 6 years (3–12). Stones were located in the renal pelvis, followed by the lower, middle and upper calyx, proximal ureter, and 51% of our patients had multiple lithiasis. Median stone size was 12 mm (5–45), the main component being calcium oxalate (34%). During immediate postoperative period, 8 patients (19%) presented complications: renal colic, hematuria and urinary tract infection. After the first ESWL, 41% of the patients (n = 17) were stone-free. Out of the 24 residual lithiasis episodes (58%), three patients (7%) underwent a second ESWL session. In the remaining 19 patients, ESWL was combined with URS or percutaneous approach to achieve complete stone clearance. Overall stone free status after combined therapy was 95% (n = 39).

Conclusion: These data support that ESWL is an effective minimally invasive technique, with low cost and morbidity, reproducible and safe for the treatment of stone disease in children. Even though lithiasis size seems to be a significant factor in ESWL success, in combination with other lithotripsy procedures it can reach very high rates of stone clearance.
Diagnostic Value of Diurnal Variability of Orthostatic Heart Rate Increment in Children and Adolescents With POTS
Authors: Cai Hong , Wang Shuo , Zou Runmei , Li Fang , Zhang Juan , Wang Yuwen , Xu Yi , Wang Cheng
Published: May 2021

Objectives: This study aims to investigate the diurnal variability of heart rate (HR) increment after standing (ΔHR) in pediatric postural tachycardia syndrome (POTS) and explore appropriate cutoff values of ΔHR at different times for the POTS diagnosis.

Materials and Methods: Seventy-eight patients (9–14 years) who presented with orthostatic intolerance symptoms were enrolled. Forty-three patients were diagnosed as POTS (ΔHR ≥40 bpm), and 35 patients were assigned to the non-POTS group (ΔHR <40 bpm). Twenty-six healthy children served as the control group. All subjects completed three standing tests in the morning, afternoon, and evening. Orthostatic HR parameters were analyzed to predict the diagnosis of POTS. Additionally, 41 patients were recruited as an external validation group.

Results: Orthostatic HR increments in both the POTS and non-POTS groups exhibited diurnal variability, which was markedly larger in the morning (P < 0.05), whereas it did not differ with the time of day in the control group. Among the POTS patients, 100% met the diagnostic criteria for POTS in the morning, 44.2% in the afternoon, and 27.9% in the evening. Almost half of the POTS patients (51.2%) displayed a positive result only in the morning standing test. However, in the three standing tests at different times, ΔHR from 1 to 10 min after standing and ΔHRmax were the highest in the POTS group compared with in the non-POTS and control groups (P < 0.05). Furthermore, the maximum ΔHR (ΔHRmax) and ΔHR at 5 and 10 min in the afternoon and evening standing tests yielded moderate predictive values for the POTS diagnosis. The external validation test showed that the afternoon ΔHRmax ≥30 bpm to diagnose POTS yielded sensitivity, specificity, and accuracy of 85, 71.4, and 78%, respectively, and the evening ΔHRmax ≥25 bpm yielded sensitivity, specificity, and accuracy of 85, 76.2, and 80.5%, respectively.

Conclusions: The orthostatic HR increment exhibits diurnal variability in children and adolescents with POTS that may affect the diagnosis of POTS. Supplementary criteria are proposed for the POTS diagnosis based on diurnal variability.
Risk Factors for Recurrent Tracheoesophageal Fistula After Gross Type C Esophageal Atresia Repair
Authors: Yang Shen , Li Siqi , Yang Zhi , Liao Junmin , Hua Kaiyun , Zhang Yanan , Zhao Yong , Gu Yichao , Li Shuangshuang , Huang Jinshi
Published: May 2021

Background: To determine the possible risk factors of recurrent tracheoesophageal fistula (rTEF) after Gross type C esophageal atresia (EA) and tracheoesophageal fistula (TEF) repair.

