bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing Single-Cell Macrophage Polarization and Heterogeneity Using Thermo-Reversible Hydrogels in Droplet-Based Microfluidics
Authors: Tiemeijer B. M. , Sweep M. W. D. , Sleeboom J. J. F. , Steps K. J. , van Sprang J. F. , De Almeida P. , Hammink R. , Kouwer P. H. J. , Smits A. I. P. M. , Tel J.
Published: October 2021

Human immune cells intrinsically exist as heterogenous populations. To understand cellular heterogeneity, both cell culture and analysis should be executed with single-cell resolution to eliminate juxtacrine and paracrine interactions, as these can lead to a homogenized cell response, obscuring unique cellular behavior. Droplet microfluidics has emerged as a potent tool to culture and stimulate single cells at high throughput. However, when studying adherent cells at single-cell level, it is imperative to provide a substrate for the cells to adhere to, as suspension culture conditions can negatively affect biological function and behavior. Therefore, we combined a droplet-based microfluidic platform with a thermo-reversible polyisocyanide (PIC) hydrogel, which allowed for robust droplet formation at low temperatures, whilst ensuring catalyzer-free droplet gelation and easy cell recovery after culture for downstream analysis. With this approach, we probed the heterogeneity of highly adherent human macrophages under both pro-inflammatory M1 and anti-inflammatory M2 polarization conditions. We showed that co-encapsulation of multiple cells enhanced cell polarization compared to single cells, indicating that cellular communication is a potent driver of macrophage polarization. Additionally, we highlight that culturing single macrophages in PIC hydrogel droplets displayed higher cell viability and enhanced M2 polarization compared to single macrophages cultured in suspension. Remarkably, combining phenotypical and functional analysis on single cultured macrophages revealed a subset of cells in a persistent M1 state, which were undetectable in conventional bulk cultures. Taken together, combining droplet-based microfluidics with hydrogels is a versatile and powerful tool to study the biological function of adherent cell types at single-cell resolution with high throughput.
Spatiotemporal Changes in Transcriptome of Odontogenic and Non-odontogenic Regions in the Dental Arch of Mus musculus
Authors: Lee Dong-Joon , Kim Hyun-Yi , Lee Seung-Jun , Jung Han-Sung
Published: October 2021

Over the past 40 years, studies on tooth regeneration have been conducted. These studies comprised two main flows: some focused on epithelial–mesenchymal interaction in the odontogenic region, whereas others focused on creating a supernumerary tooth in the non-odontogenic region. Recently, the scope of the research has moved from conventional gene modification and molecular therapy to genome and transcriptome sequencing analyses. However, these sequencing data have been produced only in the odontogenic region. We provide RNA-Seq data of not only the odontogenic region but also the non-odontogenic region, which loses tooth-forming capacity during development and remains a rudiment. Sequencing data were collected from mouse embryos at three different stages of tooth development. These data will expand our understanding of tooth development and will help in designing developmental and regenerative studies from a new perspective.
Caffeine Inhibits Choroidal Neovascularization Through Mitigation of Inflammatory and Angiogenesis Activities
Authors: Sorenson Christine M. , Song Yong-Seok , Zaitoun Ismail S. , Wang Shoujian , Hanna Barbara A. , Darjatmoko Soesiawati R. , Gurel Zafer , Fisk Debra L. , McDowell Colleen M. , McAdams Ryan M. , Sheibani Nader
Published: October 2021

Adenosine receptors (AR) are widely expressed in a variety of tissues including the retina and brain. They are involved in adenosine-mediated immune responses underlying the onset and progression of neurodegenerative diseases. The expression of AR has been previously demonstrated in some retinal cells including endothelial cells and retinal pigment epithelial cells, but their expression in the choroid and choroidal cells remains unknown. Caffeine is a widely consumed AR antagonist that can influence inflammation and vascular cell function. It has established roles in the treatment of neonatal sleep apnea, acute migraine, and post lumbar puncture headache as well as the neurodegenerative diseases such as Parkinson and Alzheimer. More recently, AR antagonism with caffeine has been shown to protect preterm infants from ischemic retinopathy and retinal neovascularization. However, whether caffeine impacts the development and progression of ocular age-related diseases including neovascular age-related macular degermation remains unknown. Here, we examined the expression of AR in retinal and choroidal tissues and cells. We showed that antagonism of AR with caffeine or istradefylline decreased sprouting of thoracic aorta and choroid/retinal pigment epithelium explants in ex vivo cultures, consistent with caffeine’s ability to inhibit endothelial cell migration in culture. In vivo studies also demonstrated the efficacy of caffeine in inhibition of choroidal neovascularization and mononuclear phagocyte recruitment to the laser lesion sites. Istradefylline, a specific AR 2A antagonist, also decreased choroidal neovascularization. Collectively, our studies demonstrate an important role for expression of AR in the choroid whose antagonism mitigate choroidal inflammatory and angiogenesis activities.
Evolving Landscape of Long Non-coding RNAs in Cerebrospinal Fluid: A Key Role From Diagnosis to Therapy in Brain Tumors
Authors: Xu Kanghong , Jiang Xinquan , Ariston Gabriel Abakundana Nsenga , Li Xiaomeng , Wang Yunshan , Xu Shuo
Published: October 2021

