bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation Analysis Between Ovarian Reserve and Thyroid Hormone Levels in Infertile Women of Reproductive Age
Authors: Wu Jie , Zhao Ying-jie , Wang Min , Tang Ming-qiang , Liu Yao-fang
Published: September 2021

Objective

To analyze the correlation between ovarian reserve and thyroid function in women with infertility.

Methods

Retrospective analysis of the data of 496 infertility patients who visited the clinic between January 2019 and December 2020. According to the TSH level, it is grouped into <2.5 mIU/L, 2.5~4.0mIU/L and ≥4.0 mIU/L or according to the positive/negative thyroid autoimmune antibody. The relationship was assessed through the ovarian reserve, thyroid function, and anti-Müllerian hormone (AMH) levels in infertile patients. On the other hand, the patients are divided into groups according to age (≤29 years old, 30-34 years old and ≥35 years old), basic FSH (<10 IU/L and ≥10 IU/L), and AMH levels. The ovarian reserve was evaluated through the AMH and the antral follicle count (AFC).

Results

The average age of the patients was 30.31 ± 4.50 years old, and the average AMH level was 5.13 ± 4.30 ng/mL. 3.63% (18/496) of patients had abnormal TSH levels (normal: 0.35-5.5 mIU/L), the positive rate of thyroid peroxidase antibody (TPOAb) was 14.52% (72/496), the positive rate of anti-thyroglobulin antibody (TgAb) was 16.94% (84/496), and the positive rate of TPOAb and TgAb was 10.48% (52/496). After grouping according to TSH level or thyroid autoimmune antibody positive/negative grouping, the analysis found that there was no statistical significance in age, AMH level and basic FSH level among the groups (P>0.05). There were no significant differences in the levels of TSH, FT3, and FT4 among different ages, AMH, and FSH levels (P>0.05).

Conclusion

There is no significant correlation between ovarian reserve and thyroid function in infertile women.
Four-Year Teriparatide Followed by Denosumab vs. Continuous Denosumab in Glucocorticoid-Induced Osteoporosis Patients With Prior Bisphosphonate Treatment
Authors: Hirooka Yasuaki , Nozaki Yuji , Okuda Saki , Sugiyama Masafumi , Kinoshita Koji , Funauchi Masanori , Matsumura Itaru
Published: September 2021

Objectives

In our previous 24-month study, we observed that teriparatide had some advantages over denosumab for bone mineral density (BMD) in glucocorticoid-induced osteoporosis (GIO) patients with prior bisphosphonate treatment. We conducted this extension study to investigate whether the advantage of teriparatide obtained in the first 2 years would be maintained after the switch to denosumab.

Materials and Methods

We switched patients who had completed 24-month daily teriparatide treatment to denosumab (switch group, n=18) and compared their BMD every 6 months up to 48 months with the group who continued to receive denosumab (denosumab group, n=16).

Results

At 48 months, the lumbar spine BMD was significantly increased from baseline in both groups (denosumab: 10.4 ± 8.7%, p<0.001; switch: 14.2 ± 6.8%, p<0.001). However, a significant increase in femoral neck BMD from baseline occurred only in the switch group (11.2 ± 14.6%, p<0.05); denosumab (4.1 ± 10.8%). The total hip BMD increased significantly from baseline in both groups (denosumab: 4.60 ± 7.4%, p<0.05; switch: 7.2 ± 6.9%, p<0.01). Femoral neck BMD was significantly increased in the switch versus the denosumab group (p<0.05).

Conclusion

In GIO patients with prior bisphosphonate treatment, the advantage of teriparatide may be maintained after the treatment period. A continuous increase in BMD can be expected with teriparatide followed by denosumab.
Tree Mortality Risks Under Climate Change in Europe: Assessment of Silviculture Practices and Genetic Conservation Networks
Authors: Petit-Cailleux Cathleen , Davi Hendrik , Lefèvre François , Verkerk Pieter Johannes , Fady Bruno , Lindner Marcus , Oddou-Muratorio Sylvie
Published: September 2021

General Context: Climate change can positively or negatively affect abiotic and biotic drivers of tree mortality. Process-based models integrating these climatic effects are only seldom used at species distribution scale.

Objective: The main objective of this study was to investigate the multi-causal mortality risk of five major European forest tree species across their distribution range from an ecophysiological perspective, to quantify the impact of forest management practices on this risk and to identify threats on the genetic conservation network.

Methods: We used the process-based ecophysiological model CASTANEA to simulate the mortality risk of Fagus sylvatica, Quercus petraea, Pinus sylvestris, Pinus pinaster, and Picea abies under current and future climate conditions, while considering local silviculture practices. The mortality risk was assessed by a composite risk index (CRIM) integrating the risks of carbon starvation, hydraulic failure and frost damage. We took into account extreme climatic events with the CRIMmax, computed as the maximum annual value of the CRIM.

Results: The physiological processes' contributions to CRIM differed among species: it was mainly driven by hydraulic failure for P. sylvestris and Q. petraea, by frost damage for P. abies, by carbon starvation for P. pinaster, and by a combination of hydraulic failure and frost damage for F. sylvatica. Under future climate, projections showed an increase of CRIM for P. pinaster but a decrease for P. abies, Q. petraea, and F. sylvatica, and little variation for P. sylvestris. Under the harshest future climatic scenario, forest management decreased the mean CRIM of P. sylvestris, increased it for P. abies and P. pinaster and had no major impact for the two broadleaved species. By the year 2100, 38–90% of the European network of gene conservation units are at extinction risk (CRIMmax=1), depending on the species.

