bluuebunny/crossref_metadata_2025 huggingface dataset:
Development the Clinical Guideline of Human Milk Bank in Iran
Authors: Yousefi Arezoo , Sadeghi Narges , Jafari-mianaei Soheila
Published: May 2021

Background

Clinical guidelines are recommendations produced by systematic methods assisting health care providers in making the right decisions. The existence of Mothers’ Milk Banks (MMBs) plays an important role in increasing exclusive breastfeeding in low birth-weight infants. More than one million infants under one year of age die annually because they are not breastfed. The present study was done to develop a clinical guideline for MMB.
Methods

The study was a multistage integrated study conducted in three steps according to the NICE model. In the first step, the components of a clinical guideline for MMB were determined through multiple data centers to search and resource integration and a draft was subsequently prepared. In the second step, each component was reviewed considering the expert agreement and the clinical guideline was finally developed. In the third step, the AGREE questionnaire was used by 10 experts to measure the utility and quality of the proposed program as well as its national feasibility. Quantitative data was analyzed in SPSS20 using descriptive statistics.
Results

The clinical guideline included the necessary measures before MMB development (establishing MMB infrastructure, enhancing awareness for supporting MMB, creating a network for communicating with different units, developing the key rules and guidelines as well as ethical points) and the necessary measures while using MMB (donors, working processes on the donated milk, and the recipients). The content was reviewed by forming a focus group and their corrective comments were considered in the clinical guideline. Utilizing the AGREE tool, the results of the survey showed that 90% of the respondents strongly recommended guideline use.
Conclusions

It is hoped that this clinical guideline, provided by the order of Neonatal Health Bureau based on the culture and religion of the Iranian community, could be an effective step to improve the care and treatment process of preterm infants. Moreover, with the proper use of it, the treatment team staff can support the premature infants and their parents by promoting breastfeeding and reducing the side effects of using formula and the mortality of this group of infants.
A Continuous Metric to Measure Endotype and Corticosteroid Interaction in Septic Shock
Authors: Wong Hector , Cvijanovich Natalie , Weiss Scott L. , Fitzgerald Julie , Bigham Michael , Jain Parag , Schwarz Adam , Lutfi Riad , Nowak Jeffrey , Allen Geoffrey , Thomas Neal , Grunwell Jocelyn , Baines Torrey , Quasney Michael , Haileselassie Bereketeab , Hart Kimberly , Sweeney Timothy , Lindsell Christopher John
Published: May 2021

The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of treatment effect. We previously reported a binary septic shock endotype classification based on expression of 100 genes. This binary classification provides information regarding prognosis and corticosteroid responsiveness but does not capture the endotypes continuum. Here, we describe a continuous metric for endotype assignment, the Z value, and its relationship with septic shock outcomes and corticosteroid responsiveness. In a derivation cohort, a lower Z value was independently associated with increased odds of mortality. When the Z value was fit using cubic splines, the odds of mortality increased considerably below a Z value of 15 among patients exposed to corticosteroids. A similar interaction between Z value and corticosteroid exposure was observed when the model was applied to pediatric and adult validation cohorts. The Z value provides more detailed evidence of patients with septic shock in whom corticosteroids are harmful.
Role of unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: A longitudinal study of the urine microbiome and metabolites
Authors: Kim Kangjin , Lee Sanghun , Park Sang-Chul , Kim Nam-Eun , Jung Youngae , Yoon Dankyu , Kim Hyeonjeong , Kim Sanghyun , Hwang Geum-Sook , Won Sungho
Published: May 2021

The authors have requested that this preprint be removed from Research Square.
Human cells based directed evolution of adenine base editors with improved efficiency
Authors: Fu Junhao , Li Qing , Liu Xiaoyu , Tu Tianxiang , Lv Xiujuan , Yin Xidi , Song Zongming , Zhang Jinwei , Li Jinsong , Gu Feng
Published: May 2021

Adenine base editors (ABE) are novel genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion in genomic DNA. However, the low activity of ABE remains a major bottleneck that precludes efficacious applications. To address this limitation, we developed a directional screening system in human cells to evolve the deaminase component of the ABE, and identified three high-activity NG-ABEmax variants: NG-ABEmax-SGK (R101S/D139G/E140K), NG-ABEmax-R (Q154R) and NG-ABEmax-K (N127K). With further engineering, we created a new, consolidated variant [NG-ABEmax-KR (N127K/Q154R)] which exhibited superior editing activity both in human cells and in mouse disease models, compared to the original NG-ABEmax. We also found that NG-ABEmax-KR efficiently introduce natural mutations in gamma globin gene promoters with more than four-fold increase in editing activity. This work provides a broadly applicable, rapidly deployable platform to directionally screen and evolve novel, user-specified traits in base editors that extend beyond augmented editing activity.
Influence of aqueous chloride and bromide anions on the reactivity of ZnO on bisphenol A degradation
Authors: Yang Yi-Chen , Sahu Rama Shanker , Shih Yang-hsin
Published: May 2021

