bluuebunny/crossref_metadata_2025 huggingface dataset:
Maxillary Canine with two roots and two canals: A case report
Authors: Victorino Fausto Rodrigo , Rocha Isabela Silva , Lazarin Rafael de Oliveira , Seron Marcelo Augusto , Sivieri-Araujo Gustavo , Almeida Ricardo Sérgio
Published: February 2021

Introduction: Knowledge of the anatomy and root canal system is of fundamental importance for a successful endodontic treatment. Maxillary canines unusually possess two root canals. Aim: The present study aims to present a maxillary canine with two roots and two canals through a clinical case. Case report: A male patient was referred for the treatment of a root perforation of the tooth 23. Clinical examination revealed the presence of vestibular fistula and mild pain with vertical and horizontal percussion. Through a tomographic examination, the presence of two roots and two root canals was observed in addition to a radiolucent lesion at the middle third of the roots but without perforation in the middle third. Coronary opening and the localization of the vestibular and palatal canals were performed. The root canal length was performed with Romi Apex A-15® foraminal locator and instrumentation was conducted by using Protaper Next® system. Due to the presence of fistula, calcium hydroxide manipulated with propylene glycol was used as intracanal medication for 30 days. After this period, the root canals were filled with gutta-percha and AH Plus® cement and a new tomographic examination was undertaken, which confirmed the complete filling of the root canals and the absence of root perforation. Conclusion: Given the above, endodontic professionals shall be aware of possible anatomical variations and make use of auxiliary resources when appropriate, such as cone beam computed tomography (CBCT), to ensure correct diagnosis and, consequently, a successful root canal treatment.
Microbiota intestinal nos primeiros mil dias de vida e sua relação com a disbiose
Authors: Almeida Juliane Monteiro de , Nader Roberta Ghetti de Melo , Mallet Aline Cristina Teixeira
Published: February 2021

A medicina moderna considera o intestino como o segundo cérebro, de modo que este é de suma importância tanto para o sistema digestório quanto para o imunológico. Sendo assim, um desequilíbrio intestino pode provocar diversas disfunções, dentre estas, destaca-se a disbiose intestinal. Nesse contexto, a nutrição desempenha um papel relevante no que diz respeito à homeostase intestinal. Portanto, foi realizada uma revisão bibliográfica sobre o tema. Através de pesquisas, foi possível perceber que alguns fatores podem ser atribuídos à alteração da microbiota, como o tipo de parto, tipo de aleitamento, introdução alimentar adequada no momento preconizado pela Organização Mundial de Saúde (OMS), em torno de seis meses. Diante disso, pode-se afirmar que o déficit na colonização e o perfil da microbiota intestinal (MI) adquirido na infância é difícil de ser revertido após os dois anos, sendo capaz de impactar o desenvolvimento neuro cognitivo, crescimento e o aparecimento de doenças.
The representation of trans women in Brazilian magazine covers
Authors: Batista Fabiano Eloy Atilio , Teixeira Débora Pires , Soares Junior Glauber , Oliveira Isadora Franco , Dias Matheus Nicolau , Dantas Ítalo José de Medeiros
Published: February 2021

This work refers to an investigation into the representations of trans women in magazine covers of the national editorial market during the decade of 2010. Methodologically, it is qualitative, descriptive, and bibliographic research. Data collection took place from documents (magazine covers) and the data were analyzed using the Image Analysis technique. As a result, in general terms, we can understand that fashion magazines, in a certain way, sell mass ideas and ways of dealing with the body based on socially imposed standards of beauty - thin, white, and aesthetically impeccable, whereas, the other magazines seek to emphasize plural bodies that are closer to real figures, based on producing cultural values that go beyond aesthetic issues. It is concluded, therefore, that the representations of this social parcel that is so marginalized and culturally stigmatized must be further investigated, to broaden discussions in the most varied contexts.
Insertos ultrassônicos na desobstrução de canais com pinos de fibra de vidro: estudo in vitro
Authors: Alves-Silva Esdras Gabriel , Medeiros Joseane Beatriz Gurgel de , Medeiros Warlenya Duarte de , Dametto Fábio Roberto , Arruda-Vasconcelos Rodrigo , Louzada Lidiane Mendes , Gomes Brenda Paula Figueiredo de Almeida , Gadê-Neto Cícero Romão
Published: February 2021

