bluuebunny/crossref_metadata_2025 huggingface dataset:
A miniPCR-duplex Lateral Flow Dipstick Platform in Combination with the Microfluidic Device for Rapid and Visual Diagnosis of Lymphatic Filariae Infection
Authors: Phuakrod Achinya , Sripumk Witsaroot , Jeamsaksiri Wutthinan , Pattamang Pattaraluck , Loymek Sumart , Brindley Paul J. , Sarasombath Patsharaporn T. , Wongkamchai Sirichit
Published: April 2021

Background: Lymphatic filariasis is a major neglected tropical disease that is a leading cause of permanent and long-term disability worldwide. Significant progress made by the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has led to a substantial decrease in the levels of infection. Accordingly, access is now needed to a cost-efficient, non-laborious diagnostic assay(s) capable of detecting low levels of microfilariae and without the need for infrastructure and expensive equipment.Methods: We developed a diagnostic assay that combines a miniPCR with a duplex lateral flow dipstick (DLFD) assay. The design of the PCR primers was guided by sequence alignments of the HhaI and SspI genes of Brugia malayi and Wuchereria bancrofti, respectively. The limits of detection, accuracy, and cross-reactivity of the assay were evaluated, after which the assay was deployed to assess infection using blood samples obtained from Myanmar study participants living along the Thailand-Myanmar border, a region in Tak province endemic W. bancrofti. In addition, blood samples were provided by from Thais in Narathiwat province residing in an area endemic for brugian filariasis. We also combined a previously reported semi-automated microfluidic device with the miniPCR-DLFD to facilitate rapid detection and species identification of microfilariae in human blood.Results: The miniPCR-DLFD assay exhibited a detection limit of two microfilariae per mililiter blood sample, and cross-amplification was not observed with from other parasites. For field validation, microfilariae and DNA of W. bancrofti were detected from two (0.6%) and five (1.5%) out of 328 (100%) blood samples, respectively. For the Narathiwat samples, microfilariae and DNA of B. malayi were detected from one (0.46%) and two (0.9%) out of 216 (100%) blood samples, respectively. A rapid and visual of species identification was accurately obtained in all microfilariae entrapped by our previously developed microfluidic device.Conclusion: A miniPCR-DLFD platform alone or coupled with the microfluidic device provided rapid and visual diagnosis of lymphatic filariasis. The microfluidic device, the miniPCR, and the DLFD are all portable. Coupled with a portable microcentrifuge for DNA extraction, this is a promising platform for the diagnosis of lymphatic filariasis in point-of-collection settings with a modest cost (~USD $ 5) per sample.
Prevalence of Periodontal Disease Among Indigenous and Non-indigenous Populations: Protocol for Systematic Review and Meta-analysis
Authors: Nath Sonia , Poirier Brianna , Ju Xiangqun , Kapellas Kostas , Haag Dandara , Jamieson Lisa
Published: April 2021

Background: Indigenous populations globally experience worse health than their non-Indigenous counterparts. This includes oral health inequities, especially periodontal disease. Globally, the occurrence of periodontal disease such as gingivitis and chronic periodontitis are high among Indigenous people. This population encounters various barriers to accessing dental care as well as social and economic disadvantages, which results in higher disease burden compared to the general population. The aim of this systematic review is to quantify at a global level, the prevalence of periodontal disease among Indigenous populations compared to non-Indigenous populations.Methods: An electronic search will be conducted using keywords and appropriate MeSH terms across several databases capturing both published and unpublished articles. The search will be conducted from the time of database inception to February 2021. After the initial search, duplicates will be removed, and remaining titles and abstracts will be assessed for eligibility. This review will consider studies that have reported prevalence of periodontal disease among Indigenous and compared against non-Indigenous populations. Studies that have no comparative population or lack of periodontal clinical assessment will be excluded. The full text of eligible studies will be assessed by two independent reviewers who will also complete the critical appraisals and data extraction. From the selected studies, we will conduct a random effects meta-analysis of observational data. Forest plots will be used for visualization of pooled prevalence of periodontitis. A subgroup analysis will be conducted based on definition of periodontitis, age, and geographical location. Heterogeneity among studies will be assessed by I2 and chi-square test. Egger’s test and funnel plots will be used to assess publication bias.Discussion: Our systematic review and meta-analysis will facilitate increased understanding of the magnitude of periodontal disease inequalities that exist globally for Indigenous populations through pooled prevalence estimates. The findings will be helpful to design selective targeted preventive and interventional strategies for periodontal disease for reducing oral health inequalities at a global level. Systematic review registration: PROSPERO CRD42020188531
Evaluating Boreal Summer Circulation Patterns of CMIP6 Climate Models Over The Asian Region
Authors: Bu Lulei , Zuo Zhiyan , An Ning
Published: April 2021

