bluuebunny/crossref_metadata_2025 huggingface dataset:
Income Inequality and Population Health in China: a Longitudinal Study From China Health and Nutrition Survey
Authors: Shi Ting , Zang Wenbin , Chen Dapeng , Xiehu Mina
Published: May 2021

Background: China’s economy has made great achievements in the past few decades. However, the income disparity has also inevitably become a much more serious and noteworthy problem, which is absolutely harmful to the equitable development in population health.Methods: Data used in this study were obtained from ten waves from 1989 to 2015 of China Health and Nutrition Survey (CHNS), and we acquired a dataset with 78,235 observations in total. Regional Gini-index was used to reflect the extent of income inequality, with several other indicators employed as outcome variables. Thus, we applied a probit model to investigate the effect of income inequality on population health status. Results: Based on a probit regression analysis, we found an inverted U-shape relationship between regional income inequality and population health status. With an increase in the income inequality level, the population health will firstly have a slight increase; however, once the threshold was exceeded, population health conditions will have a significant decrease. The possible channel for this phenomenon is that income disparity will hurt social trust as well as increasing individuals’ mental stress, which could further change their health behaviors and thus finally affect individuals’ health conditions. Since individuals’ health status could directly affect their labor force participation, the income disparity will thus be affected by population health reversely. Therefore, we also utilized a lag term of income inequality as the independent variable and found the inverted U-shape relationship also exists, which helps our results become more credible.Conclusion: High-level income inequality tends to induce unhealthy behaviors such as smoking and drinking, and thus have a negative effect on personal health conditions. With the approval of the plan for Healthy China 2030, to promote national population health conditions, the Chinese government is supposed to shed more light on the increasingly serious income disparity problem.
Genomic analysis reveals fifty years of antimicrobial resistance evolution in husbandry Escherichia coli from China
Authors: Yang Lu , Shen Yingbo , Jiang Junyao , Wang Xueyang , Shao Dongyan , Lam Margaret , Holt Kathryn , Shao Bing , Wu Congming , Shen Jianzhong , Walsh Timothy , Schwarz Stefan , Wang Yang , Shen Zhangqi
Published: May 2021

Antimicrobial agents have been used in meat production for decades and its consumption is considered an key driver for the emergence and dissemination of antimicrobial resistance (AMR). However, large-scale studies on AMR changes in animal isolates since the introduction of antimicrobial usage remain scarce. We applied whole genome sequencing analysis to 982 animal-derived Escherichia coli collected in China from 1970s to 2019 and found increasing trends for the presence of numerous antimicrobial resistance genes (ARGs), including those conferring resistance to critically important agents for veterinary (florfenicol and norfloxacin) and human medicine (colistin, cephalosporins, and meropenem). Extensive diversity and increasing complexity of ARGs and their associated mobile genetic elements (MGEs) such as plasmids were also observed. The plasmids, IncC, IncHI2, IncK, IncI, IncX and IncF played a key role as highly effective vehicles for disseminating ARGs. Correlation analysis also revealed an association between antimicrobial production and emergence of ARGs at a spatial and temporal level. Prohibiting or strictly curtailing antimicrobial use in animals will potentially negate the current trends of AMR as the bacterial genome is highly changeable and using different drugs of the same class, or even unrelated classes, may co-select for MGEs carrying a plethora of co-existing ARGs. Therefore, limiting or ceasing antimicrobial use in animals to control AMR requires careful consideration.
Risk Status of Malaria Based on Socio-Demographic and Environmental Risk Factors in Two Communities in Lagos, Nigeria
Authors: Bello Abdulrahman Babatunde
Published: May 2021

Studies highlighting the influence of sociodemographic, cultural and environmental factors on malaria incidence have been able to elucidate the risk status of malaria. The sociodemographic, cultural and environmental risk variables influencing malaria occurrence was evaluated.Blood samples were collected from 360 multistage systematically selected household heads in Epe and Orimedu. Pretested and structured questionnaires were administered to the participants to obtain data related to their sociodemography, mosquito prevention practices and environmental factors of vulnerability to malaria. Potential risk factors for malaria infection occurrence was analyzed using binary logistic regression (Odds Ratio, O.R). Chisquare (X2) was used to analyze the relationship between malaria outcome and bednet ownership, standard mosquito prevention practices awareness, presence of surrounding stagnant pools and possession of window/door nets.Malaria risk was relatively high among participants aged 60 years and above (O.R=1.35), secondary school leavers (O.R=2.51), pensioners (O.R=3.00), participants without previous episodes (1.33) and participants who are not aware of malaria (O.R=2.11). Low malaria risk was observed among participants: who sought treatment in health facilities (O.R=0.00) and who knew that malaria can be prevented (O.R=0.54). Malaria prevalence was high among participants who own bednet(s) (x̄2(3) = 1.81, P0.57>0.05), have windows/door nets (x̄2(3) = 2.33, P0.95>0.05) and who do not have surroundings stagnant pools (x̄2(3) = 1.17, P0.33>0.05).Age, educational level, occupation, previous malaria episodes, treatment facility of choice, malaria awareness and knowledge about mosquito prevention practices influence malaria risk status. However, bed net ownership, possession of window/door nets and absence of surrounding puddles do not significantly reduce malaria incidence.
Migraine Detection From Eeg Signals Using Tunable Q-Factor Wavelet Transform and Ensemble Learning Techniques
Authors: ASLAN Zülfikar
Published: May 2021