Atualmente a escolha de uma adequada restauração de dentes tratados endodonticamente é guiada em parte pela exigência estética. Os pinos intrarradiculares são utilizados quando o remanescente dental não possui um suporte adequado na retenção. Diante das dificuldades para remoção dos pinos de fibra de vidro. O objetivo deste trabalho, in vitro, foi comparar duas técnicas de desgaste de pino de fibra de vidro para desobstrução de canais radiculares. Avaliou-se o tempo para remoção do pino de fibra de vidro. Foram selecionados 26 dentes unirradiculares padronizados em 15 milímetros de comprimento real de trabalho (CRT). O Preparo químico-mecânico foi realizado com o sistema Protaper universal. Após obturação, foi desobturado 10 mm do canal, deixando 5 mm de material remanescente no terço apical. Os pinos foram cimentados de acordo com as orientações do fabricante. Os dentes foram divididos em dois grupos para a remoção do pino: No Grupo 01 (G1), o desgaste de até 7 mm do pino foi realizado utilizando uma broca esférica multilaminada nº 1 (LN), em baixa rotação, associado ao inserto ultrassônico tronco-cônico TRI 01 DA3, sob refrigeração, para o desgaste do remanescente de pino. No Grupo 02 (G2) o desgaste do pino foi feito utilizando o inserto ultrassônico tronco-cônico liso PERIOSUB, sob refrigeração. Foi realizado a cronometragem durante a remoção do pino de fibra de vidro em que G1 obteve média de 290 segundos e o G2 com média de 753 segundos estatisticamente significativo (Test t não pareado p ˂ 0,05). O grupo G1 apresentou menor tempo para remoção do pino de fibra de vidro quando comparado com o G2. A melhor opção para remoção do pino de fibra de vidro parece ser a associação da broca esférica seguido do inserto ultrassônico na remoção de pinos de fibra de vidro.
Bioactive Materials for Soft Tissue Repair
Authors: Mazzoni Elisa , Iaquinta Maria Rosa , Lanzillotti Carmen , Mazziotta Chiara , Maritati Martina , Montesi Monica , Sprio Simone , Tampieri Anna , Tognon Mauro , Martini Fernanda
Published: February 2021

Over the past decades, age-related pathologies have increased abreast the aging population worldwide. The increased age of the population indicates that new tools, such as biomaterials/scaffolds for damaged tissues, which display high efficiency, effectively and in a limited period of time, for the regeneration of the body's tissue are needed. Indeed, scaffolds can be used as templates for three-dimensional tissue growth in order to promote the tissue healing stimulating the body's own regenerative mechanisms. In tissue engineering, several types of biomaterials are employed, such as bioceramics including calcium phosphates, bioactive glasses, and glass–ceramics. These scaffolds seem to have a high potential as biomaterials in regenerative medicine. In addition, in conjunction with other materials, such as polymers, ceramic scaffolds may be used to manufacture composite scaffolds characterized by high biocompatibility, mechanical efficiency and load-bearing capabilities that render these biomaterials suitable for regenerative medicine applications. Usually, bioceramics have been used to repair hard tissues, such as bone and dental defects. More recently, in the field of soft tissue engineering, this form of scaffold has also shown promising applications. Indeed, soft tissues are continuously exposed to damages, such as burns or mechanical traumas, tumors and degenerative pathology, and, thereby, thousands of people need remedial interventions such as biomaterials-based therapies. It is known that scaffolds can affect the ability to bind, proliferate and differentiate cells similar to those of autologous tissues. Therefore, it is important to investigate the interaction between bioceramics and somatic/stem cells derived from soft tissues in order to promote tissue healing. Biomimetic scaffolds are frequently employed as drug-delivery system using several therapeutic molecules to increase their biological performance, leading to ultimate products with innovative functionalities. This review provides an overview of essential requirements for soft tissue engineering biomaterials. Data on recent progresses of porous bioceramics and composites for tissue repair are also presented.
Encapsulation of Andrographolide in poly(lactide-co-glycolide) Nanoparticles: Formulation Optimization and in vitro Efficacy Studies
Authors: Oseni Bukola A. , Azubuike Chukwuemeka P. , Okubanjo Omotunde O. , Igwilo Cecilia I. , Panyam Jayanth
Published: February 2021

Andrographolide is a potential chemopreventive and chemotherapeutic agent that suffers from poor aqueous solubility. Encapsulation in poly(lactide-co-glycolide) (PLGA) nanoparticles can overcome solubility issues and enable sustained release of the drug, resulting in improved therapeutic efficacy. In this study, andrographolide was encapsulated in PLGA nanoparticles via emulsion solvent evaporation technique. Effect of various formulation parameters including polymer composition, polymer molecular weight, polymer to drug ratio, surfactant concentration and the organic solvent used on nanoparticle properties were investigated. A selected formulation was used to determine the effect of encapsulation in nanoparticles on andrographolide’s in vitro anticancer efficacy. Nanoparticles formulated using a polymer with 85:15 lactide to glycolide ratio and ethyl acetate as the organic solvent were found to be optimal based on average hydrodynamic particle size (135 ± 4 nm) and drug loading (2.6 ± 0.6%w/w). This formulation demonstrated sustained release of andrographolide over 48 h and demonstrated significantly greater in vitro anticancer efficacy compared to free drug in a metastatic breast cancer cell line. These results suggest that additional, more in-depth efficacy studies are warranted for the nanoparticle formulation of andrographolide.
Blockchain Enabled Tracking of Physician Burnout and Stressors During the COVID-19 Pandemic
Authors: Dhillon Vikram , Xu Tailong , Parikh Chirag
Published: February 2021

