bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate genes for infertility: an in-silico study based on cytogenetic analysis
Authors: Sahota Jatinder Singh , Sharma Bhavna , Guleria Kamlesh , Sambyal Vasudha 
Published: August 2022

Abstract
Background
The cause of infertility remains unclear in a significant proportion of reproductive-age couples who fail to conceive naturally. Chromosomal aberrations have been identified as one of the main genetic causes of male and female infertility. Structural chromosomal aberrations may disrupt the functioning of various genes, some of which may be important for fertility. The present study aims to identify candidate genes and putative functional interaction networks involved in male and female infertility using cytogenetic data from cultured peripheral blood lymphocytes of infertile patients.

Methods
Karyotypic analyses was done in 201 infertile patients (100 males and 101 females) and 201 age and gender matched healthy controls (100 males and 101 females) after 72 h peripheral lymphocyte culturing and GTG banding, followed by bioinformatic analysis using Cytoscape v3.8.2 and Metascape.

Results
Several chromosomal regions with a significantly higher frequency of structural aberrations were identified in the infertile males (5q2, 10q2, and 17q2) and females (6q2, 16q2, and Xq2). Segregation of the patients based on type of infertility (primary v/s secondary infertility) led to the identification of chromosomal regions with a significantly higher frequency of structural aberrations exclusively within the infertile males (5q2, 17q2) and females (16q2) with primary infertility. Cytoscape identified two networks specific to these regions: a male specific network with 99 genes and a female specific network with 109 genes. The top enriched GO terms within the male and female infertility networks were “skeletal system morphogenesis” and “mRNA transport” respectively. PSME3, PSMD3, and CDC27 were the top 3 hub genes identified within the male infertility network. Similarly, UPF3B, IRF8, and PSMB1 were the top 3 hub genes identified with the female infertility network. Among the hub genes identified in the male- and female-specific networks, PSMB1, PSMD3, and PSME3 are functional components of the proteasome complex. These hub genes have a limited number of reports related to their respective roles in maintenance of fertility in mice model and humans and require validation in further studies.

Conclusion
The candidate genes predicted in the present study can serve as targets for future research on infertility.
Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19
Authors: Perotin Jeanne-Marie , Gierski Fabien , Bolko Lois , Dury Sandra , Barrière Sarah , Launois Claire , Dewolf Maxime , Chouabe Stéphane , Bongrain Eric , Picard Davy , Tran Eric , N’Guyen Yoann , Mourvillier Bruno , Servettaz Amélie , Rapin Amandine , Marcus Claude , Lebargy François , Kaladjian Arthur , Salmon Jean-Hugues , Deslee Gaetan 
Published: August 2022

AbstractBackgroundThe mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment.MethodsPatients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD).ResultsSixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management.Conclusions and clinical implicationWe identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia.Trial registrationThe study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840
Association of lipid profile with obesity among breast cancer survivors: a cross-sectional study
Authors: Okekunle Akinkunmi Paul , Yie Ga-Eun , Song Sihan , Kim Zisun , Youn Hyun Jo , Cho Jihyoung , Min Jun Won , Kim Yoo Seok , Lee Jung Eun 
Published: August 2022

Abstract
Background
The role of lipid metabolism in obesity and cancer manifestations cannot be underestimated, but whether alterations in lipid metabolism can manipulate the vasculature to promote obesity among breast cancer (BC) survivors is yet to be clearly understood. This study quantified plasma lipid and particle sizes using high-throughput proton (1H) nuclear magnetic resonance (NMR) and tested their associations with obesity among breast cancer (BC) survivors.

Methods
A total of 348 (225 premenopausal and 123 postmenopausal) BC survivors enrolled from five hospitals in Korea were included. We assessed thirty-four plasma lipid biomarkers using 1H NMR, and obesity status was defined as a body mass index (BMI) of 25 kg/m2 or greater. Generalized linear and logistic regression models were applied to estimate the least-square means of BMI (kg/m2) and odds ratio (OR)s of obesity, respectively, and the corresponding 95% confidence interval (CI)s across plasma lipid levels.

