bluuebunny/crossref_metadata_2025_split huggingface dataset:
Umbilical cord-derived Wharton’s jelly for treatment of knee osteoarthritis: study protocol for a non-randomized, open-label, multi-center trial
Authors: Gupta Ashim , Maffulli Nicola , Rodriguez Hugo C. , Lee Cassidy E. , Levy Howard J. , El-Amin Saadiq F. 
Published: February 2021

Abstract
Background
Osteoarthritis (OA) is the most common joint disorder in the USA, and knee OA has the highest prevalence. Inflammation and decrease in vascularization are key factors in the degeneration of articular cartilage and the associated pain and decrease in function. To combat this process, the use of biologics including umbilical cord-derived Wharton’s Jelly (UC-derived WJ) has grown. UC-derived WJ contains large quantities of regenerative factors, including growth factors (GFs), cytokines (CKs), hyaluronic acid (HA), and extracellular vesicles (EVs). The proposed study evaluates the safety and efficacy of intraarticular injection of UC-derived WJ for treatment of knee OA symptoms.

Methods and analysis
This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular UC-derived WJ in patients suffering from grade II/III OA will be assessed. Twelve patients with grade II/III OA who meet the inclusion and exclusion criteria will be recruited for this study which will be conducted at up to two sites within the USA. The participants will be followed for 1 s. Participants will be assessed using the Numeric Pain Rating Scale (NPRS), Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-item short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, satisfaction, function, and cartilage regeneration.

Discussion
This prospective study will contribute to the limited amount of data on UC-derived WJ, particularly with regard to its safety and efficacy. The outcomes from this study will also lay the groundwork for a large placebo-controlled trial of intraarticular UC-derived WJ for symptomatic knee OA.

Trial registration
ClinicalTrials.gov NCT04719793. Registered on 22 January 2021
The emerging role of KDM5A in human cancer
Authors: Yang Guan-Jun , Zhu Ming-Hui , Lu Xin-Jiang , Liu Yan-Jun , Lu Jian-Fei , Leung Chung-Hang , Ma Dik-Lung , Chen Jiong 
Published: February 2021

AbstractHistone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.
Efficacy of the erector spinae plane (ESP) block for quality of recovery in posterior thoraco-lumbar spinal decompression surgery: study protocol for a randomised controlled trial
Authors: Finnerty Dylan T. , Buggy Donal J. 
Published: February 2021

AbstractBackgroundSpinal surgery can be associated with significant postoperative pain. Erector spinae plane (ESP) block is a new regional anaesthesia technique, which promises effective postoperative analgesia compared with systemically administered opioids, but has never been evaluated in terms of patient-centred outcomes such as quality of recovery and overall morbidity after major thoraco-lumbar spinal surgery.MethodsWe are conducting a prospective, randomised, double-blind trial in two hospitals in the Republic of Ireland. The sample size will be 50 patients (25 in the intervention group and 25 in the control group). Randomisation will be done using computer-generated concealed envelopes. Both patients and investigators collecting outcome data will be masked to group allocation. Participants will be male or female, aged 18 years and over, capable of providing informed consent and ASA grade I–IV. Patients scheduled to undergo posterior approach thoraco-lumbar decompression surgery involving 2 or more levels will be recruited to the study. Participants randomised to the intervention arm of the study will receive bilateral ultrasound-guided ESP block totalling 40 ml 0.25% levo-bupivcaine (20 ml each side), post induction of general anaesthesia and before surgical incision. The control group will not receive an ESP block. Both groups will receive the same standardised analgesic protocol both intra- and postoperatively. The primary outcome will be the quality of recovery at 24 h postoperatively as determined by the QoR-15 score. This score is determined by a questionnaire which measures patient responses to 15 subjective parameters, each response graded on a scale from 0 to 10. The maximum score achievable is 150 with a potential minimum score of 0. Higher scores indicate a higher quality of recovery experience.Secondary outcomes will include area under the curve (AUC) of VRS pain versus time at rest and on movement up to 24 h postoperatively, 24 h opioid consumption, time to first analgesia in recovery, length of stay (LOS), incidence and severity of postoperative complications as measured by the Comprehensive Complication Index (CCI) score.DiscussionTo the best of our knowledge, this will be the first randomised control trial to examine the efficacy and safety of the ESP block in terms of patient-centred outcomes in the setting of major spinal surgery. The QoR-15 is a validated means of assessing the quality of recovery after surgery and gives a more holistic assessment of the recovery experience from the patient’s point of view.Trial registrationThis trial is pre-registered on ClinicalTrials.gov reference numberNCT04370951. Registered on 30 April 2020. All items from the World Health Organisation Trial Registration Data Set have been included.
Cross-species examination of X-chromosome inactivation highlights domains of escape from silencing
Authors: Balaton Bradley P. , Fornes Oriol , Wasserman Wyeth W. , Brown Carolyn J. 
Published: February 2021

Abstract
Background
X-chromosome inactivation (XCI) in eutherian mammals is the epigenetic inactivation of one of the two X chromosomes in XX females in order to compensate for dosage differences with XY males. Not all genes are inactivated, and the proportion escaping from inactivation varies between human and mouse (the two species that have been extensively studied).