Long non-coding RNAs (lncRNAs) are a type of non-coding RNAs that act as molecular fingerprints and modulators of many pathophysiological processes, particularly in cancer. Specifically, lncRNAs can be involved in the pathogenesis and progression of brain tumors, affecting stemness/differentiation, replication, invasion, survival, DNA damage response, and chromatin dynamics. Furthermore, the aberrations in the expressions of these transcripts can promote treatment resistance, leading to tumor recurrence. The development of next-generation sequencing technologies and the creation of lncRNA-specific microarrays have boosted the study of lncRNA etiology. Cerebrospinal fluid (CSF) directly mirrors the biological fluid of biochemical processes in the brain. It can be enriched for small molecules, peptides, or proteins released by the neurons of the central nervous system (CNS) or immune cells. Therefore, strategies that identify and target CSF lncRNAs may be attractive as early diagnostic and therapeutic options. In this review, we have reviewed the studies on CSF lncRNAs in the context of brain tumor pathogenesis and progression and discuss their potential as biomarkers and therapeutic targets.
One-Step Synthesis of Bifunctional Nickel Phosphide Nanowires as Electrocatalysts for Hydrogen and Oxygen Evolution Reactions
Authors: Xiang Dong , Zhang Biao , Zhang Hongsheng , Shen Liangping
Published: October 2021

The Ni2P nanowires were simply synthesized via a rapid one-step hydrothermal approach, in which deionized water, red phosphorus, nickel acetate, and hexadecyl trimethyl ammonium bromide were used as the solvent, phosphor and nickel sources, and active agent, respectively. The as-synthesized Ni2P nanowire clusters were composed of uniform nanowires with length of about 10 μm and diameter of about 40 nm. The Ni2P nanowires exhibited enhanced electrocatalytic activity for both hydrogen evolution reaction and oxygen evolution reaction This work provides good guidance for the rational design of nickel phosphides with unique nanostructures for highly efficient overall water splitting.
The Effects of Chinese Medicine QRD, Antibiotics, and Probiotics on Therapy and Gut Microbiota in Septic Rats
Authors: Cao Huiling , Zong Chunhui , Dai Wenkui , Gao Qiaoying , Li Donghua , Wu Xianzhong , Li Dongfang , Tang Yi-Wei , Wu Shangwei
Published: October 2021

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.
Coexisting With Different Human-Wildlife Coexistence Perspectives
Authors: Glikman Jenny Anne , Frank Beatrice , Ruppert Kirstie A. , Knox Jillian , Sponarski Carly C. , Metcalf Elizabeth Covelli , Metcalf Alexander L. , Marchini Silvio
Published: October 2021

Over the last decade, there has been a remarkable increase in scientific literature addressing human–wildlife interactions (HWI) and associated concepts, such as coexistence, tolerance, and acceptance. Despite increased attention, these terms are rarely defined or consistently applied across publications. Indeed, the meaning of these concepts, especially coexistence, is frequently assumed and left for the reader to interpret, making it hard to compare studies, test metrics, and build upon previous HWI research. To work toward a better understanding of these terms, we conducted two World Café sessions at international conferences in Namibia, Africa and Ontario, Canada. Here, we present the array of perspectives revealed in the workshops and build upon these results to describe the meaning of coexistence as currently applied by conservation scientists and practitioners. Although we focus on coexistence, it is imperative to understand the term in relation to tolerance and acceptance, as in many cases these latter terms are used to express, measure, or define coexistence. Drawing on these findings, we discuss whether a common definition of these terms is possible and how the conservation field might move toward clarifying and operationalizing the concept of human-wildlife coexistence.
Successful Wildlife Conservation Requires Good Governance
Authors: Pomeranz Emily F. , Hare Darragh , Decker Daniel J. , Forstchen Ann B. , Jacobson Cynthia A. , Smith Christian A. , Schiavone Michael V.
Published: October 2021

Public wildlife management in the United States is transforming as agencies seek relevancy to broader constituencies. State agencies in the United States, while tasked with conserving wildlife for all beneficiaries of the wildlife trust, have tended to manage for a limited range of benefits in part due to a narrow funding model heavily dependent on hunting, fishing, and trapping license buyers. To best meet the needs, interests, and concerns of a broader suite of beneficiaries, agencies will need to reconsider how priorities for management are set. This presents an opportunity for conservation program design and evaluation to be elevated in importance. We argue that success in wildlife conservation in the U.S. requires assessment of both decision-making processes and management results in relation to four questions: conservation of what, under what authority, for what purposes, and for whom?
Assessment of New Coronary Features on Quantitative Coronary Angiographic Images With Innovative Unsupervised Artificial Adaptive Systems: A Proof-of-Concept Study
Authors: Amato Mauro , Buscema Massimo , Massini Giulia , Maurelli Guido , Grossi Enzo , Frigerio Beatrice , Ravani Alessio L. , Sansaro Daniela , Coggi Daniela , Ferrari Cristina , Bartorelli Antonio L. , Veglia Fabrizio , Tremoli Elena , Baldassarre Damiano
Published: October 2021

Background and Purpose: The Active Connection Matrixes (ACMs) are unsupervised artificial adaptive systems able to extract from digital images features of interest (edges, tissue differentiation, etc.) unnoticeable with conventional systems. In this proof-of-concept study, we assessed the potentiality of ACMs to increase measurement precision of morphological structures (e.g., stenosis and lumen diameter) and to grasp morphological features (arterial walls) from quantitative coronary angiography (QCA), unnoticeable on the original images.