Conclusions: Using a process-based ecophysiological model allowed us to disentangle the multiple drivers of tree mortality under current and future climates. Taking into account the positive effect of increased CO2 on fertilization and water use efficiency, average mortality risk may increase or decrease in the future depending on species and sites. However, under extreme climatic events, our process-based projections are as pessimistic as those obtained using bioclimatic niche models.
Ferroptosis-Related Genes in Lung Adenocarcinoma: Prognostic Signature and Immune, Drug Resistance, Mutation Analysis
Authors: Ren Ziyuan , Hu Minghui , Wang Zhonglin , Ge Junpeng , Zhou Xiaoyan , Zhang Guoming , Zheng Hongying
Published: September 2021

Graphical Abstract

Ferroptosis genes in lung adenocarcinoma.
In vivo Estimation of Breast Cancer Tissue Volume in Subcutaneous Xenotransplantation Mouse Models by Using a High-Sensitivity Fiber-Based Terahertz Scanning Imaging System
Authors: Chen Hua , Han Juan , Wang Dan , Zhang Yu , Li Xiao , Chen Xiaofeng
Published: September 2021

Absorption contrast between the terahertz (THz) frequency range of fatty and cancer tissues allows cancer diagnosis by THz imaging. We successfully demonstrated the ability of THz imaging to measure small breast cancer volume in the subcutaneous xenotransplantation mouse models even without external comparison. We estimated the volume detection limitation of the fiber-based THz scanning imaging system using a highly sensitive cryogenic-temperature-operated Schottky diode detector to be smaller than 1 mm3, thus showing the potential application of this technique in preliminary early cancer diagnosis.
Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers
Authors: Villegas-Mirón Pablo , Acosta Sandra , Nye Jessica , Bertranpetit Jaume , Laayouni Hafid
Published: September 2021

The ability of detecting adaptive (positive) selection in the genome has opened the possibility of understanding the genetic basis of population-specific adaptations genome-wide. Here, we present the analysis of recent selective sweeps, specifically in the X chromosome, in human populations from the third phase of the 1,000 Genomes Project using three different haplotype-based statistics. We describe instances of recent positive selection that fit the criteria of hard or soft sweeps, and detect a higher number of events among sub-Saharan Africans than non-Africans (Europe and East Asia). A global enrichment of neural-related processes is observed and numerous genes related to fertility appear among the top candidates, reflecting the importance of reproduction in human evolution. Commonalities with previously reported genes under positive selection are found, while particularly strong new signals are reported in specific populations or shared across different continental groups. We report an enrichment of signals in genes that escape X chromosome inactivation, which may contribute to the differentiation between sexes. We also provide evidence of a widespread presence of soft-sweep-like signatures across the chromosome and a global enrichment of highly scoring regions that overlap potential regulatory elements. Among these, enhancers-like signatures seem to present putative signals of positive selection which might be in concordance with selection in their target genes. Also, particularly strong signals appear in regulatory regions that show differential activities, which might point to population-specific regulatory adaptations.
Ancestral Spectrum Analysis With Population-Specific Variants
Authors: Shi Gang , Kuang Qingmin
Published: September 2021

With the advance of sequencing technology, an increasing number of populations have been sequenced to study the histories of worldwide populations, including their divergence, admixtures, migration, and effective sizes. The variants detected in sequencing studies are largely rare and mostly population specific. Population-specific variants are often recent mutations and are informative for revealing substructures and admixtures in populations; however, computational methods and tools to analyze them are still lacking. In this work, we propose using reference populations and single nucleotide polymorphisms (SNPs) specific to the reference populations. Ancestral information, the best linear unbiased estimator (BLUE) of the ancestral proportion, is proposed, which can be used to infer ancestral proportions in recently admixed target populations and measure the extent to which reference populations serve as good proxies for the admixing sources. Based on the same panel of SNPs, the ancestral information is comparable across samples from different studies and is not affected by genetic outliers, related samples, or the sample sizes of the admixed target populations. In addition, ancestral spectrum is useful for detecting genetic outliers or exploring co-ancestry between study samples and the reference populations. The methods are implemented in a program, Ancestral Spectrum Analyzer (ASA), and are applied in analyzing high-coverage sequencing data from the 1000 Genomes Project and the Human Genome Diversity Project (HGDP). In the analyses of American populations from the 1000 Genomes Project, we demonstrate that recent admixtures can be dissected from ancient admixtures by comparing ancestral spectra with and without indigenous Americans being included in the reference populations.
Comprehensive Genomic Analysis of the Endophytic Bacillus altitudinis Strain GLB197, a Potential Biocontrol Agent of Grape Downy Mildew
Authors: Zeng Qingchao , Xie Jianbo , Li Yan , Gao Tantan , Zhang Xun , Wang Qi
Published: September 2021