Results
We used DNA methylation to predict the XCI status of X-linked genes with CpG islands across 12 different species: human, chimp, bonobo, gorilla, orangutan, mouse, cow, sheep, goat, pig, horse and dog. We determined the XCI status of 342 CpG islands on average per species, with most species having 80–90% of genes subject to XCI. Mouse was an outlier, with a higher proportion of genes subject to XCI than found in other species. Sixteen genes were found to have discordant X-chromosome inactivation statuses across multiple species, with five of these showing primate-specific escape from XCI. These discordant genes tended to cluster together within the X chromosome, along with genes with similar patterns of escape from XCI. CTCF-binding, ATAC-seq signal and LTR repeats were enriched at genes escaping XCI when compared to genes subject to XCI; however, enrichment was only observed in three or four of the species tested. LINE and DNA repeats showed enrichment around subject genes, but again not in a consistent subset of species.

Conclusions
In this study, we determined XCI status across 12 species, showing mouse to be an outlier with few genes that escape inactivation. Inactivation status is largely conserved across species. The clustering of genes that change XCI status across species implicates a domain-level control. In contrast, the relatively consistent, but not universal correlation of inactivation status with enrichment of repetitive elements or CTCF binding at promoters demonstrates gene-based influences on inactivation state. This study broadens enrichment analysis of regulatory elements to species beyond human and mouse.
Fermentation profiling of rice wine produced by Aspergillus oryzae KSS2 and Rhizopus oryzae KJJ39 newly isolated from Korean fermentation starter
Authors: Kim Minjoo , Seo Jeong-Ah 
Published: February 2021

AbstractThe objective of this study was to determine the fermentation characteristics of rice wine produced by koji inoculated with Aspergillus oryzae KSS2 and Rhizopus oryzae KJJ39 on moisturized wheat-bran and rice grain. We also compared rice wine samples produced in this study and three commercial Makgeolli. The alcohol content was about 12% higher in the rice wine samples fermented by wheat-bran koji than in the other samples. In all of the samples, the range of pH value was 3.8–4.6 and the total acid was below 0.5. The soluble solid content was highest in the rice wine sample prepared by the wheat-bran R. oryzae KJJ39 koji (15.5°Brix) and overall relatively higher in the samples with wheat-bran koji than rice koji. The content of reducing sugar was twofold higher in rice wine prepared by koji inoculated with R. oryzae KJJ39 than A. oryzae KSS2. The volatile acid content was higher in rice wine produced by the wheat-bran A. oryzae KSS2 koji than the others. In the analyses of five organic acids, A. oryzae KSS2 was found to produce more malic acid and fumaric acid while R. oryzae KJJ39 to do more citric acid, lactic acid and acetic acid. The rice wine sample prepared with the wheat-bran A. oryzae KSS2 koji contained much higher concentration of sucrose, maltose and amino acids. Comprehensively, the results of fermentation profiling suggest that both A. oryzae KSS2 and R. oryzae KJJ39 can be applied to the production of rice wine as a valuable fungal isolate for fermentation start.
Genomic evidence for sulfur intermediates as new biogeochemical hubs in a model aquatic microbial ecosystem
Authors: Vigneron Adrien , Cruaud Perrine , Culley Alexander I. , Couture Raoul-Marie , Lovejoy Connie , Vincent Warwick F. 
Published: February 2021

Abstract
Background
The sulfur cycle encompasses a series of complex aerobic and anaerobic transformations of S-containing molecules and plays a fundamental role in cellular and ecosystem-level processes, influencing biological carbon transfers and other biogeochemical cycles. Despite their importance, the microbial communities and metabolic pathways involved in these transformations remain poorly understood, especially for inorganic sulfur compounds of intermediate oxidation states (thiosulfate, tetrathionate, sulfite, polysulfides). Isolated and highly stratified, the extreme geochemical and environmental features of meromictic ice-capped Lake A, in the Canadian High Arctic, provided an ideal model ecosystem to resolve the distribution and metabolism of aquatic sulfur cycling microorganisms along redox and salinity gradients.

