bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between maternal food insecurity, fetal and postnatal growth: findings from the South African National Income Dynamics Study
Authors: Harper Abigail Joan , Rothberg Alan , Chirwa Esnat , Sambu Winnie , Mall Sumaya
Published: October 2020

Background: Food insecurity during pregnancy and postnatally has been associated with adverse child health outcomes including low birthweight and stunting. There are few studies that have examined the relationships between food insecurity and child health outcomes in low and middle income countries. This study aims to fill the gap by examining the relationship between food insecurity, low birthweight and stunting in children using a longitudinal sample of South African women and their offspring.Methods: The primary exposure is a multidimensional, composite measure of household food insecurity that comprises three dimensions and six indicators. The primary outcome is a dichotomous measure of child LBW (≤2500g) The secondary outcome is childhood stunting (height for age £2SD of the median) and severe stunting (height for age £3SD of the median) in the first five years of life. We used both unadjusted and adjusted regression models. Source data for the analysis came from the population-based, longitudinal data collected for wave one and three of the National Income Dynamics Study (2008 and 2012). Results: Birthweight data were available for 1381 children and stunting data were available for 1444 children. The prevalence of LBW in the sample was 13.64 %. The prevalence of stunting and severe stunting was 16.46 % and 11.87 %. The composite measure was not associated with low birthweight but was associated with underweight maternal BMI, a risk factor for low birthweight. Household dietary diversity, food expenditure below the Stats SA poverty line and the composite measure was associated with stunting and severe stunting in bivariate analyses. The measure was associated with severe stunting in the final model.Conclusions: The finding that household food insecurity is associated with severe stunting for children in the first five years of life highlights the importance of adequate food and nutrition for vulnerable children in South Africa. Future studies can elucidate the relationship between maternal food insecurity, low birthweight and other child outcomes. Policy interventions that focus on early childhood growth through alleviating food insecurity and addressing other drivers of malnutrition such as improving maternal education and dietary diversity can break the cycle of poor growth outcomes.
Morphometric study of suprascapular notch and scapular dimensions in Ugandan dry scapulae with specific reference to the incidence of completely ossified superior transverse scapular ligament
Authors: Adewale Adesanya Olamide , Segun Okeniran Olatayo , Usman Ibe Michael , Monima Ann Lemuel , Kegoye Eric Simidi , Kasozi Keneth Iceland , Nalugo Halima , Ssempijja Fred
Published: October 2020

Background: Understanding of suprascapular notch (SSN) anatomy and relationship with scapular dimensions are vital in diagnosis, prevention, and assessment of suprascapular nerve entrapment syndrome. The study aimed to assess morphometry of suprascapular notch and scapular dimensions in Ugandan dry scapulae with specific reference to scapulae with completely ossified superior transverse scapular ligaments. Methods: This was a cross-sectional analytical study conducted on 50 Ugandan dry scapulae. SSN types and prevalence of completely ossified superior transverse scapular ligament among dry scapulae were quantified and compared with previous data. Scapular dimensions were assessed by measuring scapular length (A), scapular width (B), glenoid length (C), and glenoid width (D). One-way ANOVA was used to compare scapular dimensions of scapulae with different SSN types, and Spearman’s correlation coefficient was used to evaluate the correlation coefficient of scapular dimensions amongst groups. Results: Superior transverse scapular ligament (STSL) was completely ossified in 8% of cases. There was no significant (P > 0.05) difference between scapular dimensions of scapulae with completely ossified STSL compared to scapulae with other SSN types. Scapulae with completely ossified STSL showed strong negative (r = -0.89137, r = -0.877) correlations for its A, B respectively compared against D, this finding was not true to scapulae of other SSN types. Also, there were strong positive or negative (r > 0.7, r > -0.7) correlations: for A, types I and III compared to type VI; for B, types I, III compared to VI; for C, type IV and VI; and for D, type III and VI. Conclusions: The prevalence of completely ossified STSL is moderately high in the Ugandan population. Characteristics of the scapula (scapular dimensions) are not ‘vital’ but rather important or relevant for shoulder pathology with specific reference to suprascapular nerve entrapment syndrome due to completely ossified superior transverse scapular ligaments. Further correlation analyses of scapular dimensions of different SSN types in different populations are important.
A New Method for the Empirical Conversion of Logging Data to Clay Mineral Fraction in the Nankai Accretionary Prism
Authors: Yabe Suguru , Fukuchi Rina , Hamada Yohei , Kimura Gaku
Published: October 2020

