bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of core genes prognostic for sepsis and construction of a ceRNA regulatory network
Authors: Zhang Qian , Wang Chenglin , Li Shilin , Li Yang , Chen Muhu , Hu Yingchun 
Published: February 2023

Abstract
Objective
To screen out core genes potentially prognostic for sepsis and construct a competing endogenous RNA (ceRNA) regulatory network.

Methods
Subjects included in this project were 23 sepsis patients and 10 healthy people. RNA-seq for lncRNA, miRNA and mRNA was performed in the peripheral blood samples. Differentially expressed RNAs (DER) were screened out for further analysis. GO annotation and GSEA functional clustering were performed to view the functional enrichment of DEmRNAs. Core genes of prognostic significance were screened out with the weighted correlation network analysis (WGCNA). Meta-analysis and Survival analysis was devised in different microarray datasets. RT-qPCR was conducted to validate these core genes. A ceRNA network was accordingly constructed according to the correlation analysis and molecular interaction prediction.

Results
RNA-seq and differential analysis screened out 1,044 DEmRNAs, 66 DEmiRNAs and 155 DElncRNAs. The GO and GSEA analysis revealed that DEmRNAs are mainly involved in inflammatory response, immune regulation, neutrophil activation. WGCNA revealed 4 potential core genes, including CD247, IL-2Rβ, TGF-βR3 and IL-1R2. In vitro cellular experiment showed up-regulated expression of IL-1R2 while down-regulated of CD247, IL-2Rβ, TGF-βR3 in sepsis patients. Correspondingly, a ceRNA regulatory network was build based on the core genes, and multiple lncRNAs and miRNAs were identified to have a potential regulatory role in sepsis.

Conclusion
This study identified four core genes, including CD247, IL-1R2, IL-2Rβ and TGF-βR3, with potential to be novel biomarkers for the prognosis of sepsis. In the meantime, a ceRNA network was constructed aiming to guide further study on prognostic mechanism in sepsis.
Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 8. Impact on women’s empowerment
Authors: Stollak Ira , Valdez Mario , Story William T. , Perry Henry B. 
Published: February 2023

Abstract
Background
Indigenous Maya women in the rural highlands of Guatemala have traditionally faced constraints to decision-making and participation in community affairs. Anecdotal experiences from previous Curamericas Global projects in Guatemala and Liberia have suggested that interventions using the CBIO+ Approach (which consists of implementing together the Census-Based, Impact-Oriented Approach, the Care Group Approach, and Community Birthing Centers), can be empowering and can facilitate improvements in maternal and child health. This paper, the eighth in a series of 10 papers examining the effectiveness of CBIO+ in improving the health and well-being of mothers and children in an isolated mountainous rural area of the Department of Huehuetenango, explores changes in women’s empowerment among mothers of young children associated with the Curamericas/Guatemala Maternal and Child Health Project, 2011–2015.

Methods
Knowledge, practice, and coverage (KPC) surveys and focus group discussions (FGDs) were used to explore six indicators of women’s empowerment focusing on participation in health-related decision-making and participation in community meetings. KPC surveys were conducted at baseline (January 2012) and endline (June 2015) using standard stratified cluster sampling. Seventeen FGDs (9 with women, 3 with men, 2 with mothers-in-law, and 3 with health committees), approximately 120 people in all, were conducted to obtain opinions about changes in empowerment and to identify and assess qualitative factors that facilitate and/or impede women’s empowerment.

Results
The KPC surveys revealed﻿ statistically significant increases in women’s active participation in community meetings. Women also reported statistically significant increases in rates of participation in health-related decision-making. Further, the findings show a dose-response effect for two of the six empowerment indicators. The qualitative findings from FGDs show that the Project accelerated progress in increasing women’s empowerment though women still face major barriers in accessing needed health care services for themselves and their children.

Conclusion
The Project achieved some notable improvements in women’s decision-making autonomy and participation in community activities. These improvements often translated into making decisions to practice recommended health behaviors. Traditional cultural norms and the barriers to accessing needed health services are not easily overcome, even when empowerment strategies are effective.
Investigation of bedaquiline resistance and genetic mutations in multi-drug resistant Mycobacterium tuberculosis clinical isolates in Chongqing, China
Authors: Hu Yan , Fan Jun , Zhu Damin , Liu Wenguo , Li Feina , Li Tongxin , Zheng Huiwen 
Published: February 2023

Abstract
Background
To investigate the prevalence and molecular characterization of bedaquiline resistance among MDR-TB isolates collected from Chongqing, China.

