bluuebunny/crossref_metadata_2025 huggingface dataset:
CellectSeq: In Silico Discovery of Antibodies Targeting Integral Membrane Proteins Combining In Situ Selections of Phage Displayed Synthetic Antibodies and Next-Generation Sequencing
Authors: Kelil Abdellali , Gallo Eugenio , Adams Jarrett , Moffat Jason , Sidhu Sachdev
Published: August 2020

Synthetic antibody (Ab) technologies are efficient and cost-effective platforms for the generation of monoclonal proteomic tools against human antigens. Yet, they typically depend on purified proteins, which exclude from interrogation integral membrane proteins that require the lipid bilayers to support their native form or function. Here, we present a novel Ab discovery strategy, termed CellectSeq, for targeting integral membrane proteins presented on native cells in complex environment. As proof of concept, we targeted the challenging tetraspanin receptor CD151, a target linked to cancer. First, we optimized in situ cell-based selections to enrich Ab pools for antigen-specific binders. Then, we designed novel NGS procedures to explore Ab pools diversities and abundances with enhanced accuracies. Finally, we developed novel motif-based scoring and error filtering algorithms for the comprehensive interrogation of NGS data to identify Abs with high diversities and specificities, even at extremely low abundances. We identified highly selective and diversified Abs against CD151 with abundance as low as 0.00009% for which manual sampling or identification using Abs abundances in NGS data would have been impossible. Here we show that CellectSeq enables the rapid discovery of diversified and selective antibodies against CD151, with implications for other integral membrane proteins and cell-surface receptors.
Predictive and Regenerative Medicine for Humans
Authors: Shun Shun
Published: August 2020

In human history, finding a cure for the devastating disease of cancer has been a long, ongoing battle. Recently, scientific research has shown several feasible bio-medicinal ways for the treatment of cancer. The first method is through predictive regenerative medicine, which converts (breast) cancer cells back into phenotypically benign cells using continually updated predictions from Bayesian inference models. Another common method is the rewriting of damaged coordinating genes, but this has underlying moral issues — who can authorise the right to alter human genes? To investigate these methods, this paper will discuss elementary point-set topologies, physical gene mapping, and gene sequencing. The main purpose of this paper is to establish a statistical method with the help of mathematics in our biological life science. The proposed method can be applied in the case of manipulating genetic transcription and expression with a suitable Bayesian inference model (for genetic reprogramming). The peak value of cancer cell conversion is its Bayesian regression (based on the model’s parameters) from the corresponding Bayesian inference (for the normal posterior distribution, prior and likelihood). The relevant predictive conditions can be determined from the respective model, which could be used to reveal elements that help cancer cell conversion maximisation/minimisation. Practically, we may apply both of the Bayesian optimisation and the related attribute adjustment (to the Oct4, SoX2, Klf4 and c-Myc transcription factors) that can induce the reprogramming of cancer cells. The expected outcome is that we can biomedical-engine the cancer cells conversion. To go ahead a step, one may apply my proposed Net-Seizing Theory to capture the genetic mutations that underly cancer disease. It is hope that we can design the corresponding universal strategy to heal cancer.
Migrating Dental Implants Into the Maxillary Sinus; Evaluation of Different Direct Trans-Oral Surgical Approaches
Authors: Hamdoon Zaid , Mahmood Nazhat , Talat Wael , Sattar Abier Abdul , Naeim Karrar , Qais Ahmed , Kheder Waad , Jerjes Waseem
Published: August 2020

Background: Dental implant surgery in atrophied maxilla has many risks, in some patients simultaneous sinus lifting with implant placement must be performed to increase the chances of successful implant which can cause implant migration. The aim of this study was to illustrate different surgical approaches to remove displaced dental implants into the maxillary sinus. Methods: Eleven patients were diagnosed with implant migration into the maxillary sinus. Radiographs were taken to identify the exact location of these implants which showed that they can be displaced in four anatomical area: sinus floor above the alveolar bone, near the junction of the sinus and nasal floor, near the floor of the orbit, and the most posterior aspect the sinus. The surgical removal was performed through four different trans-oral approaches depending on the location of the displaced implant. The surgical challenges, duration of surgery and postoperative complications were reported.Results: The least challenging surgical intervention was noted when removing the displaced implants from the floor of the sinus. More challenges were experienced during the surgical removal of anteriorly displaced implants near the nasal cavity using the Caldwell-Luc technique (anterior window) with noted difficulty to differentiate between the nasal cavity and maxillary sinus. Implant displacement into the maxillary sinus roof near the orbital floor can be technically challenging due to surgical access and the proximity of vital anatomical structures. Bleeding from the pterygoid venous plexus was profound with posterior lateral approach. Discussion: The choice of the appropriate surgical approach to retrieve displaced dental implants into the maxillary sinus depends on the implant’s location and the surrounding vital anatomical structures.
Multiple Isolated Extramedullary Relapse and Long-term Survival of One AML Patient
Authors: Li Jiman , Liu Yang , Li Yunzhu , weiping liu
Published: August 2020