Our confidence in future climate projection depends on the ability of climate models to simulate the current climate, and model performance in simulating atmospheric circulation affects the ability to simulate extreme events. This study uses the self-organizing map (SOM) method to evaluate the frequency, persistence, and transition characteristics of models in the Coupled Model Intercomparison Project Phase 6 (CMIP6) for different ensembles of the 500 hPa daily geopotential height (Z500) in Asia, and then ranks all ensembles according to a comprehensive ranking metric (MR). Our results show that the SOM method is a powerful tool for assessing the daily-scale circulation simulation skills in Asia, and the results are not significantly affected by different map sizes. Positive associations between the performance of ensembles for any two of frequency, persistence, and transition were found, indicating that an ensemble that performs well for one metric is good for the others. The results of the MR ranking show that the r10i1p1f1 ensemble of CanESM5 gives the best overall simulation of 500 hPa circulation in Asia, and this is also the ensemble that best simulates frequency characteristics. The MR simulation skills of the 10 best ensembles for the position of the Western North Pacific Subtropical High (WNPSH) are far better than those of the 10 worst. Such differences may lead to errors in the simulation of extreme events. This study will help future studies in the choice of ensembles with higher circulation simulation skills to improve the credibility of their conclusions.
Contrasting changes in reproductive success of birds in cities with reduced and increased human disturbance during the COVID-19 lockdown
Authors: Seress Gábor , Sándor Krisztina , Vincze Ernő , Pipoly Ivett , Bukor Boglárka , Ágh Nóra , Liker András
Published: April 2021

The ubiquitous activity of humans is a fundamental feature of urban environments affecting local wildlife in several ways. Testing the influence of human disturbance would ideally need experimental approach, however, in cities, this is challenging at relevant spatial and temporal scales. Thus, to better understand the ecological effects of human activity, we exploited the opportunity that the city-wide lockdowns due to the COVID-19 pandemic provided during the spring of 2020. We assessed changes in reproductive success of great tits (Parus major) at two urban habitats affected strikingly differently by the ‘anthropause’ and at an unaffected forest site. Although anecdotic observations suggested that urban wildlife may benefit from reduced human mobility during the lockdown, our results do not support this. First, at one of our urban sites, the strongly (-44%) reduced human disturbance in 2020 (compared to a long-term reference period) did not increase birds’ reproductive output relative to the forest habitat where human disturbance was low in all years. Second, in the other urban habitat, recreational human activity considerably increased (+ 40%) during the lockdown and this was associated with strongly reduced nestling body size compared to the pre-COVID reference year. Analyses on meteorological conditions and the lockdown-induced changes in air pollution suggest that these factors are not likely to explain our results. Our study supports that intensified human disturbance can have adverse fitness consequences in urban populations. It also highlights that a few months of ‘anthropause’ is not enough to counterweight the detrimental impacts of urbanization on local wildlife populations.
Homoarginine Treatment of Rats Improves Cardiac Function and Remodeling in Response to Pressure Overload
Authors: Koch Vitali , Ochs Marco , Weber Christophe , Buchner Kristina , Mereles Derliz , Hagenmueller Marco , Buss Sebastian J , Hein Selina , Erbel Christian , März Winfried , Frey Norbert , Hardt Stefan E , Riffel Johannes H
Published: April 2021

The authors have requested that this preprint be removed from Research Square.
Avoidance Response: A More Important Determinant of Population Immediate Decline in Guppy Fish (Poecilia Reticulata Peters, 1859) Exposed to Pesticides.
Authors: Ogunfeitimi Olusola Ojo , Amaeze N. H. , Umeokeke H. C , Soriwei E. T. , Labinjo A. S.
Published: April 2021

This study, investigated the ability of Paraquat (herbicide) and Dichlorvos (insecticide) to elicit avoidance response in population of Guppy fish, Poecilia reticulata and predict the population immediate decline (PID) of P. reticulata when exposed to both agro-chemicals. A 96-h forced system (FS) bioassay was each conducted in five duplicate systems, each with a control experiment. The avoidance response was examined using non-forced multi-compartmented static system (NFS). The guppies (n = 3 guppies per concentration of 6 compartments in quadruplet) were exposed to a gradient of Paraquat (0, 2.5, 5.0, 7.5, 10.0 and 15.0 mg/L) and Dichlorvos (0, 1.6, 2.6, 3.0, 3.2 and 4.0 mg/L). Their distributions were examined at 20 min intervals for a 3-h period (n = 9 observation periods). The results from 96-h FS were does-dependent with highest percentage mortality being 85.7% for Paraquat and 78.6% for Dichlorvos in respective highest concentrations. The 3-h NFS exposure showed statistically significant concentration-dependent spatial avoidance. The P. reticulata avoided the lowest concentration of Paraquat (2.5mg/L) and Dichlorvos (1.6 mg/L) by 68.3% and 48.3% respectively. The avoidance increased significantly (p < 0.005) to 75%, for the highest concentrations of both test chemicals (15.0 and 4.0 mg/L). The 3-hr AC50 value revealed that the guppies were more sensitive to Paraquat (0.37 mg/L) than Dichlorvos (1.73 mg/L). The PID was driven by the avoidance behaviour (NFS) of the guppies rather than mortality (FS). The FS heretofore overestimate environmental risk assessment of contamination due to mandatory exposure of mobile organisms to contaminants. Rather than the traditional FS systems, NFS should be adopted and incorporated in typical bioassays for better predictive results.
Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Upregulate MicroRNA-424-5p to Suppress Hepatocellular Carcinoma Cell Growth by Inhibiting Forkhead Box K1
Authors: Lin Zewei , Ren Qingqi , Ma Xiaofei , Jikui Liu
Published: April 2021