Methods: The medical records of 343 pediatric patients with Gross type C EA/TEF who underwent surgical repair were retrospectively analyzed. The patients were retrospectively divided into two groups according to whether they had rTEF. Univariate and multivariable logistic regression analysis were performed to identify risk factors for rTEF.

Results: After the diagnosis of EA/TEF, 343 patients (221 boys) underwent primary repairs after birth. According to the follow-up results (257 patients survived, 42 died, and 43 were lost to follow-up), 259 patients (257 survived and two died after rTEF repair) were included in the analysis. rTEF occurred in 33 patients (33/259, 12.74%), with a median onset time to recurrence of 3.8 (2.2, 8.2) months. Multivariate analysis showed that closing the original TEF with ligation and hospital stay ≥ 28.5 days were significant risk factors of rTEF with OR of 4.083 (1.481, 11.261) and 3.228 (1.431, 7.282).

Conclusions: Surgical closure technique of original TEF and the length of initial stay could influence the occurrence of rTEF after Gross type C EA/TEF repair.
Case Report: Neonatal Multi-System Inflammatory Syndrome Associated With SARS-CoV-2 Exposure in Two Cases From Saudi Arabia
Authors: Shaiba Lana A. , Hadid Adnan , Altirkawi Khalid A. , Bakheet Hind M. , Alherz Aminah Mohammed , Hussain Shaik Asfaq , Sobaih Badr H. , Alnemri Abdulrahman M. , Almaghrabi Rana , Ahmed Medina , Arafah Maria A. , Jarallah Abdullah , Bukhari Elham Essa , Alzamil Fahad A.
Published: May 2021

Background: Vertical transmission of SARS-CoV-2 is under investigation. A few reports suggest the possibility of SARS-CoV-2 transmission from mothers to their neonates. Most neonates have mild symptoms, but some develop multisystem involvement and shock.

Case Presentation: We report two cases of possible SARS-CoV-2 vertical transmission from mothers to their neonates. The first case shows maternal infection with SARS-CoV-2 in the second trimester followed by recurrent infection in the third trimester right before the delivery. The infant demonstrated respiratory distress soon after delivery along with myocardial dysfunction and multi-organ system involvement. The second case shows maternal infection with SARS-COV-2 at the time of delivery with preterm labor secondary to placental abruption, with that delivery resulting in the preterm neonate requiring non-invasive ventilation with multisystem involvement in the context of persistently positive SARS-COV-2 PCR in the neonate. Both neonates were treated with IVIG along with steroids. Both neonates recovered fully and were discharged and allowed to go home.

Conclusion: In neonates, COVID-19 usually presents as an asymptomatic or mild illness; some may develop a more severe course. Our two cases, however, demonstrate that multisystem involvement, although rare, is possible. This report also supports the current evidence of possible vertical transmission from mothers to their neonates. This multisystem involvement might be underreported and should be considered in neonates with respiratory distress when born to mothers suffering of COVID-19.

Clinical Trial Registration: [KSUMC], identifier [No#98763298].
Three Selected Edible Crops of the Genus Momordica as Potential Sources of Phytochemicals: Biochemical, Nutritional, and Medicinal Values
Authors: Muronga Mashudu , Quispe Cristina , Tshikhudo Phumudzo P. , Msagati Titus A. M , Mudau Fhatuwani N. , Martorell Miquel , Salehi Bahare , Abdull Razis Ahmad Faizal , Sunusi Usman , Kamal Ramla Muhammad , Sharifi-Rad Javad
Published: May 2021

