bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Type of Infertility and Live Birth in Couples With a Single Intrauterine Insemination Resulting in Pregnancy: A Propensity Score Matching Cohort Study
Authors: He Wen , Chen Song , Huang Jianping , Zhang Xiaofang , Hu Lili , Xue Zhigang , Qiu Yu
Published: July 2022

Background

Few studies have described the relationship between the type of infertility and live birth in patients treated with intrauterine insemination (IUI). We focused on this issue and attempted to explore it.

Methods

This retrospective study enrolled 2,256 infertile patients who underwent their first IUI cycle and were subsequently diagnosed with a clinical pregnancy at Ji’an Women and Child Health Care Hospital between 2007 and 2018. Inductees were divided into primary infertility (1,680 patients) and secondary infertility groups (876 patients). Following 1:1 propensity score matching to obtain balanced data, the COX proportional hazards model, landmark analysis, and subgroup analysis were used to assess the association between infertility types and live birth rates. Subsequently, a sensitivity analysis was employed to evaluate the potential effect of unmeasured confounding on outcomes.

Results

Of the 1,486 patients who were identified as a matched cohort, 743 were in the primary infertility group and the remaining patients were in another group. A total of 1,143 patients had live births during 431,009 person-days of follow-up (average 290.0 days). Throughout the follow-up period, patients with secondary infertility demonstrated more live births than patients with primary infertility (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.04 to 1.30; P = .007). More details were observed in the landmark analysis. Live birth rates were similar in both groups within 316 days of follow-up (HR, 0.84; 95% CI, 0.62 to 1.14; P = .269), whereas the opposite was found between 316 days of follow-up and delivery day (HR, 1.19; 95% CI, 1.06 to 1.34; P = .004). This was also obtained in a subgroup analysis of patients younger than 35 years old and patients treated with natural cycles (NCs) and IUIs.

Conclusion

Among the infertile patients who underwent a single natural or stimulated cycle followed by IUI and had later pregnancies, full-term young secondary infertility mothers (<35 years of age) had a greater chance of having viable babies than the primary infertility ones. The latter may get more benefits when undergoing ovarian stimulation and IUI rather than NC-IUI.
Bioinformatics Analysis of the Mechanisms of Diabetic Nephropathy via Novel Biomarkers and Competing Endogenous RNA Network
Authors: Guo Mingfei , Dai Yaji , Jiang Lei , Gao Jiarong
Published: July 2022

Diabetic nephropathy (DN) is one of the common chronic complications of diabetes with unclear molecular mechanisms, which is associated with end-stage renal disease (ESRD) and chronic kidney disease (CKD). Our study intended to construct a competing endogenous RNA (ceRNA) network via bioinformatics analysis to determine the potential molecular mechanisms of DN pathogenesis. The microarray datasets (GSE30122 and GSE30529) were downloaded from the Gene Expression Omnibus database to find differentially expressed genes (DEGs). GSE51674 and GSE155188 datasets were used to identified the differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), respectively. The DEGs between normal and DN renal tissues were performed using the Linear Models for Microarray (limma) package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the mechanisms of DEGs in the progression of DN. The protein–protein interactions (PPI) of DEGs were carried out by STRING database. The lncRNA–miRNA–messenger RNA (mRNA) ceRNA network was constructed and visualized via Cytoscape on the basis of the interaction generated through the miRDB and TargetScan databases. A total of 94 significantly upregulated and 14 downregulated mRNAs, 31 upregulated and 121 downregulated miRNAs, and nine upregulated and 81 downregulated lncRNAs were identified. GO and KEGG pathways enriched in several functions and expression pathways, such as inflammatory response, immune response, identical protein binding, nuclear factor kappa b (NF-κB) signaling pathway, and PI3K-Akt signaling pathway. Based on the analysis of the ceRNA network, five differentially expressed lncRNAs (DElncRNAs) (SNHG6, KCNMB2-AS1, LINC00520, DANCR, and PCAT6), five DEmiRNAs (miR-130b-5p, miR-326, miR-374a-3p, miR-577, and miR-944), and five DEmRNAs (PTPRC, CD53, IRF8, IL10RA, and LAPTM5) were demonstrated to be related to the pathogenesis of DN. The hub genes were validated by using receiver operating characteristic curve (ROC) and real-time PCR (RT-PCR). Our research identified hub genes related to the potential mechanism of DN and provided new lncRNA–miRNA–mRNA ceRNA network that contributed to diagnostic and potential therapeutic targets for DN.
Impacts of Biologically Induced Degradation on Surface Energy, Wettability, and Cohesion of Corn Stover
Authors: Leal Juan H. , Meierdierks Eric J. , Navar Ricardo , Moore Cameron M. , Ray Allison E. , Semelsberger Troy A.
Published: July 2022