Bacillus has been extensively studied for agricultural application as a biocontrol agent. B. altitudinis GLB197, an endophytic bacterium isolated from grape leaves, exhibits distinctive inhibition to grape downy mildew based on unknown mechanisms. To determine the genetic traits involved in the mechanism of biocontrol and host-interaction traits, the genome sequence of GLB197 was obtained and further analyzed. The genome of B. altitudinis GLB197 consisted of one plasmid and a 3,733,835-bp circular chromosome with 41.56% G + C content, containing 3,770 protein-coding genes. Phylogenetic analysis of 17 Bacillus strains using the concatenated 1,226 single-copy core genes divided into different clusters was conducted. In addition, average nucleotide identity (ANI) values indicate that the current taxonomy of some B. pumilus group strains is incorrect. Comparative analysis of B. altitudinis GLB197 proteins with other B. altitudinis strains identified 3,157 core genes. Furthermore, we found that the pan-genome of B. altitudinis is open. The genome of B. altitudinis GLB197 contains one nonribosomal peptide synthetase (NRPS) gene cluster which was annotated as lichenysin. Interestingly, the cluster in B. altitudinis has two more genes than other Bacillus strains (lgrD and lgrB). The two genes were probably obtained via horizontal gene transfer (HGT) during the evolutionary process from Brevibacillus. Taken together, these observations enable the future application of B. altitudinis GLB197 as a biocontrol agent for control of grape downy mildew and promote our understanding of the beneficial interactions between B. altitudinis GLB197 and plants.
Construction and Validation of an Immune Cell Signature Score to Evaluate Prognosis and Therapeutic Efficacy in Hepatocellular Carcinoma
Authors: Xu Linfeng , Jian Xingxing , Liu Zhenhao , Zhao Jingjing , Zhang Siwen , Lin Yong , Xie Lu
Published: September 2021

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with high morbidity and mortality worldwide. Tumor immune microenvironment (TIME) plays a pivotal role in the outcome and treatment of HCC. However, the effect of immune cell signatures (ICSs) representing the characteristics of TIME on the prognosis and therapeutic benefit of HCC patients remains to be further studied.

Materials and methods: In total, the gene expression profiles of 1,447 HCC patients from several databases, i.e., The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, and Gene Expression Omnibus, were obtained and applied. Based on a comprehensive collection of marker genes, 182 ICSs were evaluated by single sample gene set enrichment analysis. Then, by performing univariate and multivariate Cox analysis and random forest modeling, four significant signatures were selected to fit an immune cell signature score (ICSscore).

Results: In this study, an ICSscore-based prognostic model was constructed to stratify HCC patients into high-risk and low-risk groups in the TCGA-LIHC cohort, which was successfully validated in two independent cohorts. Moreover, the ICSscore values were found to positively correlate with the current American Joint Committee on Cancer staging system, indicating that ICSscore could act as a comparable biomarker for HCC risk stratification. In addition, when setting the four ICSs and ICSscores as features, the classifiers can significantly distinguish treatment-responding and non-responding samples in HCC. Also, in melanoma and breast cancer, the unified ICSscore could verify samples with therapeutic benefits.

Conclusion: Overall, we simplified the tedious ICS to develop the ICSscore, which can be applied successfully for prognostic stratification and therapeutic evaluation in HCC. This study provides an insight into the therapeutic predictive efficacy of prognostic ICS, and a novel ICSscore was constructed to allow future expanded application.
SOCS3 is Related to Cell Proliferation in Neuronal Tissue: An Integrated Analysis of Bioinformatics and Experiments
Authors: Yu Yeuni , Sung Soon Ki , Lee Chi Hyung , Ha Mihyang , Kang Junho , Kwon Eun Jung , Kang Ji Wan , Kim Youngjoo , Kim Ga Hyun , Heo Hye Jin , Lee Hansong , Kim Tae Woo , Lee Yoonsung , Myung Kyungjae , Oh Chang-Kyu , Kim Yun Hak
Published: September 2021

Glioma is the most common primary malignant tumor that occurs in the central nervous system. Gliomas are subdivided according to a combination of microscopic morphological, molecular, and genetic factors. Glioblastoma (GBM) is the most aggressive malignant tumor; however, efficient therapies or specific target molecules for GBM have not been developed. We accessed RNA-seq and clinical data from The Cancer Genome Atlas, the Chinese Glioma Genome Atlas, and the GSE16011 dataset, and identified differentially expressed genes (DEGs) that were common to both GBM and lower-grade glioma (LGG) in three independent cohorts. The biological functions of common DEGs were examined using NetworkAnalyst. To evaluate the prognostic performance of common DEGs, we performed Kaplan-Meier and Cox regression analyses. We investigated the function of SOCS3 in the central nervous system using three GBM cell lines as well as zebrafish embryos. There were 168 upregulated genes and 50 downregulated genes that were commom to both GBM and LGG. Through survival analyses, we found that SOCS3 was the only prognostic gene in all cohorts. Inhibition of SOCS3 using siRNA decreased the proliferation of GBM cell lines. We also found that the zebrafish ortholog, socs3b, was associated with brain development through the regulation of cell proliferation in neuronal tissue. While additional mechanistic studies are necessary, our results suggest that SOCS3 is an important biomarker for glioma and that SOCS3 is related to the proliferation of neuronal tissue.
Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer
Authors: Shi Junhong , Bao Meiyu , Wang Weifeng , Wu Xuan , Li Yueying , Zhao Changdong , Liu Weiwei
Published: September 2021

Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. PLOD3 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of PLOD3-related genes. The correlation between PLOD3 expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of PLOD3 in CRC. What’s more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. PLOD3 was highly expressed in many tumors including CRC. PLOD3 was upregulated in advanced stage CRCs, and high PLOD3 expression was associated with poor survival. High PLOD3 expression was associated with low levels of B cells, CD4+ T cells, M1 macrophages, CD8+ T cells, and multiple immunerelated characteristics. In addition, the high PLOD3 expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high PLOD3 expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of PLOD3 at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased PLOD3 expression in an immunotherapy treated dataset. PLOD3 is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high PLOD3 expression may be resistant to immune checkpoint therapy.
IgM Deficiency in Autoimmune Blistering Mucocutaneous Diseases Following Various Treatments: Long Term Follow-Up and Relevant Observations
Authors: Ahmed A. Razzaque , Aksoy Merve
Published: September 2021

IgM deficiency has been reported in patients with many autoimmune diseases treated with Rituximab (RTX). It has not been studied, in detail, in autoimmune mucocutaneous blistering diseases (AIMBD). Our objectives were: (i) Examine the dynamics of IgM levels in patients with and without RTX. (ii) Influence of reduced serum IgM levels on clinical and laboratory parameters. (iii) Explore the possible molecular and cellular basis for reduced serum IgM levels. This retrospective study that was conducted in a single-center from 2000 to 2020. Serial IgM levels were studied in 348 patients with five AIMBD (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, and ocular cicatricial pemphigoid) and found decreased in 55 patients treated with RTX, IVIG, and conventional immunosuppressive therapy (CIST). Hence the incidence of decreased serum IgM is low. The incidence of decreased IgM in patients treated with RTX was 19.6%, in patients treated with IVIG and CIST, it was 52.8% amongst the 55 patients. IgM levels in the post-RTX group were statistically significantly different from the IVIG group (p<0.018) and CIST group (p<0.001). There were no statistically significant differences between the groups in other clinical and laboratory measures. Decreased serum IgM did not affect depletion or repopulation of CD19+ B cells. Patients in the three groups achieved clinical and serological remission, in spite of decreased IgM levels. Decrease in IgM was isolated, since IgG and IgA were normal throughout the study period. Decreased IgM persisted at the same level, while the patients were in clinical remission, for several years. In spite of persistent decreased IgM levels, the patients did not develop infections, tumors, other autoimmune diseases, or warrant hospitalization. Studies on IgM deficiency in knockout mice provided valuable insights. There is no universally accepted mechanism that defines decreased IgM levels in AIMBD. The data is complex, multifactorial, sometimes contradictory, and not well understood. Nonetheless, data in this study provides novel information that enhances our understanding of the biology of IgM in health and disease.
Potential Therapeutic Applications of Pulmonary Surfactant Lipids in the Host Defence Against Respiratory Viral Infections
Authors: Ji Jianjian , Sun Ling , Luo Zichen , Zhang Ying , Xianzheng Wang , Liao Yingzhao , Tong Xie , Shan Jinjun
Published: September 2021

Pulmonary surfactant is a complex and highly surface-active material. It covers the alveolar epithelium and consists of 90% lipids and 10% proteins. Pulmonary surfactant lipids together with pulmonary surfactant proteins facilitate breathing by reducing surface tension of the air-water interface within the lungs, thereby preventing alveolar collapse and the mechanical work required to breathe. Moreover, pulmonary surfactant lipids, such as phosphatidylglycerol and phosphatidylinositol, and pulmonary surfactant proteins, such as surfactant protein A and D, participate in the pulmonary host defense and modify immune responses. Emerging data have shown that pulmonary surfactant lipids modulate the inflammatory response and antiviral effects in some respiratory viral infections, and pulmonary surfactant lipids have shown promise for therapeutic applications in some respiratory viral infections. Here, we briefly review the composition, antiviral properties, and potential therapeutic applications of pulmonary surfactant lipids in respiratory viral infections.
Mast Cells Are Identified in the Lung Parenchyma of Wild Mice, Which Can Be Recapitulated in Naturalized Laboratory Mice
Authors: Yeh Yu-Wen , Chaudhuri Arka Sen , Zhou Ling , Fang Yu , Boysen Preben , Xiang Zou
Published: September 2021

Background

It is well documented that laboratory mice bred and maintained in ultra-hygienic specific pathogen-free (SPF) barriers display reduced richness and complexity of microbiota compared with wild mice. The laboratory mice profoundly lack lung parenchymal mast cells. Hence, we aimed to investigate the lung distribution of mast cells in free-living wild mice.

Methods

Wild house mice were trapped in South-Eastern Norway and Hemtabad, West Bengal, India. C57BL/6 laboratory mice were bred in a purposefully built, closed environment with bedding material obtained from the natural environment in order to normalize the gut microbiota of these laboratory mice to that of the wild mice, and the offspring were collected for study at eight weeks of age.

Results

Mast cells were easily identified at a substantial density in the lung parenchymal tissues of wild mice from both Norway and India, which stands in clear contrast to the rare distribution of lung parenchymal mast cells in the conventional laboratory SPF mice. Consistently, wild mice also expressed higher pulmonary levels of stem cell factor, a critical growth factor for mast cell survival. Higher levels of histamine were recorded in the lung tissues of the wild mice. Interestingly, “naturalized” C57BL/6 laboratory mice which spent their entire life in a semi-natural environment developed lung parenchymal mast cells at an appreciable density.