Methods: Archive images of QCA and intravascular ultrasound (IVUS) of 10 patients (8 men, age 69.1 ± 9.7 years) who underwent both procedures for clinical reasons were retrospectively analyzed. Arterial features derived from “IVUS images,” “conventional QCA images,” and “ACM-reprocessed QCA images” were measured in 21 coronary segments. Portions of 1-mm length (263 for lumen and 526 for arterial walls) were head-to-head compared to assess quali-quantitative between-methods agreement.

Results: When stenosis was calculated on “ACM-reprocessed QCA images,” the bias vs. IVUS (gold standard) did not improve, but the correlation coefficient of the QCA–IVUS relationship increased from 0.47 to 0.83. When IVUS-derived lumen diameters were compared with diameters obtained on ACM-reprocessed QCA images, the bias (−0.25 mm) was significantly smaller (p < 0.01) than that observed with original QCA images (0.58 mm). ACMs were also able to extract arterial wall features from QCA. The bias between the measures of arterial walls obtained with IVUS and ACMs, although significant (p < 0.01), was small [0.09 mm, 95% CI (0.03, 0.14)] and the correlation was fairly good (r = 0.63; p < 0.0001).

Conclusions: This study provides proof of concept that ACMs increase the measurement precision of coronary lumen diameter and allow extracting from QCA images hidden features that mirror well the arterial walls derived by IVUS.
Influenza Vaccination and the Risk of Ventricular Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease: A Population-Based Longitudinal Study
Authors: Chen Chun-Chao , Lin Cheng-Hsin , Hao Wen-Rui , Yeh Jong-Shiuan , Chiang Kuang-Hsing , Fang Yu-Ann , Chiu Chun-Chih , Yang Tsung Yeh , Wu Yu-Wei , Liu Ju-Chi
Published: October 2021

Backgrounds: Influenza vaccination could decrease the risk of major cardiac events in patients with chronic obstructive pulmonary disease (COPD). However, the effects of the vaccine on decreasing the risk of ventricular arrhythmia (VA) development in such patients remain unclear.

Methods: We retrospectively analyzed the data of 18,658 patients with COPD (≥55 years old) from the National Health Insurance Research Database from January 1, 2001, to December 31, 2012. After a 1:1 propensity score matching by the year of diagnosis, we divided the patients into vaccinated and unvaccinated groups. Time-varying Cox proportional hazards regression was applied to assess the time to event hazards of influenza vaccination exposure.

Results: The risk of VA occurrence was significantly lower in the vaccinated group during influenza season and all seasons [adjusted hazard ratio (aHR): 0.62, 95% CI: 0.41–0.95; aHR: 0.69, 95% CI: 0.44–1.08; and aHR: 0.65, 95% CI: 0.48–0.89, in the influenza season, non-influenza season, and all seasons, respectively]. Among patients with CHA2DS2-VASc scores (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2–3, receiving one time and two to three times of influenza vaccination were associated with lower risk of VA occurrence in all seasons (aHR: 0.28, 95% CI: 0.10–0.80; aHR: 0.27, 95% CI: 0.10–0.68, respectively). Among patients without stroke, peripheral vascular disease, and diabetes, a lower risk of VA occurrence after receiving one and two to three times vaccination was observed in all seasons. Among patients with a history of asthma and patients without a history of heart failure, ischemic heart disease, angina hypertension, or renal failure, a significantly lower risk of VA occurrence was observed after the first time of vaccination in all seasons.

Conclusions: Influenza vaccination may be associated with lower risks of VA among patients with COPD aged 55–74. Further investigation is still needed to resolve this clinical question.
Sex Differences in Mitral Annular Calcification and the Clinical Implications
Authors: Seo Jiwon , Jeong Hyeonju , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young
Published: October 2021

Background: Heterogeneous mechanisms may contribute to the occurrence of mitral annular calcification (MAC), however, little is known about the sex differences in MAC and the clinical implications of these differences. This study aimed to investigate clinical and imaging differences of MAC according to sex.

Methods: In total, 537 patients (221 men) with MAC were identified by transthoracic echocardiography at a single center from January 2012 to June 2016. Moderate-to-severe MAC was defined as calcification extent ≥120° of the mitral annulus. Significant functional mitral stenosis (MS) was defined as a transmitral mean diastolic pressure gradient ≥5 mmHg.

Results: Women more frequently had moderate-to-severe MAC and concomitant mitral regurgitation than men; however, significant functional MS was comparable between sexes. In the logistic regression analysis, old age, uncontrolled hypertension, end-stage renal disease (ESRD), and obstructive hypertrophic cardiomyopathy were significantly associated with moderate-to-severe MAC in women, whereas ESRD and moderate-to-severe aortic stenosis were in men. In the Cox regression analysis, significant functional MS was associated with all-cause death in both sexes, although an independent association was found in only women.