Zinc oxide nanoparticles (ZnO NPs) have been widely investigated for applications in photocatalytic degradation of organic pollutants in wastewater. Despite the advantages of robust ZnO material, its photocatalytic activity is greatly affected by environmental factors. Halogen ions are commonly found in wastewater, which directly affect the pollutant aggregation and sedimentation, therefore it is necessary to discuss their effect on the photodegradation. The current study assesses the halogen ions effect on the photocatalytic degradation of bisphenol A (BPA) using different dosage of sodium chloride (NaCl) and sodium bromide (NaBr). The microstructural characterization of ZnO was conducted by transmission electron microscopy and hydrodynamic size was analyzed through dynamic light scattering. Degradation reactions of BPA with ZnO NPs followed pseudo-first-order kinetics. The increase of ZnO dosage from 0.01 g/L to 0.1 g/L enhanced the degradation rate constant of BPA up to 0.089 min− 1 (14.8 folds). In order to evaluate the the role halogen ions to degrade BPA, NaBr and NaCl were used. The degradation rate was reduced up to 26 folds (0.0034 min− 1) after the addition of NaBr, which was attributed to the increase in hydrodynamic particle size leading, thereby restricting the light adsorption capacity. Noteworthy, upon addition of NaCl from 10 mM to 500 mM concentration, there was only a slight decrease (2.4 folds, 0.037 min− 1) on the degradation rate of BPA. Therefore, this study unveils the role of chloride ions as an effective medium for BPA degradation by ZnO NPs, without aggregation, and provides a novel platform for the treatment of organic pollutants in saline water.
The Impact Of Urban Land Misallocation On Inclusive Green Growth Efficiency
Authors: He Qin , Du Juntao
Published: May 2021

Inclusive green growth (IGG), as a new way to attain sustainable development, aims to achieve comprehensive and coordinated economic, social, and environmental development. How to define IGG and explore its driving factors is key to realizing IGG. This study takes China as an example, using panel data from 30 provinces in mainland China from 2009 to 2018 for research. The epsilon-based measure (EBM) model and Global Malmquist–Luerberger (GML) index are used to evaluate China's inclusive green growth efficiency (IGGE), and a spatial panel regression model of the impact of urban land resource misallocation on IGGE is established. The research found that (1) China's IGGE level from 2009 to 2018 displayed an upward trend, and combined with exploratory spatial data analysis (ESDA), it was found that IGGE has an obvious spatial correlation; (2) the regression model shows that the misallocation of land resources hinders the improvement of IGGE in China; and (3) the decomposition of spatial spillover effects demonstrates that the misallocation of land resources has negative externalities, which will also have adverse effects on neighboring areas.
Comparative genome analysis of commensal segmented filamentous bacteria (SFB) from turkey and murine hosts reveals distinct metabolic features
Authors: Hedblom Grant , Dev Kamal , Bowden Steven , Baumler David
Published: May 2021

Background: Segmented filamentous bacteria (SFB) are intestinal commensal microorganisms that have been demonstrated to induce the innate and adaptive immune responses in mouse and rat hosts. SFB are Gram-positive, spore-forming bacteria that fail to grow in vitro due to unique metabolic requirements. Recently, SFB have been implicated in improved health and growth outcomes in commercial turkey flocks. To assess the nature of SFB in turkeys and how they may differ from mammalian-associated SFB, the genome of turkey-associated SFB was compared with six representative genomes from murine hosts using an in silico approach.Results: The SFB-turkey genome is 1.6 Mb in length with a G+C content of 26.14%, and contains 1,604 coding sequences (CDS). Comparative genome analyses revealed that all the seven SFB strain possesses a shared set of metabolic deficiencies and auxotrophies, specifically the inability of all the SFB strains to synthesize most of the amino acids, nucleotides and cofactors, emphasizing the importance of metabolite acquisition from the host intestinal environment. Among the seven SFB genomes, the SFB-turkey genome is the largest and contains the highest number of predicted CDS. The SFB-turkey genome possesses cellular metabolism genes that are absent in the rodent SFB strains including catabolic pathways for sucrose, stachyose, raffinose and other complex glycans. Other unique genes associated with SFB-turkey genome is loci for the biosynthesis of biotin, and degradation enzymes to recycle primary bile acids, both of which may play an important role to help turkey associated SFB survive and secure mutualism with its avian host. Conclusions: Comparative genomic analysis of seven SFB genomes revealed that each of the strains have a core set of metabolic capabilities and deficiencies that make these bacteria challenging to culture ex vivo. When compared to the murine-associated strains, turkey-associated SFB serves as a phylogenetic outgroup and a unique member among all the sequenced strains of SFB. This turkey-associated SFB strain is the first reported non-mammalian SFB genome, and highlights the impact of host specificity on the evolution of metabolic capabilities.
Spatial Scaling of Land Use/Land Cover And Ecosystem Services Across Urban Hierarchical Levels: Patterns And Relationships
Authors: Sun Xiao , Ma Qun
Published: May 2021

