bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Transcriptomic Analysis Points to Early Organelle Dysfunction in Human Astrocytes in Alzheimer’s Disease
Authors: Galea Elena , Weinstock Laura D. , Larramona-Arcas Raquel , Pybus Alyssa F. , Giménez-Llort Lydia , Escartin Carole , Wood Levi B.
Published: June 2021

BackgroundRecent gene profiling of human AD astrocytes using single-nucleus RNA sequencing is limited by the low number of differentially expressed genes detected, and the small size of cohorts. We improved on prior studies with a novel systems-biology-based approach that can be used with available data from large cohorts.Methods Brain-cell specific gene clusters were generated from RNA sequencing data from isolated healthy human brain cells using a cell-type enrichment score and clustering. The cell-specific gene clusters were localized in whole-brain transcriptomes from 766 subjects diagnosed with AD or mild cognitive impairment (MCI) by the Mount Sinai Hospital, the Mayo Clinic, and the Religious Order Study/Memory and Aging Project (ROSMAP). Gene clusters were organized into functional categories, and changes among subject groups determined by gene set variation analysis (GSVA) and principal component analysis (PCA).ResultsHierarchical clustering revealed molecular heterogeneity in individuals with the same clinical diagnosis. Particularly in the Mayo Clinic and ROSMAP cohorts, over 50% of Controls presented massive down-regulation of genes encoding synaptic proteins as described in AD, and 30% of AD patients looked like true Controls. The astrocytic gene profiles in AD patients presenting down-regulation of neuronal genes were termed ‘AD astrocytes’. According to GSVA and PCA, AD astrocytes showed down-regulation of genes encoding for mitochondrial and endolysosomal proteins, and up-regulation of genes related to perisynaptic astrocytic processes (PAP), and survival and stress responses. One limitation of the analysis is that gene clusters identified in healthy brain transcriptomes may no longer exist in AD. However, quantification of network reorganization in AD subjects using the metric ‘modular differential connectivity’ showed equal or enhanced connectivity in 95.5% of the modules, suggesting that clusters identified by co-expression analyses in healthy cells are preserved in AD. Another limitation is that changes in transcripts ubiquitous in all cell types may go undetected in our analysis relying on astrocyte-specific genes.DiscussionWe detected a profound transcriptional change in astrocytes in a high percentage of Control, MCI and AD subjects, affecting organelles and astrocyte-neuron interactions. We argue that therapies preventing organelle dysfunction in astrocytes may protect neural circuits in preclinical and clinical AD.
Isolated Adrenocorticotropic Hormone Deficiency Accompanied by Impaired Cognitive Function: A Case Report
Authors: IKENOUCHI ATSUKO , Seki Issei , Okamoto Naomichi , Konishi Yuki , Yoshimura Reiji
Published: June 2021

Background: Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is an adrenal insufficiency caused by a decrease in ACTH alone among the anterior pituitary hormones. IAD is often overlooked because it causes nonspecific symptoms. We report a case of IAD diagnosed after the appearance of mild cognitive impairment (MCI).Case presentation: Our department was consulted on a case of a 46-year-old man for whom dementia was suspected because he was speaking incoherently, wiped his nose with his hands and showed mild brain atrophy on MRI. He was previously diagnosed with some psychiatric diseases, such as narcolepsy and adjustment disorder. He could not continue working due to somnolence, general fatigue and appetite loss. At the examination, he had difficulty concentrating and sustaining attention, exhibited restlessness, and scored 25 points on the Mini Mental State Examination-Japanese (MMSE-J); MCI was observed. Blood tests showed decreased ACTH, cortisol and free thyroxine and increased thyroid-stimulating hormone levels. He received further evaluation, and he was diagnosed with IAD and primary hypothyroidism. Hydrocortisone (15 mg) was started, after which his physical problems and his difficulty concentrating disappeared. His MMSE-J score also increased to 30. His cognitive functions completely recovered. He returned to work and continued to work stably.Conclusion: This patient was diagnosed with IAD and treated with adrenocortical hormone replacement therapy. His cognitive functions recovered, his physical and mental disorders were alleviated, and he returned to society. It is important not to miss neurological and psychiatric symptoms that can be cured by physical treatment.
How does Foreign Direct Investment Influence the Environment in China? Prior and During the Covid-19 Pandemic
Authors: Salem Sultan , Kam Sanda , Lee Nicole
Published: June 2021

This study revisits the recent widely ongoing debate over the effects of FDI on the environment in China. Analysis has shown that firms seek to operate in countries with lax environmental standards, namely the PHV. However, the PHL counterargument is also prevalent. This theory stipulates FDI will bring higher environmental management standards and cleaner technologies into the host country. Empirical literature is inconclusive and at times conflicting between some hypotheses therefore this study aims to provide additional clarity on the impact of FDI on the environment in China. This study concludes the existence of both PHV and PHL hypotheses which can be explained by the impact mechanisms of FDI; scale, structural, technique and income effects. The development levels of China using the EKC model hypothesis is used to explain the varying impacts of FDI on the environment. Reflecting on these interesting recent findings in this study, policy implications are discussed and suggestions are provided to improve the impact of FDI on the environment. The future for China is expected to embody an environmental focus in promoting FDI in renewable energy and greener technologies to improve environmental quality.
The Epidemiological Characteristics of Pediatric Streptococcus Pneumoniae Isolated From Inpatients And Outpatients At Beijing Children’s Hospital
Authors: Lyu Shuang , Shi Wei , Dong Fang , Xu Baoping , Liu Gang , Wang Quan , Yao Kaihu , Yang Yong Hong
Published: June 2021