The impacts of biological degradation on surface area, surface energy, wettability, and cohesion of anatomically fractionated (i.e., leaf, stalk, and cob) and bulk corn stover are presented in this study. The physical, thermal and chemical properties of corn stover are critical material attributes that not only influence the mechanical processing and chemical conversion of corn stover, but also the bulk solids handling and transport. The measured surface areas were observed to be dependent on the degree of biological degradation (mild vs. moderate vs. severe) and on the anatomical fraction. The surface area of the bulk corn stover samples increased with the degree of biological degradation. The leaf fraction was the most sensitive to biological degradation, resulting in an increase in surface area from 0.5 m2/g (mildly degraded) to 1.2 m2/g (severely degraded). In contrast, the surface area of the cob fraction remained relatively unaffected by the degree of biological degradation (i.e., mildly degraded−0.55 m2/g, severely degraded−0.40 m2/g. All biologically degraded samples resulted in significant changes to the surface chemistry (evidenced by an increase in surface energy. As a general trend, the surface energy of bulk corn stover increased with the degree of biological degradation—the same trend was observed for the leaf and stalk anatomical fractions; however, the surface energy for the cob fraction remained unchanged. Wettability, calculated from surface energy, for bulk corn stover samples did not reveal any discernable trend with the degree of biological degradation. However, trends in wettability were observed for the anatomical fractions, with wettability increasing for the stalk and leaf fractions, and decreasing for the cob fraction. Excluding the cob fraction, the work of cohesion increased with the degree of biological degradation. Understanding the impacts of biological degradation on the physical, chemical and thermal properties of corn stover offers insights to improve the overall operational reliability, efficiency and economics of integrated biorefineries.
A Fast and Accurate Calculation Method of Line Breaking Power Flow Based on Taylor Expansion
Authors: Li Shuaihu , Zhao Xiang , Liang Wenju , Hossain Md Tanjid , Zhang Zhidan
Published: July 2022

In order to quickly obtain the voltage value of each node after the power system line is disconnected, a fast and accurate calculation method of breaking voltage based on Taylor series expansion is proposed in this study, which can calculate the value of nodal voltage of the system in a short time. At first, a breaking parameter is introduced into the admittance of the disconnected line, and a nonlinear disconnection function is constructed about the breaking parameter. After the line is disconnected, the voltage of each node and the admittance matrix of each node are functions of the relevant parameters, and then, the Taylor series is used to expand. The voltage of each node of the system before breaking is considered as the initial value of the Taylor series, and the first, second, and third derivatives of the node voltage with respect to the parameter are considered as the correction term; the voltage of each node of the system is calculated after the line is disconnected. Finally, the simulation results of the IEEE 14-node system are used to verify the correctness of the proposed method.
Hydrogeochemical Characterization, and Suitability Assessment of Drinking Groundwater: Application of Geostatistical Approach and Geographic Information System
Authors: Ghani Junaid , Ullah Zahid , Nawab Javed , Iqbal Javed , Waqas Muhammad , Ali Asmat , Almutairi Mikhlid H. , Peluso Ilaria , Mohamed Hanan R. H. , Shah Muddaser
Published: July 2022

Arsenic (As) contamination in drinking groundwater sources is a common environmental problem in Pakistan. Therefore, we collected a total of (n = 81) drinking groundwater samples from various groundwater sources, from two districts’ namely Ghotki (n = 44) and Nawab Shah (n = 37) of Sindh, Province, Pakistan. The current research aimed to investigate the hydrogeochemistry of groundwater with elevated arsenic (As), its effect on the health of local population living in the study area, potential sources of groundwater variables, and the suitability of groundwater for ingestion motive. The results showed that groundwater sample variables of both districts had moderate to high concentration levels. The cations concentrations were observed in decreasing order of Na+ > Ca+ > Mg+ > K+, for both districts, while anions abundance was HCO3− > Cl− > SO42− > F− > NO3− in the Ghotki, and HCO3− > SO42− > Cl− > NO3− > F− in the Nawab Shah, respectively. Arsenic (As) had low to high concentration levels in both districts, observed with average values of 10.1 μg/L and 21.0 μg/L in the Ghotki and Nawab Shah, respectively. The water type was mixed CaMgCl type in both districts, while the groundwater sources were saturated for CO3 minerals indicated by the saturation indices results. Principal component analysis showed the geogenic source of ion exchange, dissolution of minerals, weathering of host rocks and anthropogenic input of industrial activities, agricultural practices and domestic waste for groundwater contamination. The water quality index (WQI) exhibits that majority of groundwater samples (73.6% of Ghotki and 65.7% of Nawab Shah) were suitable for drinking. The non-carcinogenic risk (HQ) values of As were (>1) in groundwater samples of the Ghotki and Nawab Shah, while a high mean HQ value (8.78 × 100) was recorded for children in Nawab Shah. The carcinogenic risk (CR) values of As were significantly higher than the maximum threshold CR value (1 × 10–4). This study emphasized that monitoring strategies are substantially needed to mitigate the As contamination to reduce the potential health risk.
Improvement of P Use Efficiency and P Balance of Rice–Wheat Rotation System According to the Long-Term Field Experiments in the Taihu Lake Basin
Authors: Xiao Liang , Chen Guanglei , Wang Hong , Li Yixuan , Li Chi , Cheng Liang , Wu Wenge , Xiao Xin , Zhu Yiyong
Published: July 2022