Momordica species (Family Cucurbitaceae) are cultivated throughout the world for their edible fruits, leaves, shoots and seeds. Among the species of the genus Momordica, there are three selected species that are used as vegetable, and for medicinal purposes, Momordica charantia L (Bitter melon), Momordica foetida Schumach (Bitter cucumber) and Momordica balsamina L (African pumpkin). The fruits and leaves of these Momordica species are rich in primary and secondary metabolites such as proteins, fibers, minerals (calcium, iron, magnesium, zinc), β-carotene, foliate, ascorbic acid, among others. The extracts from Momordica species are used for the treatment of a variety of diseases and ailments in traditional medicine. Momordica species extracts are reputed to possess anti-diabetic, anti-microbial, anthelmintic bioactivity, abortifacient, anti-bacterial, anti-viral, and play chemo-preventive functions. In this review we summarize the biochemical, nutritional, and medicinal values of three Momordica species (M. charantia, M. foetida and M. balsamina) as promising and innovative sources of natural bioactive compounds for future pharmaceutical usage.
Guhong Injection Protects Against Apoptosis in Cerebral Ischemia by Maintaining Cerebral Microvasculature and Mitochondrial Integrity Through the PI3K/AKT Pathway
Authors: Zhou Huifen , He Yu , Zhu Jiaqi , Lin Xiaojie , Chen Juan , Shao Chongyu , Wan Haitong , Yang Jiehong
Published: May 2021

Guhong injection (GHI) can be used for the treatment of ischemic stroke. We investigated the antiapoptotic activity of GHI, its ability to repair the cerebral microvessels and mitochondria, and the PI3K/AKT signaling pathway of GHI against cerebral ischemia. Western blot and immunohistochemical analyses were used to determine the expression of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), cytochrome c (Cyt-c), basic fibroblast growth factor (BFGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and proteins in the PI3K/AKT signaling pathway. Transmission electron microscopy and scanning electron microscopy were used to evaluate the structures of the cerebral microvasculature and cells. Hoechst 33342 staining was used to evaluate the nuclear morphology. FITC-AV/PI double staining was used to measure the antiapoptotic effects. The fluorescent dye JC-1 was used to measure mitochondrial membrane potential. The enzyme-linked immunosorbent assay (ELISA) was used to detect the activities of matrix metalloproteinase-9 (MMP-9). Biochemical assay kits were used to detect the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA). Compared with the middle cerebral artery occlusion (MCAO) group, there was decreased infarct volume and significantly improved neurological deficits in the GHI group. In addition, the expression of Bcl-2 was significantly upregulated, while the expression of Cyt-c, Bax, and cleaved caspase-3 was notably downregulated. GHI administration attenuated the pathological change and morphology of the cerebral microvasculature, and immunohistochemical staining indicated that the expressions of BFGF, VEGF, and TGF-β1 were significantly increased. The cell morphology, cell viability, cell nuclei characteristics, and mitochondrial morphology normalized following GHI treatment, which decreased the release of Cyt-c and the mitochondrial membrane potential. The levels of LDH, MMP-9, and MDA decreased, while SOD increased. Moreover, GHI administration inhibited the activation of the PI3K/AKT signaling pathway in rat brain microvascular endothelial cells (rBMECs) following oxygen/glucose deprivation (OGD) injury. Therefore, our results show that GHI administration resulted in antiapoptosis of cerebral cells and repair of cerebral microvessels and mitochondria via the PI3K/AKT signaling pathway.
Patient Derived Colonoids as Drug Testing Platforms–Critical Importance of Oxygen Concentration
Authors: Skovdahl Helene Kolstad , Gopalakrishnan Shreya , Svendsen Tarjei Dahl , Granlund Atle van Beelen , Bakke Ingunn , Ginbot Zekarias G. , Thorsvik Silje , Flatberg Arnar , Sporsheim Bjørnar , Ostrop Jenny , Mollnes Tom Eirik , Sandvik Arne Kristian , Bruland Torunn
Published: May 2021