Background: Granulocytic sarcomas (GS) are very rare. If it occurs after complete remission of acute myeloblastic leukemia（AML）, it indicates a recurrence of AML and a poor prognosis. In such cases, relapse of leukemia occurs within a mean of 10 months following granulocytic sarcoma.Case presentation: Here we present an unusual case of 78-year-old male who presented with AML-M1 38 years ago. After complete remission from AML-M1 6 years later, he developed unusual multiple isolated extramedullary relapses. And the extramedullary relapse occurred 7 times and involved 8 anatomic sites during 15 years. Despite repeated relapses, treatment and physical damage, the patient managed to survive into 2016.However, we did not detect any signs of leukemia after 1992 and his bone marrow and peripheral blood remained normal Until his death. Immunohistochemical results of our case are all the same, suggesting that they were all derived from the recurrence of the same tumor.Conclusions: Extramedullary relapses may occur in AML patients after complete relieve and without the blood count and BM involvement. Accurate diagnosis of GS is important so the patient could to be treated timely. It is a challenge for the pathologist to make the diagnosis, and without immunohistochemistry (IHC), it may be misdiagnosed as another tumor.
The potential effect of the angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma patients
Authors: huo qin , li zhenwei , shao ling , chen siqi , li jiaying , xie ni
Published: August 2020

BackgroundThe 2019-nCoV epidemic is the public health emergency that has had the greatest impact on the world. Our study aimed to better understand the underlying mechanisms and function of angiotensin-converting enzyme 2 (ACE2) receptor of 2019-nCoV on lung adenocarcinoma patients (LUAD), and provide a theoretical basis for early diagnosis, prognosis and targeted therapy of 2019-nCoV. MethodsThis study focuses on the expression level, functions, mutation rate, and copy number variations (CNVs) of ACE2 in LUAD using an extensive bioinformatics data mining process. The interaction between ACE2 expression and clinical-pathological parameters of patients with LUAD was investigated using UALCAN. Also, the essential biological features, single nucleotide variations (SNVs), CNVs, and pathway activities of genes interacting with ACE2 in these cancers were further analyzed. ResultsWe found that ACE2 expression in LUAD patients increased with age, but it was not related to cancer status, patient’s race, patient’s gender, or patient’s smoking habits. Moreover, our results showed that compared to that in normal tissues, ACE2 was highly expressed in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), and stomach adenocarcinoma (STAD). However, there is no significant difference in the expression of ACE2 in patients of different ages. ConclusionsThese findings demonstrate the importance of ACE2 in LUAD, and provide insights into the regulatory mechanisms and function of ACE2.
Health-related quality of life of middle-aged and elderly people with hypertension: a cross-sectional survey from a rural area in China
Authors: Chen Qi , Ran Li , Tan Xiaodong
Published: August 2020

Background
The purpose of this study was to evaluate health-related quality of life (HRQoL) of middle-aged and elderly people with hypertension in Enshi, China, and to explore the important correlates defining HRQoL.
Methods
During the period of April through July 2018, a self-monitoring intervention program for hypertension control was implemented in a remote area of central China. Participants completed a cross-sectional survey which included demographic characteristics, the Health-related Quality of Life Survey, and the Pittsburgh Sleep Quality Index Survey. Univariate analysis was performed by analysis of variance, and multiple linear regression analysis was used to analyze the influencing factors of HRQoL in middle-aged and elderly hypertensive patients. In the multivariate analysis, the variables with P ≤ 0.05 in the single factor analysis were combined with the professional significance to establish a multiple linear regression model.
Results
Information from 500 participants was available for analysis. Among them, the scores of PCS and MCS was 31.66 ± 9.50 and 41.38 ± 10.69, respectively. Multivariable regression analyses showed that the influencing factors for PCS scores were age, education level, sleep quality status, tea-drinking habit, and exercise frequency. The influencing factors for MCS scores were family monthly income, sleep quality status, tea-drinking habit, and exercise frequency.
Conclusion
The overall HRQoL for rural middle-aged and elderly hypertensive patients in Xuan’en county of Hubei province was poor. Effective relevant measures for the above factors were urgently needed to improve the quality of life for the elderly in rural areas. Awareness of these relevant factors could help health care professionals provide better supportive care.
Development and clinical validation of A Novel 9-gene prognostic biomarkers based on multi-omics in pancreatic adenocarcinoma
Authors: Xu Dafeng , Wang Yu , Liu Xiangmei , Zhou Kailun , Wu Jincai , Chen Jiacheng , Chen Cheng , Chen Liang , Zheng Jinfang
Published: August 2020