Results
Applying complementary molecular approaches, we identified sharply contrasting microbial communities and metabolic potentials among the markedly distinct water layers of Lake A, with similarities to diverse fresh, brackish and saline water microbiomes. Sulfur cycling genes were abundant at all depths and covaried with bacterial abundance. Genes for oxidative processes occurred in samples from the oxic freshwater layers, reductive reactions in the anoxic and sulfidic bottom waters and genes for both transformations at the chemocline. Up to 154 different genomic bins with potential for sulfur transformation were recovered, revealing a panoply of taxonomically diverse microorganisms with complex metabolic pathways for biogeochemical sulfur reactions. Genes for the utilization of sulfur cycle intermediates were widespread throughout the water column, co-occurring with sulfate reduction or sulfide oxidation pathways. The genomic bin composition suggested that in addition to chemical oxidation, these intermediate sulfur compounds were likely produced by the predominant sulfur chemo- and photo-oxidisers at the chemocline and by diverse microbial degraders of organic sulfur molecules.

Conclusions
The Lake A microbial ecosystem provided an ideal opportunity to identify new features of the biogeochemical sulfur cycle. Our detailed metagenomic analyses across the broad physico-chemical gradients of this permanently stratified lake extend the known diversity of microorganisms involved in sulfur transformations over a wide range of environmental conditions. The results indicate that sulfur cycle intermediates and organic sulfur molecules are major sources of electron donors and acceptors for aquatic and sedimentary microbial communities in association with the classical sulfur cycle.
Where did they not go? Considerations for generating pseudo-absences for telemetry-based habitat models
Authors: Hazen Elliott L. , Abrahms Briana , Brodie Stephanie , Carroll Gemma , Welch Heather , Bograd Steven J. 
Published: February 2021

AbstractBackgroundHabitat suitability models give insight into the ecological drivers of species distributions and are increasingly common in management and conservation planning. Telemetry data can be used in habitat models to describe where animals were present, however this requires the use of presence-only modeling approaches or the generation of ‘pseudo-absences’ to simulate locations where animals did not go. To highlight considerations for generating pseudo-absences for telemetry-based habitat models, we explored how different methods of pseudo-absence generation affect model performance across species’ movement strategies, model types, and environments.MethodsWe built habitat models for marine and terrestrial case studies, Northeast Pacific blue whales (Balaenoptera musculus) and African elephants (Loxodonta africana). We tested four pseudo-absence generation methods commonly used in telemetry-based habitat models: (1)backgroundsampling; (2) sampling within abufferzone around presence locations; (3)correlated random walksbeginning at the tag release location; (4)reverse correlated random walksbeginning at the last tag location. Habitat models were built using generalised linear mixed models, generalised additive mixed models, and boosted regression trees.ResultsWe found that the separation in environmental niche space between presences and pseudo-absences was the single most important driver of model explanatory power and predictive skill. This result was consistent across marine and terrestrial habitats, two species with vastly different movement syndromes, and three different model types. The best-performing pseudo-absence method depended on which created the greatest environmental separation: background sampling for blue whales and reverse correlated random walks for elephants. However, despite the fact that models with greater environmental separation performed better according to traditional predictive skill metrics, they did not always produce biologically realistic spatial predictions relative to known distributions.ConclusionsHabitat model performance may be positively biased in cases where pseudo-absences are sampled from environments that are dissimilar to presences. This emphasizes the need to carefully consider spatial extent of the sampling domain and environmental heterogeneity of pseudo-absence samples when developing habitat models, and highlights the importance of scrutinizing spatial predictions to ensure that habitat models are biologically realistic and fit for modeling objectives.
Alzheimer’s disease brain contains tau fractions with differential prion-like activities
Authors: Li Longfei , Shi Ruirui , Gu Jianlan , Tung Yunn Chyn , Zhou Yan , Zhou Dingwei , Wu Ruozhen , Chu Dandan , Jin Nana , Deng Kevin , Xu Jiawei , Gong Cheng-Xin , Iqbal Khalid , Liu Fei 
Published: February 2021