With more than 54 million cases worldwide, the novel coronavirus disease 2019 (COVID-19) has disrupted every aspect of public life and poses an ever-growing burden on an already strained healthcare system. The emergence of new COVID-19 hot-spots and super-spreader events are placing an immense amount of stress on hospital systems responding to the increased influx of critically ill patients. Healthcare workers and frontline physicians disproportionately bear the additional physical and psychological burdens associated with the appearance of a new hot-spot. However, the mental health implications of COVID-19 for physicians are not well understood. In this perspective piece, we discuss widespread effects of the ongoing pandemic on physician mental health and how blockchain infrastructure can enable digital health technologies in supporting data-driven fatigue mitigation interventions. This is particularly applicable to simplifying physician workflows in newly emerging hot-spots.
MiR-199a-5p–HIF-1α-STAT3 Positive Feedback Loop Contributes to the Progression of Non-Small Cell Lung Cancer
Authors: Yang Xingping , Zheng Yuzhen , Tan Jian , Tian Renjiang , Shen Piao , Cai Weijie , Liao Hongying
Published: February 2021

Background: Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. MiR-199a-5p has been reported to play important roles in multiple tumors, inclusive of NSCLC. However, little is definitively known pertaining to its explicit mechanism of action in NSCLC.

Methods: The expressions of miR-199a-5p and hypoxia-inducible factor-1α (HIF-1α) mRNA were quantified employing qRT-PCR. H1299 and A549 cells were transiently transfected with miR-199a-5p mimics or inhibitors. Then, CCK-8 assays, flow cytometry analysis, and Transwell assay were performed for detecting cell proliferation, cell cycle, apoptosis, migration, and invasion of NSCLC cells, respectively. HIF-1α, signal transducer and activator of transcription 3 (STAT3), and p-STAT3 expressions were detected via Western blotting. Bioinformatic analysis and dual-luciferase assay were performed to investigate the interactions among miR-199a-5p, HIF-1α, and STAT3. Xenograft models were established with nude mice for further analyzing the bevacizumab resistance of NSCLC cells.

Results: MiR-199a-5p expression was markedly attenuated in NSCLC tissues and cell lines. Overexpression of miR-199a-5p repressed the proliferation, migration, and invasion but induced the apoptosis of NSCLC cells. HIF-1α was identified as a direct target of miR-199a-5p. There was a positive feedback loop among miR-199a-5p, HIF-1α, and STAT3. Co-transfection of HIF-1α or STAT3 overexpression plasmids counteracted the effects of miR-199a-5p. In vivo experiments indicated that the feedback loop was in association with the bevacizumab resistance of NSCLC cells.

Conclusion: MiR-199a-5p blocked the progression of NSCLC and sensitized NSCLC cells to bevacizumab by suppressing HIF-1α and STAT3, while the HIF-1α/STAT3 axis suppressed the expression of miR-199a-5p, which forms a positive feedback loop to promote the sustaining progression of NSCLC.
Overexpression of Long Non-coding RNA 4933425B07Rik Causes Urinary Malformations in Mice
Authors: Tan Lihong , Yu Minghui , Li Yaxin , Xue Shanshan , Chen Jing , Zhai Yihui , Fang Xiaoyan , Liu Jialu , Liu Jiaojiao , Wu Xiaohui , Xu Hong , Shen Qian
Published: February 2021

Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological mechanism of CAKUT. Recently, participation of long non-coding RNAs (lncRNAs) in the development of the circulatory and nervous systems was demonstrated; however, the role of lncRNAs in the development of the kidney and urinary tract system is unclear. In this study, we used thepiggyBac(PB) transposon-based mutagenesis to construct a mouse with lncRNA4933425B07Rik(Rik) PB insertion (RikPB/PB) and detected overexpression ofRikand a variety of developmental abnormalities in the urinary system after PB insertion, mainly including renal hypo/dysplasia. The number of ureteric bud (UB) branches in theRikPB/PBembryonic kidney was significantly decreased in embryonic kidney culture. Only bone morphogenetic protein 4 (Bmp4), a key molecule regulating UB branching, is significantly downregulated inRikPB/PBembryonic kidney, while the expression levels of other molecules involved in the regulation of UB branching were not significantly different according to the RNA-sequencing (RNA-seq) data, and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR) and immunofluorescence assays. Besides, the expression of pSmad1/5/8, a downstream molecule of BMP4 signaling, decreased by immunofluorescence. These findings suggest that abnormal expression ofRikmay cause a reduction in the UB branches by reducing the expression levels of the UB branching-related moleculeBmp4, thus leading to the development of CAKUT.
Succinylation Regulators Promote Clear Cell Renal Cell Carcinoma by Immune Regulation and RNA N6-Methyladenosine Methylation
Authors: Lu Wenqing , Che Xiaofang , Qu Xiujuan , Zheng Chunlei , Yang Xianghong , Bao Bowen , Li Zhi , Wang Duo , Jin Yue , Wang Yizhe , Xiao Jiawen , Qi Jianfei , Liu Yunpeng
Published: February 2021