Background: The epidemiological data of Streptococcus pneumoniae isolates are important for the practice of treatment and prevention. This research aimed to explore the epidemiological characteristics of pediatric S. pneumoniae isolated from outpatients and inpatients.Methods: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined by diagnostic pneumococcal antisera, and resistance against 13 antibiotics was tested by either the E-test or the disc diffusion method. The sequence types (STs) were analyzed with multilocus sequence typing (MLST).Results: The five dominant serotypes obtained from inpatients were 19F(32.9%), 19A(20.7%), 23F(10.7%), 6A(10.0%), and 14 (8.6%), while those in the outpatients were 19F (13.6%), 23F (12.9%), 6A (10.0%), 6B (10.0%), and 19A (7.9%). The coverage rates of the 7-, 10- and 13-valent pneumococcal vaccine formulations were high. The non-susceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates were 7.1%, 92.8%, 65.7%, 100%, and 85.0%, respectively, while those among the outpatient isolates were 0.7%, 50.0%, 38.6%, 96.4%, and 65.7%, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was more prevalent in inpatients.Conclusions: The pneumococcal vaccine related serotypes were still prevalent either in inpatient department or in outpatient department, which with serious antibiotic resistance. These results might be helpful for understanding the epidemiology of S. pneumoniae in Beijing. PCVs can prevent vaccine related serotypes. Therefore, universal immunization of PCVs should be implemented to prevent the spread of vaccine related serotypes of S. pneumoniae.
Industrial Ecological Efficiency of Cities in the Yellow River Basin in the Background of China's Economic Transformation: Spatial-Temporal Characteristics and Influencing Factors
Authors: Song Chengzhen , Yin Guanwen , Lu Zhilin , Chen Yanbin
Published: June 2021

At present, China's economic development has entered a "new normal." Exploring Industrial ecological efficiency (IEE) in the background of economic transformation is of great significance to promote China's industrial transformation and upgrading and achieving high-quality economic development. Based on the Super-Efficiency DEA model, this study evaluated the IEE of cities in the Yellow River Basin from 2008 to 2017. Exploratory spatial data analysis methods were used to explore the spatial-temporal evolutionary characteristics, and a panel regression model was established to explore the influencing factors of IEE. The research results showed that: The IEE in the Yellow River Basin exhibited an elongated S-shaped evolutionary trend from 2008 to 2017, and the mean IEE of cities presented a trend whereby Yellow River Basin’s regions could be ranked in the following order: lower reaches > middle reaches > upper reaches. There was significant spatial autocorrelation of the IEE in the Yellow River Basin, and the hot and cold spots showed an obvious "spatial clubs" phenomenon. The results of panel regression show that the influence factors of IEE in the Yellow River Basin showed spatial heterogeneity in their effect.
Automated Sectoral Quantitative Analysis of Parafoveal Microvascular Status and Association with Structure in Diabetic Macular Edema
Authors: Polat Nihat , Yoloğlu Saim
Published: June 2021

Purpose: To evaluate the integrity of the capillary plexuses, their relationship with each other, and their association with structural changes in a sectoral manner in diabetic macular edema (DME).Methods: The vessel density (VD) was measured in inferior, superior, nasal and temporal (İ, S, N, T) parafovea in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The integrity of the external limiting membrane (ELM) and ellipsoid zone (EZ) were evaluated in B-scan images.Results: In the SCP, only superior and nasal VD was significantly lower (P: 0.0001 and P: 0.020, respectively) while in the DCP, only temporal VD was significantly lower in the DME eyes (P: 0.034). There was no correlation between the VD of SCP and DCP in the corresponding quadrants (all P > 0.05). The FAZ area was significantly greater (both superficial and deep) in DME eyes than in control eyes (P > 0.05). ELM disruptions were not affected by the corresponding VDs in the SCP (all P> 0.05), but nasal and temporal quadrant ELM disruptions were affected by VDs in the DCP in the corresponding quadrants (P: 0.005 nasal, P: 0.001 temporal). EZ disruptions were not affected by the corresponding VDs in the SCP and DCP (all P> 0.05).Conclusions: The SCP was affected in more quadrants than the DCP and probably independently from each other. There was an association with the ELM and the DCP, especially in nasal and temporal quadrants, but there was not an association between the EZ and SCP or DCP.
Assessing the Relationship between Body Image and Quality of Life Among Rural and Urban Breast Cancer Survivors in China
Authors: An Jinghua , Zhou Kaina , Li Minjie , Li Xiaomei
Published: June 2021