Methods
A total of 205 MDR-TB isolates were collected from Chongqing Tuberculosis Control Institute between March 2019 and June 2020. The MICs of BDQ were determined by microplate alamarblue assay. All strains were genotyped by melting curve spoligotyping, and were subjected to WGS.

Results
Among the 205 MDR isolates, the resistance rate of BDQ was 4.4% (9/205). The 55 (26.8%) were from male patients and 50 (24.4%) were new cases. Furthermore, 81 (39.5%) of these patients exhibited lung cavitation, 13 (6.3%) patients afflicted with diabetes mellitus, and 170 (82.9%) isolates belonged to Beijing family. However, the distribution of BDQ resistant isolates showed no significant difference among these characteristics. Of the 86 OFX resistant isolates, 8 isolates were XDR (9.3%, 8/86). Six BDQ resistant isolates (66.7%, 6/9) and two BDQ susceptible isolates (1.0%, 2/196) carried mutations in Rv0678. A total of 4 mutations types were identified in BDQ resistant isolates, including mutation in A152G (50%, 3/6), T56C (16.7%, 1/6), GA492 insertion (16.7%, 1/6), and A274 insertion (16.7%, 1/6). BDQ showed excellent activity against MDR-TB in Chongqing.

Conclusions
BDQ showed excellent activity against MDR-TB in Chongqing. The resistance rate of BDQ was not related to demographic and clinical characteristics. Mutations in Rv0678 gene were the major mechanism to BDQ resistance, with A152G as the most common mutation type. WGS has a good popularize value and application prospect in the rapid detection of BDQ resistance.
Impaired autophagy-accelerated senescence of alveolar type II epithelial cells drives pulmonary fibrosis induced by single-walled carbon nanotubes
Authors: Zhang Xiang , Hu Xinxin , Zhang Yuqing , Liu Bin , Pan Haihong , Liu Zikai , Yao Zhuomeng , Zhu Qixing , Wu Changhao , Shen Tong 
Published: February 2023

Abstract
Background
The rapid increase in production and application of carbon nanotubes (CNTs) has led to wide public concerns in their potential risks to human health. Single-walled CNTs (SWCNTs), as an extensively applied type of CNTs, have shown strong capacity to induce pulmonary fibrosis in animal models, however, the intrinsic mechanisms remain uncertain.

Results
In vivo experiments, we showed that accelerated senescence of alveolar type II epithelial cells (AECIIs) was associated with pulmonary fibrosis in SWCNTs-exposed mice, as well as SWCNTs-induced fibrotic lungs exhibited impaired autophagic flux in AECIIs in a time dependent manner. In vitro, SWCNTs exposure resulted in profound dysfunctions of MLE-12 cells, characterized by impaired autophagic flux and accelerated cellular senescence. Furthermore, the conditioned medium from SWCNTs-exposed MLE-12 cells promoted fibroblast-myofibroblast transdifferentiation (FMT). Additionally, restoration of autophagy flux with rapamycin significantly alleviated SWCNTs-triggered senescence and subsequent FMT whereas inhibiting autophagy using 3-MA aggravated SWCNTs-triggered senescence in MLE-12 cells and FMT.

Conclusion
SWCNTs trigger senescence of AECIIs by impairing autophagic flux mediated pulmonary fibrosis. The findings raise the possibility of senescence-related cytokines as potential biomarkers for the hazard of CNTs exposure and regulating autophagy as an appealing target to halt CNTs-induced development of pulmonary fibrosis.

Graphical Abstract
Comparison of single-pore non-liposuction near-infrared laparoscopy with conventional open surgery for axillary sentinel lymph node biopsy in patients with early breast cancer: a single-center, small-sample retrospective study
Authors: Yao Cheng-cai , Liu Changchun , Xian Jiayi 
Published: February 2023

Abstract
Background
This study aimed to compare the effects of single-pore non-liposuction near-infrared (NIR) endoscopic surgery and traditional open surgery for axillary sentinel lymph node biopsy (SLNB) in patients with early breast cancer (EBC).