Sediment lithology, especially the clay mineral fraction, is basic geologic information, which is important for understanding faulting and evolutionary process of the accretionary prism. During scientific drilling, the clay mineral fraction is measured using X-ray diffraction analyses of samples from the acquired cores. However, coring in an accretionary prism is sometimes difficult, which hinders the acquisition of clay mineral fraction data. This study details the development of a new method used to empirically estimate the clay mineral fraction from the electrical resistivity and natural gamma ray logs obtained from the Kumano section of the Nankai Tough, where multiple scientific drilling expeditions have been conducted. This method is composed of two steps. First, porosity is estimated using electrical resistivity logs. In order to compensate for the effect of porosity, the natural gamma ray logs are then normalized using (1 – porosity). Second, the normalized natural gamma ray logs are converted into clay mineral fractions using an empirical conversion function. This empirical function was determined by comparing all available normalized natural gamma ray logs and clay mineral fractions data collected from the Kumano section of the Nankai Trough. As a byproduct of the porosity estimations, thermal conductivity and temperature depth profiles were also estimated for all of the logging sites. As electrical resistivity logs and natural gamma ray logs are essential measurements made during scientific drilling, this new method can be applied to future drilling expeditions in the Nankai Trough. Although the empirical conversion function established in this study is valid only at the Kumano section of the Nankai trough, the same procedure can be applicable to other subduction zones to establish local empirical conversion functions if enough data are available. The clay mineral fraction depth profile estimated using this method can provide useful information for various geological studies, including sedimentology and structural geology of the shallow accretionary prism.
A Modified Delphi to Define Drug Dosing Errors in Pediatric Critical Care
Authors: Roumeliotis Nadia , Pullenayegum Eleanor , Rochon Paula , Taddio Anna , Parshuram Chris
Published: October 2020

Background There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios.Methods We conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5 years’ experience. Outcomes were underlying principles of drug dosing, and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios. Results Forty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Altough there remained much uncertainty in defining dosing error, expert clinicians agreed that, for most medication categories and clinical scenarios, dosing over or below 10% of reference range was considered an error threshold.Conclusion Dosing principles and threshold are complex in pediatric critical care, and expert clinicians were uncertain about whether many scenarios were considered in error. For most intermittent medications, dosing over 10% below or above reference range was considered a dosing error, although this was largely influenced by clinical context and drug properties. This consensus driven error threshold will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.
Knowledge and attitudes among preschools staff in Shanghai, China, regarding epilepsy
Authors: Qiu Liyan , Shen Lixiao , Wang Junli , Ren Fang , Xu Mingyu , Jiang Fan , Sheng Xiaoyang , Li Fei , Li Feng
Published: October 2020

Background
Epilepsy is one of the most common neurological problems among children. The aim of this survey was to assess the knowledge and attitude among preschool staff in Shanghai regarding epilepsy.
Methods
A cross-sectional survey was carried out among the staff at selected preschools. A stratified random sampling method was first used to identify suitable subjects. Data were obtained using a self-completed questionnaire. A standardized collection of demographic information was performed, and participants were given a questionnaire about their knowledge and attitudes regarding epilepsy.
Results
A total of 1069 subjects completed the questionnaire. In this survey, 387 (36.2%) staff members had previously participated in related training. Overall, the subjects lacked knowledge regarding first aid for seizures. Only 17.6% of teachers knew how to provide appropriate first aid for seizures. Correct responses regarding first aid for seizures, such as laying the person on his or her side (24.9%), moving harmful objects out of the way (20.7%), protecting the head (36.1%), waiting until the seizure ends (7.9%), and dialing the emergency number (40.1%), were low. The staff members had different attitudes towards children with epilepsy: most had a positive attitude, but some had a negative attitude.
Conclusions
The level of first-aid knowledge among preschool staff in Shanghai relevant to epilepsy was low. There is an urgent need to educate staff about epilepsy and appropriate first-aid practices for seizures.
Keywords : Epilepsy; Preschool staff; First-aid knowledge; Attitudes; Training
The Combination of Trehalose and Glycerol: An Effective and Non-Toxic Recipe for Cryopreservation of Human Adipose-Derived Stem Cells
Authors: Zhang Tian-Yu , Tan Poh-Ching , Xie Yun , Zhang Xiao-Jie , Zhang Pei-Qi , Gao Ying-Ming , Zhou Shuang-Bai , Li Qing-Feng
Published: October 2020