Succinylation is a newly discovered and multienzyme-regulated post-translational modification (PTM) that is associated with the initiation and progression of cancer. Currently, no systematic analyses on the role of succinylation regulators in tumors have been reported. In this study, we performed a comprehensive pan-cancer analysis on four well-known succinylation regulators (CPT1A, KAT2A, SIRT5, and SIRT7). We found that these regulators played specific and critical roles in the prognosis of clear cell renal cell carcinoma (ccRCC). We constructed a risk score (RS) based on two independent prognostic prediction factors, CPT1A and KAT2A, and subsequently developed a nomogram model containing the RS, which showed good accuracy in the prediction of overall survival (OS) in ccRCC patients. Furthermore, we used the similar expression pattern of four succinylation regulators according to consensus clustering analysis to divide the patients into three clusters that exhibited prominently different OS as well as clinicopathological characteristics. Differently expressed genes (DEGs) and pathway enrichment analyses of three clusters indicated that succinylation regulators might promote malignant progression of ccRCC by regulating the infiltration of immune cells and RNA N6-methyladenosine (m6A) methylation. Importantly, our data suggest that CPT1A and SIRT5 might up-regulate and down-regulate the expression of LRPPRC and EIF3B, respectively. Our study systematically analyzed the prognostic predictive values of four succinylation regulators and revealed their potential mechanisms in ccRCC aggressiveness. These data provide new insight into the understanding of succinylation modification and present clinical evidence for its role in ccRCC treatments.
Transient Lipid-Protein Structures and Selective Ganglioside Uptake During α-Synuclein-Lipid Co-aggregation
Authors: Gaspar Ricardo , Idini Ilaria , Carlström Göran , Linse Sara , Sparr Emma
Published: February 2021

α-Synuclein is a membrane-interacting protein involved in Parkinson’s disease. Here we have investigated the co-association of α-synuclein and lipids from ganglioside-containing model membranes. Our study relies on the reported importance of ganglioside lipids, which are found in high amounts in neurons and exosomes, on cell-to-cell prion-like transmission of misfolded α-synuclein. Samples taken along various stages of the aggregation process were imaged using cryogenic transmission electron microscopy, and the composition of samples corresponding to the final state analyzed using NMR spectroscopy. The combined data shows that α-synuclein co-assembles with lipids from the ganglioside (GM1)-containing model membranes. The lipid-protein samples observed during the aggregation process contain non-vesicular objects not present at the final stage, thus capturing the co-existence of species under non-equilibrium conditions. A range of different lipid-protein co-assemblies are observed during the time course of the reaction and some of these appear to be transient assemblies that evolve into other co-aggregates over time. At the end of the aggregation reaction, the samples become more homogeneous, showing thin fibrillar structures heavily decorated with small vesicles. From the NMR analysis, we conclude that the ratio of GM1 to phosphatidyl choline (PC) in the supernatant of the co-aggregated samples is significantly reduced compared to the GM1/PC ratio of the lipid dispersion from which these samples were derived. Taken together, this indicates a selective uptake of GM1 into the fibrillar aggregates and removal of GM1-rich objects from the solution.
Inflammatory Cell Recruitment in Cardiovascular Disease
Authors: Marchini Timoteo , Mitre Lucía Sol , Wolf Dennis
Published: February 2021

Atherosclerosis, the main underlying pathology for myocardial infarction and stroke, is a chronic inflammatory disease of middle-sized to large arteries that is initiated and maintained by leukocytes infiltrating into the subendothelial space. It is now clear that the accumulation of pro-inflammatory leukocytes drives progression of atherosclerosis, its clinical complications, and directly modulates tissue-healing in the infarcted heart after myocardial infarction. This inflammatory response is orchestrated by multiple soluble mediators that enhance inflammation systemically and locally, as well as by a multitude of partially tissue-specific molecules that regulate homing, adhesion, and transmigration of leukocytes. While numerous experimental studies in the mouse have refined our understanding of leukocyte accumulation from a conceptual perspective, only a few anti-leukocyte therapies have been directly validated in humans. Lack of tissue-tropism of targeted factors required for leukocyte accumulation and unspecific inhibition strategies remain the major challenges to ultimately translate therapies that modulate leukocytes accumulation into clinical practice. Here, we carefully describe receptor and ligand pairs that guide leukocyte accumulation into the atherosclerotic plaque and the infarcted myocardium, and comment on potential future medical therapies.
Spectroscopic and Photophysical Investigation of Model Dipyrroles Common to Bilins: Exploring Natural Design for Steering Torsion to Divergent Functions
Authors: Staheli Clayton F. , Barney Jaxon , Clark Taime R. , Bowles Maxwell , Jeppesen Bridger , Oblinsky Daniel G. , Steffensen Mackay B. , Dean Jacob C.
Published: February 2021