Purpose
This study aimed to examine the associations between multidimensional body image and quality of life (QoL) and test whether the associations between body image and QoL are moderated by rural-urban residence in Chinese breast cancer survivors.
Methods
A cross-sectional design was adopted. Breast cancer survivors were recruited via a convenience sampling method. Two validated questionnaires (Body Image Self-Rating Questionnaire for Breast Cancer and SF-36) and questions assessing demographic and clinical covariates were administered.
Results
In our sample of 354 breast cancer survivors, half (50.28%) lived in rural areas. After adjusting for demographic and clinical variables, better perception of body image-related sexual activity change, role change, and psychological change was significantly associated with better physical and mental well-being. Better perception of body image-related social and behavior change domains was only significantly associated with better mental well-being. The association between body image and mental well-being was much stronger in urban subjects (b = -0.38, p < 0.001) than in rural subjects (b = -0.20, p < 0.001).
Conclusions
Our findings suggest that multidimensional body image is associated with physical and mental well-being in Chinese breast cancer survivors. Body image appears to play a larger role in urban breast cancer survivors’ mental well-being. Our findings indicate that incorporating interventions that address body image issues would be advantageous for survivorship care programs focused on enhancing QoL in breast cancer survivors. Considering the rural-urban differences supports strategic design of the care programs in rural and urban settings.
A Clinical Study Of Segmental Mandibulectomy For Medication-Related Osteonecrosis Of The Jaw
Authors: Otsuru Mitsunobu , Soutome Sakiko , Hayashida Saki , Rokutanda Satoshi , Yanamoto Souichi , Umeda Masahiro
Published: June 2021

Purpose

Few studies have focused on segmental mandibulectomy for the surgical treatment of patients with medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to investigate the extent of mandibular resection required and the treatment outcomes.
Methods

One hundred thirty-seven patients with MRONJ who underwent surgical treatment at the Nagasaki University Hospital between 2011 and 2019 were included in the study. A total of 168 surgeries (155 marginal mandibulectomies; 13 segmental mandibulectomies) were performed. The relationship between various clinical and imaging factors and the treatment outcomes were investigated in the 13 cases of segmental mandibulectomy.
Results

Preoperative computed tomography revealed osteolytic lesions (13/13), periosteal reaction (PR; 12/13), and osteosclerosis (12/13) in patients who underwent segmental mandibulectomies. Postoperative CT revealed no residual osteolytic lesions and PR, although osteosclerosis persisted in nine patients. The cure rate of segmental mandibulectomy was 92.3% (12/13), whereas that of marginal mandibulectomy was 67.1% (104/155). One patient relapsed after segmental mandibulectomy was cured by additional resection. Two and four patients received reconstruction with free fibula flap and reconstruction metal plate, respectively; seven patients did not undergo reconstructive surgery in consideration of their poor general condition or will. Finally, in all the 13 patients, clinical symptoms such as pain and purulent discharge disappeared and oral intake was possible.
Conclusion

Considering the end-of-life care, segmental mandibulectomy is a treatment option for refractory MRONJ, because it can eliminate clinical symptoms early. When segmental mandibulectomy is performed, the area involving osteolytic lesions and PR must be included.
Allee Effects Determine Pollinator Services at Local and Geographic Scales
Authors: Sánchez-Castro Darío , Armbruster Georg , Willi Yvonne
Published: June 2021

Climatic factors have attracted much attention in the study of species’ distributions, while little is known about the role of biotic interactions. Here, we tested for variation in pollinator service across the distribution of a plant species, and evaluated the driving mechanisms. We monitored insect pollinators using time-lapse cameras in populations of North American Arabidopsis lyrata from the southern to the northern range limit. We spotted 67 pollinating insect taxa, indicating that this plant-pollinator network is a generalist system. Pollinator service increased with latitude. Higher pollinator visitation was correlated with the richness of other flowering plants and with plant census size, which was largest in northern populations. Furthermore, pollinator service reached a maximum at intermediate local flower density. Synthesis: This study indicates that pollination service underlies Allee effects on a local and species’ range scale, and that plant populations at range limits receive only marginal pollination service if they are small.
Presentation of a New Endometriosis Mice Model Through Rat to Mice Xenograft Transplantation of Endometrium with some Modifications; A Pilot Study
Authors: Abdolmaleki Amir , Jalili Cyrus , Mansouri Kamran , Bakhtiari Mitra
Published: June 2021

