bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeepGRP: engineering a software tool for predicting genomic repetitive elements using Recurrent Neural Networks with attention
Authors: Hausmann Fabian , Kurtz Stefan 
Published: August 2021

Abstract
Background
Repetitive elements contribute a large part of eukaryotic genomes. For example, about 40 to 50% of human, mouse and rat genomes are repetitive. So identifying and classifying repeats is an important step in genome annotation. This annotation step is traditionally performed using alignment based methods, either in a de novo approach or by aligning the genome sequence to a species specific set of repetitive sequences. Recently, Li (Bioinformatics 35:4408–4410, 2019) developed a novel software tool to annotate repetitive sequences using a recurrent neural network trained on sample annotations of repetitive elements.

Results
We have developed the methods of further and engineered a new software tool . This combines the basic concepts of Li (Bioinformatics 35:4408–4410, 2019) with current techniques developed for neural machine translation, the attention mechanism, for the task of nucleotide-level annotation of repetitive elements. An evaluation on the human genome shows a 20% improvement of the Matthews correlation coefficient for the predictions delivered by , when compared to . predicts two additional classes of repeats (compared to ) and is able to transfer repeat annotations, using RepeatMasker-based training data to a different species (mouse). Additionally, we could show that predicts repeats annotated in the Dfam database, but not annotated by RepeatMasker. is highly scalable due to its implementation in the TensorFlow framework. For example, the GPU-accelerated version of is approx. 1.8 times faster than , approx. 8.6 times faster than RepeatMasker and over 100 times faster than HMMER searching for models of the Dfam database.

Conclusions
By incorporating methods from neural machine translation, achieves a consistent improvement of the quality of the predictions compared to . Improved running times are obtained by employing TensorFlow as implementation framework and the use of GPUs. By incorporating two additional classes of repeats, provides more complete annotations, which were evaluated against three state-of-the-art tools for repeat annotation.
Protective role of the alpha-1-antitrypsin in intervertebral disc degeneration
Authors: Liu Weikun , Wang Yanfu 
Published: August 2021

Abstract
Background
Intervertebral disc degeneration is a complex disease with high prevalence. It suggests that cell death, senescence, and extracellular matrix degradation are involved in the pathogenesis. Alpha-1 antitrypsin (AAT), a serine protease inhibitor, was previously correlated with inflammation-related diseases. However, its function on intervertebral disc degeneration remains unclear.

Methods
A latex-enhanced immunoturbidimetric assay measured the serum level of AAT. Real-time polymerase chain reaction (RT-qPCR) and western blot were used to testify the expression of RNA and proteins related to cell apoptosis and the Wnt/β-catenin pathway. The animal model for intervertebral disc degeneration was built by disc puncture. The degeneration grades were analyzed by safranin o staining.

Results
We showed that alpha-1 antitrypsin could ameliorate intervertebral disc degeneration in vitro and in vivo. We also found that the serum alpha-1 antitrypsin level in Intervertebral disc degeneration patients is negative related to the severity of intervertebral disc degeneration. Moreover, alpha-1 antitrypsin was also showed to suppress tumor necrosis factor-alpha (TNF-α) induced WNT/β-catenin signaling pathway activation in human nucleus pulposus cells.

Conclusions
Our study provides evidence for AAT to serve as a potential therapeutic reagent for the treatment of intervertebral disc degeneration.
Case–control study on the interplay between immunoparalysis and delirium after cardiac surgery
Authors: CheheiliSobbi Shokoufeh , Peters van Ton Annemieke M. , Wesselink Esther M. , Looije Marjolein F. , Gerretsen Jelle , Morshuis Wim J. , Slooter Arjen J. C. , Abdo Wilson F. , Pickkers Peter , van den Boogaard Mark 
Published: August 2021

Abstract
Background
Delirium occurs frequently following cardiothoracic surgery, and infectious disease is an important risk factor for delirium. Surgery and cardiopulmonary bypass induce suppression of the immune response known as immunoparalysis. We aimed to investigate whether delirious patients had more pronounced immunoparalysis following cardiothoracic surgery than patients without delirium, to explain this delirium-infection association.

Methods
A prospective matched case–control study was performed in two university hospitals. Cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and IL-10) of ex vivo lipopolysaccharide (LPS)-stimulated whole blood was analyzed in on-pump cardiothoracic surgery patients preoperatively, and at 5 timepoints up to 3 days after cardiothoracic surgery. Delirium was assessed by trained staff using two validated delirium scales and chart review.

Results
A total of 89 patients were screened of whom 14 delirious and 52 non-delirious patients were included. Ex vivo-stimulated production of TNF-α, IL-6, IL-8, and IL-10 was severely suppressed following cardiothoracic surgery compared to pre-surgery. Postoperative release of cytokines in non-delirious patients was attenuated by 84% [IQR: 13–93] for TNF-α, 95% [IQR: 78–98] for IL-6, and 69% [IQR: 55–81] for IL-10. The attenuation in ex vivo-stimulated production of these cytokines was not significantly different in patients with delirium compared to non-delirious patients (p > 0.10 for all cytokines).

