bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDSnake: Snakemake pipeline for retrieval of annotated OTUs from paired-end reads using CD-HIT utilities
Authors: Kondratenko Yulia , Korobeynikov Anton , Lapidus Alla 
Published: July 2020

Abstract
Background
Illumina paired-end reads are often used for 16S analysis in metagenomic studies. Since DNA fragment size is usually smaller than the sum of lengths of paired reads, reads can be merged for downstream analysis. In spite of development of several tools for merging of paired-end reads, poor quality at the 3′ ends within the overlapping region prevents the accurate combining of significant portion of read pairs. Recently CD-HIT-OTU-Miseq was presented as a new approach for 16S analysis using the paired-end reads, it completely avoids the reads merging process due to separate clustering of paired reads. CD-HIT-OTU-Miseq is a set of tools which are supposed to be successively launched by auxiliary shell scripts. This launch mode is not suitable for processing of big amounts of data generated in modern omics experiments. To solve this issue we created CDSnake – Snakemake pipeline utilizing CD-HIT tools for easier consecutive launch of CD-HIT-OTU-Miseq tools for complete processing of paired end reads in metagenomic studies. Usage of pipeline make 16S analysis easier due to one-command launch and helps to yield reproducible results.

Results
We benchmarked our pipeline against two commonly used pipelines for OTU retrieval, incorporated into popular workflow for microbiome analysis, QIIME2 - DADA2 and deblur. Three mock datasets having highly overlapping paired-end 2 × 250 bp reads were used for benchmarking - Balanced, HMP, and Extreme. CDSnake outputted less OTUs than DADA2 and deblur. However, on Balanced and HMP datasets number of OTUs outputted by CDSnake was closer to real number of strains which were used for mock community generation, than those outputted by DADA2 and deblur. Though generally slower than other pipelines, CDSnake outputted higher total counts, preserving more information from raw data. Inheriting this properties from original CD-HIT-OTU-MiSeq utilities, CDSnake made their usage handier due to simple scalability, easier automated runs and other Snakemake benefits.

Conclusions
We developed Snakemake pipeline for OTU-MiSeq utilities, which simplified and automated data analysis. Benchmarking showed that this approach is capable to outperform popular tools in certain conditions.
Extending rnaSPAdes functionality for hybrid transcriptome assembly
Authors: Prjibelski Andrey D. , Puglia Giuseppe D. , Antipov Dmitry , Bushmanova Elena , Giordano Daniela , Mikheenko Alla , Vitale Domenico , Lapidus Alla 
Published: July 2020

Abstract
Background
De novo RNA-Seq assembly is a powerful method for analysing transcriptomes when the reference genome is not available or poorly annotated. However, due to the short length of Illumina reads it is usually impossible to reconstruct complete sequences of complex genes and alternative isoforms. Recently emerged possibility to generate long RNA reads, such as PacBio and Oxford Nanopores, may dramatically improve the assembly quality, and thus the consecutive analysis. While reference-based tools for analysing long RNA reads were recently developed, there is no established pipeline for de novo assembly of such data.

Results
In this work we present a novel method that allows to perform high-quality de novo transcriptome assemblies by combining accuracy and reliability of short reads with exon structure information carried out from long error-prone reads. The algorithm is designed by incorporating existing hybridSPAdes approach into rnaSPAdes pipeline and adapting it for transcriptomic data.

Conclusion
To evaluate the benefit of using long RNA reads we selected several datasets containing both Illumina and Iso-seq or Oxford Nanopore Technologies (ONT) reads. Using an existing quality assessment software, we show that hybrid assemblies performed with rnaSPAdes contain more full-length genes and alternative isoforms comparing to the case when only short-read data is used.
An integrative network-driven pipeline for systematic identification of lncRNA-associated regulatory network motifs in metastatic melanoma
Authors: Singh Nivedita , Eberhardt Martin , Wolkenhauer Olaf , Vera Julio , Gupta Shailendra K. 
Published: July 2020

Abstract
Background
Melanoma phenotype and the dynamics underlying its progression are determined by a complex interplay between different types of regulatory molecules. In particular, transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) interact in layers that coalesce into large molecular interaction networks. Our goal here is to study molecules associated with the cross-talk between various network layers, and their impact on tumor progression.