Conclusion

Our observations support that environmental factors, possibly through modulation of microbiota, may impact the tissue distribution of mast cells in mouse lung parenchyma.
Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?
Authors: Bellucci Gianmarco , Rinaldi Virginia , Buscarinu Maria Chiara , Reniè Roberta , Bigi Rachele , Pellicciari Giulia , Morena Emanuele , Romano Carmela , Marrone Antonio , Mechelli Rosella , Salvetti Marco , Ristori Giovanni
Published: September 2021

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host’s genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host’s response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.
Old - New Concrete Interfacial Bond Slip Monitoring in Anchored Rebar Reinforced Concrete Structure Using PZT Enabled Active Sensing
Authors: Jiang Jian , Chen Yixuan , Dai Junwu
Published: September 2021

Post-installed anchor technology is widely used for structural strengthening and for retrofitting existing constructions. The old–new concrete interface associated with using this technology is of great significance in the shear capacity of concrete structural member under shear forces. For such members, interface failures usually occur with bond slip. In this paper, an application of a piezoceramic enabled active sensing technique is put forward to monitor Old - New concrete interfacial bond slip. Three concrete specimens (S1, S2, and S3) are fabricated and each specimen consists of two parts. Each part is made of concrete poured at different times, and both are bonded with an anchored rebar embedded inside the specimen. Two PZT aggregates bonded to opposing sides of the concrete specimen helped to realize active sensing. During the shear loading test, both the load values and the signals from sensors are acquired every 20 s. The test durations of S1, S2 and S3 lasted 960, 1,120, and 1,110 s, respectively. Furthermore, the received signal energies are quantified through wavelet packet analysis to monitor the Old - New concrete interfacial bond slip process. The experimental results show that the change of WPEI in the received signals has a direct relation with the severity of the Old - New concrete interfacial bond slip. Moreover, the PZT-based active sensing approach is feasible to monitor the shear-induced bond slip in Old - New concrete interfaces.
The Effectiveness of Convalescent Plasma for the Treatment of Novel Corona Virus Disease 2019: A Systematic Review and Meta-Analysis
Authors: Cao Huiling , Ming Li , Chen Long , Zhu Xingwang , Shi Yuan
Published: September 2021

Background: Coronavirus disease 2019 (COVID-19), sweeping across the world, has created a worldwide pandemic. Effective treatments of COVID-19 are extremely urgent.

Objective: To analyze the efficacy and safety of convalescent plasma (CCP) on patients with COVID-19.

Methods: All the relevant studies were searched from PubMed, EMBASE,Cochrane library, Scopus, Web of Science, CBM, CNKI, Wan fang, VIP, Medrxiv, Biorxiv, and SSRN on July 19, 2021. PICOS criteria were as follows: (P) the study interests were human subjects with the infection of COVID-19; (I) the intervention of interest was CCP; (C) comparator treatments contained placebo, sham therapy, and standard treatment; (O) the primary outcome was mortality rates by the novel coronavirus. The secondary outcomes included the incidence of serious adverse events, the rate of ICU admission and mechanical ventilation (MV); the length of hospital stay; the duration of MV and ICU stay; the antibody levels, inflammatory factor levels, and viral loads. (S) Only randomized controlled trials (RCTs) of CCP were included. Subanalysis, quality assessment, sensitive analysis, and publication bias were conducted by two reviewers independently.

Results: Sixteen RCTs were included and enrolled a total of 16,296 participants in this meta-analysis. The pooled data showed that no significant difference was observed in reducing the rate of overall mortality between CCP treatment group and placebo group (OR 0.96; 95% CI 0.90 to 1.03; p = 0.30; I2 = 6%). According to the results of subgroup analysis, severe or critical patients with CCP showed significant difference in reducing the 28-day mortality of compared with placebo (OR 0.58, 95% CI 0.36 to 0.93, p = 0.02, I2 = 0%). CCP groups have a significantly shorter duration of MV compared with the control group (weighted MD −1.00, 95% CI −1.86 to −0.14 d p = 0.02, I2 = 0%). No significant difference was observed in the length of hospital stay, the duration of ICU, and the rate of ICU and MV. There is no conclusive evidence about the safety of CCP.

Conclusion: Convalescent plasma can significantly reduce the 28-day mortality of severe or critical COVID-19 patients and the duration of MV. However, more evidence was needed to prove the safety of convalescent plasma.
Management of Acute Exacerbation of Idiopathic Pulmonary Fibrosis in Specialised and Non-specialised ILD Centres Around the World
Authors: Polke Markus , Kondoh Yasuhiro , Wijsenbeek Marlies , Cottin Vincent , Walsh Simon L. F. , Collard Harold R. , Chaudhuri Nazia , Avdeev Sergey , Behr Jürgen , Calligaro Gregory , Corte Tamera J. , Flaherty Kevin , Funke-Chambour Manuela , Kolb Martin , Krisam Johannes , Maher Toby M. , Molina Molina Maria , Morais Antonio , Moor Catharina C. , Morisset Julie , Pereira Carlos , Quadrelli Silvia , Selman Moises , Tzouvelekis Argyrios , Valenzuela Claudia , Vancheri Carlo , Vicens-Zygmunt Vanesa , Wälscher Julia , Wuyts Wim , Bendstrup Elisabeth , Kreuter Michael
Published: September 2021

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication associated with a high mortality. However, evidence and guidance on management is sparse. The aim of this international survey was to assess differences in prevention, diagnostic and treatment strategies for AE-IPF in specialised and non-specialised ILD centres worldwide.