Conclusion: Women had more extended MAC than men. Significant functional MS was independently associated with unfavorable clinical outcomes in patients with MAC, which was more pronounced in women than in men.
Nomogram to Predict Left Atrial Thrombus or Spontaneous Echo Contrast in Patients With Non-valvular Atrial Fibrillation
Authors: Li Zhitong , Liu Quanbo , Liu Fei , Hidru Tesfaldet H. , Tang Yuqi , Cong Tao , Gao Lianjun , Yang Xiaolei , Xia Yunlong
Published: October 2021

Background: The predictive power of the CHADS2 and CHA2DS2-VASc scores for the presence of Left atrial thrombus (LAT)/ spontaneous echo contrast (SEC) in non-valvular atrial fibrillation (NVAF) is modest. The aim of this analysis is to define clinical and ultrasonic variables associated with LAT/SEC and to propose nomograms for individual risk prediction.

Methods: Data on 1,813 consecutive NVAF patients who underwent transesophageal echocardiography (TEE) from January 2016 to January 2021 were collected. The univariate and multivariate logistic regression analyses were used to construct a nomogram. We examined the predictive ability of the risk scores by calculating the area under the curve (AUC). Moreover, the performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness.

Results: LAT/SEC was found in 260 (21.0%) and 124 (21.6%) patients in the training and validation cohorts, respectively. On multivariate analysis, independent factors for LAT/SEC were Age, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), hypertension (HTN), previous stroke or transient ischemic attack, Non-paroxysmal AF and a nomogram was built based on these variables. The calibration curve for the probability of LAT/SEC showed good prediction agreement with actual observation. The nomogram achieved good concordance indexes of 0.836 and 0.794 in predicting LAT/SEC in the training and validation cohorts, respectively. Decision curve analysis demonstrated that the nomogram would be clinically useful.

Conclusions: In this study, a nomogram was constructed that incorporated six characteristics of NVAF patients. The nomogram may be of great value for the prediction of LAT/SEC in NVAF patients.
Deep Learning for Classification and Selection of Cine CMR Images to Achieve Fully Automated Quality-Controlled CMR Analysis From Scanner to Report
Authors: Vergani Vittoria , Razavi Reza , Puyol-Antón Esther , Ruijsink Bram
Published: October 2021

Introduction: Deep learning demonstrates great promise for automated analysis of CMR. However, existing limitations, such as insufficient quality control and selection of target acquisitions from the full CMR exam, are holding back the introduction of deep learning tools in the clinical environment. This study aimed to develop a framework for automated detection and quality-controlled selection of standard cine sequences images from clinical CMR exams, prior to analysis of cardiac function.

Materials and Methods: Retrospective study of 3,827 subjects that underwent CMR imaging. We used a total of 119,285 CMR acquisitions, acquired with scanners of different magnetic field strengths and from different vendors (1.5T Siemens and 1.5T and 3.0T Phillips). We developed a framework to select one good acquisition for each conventional cine class. The framework consisted of a first pre-processing step to exclude still acquisitions; two sequential convolutional neural networks (CNN), the first (CNNclass) to classify acquisitions in standard cine views (2/3/4-chamber and short axis), the second (CNNQC) to classify acquisitions according to image quality and orientation; a final algorithm to select one good acquisition of each class. For each CNN component, 7 state-of-the-art architectures were trained for 200 epochs, with cross entropy loss and data augmentation. Data were divided into 80% for training, 10% for validation, and 10% for testing.

Results: CNNclass selected cine CMR acquisitions with accuracy ranging from 0.989 to 0.998. Accuracy of CNNQC reached 0.861 for 2-chamber, 0.806 for 3-chamber, and 0.859 for 4-chamber. The complete framework was presented with 379 new full CMR studies, not used for CNN training/validation/testing, and selected one good 2-, 3-, and 4-chamber acquisition from each study with sensitivity to detect erroneous cases of 89.7, 93.2, and 93.9%, respectively.

Conclusions: We developed an accurate quality-controlled framework for automated selection of cine acquisitions prior to image analysis. This framework is robust and generalizable as it was developed on multivendor data and could be used at the beginning of a pipeline for automated cine CMR analysis to obtain full automatization from scanner to report.
Differences on Geochemical Characteristics and Their Implicating Significances of Nitrogen in Coal-Derived Gas and Oil-typed Gas in China
Authors: Xiaobo Wang , Jian Li , Chunxia Yang , Zhisheng Li , Jianfa Chen , Yue Zheng , Yifeng Wang , Jin Li , Chunlong Yang , Aisheng Hao , Shouguo Ge
Published: October 2021