Methods
The clinical pathological data of 61 patients with EBC who underwent axillary SLNB using indocyanine green (ICG) combined with carbon nanoparticle suspension (CNS) were retrospectively collected. Thirty patients received SLNB through single-pore non-liposuction NIR endoscopic surgery (endoscopic group), and the remaining 31 received SLNB through open-incision surgery (open group). The success rate, operation time, volume of intraoperative bleeding, postoperative axillary drainage, axillary extubation time, and the occurrence of postoperative complications were compared between the groups along with the total number of sentinel lymph nodes (SLNs), luminous SLNs, stained SLNs, and the pathological positivity rate of the SLNs.

Results
All patients underwent SLNB with a 100% success rate. SLNB operation times of the endoscopic group were longer than those of the open group (t = 3.963, P = 0.000), and the volume of axillary drainage was inferior (t = 3.035, P = 0.004). However, there were no differences in the intraoperative bleeding volumes, axillary extubation times, and postoperative complications (P > 0.05). In the Open group, the mean number of SLNs was 5.12 ± 2.16, and the pathological positivity rate was 13.53%; in the Endoscopic group, these numbers were 4.89 ± 1.73 and 12.39%. The mean number of SLNs detected (t = 0.458, P = 0.649) and the pathological positivity rates (χ2 = 0.058, P = 0.810) did not differ between the two groups. All 61 patients were followed for a median of 14.6 months. There were no local recurrences or distant metastases.

Conclusions
Our single-center results reveal that single-hole non-liposuction NIR endoscopic axillary SLNB is not inferior to open SLNB and may be an appropriate option for patients with early breast cancer who desire breast preservation with fewer incisions.

Trial registration
This retrospective study was “retrospectively registered” at the Sixth Affiliated Hospital of South China University of Technology (no. 2020105) and in National Medical Research Registration and Archival Information System (https://www.medicalresearch.org.cn, number: MR-44-21-004727).
Effect of goal-directed fluid therapy based on plasma colloid osmotic pressure on the postoperative pulmonary complications of older patients undergoing major abdominal surgery
Authors: Feng Anqi , Lu Pan , Yang Yanan , Liu Ying , Ma Lei , Lv Jianrui 
Published: February 2023

Abstract
Background
As an important component of accelerated rehabilitation surgery, goal-directed fluid therapy (GDT) is one of the optimized fluid therapy strategies and is closely related to perioperative complications and mortality. This article aimed to study the effect of combining plasma colloid osmotic pressure (COP) with stroke volume variation (SVV) as a target for intraoperative GDT for postoperative pulmonary complications in older patients undergoing major abdominal surgery.

Methods
In this study, older patients (n = 100) undergoing radical resection of gastroenteric tumors were randomized to three groups: Group C (n1 = 31) received a conventional infusion regimen, Group S1 (n2 = 34) received GDT based on SVV, and Group S2 (n3 = 35) received GDT based on SVV and COP. The results were recorded, including the lung injury score (LIS); PaO2/FiO2 ratio; lactic acid value at the times of beginning (T0) and 1 h (T1), 2 h (T2), and 3 h (T3) after liquid infusion in the operation room; the total liquid infusion volume; infusion volumes of crystalline and colloidal liquids; urine production rate; pulmonary complications 7 days after surgery; and the severity grading of postoperative pulmonary complications.

Results
The patients in the S2 group had fewer postoperative pulmonary complications than those in the C group (P < 0.05) and the proportion of pulmonary complications of grade 1 and higher than grade 2 in S2 group was significantly lower than that in C group (P <0.05); the patients in the S2 group had a higher PaO2/FiO2 ratio than those in the C group (P < 0.05), lower LIS than those in the S1 and C groups (P < 0.05), less total liquid infusion than those in the C group (P < 0.05), and more colloidal fluid infusion than those in the S1 and C groups (P < 0.05).

Conclusion
The findings of our study show that intraoperative GDT based on COP and SVV can reduce the incidence of pulmonary complications and conducive to shortening the hospital stay in older patients after gastrointestinal surgery.