Human endometriosis can lead to many complications, including permanent infertility. Rodent model of endometriosis is complicated due to the impractical isolation of myometrium. In this method, we defined a new model of endometriosis with some modifications. 40 female mice were grouped as; 1st sham, 2nd mice-mice allograft uterus transplantation of mice to anterior abdominal wall of mice, 3rd mice-mice allograft uterus transplantation of mice to mesentery of mice, 4th rat-mice xenograft endometrial transplantation of rat to anterior abdominal wall of mice, 5th rat-mice xenograft endometrial transplantation of rat to mesentery of mice. In recipient animals, estrous cycle was synchronized. Endometrium was dissected in rats and transplanted in abdominal wall or mesentery layer. Angiogenetic and inflammatory factors, serum levels of CA125, oxidative stress in peritoneal fluid, physical and histopathological features, and genes expression in uterus were assessed. Peritoneal concentrations of VEGF-A, TNF-α, NO, MDA, and serum levels of CA125, IL-37 were increased significantly (P < 0.05) in transplanted groups, especially in the 4th group than control. Total body weight of animals was decreased significantly (P < 0.05), while weight and size of endometrial lesions were increased significantly (P > 0.05). Genes expression of HOXA10 and HOXA11 were decreased in endometrium of uterus. Finally, histopathological features of endometrial lesions were confirmed by H&E and Perl staining. Xenograft transplantation of endometrium from rat to anterior abdominal wall of mice can potentially mimic the human endometriosis morphologically, histologically and genetically.
The Perinatal Outcomes by Gestational Weight Gain Range at 30 Weeks of Gestation Among Pre-Pregnancy Underweight Women: A Retrospective Study
Authors: Nagao Takeshi , Fukui Sho , Ohde Sachiko , Yamanaka Michiko
Published: June 2021

Background: The antenatal weight targets of gestational weight gain (GWG) (earlier than 40 weeks) among underweight pregnant women (UPW: pre-pregnancy body mass index≤18.5 kg/m2) that are useful for the management of weight during pregnancy have not been reported. It had been recently pointed out that firm GWG restrictions have led to an increase in the number of low-birth-weight infants in Japan. Thus, this study aimed to evaluate the perinatal outcomes by GWG at 30 weeks of gestation among UPW and to discuss the effects of GWG restrictions.Methods: This retrospective cohort study was conducted at a hospital in Japan from 2003 to 2020. The UPW (n=3,643) were divided into the four quartile groups based on the GWG at 30 weeks of gestation: group A ≤ 5.7 kg, 5.7 kg < group B ≤ 7.2 kg, 7.2 kg < group C ≤ 8.8 kg, and 8.8 kg < group D. Their clinical characteristics and outcomes were compared using t-test, chi-square test, and multivariate logistic regression analysis.Results: The incidence rates of preterm births were 7.5% (n=70), 5.0% (n=45), 5.4% (n=50), and 4.9% (n=44) and the birth rates of small-for-gestational age (SGA) infants were 15.7% (n=147), 9.6% (n=87), 6.9% (n=64), and 5.9% (n=53) in groups A, B, C, and D, respectively. Multivariate logistic regression analysis showed that group A was significantly associated with preterm births [adjusted odds ratio (Adj. OR) = 1.6; 95% confidence interval (CI) = 1.0–2.3; p = 0.018], and groups A and B were significantly associated with SGA [Adj. OR = 3.0; 95% CI = 2.2–4.2; p < 0.001] [Adj. OR = 1.7; 95% CI = 1.2–2.5; p = 0.002] . No significant differences were noted in the ratio of cesarean section (CS) (p = 0.344), hypertensive disorders of pregnancy (HDP) (p = 0.954), and macrosomia (p = 0.147) among the four groups.Conclusions: The GWG at 30 weeks of >5.7 kg for preterm birth and >7.2 kg for SGA is recommended. Firm weight restrictions for UPW may have led to an increase of adverse outcomes without reducing the risk of CS, HDP, and macrosomia.
Implementation of An Organizational Intervention To Improve Low-Wage Workers' Safety, Health And Wellbeing: Findings From The Workplace Organizational Health Study
Authors: Sorensen Glorian , Peters Susan E. , Nielsen Karina , Stelson Elisabeth , Wallace Lorraine M. , Burke Lisa , Nagler Eve M. , Roodbari Hamid , Karapanos Melissa , Wagner Gregory R.
Published: June 2021

Background: Many organizational interventions aim to improve working conditions to promote and protect worker safety, health, and well-being. The Workplace Organizational Health Study used process evaluation to examine factors influencing implementation of an organizational intervention. This paper examines the extent to which the intervention was implemented as planned, the dose of intervention implemented, and ways the organizational context hindered or facilitated the implementation of the intervention.Methods: This proof-of-concept trial was conducted with a large, multinational company that provides food service through contractual arrangements with corporate clients. The 13-month intervention was launched in five intervention sites in October 2018. We report findings on intervention implementation based on process tracking and qualitative data. Qualitative data from 25 post-intervention interviews and 89 process tracking documents were coded and thematically analyzed.Results: Over the 13-month intervention, research team representatives met with site managers monthly to provide consultation and technical assistance on safety and ergonomics, work intensity, and job enrichment. Approximately two-thirds of the planned in-person or phone contacts occurred. We tailored the intervention to each site as we learned more about context, work demands, and relationships. The research team additionally met regularly with senior leadership and district managers, who provided corporate resources and guidance. By assessing the context of the food service setting in which the intervention was situated, we explored factors hindering and facilitating the implementation of the intervention. The financial pressures, competing priorities and the fast-paced work environment placed constraints on site managers’ availability and limited the full implementation of the intervention.Conclusions: Despite strong support from corporate senior leadership, we encountered barriers in the implementation of the planned intervention at the worksite and district levels. These included financial demands that drove work intensity; turnover of site and district managers disrupting continuity in the implementation of the intervention; and staffing constraints that further increased the work load and pace. Findings underscore the need for ongoing buy-in and support from both the parent employer and the host client.Trial registration: This study was retrospectively registered with the Clinical Trials.Gov Protocol and Results System on June 2, 2021 with assigned registration number NCT04913168.
Clinical Application of Robotic Orthopedic Surgery: A Bibliometric Study
Authors: Li Cheng , Jiang Nan , Wang Lei , Perka Carsten , Trampuz Andrej
Published: June 2021