Migraine is one of the major neurovascular diseases that recur, can persist for a long time, cripple or weaken the brain. This study uses electroencephalogram (EEG) signals for the diagnosis of migraine, and a computer-aided diagnosis system is presented to support expert opinion. A Tunable Q-Factor Wavelet Transform (TQWT) based method is proposed for the analysis of the oscillatory structure of EEG signals. With TQWT, EEG signals are decomposed into sub bands. Then, the features are statistically calculated from these bands. The success of the obtained features in distinguishing between migraine patients and healthy control (HC) subjects was performed using the Kruskal Wallis test. Feature values ​​obtained from each sub band were classified using well-known ensemble learning techniques and their classification performances were tested. Among the evaluated classifiers, the highest classification performance was achieved as 89.6% by using the Rotation Forest algorithm with the features obtained with Sub band 2. These results reveal the potential of the study as a tool that will support expert opinion in the diagnosis of migraine.
FKBP51 Modulates Hippocampal Size and Function in Post-translational Regulation of Parkin
Authors: Qiu Bin , Zhong Zhaohui , Righter Shawn , Xu Yuxue , Wang Jun , Deng Ran , Wang Chao , Williams Kent E , Ma Yao-Ying , Tsechpenakis Gavriil , Liang Tiebing , Yong Weidong
Published: May 2021

FK506-binding protein 51 (encoded by Fkpb51) has been associated with stress-related mental illness. To identify its function, we studied the morphological consequences of Fkbp51 deletion. Artificial Intelligence-assist morphological analysis identified that Fkbp51 knock-out (KO) mice possess more elongated CA and DG but shorter in height in coronal section when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls, pharmacological manipulation experiments suggest that this may occur through regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support that FKBP51 regulates microtubule-associated protein expression. Furthermore, in the absence of differences in mRNA expression, Fkbp51 KO hippocampus exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory of Parkin by FKBP51 and significance of their interaction on disease onset.
Fabrication of Flexible Agnws/Cellulose Hybrid Film with Heat Preservation and Antibacterial Properties for Agriculture Application
Authors: Chen Yu , Yang Shuanghong , Qiu Zhiwei , Li Yuqi , Qiu Fengxian , Zhang Tao
Published: May 2021

In the view of sustainable development and environment protection, degradable agricultural films with on-demand thermal insulation properties have attracted growing research interest in the last few decades due to the deteriorating environment and extreme climate on the growth and existence of crops. Here, a general strategy has been developed to fabricate degradable silver nanowires modified cellulose (AgNWs/cellulose) hybrid film with controllable thermal insulation and antibacterial properties by using plant cellulose and AgNWs as building blocks, as well as their agriculture application. The results showed that the AgNWs were evenly dispersed in the three-dimensional grid of cellulose, formed a film that could withstand a certain tensile force, and have good thermal stability. Due to the excellent electrical conductivity, the AgNWs/cellulose hybrid films can provide excellent Joule heating, generating rapid thermal response and uniform electrical heating at a low supply voltage of 3 V for extra warmth. In the antibacterial tests against Escherichia coli and Staphylococcus aureus, the AgNWs/cellulose hybrid film exhibit large diameters of inhibition zones, revealing the high antibacterial activity. Additionally, the AgNWs/cellulose hybrid films showed highly stretchable behavior by delivering a breaking strain of 1.5% with a tensile stress of 0.45 MPa owing to the cross-linked structures of cellulose and AgNWs. Based on the above properties, this study not only provides a potential strategy for the fabrication of flexible and biodegradable agricultural films but also may provide new insights for agricultural thermal management.
Cognitive Testing of a Survey Instrument to Assess Sexual Practices, Behaviours, and Health Outcomes: a Multi-country Study Protocol
Authors: Gonsalves Lianne , Hunter Erin C , Tucker Joseph D , Srini Megan L , Gitau Evelyn , Mercer Catherine H , Bajos Nathalie , Collins Debbie
Published: May 2021

