bluuebunny/crossref_metadata_2025_split huggingface dataset:
IsomiR_Window: a system for analyzing small-RNA-seq data in an integrative and user-friendly manner
Authors: Vasconcelos Ana M. , Carmo Maria Beatriz , Ferreira Beatriz , Viegas Inês , Gama-Carvalho Margarida , Ferreira António , Amaral Andreia J. 
Published: February 2021

AbstractBackgroundIsomiRs are miRNA variants that vary in length and/or sequence when compared to their canonical forms. These variants display differences in length and/or sequence, including additions or deletions of one or more nucleotides (nts) at the 5′ and/or 3′ end, internal editings or untemplated 3′ end additions. Most available tools for small RNA-seq data analysis do not allow the identification of isomiRs and often require advanced knowledge of bioinformatics. To overcome this, we have developed IsomiR Window, a platform that supports the systematic identification, quantification and functional exploration of isomiR expression in small RNA-seq datasets, accessible to users with no computational skills.MethodsIsomiR Window enables the discovery of isomiRs and identification of all annotated non-coding RNAs in RNA-seq datasets from animals and plants. It comprises two main components: the IsomiR Window pipeline for data processing; and the IsomiR Window Browser interface. It integrates over ten third-party softwares for the analysis of small-RNA-seq data and holds a new algorithm that allows the detection of all possible types of isomiRs. These include 3′ and 5′end isomiRs, 3′ end tailings, isomiRs with single nucleotide polymorphisms (SNPs) or potential RNA editings, as well as all possible fuzzy combinations. IsomiR Window includes all required databases for analysis and annotation, and is freely distributed as a Linux virtual machine, including all required software.ResultsIsomiR Window processes several datasets in an automated manner, without restrictions of input file size. It generates high quality interactive figures and tables which can be exported into different formats. The performance of isomiR detection and quantification was assessed using simulated small-RNA-seq data. For correctly mapped reads, it identified different types of isomiRs with high confidence and 100% accuracy. The analysis of a small RNA-seq data from Basal Cell Carcinomas (BCCs) using isomiR Window confirmed that miR-183-5p is up-regulated in Nodular BCCs, but revealed that this effect was predominantly due to a novel 5′end variant. This variant displays a different seed region motif and 1756 isoform-exclusive mRNA targets that are significantly associated with disease pathways, underscoring the biological relevance of isomiR-focused analysis. IsomiR Window is available athttps://isomir.fc.ul.pt/.
Selecting single cell clustering parameter values using subsampling-based robustness metrics
Authors: Patterson-Cross Ryan B. , Levine Ariel J. , Menon Vilas 
Published: February 2021

Abstract
Background
Generating and analysing single-cell data has become a widespread approach to examine tissue heterogeneity, and numerous algorithms exist for clustering these datasets to identify putative cell types with shared transcriptomic signatures. However, many of these clustering workflows rely on user-tuned parameter values, tailored to each dataset, to identify a set of biologically relevant clusters. Whereas users often develop their own intuition as to the optimal range of parameters for clustering on each data set, the lack of systematic approaches to identify this range can be daunting to new users of any given workflow. In addition, an optimal parameter set does not guarantee that all clusters are equally well-resolved, given the heterogeneity in transcriptomic signatures in most biological systems.

Results
Here, we illustrate a subsampling-based approach (chooseR) that simultaneously guides parameter selection and characterizes cluster robustness. Through bootstrapped iterative clustering across a range of parameters, chooseR was used to select parameter values for two distinct clustering workflows (Seurat and scVI). In each case, chooseR identified parameters that produced biologically relevant clusters from both well-characterized (human PBMC) and complex (mouse spinal cord) datasets. Moreover, it provided a simple “robustness score” for each of these clusters, facilitating the assessment of cluster quality.

Conclusion
chooseR is a simple, conceptually understandable tool that can be used flexibly across clustering algorithms, workflows, and datasets to guide clustering parameter selection and characterize cluster robustness.
Generation and identification of a conditional knockout allele for the PSMD11 gene in mice
Authors: Zhao Linlin , Zhao Jinming , Zhang Yingying , Wang Lele , Zuo Longyan , Niu Airu , Zhang Wei , Xue Xia , Zhao Suhong , Sun Chao , Li Kailin , Wang Jue , Bian Zhimin , Zhao Xiaogang , Saur Dieter , Seidler Barbara , Wang Chuanxin , Qi Tonggang 
Published: February 2021

Abstract
Background
Our previous study have shown that the PSMD11 protein was an important survival factor for cancer cells except for its key role in regulation of assembly and activity of the 26S proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11flx) in mice.