Background: Adipose-derived stem cells (ADSCs) promote tissue regeneration and repair. Cryoprotective agents (CPAs) protect cells from cryodamage during cryopreservation. Safe and efficient cryopreservation of ADSCs is critical for cell-based therapy in clinical applications. However, most CPAs are used at toxic concentrations, limiting their clinical application. Objective: The aim of this study is to develop a non-toxic xeno-free novel CPA aiming at achieving high-efficiency and low-risk ADSC cryopreservation.Methods: We explored different concentrations of trehalose (0.3 M, 0.6 M, 1.0 M, and 1.25 M) and glycerol (10%, 20%, and 30% v/v) for optimization and evaluated and compared the outcomes of ADSCs cryopreservation between a combination of trehalose and glycerol and the commonly used CPA DMSO (10%) + FBS (90%). All samples were slowly frozen and stored in liquid nitrogen for 30 days. The effectiveness was evaluated by the viability, proliferation, migration and multi-potential differentiation of the ADSCs after thawing. Results: Compared with the groups treated with individual reagents, the 1.0 M Tre + 20% Gly group showed significantly higher efficiency in preserving ADSC activities after thawing, with better outcomes in both cell viability and proliferation capacity. Compared with the 10% DMSO + 90% FBS treatment, the ADSCs preserved in 1.0 M Tre + 20% Gly showed similar cell viability, surface markers and multi-potential differentiation but a significantly higher migration capability. The results indicated that cell function preservation can be improved by 1.0 M Tre + 20% Gly. Conclusions: The 1.0 M Tre + 20% Gly treatment preserved ADSCs with a higher migration capability than 10% DMSO + 90% FBS and with viability higher than that with trehalose or glycerol alone but similar to that with 10% DMSO + 90% FBS and fresh cells. Moreover, the new CPA achieves stemness and multi-potential differentiation similar to those in fresh cells. Our results demonstrate that 1.0 M Tre + 20% Gly can more efficiently cryopreserve ADSCs and is a non-toxic CPA that may be suitable for clinical applications.
Provider-Perceived Benefits and Constraints of Complete Adherence to Antenatal Care Guideline Among Public Health Facilities, Ethiopia: A Qualitative Study
Authors: Seyoum Tewodros , Alemayehu Mekuriaw , Christensson Kyllike , Lindgren Helena
Published: October 2020

Background: In Ethiopia, health care providers’ level of adherence to the national Antenatal Care (ANC) guideline is relatively low. The reasons why they do not follow the guidelines are not well known. Therefore, this study aimed to explore the provider-perceived benefits and constraints associated with using the guideline for ANC in public health facilities in Gondar town.Methods: A qualitative study was conducted using a semi-structured interview guide. The interview was conducted among a purposive sample of nine health care providers working in four public health facilities in Gondar town. After the interviews were transcribed and coded, a content analysis was done using Atlas ti version 7.5 software packages.Result: Decreasing provider’s workload and maximizing performance, improving safe motherhood, and improving the process of service delivery were reported as the perceived benefits of following ANC guideline. Organizational problems, care providers' existing knowledge, attitude, and skills and availability of training and mentorship were the three main identified groups of factors that hinder complete providers’ adherence to ANC guideline.Conclusion: Although providers acknowledged the benefits of following ANC guideline, the guideline is not fully implemented. Refresher training should be given at the start of the updated eight-contact ANC guideline and continuing education and supervision throughout the implementation process. Health care providers call for profound and urgent revisions of the supply chain system for supplies and equipment.
Characteristic Latent Features for Analyzing Digital Mental Health Interaction and Improved Explainability
Authors: Theilig Max-Marcel , Knapp Ashley Arehart , Nicholas Jennifer , Zarnekow Rüdiger , Mohr David Curtis
Published: October 2020

Background: Using smartphones and wearable sensor technology has sparked a broad engagement of data science and machine learning methods to leverage the complex, assorted amount of data. Despite verified processes, there is a reported underdevelopment of user engagement concepts, and the desire for high accuracy or significance has shown to lead to low explicability and irreproducibility. To overcome these issues, we aim to analyze principal characteristics of everyday behavior in digital mental health. Methods: We generated five latent features based on previous research, expert opinions from digital mental health, and informed by data. The features were analyzed with descriptive statistics and data visualization. We carried out two rounds of evaluations with data from 12,400 users of IntelliCare, a mental health platform with 12 apps. First, we focused to proof concept and second, we assessed reproducibility by drawing conclusion from distribution differences. User data was drawn from both research trials and public deployment on Google Play. Results: Our algorithms showed increased rationale for the basic usage of apps with different underlying behavioral strategies. Measures of the distribution of user’s allocated attention, the user’s circadian behavior, their consecutive commitment to a specific strategy, and users’ interaction trajectory are perceived as transferable to the public data set. Because distributions between research trial and public deployment were similar, consistency was shown regarding the underlying behavioral strategies: psychoeducation and goal setting are used as a catalyst to overcome the users’ primary obstacles, sleep hygiene is addressed most regularly, while regular self-reflective thinking is avoided. Relaxation as well as cognitive reframing have increased variance in commitment among public users, indicating the challenging nature of these apps. The relative course of the engagement (learning curve) is similar in research and public data. Conclusions: The deliberate, a-priori engineered features were reproducible across app users from both data sets. These features led to improved results as well as increased interpretability, providing an increased understanding of how people engage with multiple mental health apps over time. Since we based the generation of features on generic interaction proxies, these methods are applicable to other cases in artificial intelligence and digital health.
Permaculture: Smart Growth Strategies for Juniper Forest
Authors: Akhtar Faiza , Shahkhan Safdar , Lodhi Sulman Aziz
Published: October 2020