Results
Mean (SD) values of BMI was 23.3 (3.2) kg/m2 and 90 (25.9%) had BMI of ≥ 25 kg/m2. BMI levels increased with increasing total triglycerides (TG), TG in lipoproteins and very-low-density lipoprotein (VLDL) subfractions. However, BMI levels decreased with increasing tertiles of high-density lipoprotein (HDL)-cholesterol (C) and HDL particle size (HDL-p). Similar associations were observed in the logistic regression models. The increasing and decreasing BMI trends with TG and HDL profiles respectively were predominantly limited to premenopausal BC survivors.

Conclusions
Increasing levels of plasma total TG and TG in lipoproteins were associated with increasing levels of BMI among premenopausal BC survivors. High HDL-C levels and large HDL-p were inversely associated with obesity among premenopausal BC survivors. Due to the cross-sectional design of this study, longitudinal studies are necessary to examine the association between obesity and lipid profile among BC survivors.
Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
Authors: He Xiaolie , Yang Li , Dong Kun , Zhang Feng , Liu Yuchen , Ma Bei , Chen Youwei , Hai Jian , Zhu Rongrong , Cheng Liming 
Published: August 2022

AbstractExosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.
Laccase-mimicking Mn–Cu hybrid nanoflowers for paper-based visual detection of phenolic neurotransmitters and rapid degradation of dyes
Authors: Le Thao Nguyen , Le Xuan Ai , Tran Tai Duc , Lee Kang Jin , Kim Moon Il 
Published: August 2022

Abstract
Background
Laccase-based biosensors are efficient for detecting phenolic compounds. However, the instability and high cost of laccases have hindered their practical utilization.

Results
In this study, we developed hierarchical manganese dioxide–copper phosphate hybrid nanoflowers (H–Mn–Cu NFs) as excellent laccase-mimicking nanozymes. To synthesize the H–Mn–Cu NFs, manganese dioxide nanoflowers (MnO2 NFs) were first synthesized by rapidly reducing potassium permanganate using citric acid. The MnO2 NFs were then functionalized with amine groups, followed by incubation with copper sulfate for three days at room temperature to drive the coordination interaction between the amine moieties and copper ions and to induce anisotropic growth of the petals composed of copper phosphate crystals, consequently yielding H–Mn–Cu NFs. Compared with those of free laccase, at the same mass concentration, H–Mn–Cu NFs exhibited lower Km (~ 85%) and considerably higher Vmax (~ 400%), as well as significantly enhanced stability in the ranges of pH, temperature, ionic strength, and incubation periods evaluated. H–Mn–Cu NFs also catalyzed the decolorization of diverse dyes considerably faster than the free laccase. Based on these advantageous features, a paper microfluidic device incorporating H–Mn–Cu NFs was constructed for the convenient visual detection of phenolic neurotransmitters, including dopamine and epinephrine. The device enabled rapid and sensitive quantification of target neurotransmitters using an image acquired using a smartphone.

Conclusions
These results clearly show that H–Mn–Cu NFs could be potential candidates to replace natural laccases for a wide range of applications in biosensing, environmental protection, and biotechnology.

Graphical Abstract
Lactobacillus cell envelope-coated nanoparticles for antibiotic delivery against cariogenic biofilm and dental caries
Authors: Weng Luting , Wu Lang , Guo Rongjuan , Ye Jiajia , Liang Wen , Wu Wei , Chen Liang , Yang Deqin 
Published: August 2022

Abstract
Background
Due to their prevalence, dental caries ranks first among all diseases endangering human health. Therefore, the prevention of caries is of great significance, as caries have become a serious public health problem worldwide. Currently, using nanoscale drug delivery systems to prevent caries has received increased attention. However, the preventive efficacy of these systems is substantially limited due to the unique physiological structure of cariogenic biofilms. Thus, novel strategies aimed at combating cariogenic biofilms to improve preventive efficiency against caries are meaningful and very necessary. Herein, inspired by cell membrane coating technology and Lactobacillus strains, we coated triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA-NPs) with an envelope of Lactobacillus (LA/TCS@PLGA-NPs) and investigated their potential as a nanoparticle delivery system against cariogenic biofilms and dental caries.