Phosphorus (P) accumulation in rice–wheat rotation fields around the Yangtze River delta have been enriched during the last decades. To protect the environment and save P resources, we conducted field experiments to optimize the P application scheme. First, one field experiment was designed as a series of P fertilizer application doses of 0–100 kg P2O5 hm−2. Grain yield and P uptake by crops were analyzed to calculate P surplus and P use efficiency. Soil P fractions were extracted and tested. According to the P balance, we optimized fertilization by reducing the chemical P amount, which was used by local farmers; furthermore, we substituted chemical P with organic fertilizer. To verify these management strategies, another field experiment was conducted with five treatments: no N, P, or K fertilizer (CK); only no P fertilizer (NK); farmers’ fertilization of P (90 kg P2O5 hm−2) (FFP); reducing 20% P (FFP-20%P); and reducing 20% P and replacing 20% P by manure (FFPM-36%P). The grain yield was enhanced by increased P fertilizer and reached a constant level after 75 kg P2O5 hm−2. Moreover, the annual P surplus was balanced around the input of 150 kg P2O5 hm−2. Accordingly, by optimizing fertilization (FFP-20%P) and further replacing manure (FFPM-36%P), we also achieved crop yield equivalent to that of FFP treatment (90 kg P2O5 hm−2). Thus, the 72–75 kg P2O5 hm−2 application rate is a threshold for the production of rice and wheat and P balance. Total P content in soil was enhanced by increased input of P fertilizer and mainly divided into labile Pi and middle stable Pi fractions. Soil Olsen-P content increased by P fertilization accordingly, while the content of organic P and stable P content was relatively constant. Reducing P fertilizer by 20% had similar results for soil P fractions when compared with farmers’ P fertilization treatment. Therefore, reducing at least 20% current input of P by farmers (annual 180 kg P2O5 hm−2) according to the balance of P surplus in rice and wheat rotation systems is an imperative measure to guarantee crop production with enhanced P use efficiency, and meanwhile, it can alleviate environmental risk.
Burning alters the decomposition of residual plant litters in Calamagrostis angustifolia wetlands in the Sanjiang Plain (Northeast China)
Authors: Gao Chuanyu , Wang Guoping , Cong Jinxin , Han Dongxue , Zhao Hongmei
Published: July 2022

Wetlands store >30% of the global soil carbon pool, which is important for global carbon cycling. However, with global warming and the increase in regional human activities, an increasing number of wetlands are being threatened by fires, which have serious effects on carbon cycling in wetlands. Although plant litter decomposition is one of the key stages of carbon cycling in wetlands, it is still unclear whether fires affect residual plant litter decomposition in burnt wetlands and whether the fire season also causes different effects. To address these knowledge gaps, a plant litter decomposition experiment was conducted during the growing season in autumn burnt, spring burnt, and unburnt sites in a Calamagrostis angustifolia wetland in the Sanjiang Plain (Northeast China). The results show that autumn burning promotes more mass loss (i.e., 15.9 ± 1.6% in autumn burnt sites and 14.8 ± 1.7% in autumn unburnt sites) and accelerates the decomposition of plant litter, whereas spring burning decreases the decomposition rates of plant litter (i.e., 15.7 ± 1.7% in spring burnt sites and 22.0 ± 2.5% in spring unburnt sites). As the decomposition time increased, the accumulation index indicated that carbon was released from plant litter to the surrounding environment accompanied by mass loss and nutrient elements accumulated in the residual plant litter. The N/P ratio of plant litter decreased from ca. 20 on day 26th to ca. 9 on day 121st, indicating that N acts as the limiting element for plant litter decomposition in C. angustifolia wetlands, and the limitation increased with increasing decomposition time. Our results also suggest that the autumn burning may promote more carbon loss and nutrient elements accumulated in plant litter in C. angustifolia wetlands than the spring burning.
The Penicillium chrysogenum tom1 Gene a Major Target of Transcription Factor MAT1-1-1 Encodes a Nuclear Protein Involved in Sporulation
Authors: Ramšak Barbara , Kück Ulrich
Published: July 2022

Fungal mating-type loci (MAT) encode transcription factors (TFs) MAT1-1-1 and MAT1-2-1, which govern sexual reproduction as well as other developmental processes. In Penicillium chrysogenum, the major producer of the beta-lactam antibiotic penicillin, a recent chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis identified 254 genes as direct targets of MAT1-1-1, many of which encode thus far uncharacterized proteins. Here, we characterized one of the major targets of MAT1-1-1, the tom1 gene, which encodes a protein highly conserved within the group of Eurotiomycetes fungi. Using fluorescence microscopy, we demonstrated binding of MAT1-1-1 to the tom1 promoter by reporter gene analysis. Extensive electrophoretic mobility shift assays (EMSAs) further showed that the promoter sequence of tom1 is bound in vitro by both MAT1-1-1 and MAT1-2-1. This indicated an interaction between the two TFs, which was verified by yeast two-hybrid analysis. The sequence of tom1 carries a nuclear localization sequence, and indeed its nuclear localization was verified by fluorescence microscopy. The in vivo function of tom1 was investigated using tom1 deletion strains, as well as a complementing strain where the wild-type tom1 gene was reintroduced. We found a clear sporulation defect in the deletion strain, which became more evident when the fungi were grown at an elevated temperature of 31°C.
Case Report: Gene Heterogeneity in the Recurrent and Metastatic Lesions of a Myxoid Chondrosarcoma Patient With Aggressive Transformation
Authors: He Xuanhong , Wang Yitian , Zou Chang , Zheng Chuanxi , Luo Yi , Zhou Yong , Tu Chongqi
Published: July 2022

