bluuebunny/crossref_metadata_2025 huggingface dataset:
miRNA-21 may serve as a promising noninvasive marker of glioma with a high diagnostic performance: a pooled analysis of 997 patients
Authors: Zhao Xinli , Xiao Zhihong , Li Bin , Li Hongwei , Yang Bo , Li Tian , Mei Zubing
Published: February 2021

Background:

Although various serum and tissue biomarkers have been investigated for glioma diagnosis, no gold standard has been identified. miRNA-21 was demonstrated to be a promising biomarker for the diagnosis of various brain tumors, whereas there remains uncertainty concerning whether miRNA-21 could be used as a good clinical diagnostic biomarker for glioma. The current meta-analysis aimed to evaluate the diagnostic accuracy of miRNA-21 as a potent biomarker in adults with suspected glioma.

Methods:

The Pubmed and Embase databases were searched systematically from inception to January 2020 to identify relevant research reports. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Summary receiver operating characteristic (SROC) curves were used to evaluate the overall diagnostic performance. Meta-regression and subgroup analyses were conducted to determine the source of heterogeneity and test the robustness of the results.

Results:

From 5394 citations with 997 subjects that met the inclusion criteria, 11 studies were selected. Summary estimates of the diagnostic performance of miRNA-21 were as follows: sensitivity, 0.83 [95% confidence interval (CI): 0.73–0.89]; specificity, 0.92 (95% CI: 0.85–0.96); PLR, 10.20 (95% CI: 5.10–20.30); NLR, 0.19 (95% CI: 0.12–0.31); and DOR, 54 (95% CI: 19–155). The area under the SROC curve was 0.94 (95% CI: 0.92–0.96). Deeks’s funnel plot revealed no evidence of publication bias ( p = 0.59). Meta-regression analysis suggested that study publication year could attribute to the heterogeneity. Subgroup analysis found miRNA-21 had a constant high diagnostic accuracy across different ethnicity, glioma grade, sample source, and study region.

Conclusion:

This meta-analysis demonstrated that miRNA-21 has high diagnostic performance and could serve as a promising noninvasive diagnostic marker for glioma. Further large prospective studies are needed to validate its diagnostic value and its prognostic significance and therapeutic effects.
Frontal Sinus Drainage in Acute Pediatric Sinusitis With Intracranial Complications
Authors: Chorney Stephen R. , Buzi Adva , Rizzi Mark D.
Published: February 2021

Background

The indication for frontal sinus drainage is uncertain when managing pediatric acute sinusitis with intracranial complications.

Objective

The primary objective was to determine if addressing the frontal sinus reduced need for subsequent surgical procedures in children presenting with acute sinusitis complicated by intracranial abscess.

Methods

A case series with chart review was performed at a tertiary children’s hospital between 2007 and 2019. Children under 18 years of age requiring surgery for complicated acute sinusitis that included the frontal sinus with noncontiguous intracranial abscess were included. Outcomes were compared among children for whom the frontal sinus was drained endoscopically, opened intracranially, or left undrained.

Results

Thirty-five children with a mean age of 11.1 years (95% CI: 9.9-12.3) met inclusion. Most presented with epidural abscess (37%). Hospitalizations lasted 12.9 days (95% CI: 10.2-15.5), 46% required a second surgery, 11% required three or more surgeries, and 31% were readmitted within 60 days. Initial surgery for 29% included endoscopic frontal sinusotomy, 34% had a frontal sinus cranialization and 37% did not have any initial drainage of the frontal sinus. Groups were similar with respect to demographics, severity of infection, need for repeat surgery, length of stay, and readmissions (p > .05). Further, persistence of cranial neuropathies, seizures, or major neurological sequelae after discharge were no different among groups (p > .05).