Objectives: The present study aimed to evaluate the status and trends of robotic orthopedic surgery in a clinical setting using bibliometrics.Methods: All relevant publications on the clinical use of robotic surgery in orthopedics were searched from the Web of Science database. Subsequently, data were analyzed using bibliometrics. Visualizing data of bibliographic coupling, co-citation, and co-occurrence analysis were performed using VOSviewer.Results: In total, 224 clinical studies met the included standards between 2000 to 2019. Global publications presented an increasing annual trend, with the United States found to have the largest number of publications and robotic companies active in the field (n = 99), followed by China (n = 38), and the United Kingdom (n = 27). The institution with the most contributions was the Beijing Jishuitan Hospital in China (n = 14). The most productive scholars were Tian Wei and Mont Michael A, with 14 publications each. The top 30 most cited papers list showed 29 publications to be cited on more than 40 occassions. The journal with the most related and influential publications on robotic orthopedic surgery was the Journal of Arthroplasty. Fourteen types of robots were used, with the majority applied in knee and spinal surgery. MAKO was the most widely used robot in hip and knee surgery and Mazor in spinal surgery. Most studies were small sample populations of low-quality in this field. The top 20 most frequently used keywords were identified from 950 author keywords. Research on orthopedic robots were classified into two clusters by co-occurrence networks: spinal-related robotic surgery and joint-related robotic surgery. Conclusions: The present bibliometric study summarizes the clinical research of orthopedic robots on study type, sample size, type of surgery, robot information, surgical site, most popular keywords, most cited papers, journals, authors, institutions, and countries. These findings may assist the scholars better understand the current status and research trends to guide future practice and directions.
Enhancing Virtual Screening Efficiency in the Discovery of Human TMPRSS2 Inhibitor for Combating COVID-19
Authors: Vuai Said A. H. , Ogedjo Marcelina M. , Onoka Isaac , Sahini Mtabazi G. , Shadrack Daniel M
Published: June 2021

As the coronavirus disease 19 (COVID-19) pandemic continues to pose a health and economic crisis worldwide, the quest for drugs and/or vaccines against the virus continues. The human transmembrase protease serines 2 (TMPRSS2) has attracted attention as a target for drug discovery, as inhibition of its catalytic reaction would results in the inactivation of the proteolytic cleavage of the SARS-CoV-2 S protein. As a result, the inactivation prevents viral cell entry to the host’s cell. In this work, we screened and identified two potent molecules that interact and inhibit the catalytic reaction by using computational approaches. Two docking screening experiments were performed utilizing the crystal structure and holo ensemble structure obtained from molecular dynamics in bound form. There is enhancement and sensitivity of docking results to the holo ensemble as compared to the crystal structure. Compound 1 binds more stable than nafamostat by interacting with catalytic triad residue His296 and Ser441, thereby disrupting the already establish hydrogen bond interaction. The stability of the ligand-TMPRSS2 complexes was studied by molecular dynamics simulation, and the binding energy was re-scored by using MM-PBSA binding free energy. The obtained compounds may serve as initial point towards the discovery of potent TMPRSS2 inhibitors upon further in vivo validation.
The Use of Standardized Brazilian Green Propolis Extract (EPP-AF) as an Adjunct Treatment for Hospitalized COVID-19 Patients (BeeCovid2): A Structured Summary of a Study Protocol for a Randomized Controlled Trial
Authors: Silveira Marcelo Augusto Duarte , de Souza Sergio Pinto , Galvão Erica Batista dos Santos , Teixeira Maurício Brito , Gomes Marcel Miranda Dantas , Damiani Lucas Petri , Bahiense Bruno Andrade , Cabral Julia Barros , De Oliveira Cicero Wandson Luiz Macedo , Mascarenhas Talita Rocha , Pinheiro Priscila Carvalho Guedes , Alves Milena Souza , de Melo Rodrigo Morel Vieira , Berretta Andresa Aparecida , Leite Flávia Mendes , Nonaka Carolina Kymie Vasques , Souza Bruno Solano de Freitas , Mendes Ana Verena Almeida , Guarda Suzete Farias da , Passos Rogério da Hora
Published: June 2021