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma. In view of the indolent course throughout the prolonged natural history of EMC, it was considered as a low-grade soft-tissue sarcoma. However, recent studies have revealed a high recurrence and metastatic potential in EMC, and the invasiveness of EMC may progress during the protracted clinical course. The mechanism for this aggressive transformation remains unknown. Here, we present a rare case of EMC with aggressive behavior. This case was confirmed via pathology and NR4A3 fluorescent in situ hybridization. To verify the genetic characteristics of this rare case, a total gene sequencing analyses was performed in the recurrent and metastatic lesions. Intriguingly, different gene mutations were determined in the recurrent and metastatic lesions, which implied the genetic heterogeneity among the different lesions might be related to the aggressiveness of EMC. Furthermore, we discuss a few potential agents against the mutated genes in this case, which may provide novel insights regarding the targeted therapy of EMC.
Opportunities of Genomics for the Use of Semen Cryo-Conserved in Gene Banks
Authors: Oldenbroek J. Kor , Windig Jack J.
Published: July 2022

Shortly after the introduction of cryo-conserved semen in the main farm animal species, gene banks were founded. Safeguarding farm animal genetic diversity for future use was and is the main objective. A sampling of sires was based on their pedigree and phenotypic information. Nowadays, DNA information from cryo-conserved sires and from animals in the living populations has become available. The combination of their DNA information can be used to realize three opportunities: 1) to make the gene bank a more complete archive of genetic diversity, 2) to determine the history of the genetic diversity from the living populations, and 3) to improve the performance and genetic diversity of living populations. These three opportunities for the use of gene bank sires in the genomic era are outlined in this study, and relevant recent literature is summarized to illustrate the great value of a gene bank as an archive of genetic diversity.
Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population
Authors: Zecevic Marko , Kotur Nikola , Ristivojevic Bojan , Gasic Vladimir , Skodric-Trifunovic Vesna , Stjepanovic Mihailo , Stevanovic Goran , Lavadinovic Lidija , Zukic Branka , Pavlovic Sonja , Stankovic Biljana
Published: July 2022

Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1, LURAP1L, p = 8.69 × 10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.
Identification of Dysbetalipoproteinemia by an Enhanced Sampson-NIH Equation for Very Low-Density Lipoprotein-Cholesterol
Authors: Sampson Maureen , Wolska Anna , Meeusen Jeff W. , Donato Leslie J. , Jaffe Allan S. , Remaley Alan T.
Published: July 2022

Dysbetalipoproteinemia (hyperlipoproteinemia type III, HLP3) is a genetic disorder that results in the accumulation of cholesterol on highly atherogenic remnant particles. Traditionally, the diagnosis of HLP3 depended upon lipoprotein gel electrophoresis or density gradient ultracentrifugation. Because these two methods are not performed by most clinical laboratories, we describe here two new equations for estimating the cholesterol content of VLDL (VLDL-C), which can then be used for the diagnosis of HLP3. Using results from the beta-quantification (BQ) reference method on a large cohort of dyslipidemic patients (N = 24,713), we identified 115 patients with HLP3 based on having a VLDL-C to plasma TG ratio greater than 0.3 and plasma TG between 150 and 1,000 mg/dl. Next, we developed two new methods for identifying HLP3 and compared them to BQ and a previously described dual lipid apoB ratio method. The first method uses results from the standard lipid panel and the Sampson-NIH equation 1 for estimating VLDL-C (S-VLDL-C), which is then divided by plasma TG to calculate the VLDL-C/TG ratio. The second method is similar, but the Sampson-NIH equation 1 is modified or enhanced (eS-VLDL-C) by including apoB as an independent variable for predicting VLDL-C. At a cut-point of 0.194, the first method showed a modest ability for identifying HLP3 (sensitivity = 73.9%; specificity = 82.6%; and area under the curve (AUC) = 0.8685) but was comparable to the existing dual lipid apoB ratio method. The second method based on eS-VLDL-C showed much better sensitivity (96.5%) and specificity (94.5%) at a cut-point of 0.209. It also had an excellent AUC score of 0.9912 and was superior to the two other methods in test classification. In summary, we describe two new methods for the diagnosis of HLP3. The first one just utilizes the results of the standard lipid panel and the Sampson-NIH equation 1 for estimating (VLDL-C) (S-VLDL-C) and can potentially be used as a screening test. The second method (eS-VLDL-C), in which the Sampson-NIH equation 1 is modified to include apoB, is nearly as accurate as the BQ reference method. Because apoB is widely available at most clinical laboratories, the second method should improve both the accessibility and the accuracy of the HLP3 diagnosis.
Missing Value Imputation With Low-Rank Matrix Completion in Single-Cell RNA-Seq Data by Considering Cell Heterogeneity
Authors: Huang Meng , Ye Xiucai , Li Hongmin , Sakurai Tetsuya
Published: July 2022