Context Land use/land cover (LULC) patterns seriously affect the ecosystem services (ESs), especially in highly developed urban agglomerations. Exploring how LULC and ESs change spatially across urban hierarchical levels and understanding the possible mechanisms can promote the sustainable planning of urban landscapes. Objectives By mapping the spatial patterns of LULC and ESs in three largest urban agglomerations of China, this study aimed to (1) identify the scaling relations of LULC and ESs across different urban hierarchical levels, (2) explore the possible mechanisms of these two types of spatial scaling, and (3) explore how the scaling relations of ESs response to LULC and its policy implications. Methods Based on LULC, we used the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model and other biophysical models to quantify ES indicators. Then, scalograms were used to quantify the scaling relations of LULC and ESs with respect to changing spatial extent. Results Developed land and cropland exhibited the most predictable responses with changing spatial extent. Compared to other ESs, provisioning services were the most predictable. The predictable scaling relations of ESs at different urban hierarchical levels fell into two general types: power laws at the city proper level and exponential relationships at the metropolitan region and urban agglomeration levels. Conclusions The scaling relations of both LULC and ESs varied across urban hierarchical levels. The spatial scaling of ESs was closely related to LULC patterns. Integrating the scaling relations of ESs into land use planning can help decision-makers formulate multi-scale landscape conservation strategies.
Correlation of Residents’ Performance in Competency-Based Exams and Orthopaedic In- Training Examinations (OITE)
Authors: Okoro Tosan , Mironova Polina , Sathiyamoorthy Thrmiga , Hall Jermey , Ferguson Peter , Nousianien Markku , Williams Jack , Kreder Hans , Axelrod Terry , Dwyer Tim , Safir Oleg , Kraemer William , Tomescu Sebastian , Mastrogiacomo Frank , Weiler Peter , Wright Stewart , Borland Steven , MacGregor Tyler , Zaulan Yaron , Ganz Eitan , Crookshank Meghan , Felice Hilary , Mann Jennah , Murnaghan John , Gargan Martin , Elgoff Christian , Wong Paul , Walton Christine , Whatley Ian , Peck Jonathan , Wadey Veronica
Published: May 2021

Background: The research team aimed to assess the relationship between performance in a competency-based curriculum (CBC) evaluation, and the Orthopaedic In-Training Examination (OITE) in the Postgraduate Year 1 (PGY1) cohort of 2016-2017.Methods: After development of the ‘Basic Trauma’ (BHT) and ‘Basic Arthroplasty’ (BA) CBC modules, assessment consisted of multiple-choice questions (MCQ), objective structured clinical evaluation (OSCE), structured oral panels, and the OITE were conducted annually. We collated MCQ and OSCE evaluations for BHT and BA, as well as the OITE result for the same cohort from PGY1 and the end of PGY2. We evaluated the OITE score difference for correlation with the scores attained for the two CBC modules.Results: Among all participants (n=9), there was a significant improvement in mean OITE scores from PGY1 to PGY2 (43.78% (±4.09) to 56.67% (±4.24); t-test p= 0.00). There was no significant correlation between OITE improvement, and scores attained in the BHT and BA modules, nor between BHT and BA results and the ‘Hip and Knee’ and ‘Trauma’ domains of the OITE exam.Conclusions: Improvement in OITE performance is not dependent on evaluated CBC modules. Further research to determine what factors play a role in trainee improvement in objective performance is required.
Is There a Decreased Risk of Bronchopulmonary Dysplasia Treated With High-Flow Nasal Cannulae Compared to Cpap? A Systematic Review and Meta-Analysis of Randomized Clinical Trial
Authors: Brito Sabrina , Tsopanoglou Sabrina , Galvão Endi , de Deus Franciele , Lima Vanessa
Published: May 2021

Background

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects the premature lung, and to reduce its incidence has been used non-invasive ventilatory support, such as continuous positive airway (CPAP) and high-flow nasal cannula (HFNC). Thus, the objective of this review was to assess whether the use of high flow nasal cannula (HFNC) compared to continuous positive airway pressure (CPAP) decreases the risk of bronchopulmonary dysplasia (BPD) in premature newborns.
Methods

The protocol was registered (Prospero: CRD42019136631) and the search was conducted in the MEDLINE, PEDro, Cochrane Library, CINAHL, Embase, and LILACS databases, and in the clinical trials registries, until July 2020. We included randomized clinical trials comparing HFNC versus CPAP use in premature infants born at less than 37 weeks of gestational age. The main outcome measures were the development of BPD, air leak syndrome, and nasal injury. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool and the GRADE system was used to summarize the evidence recommendations. Meta-analyses were performed using software R.
Results

No difference was found between HFNC or CPAP for the risk of BPD (RR: 1.09; 95% CI: 0.90–1.32), air leak syndrome (RR: 1.04; 95% CI: 0.57–0.90), and nasal trauma (RR: 2.37; 95% CI: 0.92–6.13), with a very low level of evidence.
Conclusion(s):

the HFNC showed similar results when compared to CPAP in relation to the risk of BPD, air leak syndrome, and nasal injury. In the literature, no randomized clinical trial has been found with BPD as the primary outcome to support possible outcomes.
Microbial sources of exocellular DNA in the ocean
Authors: Linney Morgan , Eppley John , Romano Anna , Luo Elaine , DeLong Edward , Karl David
Published: May 2021