Background
The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. To date, there is no consensus on a specific treatment. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study is once again assessing EPP-AF in hospitalized patients with coronavirus infection.
Methods
BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days who are not on invasive oxygen therapy are eligible. Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the length of hospital stay. Secondary outcomes include the need for mechanical ventilation, the rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO).
Discussion
This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19.
Trial registration:
ClinicalTrials.gov NCT04800224. Registered on March 16, 2021.
Distinction of Consciousness Fields According to Taheri from Other Conventional Physical Fields: Evaluating the Magnetic Properties of Materials
Authors: Taheri Mohammad Ali , Payervand Forouz , Ahmadkhanlou Farzad , Torabi Sara , Semsarha Farid
Published: June 2021

Magnetization hysteresis loop provides important information about the magnetic properties of materials. In this study, by examining the magnetic properties of three paramagnetic and diamagnetic materials in the vicinity of the Consciousness Fields (three types 1,2 and 3), we have investigated the nature of the Consciousness Fields in comparison with magnetic field. The magnetic properties of the materials under the influence of three distinct Consciousness Fields have changed significantly. Furthermore, the Consciousness Field 1 of the present study (with originally named Faradarmani by Taheri) has changed the magnetic properties of materials toward their physically inherent state in standard laboratory conditions. Based on the conditions and the results of the present study, it can be concluded that the Consciousness Fields are inherently neither electric nor magnetite fields and have a completely different and distinct impact on materials and their properties.
Waterpipe Smoking Among Youth and Socioeconomic Status: A Cross-Sectional Study of Students in Public Versus Private Universities
Authors: Caner Asena , Özcebe Hilal
Published: June 2021

Background Waterpipe smoking has become a global public health problem as its popularity increased over time, especially among youth. This study aims to examine waterpipe smoking patterns of university students in Ankara, Turkey, and compare the patterns in public and private universities, which have different economic and social environments. Students in these two types of universities differ, on average, in socioeconomic background and access to financial resources. Methods The survey was conducted among public (n=2685) and private (n=2485) university students via an online questionnaire. Logistic regressions (on the full sample and on the sample that excludes students who initiate before age 18) were used to test the association between ever using waterpipe and respondent characteristics such as age, gender, university type, living arrangements, and source of income. Descriptive statistics on consumption pattern (age at first use, use within last month, location of use, availability of waterpipe venues, whether it is usually shared, reasons for use, and harm perceptions) were also generated. Moreover, never, ever, and current user prevalence rates by age at first use were estimated for waterpipe and cigarettes. Results69% of students in private and 59% of students in public universities (p<0.001) were ever smokers of waterpipe. Being older, male, private university student, living alone or having roommate(s), as well as financial resources such as having access to a car, having income from work or family were associated with ever using waterpipe. Although more than half (68-70%) of ever users tried waterpipe before age 18, risk continued in university and 41-46% of those who tried before 18 were current users in university. For women who had abstained from waterpipe until university age, the risk of waterpipe use was higher in private than in public universities. ConclusionsWaterpipe smoking has increased and is highly common among university students. Students with higher socioeconomic status are at higher risk. There is an urgent need to implement the new creative interventions based on the WHO Framework Convention on Tobacco Control to prevent the young people from waterpipe smoking after 18 years old.
Development and internal validation of a predictive model for COVID-19 mass screening based on symptoms and a simple olfactory test
Authors: Azeli Youcef , Fernández Alberto , Capriles Federico , Rojewski Wojciech , Lopez-Madrid Vanesa , Lissner David , Serrano Rosa Maria , Rey-Reñones Cristina , Civit Marta , Casellas Josefina , Ouahabi Abdel , Foglia-Fernández Maria , Sarrá Salvador , Llobet Eduard
Published: June 2021

The early detection of symptoms and rapid testing are the basis of an efficient screening strategy to control COVID-19 transmission. Most COVID-19 patients show olfactory dysfunction and in many cases this is the first symptom. This study aims to develop a machine learning COVID-19 predictive tool based on symptoms and a simple olfactory test, which consists of identifying the smell of an aromatized hydroalcoholic gel (CovidGel Test). A multi-centre population-based prospective study was carried out in the city of Reus (Catalonia, Spain). A total of 519 patients were included, 386 (74.4%) had at least one symptom and 133 (25.6%) were asymptomatic. A classification tree model including sex, age, relevant symptoms and the CovidGel Test results obtained a sensitivity of 0.97 (95% CI 0.91–0.99), a specificity of 0.39 (95% CI 0.34–0.44) and an AUC of 0.87 (95% CI 0.83–0.92). This shows that the CovidGel Test is a promising mass screening tool for predicting COVID-19.
The effect of the health poverty alleviation project on the burden of congenital heart disease for Kizilsu Kirghiz Autonomous Prefecture, China
Authors: Zhang Cheng , Li Chunyu , Gulisitan Aizezi , Milinuer Ainiwa , Zhang Zhenhai , Nan Xiangping , Xu Xianggui , Chen Yan
Published: June 2021