Material and Methods: Pulmonologists working in specialised and non-specialised ILD centres were invited to participate in a survey designed by an international expert panel. Responses were evaluated in respect to the physicians' institutions.

Results: Three hundred and two (65%) of the respondents worked in a specialised ILD centre, 134 (29%) in a non-specialised pulmonology centre. Similarities were frequent with regards to diagnostic methods including radiology and screening for infection, treatment with corticosteroids, use of high-flow oxygen and non-invasive ventilation in critical ill patients and palliative strategies. However, differences were significant in terms of the use of KL-6 and pathogen testing in urine, treatments with cyclosporine and recombinant thrombomodulin, extracorporeal membrane oxygenation in critical ill patients as well as antacid medication and anaesthesia measures as preventive methods.

Conclusion: Despite the absence of recommendations, approaches to the prevention, diagnosis and treatment of AE-IPF are comparable in specialised and non-specialised ILD centres, yet certain differences in the managements of AE-IPF exist. Clinical trials and guidelines are needed to improve patient care and prognosis in AE-IPF.
Effects of Previous Kasai Surgery on Gut Microbiota and Bile Acid in Biliary Atresia With End-Stage Liver Disease
Authors: Song Wei , Sun Li-Ying , Zhu Zhi-Jun
Published: September 2021

Background and Aims: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Although the Kasai procedure can improve temporary biliary drainage in some cases, complications and liver fibrosis still develop. Liver transplantation is the ultimate treatment. The current study aimed to investigate the effect of previous Kasai surgery on gut microbiota and bile acid in BA with end-stage liver disease.

Methods: Patients with BA with end-stage liver disease were divided into two groups according to whether they had previously undergone Kasai surgery (non-Kasai: n = 8, post-Kasai: n = 8). Metagenomic sequencing and ultraperformance liquid chromatography/tandem mass spectrometry were performed to identify the gut microbiota and bile acid.

Results: Previous Kasai surgery had some effects on gut microbiota and bile acid in BA with end-stage liver disease. In the gut microbiome, the differential species were mainly distributed at the species level. Veillonella atypica had a significant increase in the non-Kasai group (P < 0.05). Bacteroides spp., Prevotella spp., Barnesiella spp., Parabacteroides spp., Heliobacterium spp., Erysipelatoclostridium spp. and Diaporthe spp. were increased in the post-Kasai group (P < 0.05). Concerning functional profiles, methionine biosynthesis was enriched in the non-Kasai group, while pyridoxal biosynthesis and riboflavin biosynthesis were enriched in the post-Kasai group (linear discriminant analysis > 2, P < 0.05). In stools, 17 bile acids were distinctly elevated in the post-Kasai group, such as cholic acid, chenodeoxycholic acid, β-muricholic acid and tauro α-muricholate (P < 0.05). Spearman correlation test showed that V. atypica had an enormously positive correlation with liver enzymes. Faecalibacterium prausnitzii and Escherichia coli were associated with derivatives of the alternative pathway of bile acid metabolism.

Conclusion: Previous Kasai surgery can improve the gut microbiota and bile acid in patients with BA with end-stage liver disease. This improvement contributes to maintaining the intestinal barrier.
COVID-19 Lockdown Increased the Risk of Preterm Birth
Authors: Lin Ting-ting , Zhang Chen , Chen Lei , Jin Li , Lin Xian-hua , Pan Jie-xue , Dennis Cindy-Lee , Mol Ben W. , Huang He-feng , Wu Yan-ting
Published: September 2021

Purpose: To estimate whether the city-specific lockdown in Shanghai induced by the COVID-19 pandemic affected preterm birth rates among uninfected pregnant women in different trimesters.

Methods: The population-based retrospective cohort study was conducted in the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai, China. Pregnant women without COVID-19 received perinatal healthcare during lockdown (from January 24, 2020 to March 24, 2020) and non-lockdown (from January 24, 2019 to March 24, 2019) period and giving birth to a live infant at IPMCH were enrolled. 1:1 propensity score matching and Inverse probability of treatment weighting were used to evaluate preterm birth (<37 weeks), very preterm birth (<34 weeks), preterm birth with premature rupture of membranes (PROM-PTB), spontaneous preterm birth with intact membranes (S-PTB), and medically induced preterm birth (MI-PTB) between two groups.

Results: 8,270 pregnant women were in the lockdown group, and 9,815 were in the non-lockdown group. Pregnant women in second trimester during lockdown had a higher risk of PTB than those during the non-lockdown period [OR: 1.43 (CI 1.01–2.02), ARD: 1.7% (CI 0.04–3.4%), p = 0.045]. Furthermore, pregnant women in third trimester during lockdown had a higher risk of PROM-PTB than those during the non-lockdown period [OR: 1.64 (CI 1.09–2.47), ARD: 0.9% (CI 0.2–1.6%), p = 0.02]; no group differences were found related to rates of VPTB, S-PTB or MI-PTB.