Permaculture creates an integrated system by incorporating those parameters which are often viewed as separate entities such as smart growth, low-impact development, habitat protection, complete streets, and other initiatives. Its gives better planning options and give policies a line of coherence and directions which provides basis for the real concept of sustainability. Presently in Pakistan, forest management policies suffer from a number of drawbacks and especially the Juniper forests in Pakistan are under constant pressure due to natural as well as anthropogenic pressures. To conserve the Juniper Forest Ecosystem a proposed Smart Growth Strategies based on Permaculture’s principles are designed to protect the Ziarat Juniper Forest that offers an unequivocal vision and strategy to gain valid sustainability in forest management.
Metatranscriptomics to characterize respiratory virome, microbiome, and host response directly from clinical samples
Authors: Rajagopala Seesandra , Bakhoum Nicole , Pakala Suman , Shilts Meghan , Rosas-Salazar Christian , Mai Annie , Boone Helen , McHenry Rendie , Yooseph Shibu , Halasa Natasha , Das Suman
Published: October 2020

We developed a metatranscriptomics method that can simultaneously capture the respiratory virome, microbiome, and host response directly from low-biomass clinical samples. Using nasal swab samples, we have demonstrated that this method captures the comprehensive RNA virome with sufficient sequencing depth required to assemble complete genomes. We find a surprisingly high-frequency of Respiratory Syncytial Virus (RSV) and Coronavirus (CoV) in healthy children, and a high frequency of RSV-A and RSV-B co-infections in children with symptomatic RSV. In addition, we have characterized commensal and pathogenic bacteria, and fungi at the species-level. Functional analysis of bacterial transcripts revealed H. influenzae was highly active in symptomatic RSV subjects. Host transcriptome shows upregulation of the innate immune system, antiviral response and inflammasome pathway, and down regulation of fatty-acids pathway. This method is broadly applicable to infer transcriptome landscape of an infected system, surveil respiratory infections, and to sequence RNA viruses directly from clinical samples.
Factors Associated With Self-Efficacy Toward Healthy Eating and Physical Activity Among Kuwaiti Adolescent Girls
Authors: AlGhanim Latifa , Alkazemi Dalal Usamah Zaid
Published: October 2020

Background: The factors that may influence adolescents’ health-related behaviors in Kuwait are unclear. We hypothesized that girls’ self-efficacy would be negatively associated with their weight statuses and positively associated with healthy eating-related behaviors. This study aimed to measure healthy eating-related parameters, including self-efficacy, dietary habits, dietary beliefs, nutrition knowledge, and physical activity, in a sample of Kuwaiti adolescent girls and assess the correlates of self-efficacy, including weight status and dietary and health behaviors. Methods: In this cross-sectional, self-administered survey at the school level, we evaluated students of three schools in different governorate locations in Kuwait. The participants were adolescent girls (n=301; mean age, 16.6±1.2 years) who attended secondary schools. The main outcome measures were self-efficacy, dietary habits, dietary beliefs, nutrition knowledge, physical activity, and weight status per body mass index (BMI) categories. Pearson’s correlation analysis was performed to determine the associations among the healthy behavior related parameter scores. The independent samples t-test was used to examine the differences in scores between participants’ characteristics and self-efficacy scores (SES). Multivariate regression analysis was used to determine the final independent correlates of SES.Results: Only 19.9% of the participants had high self-efficacy toward healthy eating behaviors, 20.9% had “satisfactory eating habits,” 11.3% had a good comprehension of the meanings of healthy and unhealthy dietary habits and food, 16.3% had good nutrition knowledge, and 29.2% had an active lifestyle. SES was negatively correlated with BMI (r=-0.074, P=0.03) and positively correlated with all domains of healthy eating and physical activity. However, SES was not associated with nutritional knowledge. The independent correlates of SES in the multivariate regression analysis were governorate, eating beliefs, healthy eating score, and physical activity (R2=38.3%).Conclusions: Adolescent girls in Kuwait demonstrated a high level of self-efficacy toward healthy eating and behaviors and had firm nutritional beliefs; however, they failed to translate their beliefs into good nutritional habits. It is necessary to develop interventional nutrition programs at the school level that aim at improving healthy behaviors among adolescents.
Improving Birth Preparedness and Complication Readiness Through an Integrated Microfinance and Health Literacy Program:Evidence From Rural India
Authors: Ahmad Danish , Mohanty Itismita , Niyonsenga Theo
Published: October 2020