Trial registration
Chinese Clinical Trial. no. ChiCTR2100045671. Registry at www.chictr.org.cn on April 20, 2021.
Clinical characteristics of venous thromboembolism onset from severe high altitude pulmonary edema in plateau regions
Authors: Liu Yanmin , Feng Xinwei , Tang Yongxue , Sun Yanqiu , Pu Xiaoyan , Feng Xiaokai 
Published: February 2023

Abstract
Background
To investigate venous thromboembolism (VTE) in hospitalized patients with severe high altitude pulmonary edema (HAPE), we performed a single center retrospective study to evaluate its clinical characteristics, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center in plateau regions.

Methods
We studied a total of 18 patients with severe HAPE from January 1, 2012 to December 31, 2021. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without VTE.

Results
Of the 18 patients hospitalized with severe HAPE (age 43 (range, 34–54) years, 14 [77.8%] men), 7 patients developed VTE (38.9%), including 5 with deep vein thrombosis (DVT) and pulmonary embolism (PE), 2 of whom had DVT only. Eighteen patients are all firstly rapid ascent to high altitudes which the mean altitude was 3700 m (3656–4050 m). Compared with patients who did not have VTE, patients with VTE had a longer time in hospital (13 [11, 19] versus 9 [7, 12]; P = 0.027), respiratory failure (6 [85.7%] versus 2 [18.2%]; P = 0.013), the shortened APTT (21.50 [19.00, 27.50] versus 26.30 [24.80, 30.10]; P = 0.044) and the higher level of D-dimer (7.81 [4.62, 9.60] versus 2.90 [1.75, 3.37]; P = 0.003). The proportion of thromboprophylaxis is too low in our cohort which 2 of 18 (11.1%) patients were given VTE prophylaxis. There was no statistically significant difference between the VTE and non-VTE groups (0 [0.0%] versus 2 [18.2%]; P = 0.497).

Conclusions
The prevalence of VTE is high in hospitalized patients with severe high altitude pulmonary edema (HAPE). Prophylaxis for venous thromboembolism may be protective in severe HAPE patients after admission. Our data seem to suggest that VTE is probably an additional prognostic factors in patients with severe HAPE.
Expanding the phenome and variome of the ROBO-SLIT pathway in congenital heart defects: toward improving the genetic testing yield of CHD
Authors: Jaouadi Hager , Jopling Chris , Bajolle Fanny , Théron Alexis , Faucherre Adèle , Gerard Hilla , Al Dybiat Sarab , Ovaert Caroline , Bonnet Damien , Avierinos Jean-François , Zaffran Stéphane 
Published: February 2023

Abstract
Background
Recent studies have shown the implication of the ROBO-SLIT pathway in heart development. Within this study, we aimed to further assess the implication of the ROBO and SLIT genes mainly in bicuspid aortic valve (BAV) and other human congenital heart defects (CHD).

Methods
We have analyzed a cohort of singleton exome sequencing data comprising 40 adult BAV patients, 20 pediatric BAV patients generated by the Pediatric Cardiac Genomics Consortium, 10 pediatric cases with tetralogy of Fallot (ToF), and one case with coarctation of the aorta. A gene-centered analysis of data was performed. To further advance the interpretation of the variants, we intended to combine more than 5 prediction tools comprising the assessment of protein structure and stability.

Results
A total of 24 variants were identified. Only 4 adult BAV patients (10%) had missense variants in the ROBO and SLIT genes. In contrast, 19 pediatric cases carried variants in ROBO or SLIT genes (61%). Three BAV patients with a severe phenotype were digenic. Segregation analysis was possible for two BAV patients. For the homozygous ROBO4: p.(Arg776Cys) variant, family segregation was consistent with an autosomal recessive pattern of inheritance. The ROBO4: c.3001 + 3G > A variant segregates with the affected family members. Interestingly, these variants were also found in two unrelated patients with ToF highlighting that the same variant in the ROBO4 gene may underlie different cardiac phenotypes affecting the outflow tract development.

Conclusion
Our results further reinforce the implication of the ROBO4 gene not only in BAV but also in ToF hence the importance of its inclusion in clinical genetic testing. The remaining ROBO and SLIT genes may be screened in patients with negative or inconclusive genetic tests.
Do polyethylene wear particles affect the development of pseudotumor in total hip arthroplasty? A minimum 15-year follow-up
Authors: Ishida Tsunehito , Tateiwa Toshiyuki , Takahashi Yasuhito , Masaoka Toshinori , Shishido Takaaki , Yamamoto Kengo 
Published: February 2023

Abstract
Background
Adverse local tissue reactions have been problematic as an implant-related complication in total hip arthroplasty (THA). Despite the absence of significant metal wear and corrosion, granulomatous pseudotumor has been reported to be caused by polyethylene wear. We performed a long-term follow-up study investigating the relationship between polyethylene wear and pseudotumor formation in THA.