Conclusion: In this cohort study in China, we found that there was an increased risk in preterm birth for non-infected women in COVID-19 lockdown who were in their second trimester.
Therapeutic Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Recovering From Murine Pulmonary Emphysema Under Cigarette Smoke Exposure
Authors: Chen Xiao-Yue , Chen Yi-Ying , Lin Willie , Chen Chien-Han , Wen Yu-Chieh , Hsiao Ta-Chih , Chou Hsiu-Chu , Chung Kian Fan , Chuang Hsiao-Chi
Published: September 2021

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were shown to have potential for immunoregulation and tissue repair. The objective of this study was to investigate the effects of hUC-MSCs on emphysema in chronic obstructive pulmonary disease (COPD). The C57BL/6JNarl mice were exposed to cigarette smoke (CS) for 4 months followed by administration of hUC-MSCs at 3 × 106 (low dose), 1 × 107 (medium dose), and 3 × 107 cells/kg body weight (high dose). The hUC-MSCs caused significant decreases in emphysema severity by measuring the mean linear intercept (MLI) and destructive index (DI). A decrease in neutrophils (%) and an increase in lymphocytes (%) in bronchoalveolar lavage fluid (BALF) were observed in emphysematous mice after hUC-MSC treatment. Lung levels of interleukin (IL)-1β, C-X-C motif chemokine ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and matrix metalloproteinase (MMP)-12 significantly decreased after hUC-MSC administration. Significant reductions in tumor necrosis factor (TNF)-α, IL-1β, and IL-17A in serum occurred after hUC-MSC administration. Notably, the cell viability of lung fibroblasts improved with hUC-MSCs after being treated with CS extract (CSE). Furthermore, the hUC-MSCs-conditioned medium (hUC-MSCs-CM) restored the contractile force, and increased messenger RNA expressions of elastin and fibronectin by lung fibroblasts. In conclusion, hUC-MSCs reduced inflammatory responses and emphysema severity in CS-induced emphysematous mice.
A Prospective Observational Study on the Efficacy and Safety of Infliximab-Biosimilar (CT-P13) in Patients With Takayasu Arteritis (TAKASIM)
Authors: Campochiaro Corrado , Tomelleri Alessandro , Sartorelli Silvia , Sembenini Camilla , Papa Maurizio , Fallanca Federico , Picchio Maria , Cavalli Giulio , De Cobelli Francesco , Baldissera Elena , Dagna Lorenzo
Published: September 2021

Objectives: Infliximab (IFX) is widely used in patients with refractory Takayasu arteritis (TAK). Recently, the IFX-biosimilar CT-P13 has been introduced for the treatment of inflammatory diseases. The aim of this study was to assess the efficacy and safety of CT-P13 in patients with refractory TAK.

Methods: In this prospective, open-label, single-center trial, TAK patients either already on treatment with IFX-originator (switch group) or never treated with IFX (naïve group) received CT-P13 for 52 weeks. The primary outcomes of the study were: (i) number of patients with active disease at month 6; (ii) incidence of treatment-emergent adverse events at month 12. Disease activity was assessed at month 6 and month 12 by clinical evaluation (ITAS-2020, ITAS-ESR, and ITAS-CRP scores) and imaging assessment [magnetic resonance angiography (MRA) and (18F)-FDG-PET].

Results: 23 patients were recruited (21 switch, 2 naïve). At baseline, 7 patients (32%) were classified as active. At month 6, one patient voluntarily dropped out and 7 patients were still active (30%), including one patient started on a different bDMARD at month 2 due to poor disease control. Mean daily dose of prednisone equivalent was significantly lower than baseline (4.2 ± 1.9 mg vs. 4.8 ± 2.1 mg, p = 0.009). At month 12, another patient was excluded because of pregnancy desire. Five patients were classified as active (24%), including two patients started on a different bDMARD at month 2 and month 6. Mean daily dose of prednisone equivalent was significantly lower than baseline (3.3 ± 2.6, p = 0.034). No patient experienced side effects during CT-P13 infusion. Overall, one patient experienced grade 1 adverse event and 9 patients experienced grade 2 adverse events. In no case hospitalization was required. CT-P13 retention rate was 90.9% at month 6 and 90.4% at month 12.

Conclusion: In this study, the use of IFX-biosimilar CT-P13 in patients with refractory TAK showed satisfying efficacy and safety profile.
Molecular Epidemiological Analysis of ST11-K64 Extensively Drug-Resistant Klebsiella pneumoniae Infections Outbreak in Intensive Care and Neurosurgery Units Based on Whole-Genome Sequencing
Authors: Xiong Liuxin , Su Lebin , Tan Hanqing , Zhao Wansha , Li Shuying , Zhu Yingmei , Lu Limiao , Huang Zhiwei , Li Baisheng
Published: September 2021