Conclusions
The post-operative attenuation of ex vivo-stimulated production of pro- and anti-inflammatory cytokines was comparable between patients that developed delirium and those who remained delirium-free after on-pump cardiothoracic surgery. This finding suggests that immunoparalysis is not more common in cardiothoracic surgery patients with delirium compared to those without.
Utilization of traditional Chinese medicine in the intensive care unit
Authors: Zhang Xia , Wang Mingqi , Wang Wen , Li Ling , Sun Xin 
Published: August 2021

AbstractPrevious studies showed that traditional Chinese medicine (TCM) may be effective for patients with critical conditions. However, the extent to which TCM is used in intensive care units (ICUs) remains less investigated. This study aimed to investigate the utilization of TCM among ICU patients. Using a cross-sectional study design, we examined the use of TCMs among ICU patients. The data were from a well-established ICU registry from a large teaching hospital in west China. Our study found that TCM was widely used among ICU, in particular TCM injections and oral liquids. The use of TCM often differed by ICUs, and TCM injections and oral liquids were mostly used in neurological ICU, while Chinese herbal medicines (CHMs) were often used in general ICU. The use of TCM was also highly associated with patient characteristics. Patients with pancreatitis were administered with most TCM, patients with cerebrovascular disease with most TCM injections and those with chronic renal failure with most oral liquids. Future efforts should include generation of high-quality evidence guidelines about clinical effects of TCM interventions among ICU patients.
Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer
Authors: Drusbosky Leylah M. , Dawar Richa , Rodriguez Estelamari , Ikpeazu Chukwuemeka V. 
Published: August 2021

AbstractMETex14 skipping mutations occur in about 3–4% of lung adenocarcinoma patients and 1–2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14 in the MET gene leads to dysregulation and inappropriate signaling that is associated with increased responsiveness to MET TKIs. Results from GEOMETRY mono-1 and VISION Phase I/II clinical trials demonstrated significant clinical activity in patients treated with the MET Exon 14 skipping mutation inhibitors capmatinib and tepotinib with tolerable toxicity profile. In the GEOMETRY mono-1 trial, capmatinib was especially active in treatment-naïve patients supporting the upfront testing of this oncogenic driver. Tepotinib demonstrated superior activity in the pretreated patients in the VISION trial. Savolitinib is another MET TKI that has shown efficacy in the first- and second-line settings, including patients with aggressive pulmonary sarcomatoid carcinoma. These studies have demonstrated that these TKIs can cross the blood brain barrier and demonstrated some activity toward CNS metastases. MET Exon 14 skipping mutation is detected by NGS-based testing of liquid or tissue biopsies, with preference for RNA-based NGS. The activity of capmatinib and tepotinib is limited by the development of acquired resistance. Current research is focused on strategies to overcome resistance and improve the effectiveness of these agents. Our aim is to review the current status of MET Exon 14 skipping mutation as it pertains NSCLC.
Epigenetic age is associated with baseline and 3-year change in frailty in the Canadian Longitudinal Study on Aging
Authors: Verschoor Chris P. , Lin David T. S. , Kobor Michael S. , Mian Oxana , Ma Jinhui , Pare Guillaume , Ybazeta Gustavo 
Published: August 2021

Abstract
Background
The trajectory of frailty in older adults is important to public health; therefore, markers that may help predict this and other important outcomes could be beneficial. Epigenetic clocks have been developed and are associated with various health-related outcomes and sociodemographic factors, but associations with frailty are poorly described. Further, it is uncertain whether newer generations of epigenetic clocks, trained on variables other than chronological age, would be more strongly associated with frailty than earlier developed clocks. Using data from the Canadian Longitudinal Study on Aging (CLSA), we tested the hypothesis that clocks trained on phenotypic markers of health or mortality (i.e., Dunedin PoAm, GrimAge, PhenoAge and Zhang in Nat Commun 8:14617, 2017) would best predict changes in a 76-item frailty index (FI) over a 3-year interval, as compared to clocks trained on chronological age (i.e., Hannum in Mol Cell 49:359–367, 2013, Horvath in Genome Biol 14:R115, 2013, Lin in Aging 8:394–401, 2016, and Yang Genome Biol 17:205, 2016).