Biliproteins are a unique class of photosynthetic proteins in their diverse, and at times, divergent biophysical function. The two contexts of photosynthetic light harvesting and photoreception demonstrate characteristically opposite criteria for success, with light harvesting demanding structurally-rigid chromophores which minimize excitation quenching, and photoreception requiring structural flexibility to enable conformational isomerization. The functional plasticity borne out in these two biological contexts is a consequence of the structural plasticity of the pigments utilized by biliproteins―linear tetrapyrroles, or bilins. In this work, the intrinsic flexibility of the bilin framework is investigated in a bottom-up fashion by reducing the active nuclear degrees of freedom through model dipyrrole subunits of the bilin core and terminus free of external protein interactions. Steady-state spectroscopy was carried out on the dipyrrole (DPY) and dipyrrinone (DPN) subunits free in solution to characterize their intrinsic spectroscopic properties including absorption strengths and nonradiative activity. Transient absorption (TA) spectroscopy was utilized to determine the mechanism and kinetics of nonradiative decay of the dipyrrole subunits, revealing dynamics dominated by rapid internal conversion with some Z→E isomerization observable in DPY. Computational analysis of the ground state conformational landscapes indicates enhanced complexity in the asymmetric terminal subunit, and the prediction was confirmed by heterogeneity of species and kinetics observed in TA. Taken together, the large oscillator strengths (f ∼ 0.6) of the dipyrrolic derivatives and chemically-efficient spectral tunability seen through the ∼100 nm difference in absorption spectra, validate Nature's "selection" of multi-pyrrole pigments for light capture applications. However, the rapid deactivation of the excited state via their natural torsional activity when free in solution would limit their effective biological function. Comparison with phytochrome and phycocyanin 645 crystal structures reveals binding motifs within the in vivo bilin environment that help to facilitate or inhibit specific inter-pyrrole twisting vital for protein operation.
IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
Authors: Kupani Manu , Sharma Smriti , Pandey Rajeev Kumar , Kumar Rajiv , Sundar Shyam , Mehrotra Sanjana
Published: February 2021

Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production.
Molecular Characterization Based on MLST and ECDC Typing Schemes and Antibiotic Resistance Analyses of Treponema pallidum subsp. pallidum in Xiamen, China
Authors: Liu Dan , He Shu-Min , Zhu Xiao-Zhen , Liu Li-Li , Lin Li-Rong , Niu Jian-Jun , Yang Tian-Ci
Published: February 2021

In total, 49 clinical samples were analyzed using two typing schemes, Enhanced Centers for Disease Control and Prevention (ECDC) and multilocus sequence typing (MLST), to describe the molecular characteristics of circulating Treponema pallidum isolates in Xiamen between 2016 and 2017. In addition, genetic mutations potentially related to antibiotic resistance of T. pallidum were also analyzed. Forty five samples were fully typed by ECDC, and 14 different subtypes were detected. The most common subtype was 16d/f (24.4%), followed by 14d/f (20.0%). All forty nine samples were successfully typed by MLST, while only four allelic profiles were identified, including three SS14-like profiles and one Nichols-like profile. Among them, the major allelic profile was 1.1.8 (85.7%). Interestingly, the allelic profile 1.3.1 widespread in Europe and North America was not detected in this region. Additionally, A2058G mutation in 23S rRNA was found in all detectable samples (38/38), and no mutation in 16S rRNA was observed (36/36). Four non-synonymous single-nucleotide polymorphisms in penicillin-binding protein genes were found in the 35 samples eligible for Sanger sequencing. Among them, the variant in tp0500 (P564I) can only be found in the SS14-like isolates. Homoplastic changes in tp0760 (I415F/I415M) and tp0705 (A506V/A506T) were found. Moreover, the variant tp0705 A506V and the variant tp0705 A506T separately appeared in the SS14-like isolates and Nichols-like isolates, respectively. This study showed that the genotypes of T. pallidum isolates in Xiamen between 2016 and 2017 were different from those in other geographic areas. The resistance-related variants of T. pallidum isolates identified in this study could provide awareness for clinicians in the treatment of syphilis.
The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes
Authors: Wang Li , Yu Xinwen , Xu Xiaoqiang , Ming Jie , Wang Zhifeng , Gao Bin , Xing Ying , Zhou Jie , Fu Jianfang , Liu Tao , Liu Xiangyang , Garstka Malgorzata A. , Wang Xiaokai , Ji Qiuhe
Published: February 2021

Objective

Mounting evidence has suggested a link between gut microbiome characteristics and type 2 diabetes (T2D). To determine whether these alterations occur before the impairment of glucose regulation, we characterize gut microbiota in normoglycemic individuals who go on to develop T2D.

Methods

We designed a nested case-control study, and enrolled individuals with a similar living environment. A total of 341 normoglycemic individuals were followed for 4 years, including 30 who developed T2D, 33 who developed prediabetes, and their matched controls. Fecal samples (developed T2D, developed prediabetes and controls: n=30, 33, and 63, respectively) collected at baseline underwent metagenomics sequencing.

Results

Compared with matched controls, individuals who went on to develop T2D had lower abundances of Bifidobacterium longum, Coprobacillus unclassified, and Veillonella dispar and higher abundances of Roseburia hominis, Porphyromonas bennonis, and Paraprevotella unclassified. The abundance of Bifidobacterium longum was negatively correlated with follow-up blood glucose levels. Moreover, the microbial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of carbohydrate metabolism, methane metabolism, amino acid metabolism, fatty acid metabolism, and membrane transport were changed between the two groups.