Methods
This study included 57 patients (64 hips) that underwent primary THA with metal-on-polyethylene or ceramic-on-polyethylene bearing over a minimum follow-up of 15 years. They were stratified into pseudotumor and non-pseudotumor groups and their linear wear rates of polyethylene liner and serum cobalt (Co) and chromium (Cr) ion levels were compared. Pseudotumor was diagnosed on metal artifact reduction sequence-MRI according to its composition and wall thickness using the Hauptfleisch classification.

Results
The incidence of pseudotumor was 34% (22/64 hips) at the mean follow-up of 16.9 years. Metal ion levels did not differ between the pseudotumor and non-pseudotumor groups, and none of the patients exceeded the Co/Cr ratio of 2.0 μg/L. Moreover, the wear rate in the pseudotumor group was 1.8 times greater than in the non-pseudotumor group (0.14 vs. 0.08 mm/year, P < 0.001). According to an analysis of the receiver operating characteristic curves, the cutoff level of the wear rate to discriminate between pseudotumor and non-pseudotumor patients at 15 years was 0.11 mm/year (area under the curve = 91%; sensitivity = 95%; specificity = 78%; accuracy = 87%).

Conclusions
Our results might provide new insights into excessive polyethylene wear potentially leading to the future development of both pseudotumor and osteolysis. Further studies are needed to clarify the direct relationship between polyethylene wear and pseudotumor and the mutual effects of osteolysis and pseudotumor in particle reactions.
Investigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions
Authors: Apsley Abner T. , Etzel Laura , Hastings Waylon J. , Heim Christine C. , Noll Jennie G. , O’Donnell Kieran J. , Schreier Hannah M. C. , Shenk Chad E. , Ye Qiaofeng , Shalev Idan 
Published: February 2023

Abstract
Background
Immune cell proportions can be used to detect pathophysiological states and are also critical covariates in genomic analyses. The complete blood count (CBC) is the most common method of immune cell proportion estimation, but immune cell proportions can also be estimated using whole-genome DNA methylation (DNAm). Although the concordance of CBC and DNAm estimations has been validated in various adult and clinical populations, less is known about the concordance of existing estimators among stress-exposed individuals. As early life adversity and acute psychosocial stress have both been associated with unique DNAm alterations, the concordance of CBC and DNAm immune cell proportion needs to be validated in various states of stress.

Results
We report the correlation and concordance between CBC and DNAm estimates of immune cell proportions using the Illumina EPIC DNAm array within two unique studies: Study 1, a high-risk pediatric cohort of children oversampled for exposure to maltreatment (N = 365, age 8 to 14 years), and Study 2, a sample of young adults who have participated in an acute laboratory stressor with four pre- and post-stress measurements (N = 28, number of observations = 100). Comparing CBC and DNAm proportions across both studies, estimates of neutrophils (r = 0.948, p < 0.001), lymphocytes (r = 0.916, p < 0.001), and eosinophils (r = 0.933, p < 0.001) were highly correlated, while monocyte estimates were moderately correlated (r = 0.766, p < 0.001) and basophil estimates were weakly correlated (r = 0.189, p < 0.001). In Study 1, we observed significant deviations in raw values between the two approaches for some immune cell subtypes; however, the observed differences were not significantly predicted by exposure to child maltreatment. In Study 2, while significant changes in immune cell proportions were observed in response to acute psychosocial stress for both CBC and DNAm estimates, the observed changes were similar for both approaches.

Conclusions
Although significant differences in immune cell proportion estimates between CBC and DNAm exist, as well as stress-induced changes in immune cell proportions, neither child maltreatment nor acute psychosocial stress alters the concordance of CBC and DNAm estimation methods. These results suggest that the agreement between CBC and DNAm estimators of immune cell proportions is robust to exposure to child maltreatment and acute psychosocial stress.