Treatment of inflammatory bowel disease (IBD) is challenging, with a series of available drugs each helping only a fraction of patients. Patients may face time-consuming drug trials while the disease is active, thus there is an unmet need for biomarkers and assays to predict drug effect. It is well known that the intestinal epithelium is an important factor in disease pathogenesis, exhibiting physical, biochemical and immunologic driven barrier dysfunctions. One promising test system to study effects of existing or emerging IBD treatments targeting intestinal epithelial cells (IECs) is intestinal organoids (“mini-guts”). However, the fact that healthy intestinal epithelium is in a physiologically hypoxic state has largely been neglected, and studies with intestinal organoids are mainly performed at oxygen concentration of 20%. We hypothesized that lowering the incubator oxygen level from 20% to 2% would recapitulate better the in vivo physiological environment of colonic epithelial cells and enhance the translational value of intestinal organoids as a drug testing platform. In the present study we examine the effects of the key IBD cytokines and drug targets TNF/IL17 on human colonic organoids (colonoids) under atmospheric (20%) or reduced (2%) O2. We show that colonoids derived from both healthy controls and IBD-patients are viable and responsive to IBD-relevant cytokines at 2% oxygen. Because chemokine release is one of the important immunoregulatory traits of the epithelium that may be fine-tuned by IBD-drugs, we also examined chemokine expression and release at different oxygen concentrations. We show that chemokine responses to TNF/IL17 in organoids display similarities to inflamed epithelium in IBD-patients. However, inflammation-associated genes induced by TNF/IL17 were attenuated at low oxygen concentration. We detected substantial oxygen-dependent differences in gene expression in untreated as well as TNF/IL17 treated colonoids in all donors. Further, for some of the IBD-relevant cytokines differences between colonoids from healthy controls and IBD patients were more pronounced in 2% O2 than 20% O2. Our results strongly indicate that an oxygen concentration similar to the in vivo epithelial cell environment is of essence in experimental pharmacology.
Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer’s Disease
Authors: Cheng Dan , Yang Xin-Jing , Zhang Lu , Qin Zong-Shi , Li Wen-Qi , Xu Hai-Chun , Zhang Zhang-Jin
Published: May 2021

Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer’s disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aβ25–35 served as an in vitro model of Alzheimer’s disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml–200 µg/ml, followed by co-incubation with 20 μM Aβ25–35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aβ-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aβ-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aβ exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.
Dynamics of an SIR-Based COVID-19 Model With Linear Incidence Rate, Nonlinear Removal Rate, and Public Awareness
Authors: Ajbar Abdelhamid , Alqahtani Rubayyi T. , Boumaza Mourad
Published: May 2021

The paper studies the dynamics of the classical susceptible-infectious-removed (SIR) model when applied to the transmission of COVID-19 disease. The model includes the classical linear incidence rate but considers a nonlinear removal rate that depends on the hospital-bed population ratio. The model also includes the effects of media on public awareness. We prove that when the basic reproduction number is less than unity the model can exhibit a number of nonlinear phenomena including saddle-node, backward, and Hopf bifurcations. The model is fitted to COVID-19 data pertinent to Saudi Arabia. Numerical simulations are provided to supplement the theoretical analysis and delineate the effects of hospital-bed population ratio and public awareness on the control of the disease.
The Effect of CO2 on Resting-State Functional Connectivity: Isocapnia vs. Poikilocapnia
Authors: McKetton Larissa , Sam Kevin , Poublanc Julien , Crawley Adrian P. , Sobczyk Olivia , Venkatraghavan Lakshmikumar , Duffin James , Fisher Joseph A. , Mikulis David J.
Published: May 2021