Results
LA/TCS@PLGA-NPs were successfully prepared with favorable properties, including a coated envelope, controllable size, negative charge, sustained drug-release kinetics and so on. The LA/TCS@PLGA-NPs inherited native properties from the source cell surface, thus the LA/TCS@PLGA-NPs adhered to S. mutans, integrated into the S. mutans biofilm, and interfered with the biofilm formation of S. mutans. The nanoparticles significantly inhibited the activity, biomass and virulence gene expression of S. mutans biofilms in vitro. Additionally, LA/TCS@PLGA-NPs exhibited a long-lasting inhibitory effect on the progression of caries in vivo. The safety performance of the nanoparticles is also favorable.

Conclusions
Our findings reveal that the antibiofilm effect of LA/TCS@PLGA-NPs relies not only on the inheritance of native properties from the Lactobacillus cell surface but also on the inhibitory effect on the activity, biomass and virulence of S. mutans biofilms. Thus, these nanoparticles could be considered feasible candidates for a new class of effective drug delivery systems for the prevention of caries. Furthermore, this work provides new insights into cell membrane coating technology and presents a novel strategy to combat bacterial biofilms and associated infections.

Graphical Abstract
Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting
Authors: Wu Peipei , Tang Yuting , Jin Can , Wang Min , Li Linli , Liu Zhong , Shi Hui , Sun Zixuan , Hou Xiaomei , Chen Wenya , Xu Wenrong , Qian Hui 
Published: August 2022

AbstractHuman umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.
Impact of aspartate aminotransferase–to–platelet ratio index based score to assess posthepatectomy liver failure in patients with hepatocellular carcninoma
Authors: Yugawa Kyohei , Maeda Takashi , Nagata Shigeyuki , Shiraishi Jin , Sakai Akihiro , Yamaguchi Shohei , Konishi Kozo , Hashimoto Kenkichi 
Published: August 2022

Abstract
Background
Posthepatectomy liver failure (PHLF) is a life-threatening complication following hepatic resection. The aspartate aminotransferase-to-platelet ratio index (APRI) is a non-invasive model for assessing the liver functional reserve in patients with hepatocellular carcinoma (HCC). This study aimed to establish a scoring model to stratify patients with HCC at risk for PHLF.

Methods
This single-center retrospective study included 451 patients who underwent hepatic resection for HCC between 2004 and 2017. Preoperative factors, including non-invasive liver fibrosis markers and intraoperative factors, were evaluated. The predictive impact for PHLF was evaluated using receiver operating characteristic (ROC) curves of these factors.

Results
Of 451 patients, 30 (6.7%) developed severe PHLF (grade B/C). Multivariate logistic analysis indicated that APRI, model for end-stage liver disease (MELD) score, operating time, and intraoperative blood loss were significantly associated with severe PHLF. A scoring model (over 0–4 points) was calculated using these optimal cutoff values. The area under the ROC curve of the established score for severe PHLF was 0.88, which greatly improved the predictive accuracy compared with these factors alone (p < 0.05 for all).

Conclusions
The scoring model-based APRI, MELD score, operating time, and intraoperative blood loss can predict severe PHLF in patients with HCC.
Exosomes derived from myeloid-derived suppressor cells facilitate castration-resistant prostate cancer progression via S100A9/circMID1/miR-506-3p/MID1
Authors: Gao Feng , Xu Qiaoping , Tang Zhe , Zhang Nan , Huang Yasheng , Li Zhongyi , Dai Yuliang , Yu Qiqi , Zhu Jingyu 
Published: August 2022

Abstract
Background
Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear.

Methods
In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray.

Results
The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression.

Conclusion
Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.
LINC00665 knockdown confers sensitivity in irradiated non-small cell lung cancer cells through the miR-582-5p/UCHL3/AhR axis
Authors: Xu Li-Ming , Yuan Ya-Jing , Yu Hao , Wang Shuai , Wang Ping 
Published: August 2022

Abstract
Background
The resistance to radiotherapy remains a major obstacle that limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study aims to illustrate the molecular mechanism underlying the role of LINC00665 in the radiosensitivity of NSCLC, which involves ubiquitin C-terminal hydrolase L3 (UCHL3).