Background: Population level data on sexual practices, behaviours and health-related outcomes can ensure that responsive, relevant health services are available for all people of all ages. However, while billions of dollars have been invested in attempting to improve sexual and reproductive health (including HIV) outcomes, far less is understood about associated sexual practices and behaviours. Therefore, the World Health Organization embarked on a global consultative process to develop a short survey instrument to assess sexual health practices, behaviours and health outcomes. In order for the resulting draft survey instrument to be published as a ‘global’ standard instrument, it is important to first determine that the proposed measures are globally comprehensible and applicable. This paper describes a multi-country study protocol to assess the validity and comparability of the survey instrument in a number of diverse countries.Methods:This study will use cognitive interviewing, a qualitative data collection method that uses semi-structured interviews to explore how participants process and respond to survey instruments. We aim to include study sites in up to 20 countries. The study procedures consist of: 1) localizing the instrument using forward and back-translation; 2) using a series of cognitive interviews to understand how participants engage with each survey question; 3) revising the core instrument based on interview findings; and 4) conducting an optional second round of cognitive interviews. Data generated from interviews will be summarised into a predeveloped analysis matrix. The entire process (a ‘wave’ of data collection) will be completed simultaneously by 6-7 countries. This stepwise approach facilitates iterative improvements and sharing across countries. Discussion:An important output from this research will be a revised survey instrument, which when subsequently published, can contribute to improving the comparability across contexts of measures of sexual practices, behaviours and health-related outcomes. Site-specific results of the feasibility of conducting this research may help shift perceptions of who and what can be included in sexual health-related research.
Different p53 Genotypes Regulate PPARγ Post-Translational Modification in The Adipogenic Differentiation of Cancer Cells
Authors: Zhang Kexin , Zhao Qi , Li Zugui , Zhang Hao , Fu Fangmei , Fu Junjie , Zheng Minying , Zhang Shiwu
Published: May 2021

Background: Our previous studies confirmed that high concentrations of cobalt chloride (CoCl2) can induce the formation of polyploid giant cancer cells (PGCCs). PGCCs have the properties of cancer stem cell. In this study, we demonstrate that PGCCs can be induced to differentiate into adipose in vitro and in vivo. In addition, the molecular mechanism of adipogenic differentiation of PGCCs with daughter cells was investigated by detecting the expression of adipocyte differentiation related proteins in mutant and wild-type p53 cancer cell lines. Methods: HEY and MDA-MB-231 control cells and PGCCs with daughter cells were cultured with adipogenic differentiation medium and the cell cycle was detected by flow cytometry. The expression of adipocyte differentiation related proteins, and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation. Immunoprecipitation was used to analyze the post-translational modification of peroxisome proliferator-activator receptor-γ (PPARγ) and P53 in HEY and MDA-MB-231 control cells and PGCCs with daughter cells cultured with adipogenic differentiation medium. Animal xenograft models were used to study the adipogenic differentiation of PGCCs with daughter cells.Results: Dexamethasone, rosiglitazone, insulin, and 3-isobutyl-1-methylxanthine (IBMX) can force the trans-differentiation of PGCCs into post-mitotic and functional adipocytes. Activation of PPARγ is a critical step in the process of adipogenic differentiation. The expression levels of p-CREBser133, PPARγ, C/EBPα, C/EBPβ were higher in PGCCs with daughter cells after adipogenic differentiation compared with those without adipogenic differentiation in HEY and MDA-MB-231. P53 regulates the acetylation and phosphorylation of PPARγ and the expression of P300- Acetyl-PPARγ(Lys)- FABP4 and ERK- Phospho-PPARγ (Ser112)-FABP4 depended upon the genotype of p53 in HEY and MDA-MB-231 cells after cultured with adipogenic differentiation medium. The invasion and migration abilities of PGCCs with their daughter cells after adipogenic differentiation decreased compared with those cells without adipogenic differentiation.Conclusion: P300-P53-ERK-CREB-PPARγ-CEBPα/β-FABP4 pathway may participate in the adipogenic differentiation of HEY, MDA-MB-231 PGCCs with daughter cells, which associated with genotype of p53.
Observation of Multiple Charge Density Wave Phases in Epitaxial Monolayer 1T-VSe2 Film
Authors: Zong Junyu , Xie Yang , Meng Qinghao , Tian Qichao , Chen Wang , Xie Xuedong , Jin Shaoen , Zhang Yongheng , Wang Li , Ren Wei , Chen Jian , Chen Aixi , Li Fangsen , Dong Zhaoyang , Wang Can , Li Jian-Xin , Zhang Yi
Published: May 2021

As a special order of electronic correlation induced by spatial modulation, the charge density wave (CDW) phenomena in condensed matters attract enormous research interests. Here, using scanning-tunneling microscopy in various temperatures, we observe a new (2×1) CDW phase besides the (√7×√3) CDW phase in epitaxial monolayer 1T-VSe2 film. Combining the variable-temperature angle-resolved photoemission spectroscopic (ARPES) measurements, we discover an anisotropic CDW gap and a two-step transition associated with the different CDW phases, which were observed below 135 K for the (√7×√3) CDW phase and between 135 K to 330 K for the (2×1) CDW phase respectively. The (√7×√3) CDW phase results a full gap, while the (2×1) CDW phase shows highly momentum dependence and results a partial gap structure at the Fermi surface. This two-step transition with anisotropic gap opening and the resulted evolution in ARPES spectra are corroborated by our theoretical calculation based on a phenomenological form for the self-energy containing a two-gap structure. Our findings provide significant information and deep understanding on the CDW phases in monolayer 1T-VSe2 film as a 2D material.
Determination of the activation energies of phase transition for calcium orthophosphates based on powder X-ray diffraction data
Authors: Vasylenko Kateryna , Sakhno Yuriy , Jaisi Deb , Nikolenko Mykola
Published: May 2021