Results
To elucidate their contribution to disease, we developed an integrative computational pipeline to construct and analyze a melanoma network focusing on lncRNAs, their miRNA and protein targets, miRNA target genes, and TFs regulating miRNAs. In the network, we identified three-node regulatory loops each composed of lncRNA, miRNA, and TF. To prioritize these motifs for their role in melanoma progression, we integrated patient-derived RNAseq dataset from TCGA (SKCM) melanoma cohort, using a weighted multi-objective function. We investigated the expression profile of the top-ranked motifs and used them to classify patients into metastatic and non-metastatic phenotypes.

Conclusions
The results of this study showed that network motif UCA1/AKT1/hsa-miR-125b-1 has the highest prediction accuracy (ACC = 0.88) for discriminating metastatic and non-metastatic melanoma phenotypes. The observation is also confirmed by the progression-free survival analysis where the patient group characterized by the metastatic-type expression profile of the motif suffers a significant reduction in survival. The finding suggests a prognostic value of network motifs for the classification and treatment of melanoma.
Exogenous 2-(3,4-Dichlorophenoxy) triethylamine alleviates salinity stress in maize by enhancing photosynthetic capacity, improving water status and maintaining K+/Na+ homeostasis
Authors: Li Lijie , Gu Wanrong , Zhang Liguo , Li Congfeng , Chen Xichang , Qian Chunrong , Wang Zhenhua , Li Wenhua , Zuo Shiyu , Wei Shi 
Published: July 2020

Abstract
Background
Soil salinity restricts plant growth and productivity. 2-(3,4-dichlorophenoxy) triethylamine (DCPTA) can alleviate salinity stress in plants. However, the mechanism of DCPTA-mediated salinity tolerance has not been fully clarified. We aimed to investigate its role in enhancing photosynthetic capacity, improving water status, maintaining K+/Na+ homeostasis and alleviating salinity stress in maize (Zea mays L.).

Results
In present study, maize seedlings were grown in nutrient solutions with a combination of NaCl (0, 150 mM) and DCPTA (0, 20, 100, and 400 μM). And photosynthesis, water status, ion homeostasis and the expression of genes involved in ion uptake and transport were evaluated in the maize seedlings. The results demonstrated that DCPTA alleviated the growth inhibition of maize seedlings exposed to salinity stress by increasing the net photosynthetic rate (Pn) and the quantum efficiency of photosystem II (PSII) photochemistry. DCPTA improved the root hydraulic conductivity, which help maintained the water status. A relatively high K+ concentration but a relatively low Na+ concentration and the Na+/K+ ratio were observed in the presence of DCPTA under salinity stress. Additionally, DCPTA altered the expression of four genes (ZmSOS1, ZmHKT1, ZmNHX1 and ZmSKOR) that encode membrane transport proteins responsible for K+/Na+ homeostasis.

Conclusions
DCPTA improved the salinity tolerance of maize may be associated with enhanced photosynthetic capacity, maintenance of water status and altered expression of genes involved in ion uptake and transport.
Integrated metabolomic and transcriptomic analysis of the anthocyanin regulatory networks in Salvia miltiorrhiza Bge. flowers
Authors: Jiang Tao , Zhang Meidi , Wen Chunxiu , Xie Xiaoliang , Tian Wei , Wen Saiqun , Lu Ruike , Liu Lingdi 
Published: July 2020

Abstract
Background
The objectives of this study were to reveal the anthocyanin biosynthesis metabolic pathway in white and purple flowers of Salvia miltiorrhiza using metabolomics and transcriptomics, to identify different anthocyanin metabolites, and to analyze the differentially expressed genes involved in anthocyanin biosynthesis.

Results
We analyzed the metabolomics and transcriptomics data of S. miltiorrhiza flowers. A total of 1994 differentially expressed genes and 84 flavonoid metabolites were identified between the white and purple flowers of S. miltiorrhiza. Integrated analysis of transcriptomics and metabolomics showed that cyanidin 3,5-O-diglucoside, malvidin 3,5-diglucoside, and cyanidin 3-O-galactoside were mainly responsible for the purple flower color of S. miltiorrhiza. A total of 100 unigenes encoding 10 enzymes were identified as candidate genes involved in anthocyanin biosynthesis in S. miltiorrhiza flowers. Low expression of the ANS gene decreased the anthocyanin content but enhanced the accumulation of flavonoids in S. miltiorrhiza flowers.