Results
We show that in 1446 participants, phenotype/mortality-trained clocks outperformed age-trained clocks with regard to the association with baseline frailty (mean = 0.141, SD = 0.075), the greatest of which is GrimAge, where a 1-SD increase in ΔGrimAge (i.e., the difference from chronological age) was associated with a 0.020 increase in frailty (95% CI 0.016, 0.024), or ~ 27% relative to the SD in frailty. Only GrimAge and Hannum (Mol Cell 49:359–367, 2013) were significantly associated with change in frailty over time, where a 1-SD increase in ΔGrimAge and ΔHannum 2013 was associated with a 0.0030 (95% CI 0.0007, 0.0050) and 0.0028 (95% CI 0.0007, 0.0050) increase over 3 years, respectively, or ~ 7% relative to the SD in frailty change.

Conclusion
Both prevalence and change in frailty are associated with increased epigenetic age. However, not all clocks are equally sensitive to these outcomes and depend on their underlying relationship with chronological age, healthspan and lifespan. Certain clocks were significantly associated with relatively short-term changes in frailty, thereby supporting their utility in initiatives and interventions to promote healthy aging.
Prediction of vaccine hesitancy based on social media traffic among Israeli parents using machine learning strategies
Authors: Bar-Lev Shirly , Reichman Shahar , Barnett-Itzhaki Zohar 
Published: August 2021

Abstract
Introduction
Vaccines have contributed to substantial reductions of morbidity and mortality from vaccine-preventable diseases, mainly in children. However, vaccine hesitancy was listed by the World Health Organization (WHO) in 2019 as one of the top ten threats to world health.

Aim
To employ machine-learning strategies to assess how on-line content regarding vaccination affects vaccine hesitancy.

Methods
We collected social media posts and responses from vaccination discussion groups and forums on leading social platforms, including Facebook and Tapuz (A user content website that contains blogs and forums). We investigated 65,603 records of children aged 0–6 years who are insured in Maccabi’s Health Maintenance Organization (HMO). We applied three machine learning algorithms (Logistic regression, Random forest and Neural networks) to predict vaccination among Israeli children, based on demographic and social media traffic.

Results
Higher hesitancy was associated with more social media traffic, for most of the vaccinations. The addition of the social media traffic features improved the performances of most of the models.
However, for Rota virus, Hepatitis A and hepatitis B, the performances of all algorithms (with and without the social media features) were close to random (accuracy up to 0.63 and F1 up to 0.65). We found a negative association between on-line discussions and vaccination.

Conclusions
There is an association between social media traffic and vaccine hesitancy. Policy makers are encouraged to perceive social media as a main channel of communication during health crises. Health officials and experts are encouraged to take part in social media discussions, and be equipped to readily provide the information, support and advice that the public is looking for, in order to optimize vaccination actions and to improve public health
Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease
Authors: Chevalier Grégoire , Laveissière Arnaud , Desachy Guillaume , Barnich Nicolas , Sivignon Adeline , Maresca Marc , Nicoletti Cendrine , Di Pasquale Eric , Martinez-Medina Margarita , Simpson Kenneth William , Yajnik Vijay , Sokol Harry ,   MOBIDIC Study Investigators, Adegbamigbe Temitayo , Ahmad Tariq , Arnott Ian , Bouhnik Yoram , Carbonnel Franck , Colombel Jean-Frédéric , Doherty Glen , Cummings J. R. Fraser , Hébuterne Xavier , Herfarth Hans , Kevans David , de Chambrun Guillaume Pineton , Nachury Maria , Nancey Stéphane , Roblin Xavier , Tremelling Mark A. W. , Plassais Jonathan , Strozzi Francesco , Cervino Alessandra , Morra Rachel , Bonny Christophe 
Published: August 2021

Abstract
Background
An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn’s Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD. Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS. Therefore, targeting the bacterial adhesion of FimH-expressing bacteria seems a promising therapeutic approach, consisting of disarming bacteria without killing them, representing a selective strategy to suppress a potentially critical trigger of intestinal inflammation, without disturbing the intestinal microbiota.

Results
We analyzed the metagenomic composition of the gut microbiome of 358 patients with CD from two different cohorts and characterized the presence of FimH-expressing bacteria. To assess the pathogenic role of FimH, we used human intestinal explants and tested a specific FimH blocker to prevent bacterial adhesion and associated inflammation. We observed a significant and disease activity-dependent enrichment of Enterobacteriaceae in the gut microbiome of patients with CD. Bacterial FimH expression was functionally confirmed in ileal biopsies from 65% of the patients with CD. Using human intestinal explants, we further show that FimH is essential for adhesion and to trigger inflammation. Finally, a specific FimH-blocker, TAK-018, inhibits bacterial adhesion to the intestinal epithelium and prevents inflammation, thus preserving mucosal integrity.