Single-cell RNA-sequencing (scRNA-seq) technologies enable the measurements of gene expressions in individual cells, which is helpful for exploring cancer heterogeneity and precision medicine. However, various technical noises lead to false zero values (missing gene expression values) in scRNA-seq data, termed as dropout events. These zero values complicate the analysis of cell patterns, which affects the high-precision analysis of intra-tumor heterogeneity. Recovering missing gene expression values is still a major obstacle in the scRNA-seq data analysis. In this study, taking the cell heterogeneity into consideration, we develop a novel method, called single cell Gauss–Newton Gene expression Imputation (scGNGI), to impute the scRNA-seq expression matrices by using a low-rank matrix completion. The obtained experimental results on the simulated datasets and real scRNA-seq datasets show that scGNGI can more effectively impute the missing values for scRNA-seq gene expression and improve the down-stream analysis compared to other state-of-the-art methods. Moreover, we show that the proposed method can better preserve gene expression variability among cells. Overall, this study helps explore the complex biological system and precision medicine in scRNA-seq data.
More Than One-Third of Pregnant Women in Ethiopia Had Dropped Out From Their ANC Follow-Up: Evidence From the 2019 Ethiopia Mini Demographic and Health Survey
Authors: Tariku Mandaras , Tusa Biruk Shalmeno , Weldesenbet Adisu Birhanu , Bahiru Nebiyu , Enyew Daniel Berhanie
Published: July 2022

Background

In Ethiopia, the magnitude of antenatal care (ANC) practice and institutional delivery is low as compared with developed countries. The majority of the pregnant women have not completed their ANC follow-up and only 43% of women have reached the four and above ANC. This study was conducted to determine the magnitude of ANC dropout and associated factors among pregnant women in Ethiopia.

Methods

Secondary data analysis was conducted using the 2019 Ethiopia Mini Demographic and Health Survey 2019 (2019 EMDHS). The sample was selected using a stratified, two-stage cluster sampling design and the data were analyzed using the binary logistic regression model to identify factors associated with ANC dropout. Adjusted odds ratio (AOR) with 95% CI was reported to declare significance and strength of association. A total weighted sample of 2,143 women who had antenatal care follow-up during pregnancy was included. In the multivariate logistic regression analysis, variables having a p-value < 0.05 were considered to have a significant association with ANC dropout.

Result

The magnitude of ANC dropout was 39.12% (95% CI: 37.07 and 41.20%) among women who had ANC follow-up in Ethiopia. Aged 30–49 years [AOR = 0.71; 95% CI: (0.54, 0.94)], attended primary [AOR = 0.79; 95% CI: (0.62, 0.99)], secondary [AOR = 0.63; 95% CI: (0.44, 0.87)], and higher education [AOR = 0.39; 95% CI: (0.25, 0.62)], were in first trimesters [AOR = 0.49; 95% CI: (0.40, 0.60)] at the time of first ANC visit, and had access to laboratory service [AOR = 0.25; 95% CI: (0.13, 0.51)] were found to be a negative significant associated factors of ANC dropouts, whereas being rural resident [AOR = 1.53; 95% CI: (1.11, 2.10)] has a positive significant association with ANC dropouts.

Conclusion

More than one-third of the pregnant women in Ethiopia had dropped out from their ANC follow-up in the study period. Being old-aged, educated, urban resident, having a first ANC visit in the first trimester, and having access to laboratory service were negatively associated with ANC dropouts. Therefore, we recommended encouraging women to have ANC visit at an early stage of pregnancy and conducting basic laboratory investigations during their visit. When undertaking that, due attention should be given to young, uneducated, and rural dweller women.
No sex differences in the incidence, risk factors and clinical impact of acute kidney injury in critically ill patients with sepsis
Authors: Peng Junnan , Tang Rui , Yu Qian , Wang Daoxin , Qi Di
Published: July 2022

Background

Sex-stratified medicine is an important aspect of precision medicine. We aimed to compare the incidence and risk factors of acute kidney injury (AKI) for critically ill men and women with sepsis. Furthermore, the short-term mortality was compared between men and women with sepsis associated acute kidney injury (SA-AKI).

Method

This was a retrospective study based on the Medical Information Mart for Intensive Care IV database. We used the multivariable logistic regression analysis to evaluate the independent effect of sex on the incidence of SA-AKI. We further applied three machine learning methods (decision tree, random forest and extreme gradient boosting) to screen for the risk factors associated with SA-AKI in the total, men and women groups. We finally compared the intensive care unit (ICU) and hospital mortality between men and women with SA-AKI using propensity score matching.

Results

A total of 6463 patients were included in our study, including 3673 men and 2790 women. The incidence of SA-AKI was 83.8% for men and 82.1% for women. After adjustment for confounders, no significant association was observed between sex and the incidence of SA-AKI (odds ratio (OR), 1.137; 95% confidence interval (CI), 0.949-1.361; p=0.163). The machine learning results revealed that body mass index, Oxford Acute Severity of Illness Score, diuretic, Acute Physiology Score III and age were the most important risk factors of SA-AKI, irrespective of sex. After propensity score matching, men had similar ICU and hospital mortality to women.

Conclusions

The incidence and associated risk factors of SA-AKI are similar between men and women, and men and women with SA-AKI experience comparable rates of ICU and hospital mortality. Therefore, sex-related effects may play a minor role in developing SA-AKI. Our study helps to contribute to the knowledge gap between sex and SA-AKI.
Lactobacillus reuteri 1 Enhances Intestinal Epithelial Barrier Function and Alleviates the Inflammatory Response Induced by Enterotoxigenic Escherichia coli K88 via Suppressing the MLCK Signaling Pathway in IPEC-J2 Cells
Authors: Gao Jingchun , Cao Shuting , Xiao Hao , Hu Shenglan , Yao Kang , Huang Kaiyong , Jiang Zongyong , Wang Li
Published: July 2022