Background:Despite maternal mortality rate almost halving over the past two decades, approximately 295,000 deaths occurred annually in 2017 globally. They occur in high burden regions where most preventable deaths are precipitated by delays in maternal care provision. Recently, a novel rapidly scalable community-based program combining maternal health literacy delivery through microfinance-based women-only self-help groups (SHG) was implemented in rural India. We evaluated the impact of the IMFHL program on BPCR practice by women in one of India’s poorest states-Uttar Pradesh, adjusting for community, household and individual variables. We also investigated if there is a diffusion of knowledge of BPCR from SHG members receiving the health literacy intervention to non-members in program villages.Method: Using secondary survey data from the IMFHL project, we analysed data from 17,244 women across SHG and non-member households in Uttar Pradesh. We performed multivariable logistic regressions to estimate adjusted IMFHL program’s effects on maternal BPCR practice.Results: Membership in SHG alone is positively associated with BPCR practice with 17 percent higher odds compared to women in villages without the programs. Furthermore, the odds of practising complete BPCR increases by almost fifty percent when a maternal health literacy component is added to the SHGs. A diffusion effect was found for BPCR practice from SHG members to non-members only when an added health literacy component was integrated into the SHG model. The main effect of the IMFHL program on BPCR practice remained stable in the presence of confounders suggesting that the delivery of health messages is undiluted by other non-programmatic factors at the individual, household and community level. Among confounders, only the poorest households as captured by the wealth quintile were significantly negatively associated with BPCR practice.Conclusion: The public health literature promotes the adoption of BPCR practices to improve maternal health outcomes. This study shows that SHGs exert both a dissemination effect of planned health behaviour within members, as well as facilitate a diffusion effect of the natural transfer of BPCR from members to non-members when SHGs are enriched with a health literacy component
Factors Influencing Taxpayers Engaged in Tax Evasion Evidence From Woldia City Administration Micro, Small and Large Enterprise Taxpayers
Authors: Tarko Erstu
Published: October 2020

The main purpose of this study is to investigate factors that influencing taxpayers to engage in tax evasion. The researcher used descriptive and explanatory research design and has been followed by a quantitative research approach. The data was collected by dispatching self-administered questionnaires. After data collection has been performed, exploratory factor analysis (EFA) was conducted. EFA results showed that the Kaiser-Mayer Olkin result 0.883 and the Bartlett test of 0.00 is suitable for the analysis. The data were analyzed with the Promax rotation method and extracted by the principal component analysis extraction method. All six factors were statistically significant for factor analysis. The explained variance of the first factor was 31.782%, the second factor explained 11.74% of the variance, the third factor explained 8.25% of the variance, the fourth factor explained 6.72% of the variance and the fifth factor explained 5.23% of the variance and the six-factor explained 4.12% of the variance. The extracted factors explained 67.84% of the variation of factors influencing taxpayers engaged in tax evasion. The finding of the study indicates that the relationship between the study variables was positive and statistically significant. The regression analysis also indicates that tax fairness, tax knowledge, and moral obligation significantly influence taxpayers to engage in tax evasion, and the remaining moral obligation and subjective norms were not statistically significant to influence taxpayers to engage in tax evasion.
Malaria Parasite Detection in Thick Blood Smear Microscopic Images Using Modified YOLOV3 and YOLOV4 Models
Authors: Abdurahman Fetulhak , Anlay Kinde Fante , Aliy Mohammed
Published: October 2020

Background Information: Manual microscopic examination is still the ”golden standard” for malaria diagnosis. The challenge in the manual microscopy is the fact that its accuracy, consistency and speed of diagnosis depends on the skill of the laboratory technician. It is diﬃcult to get highly skilled laboratory technicians in the remote areas of developing countries. In order to alleviate this problem, in this paper, we propose and investigate the state-of-the-art one-stage and two-stage object detection algorithms for automated malaria parasite screening from thick blood slides. Methods: YOLOV3 and YOLOV4 are state-of-the-art object detectors both in terms of accuracy and speed; however, they are not optimized for the detection of small objects such as malaria parasite in microscopic images. To deal with these challenges, we have modiﬁed YOLOV3 and YOLOV4 models by increasing the feature scale and by adding more detection layers, without notably decreasing their detection speed. We have proposed one modiﬁed YOLOV4 model, called YOLOV4-MOD and two modiﬁed models for YOLOV3, which are called YOLOV3-MOD1 and YOLOV3-MOD2. In addition, we have generated new anchor box scales and sizes by using the K-means clustering algorithm to exploit small object detection learning ability of the models. Results: The proposed modiﬁed YOLOV3 and YOLOV4 algorithms are evaluated on publicly available malaria dataset and achieve state-of-the-art accuracy by exceeding the performance of their original versions, Faster R-CNN and SSD in terms of mean average precision (mAP), recall, precision, F1 score, and average IOU. For 608 x 608 input resolution YOLOV4-MOD achieves the best detection performance among all the other models with mAP of 96.32%. For the same input resolution YOLOV3-MOD2 and YOLOV3-MOD1 achieved mAP of 96.14% and 95.46% respectively. Conclusions: Th experimental results demonstrate that the performance of the proposed modiﬁed YOLOV3 and YOLOV4 models are reliable to be applied for detection of malaria parasite from images that can be captured by smartphone camera over the microscope eyepiece. The proposed system can be easily deployed in low-resource setting and it can save lives.
Rapid Custom Prototyping of Soft Poroelastic Biosensor for Simultaneous Epicardial Recording and Imaging
Authors: Kim Bongjoong , Soepriatna Arvin , Park Woohyun , Cox Abigail , Moon Haesoo , Zhao Jianchao , Gupta Nevin , Park Chi Hoon , Kim Kyunghun , Lee Hyowon , Jeon Yale , Jang Hanmin , Kim Dong Rip , Lee Kwan-Soo , Goergen Craig , Lee Chi Hwan
Published: October 2020