Conclusions

We found that fecal microbiota of healthy individuals who go on to develop T2D had already changed when they still were normoglycemic. These alterations of fecal microbiota might provide insights into the development of T2D and a new perspective for identifying individuals at risk of developing T2D.
A Dataset of Pulmonary Lesions With Multiple-Level Attributes and Fine Contours
Authors: Li Ping , Kong Xiangwen , Li Johann , Zhu Guangming , Lu Xiaoyuan , Shen Peiyi , Shah Syed Afaq Ali , Bennamoun Mohammed , Hua Tao
Published: February 2021

Lung cancer is a life-threatening disease and its diagnosis is of great significance. Data scarcity and unavailability of datasets is a major bottleneck in lung cancer research. In this paper, we introduce a dataset of pulmonary lesions for designing the computer-aided diagnosis (CAD) systems. The dataset has fine contour annotations and nine attribute annotations. We define the structure of the dataset in detail, and then discuss the relationship of the attributes and pathology, and the correlation between the nine attributes with the chi-square test. To demonstrate the contribution of our dataset to computer-aided system design, we define four tasks that can be developed using our dataset. Then, we use our dataset to model multi-attribute classification tasks. We discuss the performance in 2D, 2.5D, and 3D input modes of the classification model. To improve performance, we introduce two attention mechanisms and verify the principles of the attention mechanisms through visualization. Experimental results show the relationship between different models and different levels of attributes.
A Monte Carlo Model of Gas-Liquid-Hydrate Three-phase Coexistence Constrained by Pore Geometry in Marine Sediments
Authors: Chen Jiangzhi , Rempel Alan W. , Mei Shenghua
Published: February 2021

Gas hydrates form at relatively high pressures in near-surface, organic-rich marine sediments, with the base of the hydrate stability field and the onset of partial gas saturation determined by temperature increases with depth. Because of pore-scale curvature and wetting effects, the transition between gas hydrate and free gas occurrence need not take place at a distinct depth or temperature boundary, but instead can be characterized by a zone of finite thickness in which methane gas bubbles and hydrate crystals coexist with the same aqueous solution. Previous treatments have idealized pores as spheres or cylinders, but real pores between sediment grains have irregular, largely convex walls that enable the highly curved surfaces of gas bubbles and/or hydrate crystals within a given pore to change with varying conditions. In partially hydrate-saturated sediments, for example, the gas–liquid surface energy perturbs the onset of gas–liquid equilibrium by an amount proportional to bubble-surface curvature, causing a commensurate change to the equilibrium methane solubility in the liquid phase. This solubility is also constrained by the curvature of coexisting hydrate crystals and hence the volume occupied by the hydrate phase. As a result, the thickness of the three-phase zone depends not only on the pore space geometry, but also on the saturation levels of the hydrate and gaseous phases. We evaluate local geometrical constraints in a synthetic 3D packing of spherical particles resembling real granular sediments, relate the changes in the relative proportions of the phases to the three-phase equilibrium conditions, and demonstrate how the boundaries of the three-phase zone at the base of the hydrate stability field are displaced as a function of pore size, while varying with saturation level. The predicted thickness of the three-phase zone varies from tens to hundreds of meters, is inversely dependent on host sediment grain size, and increases dramatically when pores near complete saturation with hydrate and gas, requiring that interfacial curvatures become large.
Asymmetric Relationship Between Mid-latitude Eurasian Circulation and Summer Rainfall in Hong Kong in Different Phases of ENSO
Authors: Li Yana , Cheung Ho-Nam , Zhou Wen
Published: February 2021

During the period 1979–2019, the interannual variation of summer rainfall in Hong Kong (HK), located on the South China coast, is weakly correlated with tropical forcing, including the El Niño/Southern Oscillation (ENSO). Instead, HK summer rainfall is strongly correlated with the mid-latitude circulation over the Urals and the preceding spring sea surface temperature (SST) over the North Atlantic (SST-Atl). The above relationship is stronger in negative ENSO summers, where the SST-Atl anomaly tends to persist from spring to summer. The persistence of the warm SST-Atl anomaly is associated with a Rossby wave train propagating from the North Atlantic to East Asia, with a low over the Urals and a high over the high latitudes of Asia. Correspondingly, the upper-tropospheric westerly jet in East Asia becomes stronger and shifts southward toward South China. The enhanced westerly wind over South China is accompanied by an anomalous Philippine Sea anticyclone, which transports more water vapor to the South China coast and causes more rainfall in HK. On the other hand, during positive ENSO summers, HK summer rainfall is affected by variation in the subtropical westerly jet over South China, which is related to water vapor transport from the Indian Ocean and Bay of Bengal. This is also associated with a height anomaly over northeastern China and the spring sub-polar North Atlantic SST. Therefore, it is important to investigate the impact of mid-latitude forcing on summer rainfall on the South China coast.
A Journey of Difference: The Voices of Women Leaders
Authors: Showunmi Victoria
Published: February 2021