Background: The implement of the health poverty alleviation project is a very important initiative for reducing poverty. Although previous studies have analyzed the effect of impoverishment, few papers compared the differences of the economy and the morbidity after the implement of the health poverty alleviation project in China. Methods: To analyze the effect of the health poverty alleviation project on the burden of congenital heart disease, we collected the hospitalization expenses and epidemiology data of congenital heart disease in Kizilsu Kirghiz Autonomous Prefecture from 2016 to 2018, in which the health poverty alleviation project was implemented. SPSS 23.0 and Disability Adjusted Life Years were applied to analyze the burden of the disease. Results: Our study found that the prevalence rate of congenital heart disease was increasing year by year. In total, 4719 poor people enjoyed the welfare of health poverty alleviation in the People's Hospital of Kezhou. The out-of-pocket ratio was only 2.25%. After the health poverty alleviation project, the loss of Disability Adjusted Life Years was smaller and smaller. 24 sessions have been carried out to operate 208 patients with congenital heart disease, all of which have been successful. Conclusions: This study found that the health poverty alleviation project not only bringed healthy life expectancy to poor families, but also greatly reduces their financial burden.
In Vitro CSC-derived Cardiomyocytes Exhibit the Typical microRNA-mRNA Blueprint of Endogenous Cardiomyocytes
Authors: Scalise Mariangela , Marino Fabiola , Salerno Luca , Teresa Mancuso , Cappetta Donato , Barone Antonella , Parrotta Elvira , Torella Annalaura , Palumbo Domenico , Veltri Pierangelo , De Angelis Antonella , Berrino Liberato , Rossi Francesco , Weisz Alessandro , Rota Marcello , Urbanek Konrad , Nadal-Ginard Bernardo , Torella Daniele , Cianflone Eleonora
Published: June 2021

miRNAs modulate cardiomyocyte specification in embryonic hearts and in pluripotent stem cells by targeting mRNAs of cell cycle regulators and acting in gene regulatory loops that complete commitment to the cardiac muscle lineage. It is still unknown if/to-what-extent these miRNA/mRNA networks are operative during cardiomyocyte differentiation of adult cardiac stem/progenitor cells (CSCs). Clonally-derived mouse CSCs differentiated into contracting cardiomyocytes in vitro (iCMs). RNASeq comparison of “CSCs vs. iCMs” mRNome and microRNome showed a balanced up-regulation of sarcomere and mitochondrial related mRNAs together with a down-regulation of cell cycle and DNA replication mRNAs. The down-regulation of cell cycle genes and the up-regulation of the mature myofilament genes in iCMs did not reach the levels of mouse terminally differentiated adult cardiomyocytes (aCMs), while they get to intermediate levels between those of fetal and neonatal cardiomyocytes. Cardiomyo-miRs were up-regulated in iCMs while those miRs positively regulating stem cell expansion and self-renewal were down-regulated. The specific networks of miRNA/mRNAs operative in iCMs closely resembled miRNA/mRNA networks of aCMs. Two of these miRs, miR-1 and miR-499, enhanced myogenic commitment toward terminal differentiation of iCMs. In conclusions, CSC specification/differentiation into contracting iCMs follows known cardiomyo-MiR-dependent developmental cardiomyocyte differentiation trajectories and iCMs transcriptome/miRNome resembles that of aCMs.
Bounded States for Breathers–Soliton and Breathers of Sine–Gordon Equation
Authors: JIA Man
Published: June 2021

The Wronskians solutions to the sine-Gordon (sG) equation that can provide interaction of different kinds of solutions are revisited. A novel expression N-soliton solution with a nonzero background is presented which is used to construct the soliton and breather solutions. Due to the existences of abundant structures of the solitons and breathers, it is possible to search for the coherent structures, or bounded states of solitons and breathers. By introducing the velocity resonant conditions, the sG equation is proved to possess the bounded state for breathers-soliton, or breather-soliton molecules (BSMs) and the bounded state for breathers, or breather molecules (BMs) by different parameters selections. In addition, an approximately bounded state for solitons is demonstrated. The interesting thing is the interactions among the BSMs, BMs and solitons, breathers may be nonelastic by the particular meaning the sizes of the BSMs and BMs change.
The Changes in Fear of Childbirth in Pregnancy During and Before the COVID-19 Pandemic
Authors: Soysal Cenk , Erten Özlem , Işıkalan Mehmet Murat , Bıyık İsmail , Taşçı Yasemin , Keskin Nadi
Published: June 2021

Background: We aimed to compare the changes experienced by pregnant women before and during the pandemic regarding fear of childbirth andhow much they were affected by factors such as age, education level, and planned delivery type.Materials and Methods: This cross-sectional study comparedthe pre-pandemic pregnant group (July 2019 and December 2019) and the pandemic group (November 2020 and May 2021) of patients atKütahya Health Sciences University Evliya Çelebi Training and Research Hospital. A total of 696 pregnant womenin their second trimesterwere included in the study. All of them were literate andvoluntarily agreed to participate in the study. Data were collected with the Wijma Delivery Expectancy/Experience Questionnaire (WDEQ-A), and the outpatient doctor asked the questions face-to-face.Results: The mean age of the pregnant women participating in the study was 31.6±6.8 years. While the total Wijma score was 62.1±25.1 in the pre-pandemic group, it was 61.3±26.4 in the pandemic group, and there was no significant difference between the two groups (p=0.738).While 25.7% (n=179) of all participants had a normal fear of childbirth, 22% (n=153) had a mild fear of childbirth, 27% (n=188) had a moderate fear of childbirth, and 25.3% (n=176) had a severe fear of childbirth (Wijma score of 85 and above). When the pre-pandemic and the pandemic period were compared, the fear of childbirth wasunchanged in pregnant women at all education levels (p=0.079, p=0.957, p=0.626, p=0.539, p=0.202).Conclusion: When the pre-pandemic and pandemic periods are compared, it is seen that the fear of childbirth didnot change within each education level. Informing pregnant women about the effects of COVID-19 during the pandemic period may be effective in reducing fear of childbirth and reducing the numberof cesarean sections due to fear of birth.
Invadopodia enable cooperative invasion and metastasis of breast cancer cells
Authors: Perrin Louisiane , Bayarmagnai Battuya , Tuzel Erkan , Gligorijevic Bojana
Published: June 2021