Background: The prognosis of patients with pancreatic cancer remains poor due to the lack of biomarkers for early diagnosis and effective prognosis. Methods: RNA-Seq, SNP, CNV data were downloaded from The Cancer Genome Atlas(TCGA); Univariant cox regression was used to identify prognosis-related genes; GISTIC 2.0 was used to identify significantly amplified or deleted genes; Lasso method was used to construct risk prognosis model, which was then validated in GEO and ICGC cohorts. rms package was used to evaluate the overall predictive performance of the model by calculating and comparing the C-index values with other models. Experiments of western blot were performed to evaluate the expression of genes. Results: 54 candidate genes were obtained after integrating the genomic mutated genes and prognosis-related genes. The Lasso method was conducted to finally ascertain nine characteristic genes, including UNC13B, TSPYL4, MICAL1, KLHDC7B, KLHL32, AIM1, ARHGAP18, DCBLD1, and CACNA2D4. The 9-gene signature model can help with stratifying samples at risk in the training cohort and external validation cohort. In addition, the overall predictive performance of our model is superior to the others. We found that AIM1 and DCBLD1 were highly expressed in tumor tissues, while ARHGAP18, CACNA2D4, and TSPYL4 were lowly expressed in tumor tissues at the protein and transcription levels. Conclusion: The nine-gene signatures constructed in this study can be used as the novel prognostic markers to predict the survival of PAAD patients.
Reporting of Screening and Diagnostic AI Rarely Acknowledges Ethical, Legal and Social Implications: A Mass Media Frame Analysis
Authors: Frost Emma Kellie , Carter Stacy M
Published: August 2020

Introduction. Healthcare is a rapidly expanding area of application for Artificial Intelligence (AI). Although there is considerable excitement about its potential, there are also substantial concerns about the negative impacts of these technologies. Since screening and diagnostic AI tools now have the potential to fundamentally change the healthcare landscape, it is important to understand how these tools are being represented to the public via the media. Methods. Using a framing theory approach, we analysed how screening and diagnostic AI was represented in the media and the frequency with which media articles addressed the benefits and the ethical, legal, and social implications (ELSIs) of screening and diagnostic AI. Results. All the media articles coded (n = 136) fit into one of three frames: social progress (n = 132), economic development (n = 59), and alternative perspectives (n = 9). The vast majority of the articles were positively framed, with 135 of the articles discussing benefits of screening and diagnostic AI, and only 9 articles discussing the ethical, legal, and social implications. Conclusions. We found that media reporting of screening and diagnostic AI was overwhelmingly positive. Screening and diagnostic AI may be represented more positively in the mass media than AI in general. This represents an opportunity for health journalists to provide publics with deeper analysis of the ethical, legal and social implications of screening and diagnostic AI, and to do so now before these technologies become firmly embedded in everyday healthcare delivery.
Analysis of Stress, Strain, and Fatigue Strength of the Rotary Table of Boom-type Roadheaders
Authors: Tian Jie , zhang lansheng , yao haifeng , Wu miao
Published: August 2020

The rotary table is the key component in the optimal design of roadheaders. In this study, a simulation model of the cutting part and a rotary table is established in SolidWorks, and stress analysis and strength evaluation of the structure of the rotary table are performed. To this end, finite element analysis is performed on the basis of the dynamic theory of a coupled multibody system comprising rigid and flexible bodies. Considering actual working conditions, the load file of the cutting head is calculated based on the development of the “Roadheader Machine load Calculation Program”, and the stress and strain cloud map of the cutting head running to the bottom left, middle end, and right end of the rotary table is obtained through Adams simulation. Then, the 6-order modal analysis is carried out, and the S-N curve of the turntable is finally established. In addition, the fatigue life reliability of the turntable is analyzed using the AWE fatigue module. The results show that, provided reliable working conditions, the EBZ160 type roadheader machine during the normal service life shows no risk of fatigue failure under normal working load.
Cardiac Troponin I Associated with Poor Prognosis and Death Risk in 726 Severe and Critical COVID-19 Patients: A Retrospective Cohort Study
Authors: Chen Huilong , Li Xinjie , Marmar Tuohutaerbieke , Xu Qiang , Tu Jing , Li Tong , Han Jun , Xu Dong , Shen Tao
Published: August 2020