Results
It was found that homozygous PSMD11 flx/flx mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11flx/flx and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11−/−) were identified in E7.5–8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26CAG − CreERT2/+; PSMD11flx/flx, and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive apoptosis in MEFs.

Conclusions
In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 flx/flx mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.
Etomoxir regulates the differentiation of male germ cells by specifically reducing H3K27ac level
Authors: Xu Yushan , Xie Jue 
Published: February 2021

Abstract
Background
Fatty acid oxidation plays an important role in a variety of developing and mature organ systems. However, the role of this metabolic pathway in different stages of testis development remains unknown. Here, we elucidate the mechanisms by which fatty acid oxidation regulates the maintenance and differentiation of gonocytes and spermatogonial stem cells.

Results
During E13.5-E15.5, male germ cells gradually enter the mitotic arrest phase, while the expression of CPT1A, a rate-limiting enzyme for fatty acid oxidation, gradually increases. Therefore, we treated pregnant mice (E13.5 to E15.5) with etomoxir, which is an inhibitor of CPT1A. Etomoxir-treated mice showed no difference in embryonic morphology; however, etomoxir-treated male gonocytes exited mitotic arrest, and cells of the gonad underwent apoptosis. In addition, etomoxir-treated mice at P7 displayed impaired homing of spermatogonia and increased cell apoptosis. We further demonstrated that inhibition of fatty acid oxidation in gonads was associated with gonocyte differentiation events and the histone modification H3K27ac.

Conclusions
Inhibiting fatty acid oxidation can specifically reduce the level of H3K27ac in the reproductive crest, which may be the cause of the down-regulation of male differentiation-specific gene expression, which ultimately leads to the male primordial germ cells exited from mitotic arrest. Our work uncovers metabolic reprogramming during male gonadal development, revealing that it plays an important role in the maintenance of gonocytes in a differentiated and quiescent state during foetal testis development.
Identification of genes associated with the biosynthesis of unsaturated fatty acid and oil accumulation in herbaceous peony ‘Hangshao’ (Paeonia lactiflora ‘Hangshao’) seeds based on transcriptome analysis
Authors: Meng Jia-Song , Tang Yu-Han , Sun Jing , Zhao Da-Qiu , Zhang Ke-Liang , Tao Jun 
Published: February 2021

Abstract
Background
Paeonia lactiflora ‘Hangshao’ is widely cultivated in China as a traditional Chinese medicine ‘Radix Paeoniae Alba’. Due to the abundant unsaturated fatty acids in its seed, it can also be regarded as a new oilseed plant. However, the process of the biosynthesis of unsaturated fatty acids in it has remained unknown. Therefore, transcriptome analysis is helpful to better understand the underlying molecular mechanisms.

Results
Five main fatty acids were detected, including stearic acid, palmitic acid, oleic acid, linoleic acid and α-linolenic acid, and their absolute contents first increased and then decreased during seed development. A total of 150,156 unigenes were obtained by transcriptome sequencing. There were 15,005 unigenes annotated in the seven functional databases, including NR, NT, GO, KOG, KEGG, Swiss-Prot and InterPro. Based on the KEGG database, 1766 unigenes were annotated in the lipid metabolism. There were 4635, 12,304, and 18,291 DEGs in Group I (60 vs 30 DAF), Group II (90 vs 60 DAF) and Group III (90 vs 30 DAF), respectively. A total of 1480 DEGs were detected in the intersection of the three groups. In 14 KEGG pathways of lipid metabolism, 503 DEGs were found, belonging to 111 enzymes. We screened out 123 DEGs involved in fatty acid biosynthesis (39 DEGs), fatty acid elongation (33 DEGs), biosynthesis of unsaturated fatty acid (24 DEGs), TAG assembly (17 DEGs) and lipid storage (10 DEGs). Furthermore, qRT-PCR was used to analyze the expression patterns of 16 genes, including BBCP, BC, MCAT, KASIII, KASII, FATA, FATB, KCR, SAD, FAD2, FAD3, FAD7, GPAT, DGAT, OLE and CLO, most of which showed the highest expression at 45 DAF, except for DGAT, OLE and CLO, which showed the highest expression at 75 DAF.