Kinetic studies of the transformation of calcium orthophosphates metastable precipitates were performed under different synthesis conditions. Phase composition and degree of crystallinity were investigated by X-ray powder diffraction analysis. In acidic solution, precipitates of CaHPO4⋅2H2O (DCPD) and CaHPO4 (DCPA) are formed at the early stage of precipitation, with the degree of crystallinity at the range of 17–35%. Specifically, DCPD precipitates at 30°C and anhydrous DCPA at 50°C. In alkaline solution (pH 8–10), only amorphous forms of calcium orthophosphate is precipitated, which is explained by the high degree of supersaturation (i.e., the high rate of precipitation compared to that in acidic media). The diffraction peaks of DCPD and DCPA are found to be 0.3–0.45 degrees lower relative to their reference data, which is caused by decrease of lattice strain during early stage of crystallization. Furthermore, the initial molar ratio of Ca/P in reagent mixture was found to play subordinary role in determining the composition of final calcium phosphate precipitates. The effect of pH on the composition of precipitates is illustrated by the solubility isotherms of pure calcium orthophosphates. Given that the intensities of diffraction peaks are proportional to planar density of the material in the given plane, we propose, for the first time, to determine activation energy of phase transformation of calcium orthophosphate from X-ray powder diffraction patterns. Based on this relationship developed, the activation energy for the recrystallization DCPD and DCPA are 10.2 and 13.1 kJ/mol, respectively and for the phase transition of DCPD to DCPA – 36.7 kJ/mol. Further recrystallization to most thermodynamically stable Ca10(PO4)6(OН)2 hydroxyapatite (HA) occurs at the activation energy of 5.2 kJ/mol. These findings are critical on phase transition and transformation of calcium phosphate minerals.
Venoarterial Extracorporeal Membrane Oxygenation as Mechanical Circulatory Support in Adult Septic Shock: A Systematic Review and Meta-Analysis with Individual Participant Data Meta-Regression Analysis.
Authors: Ling Ryan Ruiyang , Ramanathan Kollengode , Poon Wynne Hsing , Tan Chuen Seng , Brechot Nicolas , Brodie Daniel , Combes Alain , MacLaren Graeme
Published: May 2021

Background: While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA-ECMO, and identify factors associated with survival.Methods: We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st April 2021, and included all relevant publications reporting on >5 adult patients requiring VA-ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted. Data synthesis: We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI] :23.6%-50.1%). Survival among patients with left ventricular ejection fraction (LVEF) <20% (62.0%, 95%CI: 51.6%-72.0%) was significantly higher than those with LVEF>35% (32.1%, 95%CI: 8.69%-60.7%, p=0.05). Survival reported in studies from Asia (19.5%, 95%CI: 13.0%-26.8%) was notably lower than those from Europe (61.0%, 95%CI: 48.4%-73.0%) and North America (45.5%, 95%CI: 16.7%-75.8%). Extracorporeal cardiopulmonary resuscitation was associated with reduced chances of survival (Risk ratio: 0.403, 95%CI: 0.197-0.826, p=0.01). GRADE assessment indicated high certainty of evidence for pooled survival.Conclusions: When treated with VA-ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock but without severe left ventricular depression. VA-ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.
Identification and Physical Characterization of a Spontaneous Mutation of the Tobacco Mosaic Virus in the Laboratory Environment
Authors: Lumata Jenica L. , Ball Darby , Shahrivarkevishahi Arezoo , Luzuriaga Michael A. , Herbert Fabian C. , Brohlin Olivia , Lee Hamilton , D’Arcy Sheena , Gassensmith Jeremiah J. , Hagge Laurel M.
Published: May 2021

Virus-like particles are an emerging class of nano-biotechnology with the Tobacco Mosaic Virus (TMV) having found a wide range of applications in imaging, drug delivery, and vaccine development. TMV is typically produced in planta, and, as an RNA virus, is highly susceptible to natural mutation that may impact its properties. Over the course of two years, from 2018 until 2020, our laboratory followed a spontaneous point mutation in the TMV coat protein—first observed as a 30 Da difference in electrospray ionization mass spectrometry (ESI-MS). The mutation would have been difficult to notice by electrophoretic mobility in agarose or SDS-PAGE and does not alter viral morphology as assessed by transmission electron microscopy. The mutation responsible for the 30 Da difference between the wild-type (wTMV) and mutant (mTMV) coat proteins was identified by a bottom-up proteomic approach as a change from glycine to serine at position 155 based on collision-induced dissociation data. Since residue 155 is located on the outer surface of the TMV rod, it is feasible that the mutation alters TMV surface chemistry. However, enzyme-linked immunosorbent assays found no difference in binding between mutant and wild-type TMV. Functionalization of a nearby residue, tyrosine 139, with diazonium salt, also appears unaffected. Overall, this study highlights the necessity of standard workflows to quality-control viral stocks. We suggest that ESI-MS is a straightforward and low-cost way to identify emerging mutants in coat proteins.
Orbital torque in magnetic bilayers
Authors: Lee Dongjoon , Go Dongwook , Park Hyeon-Jong , Jeong Wonmin , Ko Hye-Won , Yun Deokhyun , Jo Daegeun , Lee Soogil , Go Gyungchoon , Oh Jung Hyun , Kim Kab-Jin , Park Byong-Guk , Min Byoung-Chul , Koo Hyun Cheol , Lee Hyun-Woo , Lee OukJae , Lee Kyung-Jin
Published: May 2021