Natural gases in China are mainly coal-derived gas, with assistance from oil-typed gas. At present, many genetic identification methods, from hydrocarbon composition and isotope to light hydrocarbon and biomarker indexes, have been formed, but combined methods from non-hydrocarbon gases are lacking. Based on compositions and isotopes geochemical characteristics and the differences of non-hydrocarbon nitrogen gas in coal-derived gas and oil-typed gas, and combining the isotopic geochemical characteristics of non-hydrocarbon helium, the comprehensive identification methods of coal-derived gas and oil-typed gas for hydrocarbon gases according to the associated non-hydrocarbon gases of nitrogen and helium are established and the preliminary applications have been engaged. The main recognitions are as follows:1)Coal-derived gas generally has relatively lower nitrogen abundance, mainly distributed from 0 to 31.2% with main frequency from 0 to 2%. Oil-typed gas, on the other hand, usually has relatively higher nitrogen abundance, mainly distributed from 1.1 to 57.1% with main frequency from 2 to 16%. 2) Coal-derived gas generally has relatively heavier nitrogen isotope values, mainly distributed from -8 to 19.3‰ with main frequency from -8 to 8‰.Oil-typed gas usually has relatively lower nitrogen isotope values, mainly distributed from -10.6 to 4.6‰ with main frequency from -8 to 4‰.3)The geochemical characteristic differences of coal-derived gas and oil-typed gas are mainly due to the fact that the sapropel parent material is relatively rich in nitrogen element and rich in light δ14N, while the humic parent material is relatively poor in nitrogen element and rich in heavy δ15N. The differences on thermal maturity of source rocks, the redox conditions of source rock sedimentary environment, and the salinity of water body are also important effective factors.4)Differences on nitrogen abundances and isotopes in coal-derived gas and oil-typed gas have great significance in genetic identification. The genetic identification chart of R/Ra-δ15N for organic and inorganic nitrogen in natural gas and the comprehensive joint identification charts of R/Ra-δ15N-N2 of nitrogen and helium for coal-derived gas and oil-typed gas have been established, and are of great reference in investigating the origins and sources of natural gas and guiding natural gas exploration in China.
VSP Imaging Using Free-Surface Multiples With Wavefield Decomposition: Synthetic and Field Data Examples
Authors: Zheng Yikang , Wang Yibo , Chang Xu
Published: October 2021

Vertical seismic profiling (VSP) is an effective technique to provide high-resolution seismic images of the reservoir area. However, the quality of the images is limited by the poor illumination of primary reflection wave. In conventional VSP imaging, only the upgoing primaries are used. Adding free-surface–related multiples into the imaging process can significantly improve the coverage of the illuminated area. Conventional migration methods using multiples need the complex process of multiple prediction. Data-to-data migration (DDM) is an effective imaging technique for multiples in which the recorded data is migrated directly. To improve the imaging quality of DDM in VSP imaging, we propose separating the wavefield into downgoing and upgoing components using Hilbert transform when reverse-time migration (RTM) is implemented in DDM, and the inverse-scattering imaging condition is further applied to the decomposed wavefields. The proposed method eliminates low-frequency noises and false images generated from the conventional cross-correlation imaging condition, and further enhance the illumination in the VSP imaging. Synthetic examples and application to a walkaway field data demonstrate that it can attenuate the noise and improve the imaging resolution effectively. By using DDM with inverse scattering imaging condition and wavefield decomposition based on Hilbert transform, VSP imaging using free-surface–related multiples becomes a practical complement for conventional VSP imaging.
Study on the Stability of Coal Pillars Under the Disturbance of Repeated Mining in a Double-Roadway Layout System
Authors: Liu Shuaigang , Bai Jianbiao , Wang Xiangyu , Wang Guanghui , Wu Bowen , Li Yanhui , Zhao Jiaxin
Published: October 2021

The double-roadway layout system, which is extensively applied in large mines, has the potential to significantly balance excavation-mining and improve mine ventilation and transportation capacity. However, the coal pillar in the double-roadway layout system is easily destabilized due to the disturbance of repeated mining, which has a significant impact on the safety and reliability of coal mines. This paper takes the coal pillar and its supporting structure of the double-roadway layout system as the research object, establishes a UDEC trigon numerical calculation model, and systematically corrects the input parameters, while explaining the excavation method of roadways and the simulation method of the supporting structure element. The numerical simulation results show that under the conventional support intensity conditions, the internal damage of the coal pillar during the excavation period is about 20%, while the internal damage to the coal pillar develops to 55% throughout the first-panel mining. During the disturbance of repeated mining, the damage in the coal pillar increased to 90%, and the coal pillar was already in a state of failure. Under the combined control of rock bolts and counter-pulled anchor cables, the coal pillar damage does not change significantly during the excavation and first-panel mining. During the disturbance of repeated mining, the damage of the coal pillar is reduced to 63%. There is a certain low damage area in the coal pillar, which can ensure the stability of the coal pillar and its supporting structure as a whole. Furthermore, the on-site monitoring results show that the maximum value of the floor-to-roof and rib-to-rib convergence of a W1310 tailgate during the repeated mining disturbance stage is 730 and 620 mm, respectively. The findings of this study give an approach to—as well as estimated values for the design of, including its “small structure” control technical parameters—the double-roadway layout system.
Thyroid Gene Mutations in Pregnant and Breastfeeding Women Diagnosed With Transient Congenital Hypothyroidism: Implications for the Offspring’s Health
Authors: Opazo Maria C. , Rivera Juan Carlos , Gonzalez Pablo A. , Bueno Susan M. , Kalergis Alexis M. , Riedel Claudia A.
Published: October 2021