Methods and results
The expression of UCHL3 was determined in clinical tissue samples collected from NSCLC patients and NSCLC cell lines. We found that UCHL3 overexpression occurred in both NSCLC tissues and cells, associated with poor prognosis in NSCLC patients. Mechanistically, UCHL3 stabilized aryl hydrocarbon receptor (AhR) protein through deubiquitination, thereby promoting PD-L1 expression. UCHL3 reduced the radiosensitivity of NSCLC cells by stabilizing AhR protein. Upstream microRNAs (miRNAs) and lncRNAs of UCHL3 were predicted by microarray profiling and validated by functional experiments. LINC00665 functioned as a sponge of miR-582-5p and thus up-regulated the expression of the miR-582-5p target UCHL3. Gain- and loss- of function assays were performed to assess the effects of LINC00665, UCHL3 and miR-582-5p on the in vitro cell malignant behaviors and immune escape as well as on the in vivo tumor growth. Silencing LINC00665 or overexpressing miR-582-5p enhanced the sensitivity of NSCLC cells to radiotherapy. LINC00665 augmented the immune escape of NSCLC cells in vitro and in vivo through stabilizing AhR protein via the miR-582-5p/UCHL3 axis.

Conclusions
Overall, LINC00665 reduced the radiosensitivity of NSCLC cells via stabilization of AhR through the miR-582-5p/UCHL3 axis.
Non-coding RNAs in lung cancer: emerging regulators of angiogenesis
Authors: Liao Yajie , Wu Xudong , Wu Mengyu , Fang Yuan , Li Jie , Tang Weiqiang 
Published: August 2022

AbstractLung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.
A fetal fraction enrichment method reduces false negatives and increases test success rate of fetal chromosome aneuploidy detection in early pregnancy loss
Authors: Qiao Longwei , Zhang Bin , Wu Xiaojuan , Zhang Chunhua , Xue Ying , Tang Hui , Tang Haoyu , Shi Jingye , Liang Yuting , Yu Bin , Wang Ting 
Published: August 2022

Abstract
Objective
We and others have previously demonstrated that the size-selection enrichment method could remarkably improve fetal fraction (FF) in the early gestational age (GA, 12–13 weeks), suggesting that 9 or 10 weeks should not be used as a threshold for GA in size-selection noninvasive prenatal screening (NIPS). Here, we assessed whether this method was reliable for detecting fetal chromosomal aneuploidy at the earliest GA (6–8 weeks).

Methods
Size-selection NIPS for fetal chromosomal aneuploidy was applied to 208 pregnancy plasma samples (102 male and 106 female fetuses), while the 169 pregnancy samples with male fetuses also underwent standard NIPS. Multivariable linear regression models were used to evaluate the association between fold-change of FF and experimental factors.

Results
The sensitivity of the cell-free DNA (cfDNA) test in detecting aneuploidy was 100% when screened with FF enrichment, whereas the sensitivity of the same patients was only 62.5% (5/8) without FF enrichment. In the 102 pregnancy samples with male fetuses, FF increased from 6.1% to 15.7%, and the median increase in FF was 2.8-fold with enrichment. Moreover, there was a trend toward an increasing success rate of the cfDNA test from 6 to 13 weeks of gestation, especially when the test success rate reached 100% after 7 weeks with FF enrichment. Multivariate linear regression analysis demonstrated that a lower initial FF, shorter cfDNA size, increased body mass index (BMI), and later GA were all independent predictors of a higher fold-change of FF. Compared with ≤ 120 bp cfDNA fragments, the mean fold-change of FF differences was 0.820 for 121–125 bp, 0.229 for 126–130 bp, − 0.154 for 131–135 bp, − 0.525 for 136–140 bp and − 0.934 for > 140 bp (Ptrend < 0.0001), suggesting that fold-change of FF significantly decreased with cfDNA fragments > 125 bp. These results were statistically significant after adjusting for confounding factors in the models for fold-change of FF.

Conclusions
The FF enrichment method is a reasonable strategy to detect fetal chromosomal aneuploidy in early pregnancy loss with reduced false negatives and increased test success rate after 7 weeks of GA and should be recommended for patients with early pregnancy loss.