The spin Hall effect describes an electric-field-induced generation of spin currents through spin-orbit coupling. Since the spin-orbit coupling alone cannot generate the angular momentum, there must be a more fundamental process of the spin Hall effect. Theories suggested that an electric-field-induced generation of orbital currents, called orbital Hall effect, is the fundamental process, and spin currents are subsequently converted from orbital currents. Despite its fundamental importance, the orbital Hall effect has not been confirmed experimentally. Motivated by a recent theoretical proposal of torque generation by orbital angular momentum injection, we examine the current-induced torque experimentally in various ferromagnet/heavy metal bilayers. We find that the net torque in Ni/Ta bilayers is opposite in sign to the spin Hall theory prediction but instead consistent with the orbital Hall theory, which confirms the orbital torque generated by the orbital Hall effect. It will invigorate researches on spin-orbit-coupled phenomena based on orbital engineering.
Enhanced Performance of Hydrogen Peroxide Modified Pozzolan-based Geopolymer for Abatement of Methylene blue from Aqueous Medium
Authors: Hermann Dzoujo Tamaguelon , Sylvain Tome , Shikuku Victor O , Tchuigwa Jean T , Spieß Alex , Janiak Christoph , Etoh Marie Annie , Dina David
Published: May 2021

Pozzolan-based eco-adsorbents were synthesized by geopolymerization with addition of hydrogen peroxide (H2O2) with mass ratios 0% (GP0) and 1% (GP1) and the products used to sorb cationic methylene blue (MB) dye from water. The chemical composition, textural properties, mineral composition, surface functions, as well as morphology and internal structure of these samples were determined by the X-ray fluorescence, adsorption of nitrogen by the B.E.T (Bruamer Emmet Teller) method, X-ray diffraction, Fourier Transformed Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM), respectively. The effects of contact time, dye initial concentration, adsorbent dosage, pH and temperature were examined and are herein reported. Incorporation of 1% H2O2 increased the specific surface area from 4.344 to 5.610 m2/g representing ~ 29% increase in surface area. This translated an increase in the MB adsorption capacity by 15 orders of magnitude from 24.4 to 366.2 mg/g for GP0 and GP1, respectively. The adsorption rates of methylene blue on the two geopolymers were best described by the pseudo-second order kinetic model. The adsorption equilibrium data were best described by the Sips and Freundlich isotherms models for GP0 and GP1, respectively. Thermodynamically, it was determined that the adsorption of methylene blue onto GP0 and GP1 is a physical and endothermic process. The results show that incorporation of low amount of hydrogen peroxide into pozzolan-based geopolymers increases their adsorption capacity for methylene blue dye stupendously while preserving the surface chemistry.
Engineered Campylobacter jejuni Cas9 variant with enhanced activity
Authors: Nakagawa Ryoya , Ishiguro Soh , Okazaki Sae , Mori Hideto , Tanaka Mamoru , Aburatani Hiroyuki , Yachie Nozomu , Nishimasu Hiroshi , Nureki Osamu
Published: May 2021

The RNA-guided DNA endonuclease Cas9 is a versatile genome-editing tool. However, the molecular weight of the commonly used Streptococcus pyogenes Cas9 is relatively large. Consequently, its gene cannot be efficiently packaged into an adeno-associated virus vector, thereby limiting its applications for therapeutic genome editing. Here, we biochemically characterized the compact Cas9 from Campylobacter jejuni (CjCas9) and found that CjCas9 has a previously unrecognized preference for the N3VRYAC protospacer adjacent motif. We thus rationally engineered a CjCas9 variant (enCjCas9), which exhibits enhanced cleavage activity and a broader targeting range both in vitro and in human cells, as compared with CjCas9. Furthermore, a nickase version of enCjCas9, but not CjCas9, fused with a cytosine deaminase mediated C-to-T conversions in human cells. Overall, our findings expand the CRISPR-Cas toolbox for therapeutic genome engineering.
Bioinformatics Analysis of Differentially Expressed Genes Involved in Irritable Bowel Syndrome With Diarrhea
Authors: Lou Yuan-Mei , Ge Yan-Zhi , Chen Wen , Su Lin , Zhang Jia-Qi , Wang Gui-Yue , Qi Ya-Qin , Yang Jin-Ying , Chen Zu-Xiang , Song Hong
Published: May 2021