Fetus and infants require appropriate thyroid hormone levels and iodine during pregnancy and lactation. Nature endorses the mother to supply thyroid hormones to the fetus and iodine to the lactating infant. Genetic variations on thyroid proteins that cause dyshormonogenic congenital hypothyroidism could in pregnant and breastfeeding women impair the delivery of thyroid hormones and iodine to the offspring. The review discusses maternal genetic variations in thyroid proteins that, in the context of pregnancy and/or breastfeeding, could trigger thyroid hormone deficiency or iodide transport defect that will affect the proper development of the offspring.
Meiotic Chromosome Synapsis and XY-Body Formation In Vitro
Authors: Lei Qijing , Zhang Eden , van Pelt Ans M. M. , Hamer Geert
Published: October 2021

To achieve spermatogenesis in vitro, one of the most challenging processes to mimic is meiosis. Meiotic problems, like incomplete synapsis of the homologous chromosomes, or impaired homologous recombination, can cause failure of crossover formation and subsequent chromosome nondisjunction, eventually leading to aneuploid sperm. These meiotic events are therefore strictly monitored by meiotic checkpoints that initiate apoptosis of aberrant spermatocytes and lead to spermatogenic arrest. However, we recently found that, in vitro derived meiotic cells proceeded to the first meiotic division (MI) stage, despite displaying incomplete chromosome synapsis, no discernible XY-body and lack of crossover formation. We therefore optimized our in vitro culture system of meiosis from male germline stem cells (mGSCs) in order to achieve full chromosome synapsis, XY-body formation and meiotic crossovers. In comparison to previous culture system, the in vitro-generated spermatocytes were transferred after meiotic initiation to a second culture dish. This dish already contained a freshly plated monolayer of proliferatively inactivated immortalized Sertoli cells supporting undifferentiated mGSCs. In this way we aimed to simulate the multiple layers of germ cell types that support spermatogenesis in vivo in the testis. We found that in this optimized culture system, although independent of the undifferentiated mGSCs, meiotic chromosome synapsis was complete and XY body appeared normal. However, meiotic recombination still occurred insufficiently and only few meiotic crossovers were formed, leading to MI-spermatocytes displaying univalent chromosomes (paired sister chromatids). Therefore, considering that meiotic checkpoints are not necessarily fully functional in vitro, meiotic crossover formation should be closely monitored when mimicking gametogenesis in vitro to prevent generation of aneuploid gametes.
Research on Adaptive Hybrid Energy Consumption Model Based on Data Driven under Variable Working Conditions
Authors: Su Yujun , Zou Mingyao , Jiang Cheng , Qian Hong
Published: October 2021

As to the nonlinear and time-varying problems of the energy consumption model, this paper proposes an adaptive hybrid modeling method. Firstly, the recursive least squares algorithm with adaptive forgetting factor based on fuzzy algorithm and recursive least squares algorithm is used to identify the simplified mechanism energy consumption model, which solves the data saturation phenomenon and the weights of the “old and new” data during the online identification process and guarantees the adaptability of the mechanism model. Secondly, because there is a deviation between the identified model and the simplified mechanism energy consumption model, the deviation compensation model of mechanism model is established through kernel partial least squares algorithm and the model updating strategy with sliding window, which is used to update the deviation compensation model, and then the adaptive hybrid model is established by combining with the mechanism model identified online and updated deviation compensation model. Finally, the effectiveness, generalization and adaptability of the model are verified by the actual operating data of a single working condition and variable working conditions. And comparing with the mechanism model and the data model, The comparison results show that the adaptive hybrid model has higher calculation accuracy with adaptation.
TUBA1C is a Prognostic Marker in Low-grade Glioma and Correlates with Immune Cell Infiltration in the Tumor Microenvironment
Authors: Zhu Hua , Hu Xinyao , Gu Lijuan , Jian Zhihong , Li Liqin , Hu Siping , Qiu Sheng , Xiong Xiaoxing
Published: October 2021

TUBA1C, a microtubule component, contributes to the development of several cancers. Our purpose was to study the expression of TUBA1C, its potential prognostic value, and its effects on the infiltration of immune cells of low-grade glioma (LGG). Through applying multiple bioinformatics analyses, we extracted and analyzed datasets from TCGA, TIMER, GTEx, GEPIA, and HPA to investigate the potential oncogenic mechanisms of TUBA1C, including the correlation between TUBA1C and prognosis, immune-checkpoints, tumor microenvironment (TME), and infiltration of immune cells in LGG. GO functional annotations and KEGG pathway analyses were further applied to investigate the potential action of TUBA1C in LGG. We revealed that the mRNA levels of TUBA1C were increased in LGG tumor tissues than in normal tissues. Additionally, TUBA1C was up-regulated in the grade III of LGG than in grade II. Moreover, we found that TUBA1C may be an independent prognostic factor of LGG, and high TUBA1C expression correlated to a poor prognosis of LGG. TUBA1C expression was positively associated with the infiltration of B cells, CD8 T+ cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils. TUBA1C was also verified to be co-expressed with immune-related genes and immune-checkpoints. GO and KEGG pathway analyses indicated that TUBA1C may potentially regulate the pathogenesis of LGG through immune-related pathways, including chemokine pathway; JAK-STAT pathway; natural killer cell mediated cytotoxicity; T cell receptor pathway; leukocyte migration; negative regulation of immune system process; regulation of lymphocyte activation; T cell activation and other pathways. In conclusion, TUBA1C expression is increased in LGG and high TUAB1C expression is related to a poor prognosis. TUBA1C may influence tumor development by regulating the tumor-infiltrating cells in the TME. TUBA1C may be a potential target for immunotherapy.
Studies on Novel Diagnostic and Predictive Biomarkers of Intrahepatic Cholestasis of Pregnancy Through Metabolomics and Proteomics
Authors: Dong Ruirui , Ye Ningzhen , Zhao Shaojie , Wang Gaoying , Zhang Yan , Wang Tiejun , Zou Ping , Wang Jing , Yao Tingting , Chen Minjian , Zhou Conghua , Zhang Ting , Luo Liang
Published: October 2021