Klebsiella pneumoniae (Kp) is the primary causative bacteria for nosocomial infections and hospital outbreaks. In particular, extensively drug-resistant K. pneumoniae (XDRKp) causes severe clinical infections in hospitalized patients. Here, we used pulsed-field gel electrophoresis (PFGE), drug susceptibility tests, and the whole-genome sequencing (WGS) technology to examine genetic relatedness and phenotypic traits of the strains isolated during an outbreak period. Based on PFGE, a distinct clones cluster comprised of eight XDRKp was observed. These strains were confirmed as ST11-K64 via multiple-locus sequence typing database of Kp. The strains also had genes related to the regulation of biofilm biosynthesis (type 1 & 3 fimbriae, type IV pili biosynthesis, RcsAB, and type VI secretion system) and multiple drug resistance (β-lactamase and aminoglycoside antibiotic resistance). WGS data based on core-single nucleotide polymorphisms and epidemiological investigation showed that the neurosurgery unit was likely the source of the outbreak, the strain was likely to have been transmitted to the ICU through patients. In addition, the two highly probable transmission routes were in the ICU (exposure through shared hospital beds) and the neurosurgery units (all cases were treated by the same rehabilitation physician and were most likely infected during the physical therapy). Notably, the bed mattress had played a crucial transmission role of this outbreak, served as a pathogen reservoir.
Development of the Inactivated QazCovid-in Vaccine: Protective Efficacy of the Vaccine in Syrian Hamsters
Authors: Zhugunissov Kuandyk , Zakarya Kunsulu , Khairullin Berik , Orynbayev Mukhit , Abduraimov Yergali , Kassenov Markhabat , Sultankulova Kulyaisan , Kerimbayev Aslan , Nurabayev Sergazy , Myrzakhmetova Balzhan , Nakhanov Aziz , Nurpeisova Ainur , Chervyakova Olga , Assanzhanova Nurika , Burashev Yerbol , Mambetaliyev Muratbay , Azanbekova Moldir , Kopeyev Syrym , Kozhabergenov Nurlan , Issabek Aisha , Tuyskanova Moldir , Kutumbetov Lespek
Published: September 2021

In March 2020, the first cases of the human coronavirus disease COVID-19 were registered in Kazakhstan. We isolated the SARS-CoV-2 virus from clinical materials from some of these patients. Subsequently, a whole virion inactivated candidate vaccine, QazCovid-in, was developed based on this virus. To develop the vaccine, a virus grown in Vero cell culture was used, which was inactivated with formaldehyde, purified, concentrated, sterilized by filtration, and then adsorbed on aluminum hydroxide gel particles. The formula virus and adjuvant in buffer saline solution were used as the vaccine. The safety and protective effectiveness of the developed vaccine were studied in Syrian hamsters. The results of the studies showed the absolute safety of the candidate vaccine in the Syrian hamsters. When studying the protective effectiveness, the developed vaccine with an immunizing dose of 5 μg/dose specific antigen protected animals from a wild homologous virus at a dose of 104.5TCID50/mL. The candidate vaccine induced the formation of virus-neutralizing antibodies in vaccinated hamsters at titers of 3.3 ± 1.45 log2 to 7.25 ± 0.78 log2, and these antibodies were retained for 6 months (observation period) for the indicated titers. No viral replication was detected in vaccinated hamsters, protected against the development of acute pneumonia, and ensured 100% survival of the animals. Further, no replicative virus was isolated from the lungs of vaccinated animals. However, a virulent virus was isolated from the lungs of unvaccinated animals at relatively high titers, reaching 4.5 ± 0.7 log TCID50/mL. After challenge infection, 100% of unvaccinated hamsters showed clinical symptoms (stress state, passivity, tousled coat, decreased body temperature, and body weight, and the development of acute pneumonia), with 25 ± 5% dying. These findings pave the way for testing the candidate vaccine in clinical human trials.
Molecular Characterisation of Vancomycin-Resistant Enterococcus faecium Isolates Belonging to the Lineage ST117/CT24 Causing Hospital Outbreaks
Authors: Lisotto Paola , Couto Natacha , Rosema Sigrid , Lokate Mariëtte , Zhou Xuewei , Bathoorn Erik , Harmsen Hermie J. M. , Friedrich Alexander W. , Rossen John W. A. , Chlebowicz-Fliss Monika A.
Published: September 2021

Background: Vancomycin-resistant Enterococcus faecium (VREfm) is a successful nosocomial pathogen. The current molecular method recommended in the Netherlands for VREfm typing is based on core genome Multilocus sequence typing (cgMLST), however, the rapid emergence of specific VREfm lineages challenges distinguishing outbreak isolates solely based on their core genome. Here, we explored if a detailed molecular characterisation of mobile genetic elements (MGEs) and accessory genes could support and expand the current molecular typing of VREfm isolates sharing the same genetic background, enhancing the discriminatory power of the analysis.

Materials/Methods: The genomes of 39 VREfm and three vancomycin-susceptible E. faecium (VSEfm) isolates belonging to ST117/CT24, as assessed by cgMLST, were retrospectively analysed. The isolates were collected from patients and environmental samples from 2011 to 2017, and their genomes were analysed using short-read sequencing. Pangenome analysis was performed on de novo assemblies, which were also screened for known predicted virulence factors, antimicrobial resistance genes, bacteriocins, and prophages. Two representative isolates were also sequenced using long-read sequencing, which allowed a detailed analysis of their plasmid content.

Results: The cgMLST analysis showed that the isolates were closely related, with a minimal allelic difference of 10 between each cluster’s closest related isolates. The vanB-carrying transposon Tn1549 was present in all VREfm isolates. However, in our data, we observed independent acquisitions of this transposon. The pangenome analysis revealed differences in the accessory genes related to prophages and bacteriocins content, whilst a similar profile was observed for known predicted virulence and resistance genes.

Conclusion: In the case of closely related isolates sharing a similar genetic background, a detailed analysis of MGEs and the integration point of the vanB-carrying transposon allow to increase the discriminatory power compared to the use of cgMLST alone. Thus, enabling the identification of epidemiological links amongst hospitalised patients.