Bone marrow mesenchymal stem cells (BM-MSCs) have been shown to exert a potential therapeutic effect during tumor treatment and it has been proved that exosomes derived from BM-MSCs play crucial roles in the progression of malignant tumors. The current study aims to investigate the effect of BM-MSC-derived exosomal microRNA-424-5p (miR-424-5p) on hepatocellular carcinoma (HCC) progression. The expression of miR-424-5p was compared between HCC and adjacent normal tissues, and its prognosis value was analyzed. Additionally, exosomes were extracted from the BM-MSCs and their identity was verified. Luciferase reporter assay was conducted to identify the putative binding sites between miR-424-5p and the 3’-UTR of forkhead box K1 (FOXK1). The BM-MSC-derived exosomes were co-cultured with HCC cells to assess the effect of the BM-MSC-derived exosomes, miR-424-5p, and FOXK1 on the proliferation, migration, invasion, and in vivo tumorigenesis of the HCC cells. Then, the expression of FOXK1 was also examined in HCC and normal tissues. miR-424-5p was downregulated and FOXK1 was upregulated in HCC tissues and cells. BM-MSC-derived exosomes upregulated miR-424-5p expression to suppress the proliferation, migration, invasion, and in vivo tumorigenesis of HCC cells. Knockdown of FOXK1 also repressed the malignant behavior of the HCC cells, and FOXK1 was verified as the target of miR-424-5p. The role of FOXK1 silencing in HCC cells was reversed by miR-424-5p downregulation. Our results suggested that BM-MSC-derived exosomes upregulated miR-424-5p expression to restrain HCC cell growth and invasion via inhibition of FOXK1 expression and as a result, decelerating HCC development.
Gabapentin and Intrathecal Morphine Combination Therapy Results in Decreased Oral Narcotic Use and More Consistent Pain Scores After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Authors: Li Ying , Swallow Jennylee , Robbins Christopoher , Caird Michelle S. , Leis Aleda , Hong Rebecca
Published: April 2021

Background: Gabapentin and intravenous patient-controlled analgesia (PCA) can reduce postoperative pain scores, postoperative opioid use, and time to completing physical therapy compared to PCA alone after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Gabapentin combined with intrathecal morphine has not been studied. The primary purpose of this retrospective study was to evaluate whether perioperative gabapentin and intrathecal morphine provide more effective pain control than intrathecal morphinealone after PSF for AIS. Methods: Patients aged 11 to 18 years who underwent PSF for AIS were identified. Patients who received intrathecal morphine only (ITM group) were matched by age and sex to patients who received intrathecal morphine and perioperative gabapentin (ITM+GABA group). The ITM+GABA group received gabapentin preoperatively and for up to 2 days postoperatively. Both groups received oxycodone and the same non-narcotic adjuvant medications.Results: Our final study group consisted of 50 patients (25 ITM, 25 ITM+GABA). The ITM+GABA group had significantly lower mean total oxycodone consumption during the hospitalization (0.798 vs 1.036 mg/kg, P<0.015). While the ITM group had a lower mean pain score between midnight and 8 am on POD 1 (2.4 vs 3.7, P=0.026), pain scores were significantly more consistent throughout the postoperative period in ITM+GABA group. The ITM+GABA group experienced less nausea/vomiting (52% vs 84%, P=0.032) and pruritus (44% vs 72%, P=0.045). Time to physical therapy discharge and length of hospital stay were similar.Conclusion: Addition of gabapentin resulted in reduced oral opioid consumption and more consistent postoperative pain scores after PSF for AIS. The patients who received intrathecal morphine and gabapentin also experienced a lower rate of nausea/vomiting and pruritus.Trial registration: All data was collected retrospectively from chart review, with institutional IRB approval. Trial registration not applicable.
Immune Implication of ASF1B Gene in Hepatocellular Carcinoma
Authors: Meng Tao , Tong Zhong , Yang Ming-Ya , Wang Jing-Jing , Zhu Li-Xin , Zhang Yan , Liu Yu , Wang Zhen-Zhen
Published: April 2021