Background: A few patients with coronavirus disease 2019 (COVID-19) may progress into irreparable outcomes. Early identification of patients with serious symptoms who may develop critical illness and even death is of considerable importance for personalizing treatment and balancing medical resources.Methods: In this retrospective study, demographic, clinical characteristics and laboratory tests from 726 patients with serious COVID-19 from Tongji Hospital (Wuhan, China) were analyzed. The standards for the serious type are guided by the Chinese management guideline for COVID-19. Patients were classified into critical group (174 cases) and severe group (552 cases) based on whether the composite endpoint was reached, and the former group was divided into the survivors (47 cases) and non-survivors (127 cases). Univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were performed to investigate the risk factors associated with poor prognosis and mortality outcomes.Results: Male patients accounted for 62.1% and 51.6% in the critical group and severe group, with a median age of 68 and 65 years, respectively. Among critical cases there was a higher prevalence of chronic obstructive lung disease (p = 0.029) and chest distress (p = 0.040) than in severe cases. In the multivariable analysis, the risk factors associated with poor prognosis in severe cases were advanced age (p = 0.002), high respiratory rate (RR) (p < 0.0001), high lactate dehydrogenase (LDH) level (p = 0.021), high hypersensitive cardiac troponin I (hs-cTnI) level (p < 0.0001), and low platelet counts (p = 0.005) at admission. In the adjusted models, higher mortality outcomes in critical patients were associated with high hs-cTnI level (p = 0.037). By plotting ROC curves of different indices, hs-cTnI and LDH were found to be predictive factors for poor prognosis in patients with severe COVID-19.Conclusions: For the risk assessment of serious COVID-19 patients on admission, advanced age, high level of RR, LDH, hs-cTnI, and low platelet counts, constitute important risk factors for poor prognosis in severe cases, and the hs-cTnI level can be helpful in predicting fatal outcomes in critically ill patients.
Exploring the potential for item banking in assessing quality of life for evaluating adolescent health interventions
Authors: Khadka Jyoti , Chen Gang , Ratcliffe Julie
Published: August 2020

Background

To develop and validate an item bank using existing items from both preference and non-preference-based health-related quality of life (HRQoL) instruments targeted for application with adolescent populations.
Methods

Australian adolescents completed the Child Health Utility 9D (CHU9D), demographic details, self-rated health status, disability and one other instrument (either preference-based: Health Utilities Index (HUI) or EuroQoL-5 Dimension-Youth (EQ-5D-Y) or Assessment of Quality of Life (AQoL)-6D Adolescent or non-preference-based: Pediatric Quality of Life Inventory (PedsQL) Short Form 15 or KIDSCREEN-10) using online survey portals. Data from all the instruments were pooled together to create an item bank, which was then subjected to Rasch analysis to tests its psychometric properties. Validity of the item bank was assessed by testing its ability to discriminate varying levels of self-reported health, disability and socio-economic status (as approximated by the Family Affluence Scale).
Results

A total of 4,352 Australian adolescents aged 11–17 years from the general population participated. The CHU9D (common instrument) items were used as anchor items to create the item bank. Rasch analysis demonstrated that 2 of the 75 items (2.7%) misfit and were removed from the item bank. The 73-item item bank had adequate precision, no misfitting items, no item bias and demonstrated sufficient unidimensionality. In general boys exhibited higher HRQoL scores than girls (p = 0.001). More severe health status/disability and lower socio-economic status being associated with lower HRQoL (p < 0.0001).
Conclusions

The item bank demonstrated adequate Rasch-based psychometric properties and validity demonstrating the feasibility of the construction of an item bank in this context. The addition of more targeted items for adolescents in the general population and the addition of participants with more health impairments may improve the general applicability of the item bank for both general population and patient cohorts.
Species Structure, Diversity, and Tree Regeneration on Stumps in Second-Growth Temperate Rainforests of British Columbia, Canada
Authors: Wang Qing , Srivast Vivek , Super Laura , Wang Tongli , El-Kassaby Yousry A.
Published: August 2020

Background: The significance of stumps and other coarse woody debris (CWD) in maintaining biodiversity has been widely recognized. However, there is a paucity of research on the role of stumps in tree regeneration. We studied vascular plant structure, diversity, and tree regeneration on stumps in temperate rainforests across three sites in British Columbia, Canada (Malcom Knapp Research Forest, MKRF; Pacific Spirit Regional Park, PSRP; and Stanley Park, SP).Results: 1) There were 19 vascular plant species found on stumps, including eight tree species, 2) Overall seedling abundance was higher on stumps than the nearby ground, 3) The number of established plants showed a positive linear (MKRF, SP) or Gaussian (PSRP) relationship with stump basal diameter, 4) Vegetation abundance varied with site (MKRF > SP > PSRP), 5) The overall species established on stumps were positively associated in MKRF (Variance ratio = 2.74) and SP (Variance ratio = 1.37), but negatively associated in PSRP (Variance ratio = 0.57), and 6) Tree species appeared to compete with each other on stumps and were likely to co-occur with understorey species.Conclusion: Our results highlight community and species associations on stumps. We found that stump diameter is a major factor affecting tree regeneration in these second-growth temperate rainforests. To aid future research on stump-vegetation relationships, we synthesize our results in a schematic of vascular plant biodiversity and tree regeneration on stumps. Our work and this schematic can be used to stimulate ideas for new hypothesis generation and for studies relevant for conservation, management and basic science research.
Enhancing Early Engagement (E3) in Mental Health Services Training for Children's Advocacy Center's Victim Advocates: Protocol for a Randomized Clinical Trial
Authors: Taylor Erin K , Dopp Alex R , Lounsbury Kaitlin , Thompson Yutian , Miller Michelle , Jorgensen Ashley G. , Silovsky Jane F
Published: August 2020