Conclusion

Drainage of the frontal sinus, when technically feasible, was not associated with reduced surgical procedures or increased complications and there is unclear benefit on measured clinical outcomes.
Staying SHARP in times of crisis – The impact of COVID-19 on anaesthesiology residency
Authors: Lim Denise Yan Yin , Ng Von Vee , Tan Zihui , Koh Darren LK
Published: February 2021

The COVID-19 pandemic is an unprecedented crisis that has taken the world by storm, and it has taken an especially immense toll on the healthcare sector. Although much effort has been made to make changes in key areas such as clinical practice, national policy and research, we believe that it is just as important to evaluate the impact of the crisis on postgraduate medical training. To this end, we would like to share our experience within an anaesthesiology residency programme in Singapore, the SingHealth Anaesthesiology Residency Programme, which we hope will benefit other training programmes and anyone involved in postgraduate medical education as a whole. Key challenges identified include restrictions on teaching events, difficulties in completing core posting requirements, changes in clinical workload, postponement of examinations, exposure risk (particularly in relation to aerosol-generating procedures) and psychological burden. Strategies that have been implemented to tackle these challenges are also described, including the use of online platforms, modifications to posting and promotion requirements, manpower adjustments, provision of protective equipment and training in infectious disease protocols. Ultimately, we believe that a supportive work environment is essential to ensure the wellbeing of residents in times of crisis.
Young survivor of a rare primary anaplastic large cell lymphoma of the trachea
Authors: Shahid Jehanzeb , Khan Faheemullah , Tariq Muhammad Usman , Jehan Faisal , Ahmad Wiqar
Published: February 2021

Primary anaplastic large cell lymphoma of the trachea is a very rare tumor. Diagnosis is often missed for a long time because the presentation often resembles that of obstructive airway disease. A 24-year-old non-smoker male presented at an outpatient clinic complaining of gradual development of stridor and shortness of breath over a recent period of four weeks. Imaging workup revealed a large lobulated, soft tissue, mildly enhancing, eccentrically placed intraluminal proximal tracheal mass, which showed extension outside of the tracheal lumen in the peritracheal fat. The patient underwent surgery. A biopsy of the resected mass reported anaplastic large cell lymphoma. Post-operation, the patient underwent chemotherapy consisting of four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone). Follow-up imaging showed non-visualization of the mass. Primary lymphoma (anaplastic large cell lymphoma, which is a rare type of non-Hodgkin’s lymphoma) of the trachea is a rare tumor. Early curative resection with post-operative chemotherapy has a favorable outcome, as in our case.
Vanillin based polymers: V. Poly(hydrovanilloin–urethane)
Authors: Amarasekara Ananda S , Garcia-Obregon Rocio
Published: February 2021

Renewable resources based hydrovanilloin [1,2- bis(4-hydroxy-3-methoxyphenyl)-1,2-ethanediol] was synthesized in 86% yield by electrochemical dimerization of vanillin in aqueous NaOH. This symmetrical bis-phenol monomer was then used for the preparation of urethane polymers by two different methods. In the first method a 1:2 mole ratio mixture of hydrovanilloin and diisocyanate was polymerized in DMF using 1,4-diazabicyclo[2,2,2]octane as the catalyst at 60°C, for 1 h to give poly(hydrovanilloin–urethane)s. In the second method diisocyanates were first reacted with polyethylene glycol-400 to give pre-polymers. Then prepolymers were reacted with equivalent amount of hydrovanilloin at 60°C for 4 days to produce poly(hydrovanilloin-ethylene glycol-urethane)s. The first method resulted hard poly(hydrovanilloin–urethane)s showing Tg values in the range of 121–172°C. The second method yielded softer poly(hydrovanilloin-ethylene glycol-urethane)s and these polymers failed to show distinct glass transition temperatures in the DSC analysis. However, poly(hydrovanilloin-ethylene glycol-urethane)s showed better thermal stabilities than polymers without polyethylene glycol units.
Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure
Authors: Zhang Jiabin , Chan Hon Fai , Wang Haixia , Shao Dan , Tao Yu , Li Mingqiang
Published: February 2021