Dissolved DNA (D-DNA) is operationally defined as DNA that passes through a 0.1 micrometer filter. It is composed of vesicles, viruses, and exocellular free DNA (F-DNA) and is ubiquitous in all aquatic systems, although the sources, sinks, and ecological consequences are largely unknown. Using a method that provides separation of vesicles, viruses, and F-DNA, we compared open ocean depth profiles of metagenomic DNA associated with each fraction. Pelagibacter-like DNA dominated the vesicle fractions for all samples examined over a depth range of 75–500 m. The viral DNA fraction was composed predominantly of myovirus-like and podovirus-like DNA, and contained the highest proportion of unannotated sequences. Euphotic zone F-DNA (75–125 m) contained mostly bacterial and viral sequences, with bacteria dominating in the mesopelagic (500–1000 m). A high proportion of mesopelagic (500 and 1000 m) F-DNA sequences appeared to originate from surface waters, including a large amount of DNA contributed by high-light Prochlorococcus species. Throughout the water-column, but especially in the mesopelagic, the composition of F-DNA sequences was not always reflective of co-occurring microbial communities that inhabit the same sampling depth. These results highlight the composition of F-DNA in different regions of the water-column (euphotic and mesopelagic zones), with implications for dissolved organic matter cycling and export (by way of sinking particles and/or migratory zooplankton) as a delivery mechanism.
Underlying factors and challenges of implementing an urban family physician program in Iran
Authors: Mehrolhassani Mohammad Hossein , Jahromi Vahid Kohpeima , Dehnavieh Reza , Iranmanesh Mahla
Published: May 2021

Background: the family physician program was launched in 2005 in rural areas, and also as a pilot in 2012 in cities of Fars and Mazandaran provinces due to insufficient coverage of health system in these cities. However, despite its pivotal role in the health system programs, it has not progressed according to its initial policies. Therefore, the purpose of this study was to explain the underlying factors and challenges of implementing an urban family physician program in Iran.Methods: This is a qualitative study, which was conducted on 44 policymakers and managers at national and provincial levels who entered the study with snowball and purposeful sampling with maximum variation. MAXQDA-2020 software was used to manage the data, which were analyzed by directed content analysis. For this purpose, a triangulation method was used.Results: Data analysis resulted in the formation of 10 main categories, 18 sub-categories and 29 codes. Most challenges in the dimension of underlying factors included precipitancy, economic sanctions, believing in traditional medicine, believing in the expertise of previous physician, and global ranking of countries. Also, in the dimension of program implementation, most challenges included diversity of insurance organizations, budget allocation, referral system, electronic file, educational system and culture building.Conclusions: the findings showed that the most important challenge in the dimension of underlying factors included international pressure for reforms and precipitancy in the implementation of programs due to changes in management. Also, these challenges in the dimension of program implementation included budget provision and interaction with insurance organizations. Therefore, for the expansion of program to other provinces in Iran, the factors identified in this study should be carefully considered so that, sufficient confidence, commitment and guarantee would be created for all stakeholders.
Real-Time Decision-Making on Whether to Incorporate Neurorehabilitation Technology: Informing Developers on a Day in the Life of a Therapist
Authors: Celian Courtney , Swanson Veronica , Shah Maahi , Newman Caitlin , Fowler-King Bridget , Gallik Sarah , Reilly Kaitlin , Reinkensmeyer David J. , Patton James , Rafferty Miriam R.
Published: May 2021

Background
Neurorehabilitation engineering faces numerous challenges to translating new technologies, but it is unclear which of these challenges are most limiting. Here we focus on tracing the real-time behavior and rehabilitation technology (RT) use decisions of the primary gatekeepers of RT: rehabilitation therapists.
Methods
Three OTs and two PTs employed at a major, technology-encouraging rehabilitation hospital wrote vignettes from a written prompt describing their RT use decisions during treatment sessions with nine patients (4 with stroke, 2 traumatic brain injury, 1 spinal cord injury, 1 with multiple sclerosis). We then coded the vignettes using deductive qualitative analysis from 17 constructs derived from the RT literature and the Consolidated Framework for Implementation Research (CFIR) to analyze the vignettes. Data were synthesized using summative content analysis.
Results
Of the constructs recorded, the five most prominent are from CFIR determinants of: (i) relative advantage, (ii) personal attributes of the patients, (iii) clinician knowledge and beliefs of the device/intervention, (iv) complexity of the devices including time and setup, and (v) organizational readiness to implement. Therapists characterized candidate RT as having a relative disadvantage compared to conventional treatment due to lack of relevance to functional training. RT design also often failed to take into account the multi-faceted personal attributes of the patients, including diagnoses, goals, and physical and cognitive limitations. Clinicians’ comfort with RT was increased by their previous training but was decreased by the perceived complexity of RT. Finally, therapists have limited time to gather, setup, and use RT.
Conclusions
Despite decades of design work aimed at creating clinically useful RT, many lack compatibility with clinical translation needs in inpatient neurologic rehabilitation. New RT continue to impede the immediacy, versatility, and functionality of hands-on therapy mediated treatment with simple everyday objects.
A novel machine learning-based approach for the computational functional assessment of pharmacogenomic variants
Authors: Pandi Maria-Theodora , Koromina Maria , Tsafaridis Iordanis , Patsilinakos Sotirios , Christoforou Evangelos , Spek Peter J van der , Patrinos George P
Published: May 2021