Background: Anti-silencing function 1B (ASF1B) has been demonstrated to contribute to tumorigenesis. However, its carcinogenic and immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify immune role of ASF1B in HCC.Methods: HCC datasets obtained from The Cancer Genome Atlas (TCGA) database were used to investigate the role of ASF1B gene in HCC, followed by validation using Gene Expression Omnibus (GEO) datasets and Gene Expression Profiling Interactive Analysis (GEPIA) website. CIBERSORT analysis was performed to evaluate immune cell infiltration levels. The TISIDB and cBioPortal network tool were used to seek ASF1B-associated immunomodulators and its co-expressed genes. TCGA cohort was divided into train set and test set according to the ratio of 7:3. Cox regression was used to identify ASF1B-associated prognostic immunomodulators in train set, followed by internal validation using the test set. Based on the median risk-score, HCC patients were divided into high- and low-risk group for the further survival curves and receiver operating characteristic (ROC) analysis, as well as nomogram and calibration curves analysis. Finally, the dataset collected from the GEO was adopted for external validation.Results: ASF1B was over-expressed in TCGA HCC cohort and contributed poor prognosis, which was verified in two GEO datasets (GSE14520 and GSE6764) and GEPIA, as well as Kaplan Meier Plotter network tool. The immune cell infiltration levels were found to be associated with the ASF1B copy numbers and mRNA expression. A total of 78 ASF1B-associated genes were screened out, including 7 immunoinhibitors, 21 immunostimulators and 50 tightly co-expressed genes. Finally, 5 ASF1B-associated genes (TNFSF4, TNFRSF4, KDR, MICB and CST7) were identified to be strongly related to HCC survival. Survival analysis demonstrated that the prognosis of patients in high-risk group was poor. The prognosis predict model, which was established by nomogram based on risk-score, and was validated in both TCGA test set and GEO validated datasets, exerted excellent predictive power in this study.Conclusion: Our findings showed that the ASF1B was associated with HCC immunity. The selected ASF1B-asociated immune markers could be promising biomarkers for the prognosis of HCC.
Analysis of macro-and microplastics in the water, soil/sediment in riverine, riverbanks and irrigated farms in Arusha Tanzania
Authors: Kundu Mercy Nasimiyu , Komakech Hans , Lugomela George
Published: April 2021

Microplastics and macroplastics have been reported in different urban rivers and agricultural soil across the globe. However, the interlink between them has not been previously assessed therefore, the present study evaluated the relationship between macro-and microplastics in the water columns and sediments in riverine, riverbanks, and soils from irrigated farms in Arusha, Tanzania. Detached pieces from macroplastics and suspected particles of microplastics from the samples were analyzed using the total attenuated reflectance - Fourier transform Infrared spectroscopy, where statistical analysis showed that the number of microplastics in the sediments was higher than in the water columns and that in irrigated farms than in the riverine by a magnitude of 4. Besides, the numbers of microplastics and macroplastics in the irrigation farms were exponentially-related while the macroplastics from the riverbanks had an inverse relationship with the rivers’ profile elevation. Polyethylene was the dominating macroplastic in the riverbanks and irrigated farms with a 100% frequency of occurrence while polystyrene was abundant in all samples of microplastics. However, the irrigated farms adjacent to canals had a greater number of microplastics and macroplastics. In generally, the findings showed a similar trend of plastic distribution in urban rivers and irrigated farms, suggesting an interaction between them.
CK2-mediated phosphorylation of Che-1/AATF is required for its pro-proliferative activity
Authors: Catena Valeria , Bruno Tiziana , Iezzi Simona , Matteoni Silvia , Salis Annalisa , Sorino Cristina , Damonte Gianluca , Fanciulli Maurizio
Published: April 2021

Background
Che-1/AATF (Che-1) is an RNA polymerase II binding protein involved in several cellular processes, including proliferation, apoptosis and response to stress. We have recently demonstrated that Che-1 is able to promote cell proliferation by sustaining global histone acetylation in Multiple Myeloma (MM) cells where it interacts with histone proteins and competes with HDAC class I members for binding.
Methods
Site-directed Mutagenesis was performed to generate a Che-1 mutant (Che-1 3S) lacking three-serine residue (Ser316, Ser320 and Ser321) in 308–325 AA region. Western blot experiments were conducted to examine the effect of depletion or over-expression of Che-1 and Che-1 3S mutant on histone acetylation, in different human cancer cell lines. Proliferation assays were assessed to estimate the change in cells number when Che-1 was over-expressed or deleted. Immunoprecipitation assays were performed to evaluate Che-1/histone H3 interaction when Ser316, Ser320 and Ser321 were removed. The involvement of CK2 kinase in Che-1 phosphorylation at these residues was analysed by in vitro kinase, 2D gel electrophoresis assays and mass spectrometry analysis.
Results
Here, we confirm that Che-1 depletion reduces cell proliferation with a concomitant general histone deacetylation in several tumor cell lines. Furthermore, we provided evidence that CK2 protein kinase phosphorylates Che-1 at Ser316, Ser320 and Ser321 and that these modifications are required for Che-1/histone H3 binding. These results improve our understanding onto the mechanisms by which Che-1 regulates histone acetylation and cell proliferation.
Conclusions
Che-1 phosphorylation at Ser316, Ser320 and Ser321 by CK2 promotes the interaction with histone H3 and represents an essential requirement for Che-1 pro-proliferative ability.
One Year Later: Global Impact of COVID-19 on Nuclear Medicine Departments; an International Follow-up Survey
Authors: Giammarile Francesco , Bolton Roberto C. Delgado , Haj Noura El , Freudenberg Lutz S. , Herrmann Ken , Mikhail Miriam , Morozova Olga , Orellana Pilar , Pellet Olivier , L. Enrique Estrada , Vinjamuri Sobhan , Gnanasegaran Gopinath , Pynda Yaroslav , M. Maria C. Navarro , Choudhary Partha , Paez Diana
Published: April 2021