Liver failure is a lethal condition with hepatocellular dysfunction, and liver transplantation is presently the only effective treatment. However, due to the limited availability of donors and the potential immune rejection, novel therapeutic strategies are actively sought to restore the normal hepatic architectures and functions, especially for livers with inherited metabolic dysfunctions or chronic diseases. Although the conventional cell therapy has shown promising results, the direct infusion of hepatocytes is hampered by limited hepatocyte sources, poor cell viability, and engraftment. Hence, this review mainly highlights the role of stem cells and progenitors as the alternative cell source and summarizes the potential approaches based on tissue engineering to improve the delivery efficiency of cells. Particularly, the underlying mechanisms for cell therapy using stem cells and progenitors are discussed in two main aspects: paracrine effect and cell differentiation. Moreover, tissue-engineering approaches using cell aggregates and decellularized liver scaffolds for bioengineering of functional hepatic constructs are discussed and compared in terms of the potential to replicate liver physiological structures. In the end, a potentially effective strategy combining the premium advantages of stem cell aggregates and decellularized liver scaffolds is proposed as the future direction of liver tissue engineering and regeneration.
Phishing for Long Tails: Examining Organizational Repeat Clickers and Protective Stewards
Authors: Canham Matthew , Posey Clay , Strickland Delainey , Constantino Michael
Published: February 2021

Organizational cybersecurity efforts depend largely on the employees who reside within organizational walls. These individuals are central to the effectiveness of organizational actions to protect sensitive assets, and research has shown that they can be detrimental (e.g., sabotage and computer abuse) as well as beneficial (e.g., protective motivated behaviors) to their organizations. One major context where employees affect their organizations is phishing via email systems, which is a common attack vector used by external actors to penetrate organizational networks, steal employee credentials, and create other forms of harm. In analyzing the behavior of more than 6,000 employees at a large university in the Southeast United States during 20 mock phishing campaigns over a 19-month period, this research effort makes several contributions. First, employees’ negative behaviors like clicking links and then entering data are evaluated alongside the positive behaviors of reporting the suspected phishing attempts to the proper organizational representatives. The analysis displays evidence of both repeat clicker and repeat reporter phenomena and their frequency and Pareto distributions across the study time frame. Second, we find that employees can be categorized according to one of the four unique clusters with respect to their behavioral responses to phishing attacks—“Gaffes,” “Beacons,” “Spectators,” and “Gushers.” While each of the clusters exhibits some level of phishing failures and reports, significant variation exists among the employee classifications. Our findings are helpful in driving a new and more holistic stream of research in the realm of all forms of employee responses to phishing attacks, and we provide avenues for such future research.
Benefits of Computer Engagement in Older Adults with Dementia
Authors: Sautter Scott W. , Ord Anna S. , Azher Aisha , Chidester Amy , Aravich Paul F.
Published: February 2021

Objectives: Two pilot studies aimed to determine the effects of individual computer engagement on behavioral health outcomes in individuals with dementia. The focus was on participants’ mental health, challenging behaviors, antipsychotic medications, and professional caregiver stress. Methods: Two pilot randomized control trials were conducted. First trial involved residents with advanced dementia in a long-term care facility. The second trial involved residents with mild dementia in an assisted living setting. The participants in the experimental group in both studies were provided with guided iN2L computer engagement followed by unrestricted use. Results: Statistically reliable improvements were found in both studies for participants’ emotional well-being and professional caregiver stress. Reliable improvements in cognition and depression were found in the mild dementia study, but not in the advanced dementia study. No statistically reliable changes were observed for antipsychotic medications or challenging behaviors. Discussion: Computer engagement was associated with improvements in participants’ emotional well-being and with a reduction in professional caregiver stress. Results should be interpreted with caution in the context of high attrition. Future studies may build upon these pilot findings and examine effects of technology use on mood and cognition in larger samples of older adults across a wider range of outcome measures.
The Provincial Patient and Family Group (PFG) for Alberta Health Services Transforms How Care is Planned and Delivered: A Decade of Experience
Authors: Picklyk Deanna , Volk Shawn , Burns Katharina Kovacs
Published: February 2021