The normal variability in breath size and frequency results in breath-to-breath variability of end-tidal PCO2 (PETCO2), the measured variable, and arterial partial pressure of carbon dioxide (PaCO2), the independent variable affecting cerebral blood flow (CBF). This study examines the effect of variability in PaCO2 on the pattern of resting-state functional MRI (rs-fMRI) connectivity. A region of interest (ROI)-to-ROI and Seed-to-Voxel first-level bivariate correlation, hemodynamic response function (hrf)-weighted analysis for measuring rs-fMRI connectivity was performed during two resting-state conditions: (a) normal breathing associated with breath-to-breath variation in PaCO2 (poikilocapnia), and (b) normal breathing with breath-to-breath variability of PETCO2 dampened using sequential rebreathing (isocapnia). End-tidal PCO2 (PETCO2) was used as a measurable surrogate for fluctuations of PaCO2. During poikilocapnia, enhanced functional connections were found between the cerebellum and inferior frontal and supramarginal gyrus (SG), visual cortex and occipital fusiform gyrus; and between the primary visual network (PVN) and the hippocampal formation. During isocapnia, these associations were not seen, rather enhanced functional connections were identified in the corticostriatal pathway between the putamen and intracalacarine cortex, supracalcarine cortex (SCC), and precuneus cortex. We conclude that vascular responses to variations in PETCO2, account for at least some of the observed resting state synchronization of blood oxygenation level-dependent (BOLD) signals.
The Cholinergic and ACE-2-Dependent Anti-Inflammatory Systems in the Lung: New Scenarios Emerging From COVID-19
Authors: Di Maro Martina , Cataldi Mauro , Santillo Mariarosaria , Chiurazzi Martina , Damiano Simona , De Conno Barbara , Colantuoni Antonio , Guida Bruna
Published: May 2021

The renin angiotensin system and the cholinergic anti-inflammatory pathway have been recently shown to modulate lung inflammation in patients with COVID-19. We will show how studies performed on this disease are starting to provide evidence that these two anti-inflammatory systems may functionally interact with each other, a mechanism that could have a more general physiological relevance than only COVID-19 infection.
Nitrogen Uptake Efficiency, Mediated by Fine Root Growth, Early Determines Temporal and Genotypic Variations in Nitrogen Use Efficiency of Winter Oilseed Rape
Authors: Vazquez-Carrasquer Victor , Laperche Anne , Bissuel-Bélaygue Christine , Chelle Michaël , Richard-Molard Céline
Published: May 2021

Maintaining seed yield under low N inputs is a major issue for breeding, which requires thoroughly exploiting the genetic diversity of processes related to Nitrogen Use Efficiency (NUE). However, dynamic analysis of processes underlying genotypic variations in NUE in response to N availability from sowing to harvest are scarce, particularly at the whole-plant scale. This study aimed to dynamically decipher the contributions of Nitrogen Uptake Efficiency (NUpE) and Nitrogen Utilization Efficiency (NUtE) to NUE and to identify traits underlying NUpE genetic variability throughout the growth cycle of rapeseed. Three experiments were conducted under field-like conditions to evaluate seven genotypes under two N conditions. We developed NUE_DM (ratio of total plant biomass to the amount of N available) as a new proxy of NUE at harvest, valid to discriminate genotypes from the end of inflorescence emergence, and N conditions as early as the beginning of stem elongation. During autumn growth, NUpE explained up to 100% of variations in NUE_DM, validating the major role of NUpE in NUE shaping. During this period, under low N conditions, up to 53% of the plant nitrogen was absorbed and NUpE genetic variability resulted not from differences in Specific N Uptake but in fine-root growth. NUtE mainly contributed to NUE_DM genotypic variation during the reproductive phase under high-N conditions, but NUpE contribution still accounted for 50–75% after flowering. Our study highlights for the first time NUpE and fine-root growth as important processes to optimize NUE, which opens new prospects for breeding.
Defining Spotting in Dance: A Delphi Method Study Evaluating Expert Opinions
Authors: Haber Catherine , Schärli Andrea
Published: May 2021