Aim: As a follow-up to the international survey conducted in April 2020, this survey aims to provide a situational snapshot of the COVID-19 impact on nuclear medicine services worldwide, one year later. The survey was designed to determine the impact of the pandemic at two specific time-points: June and October 2020 and compare them to the previously collected data.Materials and Methods: A web-based questionnaire, in the same format as the April 2020 survey was disseminated to nuclear medicine facilities worldwide. Survey data was collected using a secure software platform hosted by the International Atomic Energy Agency (IAEA); it was made available for 6 weeks, from November 23 to December 31, 2020.Results: From 505 replies from 96 countries, data was extracted from 355 questionnaires (of which 338 were fully completed). The responses came from centres evenly distributed in different regions of the world and with different income status. Regional differences and challenges across the world were identified and analysed. Globally, the volume of nuclear medicine procedures decreased by 73.3% in June 2020 and 56.9% in October 2020. Among the nuclear medicine procedures, oncological PET studies showed less of a decline in utilization compared to conventional nuclear medicine and particularly nuclear cardiology. The impact was also significantly less in high-income countries. A trend towards a return to the pre-COVID-19 situation of the supply chains of radioisotopes, generators, and other essential materials was evident.Conclusion: The impact of the COVID-19 pandemic was associated with a significant reduction in nuclear medicine diagnostic and therapeutic procedures throughout 2020. In June, the global decline recorded in the survey was greater than in October when there was a slight improvement. However, the total number of procedures continued below that recorded in April 2020, and less than half of the volumes normally carried out before the pandemic
Force-displacement relationship modelling of masonry infilled walls with openings in hinged steel frames
Authors: Zuo Haoran , Zhang Weiping , Wang Baotong , Gu Xianglin
Published: April 2021

Seismic behaviour of masonry infilled frames has attracted extensive attentions from researchers, and it was found that infills normally experienced a diagonal compression under lateral loading. Infill was therefore assumed as an equivalent diagonal strut in structural response estimations of infilled frames, and a force-displacement curve was adopted to describe the mechanical properties of the strut. However, the influences of infill aspect ratio, vertical load acting on the surrounding frames, and opening were not systematically addressed in establishing the force-displacement relationship of infills. To investigate the effects of these influential parameters on the lateral responses of infilled walls including initial stiffness and strength, detailed three-dimensional finite element (FE) models of masonry infilled hinged steel frames are developed in ABAQUS in the present study, and a wide parametric study with respect to various aspect ratios, vertical loads, and opening sizes and locations is performed. A generalized force-displacement relationship model of infilled walls is proposed based on regression analyses of numerical results. The efficacy of the proposed model is examined by using the existing experimental test results, and it shows that the model can accurately predict the lateral stiffness and load carrying capacity of infilled walls and thus has great potential applications in structural designs and analyses for masonry infilled steel frames.
Reflecting on Exchanged Students' Learning: Bedside Demonstration, Case Reporting and Clinical Reasoning
Authors: Xu Dan , Feng Shaoting , Yang Suqing , Ding Shuqing , Yap Timothy , Chi Christopher , Tan Nicole , Nair Ankith , Nixon Dennis , Wee Cleo , Rosman Johan , Sandover Sally , Wang Jingsong , Kuang Ming , Xiao Haipeng
Published: April 2021

Background: The increasing opportunities for medical students to participate in international, supervised and structured electives have been shown in our recent study, which enhanced students’ professionalism, cultural competence and clinical reasoning skills in preclinical years. However, evidence is scant in achieving the specific learning objectives and improving clinical reasoning during clinical years. This study aims to demonstrate how the short-term supervised elective can improve students’ clinical reasoning skills, skills of case report writing and satisfactory academic performance.Results: We recorded daily discussions on the demonstrated skills and cases collection with six Curtin Medical School students from Australia during a 19-day supervised elective at the First Affiliated hospital, Sun Yat-sen University, China. The daily clinical reasoning discussions, case collection and bedside demonstrations in different disciplines became the main content of the reflections discussed in this article. Their feedback was recorded post-elective to examine the impact of the exchange in their ongoing case report writing, clinical reasoning skills development and academic performance. The main themes of case-based clinical reasoning identified in the daily discussions and feedbacks were described by the students in two frameworks. Learning through clinical reasoning is well demonstrated during students-supervisors daily debrief. The students have used these clinical reasoning skills in their ensuing clinical placement with satisfactory academic performances. The students have completed two case reports individually with cases for publication in both Australian Doctor and BMJ case report. The supervisors obtained students’ feedbacks at the time of the elective, 6-month and 12-month post-elective, and feedback summary is highlighted in three aspects including improved clinical reasoning skills, scientific writing skills and satisfactory academic performance.Conclusions: These reflections provide insight into how this exchange elective may improve students’ clinical reasoning, enhance scientific writing skills and strengthen academic performance.
Associations among autistic traits, cognitive and affective empathy, and personality in adults with autism spectrum disorder and no intellectual disability or language delay
Authors: Shirayama Yukihiko , Matsumoto Kazuki , Hamatani Sayo , Muneoka Katsumasa , Okada Akihiro , Sato Koichi
Published: April 2021