Background: Child maltreatment is a major public issue in the United States, yet most children affected by abuse or neglect never engage in evidence-based practices (EBP) for child mental health. Children’s Advocacy Centers (CACs’) are uniquely situated to serve as Family Navigators who connect children impacted by maltreatment to appropriate EBPs. In fact, the CAC position of Victim Advocate mirrors the Mental Health Family Navigator national initiative. Methods: We will develop, implement, and evaluate web-based and consultative training for Victim Advocates to enhance early engagement in services (E3 training). The interactive web-based training will embed key targets of knowledge and skills related to family engagement, trauma, and EBP services. Participating CACs will be randomized to E3 webinar-based training, E3 webinar plus consultation, or delayed training. The project will test the E3 training’s impact on key mechanisms of change (e.g., knowledge, skills) to improve rates of screening, referral, and access to EBP services. The feasibility of implementing the training program, and differential impact and costs by level of training will be examined.Discussion: The overarching goal of this project is to test a training that is readily implemented through CACs and examine the mechanisms for improving early engagement and, ultimately, child and adolescent mental health outcomes. Results and cost findings will be used to plan a large-scale comprehensive, mixed-methods Hybrid Type II effectiveness-implementation and cost-effectiveness trial of Family Navigator E3 training. If outcomes are positive, considerable infrastructure exists to support the scale-up and sustainability of E3 training nationwide, by embedding the training in national CAC training protocols.Trial registration: NCT04221633
The COVID-19 Pandemic in Francophone West Africa: From the First Cases to Responses in Seven Countries
Authors: Bonnet Emmanuel , Bodson oriane , Marcis Fréderic Le , Faye Adama , Sambieni Emmanuel , Fournet Florence , Boyer Florence , Coulibaly Abdourahmane , Kadio Kadidiatou , Diongue Fatoumata Binetou , Ridde Valery
Published: August 2020

Background: In early March 2020, the COVID-19 pandemic hit West Africa. Countries in the region quickly set up crisis management committees and organised drastic measures to stem the spread of the coronavirus. The objective of this article is to analyse the epidemiological evolution of COVID-19 in seven Francophone West African countries (Benin, Burkina Faso, Côte d'Ivoire, Guinea, Mali, Niger, Senegal) as well as the public health measures decided upon during the first four months of the pandemic. Methods: Our method is based on quantitative and qualitative data from the pooling of information from a COVID-19 data platform and collected by a network of interdisciplinary collaborators present in the seven countries. Descriptive and spatial analyses of quantitative epidemiological data and content analyses of qualitative data on public measures and management committees were performed. Results: Attack rates for COVID-19 range from less than 10 per 100,000 inhabitants (Benin) to more than 45 per 100,000 inhabitants (Guinea). The spatio-temporal analysis shows three phases of incidence clusters. By the end of June 2020, case numbers had plateaued in some countries (Burkina Faso, Niger, Mali) while others continued to see the number of infections increasing (Benin, Côte d'Ivoire, Guinea, Senegal). The countries all reacted quickly to the crisis, in some cases before the first reported infection, and implemented public measures in a relatively homogeneous manner. None of the countries implemented country-wide lockdowns, but in some cases implemented partial or local containment measures. At the end of June 2020, countries began to lift certain restrictive measures, sometimes under pressure from the general population or from certain economic sectors. All the countries have adopted response plans and organized multiple crisis management committees, although their content and functioning have not always been transparent or easy to understand. Conclusion: Much research remains to be done in West Africa. It will be necessary to better understand the dynamics of the pandemic, which appears to be largely under control, as well as the effectiveness and implementation of the state responses, which have been rapidly formulated.
Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms
Authors: Kato Yasuhiko , Kuwabara Hitoshi , Okada Takashi , Munesue Toshio , Benner Seico , Kuroda Miho , Kojima Masaki , Yassin Walid , Eriguchi Yosuke , Kameno Yosuke , Murayama Chihiro , Kasai Kiyoto , Ozaki Norio , Kosaka Hirotaka , Yamasue Hidenori
Published: August 2020

Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6 week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N=106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (False discovery rate (FDR) corrected P=0.043, d=0.74, N=83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR=0.004, d=1.13, N=60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR=0.006, r=-0.485, N=43) and deteriorations between 2 and 4 weeks (PFDR=0.032, r=0.415, N=37).Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood, and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-Methyl-D-Aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.Trial registration: A multicenter, parallel group, placebo-controlled, double blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders. (The date registered: 30th Oct 2020; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264)
Changes in day/night activity in the 6-OHDA-induced experimental model of Parkinson´s disease: Exploring prodromal biomarkers
Authors: Requejo Catalina , de-Ipiña Karmele Lopez , Ruiz-Ortega José Ángel , Fernández Elsa , Calvo Pilar M. , Morera-Herreras Teresa , Miguelez Cristina , Cardona-Grifoll Laura , Cepeda Hodei , Ugedo Luisa , Lafuente José Vicente
Published: August 2020