Background

Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and is associated with increased risks in fetal complications. Currently, the exact mechanism of this disease is unknown. The purpose of this study was to develop potential biomarkers for the diagnosis and prediction of ICP.

Methods

We enrolled 40 pregnant women diagnosed with ICP and 40 healthy pregnant controls. The number of placental samples and serum samples between the two groups was 10 and 40 respectively. Ultra-performance liquid chromatography tandem high-resolution mass spectrometry was used to analyze placental metabolomics. Then, we verified the differentially expressed proteins and metabolites, both placental and blood serum, in the first, second, and third trimesters.

Results

Metabolomic analysis of placental tissue revealed that fatty acid metabolism and primary bile acid biosynthesis were enriched. In the integrated proteomic and metabolomic analysis of placental tissue, peroxisomal acyl-CoA oxidase 1 (ACOX1), L-palmitoylcarnitine, and glycocholic acid were found to be three potential biomarkers. In a follow–up analysis, expression levels of both placental and serum ACOX1, L-palmitoylcarnitine, and glycocholic acid in both placenta and serum were found to be significantly higher in third-trimester ICP patients; the areas under the ROC curves were 0.823, 0.896, and 0.985, respectively. Expression levels of serum ACOX1, L-palmitoylcarnitine, and glycocholic acid were also significantly higher in first- and second-trimester ICP patients; the areas under the ROC curves were 0.726, 0.657, and 0.686 in the first trimester and 0.718, 0.727, and 0.670 in the second trimester, respectively. Together, levels of the three aforementioned biomarkers increased the value for diagnosing and predicting ICP (AUC: 0.993 for the third, 0.891 for the second, and 0.932 for the first trimesters).

Conclusions

L-palmitoylcarnitine, ACOX1, and glycocholic acid levels taken together may serve as a new biomarker set for the diagnosis and prediction of ICP.
Genetic Modification of Cytokine Signaling to Enhance Efficacy of CAR T Cell Therapy in Solid Tumors
Authors: Ghahri-Saremi Navid , Akbari Behnia , Soltantoyeh Tahereh , Hadjati Jamshid , Ghassemi Saba , Mirzaei Hamid Reza
Published: October 2021

Chimeric antigen receptor (CAR) T cell therapy has shown unprecedented success in treating advanced hematological malignancies. Its effectiveness in solid tumors has been limited due to heterogeneous antigen expression, a suppressive tumor microenvironment, suboptimal trafficking to the tumor site and poor CAR T cell persistence. Several approaches have been developed to overcome these obstacles through various strategies including the genetic engineering of CAR T cells to blunt the signaling of immune inhibitory receptors as well as to modulate signaling of cytokine/chemokine molecules and their receptors. In this review we offer our perspective on how genetically modifying cytokine/chemokine molecules and their receptors can improve CAR T cell qualities such as functionality, persistence (e.g. resistance to pro-apoptotic signals) and infiltration into tumor sites. Understanding how such modifications can overcome barriers to CAR T cell effectiveness will undoubtedly enhance the potential of CAR T cells against solid tumors.
Endogenous α7 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier
Authors: He Xiaolong , Wang Lei , Liu Liqun , Gao Jie , Long Beiguo , Chi Feng , Hu Tongtong , Wan Yu , Gong Zelong , Li Li , Zhen Peilin , Zhang Tiesong , Cao Hong , Huang Sheng-He
Published: October 2021

Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) is critical for the pathogenesis of Escherichia coli (E. coli) K1 meningitis, a severe central nervous system infection of the neonates. However, little is known about how E. coli K1 manipulates α7 nAChR signaling. Here, through employing immortalized cell lines, animal models, and human transcriptional analysis, we showed that E. coli K1 infection triggers releasing of secreted Ly6/Plaur domain containing 1 (SLURP1), an endogenous α7 nAChR ligand. Exogenous supplement of SLURP1, combined with SLURP1 knockdown or overexpression cell lines, showed that SLURP1 is required for E. coli K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Furthermore, we found that SLURP1 is required for E. coli K1-induced α7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the α7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate α7 nAChR and facilitate its pathogenesis, and blocking SLURP1-α7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis.
Case Report: Deficiency of Adenosine Deaminase 2 Presenting With Overlapping Features of Autoimmune Lymphoproliferative Syndrome and Bone Marrow Failure
Authors: Dell’Orso Gianluca , Grossi Alice , Penco Federica , Caorsi Roberta , Palmisani Elena , Terranova Paola , Schena Francesca , Lupia Michela , Ricci Erica , Montalto Shana , Pierri Filomena , Ceccherini Isabella , Fioredda Francesca , Dufour Carlo , Gattorno Marco , Miano Maurizio
Published: October 2021