Background: The field of pharmacogenomics focuses on the way a person’s genome affects his or her response to a certain dose of a specified medication. The main aim is to utilize this information to guide and personalize the treatment in a way that maximizes the clinical benefits and minimizes the risks for the patients, thus fulfilling the promises of personalized medicine. Technological advances in genome sequencing, combined with the development of improved computational methods for the efficient analysis of the huge amount of generated data, have allowed the fast and inexpensive sequencing of a patient’s genome, hence rendering its incorporation into clinical routine practice a realistic possibility. Results: The potential availability of a vast number of identified genetic variants in a clinical setting highlights the necessity of developing a method to evaluate and prioritize this information towards its exploitation in guiding medication or dosing scheme systematically and effectively. In this direction, the present study examines the development of a computational model that can classify new variants according to their possible effects on protein function, which in turn affects drug response, by using as a training set a dataset of functionally validated single nucleotide variants (SNVs) located in pharmacogenes. Conclusion: Overall, the proposed model holds promise to lead to an extremely useful variant prioritization and scoring tool with interesting clinical applications in pharmacogenomics.
Probability of the Alzheimer’s disease based on common and rare genetic variants
Authors: Escott-Price Valentina , Schmidt Karl Michael
Published: May 2021

Background: Alzheimer’s disease, among other neurodegenerative disorders, spans decades in individuals’ life and exhibits complex progression, symptoms and pathophysiology. Early diagnosis is essential for disease prevention and therapeutic intervention. Genetics may help identify individuals at high risk. As thousands of genetic variants may contribute to the genetic risk of Alzheimer’s disease, the polygenic risk score (PRS) approach has been shown to be useful for disease risk prediction. The APOE- ε4 allele is a known common variant associated with high risk to AD, but also associated with earlier onset. Rare variants usually have higher effect sizes than common ones; their impact may not be well captured by the PRS. Instead of standardised PRS, we propose to calculate the disease probability as a measure of disease risk that allows comparison between individuals. Methods: We estimate AD risk as a probability based on PRS and separately accounting for APOE, AD rare variants and the disease prevalence in age groups. The mathematical framework makes use of genetic variants effect sizes from summary statistics and AD disease prevalence in age groups. Results: The AD probability varies with respect to age, APOE status and presence of rare variants. In age group 65+ the probability of AD grows from 0.03 to 0.18 (without APOE), and 0.07 to 0.7 (APOE e4e4 carriers) as PRS increases. In 85+, these values are 0.08-0.6 and 0.3-0.85. Presence of rare mutations, e.g. in TREM2, may increase the probability (in 65+) from 0.02 at the negative tail of the PRS to 0.3.Conclusions: Our approach accounts for the varying disease prevalence in different genotype and age groups when modelling the APOE and rare genetic variants risk in addition to PRS. This approach can be directly implemented in a clinical setting and easily updated for novel rare variants and for other populations when appropriate ethnic GWASes appear.
Effect of HMG on Pregnancy Outcomes in Patients undergoing IUI Cycle -An Analysis of 1230 IUI Cycles
Authors: Ou Miaoxian , Lin Han , Xu Pei , Ma Kaichi , Liu Mingxing
Published: May 2021

Background: This aim of this study was to evaluate the effect of human menopause gonadotropin (HMG) on pregnancy outcomes of infertility patients with intrauterine insemination (IUI) treatments.Methods: This retrospective cohort study analyzed couples using 75 IU HMG as initiate ovarian stimulation method for IUI from January 2015 to December 2019. Couples were divided into four groups according to a total dose of HMG: 189 cycles with a dose <500 IU, 601 with a dose 500 to1000 IU, 199 with a dose 1000 to 1500 IU and 241 with a dose ＞1500 IU. The differences in baseline characteristics and pregnancy outcomes including among the four groups were investigated. We used a logistic regression model to further study the association between various doses of HMG and pregnancy outcomes and adjusted for confounding factors.Results: The study included 792 couples with 1230 cycles, and pregnancy was achieved in 212 (17.2%) cycles, while live birth was achieved in 176 (14.3%) cycles. Stratified analyses revealed that a higher dose of HMG was associated with increased pregnancy rate (PR), live birth rate (LBR), endometrial thickness (EMT) on insemination day, number of follicle ≥18 mm, serum estrogen 2( E2) level, and EMT on the trigger day among four groups, which were all statistically different (P＜0.05). The logistic regression indicated that both PR and LBR were positively associated with the total dose and day of HMG, which were statistically different (P＜0.05).Conclusion: Increasing the total dose and day of HMG may benefit the serum E2 level, EMT, follicle development, and pregnancy outcomes in 75IU HMG stimulated IUI cycles.
Circulating levels of asprosin and its association with insulin resistance and renal function in type2 diabetes mellitus and diabetic nephropathy patients
Authors: Goodarzi Golnoosh , Setayesh Leila , Fadaei Reza , Khamseh Mohammad Ebrahim , Aliakbari Fereshteh , Hosseini Jalil , Moradi Nariman
Published: May 2021