Background:

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder for which there is not currently a cure and when it is clinically diagnosed is likely too late. The search for experimental models mimicking an early stage of PD before motor manifestations is fundamental in order to explore early signs and get a better prognosis. Interestingly, our previous studies have indicated that 6-hydroxydopamine (6-OHDA) is a suitable model to induce an early degeneration of the nigrostriatal system without any gross motor impairment. Considering our previous findings, we aim to implement a novel system to monitor rats after intrastriatal injection of 6-OHDA to detect and analyze physiological changes underlying prodromal PD.
Methods:

Rats were unilaterally injected with 6-OHDA or saline solution into the striatum and placed in enriched environment cages where the activity was monitored. After two weeks, the amphetamine test was performed before the sacrifice. Immunohistochemistry was developed for the morphological evaluation and western blot analysis to assess molecular changes.
Results:

Home-cage monitoring revealed behavioral changes in response to 6-OHDA administration including significant hyperactivity and hypoactivity during the light and dark phase respectively turning out in a change of the circadian timing. A preclinical stage of PD was functionally confirmed with the amphetamine test. Moreover, the loss of tyrosine hydroxylase expression was significantly correlated with the motor results, and 6-OHDA induced early proapoptotic events.
Conclusions:

Our findings provide evidence for a novel prodromal 6-OHDA model following a customized monitoring system that could give insights to detect non-motor deficits and molecular targets to test neuroprotective/neurorestorative agents.
EQ-5D-3L Health State Utility Values in Transfusion-dependent thalassemia Patients in Malaysia: A Cross-sectional Assessment
Authors: Shafie Asrul Akmal , Chhabra Irwinder Kaur , Wong Jacqueline Hui Yi , Mohammed Noor Syahireen
Published: August 2020

Purpose: There is a gap of information describing the health state utility values (HSUVs) of Transfusion-dependent Thalassemia (TDT) patients in Malaysia. These values are useful in the assessment of health-related quality of life (HRQoL), economic evaluations and provide guidance to disease management decisions. The objective of this study was to estimate and derive HSUVs associated with the treatment and complications of TDT patients in Malaysia using the EQ-5D-3L instrument.Methods: A cross-sectional survey using the EQ-5D-3L instrument was conducted between May to September 2018 across various public hospitals in Malaysia. Using a multi-stage sampling, patients diagnosed with TDT and receiving iron chelating therapy were sampled. The findings on the EQ-5D-3L survey were converted into utility values using local tariff values. A two-part model was used to examine and derive health state utility values associated with the treatment and complications of iron overload in TDT. Results: A total of 585 patients were surveyed. The unadjusted mean (SD) EQ-5D-3L utility value for TDT patients were 0.893 (0.167) while mean (SD) EQ VAS score was 81.22 (16.92). Patients who had more than two iron overload complications had a significant decline in HRQoL. Patients who were on oral monotherapy had a higher utility value of 0.9180 compared to other regimen combinations.Conclusion: Lower EQ-5D-3L utility values were associated with patients who developed iron overload complications and were on multiple iron chelating agents. Emphasizing compliance to iron chelating therapy to prevent the development of complications is crucial in the effort to preserve the HRQoL of TDT patients.
Safety and Efficacy Profile of Mogamulizumab (Poteligeo) in the Treatment of Cancers: An Update Evidence From 14 Studies
Authors: Zhang Ting , Sun Jing , Li Jinying , Zhao Yunuo , Zhang Tao , Yang Ruoning , Ma Xuelei
Published: August 2020

Background: CC chemokine receptor 4 (CCR4) is the receptor for CCL22 and CCL17, which is expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4 positive Treg cells, the mogamulizumab can boost antitumor immunity and achieve anti-tumor effects.Methods: We examined the PubMed and ClinicalTrials.gov without any language restrictions until 1 February 2020. Considering variability in different studies, the overall survival (OS), progression‐free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) were selected to evaluate the efficacy. Besides, adverse events (AEs) were calculated to assess the safety.Results: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while lymphopenia, neutropenia and rash were the top 3 grade ≥3 AEs. In combination therapies, the top 3 all-grade AEs were neutropenia, anaemia, and lymphopenia, and lymphopenia is the most common grade ≥3 AE. Besides, the overall ORR is 0.430 (95% CI: 0.393-0.469) and the pooled mean PFS is 1.060 months (95% CI: 1.043-1.077) in mogamulizumab monotherapy. In combination therapies, the overall ORR is 0.203 (95% CI: 0.022-0.746) while the overall PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively.Conclusions: On the basis of present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which had a considerable potential in treating patients with cancers.
Prevalence of Obstructive Sleep Apnoea in Patients with Hypertension: Study from a Tertiary Care Hospital
Authors: Kareem Ozaifa , Tanvir Masood , Bader Ghulam Nabi
Published: August 2020