Multiple clones of cancer cells can seed metastases via collective invasion and dissemination. While it is known that cancer clones can cooperate during invasion, the events leading to it and the effects it may have on metastasis are not known. In this study, we demonstrate that, when mixed in 3D spheroids, the isogenic 4T1 and 67NR breast cancer cells sort from each other, followed by their cooperative invasion. By time-lapse microscopy of heterogenous spheroids embedded in collagen I, we show that the invasive 4T1 cells that reach the spheroid edge remain there, while the non-invasive 67NR cells move randomly. This results in cell sorting and enrichment of invasive 4T1 cells at the spheroid periphery. Following cell sorting, 4T1 cells lead the 67NR cells in cooperative invasion. Elimination of invadopodia in 4T1 cells, by knockdown of the protein Tks5, blocks invasion and demonstrates that invasion requires invadopodia only in leader cells and not in follower cells. Importantly, using syngeneic mouse model, we demonstrate that cells with and without invadopodia can also engage in cooperative metastasis. Altogether, our results suggest that a few clones with invadopodia could drive the metastasis of cell clusters from heterogeneous tumors.
Projected increase of Arctic coastal erosion and its sensitivity to warming in the 21st Century
Authors: Nielsen David , Pieper Patrick , Barkhordarian Armineh , Overduin Paul , Ilyina Tatiana , Brovkin Victor , Baehr Johanna , Dobrynin Mikhail
Published: June 2021

Arctic coastal erosion damages infrastructure, threatens coastal communities, and releases organic carbon from permafrost. However, the magnitude, timing and sensitivity of coastal erosion increase to global warming remain unknown. Here, we project the Arctic-mean erosion rate to roughly double by 2100 and very likely exceed its historical range of variability by mid-21st century. The sensitivity of erosion to warming also doubles, reaching 0.4-0.5 m year-1 oC-1 and 2.3-2.8 TgC year-1 oC-1 by the end of the century under moderate and high-emission scenarios. Our first 21st-century pan-Arctic coastal erosion rate projections should inform policy makers on coastal conservation and socioeconomic planning. Our organic carbon flux projections also lay out the path for future work to investigate the impact of Arctic coastal erosion on the changing Arctic Ocean, on its role as a global carbon sink, and on the permafrost-carbon feedback.
The Complex Nonlinear Causal Coupling Patterns between PM2.5 and Meteorological Factors in Tibetan Plateau: A Case Study in Xining
Authors: Zou Zhixiao , Cheng Changxiu , Shen Shi
Published: June 2021

PM2.5 pollution influences the population health and people’s daily life. Because meteorological factors are main factor affecting the formation of PM2.5, the interaction between PM2.5 and meteorological factors needs to be better understood, both for air quality management and for PM2.5 projection. Here, we use a nonlinear state space method called the convergent cross mapping method to identify the complex coupling patterns between PM2.5 and meteorological factors in a plateau city: Xining. The results prove that PM2.5-meteorological coupling patterns change with seasons and PM2.5-meteorological coupling patterns are fixed in spring, autumn and winter. In spring, there is a negative unidirectional effect from precipitation to PM2.5 and a negative bidirectional effect between relative humidity and PM2.5. In autumn, there are some negative bidirectional effects between PM2.5 and relative humidity, precipitation, and air pressure, while solar radiation has a positive bidirectional effect on PM2.5. In winter, there are negative bidirectional couplings between PM2.5 and wind speed and temperature and a positive bidirectional coupling between relative humidity and PM2.5. Furthermore, relative humidity is a consistent driving factor affecting PM2.5. Air quality managers may alleviate PM2.5 by increasing relative humidity. Thus, the results provide a meteorological means for improving air quality in plateau cities.
A One-Minute Blood Test Detects Decreased Immune Function and Increased Clinical Risk in COVID-19 Patients
Authors: Deb Chirajyoti , Salinas Allan , Zheng Tianyu , Middleton Aurea , Kern Katelyn , Penoyer Daleen , Borsadia Rahul , Hunley Charles , Abomoelak Bassam , Mehta Vijay , Irastorza Laura , Mehta Devendra , Huo Qun
Published: June 2021

Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient’s immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.