Although many health care organizations made significant headway in building relationships with patients and families at the point of care, there continues to be opportunities to partner with them at the system level. One such opportunity is the Patient and Family Advisory Group (PFG) at Alberta Health Services (AHS). Developed 10 years ago as a formal group of patient and family volunteers, PFG has provided advice on over 350 key organization initiatives, including the Patient First Strategy and the Family Visitation policies and guidelines. Through the formal partnership with PFG and its members who bring their lived experiences with the health system and its services, AHS has demonstrated its commitment to designing and improving services with the user in mind. Now entering its second decade, PFG, supported by AHS leadership, continues to explore new strategic approaches with internal and external stakeholders to reinforce the importance of Patient and Family-Centered Care.
Time-dependent seismic hazard and risk due to wastewater injection in Oklahoma
Authors: Grigoratos Iason , Bazzurro Paolo , Rathje Ellen , Savvaidis Alexandros
Published: February 2021

In the past decade, Oklahoma has experienced unprecedented seismicity rates, following an increase in the volumes of wastewater that are being disposed underground. In this article, we perform a probabilistic assessment of the time-dependent seismic hazard in Oklahoma and incorporate these results into an integrated seismic risk model to assess the evolution of the statewide economic losses, including a conservative forecast through 2030. Our risk model employs an injection-driven earthquake rate model, a region-specific ground motion model, a recent Vs30 map, HAZUS exposure data and updated vulnerability curves for both structural and nonstructural elements, and contents. The calculations are performed using a stochastic Monte Carlo–based approach implemented in the OpenQuake engine. The resulting seismic hazard maps illustrate the incompatibility of the regional seismic provisions with the current seismicity. In 2015, in particular, the induced seismic hazard in several places in Oklahoma was higher than along the San Andreas fault. During the peak of seismicity in 2015, the seismic risk was 275 times higher than the background level, with the vast majority of losses originating from damages to nonstructural elements and contents. Our direct economic loss estimates are in reasonable agreement with the paid insurance claims, but show significant sensitivity to the ground motion model selection. The proposed risk model, with possible regular updates on the seismicity rate forecast, can help stakeholders define acceptable production levels.
The photogeochemical cycle of Mn oxides on the Earth's surface
Authors: Lu Anhuai , Li Yan , Liu Feifei , Liu Yuwei , Ye Huan , Zhuang Ziyi , Li Yanzhang , Ding Hongrui , Wang Changqiu
Published: February 2021

Manganese (Mn) oxides have been prevalent on Earth since before the Great Oxidation Event and the Mn cycle is one of the most important biogeochemical processes on the Earth's surface. In sunlit natural environments, the photochemistry of Mn oxides has been discovered to enable solar energy harvesting and conversion in both geological and biological systems. One of the most widespread Mn oxides is birnessite, which is a semiconducting layered mineral that actively drives Mn photochemical cycling in Nature. The oxygen-evolving centre in biological photosystem II (PSII) is also a Mn-cluster of Mn4CaO5, which transforms into a birnessite-like structure during the photocatalytic oxygen evolution process. This phenomenon draws the potential parallel of Mn-functioned photoreactions between the organic and inorganic world. The Mn photoredox cycling involves both the photo-oxidation of Mn(II) and the photoreductive dissolution of Mn(IV/III) oxides. In Nature, the occurrence of Mn(IV/III) photoreduction is usually accompanied with the oxidative degradation of natural organics. For Mn(II) oxidation into Mn oxides, mechanisms of biological catalysis mediated by microorganisms (such asPseudomonas putidaandBacillusspecies) and abiotic photoreactions by semiconducting minerals or reactive oxygen species have both been proposed. In particular, anaerobic Mn(II) photo-oxidation processes have been demonstrated experimentally, which shed light on Mn oxide emergence before atmospheric oxygenation on Earth. This review provides a comprehensive and up-to-date elaboration of Mn oxide photoredox cycling in Nature, and gives brand-new insight into the photochemical properties of semiconducting Mn oxides widespread on the Earth's surface.
SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A
Authors: Ji Hao , Wang Juan , Lu Binbin , Li Juan , Zhou Jing , Wang Li , Xu Shufen , Peng Peng , Hu Xuezhen , Wang Keming
Published: February 2021

Background

LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration.

Methods

We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1.

Results

AGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA.