AbstractNeurofibrillary tangles (NFTs) made of abnormally hyperphosphorylated tau are a hallmark of Alzheimer’s disease (AD) and related tauopathies. Regional distribution of NFTs is associated with the progression of the disease and has been proposed to be a result of prion-like propagation of misfolded tau. Tau in AD brain is heterogenous and presents in various forms. In the present study, we prepared different tau fractions by sedimentation combined with sarkosyl solubility from AD brains and analyzed their biochemical and pathological properties. We found that tau in oligomeric fraction (O-tau), sarkosyl-insoluble fractions 1 and 2 (SI1-tau and SI2-tau) and monomeric heat-stable fraction (HS-tau) showed differences in truncation, hyperphosphorylation, and resistance to proteinase K. O-tau, SI1-tau, and SI2-tau, but not HS-tau, were hyperphosphorylated at multiple sites and contained SDS- and β-mercaptoethanol–resistant high molecular weight aggregates, which lacked the N-terminal portion of tau. O-tau and SI2-tau displayed more truncation and less hyperphosphorylation than SI1-tau. Resistance to proteinase K was increased from O-tau to SI1-tau to SI2-tau. O-tau and SI1-tau, but not SI2-tau or HS-tau, captured tau from cell lysates and seeded tau aggregation in cultured cells. Heat treatment could not kill the prion-like activity of O-tau to capture normal tau. Hippocampal injection of O-tau into 18-month-old FVB mice induced significant tau aggregation in both ipsilateral and contralateral hippocampi, but SI1-tau only induced tau pathology in the ipsilateral hippocampus, and SI2-tau and HS-tau failed to induce any detectable tau aggregation. These findings suggest that O-tau and SI1-tau have prion-like activities and may serve as seeds to recruit tau and template tau to aggregate, resulting in the propagation of tau pathology. Heterogeneity of tau pathology within AD brain results in different fractions with different biological and prion-like properties, which may pose a major challenge in targeting tau for development of effective therapeutic treatments.
Determinants of stillbirths among women who gave birth at Hawassa university comprehensive specialized hospital, Hawassa, Sidama, Ethiopia 2019: a case-control study
Authors: Fikre Rekiku , Ejeta Samuel , Gari Taye , Alemayhu Akalewold 
Published: February 2021

Abstract
Background
Globally over 2.6 million pregnancy ends with stillbirth annually. Despite this fact, only a few sherds of evidence were available about factors associated with stillbirth in Ethiopia. Therefore, the study aimed to spot factors related to stillbirth among women who gave birth at Hawassa University Comprehensive Specialized Hospital Hawassa, Sidama Ethiopia, 2019.

Methods
Facility-based unmatched case-control study was conducted at Hawassa University Comprehensive Specialized Hospital. Cases were selected using simple random sampling technique and controls were recruited to the study consecutively after every case selection with case to control ratio of 1 to 3. Data were coded and entered into Epi-data version 3.1 and exported to SPSS version 24 for analysis.

Results
A total of 106 cases and 318 controls were included in the study. Number of antenatal care visit [AOR = 0.38, 95% CI (0.15, 0.95)], lack of partograph utilization [AOR = 4.1 95% CI (2.04, 10.5)], prolonged labor [AOR = 6.5, 95% CI (2.9, 14.4)], obstructed labor [AOR = 3.5, 95% CI (1.5, 9.4)], and congenital defect [AOR = 9.7, 95% CI (4.08, 23.0)] were significantly associated with stillbirth.

Conclusion
Absence of partograph utilization, prolonged labor, obstructed labor, antepartum hemorrhage and congenital anomaly were found to have positive association with stillbirth.
Development and analysis of long non-coding RNA-associated competing endogenous RNA network for osteosarcoma metastasis
Authors: Fu Yucheng , Liu Qi , Bao Qiyuan , Wen Junxiang , Liu Zhuochao , Hu Yuehao , He Guoyu , Peng Cheng , Xu Yiqi , Zhang Weibin 
Published: February 2021

Abstract
Background
Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs’ roles in osteosarcoma metastasis are still unknown.

Methods
Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves.

Results
Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients’ prognosis.

Conclusions
The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.
The influence of teacher annotations on student learning engagement and video watching behaviors
Authors: Tseng Sheng-Shiang 
Published: February 2021

AbstractWhile course videos are powerful teaching resources in online courses, students often have difficulty sustaining their attention while watching videos and comprehending the content. This study adopted teacher annotations on videos as an instructional support to engage students in watching course videos. Forty-two students in an undergraduate course at a university in Taiwan were randomly divided into a control group that watched a course video without teacher annotations, and an experimental group that watched a course video with teacher annotations. The collected data included a learning engagement survey, students’ video watching behaviors, and student interviews. The results showed that there were differences in student learning engagement between the control and experimental groups. The teacher annotations increased students’ behavioral and cognitive engagement in watching the video but did not increase their emotional engagement. In addition, this study identified how students learned when watching the course video with the teacher annotations through highlights of the video content, literal questions, reflective questions and inferential questions. The results concluded that teacher annotations and student learning engagement were positively correlated. The students acknowledged that their retention and comprehension of the video content increased with the support of the teacher annotations.