Spotting is a typical isolated head coordination used by many dancers during rotation. However, with sporadic and inconclusive explanations as to why dancers spot, the critical characteristics and functionalities of spotting have yet to be identified. Therefore, a Delphi method survey was used as a novel methodology for providing greater insights into this under-examined motor behavior, bringing together experts from various disciplines to generate ideas and identify the crucial elements of spotting. Following the selection of experts, three rounds of data collection and analysis were conducted to narrow down relevant topics and evaluate consensus. To gather opinions in Round 1, experts were asked to respond freely to three prompts regarding the reasoning, characteristics, and uses of successfully spotting; responses were then grouped into predominant items. To rate agreement in Round 2, experts rated their agreement on the relevance of the grouped items from Round 1 on a 5-point Likert scale; items rated 4 or 5 by at least 70% of the experts were taken as those consensually relevant to the group. To rank importance in Round 3, Best-Worst Scaling was used to determine individual rankings of the relevant items from Round 2. In a series of comparisons, experts were prompted to select the most and least important items in multiple sub-groupings. Group mean ranking of items as well as ranking concordance and differentiation were analyzed to determine the most important items and the strength of consensus, respectively. Overall, consensus and differentiation in experts’ item rankings were low; however, novel insights were presented. As characteristics of successfully spotting, experts emphasized head isolation, timing, and gaze specificity alongside functional characteristics, substantiating spotting as purposeful action in rotation. Building on traditional notions of spotting for reduced dizziness and maintaining balance, successfully spotting was further deemed useful for multiple turns, orientation, and rhythm. The findings of this study thus provide informed guidelines for future analysis and training of this complex head coordination in rotations.
Expectation and Evaluation of Spouse’s Filial Piety and Marital Satisfaction in China
Authors: Gui Yongxia
Published: May 2021

The present study examined the effect of expectation and evaluation of spouse’s filial piety on marital satisfaction among young Chinese couples. We administered scales assessing gender role attitude, marital satisfaction, and expectation and evaluation of spouse’s filial piety on 422 married participants and explored the relationships among these variables. The results showed the following: (1) gender role attitude mediated the relationship between participants’ gender and evaluation of their spouse’s filial piety. There was no significant gender difference in the evaluation of spouse’s filial piety; however, men were more likely to have a traditional gender role attitude, and a traditional gender role attitude leads to lower evaluation of spouse’s filial piety. Furthermore, it was found that the wife’s sibling condition influenced the participants’ expectation and evaluation of spouse’s filial piety as compared to the husband’s; (2) the evaluation of spouse’s filial piety was significantly positively correlated with marital satisfaction; and (3) women’s expectations of their husband’s filial piety moderated this relationship. The positive effects of the evaluation of spouse’s filial piety on marital satisfaction were significantly stronger when they had high expectations in this regard.
Public Perception and Hand Hygiene Behavior During COVID-19 Pandemic in Indonesia
Authors: Dwipayanti Ni Made Utami , Lubis Dinar Saurmauli , Harjana Ngakan Putu Anom
Published: May 2021

Hand hygiene practices are important not only during the corona virus disease 2019 (COVID-19) pandemic, but also critical to prevent the possible spread of other infectious diseases. This study aims to examine the current hand hygiene behaviors during the COVID-19 pandemic, post pandemic behavior intentions, and the relationship between behavior, psychosocial and contextual factors. A cross-sectional online survey was conducted from 28 May to 12 June 2020, with 896 valid responses obtained from Indonesian citizens over 18 years old. The survey questions included demographic characteristics, individual practices, risk perceptions, attitude, norm factors and ability factors related to hand hygiene during the COVID-19 pandemic. Descriptive analysis, chi square and multiple logistic regression tests were used to analyse the data. The results showed that 82.32% of female respondents and 73.37% male respondents reported handwashing practice 8 times or more per day during COVID-19 pandemic. Participants who perceived themselves at higher risk of contracting SARS-CoV-2 (OR 7.08, 2.26–22.17), had less negative perception toward the practice (OR 1.93, 1.32–2.82), perceived handwashing as an effective preventive measure (OR 1.77, 1.23–2.54), were female (OR 1.71, 1.21–2.41), perceived a more supportive norm (OR 1.68, 1.15–2.44) and noticed more barriers in access to handwashing facilities (OR 1.57, 1.05–2.36) were more likely to engage in hand hygiene practice more frequently during the pandemic. In conclusion, the majority of respondents did increase their frequency of hand hygiene practices during COVID-19 pandemic. In line with previous studies in other pandemic contexts, sex, perceived susceptibility and effectiveness are important predictors of hand hygiene practices, which are similar to findings from previous studies in other pandemic contexts. Addressing social norm related to the perceived hand hygiene practices of friends and important people is a potential health promotion strategy by creating hand hygiene norms in the community.
Containing Future Epidemics With Trustworthy Federated Systems for Ubiquitous Warning and Response
Authors: Carrillo Dick , Duc Nguyen Lam , Nardelli Pedro H. J. , Pournaras Evangelos , Morita Plinio , Rodríguez Demóstenes Z. , Dzaferagic Merim , Siljak Harun , Jung Alexander , Hébert-Dufresne Laurent , Macaluso Irene , Ullah Mehar , Fraidenraich Gustavo , Popovski Petar
Published: May 2021