Conclusions
We predicted that MCAT, KASIII, FATA, SAD, FAD2, FAD3, DGAT and OLE were the key genes in the unsaturated fatty acid biosynthesis and oil accumulation in herbaceous peony seed. This study provides the first comprehensive genomic resources characterizing herbaceous peony seed gene expression at the transcriptional level. These data lay the foundation for elucidating the molecular mechanisms of fatty acid biosynthesis and oil accumulation for herbaceous peony.
Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep
Authors: Han Fuhui , Li Jing , Zhao Ranran , Liu Lirong , Li Lanlan , Li Qian , He Jianning , Liu Nan 
Published: February 2021

AbstractBackgroundIntramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China’s most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12).ResultsWe identified a total of 26,247 genes and 6935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. One pathway was significantly enriched, namely tight junction. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed a lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4, MSTRG.16157.3-ULK1,MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1,MSTRG.12864.1-FHL1, MSTRG.2469.2-EXOC6and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR.ConclusionsOur study identified the differentially expressed mRNAs and lncRNAs during intramuscular lipid deposition in Aohan fine-wool sheep. The work may widen the knowledge about the annotation of the sheep genome and provide a working basis for investigating intramuscular fat deposition in sheep.
Fruit ripening-associated leucylaminopeptidase with cysteinylglycine dipeptidase activity from durian suggests its involvement in glutathione recycling
Authors: Panpetch Pawinee , Sirikantaramas Supaart 
Published: February 2021

Abstract
Background
Durian (Durio zibethinus L.) is a highly popular fruit in Thailand and several other Southeast Asian countries. It is abundant in essential nutrients and sulphur-containing compounds such as glutathione (GSH) and γ-glutamylcysteine (γ-EC). Cysteinylglycine (Cys-Gly) is produced by GSH catabolism and occurs in durian fruit pulp. Cysteine (Cys) is a precursor of sulphur-containing volatiles generated during fruit ripening. The aforementioned substances contribute to the strong odour and flavour of the ripe fruit. However, the genes encoding plant Cys-Gly dipeptidases are unknown. The aim of this study was to measure leucylaminopeptidase (LAP) activity in durian fruit pulp.

Results
We identified DzLAP1 and DzLAP2, which the former was highly expressed in the fruit pulp. DzLAP1 was expressed at various ripening stages and in response to ethephon/1-MCP treatment. Hence, DzLAP1 is active at the early stages of fruit ripening. DzLAP1 is a metalloenzyme ~ 63 kDa in size. It is activated by Mg2+ or Mn2+ and, like other LAPs, its optimal alkaline pH is 9.5. Kinetic studies revealed that DzLAP1 has Km = 1.62 mM for its preferred substrate Cys-Gly. DzLAP1-GFP was localised to the cytosol and targeted the plastids. In planta Cys-Gly hydrolysis was confirmed for Nicotiana benthamiana leaves co-infiltrated with Cys-Gly and expressing DzLAP1.

Conclusions
DzLAP1 has Cys-Gly dipeptidase activity in the γ-glutamyl cycle. The present study revealed that the LAPs account for the high sulphur-containing compound levels identified in fully ripened durian fruit pulp.
Is age and not antiretroviral therapy the strongest risk factor for chronic pain in HIV-infected population?
Authors: Kowalski Marcin , Horban Andrzej , Slomka Bartosz , Shahnazaryan Karen , Rongies Witold 
Published: February 2021