Introduction
: Adipokines have an important role in development and progression of type 2 diabetes mellitus (T2DM) and its complications such as nephropathy. Asprosin is a recently discovered adipokine that involve in glucose metabolism and inflammation process. The present study sought to evaluate asprosin levels in patients with T2DM and T2DM + nephropathy (NP) compared to controls and its relation with markers of insulin resistance, inflammation and renal function.
Methods
Serum levels of asprosin, adiponectin, IL-6 and TNF-α were measured in 55 control, 54 T2DM and 55 T2DM + NP patients using ELISA kits.
Results
Asprosin was found to be higher in T2DM (6.73 ± 1.67) and T2DM + NP (7.11 ± 1.54) compared to controls (4.81 ± 1.09) (p < 0.001), while adiponectin indicated a lower concentration in both patient groups compared with controls. Moreover, IL-6 and TNF-α indicated higher levels in both patients group compared with controls. Asprosin indicated a positive correlation with HbA1c, FBG, TC, LDL-C, IL-6 and TNF-α in T2DM group. In the patients with T2DM + NP asprosin positively correlated with BMI, HbA1c, insulin, HOMA-IR, Cr, UAE, IL-6 and TNF-α and inversely correlated with eGFR.
Conclusion
Higher concentration of asprosin in T2DM and T2DM + NP and its relation with glucose and lipid metabolism, and markers of renal function and inflammation suggested a possible role for this adipokine in the pathogenesis of T2DM and nephropathy.
Autoantibody of Interleukin-17A Induced by Recombinant Mycobacterium Smegmatis Attenuates Airway Inflammation in Neutrophilic Asthma
Authors: Chen Ling , Xu Wanting , Mao Song , Zhu Ruochen , Zhang Jianhua
Published: May 2021

Asthma is a chronic inflammatory disorder, previous studies have shown Interleukin (IL)-17A is an important contributor to the development of severe asthma characterized by intense neutrophilic inflammation and less responsive to corticosteroid. Hence, IL-17A-neutrophil axis may be a potential therapeutic target for asthma. In our previous work, we constructed a recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS) and confirmed that it could induce the production of IL-17A autoantibody in vivo. Here, in the present study, we aim to further investigate the effects of the rMS on airway inflammation and explore the underlying mechanisms in a murine model of neutrophilic asthma. The murine model of neutrophilic asthma was established with ovalbumin (OVA), and mice were intranasally vaccinated with rMS, then IL-17A autoantibody in sera was detected, and its anti-inflammatory effects on inflammatory cell infiltration and expression of inflammatory mediators involved in IL-17A-neutrophil axis in bronchoalveolar lavage fluid (BALF) as well as histopathological changes of lung tissues were evaluated. The data showed that sustained high-titer of IL-17A autoantibody was detected in rMS group, intranasal vaccination significantly decreased inflammatory cells, cytokines and chemokines related to IL-17A-neutrophil axis in BALF, suppressed the activity of neutrophil enzyme, and histological analysis manifested the rMS remarkably reduced inflammatory cell infiltration, mucus secretion and airway epithelial thickness. Overall, these results demonstrate the rMS ameliorated airway inflammation in mice with neutrophilic asthma via inducing IL-17A autoantibody and regulating the IL-17A-neutrophil axis, thus providing a possible novel treatment in neutrophilic asthma.
Evaluating Polymers Interplay to Investigate Lignocellulose Recalcitrance
Authors: Leroy Amandine , Falourd Xavier , Foucat Loïc , Méchin Valérie , Guillon Fabienne , Paës Gabriel
Published: May 2021

Background : Biomass recalcitrance is governed by various molecular and structural factors but there is still a lack of understanding on the interplay between these multiscale factors. In this study, hot water pretreatment (HWP) was applied to maize stem internode in order to highlight the impact of polymer interactions and their ultrastructure on the accessibility and recalcitrance of the lignocellulosic biomass. The impact of HWP were analysed at different scales, from the polymers ultrastructure or water mobility to the cell wall organization by combining complementary compositional, spectral and NMR analysis. Result : HWP increased the kinetics and yield of saccharification. The chemical characterization showed that HWP altered cell wall composition with a loss of hemicelluloses (up to 45% for HWP 40 min) and of ferulic acid cross-linking, associated with a lignin enrichment. The lignin structure was also altered (up to 35% decrease of β-O-4 bonds), associated to a slight depolymerization/repolymerization depending on the treatment time. The increase of the T 1 ρ H , T HH and specific surface area (SSA) showed that the cellulose environment was looser after pretreatment. These changes were related to an increase of the accessibility of more constrained water to the cellulose across 5–15 nm pore size range. Conclusion : The loss of hemicelluloses and changes in polymers structural features induced by HWP leads to reorganization of the lignocellulosic matrix. These modifications led to an increase in the SSA and a water redistribution allowing an increase in the accessibility of cellulases and an enhancement of the hydrolysis. Interestingly, the lignin content had no negative effect on the enzymatic hydrolysis but a higher lignin condensed state seemed to promote saccharification. The environment and organization of lignin is thus more important to consider than its concentration to explain cellulose accessibility. Elucidating the interactions between polymers is the key to understanding LB recalcitrance and to find the best severity conditions to optimise HWP in sustainable biorefineries.
Strata and Surface Influence Range of Deep Coal Mining for Mine Land Reuse
Authors: Li Huaizhan , Guo Kaikai , Guo Guang-li
Published: May 2021