The growing need for the implementation of stretchable biosensors in the human body and organ systems has driven a new rapid prototyping scheme through the direct ink writing (DIW) of multidimensional functional architectures in an arbitrary shape and size to meet the requirement of adapting the geometric nonlinearity of a specific biological site. Recent approaches involve the use of biocompatible viscoelastic inks that are dispensable through an automated nozzle injection system. However, their pragmatic application remains challenged in particular medical practices that demand long-term reliable recording under periodic large strain cycles, such as the cardiac cycle, due to their viscoelastic nature that produces both mechanical and electrical hysteresis. Herein, we report a new class of a poroelastic silicone composite that is adaptable for high-precision DIW of a custom-designed biosensor, which is exceptionally soft and insensitive to mechanical strain without generating significant hysteresis. The unique structural property of the composite material yields a robust and seamless coupling to living tissues, thereby enabling both high-fidelity recording of spatiotemporal electrophysiological activity and real-time ultrasound imaging for visual feedback. In vivo evaluation of a custom-fit biosensor in a murine acute myocardial infarction model demonstrates a potential clinical utility in the simultaneous intraoperative recording and imaging on the epicardial surface, which may guide a definitive surgical treatment.
A Combination of Pirfenidone and Inhibition of TGF-β Mitigates Cystic Echinococcosis–Associated Hepatic Injury
Authors: Wang Erqiang , Liao Zhenyu , Wang Lianghai , Liao Yuan , Xu Xiaodan , Liu Ping , Wang Xian , Hou Jun , Jiang Huijiao , Wu Xiangwei , Chen Xueling
Published: October 2020

Background & Aims: TGF-β not only inhibits the function of NK cells, but also promotes liver fibrosis. It is unclear whether the inhibition of TGF-β signaling pathway could relieve the CE-related liver fibrosis.Methods: By using the model of CE infected mouse liver, the effect of the infection of CE exerted on NK cells was identified. In vivo, SB525334 and Pirfenidone were applied to intervene the TGF-β signaling pathway.Results: During the infection of Echinococcus granulosus, the inhibitory receptors on the surface of NK cells increased, while the activated receptors decreased. TGF-β1 secretion was increased in liver tissues and mainly derived from macrophages. At the same time, the combination of drugs could also reduce the expression of TGF-β1 signaling pathway-related proteins and collagen. For the secretion of TGF-β1, only the pirfenidone group had an depressing effect. In addition, the combination of drugs can reduce liver cell damage and restore liver function.Conclusions: During the infection the of Echinococcus granulosus, the dysfunction of NK cells may be caused by increased secretion of TGF-β1 from macrophages. Echinococcus granulosus infection was a process of occupying lesions. This persistent pressure was accompanied by senescent hepatocytes. Senescent hepatocytes induced the secretion of TGF-β1 derived from macrophages, and promoted the activation of hepatic stellate cells and accelerated Echinococcus granulosus-associated liver fibrosis. By combining pirfenidone and SB525334, liver function, senescent hepatocytes, fibrosis associated with Echinococcus granulosus infection could be alleviated. Moreover, the functional status of NK cells also received partially amelioration. In summary, our work offered an experimental basis for clinical treatment.
Are smaller microplastics missing?
Authors: Aoki Kunihiro , Furue Ryo
Published: October 2020

The size distribution of marine microplastics (< 5 mm) provides a fundamental data source for understanding the dispersal, break down, and biotic impacts of the microplastics in the ocean. The observed size distribution generally shows, from large to small sizes, a gradual increase followed by a rapid decrease. This decrease has led to the hypothesis that the smallest fragments are selectively removed by sinking or biological uptake. Here we propose a new model of size distribution without any removal of material from the system. The model uses an analogy with black-body radiation and the resultant size distribution is analogous to Planck's law. In this model, the original large plastic piece is broken into smaller pieces once by the application of “energy” or work by waves or other processes, under two assumptions, one that fragmentation into smaller pieces requires larger energy and the other that the probability distribution of the “energy” follows the Boltzmann distribution. Our formula well reproduces observed size distributions over wide size ranges from micro- (< 5 mm) to mesoplastics ( > 5 mm). According to this model, the smallest fragments are fewer because large “energy” required to produce such small fragments occurs more rarely.
Process Development and Safety Evaluation of ABCB5+ Limbal Stem Cells as Advanced-therapy Medicinal Product to Treat Limbal Stem Cell Deficiency
Authors: Norrick Alexandra , Esterlechner Jasmina , Niebergall-Roth Elke , Dehio Ulf , Sadeghi Samar , Schröder Hannes M. , Ballikaya Seda , Stemler Nicole , Ganss Christoph , Dieter Kathrin , Dachtler Ann-Kathrin , Merz Patrick , Sel Saadettin , Chodosh James , Cursiefen Claus , Frank Natasha Y. , Auffarth Gerd U , Ksander Bruce , Frank Markus H. , Kluth Mark Andreas
Published: October 2020