Purpose: Irritable bowel syndrome with diarrhea (IBS-D) is a common functional gastrointestinal disorder around the world. However, the molecular mechanisms of IBS-D are still not well understood. This study was designed to identify key biomarkers and immune infiltration in the rectal mucosa of IBS-D by bioinformatics analysis. Methods: The gene expression profiles of GSE36701 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified and functional enrichment and pathway analyses were performed. Using STRING and Cytoscape, protein-protein interaction (PPI) networks were constructed and core genes were identified. Subsequently, 22 immune cell types of IBS-D tissues were explored by the Cell type Identification by Estimating Relative Subsets of RNA Transcripts. Finally, the co-expression network of DEGs was estimated by the weigh gene co-expression network analysis method to identify IBS-D-related modules and deeply hub genes. Results: 224 up-regulated and 171 down-regulated genes in IBS-D patients: Our analysis indicated that several DEGs might play crucial roles in IBS-D, such as CDC20, UBE2C, AURKA, CDC26, CKS1B and PSMB3. Later, we found that immune infiltrating cells such as T cells CD4 memory resting, M2 macrophages are crucial in IBS-D progression. In the end, a total of 9 co-expression gene modules were calculated and the black module was found to have the highest correlation. 15 hub genes were identified both in DEGs and the black module. Conclusions: This study identified molecular mechanisms and a series of candidate genes as well as significant pathways from the bioinformatics network, which may provide a diagnostic method and therapeutic targets for IBS-D.
Genetic Depletion of Amylin/Calcitonin Receptors Improves Memory and Learning in Transgenic Alzheimer’s Disease Mouse Models.
Authors: Patel Aarti , Kimura Ryoichi , Fu Wen , Soudy Rania , MacTavish David , Westaway David , Yang Jing , Davey Rachel , Zajac Jeffrey , Jhamandas Jack H.
Published: May 2021

Based upon its interactions with amyloid β peptide (Aβ), the amylin receptor, a Class B G protein-coupled receptor (GPCR), is a potential modulator of Alzheimer’s disease (AD) pathogenesis. However, past pharmacological approaches have failed to resolve whether activation or blockade of this receptor would have greater therapeutic benefit. To address this issue, we generated compound mice expressing a human amyloid precursor protein gene with familial AD mutations in combination with deficiency of amylin receptors produced by hemizygosity for the critical calcitonin receptor subunit of this heterodimeric GPCR. These compound transgenic AD mice demonstrated attenuated responses to human amylin- and Aβ-induced depression of hippocampal long term potentiation (LTP) in keeping with the genetic depletion of amylin receptors. Both the LTP responses and spatial memory (as measured with Morris Water Maze) in these mice were improved compared to AD mouse controls and, importantly, a reduction in both the amyloid plaque burden and markers of neuroinflammation was observed. Our data support the notion of further development of antagonists of the amylin receptor as AD-modifying therapies.
The Effect of a Sustainable Technology of Delignification and Tcf Bleaching on Physical Properties of Recovered Cardboard
Authors: Aguilar-Rivera Noe
Published: May 2021

Old Corrugated Containers (OCC), also known as waste corrugated cardboard, multilayer packaging and wrapping sacks are complex and heterogeneous materials composed of various sources of unbleached cellulose pulp derived from several raw material processes. However, OCC pulp have a high proportion of long fiber because are mainly manufactured from softwood pulp by the kraft process. OCC are the main category of recovered paper; however, due to their high lignin content, hornification and other problems resulting from the pulp to cardboard conversion processes, additives and pollutants, their physical properties decrease with each recycling which justifies evaluating various treatments with existing technologies to improve it. The objective of this work was to obtain improved unbleached and bleached old corrugated container (OCC) pulp more ecologically justifiable than wood for higher grade papers using sustainable processes evaluated in pilot scale tests OCC were collected from a landfill, cleaned, repulped, and treated with extended delignification with the alkaline soda process, obtaining a pulp with significant physical-mechanical improvements in relation to the original material, such as tensile strength, tearing resistance, bursting strength and folding endurance. The OCC soda pulp was bleached by a sequence totally free of chlorinated compounds (TCF), obtaining bleached pulp with optical and mechanical properties comparable to virgin pulps of annual plants such as bagasse but with improved drainage properties and lower processing costs. According to their properties, it is a competitive pulp obtained with existing technologies, available for use in various grades of printing and writing paper replacing totally or partially bleached wood pulp.
Evaluation of Real Brain Activity Using an Ultracompact Brain Activity Sensor for the Assessment of Cognitive Function
Authors: Yasumitsu Tatsuo
Published: May 2021

Background: The present study purpose aims to improve cognitive function at the preclinical stage of dementia and measure real-time brain activity levels in participants wearing an ultracompact brain activity sensor called XB-01. Methods: Four healthy people (two males and two females) aged 20–50 years involved in the dementia prevention program participated in the study. During the experiment, the participants wore XB-01, which was connected to their iPhone by Bluetooth to collect data. XB-01 data indicating the brain activity (blood flow) during the program was demonstrated by real-time color changes on the connected iPhone to evaluate the results on a 100-point scale. We examined 21 programs in total, including those reported to increase brain activity. Results: We conducted an analysis of variance for each of the four programs in the upper and lower positions detected to compare brain activity, resulting in finding a main effect of the program, F(7,21) = 4.35, p <.05. Conclusions: An exercise program including a dual-task with large limb movements was highly effective in increasing brain activity in the dorsolateral prefrontal cortex (DLPFC). Moreover, slightly higher speed, pace, and difficulty level of the program most suitable for participants were more effective. Brain activity increased in the DLPFC during the program and several minutes after its completion. These findings can help develop programs that prevent and improve cognitive function.Trial Registration: The research ethics committee at PCY, Ltd. Trial Registry, approval number 20-2. Registered 04 January 2020. Retrospectively registered.
Breastfeeding Media Coverage and Beliefs During the COVID-19 Pandemic in Mexico: Implications for Breastfeeding Equity.
Authors: Vilar-Compte Mireya , Gaitán-Rossi Pablo , Rhodes Elizabeth C. , Cruz-Villaba Valeria , Pérez-Escamilla R.
Published: May 2021