Background: Obstructive Sleep Apnoea (OSA), a condition characterized by a complete or partial cessation of airflow during sleep, can cause various cardiovascular disorders including hypertension. The aim of the study was to determine the prevalence of OSA in patients with hypertension. Methods: A cross-sectional prospective cohort study of 504 patients with hypertension was undertaken at a tertiary care hospital of India for a period of six months. OSA was evaluated using the Berlin questionnaire and the Epworth Sleepiness Scale. Data analysis was done using SPSS v. 20. Results: High risk of OSA was identified in 120 (23.8%) patients and the prevalence of sleepiness (Epworth Sleepiness score ˃16) was found to be 32.5% (95% CI, p˂0.001) in these patients. The mean neck circumference, waist circumference and waist-to-hip ratio for high-risk OSA group were 14.75 ± 1.338 inches, 105.90 ± 11.28 cm and 1.01 ± 0.065 respectively while for the low-risk group, these parameters were 13.97 ± 1.045 inches, 98.75 ± 10.87 cm and 0.99 ± 0.080 respectively (95% CI, p˂0.001). The mean blood pressure (BP) ≥133.52/84.37 mm Hg was recorded in patients with a high risk of OSA (95% CI, P<0.05), and resistant hypertension (3.3%) was significantly associated with the risk of OSA (95% CI, P<0.05).Conclusion: In the tertiary health care setting, the prevalence of high-risk of OSA in patients with hypertension is high. Screening for OSA should be a part of the hypertensive medical investigation and patients may benefit from a proper evaluation of OSA.
Neonatal COVID-19: a clinical case report from the Democratic Republic of Congo (DRC)
Authors: ZIGABE Serge , Kajibwami Etienne , Mateso Guy-Quesney , Ntaligeza Benjamin
Published: August 2020

COVID-19 started as a cluster of pneumonia cases in Wuhan City, the Province of Hubei, China, in December 2019. It spread to many regions of China, outside of China and was declared a pandemic by the World Health Organization (WHO) on March 11th, 2020. Initially Africa had no case and now the continent is reporting an increasing number of confirmed cases in an exponential manner (1,2).
The Effects of a Theacrine-based Supplement on mRNAs Related to Various Metabolic Processes and Sirtuin Activity in vitro
Authors: Mumford Petey , Osburn Shelby , Roberts Michael D.
Published: August 2020

There is evidence in rodents to suggest theacrine-based supplements modulate tissue sirtuin activity as well as other biological processes associated with aging. Herein, we examined if a theacrine-based supplement (NAD3) altered sirtuin activity in vitro while also affecting markers of mitochondrial biogenesis and the mRNA expression of genes related to various cellular processes in muscle. The murine C2C12 myoblast cell line was used for experimentation. Following 7 days of differentiation, myotubes were treated with 0.45 mg/mL of NAD3 (containing ~ 2 mM theacrine) for 3 and 24 hours (n=6 treatment wells per time point). Control treatments consisted of cellulose-only treatments at the same time points. Relative to CTL-treated cells, NAD3 treatments increased (p<0.05) Sirt1 mRNA levels at 3 hours, as well as global sirtuin activity at 3 and 24 hours. While NAD3 treatments decreased mRNA levels of Nfe2l2 at 3 hours and increased levels at 24 hours relative to CTL-treated cells (a gene involved in mitochondrial biogenesis, p<0.05), citrate synthase activity levels (a surrogate of mitochondrial density) remained unaltered between treatments. NAD3 treatments for 3 and 24 hours decreased Nlrp3 mRNA levels relative to CTL-treated cells (an inflammatory marker, p<0.05). Additionally, NAD3 treatments decreased Map1lc3b mRNA levels (an autophagy marker) after 24-hour treatments (p<0.05). Although these data are limited to select biomarkers in vitro, these preliminary findings suggest a theacrine-based supplement can modulate various skeletal muscle biomarkers related to sirtuin activity, inflammation, and autophagy. Muscle biopsy studies in humans are needed to confirm these current findings.
Bridging the science-to-service gap: Implementation of a supervised HIV self-testing intervention among young adults at a tertiary education institution in Zimbabwe
Authors: Mukora-Mutseyekwa Fadzai , Mundagowa Paddington Tinashe , Kangwende Rugare Abigail , Murapa Tsitsi , Tirivavi Mandla , Mukuwapasi Waraidzo , Uzande Charles , Mutibura Queen , Chadambuka Elizabeth Marian , Machinga Mazvita
Published: August 2020