Intestinal epithelial barrier injury disrupts immune homeostasis and leads to many intestinal disorders. Lactobacillus reuteri (L. reuteri) strains can influence immune system development and intestinal function. However, the underlying mechanisms of L. reuteri LR1 that regulate inflammatory response and intestinal integrity are still unknown. The present study aimed to determine the effects of LR1 on the ETEC K88-induced intestinal epithelial injury on the inflammatory response, intestinal epithelial barrier function, and the MLCK signal pathway and its underlying mechanism. Here, we showed that the 1 × 109 cfu/ml LR1 treatment for 4 h dramatically decreased interleukin-8 (IL-8) and IL-6 expression. Then, the data indicated that the 1 × 108 cfu/ml ETEC K88 treatment for 4 h dramatically enhanced IL-8, IL-6, and tumor necrosis factor-α (TNF-α) expression. Furthermore, scanning electron microscope (SEM) data indicated that pretreatment with LR1 inhibited the ETEC K88 that adhered on IPEC-J2 and alleviated the scratch injury of IPEC J2 cells. Moreover, LR1 pretreatment significantly reversed the declined transepithelial electrical resistance (TER) and tight junction protein level, and enhanced the induction by ETEC K88 treatment. Additionally, LR1 pretreatment dramatically declined IL-8, IL-17A, IL-6, and TNF-α levels compared with the ETEC K88 group. Then, ETEC K88-treated IPEC-J2 cells had a higher level of myosin light-chain kinase (MLCK), higher MLC levels, and a lower Rho-associated kinase (ROCK) level than the control group, while LR1 pretreatment significantly declined the MLCK and MLC expression and enhanced ROCK level in the ETEC K88-challenged IPEC-J2 cells. Mechanistically, depletion of MLCK significantly declined MLC expression in IPEC-J2 challenged with ETEC K88 compared to the si NC+ETEC K88 group. On the other hand, the TER of the si MLCK+ETEC K88 group was higher and the FD4 flux in the si MLCK+ETEC K88 group was lower compared with the si NC+ETEC K88 group. In addition, depletion of MLCK significantly enhanced Claudin-1 level and declined IL-8 and TNF-α levels in IPEC-J2 pretreated with LR1 followed by challenging with ETEC K88. In conclusion, our work indicated that L. reuteri LR1 can decline inflammatory response and improve intestinal epithelial barrier function through suppressing the MLCK signal pathway in the ETEC K88-challenged IPEC-J2.
A Knowledge-Based Discovery Approach Couples Artificial Neural Networks With Weight Engineering to Uncover Immune-Related Processes Underpinning Clinical Traits of Breast Cancer
Authors: Zhang Cheng , Correia Cristina , Weiskittel Taylor M. , Tan Shyang Hong , Meng-Lin Kevin , Yu Grace T. , Yao Jingwen , Yeo Kok Siong , Zhu Shizhen , Ung Choong Yong , Li Hu
Published: July 2022

Immune-related processes are important in underpinning the properties of clinical traits such as prognosis and drug response in cancer. The possibility to extract knowledge learned by artificial neural networks (ANNs) from omics data to explain cancer clinical traits is a very attractive subject for novel discovery. Recent studies using a version of ANNs called autoencoders revealed their capability to store biologically meaningful information indicating that autoencoders can be utilized as knowledge discovery platforms aside from their initial assigned use for dimensionality reduction. Here, we devise an innovative weight engineering approach and ANN platform called artificial neural network encoder (ANNE) using an autoencoder and apply it to a breast cancer dataset to extract knowledge learned by the autoencoder model that explains clinical traits. Intriguingly, the extracted biological knowledge in the form of gene–gene associations from ANNE shows immune-related components such as chemokines, carbonic anhydrase, and iron metabolism that modulate immune-related processes and the tumor microenvironment play important roles in underpinning breast cancer clinical traits. Our work shows that biological “knowledge” learned by an ANN model is indeed encoded as weights throughout its neuronal connections, and it is possible to extract learned knowledge via a novel weight engineering approach to uncover important biological insights.
MiR-7 Regulates Pathogen-Induced Immune Response via PAK1 in the Sea Cucumber Apostichopus japonicus
Authors: Zhao Tanjun , Ren Liyuan , Li Chengda , Liu Li , Zou Yang , Yan Hanyu , Zhan Yaoyao , Chang Yaqing
Published: July 2022

MicroRNA-7 (miR-7) is a highly conserved short non-coding RNA involved in various bioprocesses via the regulation of multiple target genes. To enrich our knowledge of the functions of miR-7 in innate immune regulation in echinoderms, we first investigated the targeting relationship between miR-7 and PAK1 in the sea cucumber Apostichopus japonicus and then explored the functions of miR-7, the PAK1 gene, and the miR-7/PAK1 axis in the pathogen-induced immune response of A. japonicus. Our results showed that miR-7 can bind to the 3ʹUTR of PAK1 and negatively regulate the expression of PAK1 in A. japonicus. Overexpression and inhibition of miR-7 and inhibition of the expression of PAK1 can alter phagocytosis, cellular agglutination, and lysozyme contents in A. japonicus. Both miR-7 and the PAK1 gene are involved in immune defense against Vibrio splendidus infection; the miR-7/AjPAK1 axis showed immune regulatory function at 48 to 72 h post-infection (hpi) after V. splendidus infection in A. japonicus. In summary, the results of this study established that miR-7 regulates the pathogen-induced immune response by targeting PAK1 in A. japonicus.
2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21
Authors: Zhao Kuan , Guo Xiao-Ran , Liu Shuai-Feng , Liu Xiao-Na , Han Ying , Wang Lu-Lu , Lei Bai-Shi , Zhang Wu-Chao , Li Li-Min , Yuan Wan-Zhe
Published: July 2022