Background: Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. Method: We evaluated 28 adults with ASD and no intellectual disability or language delay and 24 age-matched healthy control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO-PI-R). Results: Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. Only within the ASD group, significant correlations were revealed between personal distress on the IRI with emotional contagion, proximal responsivity, and affective empathy on the QCAE. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO-PI-R compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. There were significant correlations of online simulation and affective empathy on the QCAE with extraversion on the NEO-PI-R only within the ASD group. Multiple regression analysis demonstrated that perspective taking score on the QCAE and extraversion score on the NEO-PI-R were good predictor variables to autistic traits on the AQ. Conclusions: These findings help our understanding of ASD adults with no intellectual disability or language delay.
Early Prediction of Hemodynamic Shock in the Intensive Care Units with Deep Learning on Thermal Videos
Authors: Vats Vanshika , Nagori Aditya , Singh Pradeep , Dutt Raman , Bandhey Harsh , Wason Mahika , Lodha Rakesh , Sethi Tavpritesh
Published: April 2021

Shock is one of the major killers in Intensive Care Units and early interventions can potentially reverse it. In this study, we advance a non-contact thermal imaging modality to continuous monitoring of hemodynamic shock working on 103,936 frames from 406 videos recorded longitudinally upon 22 patients. Deep learning was used to preprocess and extract the Center-to-Peripheral Difference (CPD) in temperature values from the videos. This time-series data along with heart rate was finally analyzed using Long-Short Term Memory models to predict the shock status up to the next 6 hours. Our models achieved the best area under the receiver operating characteristics curve of 0.81 ± 0.06 and area under the precision-recall curve of 0.78 ± 0.05 at 5 hours, providing sufficient time to stabilize the patient. Our approach, thus, provides a reliable shock prediction using an automated decision pipeline, that can provide better care and save lives.
Obtaining a Vaccine Candidate Against Tumors Expressing the E7 Antigen of Human Papillomavirus type 18
Authors: Rodríguez Nadia Rodríguez , Chaviano Alain B Alfonso , Rodríguez Milaid Granadillo , Figueredo Aileen Batte , Madrazo Isis del Carmen Torréns
Published: April 2021

Background: Cervical cancer is the fourth most common cancer in women worldwide and was the leading cause of death among approximately 300 000 cases in 2018. The main risk factor for developing this disease is the persistent infection of high-risk types of human papillomavirus (HPV); specifically HPV-18 is recognized as one of the major contributors for adenocarcinoma and squamous cancer. There are three prophylactic vaccines to prevent infection by HPV, but these vaccines are not effective in infected people. On the other hand, despite the success of various types of therapeutic vaccine candidates in clinical trials, none of them is commercially available to treat women with HPV-related malignancies. As the methods used for obtaining those therapeutic candidates are awfully expensive, they could be inaccessible for developing countries. In this scenario, E7 antigen of HPV is considered and ideal target for developing therapeutic vaccines. In accordance with this, the aim of this work is to obtain a vaccine candidate with high levels of purity through a profitable process, for treating tumors expressing the E7 antigen of HPV-18.Results: We have obtained the novel therapeutic vaccine candidate CIGB550-E718 that comprises the fusion between an E7 mutein of HPV-18 and the cell-penetrating peptide with immunostimulatory properties CIGB550. The expression of the fusion protein evaluated using two strains of E. coli and 16 culture media with different composition enabled us to choose the best setting in which the interest protein accounted for approximately 16% of the total cellular protein. The best results were obtained using BL21(DE3) cells as host system grown in a culture medium containing M9 salt, casein hydrolysate and glycerol as a carbon source. The recombinant protein was purified by a single affinity chromatographic step up to 90% purity. Yields of 32 mg of the CIGB550-E718 per liter of culture were achieved from 2.5 L scale.Conclusions: These results are a promising and cost-effective approach for the future production and scale-up of the protein CIGB550-E718, which could be a therapeutic alternative for treating women with lesions associated to HPV-18 infection.
Hammer Chyme: The Russian-Doll Effect Limits Reconstructing Marine Trophic Food Webs
Authors: de Bruyn Mark , Barbato Matteo , DiBattista Joseph D. , Broadhurst Matt K.
Published: April 2021

Increasing fishing effort, including bycatch and discard practices, are impacting marine biodiversity, particularly among slow-to-reproduce taxa such as elasmobranchs, and specifically sharks. While some fisheries involving sharks are sustainably managed, collateral mortalities continue, contributing towards >35% of species being threatened with extinction. To effectively manage shark stocks, life-history information, including resource use/feeding ecologies is pivotal, especially among those species with wide-ranging distributions and habitats. Two cosmopolitan sharks bycaught off eastern Australia are the common blacktip shark (Carcharhinus limbatus; globally classified as Near Threatened) and great hammerhead (Sphyrna mokarran; Critically Endangered). We opportunistically sampled the digestive tracts of these two species and also any whole prey; (termed the ‘Russian-doll’ approach) caught in bather-protection gillnets off northern New South Wales to investigate their regional feeding ecologies and the capacity for DNA metabarcoding to delineate trophic interactions. Sphyrna mokkaran fed predominantly on Myliobatiformes and Rajiformes, but also teleosts, while C. limbatus mostly consumed teleosts, with some inter-specific dietary overlap of prey items. Extensive cross-contamination of predator and prey digestive tracts, likely via the predator’s stomach chyme, was evident from the metabarcoding assays limiting the opportunity to delineate trophic interactions from these data. This Russian-doll effect requires further investigation in DNA metabarcoding studies focused on dietary preferences, but implies any outcomes will need to be interpreted concomitant with traditional visual approaches.
Melanin as an Endogenous MRI Contrast Agent for Stem Cell Delivery in Stroke
Authors: Chang Randy , Jones Jesse
Published: April 2021