Background: Breastfeeding offers short- and long- term health benefits to mothers and children and constitutes a priority for public health. Evidence shows that SARS-CoV-2 is not likely to be transmitted via breastmilk. Moreover, antibodies against SARS-CoV-2 are presumably contained in breastmilk of mothers with history of COVID-19 infection or vaccination. Direct breastfeeding is the preferred infant feeding option during the pandemic, but conflicting practices have been adopted, which could widen existing disparities in breastfeeding. This study aims to describe how was information about breastfeeding communicated in Mexican media during the pandemic and assess Mexican adults’ beliefs regarding breastfeeding among mothers infected with COVID-19.Methods: A retrospective content analysis of media coverage on breastfeeding in Mexico between March 1 and September 24, 2020, excluding advertisements, was done. For the content analysis, both a sentiment analysis and an analysis based on strengths, weaknesses, opportunities and threats for breastfeeding promotion were performed. Also, we incorporated a descriptive analysis from the July 2020 wave of the ENCOVID-19 survey, which included questions on beliefs about breastfeeding. This information was stratified by gender, age, and socioeconomic status.Results: 1014 publications on breastfeeding were identified in internet, newspapers, TV, and magazines. Most information was published during World Breastfeeding Week, celebrated in August. Based on the sentiment analysis, 57.2% of all information was classified as positive, and based on the SWOT analysis, most information was classified either as strengths or opportunities for breastfeeding promotion. However, the ENCOVID-19 data showed that 67.3% of people living in households with children under 3 years of age believe that mothers with COVID-19 should not breastfeed, and 19.8% stated that they simply didn’t know. These beliefs showed differences both by gender and by socioeconomic status.Conclusions: While the Mexican government endorsed the recommendations on breastfeeding during the COVID-19 pandemic, communication of those messages was sporadic, inconstant and unequal across types of media. Moreover, there were also negative messages for breastfeeding circulating on the media. There continues to be a widespread notion that mothers with COVID-19 should not breastfeed and, due to differences on beliefs by socioeconomic status, health inequities could be exacerbated.
Synbiotic (Lactobacillus Pentosus GSSK2 And Isomalto-Oligosaccharides) Supplementation Modulates Pathophysiology And Gut Dysbiosis In Experimental Metabolic Syndrome
Authors: Khanna Sakshi , Kondepudi Kanthi Kiran , Bishnoi Mahendra , Shukla Geeta
Published: May 2021

Metabolic syndrome a lifestyle disease, where diet and gut microbiota play a prodigious role in its initiation and progression. Prophylactic bio-interventions employing probiotics and prebiotics offer an alternate nutritional approach towards attenuating its progression. The present study aimed to evaluate the protective efficacy of a novel synbiotic (L. pentosus GSSK2 + isomalto- oligosaccharides) in comparison to orlistat in an experimental model of metabolic syndrome. It was observed that supplementation of synbiotic for 12 weeks to Sprague Dawley rats fed with high fat diet, ameliorated the anthropometric parameters i.e. weight gain, abdominal circumference, Lee’s index, BMI and visceral fat deposition along with significantly increased fecal Bacteroidetes to Firmicutes ratio, elevated population of Lactobacillus spp., Akkermansia spp., Faecalibacterium spp., Roseburia spp. and decreased Enterobacteriaceae compared with HFD animals. Additionally, synbiotic administration to HFD animals exhibited improved glucose clearance, lipid biomarkers, alleviated oxidative stress, prevented leaky gut phenotype, reduced serum lipopolysaccharides and modulated the inflammatory, lipid and glucose metabolism genes along with restored histomorphology of adipose tissue, colon and liver compared with HFD animals. Taken together, the study highlights the protective potential of synbiotic in comparison with its individual components in ameliorating HFD-induced metabolic complications.
Deprescribing To Reduce Polypharmacy: Study Protocol For A Randomised Controlled Trial Assessing Deprescribing of Anticholinergic and Sedative Drugs In A Cohort of Frail Older People Living In The Community
Authors: Bergler Ulrich , Ailabouni Nagham , Pickering John W. , Hilmer Sarah , Mangin Dee , Nishtala Prasad , Jamieson Hamish
Published: May 2021