This paper offers a view on narrative inquiries based upon leadership, in order to shed light on women’s of color and multicultural groups experience and nuance understanding of their leadership career path. Since black and other ethnic group women are ‘theoretically erased’ (Crenshaw, 1989: 139), this empirical study offers an insight into how gender, class and race influence on women’s leadership practices in three countries, while it adds to theorizing identity and leadership at schools in different international contexts. This paper intends to give voice to women leaders who are making a difference in their organization. During the past decade, interest in gender and leadership has grown to the extent that it is slowly becoming part of the leadership norm. Narrative inquiries are treated as a means of a systematic data gathering and analysis which challenges the traditional views of gender discussions (thus gender is predominantly about white women) and incorporating ethnic minority around leadership. Unfolding the stories of women—from multi-ethnic groups and mixed social class-higher education leadership positions in England, and Pakistan, may expose differences of interpretations offered by researchers from a racially and ethnically diverse background (black and white Europeans). Hence, an issue that arises is whether researchers’ cultural background affects data interpretation of studies with a highly qualitative stance.
Maternal Serum Melatonin Increases During Pregnancy and Falls Immediately After Delivery Implicating the Placenta as a Major Source of Melatonin
Authors: Ejaz Haroon , Figaro Juliana K. , Woolner Andrea M. F. , Thottakam Bensita M. V. , Galley Helen F.
Published: February 2021

Melatonin is a neuroendocrine hormone which regulates circadian rhythm and is also an antioxidant. The role of melatonin in pregnancy is emerging. The enzymes needed for endogenous synthesis of melatonin have been identified in the placenta, although the contribution to circulating maternal melatonin in normal pregnancy is unclear. This work aimed to determine serum levels of melatonin and its major metabolite 6-hydroxymelatonin sulfate (6-OHMS) in normal pregnant women during each trimester of pregnancy, and immediately after delivery. Blood samples were obtained from a cohort of healthy pregnant women during each trimester of pregnancy (n = 26), from women scheduled for elective Cesarean section (CS) before and after delivery (n = 15), along with placental samples, and from healthy non-pregnant women as controls (n = 30). Melatonin and its major metabolite, 6-OHMS, were measured using enzyme immunoassay. Levels of serum melatonin were significantly higher during pregnancy than in non-pregnant women (P = 0.025) and increased throughout pregnancy (P < 0.0001). In women undergoing CS, serum melatonin decreased markedly 24 h after delivery (P = 0.0013). Similar results were seen for serum levels of 6-OHMS, and placental tissue 6-OHMS levels correlated with week of gestation at delivery (p = 0.018). In summary, maternal melatonin production is higher in pregnant than in non-pregnant women, increases significantly during pregnancy with highest levels in the third trimester, and decreases abruptly after delivery. These results suggest that the placenta is a major source of melatonin and supports a physiological role for melatonin in pregnancy.
A Comparison of the Efficacy of Immediate Versus Delayed Frozen–Thawed Embryo Transfer on the Ongoing Pregnancy Rate After a Failed IVF Attempt: Study Protocol for a Randomized, Non-Inferiority, Parallel-Group, Controlled Trial
Authors: Liu Zhuo , Dong Fengyi , Wang Yunhan , Zheng Mingming , Song Mengyang , Wang Yixuan , Song Jingyan
Published: February 2021

Introduction

In clinical practice, the ideal time at which to perform a Frozen–thawed Embryo Transfer (FET) after a failed In-vitro Fertilization-embryo Transfer (IVF-ET) is still unclear to most practicing physicians. In addition, physicians often delay the introduction of FET due to concerns on the possible residual effects of ovarian hyperstimulation, which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective with contradictory findings, it is crucial to provide evidence-based randomized control guides for clinical practice.

Methods/analysis

The study is a randomized, non-inferiority, parallel-group, controlled trial that will enroll a total of 732 women undergoing their first FET after a failed fresh embryo transfer (ET) cycle. The participants will then be randomized into two groups based on a computer-generated randomized list. The two groups include: (i) an immediate group were FET will be carried out during the first menstrual cycle after a failed fresh ET cycle and (ii) a delayed group where FET will be carried out during the second menstrual cycle after a failed fresh ET cycle. Primary outcomes will be defined as viable pregnancies with fetal heartbeats, diagnosed through pelvic ultrasonography after twelve weeks of gestation.

Ethics and dissemination

The study was approved by the Ethics Committee of the Assisted Reproductive Medicine at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (SDTCM/E-2020.2.01). In addition, written informed consent will be obtained from all the participants before the study. The results of this trial will be disseminated in a peer-reviewed journal.

Discussion

Currently, there is no consensus with regard to the duration after which the effects of ovarian stimulation are observed after a failed fresh ET and the optimal time required to begin FET. Moreover, no randomized controlled trial exists that compares the ongoing pregnancy rates after immediate versus delayed FET following a failed fresh ET cycle. Therefore, it is important to conduct a well-designed randomized trial to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh ET.

Clinical Trial Registration

ChiCTR2000033313 (http://www.chictr.org.cn/enIndex.aspx).
Ferroptosis Enhanced Diabetic Renal Tubular Injury via HIF-1α/HO-1 Pathway in db/db Mice
Authors: Feng Xiaomeng , Wang Shuo , Sun Zhencheng , Dong Hengbei , Yu Haitian , Huang Mengxiu , Gao Xia
Published: February 2021

Background

Ferroptosis is a recently identified iron-dependent form of cell death as a result of increased reactive oxygen species (ROS) and lipid peroxidation. In this study, we investigated whether ferroptosis aggravated diabetic nephropathy (DN) and damaged renal tubules through hypoxia-inducible factor (HIF)-1α/heme oxygenase (HO)-1 pathway in db/db mice.