Conclusions

We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.
DeepGRN: prediction of transcription factor binding site across cell-types using attention-based deep neural networks
Authors: Chen Chen , Hou Jie , Shi Xiaowen , Yang Hua , Birchler James A. , Cheng Jianlin
Published: February 2021

Background

Due to the complexity of the biological systems, the prediction of the potential DNA binding sites for transcription factors remains a difficult problem in computational biology. Genomic DNA sequences and experimental results from parallel sequencing provide available information about the affinity and accessibility of genome and are commonly used features in binding sites prediction. The attention mechanism in deep learning has shown its capability to learn long-range dependencies from sequential data, such as sentences and voices. Until now, no study has applied this approach in binding site inference from massively parallel sequencing data. The successful applications of attention mechanism in similar input contexts motivate us to build and test new methods that can accurately determine the binding sites of transcription factors.

Results

In this study, we propose a novel tool (named DeepGRN) for transcription factors binding site prediction based on the combination of two components: single attention module and pairwise attention module. The performance of our methods is evaluated on the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge datasets. The results show that DeepGRN achieves higher unified scores in 6 of 13 targets than any of the top four methods in the DREAM challenge. We also demonstrate that the attention weights learned by the model are correlated with potential informative inputs, such as DNase-Seq coverage and motifs, which provide possible explanations for the predictive improvements in DeepGRN.

Conclusions

DeepGRN can automatically and effectively predict transcription factor binding sites from DNA sequences and DNase-Seq coverage. Furthermore, the visualization techniques we developed for the attention modules help to interpret how critical patterns from different types of input features are recognized by our model.
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

Background

IsomiRs 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.

Methods

IsomiR 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.

Results

IsomiR 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

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

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

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

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

Background

Intramuscular 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).

Results

We 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.

Conclusions

Our 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

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

Background

Chronic 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.

Methods

We 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.

Results

In 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]).

Conclusions

The 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

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

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.
The effect of inhaling mother’s breast milk odor on the behavioral responses to pain caused by hepatitis B vaccine in preterm infants: a randomized clinical trial
Authors: Rad Zahra Akbarian , Aziznejadroshan Parvin , Amiri Adeleh Saebi , Ahangar Hemmat Gholinia , Valizadehchari Zahra
Published: February 2021

Background

Nowadays, it is generally assumed that non-pharmacologic pain relief in preterm infants is an important measure to consider. Research findings suggest that familiar odors have soothing effects for neonates. The aim of this study was to compare the effect of maternal breast milk odor (MBMO) with that of another mother’s breast milk odor (BMO) on the behavioral responses to pain caused by hepatitis B (HB) vaccine injection in preterm infants.

Methods

This single-blind randomized clinical trial was performed over the period between February 2019 and March 2020 in the neonatal intensive care unit of Babol Rouhani Hospital, Iran. Ninety preterm infants, who were supposed to receive their HB vaccine, were randomly assigned into three groups: MBMO (A), another mother’s BMO (B), and control with distilled water(C). Oxygen saturation (SaO2), blood pressure (BP) and heart rate (HR) were recorded for all participants through electronic monitoring. In addition, premature infant pain profiles (PIPP) were determined through video recording for all three groups during intervention. The chi-square, ANOVA and ANCOVA were used for analyzing the data, and P < 0.05 was considered significant in this study.

Results

No significant differences were found between the three groups in mean ± SD of HR, BP, and Sao2 before the intervention (P > 0.05). After the intervention, however, the means for heart rate in groups A, B, and C were 146 ± 14.3, 153 ± 17.5 and 155 ± 17.7, respectively (P = 0.012). Moreover, the means for PIPP scores in groups A, B and C were 6.6 ± 1.3, 10 ± 2, and 11.4 ± 1.9, respectively (P < 0.001). There was no significant difference found between groups in their means of SaO2, systolic and diastolic blood pressure after the intervention (P > 0.05).

Conclusions

The results indicate that stimulation with MBMO is effective in reducing pain in preterm infants; therefore, it can be postulated that this technique can be considered in less invasive procedures such as needling.

Trial registration

IRCT, IRCT20190220042771N1. Registered 18 May 2019- Retrospectively registered,