Background: Targeted deprescribing of anticholinergic and sedative medications in older people can improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community. Methods and analysis: The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve three groups of older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomised controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients.Study population: Community dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly.Intervention: New Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend to general practitioners’ anticholinergic and sedative medications that could be deprescribed. Total use of anticholinergic and sedative medications will be quantified using the Drug Burden index (DBI).Outcomes: The primary outcome will be the change in total DBI between baseline and six-months follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalisation, and death.Data collection points: Data will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3).Ethics and dissemination: Ethics approval has been obtained from the Human, Disability and Ethics Committee. Ethical number (17CEN265).Trial registration: The trial was registered on 2 May 2018 with the Australian New Zealand Clinical Trials Registry: ACTRN12618000729224 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374924)
Findings from Precision Oncology in the Clinic: Rare, Novel Variants are a Significant Contributor to Scaling Molecular Diagnostics
Authors: Doig Kenneth Douglas , Love Christopher G. , Conway Thomas , Seleznev Andrei , Ma David , Fellowes Andrew , Blombery Piers , Fox Stephen B.
Published: May 2021

Background: Next generation sequencing for oncology patient management is now routine in clinical pathology laboratories. Although wet lab, sequencing and pipeline tasks are largely automated, the analysis of variants for clinical reporting remains largely a manual task. The increasing volume of sequencing data and the limited availability of genetic experts to analyse and report on variants in the data is a key scalability limit for molecular diagnostics.Method: To determine the impact and size of the issue, we examined the longitudinally compiled genetic variants from 48,036 cancer patients over a six year period in a large cancer hospital from ten targeted cancer panel tests in germline, solid tumour and haematology contexts using hybridization capture and amplicon assays. This testing generated 24,168,398 sequenced variants of which 23,255 (8,214 unique) were clinically reported. Results: Of the reported variants, 17,240 (74.1%) were identified in more than one assay which allowed curated variant data to be reused in later reports. The remainder, 6,015 (25.9%) were not subsequently seen in later assays and did not provide any reuse benefit. The number of new variants requiring curation has significantly increased over time from 1.72 to 3.73 variants per sample (292 curated variants per month). Analysis of the 23,255 variants reported, showed 28.6%(n=2,356) were not present in common public variant resources and therefore required de novo curation. These in-house only variants were enriched for indels, tumour suppressor genes and from solid tumour assays.Conclusion: This analysis highlights the significant percentage of variants not present within common public variant resources and the level of non-recurrent variants that consequently require greater curation effort. Many of these variants are unique to a single patient and unlikely to appear in other patients reflecting the personalised nature of cancer genomics. This study depicts the real-world situation for pathology laboratories faced with curating increasing numbers low-recurrence variants while needing to expedite the process of manual variant curation. In the absence of suitably accurate automated methods, new approaches are needed to scale oncology diagnostics for future genetic testing volumes.
HBV Genome-Enriched Single Cell Sequencing Revealed Heterogeneity in HBV-Driven HCC
Authors: Wang Wenhui , Chen Yan , Wu Liang , Zhang Yi , Yoo Seungyeul , Chen Quan , Liu Shiping , Hou Yong , Chen Xiao-ping , Chen Qian , Zhu Jun
Published: May 2021

Background: HBV-HCC is heterogeneous and frequently contains multifocal tumors. To interrogate heterogeneity of HBV-HCC, we developed a HBV genome enriched single cell sequencing (HGE-scSeq) procedure and a computational method to identify HBV integration sites and infer DNA copy number variations (CNVs). Results: We performed HGE-scSeq on 269 cells from 4 tumor sites and 2 tumor thrombi of a HBV-HCC patient. HBV integrations were identified in 142 out of 269 (53%) cells sequenced, and were enriched in two HBV integration hot spots chr1:34,397,059 (CSMD2) and chr8:118,557,327 (MED30/EXT1). There were also 162 rare integration sites. HBV integration sites were enriched in DNA fragile sites and sequences around HBV integration sites were enriched for microhomologous sequences between human and HBV genomes. Cells were grouped into 4 clonal groups based on CNVs. The HBV integration heterogeneity was associated with single cell’s CNVs. All of 269 cells carried chromosome 1q amplification, a recurrent feature of HCC tumors, suggesting that 1q amplification occurred before HBV integration events in this case study. Further, we performed simulation studies to demonstrate that the sequential events (HBV infecting transformed cells) could result in the observed phenotype with biologically reasonable parameters. Conclusion: Our HGE-scSeq data reveals high heterogeneity of HCC tumor cells in terms of both HBV integrations and CNVs.
Study of Awareness Regarding Covid-19 Vaccines Among General Population
Authors: Patel Vishani , Patel Krishani
Published: May 2021

BACKGROUND:The COVID-19 pandemic is an ongoing global pandemic of coronavirus disease 2019 caused by SARS-Cov-2. COVID-19 Vaccines are developed to provide immunity against covid-19 and first mass vaccination started in early December 2020.METHOD:This survey aims to provide knowledge of different types of vaccines, benefits, mechanisms, efficacy and concerns about people regarding vaccination.230 people participated from different countries like INDIA, USA, CANADA, AUSTRALIA, KENYA and LONDON. It was conducted from 28 march 2021 to 8 April 2021. The randomized study was done and people from above countries who agreed to participate were included.There were 128 female and 102 male.CONCLUSION:From above survey, we conclude that:55.7% of people are vaccinated and 44.3% of people are still not vaccinated.Out of the above 44.3% of people who are not vaccinated, 32.6% of people want to be vaccinated as soon as possible. Most of the people think that vaccines should be made compulsory and more awareness related to vaccines is required.