Background: While therapeutic success of limbal tissue or cell transplantation to treat severe cases of limbal stem cell (LSC) deficiency (LSCD) strongly depends on the percentage of LSCs within the transplanted cells, prospective LSC enrichment has been hampered by the intranuclear localization of the previously reported LSC marker p63. The recent identification of the ATP-binding cassette transporter ABCB5 as a plasma membrane-spanning marker of LSCs that are capable of restoring the cornea and the development of an antibody directed against an extracellular loop of the ABCB5 molecule stimulated us to develop a novel treatment strategy based on the utilization of in-vitro expanded allogeneic ABCB5+ LSCs derived from human cadaveric limbal tissue.Methods: We developed and validated a Good Manufacturing Practice- and European Pharmacopoeia-conform production and quality-control process, by which ABCB5+ LSCs are derived from human corneal rims, expanded ex vivo, isolated as homogenous cell population and manufactured as an advanced-therapy medicinal product (ATMP). This product was tested in a preclinical study program investigating the cells’ engraftment potential, biodistribution behavior and safety.Results: ABCB5+ LSCs were reliably expanded and manufactured as an ATMP that contains comparably high percentages of cells expressing transcription factors critical for LSC stemness maintenance (p63) and corneal epithelial differentiation (PAX6). Preclinical studies confirmed local engraftment potential of the cells and gave no signals of toxicity and tumorgenicity. These findings were sufficient for the product to be approved by the German Paul Ehrlich Institute and the U.S. Food & Drug Administration to be tested in an international multicenter phase I/IIa clinical trial (NCT03549299) to evaluate the safety and therapeutic efficacy in patients with LSCD.Conclusion: Building upon these data in conjunction with the previously shown cornea-restoring capacity of human ABCB5+ LSCs in animal models of LSCD, we provide an advanced allogeneic LSC-based treatment strategy that shows promise for replenishment of the patient’s LSC pool, recreation of a functional barrier against invading conjunctival cells and restoration of a transparent, avascular cornea.
Analysis of the Effect of Proton Pump Inhibitors on the Course of Common COVID-19
Authors: ZHANG xiaoyu , Wu Haibing , Ling Yun , Chen Liang
Published: October 2020

Background/aims: This study is to evaluate the effect of proton pump inhibitors on the course of common COVID-19.Methods: Clinical data of common COVID-19 patients admitted to the Shanghai Public Health Clinical Center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.Results: A total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of the SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of the hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of the SARS-CoV-2 clearance and the discharge, all P > 0.05. Multivariate analysis showed that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of the hospital stay in COVID-19 patients was shortened by the SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.Conclusion: Proton pump inhibitors use has no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.
Factor VIII Inhibitor Bypass Activity (FEIBA) for the Reduction of Transfusion in Cardiac Surgery: A Randomized, Double-Blind, Placebo-controlled, Pilot Trial
Authors: Sera Valerie A , Stevens Ann E , Song Howard K , Rodriguez Victor M , Tibayan Frederick A , Treggiari Miriam
Published: October 2020

BackgroundUncontrolled bleeding after cardiac surgery can be life threatening. Factor eight inhibitor bypassing activity (FEIBA) is a prothrombin complex concentrate empirically used as rescue therapy for correction of refractory bleeding diathesis post cardiopulmonary bypass (CPB). FEIBA use as rescue therapy for bleeding diathesis after CPB has been associated with a low incidence of complications and a reduction in transfusion requirement and re-exploration. The feasibility and efficacy of early administration of FEIBA after termination of CPB have not been studied.MethodsWe designed a small randomized, double-blinded, placebo-controlled pilot trial to determine the feasibility of a larger trial testing the hypothesis that FEIBA decreases transfusion requirements after CPB. Twelve adult patients undergoing elective major aortic cardiovascular surgery at a tertiary referral hospital were equally randomized to receive a single dose of either FEIBA or matched placebo intraoperatively at the end of CPB. The study was designed to evaluate the feasibility of a larger pivotal trial to determine the effectiveness of FEIBA in reducing the total volume of blood products transfused perioperatively, and its safety profile.ResultsThere were no protocol deviations or events of unblinding, and adverse events were not different between groups. Patients in the FEIBA group were older, more likely to be female, had higher BMI, lower hematocrit, and longer hypothermic circulatory arrest. There were no differences in post randomization blood product transfusions (difference FEIBA vs. placebo: -899 mL; 95%CI: -5,206 to 3,409, p=0.65).ConclusionsThis pilot trial confirmed the adequacy of the trial design that involved the early, blinded administration of FEIBA, by demonstrating excellent protocol adherence. We conclude that a larger trial establishing the effectiveness of early prothrombin complex concentrate administration to reduce the use of blood products in the setting of high-risk cardiac surgery is feasible. Trial RegistrationClinicalTrials.gov NCT02577614, Registered 16 October, 2015, https://clinicaltrials.gov/ct2/show/NCT02577614
Tai Chi Exercise Improves Age-associated Decline in Cerebrovascular Function: A Cross-sectional Study
Authors: Li Lili , Wang Jingjing , Guo Shaoying , Xing Yangqi , Ke Xiongwen , Chen Yinghao , He Yuan , Wang Shun , Wang Jiayu , Cui Xinwu , Wang Zhihua , Tang Lixu
Published: October 2020