AbstractBackgroundChronic pain in HIV-infected patients on effective antiretroviral therapy (ART) limits patients’ normal functioning both somatically and psychologically. The current state of knowledge on the topic is insufficient, with the underlying causes of this pain unexplained. Therefore we analyzed the frequency and factors associated with chronic pain in HIV-infected patients on ART.MethodsWe conducted a prospective, survey study, including consecutive HIV-infected patients under specialist care at the HIV Outpatient Clinic of the Hospital for Infectious Disease in Warsaw between February 2014 and December 2016. During their routine visit all patients who agreed to participate in the study were surveyed using a study questionnaire. For all patients reporting any pain the Brief Pain Inventory (BPI) form and Douleur Neuropathique 4 Questions form (DN4) were completed. Data on history and current ART and laboratory measurements were obtained from electronical database. Chi-squared and Kruskal-Wallis tests were used for group comparison. The potential factors associated with chronic pain were identified via logistic regression models.ResultsIn total 196 HIV-infected patients were included in the study, 57 (29,1%) of them reported chronic pain. The reported pain was mostly (75%) limited to a single area of the body. In univariable logistic regression model the odds of chronic pain were significantly higher with increasing age (OR 1.36 [95%CI:1.17–1.58]), time under specialist care (OR 2.25 [95%CI:1.42–35.7]), time on ART (OR2.96 [95%CI:1.60–5.49]), previous ART with zidovudine (OR 2.00[95%CI:1.06–1.55]) and previous treatment with ddI, ddC or d4T (OR4.13 [95%CI:1.92–8.91]). Homosexual route of HIV infection as compared to injecting drug use was decreasing the odds of chronic pain (OR0.33 [95%CI: 014–0.75]). In multivariable analyses, adjusting for all above the only factor associated with chronic pain was age (OR1.28 [95%CI:1.06–1.55]).ConclusionsThe prevalence of chronic pain in the studied population of HIV-infected Polish patients was high. The only risk factor for chronic pain identified was age. With ageing HIV population it is therefore imperative to develop cooperation protocols for specialist HIV treatment clinics, pain treatment clinics, and rehabilitation units.
Consent in pregnancy - an observational study of ante-natal care in the context of Montgomery: all about risk?
Authors: Nicholls Jacqueline A. , David Anna L. , Iskaros Joseph , Siassakos Dimitrios , Lanceley Anne 
Published: February 2021

Abstract
Background
How to best support pregnant women in making truly autonomous decisions which accord with current consent law is poorly understood and problematic for them and their healthcare professionals. This observational study examined a range of ante-natal consultations where consent for an intervention took place to determine key themes during the encounter.

Methods
Qualitative research in a large urban teaching hospital in London. Sixteen consultations between pregnant women and their healthcare professionals (nine obstetricians and three midwives) where ante-natal interventions were discussed and consent was documented were directly observed. Data were collectively analysed to identify key themes characterising the consent process.

Results
Four themes were identified: 1) Clinical framing - by framing the consultation in terms of the clinical decision to be made HCPs miss the opportunity to assess what really matters to a pregnant woman. For many women the opportunity to feel that their previous experiences had been ‘heard’ was an important but sometimes neglected prelude to the ensuing consultation; 2) Clinical risk dominated narrative - all consultations were dominated by information related to risk; discussion of reasonable alternatives was not always observed and women’s understanding of information was seldom verified making compliance with current law questionable; 3) Parallel narrative - woman-centred experience – for pregnant women social factors such as the place of birth and partner influences were as or more important than considerations of clinical risk yet were often missed by HCPs; 4) Cross cutting narrative - genuine dialogue - we observed variably effective interaction between the clinical (2) and patient (3) narratives influenced by trust and empathy and explicit empowering language by HCPs.

Conclusion
We found that ante-natal consultations that include consent for interventions are dominated by clinical framing and risk, and explore the woman-centred narrative less well. Current UK law requires consent consultations to include explicit effort to gauge a woman’s preferences and values, yet consultations seem to fail to achieve such understanding. At the very least, consultations may be improved by the addition of opening questions along the lines of ‘what matters to you most?’
Anesthesia, sex and miscarriage history may influence the association between cesarean delivery and autism spectrum disorder
Authors: Yang Ye , Lin Jingjing , Lu Xiaozi , Xun Guanglei , Wu Renrong , Li Yamin , Ou Jianjun , Shen Yidong , Xia Kun , Zhao Jingping 
Published: February 2021

Abstract
Background
To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association.

Methods
In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD.

Results
CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311–1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273–2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392–5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094–4.291; aOR = 2.919, 95% CI = 1.789–4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (β = − 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD.

Conclusions
The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.