Senecavirus A (SVA), also known as Seneca Valley virus, is a recently discovered picornavirus that can cause swine vesicular disease, posing a great threat to the global swine industry. It can replicate efficiently in cells, but the molecular mechanism remains poorly understood. This study determined the host’s differentially expressed proteins (DEPs) during SVA infection using dimethyl labeling based on quantitative proteomics. Among the DE proteins, DDX21, a member of the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase (DDX) family, was downregulated and demonstrated inhibiting SVA replication by overexpression and knockdown experiment. To antagonize this antiviral effect of DDX21, SVA infection induces the degradation of DDX21 by 2B and 3C proteins. The Co-IP results showed that 2B and 3C did not interact with DDX21, suggesting that the degradation of DDX21 did not depend on their interaction. Moreover, the 3C protein protease activity was necessary for the degradation of DDX21. Furthermore, our study revealed that the degradation of DDX21 by 2B and 3C proteins of SVA was achieved through the caspase pathway. These findings suggest that DDX21 was an effective antiviral factor for suppressing SVA infection and that SVA antagonized its antiviral effect by degrading DDX21, which will be useful to guide further studies into the mechanism of mutual regulation between SVA and the host.
Construction and Validation of an Epigenetic Regulator Signature as A Novel Biomarker For Prognosis, Immunotherapy, And Chemotherapy In Hepatocellular Carcinoma
Authors: Cai Jialiang , Wu Suiyi , Zhang Feng , Dai Zhi
Published: July 2022

Background

Epigenetic modification regulates various aspects of cancer biology, from tumor growth and invasion to immune microenvironment modulation. Whether epigenetic regulators (EGRs) can decide tumor malignant degree and risk of immune evasion in liver hepatocellular carcinoma (LIHC) remains unclear.

Method

An EGR signature called “EGRscore” was constructed based on bulk RNA-seq data of EGR in hepatocellular carcinoma (HCC). The correlation between EGRscore and overall survival (OS) was validated in HCC cohorts and other tumor cohorts. Mutation profiles, copy number alterations (CNAs), enriched pathways, and response to immunotherapy and chemotherapy were compared between EGRscore-high and EGRscore-low patients.

Results

We found that EGRscore was associated with OS in HCC as well as several tumors including glioma, uveal melanoma (UVM), and kidney tumors. A mechanism study demonstrated that the distinct mutation profile of TP53 was present in EGRscore-high and EGRscore-low patients. Meanwhile, EGRscore-low patients were characterized with immune cells that promote killing tumors. Furthermore, EGRscore was associated with genes regulating drug resistance in HCC. Finally, we indicated that EGRscore-low patients had higher response rates to immunotherapy and targeted therapy.

Conclusions

EGRscore could be used to distinguish OS, tumor progression, mutation pattern, and immune microenvironment. The present study contributes to improving hepatocellular carcinoma patient prognosis and predicting response to immunotherapy.
Metabolomics Analysis Reveals the Differential Metabolites and Establishes the Therapeutic Effect Prediction Nomogram Among CP/CPPS Patients Who Respond or Do Not Respond to LiST
Authors: Meng Jialin , Jin Chen , Li Jiawei , Zhang Song , Zhang Meng , Hao Zongyao , Chen Xianguo , Song Zhengyao , Zhang Li , Liang Chaozhao
Published: July 2022

Objective

Low-intensity shockwave therapy (LiST) has been applied in the clinical treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but few studies have focused on the prediction of its therapeutic effect before treatment.

Methods

Seventy-five CP/CPPS patients from our institute between July 2020 and May 2021 were enrolled and received 3 Hz, 0.25 mJ/mm2 LiST once a week over the course of four weeks. The scores of the NIH-CPSI, IPSS questionnaire and demographic features before treatment were recorded. The plasma before LiST treatment was also collected, while liquid chromatography-tandem mass spectrometry was used to detect the metabolites. Least absolute shrinkage and selection operator (LASSO) regression analysis was employed to identify the prediction metabolites and generate the metabolism score. Receiver operating characteristic curves and calibration curves were drawn to assess the prediction accuracy of the nomogram.

Results

Twelve metabolites were identified at incomparable levels before and after LiST treatment. The metabolism score generated by LASSO analysis presented a perfect prediction value (AUC: 0.848, 95% CI: 0.719-0.940) in the training cohort and further increased to 0.892 (95% CI: 0.802-0.983) on the nomogram, which accompanied with the NIH-CPSI scores and age. Similar results of the metabolism score (AUC: 0.732, 95% CI: 0.516-0.889) and total nomogram (AUC: 0.968, 95% CI: 0.909-1.000) were obtained in the testing cohort. Further enrichment of the 12 metabolites indicated that the glycine and serine metabolism pathway was involved in the LiST treatment.