Background: The evidence-based practices of implementation science constitute the integration of study findings into routine practice of public health interventions such as HIV testing services (HTS). While young people are at high risk of HIV infection, a national survey showed that adolescents and youths were less likely to go for an HIV test. This study aimed to develop and implement a systematic and multifaceted HIV self-testing (HIVST) intervention to promote the uptake of HTS among young people. Methods: The study was conducted at Africa University, Mutare where desk and literature review was conducted to gather evidence on HIVST. Multiple stakeholder consultation was carried out to understand contextual enablers and barriers that either promote or undermine adoption of the intervention. Strategies for situation analysis and evidence gathering included community engagement meetings, training of implementers and conducting a baseline survey. A consensus group adapted the Consolidated Framework for Implementation Research (CFIR) to understand the realities of context and intervention while the Reach, effectiveness, adoption, implementation, maintenance (RE-AIM) guide was used to analyze the intervention implementation and evaluation survey. Results: The baseline enquiry indicated that the CFIR dimensions which positively influences intervention implementation were: network, network and communications, preparation of implementation, availability of resources, planification, implication and formally appointed internal leadership while origin of intervention and self-efficacy had negatively influenced implementation. Evaluating the intervention fidelity using the RE-AIM framework revealed that high performance with regard to reach, effectiveness, adoption and implementation but low maintenance. This study also applied the APEASE criteria (affordability, practicability, effectiveness, acceptability, side effects, and equity) for selecting the final components used in implementation. Conclusion: Combining literature search, documents review, stakeholder consultation, together with provider and end-user engagement can potentially improve intervention delivery for closed populations such as Universities. Blending program agents with systematic process of activities correspondingly enhance HTS uptake among young people. The utilization of the CFIR and RE-AIM analytical frameworks in this study, offered flexible and simplified implementation and analysis of the intervention.
Diagnostic significance and carcinogenic mechanism of pan-cancer gene POU5F1 in liver hepatocellular carcinoma
Authors: He Dingdong , Zhang Xiaokang , Tu Jiancheng
Published: August 2020

Background
The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers is disputable heretofore. The diagnostic value and function mechanism of POU5F1 in liver hepatocellular carcinoma (LIHC) have not been studied thoroughly.
Methods
An integrative strategy of meta-analysis, bioinformatics and wet-lab approach was used to explore the diagnostic and prognostic significance of POU5F1 in various types of tumors, especially in LIHC. Meta-analysis was utilized to investigate the impact of POU5F1 on prognosis and clinicopathological parameters in various cancers. The expression level and diagnostic value of POU5F1 were assessed by qPCR in plasma collected from LIHC patients and controls. The correlation between POU5F1 and tumor infiltrating immune cells (TIICs) in LIHC was evaluated by CIBERSORT. Gene set enrichment analysis (GSEA) was performed based on TCGA. Hub genes and related pathways were identified on the basis of co-expression genes of POU5F1.
Results
Elevated POU5F1 was associated with poor OS, DFS, RFS and DSS in various cancers. POU5F1 was confirmed as an independent risk factor for LIHC and correlated with tumor occurrence, stage and invasion depth. The combination of POU5F1 and AFP in plasma was with high diagnostic validity (AUC = 0.902, P < 0.001). Specifically, the level of POU5F1 was correlated with infiltrating levels of B cells, T cells, dendritic cells and monocytes in LIHC. GSEA indicated POU5F1 participated in multiple cancer related pathways and cell proliferation pathways. Moreover, CBX3, CCHCR1 and NFYC were filtered as the central hub genes of POU5F1.
Conclusions
Our study identified POU5F1 as a pan-cancer gene could not only be a prognostic and diagnostic biomarker in various cancers, especially in LIHC, but functionally carcinogenic in LIHC.
Smartphone Usage Posture (Sitting and Lying Down) and Musculoskeletal Symptoms among school-aged children (6-12 years old) in Nakhon Si Thammarat ,Thailand
Authors: Mongkonkansai Jittaporn , Madardam Uraiwan , Veerasakul Siriluk
Published: August 2020

Background: The posture while using smartphone in school-aged children is at risk on occurring musculoskeletal symptoms. The purpose of this study is to study the postures while using a smartphone and the factors related to the abnormalities of the musculoskeletal symptoms of school-aged children. Method: Experimental study is a method of this research. The samples were 233 school-aged children in Nakhon Si Thammarat, Thailand. Multi-stage sampling and data collection consisted questionnaire for the musculoskeletal symptoms by applying from the Nordic Musculoskeletal Questionnaire, ISO 11226: 2000 Ergonomics-Evaluation of static postures, which was a smartphone using posture evaluation form with data analysis using percentage, mean, standard deviation and Chi square. Result: The smartphone usage posture are mostly a lying position, which is 52.4%. 91.5 % of children has unacceptable risky smartphone usage posture. Mostly, the lying position has various organs tilted at angles, compared to the body's symmetrical axis, rather than the sitting position. The school-aged children had a prevalence of musculoskeletal symptoms of 20.2%, with the lying position having a higher rate of musculoskeletal symptoms, which is 10.7%. The smartphone usage posture is statistically significant correlated with the symptoms occurring in the head area. The risk of ergonomics and the musculoskeletal symptoms are statistically significant. Conclusion: The smartphone usage posture among students is at high risk especially lying position and has a chance of a musculoskeletal symptoms, higher than the sitting position. Educating to provide knowledge about safe use of smartphones to students, parents and relevant government agencies is very important.