The rational assessment and determination of strata and surface influence range of underground coal mining is straightly associated to the safe production of the wellbore, the reuse of mine land and the regional development. With the depth of coal mining in the world increasing, if the boundary curve of strata and surface movement continues to be considered as a straight line, there will be a great deviation from the real situation, which will seriously waste the land resources of mining area. To solve this issue, the numerical simulation methods were employed to investigate the stratum and surface movement boundary curves of deep caving and backfilling mining in this paper. The findings indicated that: 1) The strata and surface movement boundary of deep caving and backfilling mining were all curves, and they were in accordance with the exponential function, but the influence range of strata and surface movement of deep different mining methods were different; 2) The backfilling rate of deep backfilling mining had an influence on movement boundary of strata and surface. With the backfilling rate decreasing, the influence range of strata and surface movement boundary were increased. 3) The research results were applied to a case in order to confirm the new methods for determining the influence range of strata and surface movement of deep mining. Example application shows that the safe production of the wellbore not only can be guaranteed, but also the reuse area of the mine field can be enhanced.
ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition
Authors: Zhang Qinglin , Nie He , Sun Jing , Pan Jiadong , qiang zhan
Published: May 2021

Background: Irradiation-induced radioresistance often leads to the therapeutic failure of colon cancer. By regulating the redistribution of intracellular zinc, ZIP7 plays a dominating role in the activation of many critical signaling pathways in the progression of tumors. However, the relationship between ZIP7 and radioresistance is still unclear. Methods: ZIP7 expression of colon cancer was evaluated by analyzing public data from the GEPIA and CPTAC databases and validated based on immunohistochemistry (IHC) staining. Clonogenic survival assay was employed to examine the influence of intracellular zinc interference and ZIP7 knockdown on radioresistance of colon cancer, based on radioresistant colon cancer cells. At last, Western blot was performed to preliminarily explore the potential mechanisms. Results: ZIP7 was significantly upregulated in human colon cancers compared with adjacent normal tissues. ZIP7 knockdown could significantly reduce the radioresistance of colon cancer cells, while transmembrane ionophore of zinc could partially reverse this effect. In terms of mechanisms, ZIP7 knockdown significantly reversed the radiation-induced expression of elevated ZEB1 and down-regulated E-cadherin through regulating zinc. Conclusion: ZIP7 is crucial to maintain radioresistance of colon cancer cells through regulation of zinc distribution, and at least partially by maintenance of epithelial-mesenchymal transition (EMT).
Characteristics and recognition of guardians living in the urgent protective action planning zone of the Genkai Nuclear Power Plant, Saga Prefecture, Japan who wished to receive pre-distribution stable iodine for their children
Authors: Matsunaga Hitomi , Orita Makiko , Taira Yasuyuki , Takamura Noboru
Published: May 2021

Purpose：The aim of this study was to clarify the characteristics and the awareness of nuclear prevention measures including prophylactic stable iodine (SI) of guardians of 0- to 6-year-old children living in the urgent protective action planning zone (UPZ) of the Genkai Nuclear Power Plant (GNPP), Japan. Methods：Of these 1172 guardians, 973 responded that they wished to receive pre-distribution of stable iodine (PDSI) and 199 did not wish to receive PDSI. Results: Logistic regression analysis showed that the following items were independently associated with guardians who wished to receive PDSI for their children: thinking that pregnant women should take prophylactic SI (odds ratio [OR]=6.57, 95% confidence interval [CI]: 4.62–9.35; p<0.01); wishing to participate in a lecture about the health effects of radiation exposure (OR=1.99, 95%CI: 1.40–2.82; p<0.01); thinking that SI can prevent exposure from all radionuclides (OR=1.93, 95%CI: 1.24–2.99; p<0.01); awareness of SI before the study (OR=1.91, 95%CI: 1.35–3.00; p<0.01); and anxiety about prophylactic SI for their children (OR=0.33, 95%CI: 0.20–0.55; p<0.01). The GNPP was one of the nuclear power plants in Japan that resumed operations after the Fukushima Dai-ichi Nuclear Power Plant accident in 2011. Conclusion: These results suggest that some residents have incomplete knowledge about nuclear prevention, including SI. Therefore, it is essential to educate residents and communicate the health risks of radiation exposure with residents living around nuclear power plants. Furthermore, it is important to train specialists to educate and communicate with residents to prepare for a nuclear accident.
Human Umbilical Cord Mesenchymal Stem Cell (HUCMSC)-derived Exosomes as a Cell-Free Therapy for Soluble Fms-like Tyrosine Kinase-1 (Sflt-1)-induced Endothelial Dysfunction in Preeclampsia
Authors: CHANG XINWEN , HE QIZHI , WANG MINGMIN , JIA LINYAN , DUAN TAO , WANG KAI
Published: May 2021