In vivo measures of survival, growth, and migration of stem cell transplants for stroke therapy remain inadequate. Since such biomarkers in the central nervous system do not exist, we sought to investigate the potential of melanin as an endogenous MR contrast medium for monitoring cell lineage transplants. Expression of a human gene, tyrosinase, induces melanogenesis, but unlike particle-based tracking agents, tyrosinase incorporated into the host genome will be replicated during mitosis.Tyrosinase and the gene for a co-enzyme, tyrosinase-related protein 1, were placed under the CMV promoter. The construct was inserted into 293 HEK (human embryonal kidney) and iPS NPC (induced pluripotent neural progenitor) cells via plasmid transfection and viral transduction, respectively. Stroked mice were injected with melanin-producing cells. Control mice were injected with native cell lines. In vitro expression was measured by fluorescent microscopy, immunocytochemistry, spectroscopy, PCR, and MRI.Robust in vitro melanin production was achieved in both cell lineages demonstrated by significant T1 shortening on in vivo MRI. Pathologic correlation demonstrated colocalization of pigmented regions in the injection sites with human antinuclear antibody staining. Through induction of melanogenesis that is reproducible across multiple cell divisions, MR-based imaging of clinically relevant cell lineage transplants is possible.
Triptolide Inhibited Liver Cancer Growth Based Through SPTLC2-S1P Signal Pathway
Authors: Tan Qinyou , Zhu Shengnan , Zhu Mingfei , Huang Lingyue , Xu Siyuan , Luo Yuqin , Xiao Juan , Su Huazhen , Huang Shaoyuan , Jia Lulu
Published: April 2021

Background: Hepatocellular carcinoma is a cancer that has a high incidence in men, and its incidence is increasing year by year. Studies show that angiogenesis plays an important role in the formation of tumors, not only providing nutrients to tumor cells, but also closely related to tumor growth and metastasis. So, how to find new anti-vascular and anti-tumor targets for the pathogenesis of liver cancer is a key issue that needs to be resolved. Methods: After treating HUVEC and HepG2 cells with different concentrations of TP, the relationship between TP's anti-vascular and anti-tumor activities and sphingolipids was investigated respectively. Then, the three-dimensional co-culture model was used to explore the correlation between HUVEC and HepG2 cells, and to find the relationship between it and sphingolipids. Results: TP can inhibit the tube formation process of HUVEC cells. Through PCR Array, PCR and Western Blot experiments, it is found that it may achieve this effect by down-regulating SPTLC2. TP can also inhibit the proliferation, migration and invasion of HepG2 cells through the same mechanism. In the three-dimensional co-culture model of HUVEC and HepG2 cells, it was found for the first time that HUVEC can promote the biological process of HepG2 cells. It was found through ELISA and Western Blot experiments that it may be achieved through the S1P/S1PRS pathway, and TP was found in the dosing experiment. It can significantly inhibit the induction of HUVEC on HepG2 cells. Conclusions: These data confirm that the level of SPTLC2 may be related to the anti-vascular and anti-tumor effects of TP. The data also showed that there is a correlation between the viability of HepG2 cells and HUVEC cells, which may be related to the expression of S1P/S1PRS. Ultimately, these data may help discover new anti-tumor targets.
Surface model of the human red blood cell simulating changes in membrane curvature under strain
Authors: Kuchel Philip W. , Cox Charles D. , Daners Daniel , Shishmarev Dmitry , Galvosas Petrik
Published: April 2021

The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a special apparatus inside an NMR spectrometer. However, direct mathematical predictions of the shapes of the morphed cells have not been reported before. We used recently available functions in Mathematica to triangularize and then compute four types of curvature. The RBCs were described by a previously presented quartic equation in three dimensional (3D) Cartesian space. A key finding was the extent to which the maximum and minimum Principal Curvatures were localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. The simulations, on the nano-metre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions that persist for many hours. This view is consistent with a recent proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. On the other hand, if the curvature that gates Piezo1 is at a much finer length scale, then membrane tension will determine local curvature and micron scale curvature as described here will be less likely to influence Piezo1 activity. The geometrical reorganization of the simulated cytoskeleton helps understanding of the concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.
Electric Toy Car to Reduce Anxiety Before a Cardiac Catherization: Randomized Controlled Trial
Authors: Chambon Edouard , Fournier Emmanuelle , Tagorti Maha , Lecerf Florence , Chaouche Nadera , Ion Iolanda , Bojan Mirela , Cohen Sarah , Aerschot Isabelle Van , Kara Meriem , Batteux Clément , Petit Jérome , Hascoet Sébastien
Published: April 2021