Background: Tai Chi exercise has been reported to enhance physical and mental health in the elderly; however, the mechanism remains elusive.Trial Design: We recruited 289 elderly people practicing Tai Chi for over 3 years, together with 277 age-matched old people and 102 young adults as controls. 168 Tai Chi players were successfully matched to 168 elderly controls aged 60-69 based on a propensity score for statistics.Methods: Cerebrovascular function was evaluated by measuring the hemodynamics of the carotid artery. Spearman correlation was performed to validate the age-associated physiological parameters. Results: Cerebrovascular function in the elderly significantly degenerated compared with young people, and was substantially correlated with age. Compared with the elderly control group, Tai Chi players showed significant improvements in CVHI (cerebral vascular hemodynamics indices) Score (P = 0.002), mean blood flow velocity (P = 0.014), maximal blood flow velocity (P = 0.04) and minimum blood flow velocity (P < 0.001), whereas the age-related increases in pulse wave velocity (P = 0.022), characteristic impedance (P = 0.021) and peripheral resistance (P = 0.044) were lowered. Conclusion: These data demonstrate a rejuvenation role of Tai Chi in improving the age-related decline of the cerebrovascular function.Trial registration: Chinese Clinical Trial Registry (ChiCTR1900025187).
In-House Development, Standardization, and Validation of a RT-qPCR Assay for the Detection of SARS-CoV-2 Virus in Ecuador.
Authors: Torre David De la , Pibaque Ronny , Veloz Tatiana , Beltrán Paúl , Baldeón Lucy
Published: October 2020

The World Health Organization (WHO) reported about 30 million cases of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and around 1 million deaths worldwide. Ecuador is the country with the highest mortality rate of confirmed cases in South America where both the poor ability to identify SARS-CoV-2 carriers and shortages in reagent supply have contributed the high infection rate observed. Hence, there is an urgent need to develop, standardize and validate an in-house protocol that cannot only reduces testing costs, but also increase the ability to screen widely the population. Primer-probe sets for the SARS-CoV-2 envelope protein E and the human ribonuclease P (RP) were validated for a duplex quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) for the Coronavirus Disease-19 (COVID-19) detection. Optimal E primers concentration was 400 nM and TaqMan probe 200 nM. The primer efficiency was set at 94.9% and R2 value at 0.99, which was comparable to commercial kits. The lower detection limit was found at 15 copies/ μL (50 copies/rx). In comparison to a Loop-mediated Isothermal Amplification (LAMP) commercial kit, there was a higher detection rate (30%) and results were highly reproducible (95%). We were able to develop a highly sensitive and low-cost duplex in-house RT-qPCR test for COVID-19 detection comparable to other commercially available kits.
7,8-dihydroxyflavone Improves Neuropathological Changes in the Brain of Tg26 Mice, A Model for HIV-associated Neurocognitive Disorder
Authors: Bryant Joseph , Andhavarapu Sanketh , Bever Christopher , Guda Poornachander , Katuri Akhil , Gupta Udit , Arvas Muhammed Ikbal , Asemu Girma , Heredia Alonso , Gerzanich Volodymyr , Simard Marc J , Makar Tapas Kumar
Published: October 2020

Background: The combined antiretroviral therapy (cART) era has significantly increased the lifespan of HIV patients, turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In HIV+ patients, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile.Methods: We investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. We immunohistochemically stained brain tissue sections from vehicle-treated wild type (WT), vehicle-treated Tg26, and DHF (5 mg/kg, i.p)-treated Tg26 mice to examine activation of TrkB and downstream signaling, expression of HIV-1 chemokine co-receptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. A one-way ANOVA with a Bonferroni Comparison post-hoc test was performed to analyze the data sets. Results: In the brain regions of Tg26 mice, we observed astrogliosis, increased CXCR4 and CCR5 expression, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB-Akt-NFkB signaling pathway in mediating these pathological hallmarks.Conclusions: Our study provides an overview of how targeting BDNF-TrkB signaling in the pathophysiology of HAND may be relevant for future therapies, and sheds light on 7,8 Dihydroxyflavone as a potential adjunct therapeutic agent to current antiviral therapy.