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, such as vasculitis, inflammation, and hematologic manifestations. Some associations of clinical features can mimic autoimmune lymphoproliferative syndrome (ALPS). We report a case of a female patient who fulfilled the 2009 National Institute of Health revised criteria for ALPS and received a delayed diagnosis of DADA2. During her childhood, she suffered from autoimmune hemolytic anemia, immune thrombocytopenia, and chronic lymphoproliferation, which partially responded to multiple lines of treatments and were followed, at 25 years of age, by pulmonary embolism, septic shock, and bone marrow failure with myelodysplastic evolution. The patient died from the progression of pulmonary disease and multiorgan failure. Two previously unreported variants of gene ADA2/CECR1 were found through next-generation sequencing analysis, and a pathogenic role was demonstrated through a functional study. A single somatic STAT3 mutation was also found. Clinical phenotypes encompassing immune dysregulation and marrow failure should be evaluated at the early stage of diagnostic work-up with an extended molecular evaluation. A correct genetic diagnosis may lead to a precision medicine approach consisting of the use of targeted treatments or early hematopoietic stem cell transplantation.
Is Human Chorionic Gonadotropin Trigger Beneficial for Natural Cycle Frozen-Thawed Embryo Transfer?
Authors: Gao Dan-Dan , Li Li , Zhang Yi , Wang Xiao-Xuan , Song Jing-Yan , Sun Zhen-Gao
Published: October 2021

Objective: The aim of this study is to investigate, in ovulatory patients, whether there is a difference in reproductive outcomes following frozen-thawed embryo transfer (FET) in natural cycles (NC) compared to modified natural cycles (mNC).

Methods: This retrospective cohort study, performed at the public tertiary fertility clinic, involved all infertile patients undergoing endometrial preparation prior to FET in NC and mNC from January, 2017 to November, 2020. One thousand hundred and sixty-two patients were divided into two groups: mNC group (n = 248) had FET in a NC after ovulation triggering with human chorionic gonadotropin (hCG); NC group (n = 914) had FET in a NC after spontaneous ovulation were observed. The primary outcome was live birth rate. All pregnancy outcomes were analyzed by propensity score matching (PSM) and multivariable logistic regression analyses.

Results: The NC group showed a higher live birth rate [344/914 (37.6%) vs. 68/248 (27.4%), P = 0.003; 87/240 (36.3%) vs. 66/240 (27.5%), P = 0.040] than the mNC group before and after PSM analysis. Multivariable analysis also showed mNC to be associated with a decreased likelihood of live birth compared with NC [odds ratio (OR) 95% confidence interval (CI) 0.71 (0.51–0.98), P = 0.039].

Conclusion: For women with regular menstrual cycles, NC-FET may have a higher chance of live birth than that in the mNC-FET cycles. As a consequence, it's critical to avoid hCG triggering as much as possible when FETs utilize a natural cycle strategy for endometrial preparation. Nevertheless, further more well-designed randomized clinical trials are still needed to determine this finding.
Lactitol Supplementation Modulates Intestinal Microbiome in Liver Cirrhotic Patients
Authors: Lu Haifeng , Chen Liang , Pan Xiaxia , Yao Yujun , Zhang Hua , Zhu Xiaofei , Lou Xiaobin , Zhu Chunxia , Wang Jun , Li Lanjuan , Wu Zhongwen
Published: October 2021

Background: Cirrhosis is a common chronic liver disease characterized by irreversible diffuse liver damage. Intestinal microbiome dysbiosis and metabolite dysfunction contribute to the development of cirrhosis. Lactitol (4-β-D-galactopyranosyl-D-glucitol) was previously reported to promote the growth of intestinal Bifidobacteria. However, the effect of lactitol on the intestinal microbiome and fecal short-chain fatty acids (SCFAs) and bile acids (BAs) and the interactions among these factors in cirrhotic patients pre- and post-lactitol treatment remain poorly understood.

Methods: Here, using shotgun metagenomics and targeted metabolomics methods.

Results: we found that health-promoting lactic acid bacteria, including Bifidobacterium longum, B.pseudocatenulatum, and Lactobacillus salivarius, were increased after lactitol intervention, and significant decrease of pathogen Klebsiella pneumonia and associated antibiotic resistant genes /virulence factors. Functionally, pathways including Pseudomonas aeruginosa biofilm formation, endotoxin biosynthesis, and horizontal transfer of pathogenic genes were decreased in cirrhotic patients after 4-week lactitol intervention compared with before treatment.

Conclusion: We identified lactitol-associated metagenomic changes, and provide insight into the understanding of the roles of lactitol in modulating gut microbiome in cirrhotic patients.