In this paper, we propose a global digital platform to avoid and combat epidemics by providing relevant real-time information to support selective lockdowns. It leverages the pervasiveness of wireless connectivity while being trustworthy and secure. The proposed system is conceptualized to be decentralized yet federated, based on ubiquitous public systems and active citizen participation. Its foundations lie on the principle of informational self-determination. We argue that only in this way it can become a trustworthy and legitimate public good infrastructure for citizens by balancing the asymmetry of the different hierarchical levels within the federated organization while providing highly effective detection and guiding mitigation measures toward graceful lockdown of the society. To exemplify the proposed system, we choose a remote patient monitoring as use case. This use case is evaluated considering different numbers of endorsed peers on a solution that is based on the integration of distributed ledger technologies and NB-IoT (narrowband IoT). An experimental setup is used to evaluate the performance of this integration, in which the end-to-end latency is slightly increased when a new endorsed element is added. However, the system reliability, privacy, and interoperability are guaranteed. In this sense, we expect active participation of empowered citizens to supplement the more usual top-down management of epidemics.
Deep Learned Quantization-Based Codec for 3D Airborne LiDAR Point Cloud Images
Authors: Tamilmathi A. Christoper , Chithra P. L.
Published: May 2021

This paper introduces a novel deep learned quantization-based coding for 3D Airborne LiDAR (Light detection and ranging) point cloud (pcd) image (DLQCPCD). The raw pcd signals are sampled and transformed by applying the Nyquist signal sampling and Min-max signal transformation techniques, respectively for improving the efficiency of the training process. Then, the transformed signals are feed into the deep learned quantization module for compressing the data. To the best of our knowledge, this proposed DLQCPCD is the first deep learning-based model for 3D airborne LiDAR pcd compression. The functions of Mean Squared Error and Stochastic Gradient Descent optimization function enhance the quality of the decompressed image by 67.01 percent on average, compared to other functions. The model’s efficiency has been validated with established well-known compression techniques such as the 7-Zip, WinRAR, and tensor tucker decomposition algorithm on the three inconsistent airborne datasets. The experimental results show that the proposed model compresses every pcd image into constant 16 Number of Neurons of data and decompresses the image with approximately 160 dB of PSNR value, 174.46 s execution time with 0.6 s execution speed per instruction, and proved that it outperforms the other existing algorithms regarding space and time.
Adverse Childhood Experiences Predict Early Initiation of Opioid Use Behaviors
Authors: Guarino Honoria , Mateu-Gelabert Pedro , Quinn Kelly , Sirikantraporn Skultip , Ruggles Kelly V. , Syckes Cassandra , Goodbody Elizabeth , Jessell Lauren , Friedman Samuel R.
Published: May 2021

Introduction: Although a substantial body of research documents a relationship between traumatic stress in childhood and the initiation of substance use later in the life course, only limited research has examined potential linkages between adverse childhood experiences (ACEs) and the initiation of non-medical prescription opioid use and other opioid use behaviors. The present study contributes to this growing body of work by investigating the association of childhood trauma with early initiation of a series of opioid use behaviors.