BackgroundPreeclampsia is a unique multisystem disorder that affects 5-8% of pregnancies. A high level of soluble fms-like tyrosine kinase-1 (sFlt-1) is a hallmark of preeclampsia that causes endothelial dysfunction. Exosomes derived from mesenchymal stem cells (MSCs) have been indicated to improve endothelial performances by transporting signals to target cells. We hypothesized that exosomes derived from MSCs have potential effects against preeclampsia. MethodsWe collected human umbilical cord MSC-derived exosomes (HUCMSC-exos) by ultracentrifugation. The size and morphology of the exosomes were examined using a transmission electron microscope and nanoparticle tracking analysis. Pregnant mice were injected with murine sFlt-1 adenovirus to build the preeclampsia-like mouse model and then treated with HUCMSC-exos. Human umbilical vein endothelial cells (HUVECs) were infected with lentiviruses expressing tet-on-sFlt-1 to obtain cells overexpressing sFlt-1. Cell proliferation and migration assays were used to measure the endothelial functions. The exosomes enriched proteins underlying mechanisms were explored by proteomic analysis.ResultsIn the current study, we successfully collected the cup-shaped HUCMSC-exos with diameters of 30-150 nm. In the sFlt-1-induced preeclampsia mouse model, HUCMSC-exos exhibited beneficial effects on adverse birth events by decreasing blood pressure and improving fetal birth weight. In addition, preeclamptic dams that were injected with HUCMSC-exos had rebuilt dense placental vascular networks. Furthermore, we observed that HUCMSC-exos partially rescued sFlt-1-induced HUVECs dysfunction in vitro. Proteomics analysis of HUCMSC-exos displayed functional enrichment in biological processes related to vesicle-mediated transport, cell communication, cell migration, and angiogenesis.ConclusionWe propose that exosomes derived from HUCMSCs play beneficial roles in the birth outcomes of sFlt-1-induced preeclamptic mice by promoting angiogenesis.
Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice
Authors: Yang Chunxing , Qiao Tao , Yu Jia , Wang Hongyan , Guo Yangsu , Salameh Johnny , Metterville Jake , Parsi Sepideh , Brown Robert H. , Cai Huaibin , Xu Zuoshang
Published: May 2021

Background: Modestly elevated levels of transactive response DNA binding protein (TDP-43) gene have been reported in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neuromuscular diseases. However, whether this modest elevation triggers neurodegeneration is not known. Although high levels of TDP-43 overexpression have been modeled in mice and shown to cause early death, models with low-level overexpression that mimic the human condition have not been established. In this study, we tried to fill this knowledge gap.Methods: Transgenic mice overexpressing wild type TDP-43 at less than 60% above the endogenous CNS levels were constructed, and their phenotypes were analyzed by a variety of techniques, including biochemical, molecular, histological, behavioral techniques and electromyography.Results: The TDP-43 transgene was expressed in neurons, astrocytes, and oligodendrocytes in the cortex and predominantly in astrocytes and oligodendrocytes in the spinal cord. The mice developed a reproducible progressive weakness ending in paralysis in mid-life. Detailed analysis showed ~30% loss of large pyramidal neurons in the layer V motor cortex; in the spinal cord, severe demyelination was accompanied by oligodendrocyte injury, protein aggregation, astrogliosis and microgliosis, and elevation of neuroinflammation. Surprisingly, there was no loss of lower motor neurons in the lumbar spinal cord despite the complete paralysis of the hindlimbs. However, denervation was detected at the neuromuscular junction.Conclusions: Low-level TDP-43 overexpression can cause diverse aspects of ALS, including late-onset and progressive motor dysfunction, neuroinflammation, and neurodegeneration. These results demonstrate that modest elevations in TDP-43 expression may underlie not only ALS but also other neuromuscular disorders involving TDP-43 proteinopathy. Because of the predictable and progressive clinical paralytic phenotype, this transgenic mouse model may also be useful in preclinical trial of therapeutics targeting neurological disorders associated with elevated levels of TDP-43.
Health Status Transitions Related to Traumatic Brain Injury.
Authors: Escobar Michael , Mollayeva Tatyana , Tran Andrew , Chan Vincy , Colantonio Angela , Sutton Mitchell
Published: May 2021

For centuries, the study of traumatic brain injury (TBI) has been centred on historical observation and analyses of personal, social, and environmental processes, which have been examined separately. Today, however, computation implementation and vast patient data repositories are producing datasets of such volume and complexity as to challenge traditional scientific methodology. Drastically different approaches show great promise for research on TBI. We report a computational analysis of health status over time using population-wide health administrative data of patients with TBI. Our approach facilitates health status at injury event evaluation and classification, and unfolds health status trajectories, from that of preceding injury to the injury event itself, as they concern external causes of injury and injury severity. Taken together, the contrasting and interwoven aspects of health status on a time continuum can influence injury event trajectories and should be considered in TBI risk analysis for the improvement of diagnosis, treatment, and prevention.
Remimazolam protects against LPS-induced endotoxicity improving survival of endotoxemia mice
Authors: Liu Xiaolei , Lin Shaoping , Zhong Yiyue , Shen Jiaojiao , Zhang Xuedi , Luo Shuhua , Zhang Liangqing , Zhou Shuangnan , Tang Jing
Published: May 2021

Background: Remimazolam is a new benzodiazepine of sedative drugs with an ultra-short-acting anesthetic effect, being commonly used for critically ill patients (especially septic patients) in intensive care units (ICUs). Although some anesthetics have been reported to show certain anti-inflammatory effects, the role of remimazolam in inflammation is still remained unknown.Methods: In the present study, LPS-induced endotoxemia mice were used to observe the effect of remimazolam in vivo. LPS-stimulated bone marrow cells and Raw 264.7 cells were used to evaluate the influence of remimazolam on macrophage in vitro.Results: Compared with LPS treatment group, remimazolam remarkably improved survival rate of endotoxemia mice and decreased the release of LPS-induced inflammatory mediators, such as TNF-a, IL-6 and IL-1b. Remimazolam not only inhibited the activation of MyD88 and PI3K signal pathway at 15min after LPS treatment but also disturb Rab5a related TLR4 expression at cell surface in response to LPS at later time.Conclusions: Remimazolam inhibit LPS‑induced inflammatory responses of macrophages and obviously improve the survival rate of endotoxemia mice.