Conclusion

We used our system to accurately and quantitatively measure plasma metabolites and establish a predictive model to identify suitable patients for LiST treatment.
Restorative therapy using microglial depletion and repopulation for central nervous system injuries and diseases
Authors: Shi Weipeng , Zhang Jing , Shang Zhen , Zhang Yingze , Xia Yanzhi , Fu Haitao , Yu Tengbo
Published: July 2022

Microglia are important resident immune cells in the central nervous system (CNS) and play an important role in its development, homeostasis, and disease treatments. Activated microglia perform diverse functions in mouse models of CNS neurodegenerative diseases or deficits. In humans, microglia have been linked to various neurodegenerative diseases. Following brain or spinal cord injury, microglia express pro- and anti-inflammatory phenotypes at different stages of recovery. With the development of pharmacological and genetic tools for microglial depletion, studies have demonstrated that microglial depletion exerts both positive and negative effects in the treatment of CNS diseases. Notably, microglial depletion provides an empty niche that stimulates production of new microglia. Microglial depletion and repopulation can not only treat diseases by eliminating dysfunctional microglia but can also provide an indication of the molecular mechanisms of diseases. Although this approach has shown impressive results, its use is still in its infancy. In this review, we summarize the current pharmacological and genetic tools for microglial depletion and highlight recent advances in microglial repopulation therapy for the treatment and functional recovery of neurological diseases and deficits. Finally, we briefly discuss the therapeutic challenges and prospective uses of microglial repopulation therapy.
Dive Behavior and Activity Patterns of Fin Whales in a Migratory Habitat
Authors: Fonseca Catarina T. , Pérez-Jorge Sergi , Prieto Rui , Oliveira Cláudia , Tobeña Marta , Scheffer Annette , Silva Mónica A.
Published: July 2022

Efficient use of the energy budget is of fundamental importance for long-distance migrants, which must cope with seasonal energy demands and environmental conditions. Time-activity budgets can provide information on how animals balance energy use and acquisition over their annual cycle, and on the costs and benefits of different migratory strategies. Baleen whales, such as the fin whale, perform long migrations between feeding and breeding grounds. Although there are now a handful of studies describing the diving and foraging behavior of fin whales, most were carried out at their high-latitude foraging grounds, and very little is known about their behavior in wintering habitats or during migration. We analyzed time-depth recorder data to describe the diving behavior and activity patterns of fin whales in a migratory habitat. Using a hierarchical cluster analysis based on a set of dive variables, we identified six dive types. Four of these dive types (shallow exploratory, shallow active, deep exploratory and deep active) were likely associated to foraging. The other two comprised long non-active dives and dives of variable shape, which may represent resting, traveling or even vocalizing behavior. Shallow exploratory dives were the most frequent dive type (23%) and shallow active were the least frequent (5%). The two deepest dive types, deep active and exploratory, were predominantly carried out during the day, and night dives were significantly shallower than daylight dives, suggesting that fin whales tracked the vertical migration of prey. Whales spent 60% of their dive time engaged in dives associated with feeding and/or prey searching, suggesting they prioritized energy intake over energy conservation. Finally, we found that whales spent more time at or close (<15 m depth) to the surface at night (73%) than during the day (55%), indicating a higher vulnerability to ship strikes during this period. Our study provides novel information on the behavioral patterns and time-activity budgets of fin whales in a migratory habitat. This information is essential for bioenergetic analyses and to predict how fin whales respond to human activities and ongoing environmental changes.
Warming Disadvantages Phytoplankton and Benefits Bacteria During a Spring Bloom in the Mediterranean Thau Lagoon
Authors: Courboulès Justine , Mostajir Behzad , Trombetta Thomas , Mas Sébastien , Vidussi Francesca
Published: July 2022

To assess the response of a natural plankton community to the future scenario of a warming of +3°C predicted for coastal Mediterranean regions, an in situ mesocosm experiment was carried out over 19 days in a Mediterranean coastal lagoon in 2018. During this experiment, a phytoplankton bloom occurred and the abundances of several cytometric groups of phytoplankton (cyanobacteria, picophytoplankton and nanophytoplankton) and bacteria (low- and high-nucleic acid bacteria), as well as their growth and grazing mortality rates and their carbon biomass, were studied over the course of the experiment. Experimental warming led to a significant reduction of 47% of the phytoplankton biomass in average, based on Chl-a concentrations. This reduction was also observed for nanophytoplankton abundances during the whole experiment and for eukaryotic picophytoplankton only during the bloom period. This result coincided with a significant decrease in orthophosphate concentrations under warming during the prebloom and bloom periods simultaneous to an increase in bacterial abundances. At the same time, the higher growth rates of bacteria and the lower ones of phytoplankton observed at the beginning of the bloom could suggest that competition between phytoplankton and bacteria for orthophosphate might have contributed to the phytoplankton biomass decrease under warming. In addition, higher grazing mortality rates of phytoplankton groups under warming, notably nanophytoplankton at the end of the bloom and in postbloom (by 59 to 626%), as well as eukaryotic picophytoplankton over the course of the experiment (by 58 to 255%) could also have contributed to the lower phytoplankton biomass under warming. Based on these results, estimations of average phytoplankton carbon biomass production and transfer showed reductions of 42 and 45%, respectively, under warming, whereas those of bacteria were enhanced by 13 and 8%, respectively. These results indicated that warming induced a shift at the base of the microbial food web, going toward a more bacteria-based system. This suggested that under future warming scenarios, the microbial food web could become less productive and could negatively affect the functioning of the whole food web in coastal waters.