Conclusions
We propose that TAK-018, which is safe and well tolerated in humans, is a promising candidate for the treatment of CD and in particular in preventing its recurrence.
Circulating MicroRNAs predict glycemic improvement and response to a behavioral intervention
Authors: Flowers Elena , Allen Isabel Elaine , Kanaya Alka M. , Aouizerat Bradley E. 
Published: August 2021

Abstract
Background
MicroRNAs may be important regulators of risk for type 2 diabetes. The purpose of this longitudinal observational study was to assess whether circulating microRNAs predicted improvements in fasting blood glucose, a major risk factor for type 2 diabetes, over 12 months.

Methods
The study included participants (n = 82) from a previously completed trial that tested the effect of restorative yoga on individuals with prediabetes. Circulating microRNAs were measured using a flow cytometry miRNA assay. Linear models were used to determine the optimal sets of microRNA predictors overall and by intervention group.

Results
Subsets of microRNAs were significant predictors of final fasting blood glucose after 12-months (R2 = 0.754, p < 0.001) and changes in fasting blood glucose over 12-months (R2 = 0.731, p < 0.001). Three microRNAs (let-7c, miR-363, miR-374b) were significant for the control group only, however there was no significant interaction by intervention group.

Conclusions
Circulating microRNAs are significant predictors of fasting blood glucose in individuals with prediabetes. Among the identified microRNAs, several have previously been associated with risk for type 2 diabetes. This is one of the first studies to use a longitudinal design to assess whether microRNAs predict changes in fasting blood glucose over time. Further exploration of the function of the microRNAs included in these models may provide new insights about the complex etiology of type 2 diabetes and responses to behavioral risk reduction interventions.

Trial registration
This study was a secondary analysis of a previously completed clinical trial that is registered at clinicaltrials.gov (NCT01024816) on December 3, 2009.
Pectinolytic lyases: a comprehensive review of sources, category, property, structure, and catalytic mechanism of pectate lyases and pectin lyases
Authors: Zheng Ling , Xu Yinxiao , Li Qian , Zhu Benwei 
Published: August 2021

AbstractPectate lyases and pectin lyases have essential roles in various biotechnological applications, such as textile industry, paper making, pectic wastewater pretreatment, juice clarification and oil extraction. They can effectively cleave the α-1,4-glycosidic bond of pectin molecules back bone by β-elimination reaction to produce pectin oligosaccharides. In this way, it will not generate highly toxic methanol and has the advantages of good enzymatic selectivity, less by-products, mild reaction conditions and high efficiency. However, numerous researches have been done for several decades; there are still no comprehensive reviews to summarize the recent advances of pectate lyases and pectin lyases. This review tries to fill this gap by providing all relevant information, including the substrate, origin, biochemical properties, sequence analysis, mode of action, the three-dimensional structure and catalytic mechanism.
Spectrum of common Hodgkin lymphoma and non-Hodgkin lymphomas subtypes in Zambia: a 3-year records review
Authors: Polepole Pascal , Mudenda Victor C. , Munsaka Sody M. , Zhang Luwen 
Published: August 2021

Abstract
Background
Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored.

Objectives
To study the spectrum of lymphoma subtypes prevalent within the Zambian population.

Methods
Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher’s exact test was used for significance testing.

Results
During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin’s lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin’s lymphoma (CHL) was seen in 39 (16.3%). Burkitt’s lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002).

Conclusion
Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.
RNA sequencing analyses in infants patients with coarctation of the aorta
Authors: Liu Aijun , Li Bin , Yang Ming , Gu Yan , Qi Lihua , Su Junwu 
Published: August 2021

Abstract
Background
Coarctation of the aorta (CoA) is a serious innate heart disease. Although surgery results are generally good, some complications such as recoarctation and aortic aneurysm or persistent hypertension were serious threats to patient’s health. To better understand the pathology of CoA and its underlying molecular mechanism is particularly important for early diagnosis and preventing the occurrence of its complications. However, the mechanisms of CoA remain unclear, especially for infants.

Methods
RNA sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs) in vascular tissues of 12 patients with CoA and 10 normal participants form 3- to 34-month-old infants. The characteristic of DEGs were validated by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC) in vessels of patients with CoA and normal infants.

Results
A total of 2491 DEGs with the false discovery rate less than 0.05(> 1.5-fold, P < 0.05 change) were identified, including 443 upregulated genes and 2048 downregulated genes. The Gene Ontology enrichment analysis showed that 26 out of the 2491 DEGs identified were associated with cardiovascular diseases. These 26 genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs) differentiation. Three DEGs, that is, CNN1 (calponin), α-actinin1 and myosin heavy chain 11 MYH11, were validated using qRT-PCR and Western blot analysis. In addition, immunochemical staining showed that calponin and MYH11 were highly expressed on the surface and in the deep layers of the thickened intima respectively.

Conclusion
This study comprehensively characterized the CoA transcriptome. Migration of extracellular matrix (ECM) and smooth muscle cells (SMCs) to the subendothelial space may be the major characteristic of CoA in infants.