Methods: New York City young adults (n = 539) ages 18–29 who reported non-medical use of prescription opioids or heroin use in the past 30 days were recruited using Respondent-Driven Sampling in 2014–16. Ten ACEs were assessed via self-report with the ACE Questionnaire. Associations between number of ACEs and self-reported ages of initiating seven opioid use behaviors (e.g., non-medical prescription opioid use, heroin use, heroin injection) were estimated with multivariable logistic regression.

Results: Eighty nine percent of participants reported at least one ACE, and 46% reported four or more ACEs, a well-supported threshold indicating elevated risk for negative health consequences. Every increase of one trauma was associated with a 12–23% increase in odds of early initiation across the seven opioid use behaviors. Findings also document that the mean age at initiation increased with increasing risk severity across the behaviors, contributing to evidence of a trajectory from opioid pill misuse to opioid injection.

Discussion: Increasing number of childhood traumas was associated with increased odds of earlier initiation of multiple opioid misuse behaviors. In light of prior research linking earlier initiation of substance use with increased substance use severity, present findings suggest the importance of ACEs as individual-level determinants of increased opioid use severity. Efforts to prevent onset and escalation of opioid use among at-risk youth may benefit from trauma prevention programs and trauma-focused screening and treatment, as well as increased attention to ameliorating upstream socio-structural drivers of childhood trauma.
Sex and Age-Group Differences in Strength, Jump, Speed, Flexibility, and Endurance Performances of Swedish Elite Gymnasts Competing in TeamGym
Authors: Höög Stefan , Andersson Erik P.
Published: May 2021

Purpose:To analyze sex and age group differences in strength, jump, speed, flexibility, and endurance performances of TeamGym athletes.

Methods:A total of 91 Swedish elite gymnasts (junior female,n= 26, age = 15.4 y; senior female,n= 23, age = 20.0 y; junior male,n= 19, age = 15.6 y; senior male,n= 23, age = 20.6 y) participated in three testing sessions on three separate days. These were: (1) a series of flexibility tests for the lower- and upper-body; (2) strength tests for the lower- and upper-body; and (3) various types of jumps, a 20-m sprint-run, and a 3,000-m run test.

Results:Males were 24% stronger in the back squat one-repetition maximum (relative to body mass) compared to females (P< 0.001,Hg= 1.35). In the pull-ups and dips, 2.4 and 2.3 times more repetitions were completed by the males compared to the females (bothP< 0.001, 0.70 ≤R≤ 0.77). However, females were similarly strong as males in the hanging sit-ups test (P= 0.724). The males jumped 29, 34, 33, and 17% higher in the squat jump (SJ), countermovement jump (CMJ), countermovement jump with arm swing (CMJa), and drop jump (DJ), respectively, compared to the females (allP≤ 0.002, 0.14 ≤ηp2 ≤0.60). In the 20-m sprint run, males were 4% faster than females (P< 0.001,R= 0.40). Moreover, the females had significantly better flexibility than the males in the trunk forward bending, front split, and side split tests (allP< 0.001, 0.24 ≤ηp2≤ 0.54). In the 3,000-m run test, males were 11% faster than females (P< 0.001,ηp2≤ 0.54). Compared to junior athletes, seniors performed better in the pull-ups, dips, SJ, CMJ, CMJa, and 20-m sprint-run tests (allP≤ 0.012, 0.31 ≤R≤ 0.56, 0.16 ≤ηp2≤ 0.25), with separate within-sex age-group differences (i.e., juniors vs. seniors) that were significant for the males but not for the females in the SJ, CMJ, CMJa, and 20-m sprint-run tests (males: allP< 0.001, 0.67 ≤R≤ 0.69, 1.37 ≤Hg≤ 2.01; females: allP= 0.298–732).

Conclusions:Large sex and age-group differences were observed for most physical performance metrics with specific within-sex age-group differences only observed for male athletes, with male seniors performing better than juniors in the SJ, CMJ, CMJa, and 20-m sprint-run tests.