Methods

Db/db mice were administered with or without ferroptosis inhibitor Ferrostatin-1 treatment, and were compared with db/m mice.

Results

Db/db mice showed higher urinary albumin-to-creatinine ratio (UACR) than db/m mice, and Ferrostatin-1 reduced UACR in db/db mice. Db/db mice presented higher kidney injury molecular-1 and neutrophil gelatinase-associated lipocalin in kidneys and urine compared to db/m mice, with renal tubular basement membranes folding and faulting. However, these changes were ameliorated in db/db mice after Ferrostatin-1 treatment. Fibrosis area and collagen I were promoted in db/db mouse kidneys as compared to db/m mouse kidneys, which was alleviated by Ferrostatin-1 in db/db mouse kidneys. HIF-1α and HO-1 were increased in db/db mouse kidneys compared with db/m mouse kidneys, and Ferrostatin-1 decreased HIF-1α and HO-1 in db/db mouse kidneys. Iron content was elevated in db/db mouse renal tubules compared with db/m mouse renal tubules, and was relieved in renal tubules of db/db mice after Ferrostatin-1 treatment. Ferritin was increased in db/db mouse kidneys compared with db/m mouse kidneys, but Ferrostatin-1 reduced ferritin in kidneys of db/db mice. Diabetes accelerated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived ROS formation in mouse kidneys, but Ferrostatin-1 prevented ROS formation derived by NADPH oxidases in db/db mouse kidneys. The increased malondialdehyde (MDA) and the decreased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GSH-Px) were detected in db/db mouse kidneys compared to db/m mouse kidneys, whereas Ferrostatin-1 suppressed MDA and elevated SOD, CAT, and GSH-Px in db/db mouse kidneys. Glutathione peroxidase 4 was lower in db/db mouse kidneys than db/m mouse kidneys, and was exacerbated by Ferrostatin-1 in kidneys of db/db mice.

Conclusions

Our study indicated that ferroptosis might enhance DN and damage renal tubules in diabetic models through HIF-1α/HO-1 pathway.
The Plasticity and Developmental Potential of Termites
Authors: Revely Lewis , Sumner Seirian , Eggleton Paul
Published: February 2021

Phenotypic plasticity provides organisms with the potential to adapt to their environment and can drive evolutionary innovations. Developmental plasticity is environmentally induced variation in phenotypes during development that arise from a shared genomic background. Social insects are useful models for studying the mechanisms of developmental plasticity, due to the phenotypic diversity they display in the form of castes. However, the literature has been biased toward the study of developmental plasticity in the holometabolous social insects (i.e., bees, wasps, and ants); the hemimetabolous social insects (i.e., the termites) have received less attention. Here, we review the phenotypic complexity and diversity of termites as models for studying developmental plasticity. We argue that the current terminology used to define plastic phenotypes in social insects does not capture the diversity and complexity of these hemimetabolous social insects. We suggest that terminology used to describe levels of cellular potency could be helpful in describing the many levels of phenotypic plasticity in termites. Accordingly, we propose a conceptual framework for categorizing the changes in potential of individuals to express alternative phenotypes through the developmental life stages of termites. We compile from the literature an exemplar dataset on the phenotypic potencies expressed within and between species across the phylogeny of the termites and use this to illustrate how the potencies of different life stages of different species can be described using this framework. We highlight how this conceptual framework can help exploit the rich phenotypic diversity of termites to address fundamental questions about the evolution and mechanisms of developmental plasticity. This conceptual contribution is likely to have wider relevance to the study of other hemimetabolous insects, such as aphids and gall-forming thrips, and may even prove useful for some holometabolous social insects which have high caste polyphenism.
Aberrant Expression of Long Non-coding RNAs in Exosomes in Follicle Fluid From PCOS Patients
Authors: Wang Liping , Fan Hairui , Zou Yinggang , Yuan Qiuyue , Hu Xuming , Chen Xujing , Zhu Chunhui , Zhang Xiaomei , Cui Hengmi
Published: February 2021

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease characterized by persistent anovulation and hyperandrogenism, affecting approximately 8–10% of women of childbearing age and occupying an important position in the etiology of infertility. There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the development of PCOS, but the potential regulatory mechanism is still unclear. This study performed high-throughput lncRNA sequencing of follicular fluid exosomes in non-PCOS infertility patients and PCOS infertility patients. The sequencing results led to the identification of 1,253 upregulated and 613 downregulated lncRNAs from a total of 1,866 detected candidates. There was no significant difference between the PCOS patients and non-PCOS patients in body mass index (BMI) or the fasting blood glucose (FBG) level. However, luteinizing hormone (LH), estradiol (E2), testosterone (T), serum prolactin (PRL), and anti-Mullerian hormone (AMH) levels were clearly upregulated in PCOS patients compared to those in non-PCOS patients. There was also an increase in LH/FSH (>2) in the PCOS patients. Functional analysis showed pathways related to endocytosis, the Hippo, the MAPK, and HTLV-1 infection. These results suggest that lncRNAs may play an important role in the pathogenesis of PCOS and may be potential targets for the diagnosis and treatment of PCOS.