Anxiety before an invasive intervention is associated in children with persistent psychological disorders. We studied the effect of the transfer to the catheterization room by an electric toy-car on the anxiety of children and their parents before a cardiac catheterization. Forty-eight children with a median age of 5.6 years [4.2-7.0] were randomized to either riding on an electric car to go to the catheterization laboratory or being transported lying supine on a gurney. Anxiety assessments were performed by a physician blinded to allocation group on the day before the procedure (T0) and at anesthesia induction (T1). The modified Yale score (mYPAS-SF) and visual analog scale for anxiety (VAS-A) were used in the children, and the VAS-A in the parents. The mYPAS-SF, VAS-A-child and the VAS-A-parent scores were significantly higher at T1 than at T0 (P < 0.001, P < 0.001, and P = 0.005, respectively). The primary outcome (the median mYPAS-SF score at T1) was not significantly different in the two groups when males and females were combined. At T1, the VAS-A-child score, however, was significantly lower in the intervention than the control group (22 versus 55, P < 0.001). In the boys, the median mYPAS-SF score at T1 was significantly lower in the intervention group (25.0 versus 51.0, P = 0.024). No difference was observed in girls. The VAS-A parent score was lower at T1 in the intervention group (60 versus 87, P = 0.05). Conclusion: Riding to the catheterization laboratory on an electric toy car decreased anxiety at anesthesia induction in boys and also decreased parental anxiety.Clinical trial Registration: Registration number: ID-RCB: 2019-A00459-48. Date of registration: March 27th 2019.
Role of the Trace Amine Associated Receptors 5 (TAAR5) in Sensorimotor Functions
Authors: Kalinina Daria , Ptukha Maria , Goriainova Anastasia , Merkulyeva Natalia , Kozlova Alena , Volnova Anna , Gainetdinov Raul , Musienko Pavel
Published: April 2021

Monoamines are critical modulators of the sensorimotor neural networks. Using trace amine associated receptor 5 (TAAR5) knockout mice that express beta-galactosidase marker, we observed TAAR5 expression in the medial vestibular nucleus and Purkinje cells in the cerebellum suggesting that TAAR5 might be involved in gaze stabilization, vestibular and motor control. Accordingly, in various behavioral tests TAAR5-KO mice demonstrated lower endurance but better coordination and balance compared to wild type mice. Furthermore, we found specific changes in striatal local field potentials and motor cortex ECoG such as а decrease in delta andan increase in theta oscillations of power spectra respectively. The data obtained suggest that TAAR5 plays a considerable role in the regulation of postural stability, muscle force, balance and motor coordination during active movements, likely via modulation of monoaminergic systems on different levels of sensorimotor control, including brainstem, cerebellum and forebrain.
A nomogram for predicting the residual back pain after percutaneous vertebroplasty for osteoporotic vertebral compression fractures
Authors: Li Qiujiang , Long Xingxia , Shi Lin , Wang Yinbin , Guan Tao , Jiang Xiaocheng , Guo Donggeng , Lv Jinhan , Cai Lijun
Published: April 2021

Background: Current findings suggest that percutaneous vertebroplasty(PVP) is a suitable therapeutic approach for osteoporotic vertebral compression fractures (OVCFs). However, a significant minority of patients still experience residual back pain after PVP. The present retrospective study was designed to determine the risk factors for residual back pain after PVP and provides a nomogram for predicting the residual back pain after PVP.Methods: We retrospectively reviewed the medical records of patients with single-segment OVCFs who underwent bilateral percutaneous vertebroplasty. Patients were divided into group N and group R according to the postoperative VAS score. Group R is described as the VAS score of residual back pain≥4. Pre- and post-operative factors that may affect back pain relief were evaluated between two groups. Univariate and multivariate logistic regression analysis were performed to identify risk factors affecting residual back pain after PVP. We provided a nomogram for predicting the residual back pain and used the receiver operating characteristic curve (ROC), concordance index (c-index), calibration curve, and decision curve analyses(DCA) to evaluated the prognostic performance.Results: Among 268 patients treated with PVP, 37(13.81%) patients were classified postoperative residual back pain.The results of the multivariate logistical regression analysis showed that the presence of an intravertebral vacuum cleft(IVC)(OR 3.790, P=0.026), posterior fascia oedema(OR 3.965, P=0.022), server paraspinal muscle degeneration(OR 5.804, P=0.01; OR 13.767,P<0.001) and blocky cement distribution(OR 2.225, P=0.041) were independent risk factors for residual back pain after PVP. The AUC value was 0.780, suggesting that the predictive ability was excellent. The prediction nomogram presented good discrimination, with a C-index of 0.774(0.696~0.852), and was validated to be 0.752 through bootstrapping validation. The calibration curve of the nomogram demonstrated a good consistency between the probabilities predicted by the nomogram and the actual probabilities. The nomogram showed net benefits in the range from 0.06 to 0.66 in DCA.Conclusions: The presence of IVC, posterior fascia oedema, blocky cement distribution and severe paraspinal muscle degeneration were significant risk factors for residual back pain after PVP for OVCFs. Patients with OVCFs after PVP who have these risk factors should be carefully monitored for the possible development of residual back pain. We provide a nomogram for predicting the residual back pain after PVP.