Conclusions
Our results provide valuable information on the anthocyanin metabolites and the candidate genes involved in the anthocyanin biosynthesis pathways in S. miltiorrhiza.
Misdiagnosis of peripheral abscess caused by duodenal foreign body: a case report and literature review
Authors: Wang Zhihui , Du Zhiqiang , Zhou Xiangrong , Chen Tianming , Li Chunyan 
Published: July 2020

Abstract
Background
The induction of chronic inflammation, perforation, and abscess by foreign bodies (FBs) in adults is uncommon. We present a delayed diagnosis case for a patient who had a fishbone stuck in the duodenal bulb, resulting in chronic abdominal pain for nearly 3 months. We present the diagnosis and treatment procedures for chronic patients, which differ from those for acute and emergency FB ingestion, and also summarize the characteristics of such patients through a systematic literature review.

Case presentation
A 68-year-old woman was brought to our hospital with repeated right upper abdominal pain lasting for 3 months and aggravation for 9 h. Computed tomography (CT) showed a streaky high-density shadow (approximately 3 cm in length) on the posterior wall of the gastric antrum extending outside the wall. Endoscopic ultrasonography showed hyperechoic space with a cross-section of approximately 0.1 × 0.1 cm in the deep submucosal layer of the local stomach, accompanied by an acoustic shadow in the rear. The possibility of a fishbone as well as perforation was considered and the object was removed using FB forceps. Fasting as well as acid inhibition and anti-infection medication were prescribed for the patient. She eventually recovered and was discharged from the hospital.

Conclusion
Endoscopic intervention can be recommended as the first option for patients with gastrointestinal FBs.
Noninfectious mixed cryoglobulinaemic glomerulonephritis and monoclonal gammopathy of undetermined significance: a coincidental association?
Authors: Flavell Adam L. , Fullinfaw Robert O. , Smith Edward R. , Holt Stephen G. , Finlay Moira J. , Barbour Thomas D. 
Published: July 2020

AbstractBackgroundCryoglobulins are cold-precipitable immunoglobulins that may cause systemic vasculitis including cryoglobulinaemic glomerulonephritis (CGN). Type 1 cryoglobulins consist of isolated monoclonal immunoglobulin (mIg), whereas mixed cryoglobulins are typically immune complexes comprising either monoclonal (type 2) or polyclonal (type 3) Ig with rheumatoid activity against polyclonal IgG. Only CGN related to type 1 cryoglobulins has been clearly associated with monoclonal gammopathy of undetermined significance (MGUS) using the conventional serum-, urine- or tissue-based methods of paraprotein detection.Case presentationWe present four patients with noninfectious mixed (type 2 or 3) CGN and MGUS. Two patients had type 2 cryoglobulinaemia, one had type 3 cryoglobulinaemia, and one lacked definitive typing of the serum cryoprecipitate. The serum monoclonal band was IgM-κ in all four cases. Treatments included corticosteroids, cyclophosphamide, plasma exchange, and rituximab. At median 3.5 years’ follow-up, no patient had developed a haematological malignancy or advanced chronic kidney disease. Other potential causes of mixed cryoglobulinaemia were also present in our cohort, notably primary Sjögren’s syndrome in three cases.ConclusionOur study raises questions regarding the current designation of type 2 CGN as a monoclonal gammopathy of renal significance, and the role of clonally directed therapies for noninfectious mixed CGN outside the setting of haematological malignancy.
An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report
Authors: Galante J. R. , Daruwalla C. P. , Roberts I. S. D. , Haynes R. , Storey B. C. , Bottomley M. J. 
Published: July 2020

Abstract
Background
A number of disease processes can culminate in rapidly progressive glomerulonephritis, including pauci-immune focal segmental necrotising glomerulonephritis, usually seen with positive serum antineutrophil cytoplasmic antibodies (ANCA). Propylthiouracil (PTU) has been associated with drug-induced ANCA-associated vasculitis (AAV), with antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) present individually and together having been recognised. ‘Double-positive’ vasculitis with ANCA and anti-glomerular basement membrane (GBM) antibodies has also been reported in association with PTU treatment. We present a case of PTU-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate.

Case presentation
A 51-year-old man presented 2 weeks after re-commencing propylthiouracil (PTU) treatment for Graves’ disease, with a severe acute kidney injury and haemato-proteinuria. He demonstrated positive titres for autoantibodies to PR3 (76.9 IU/mL), MPO (28.8 IU/mL) and GBM (94 IU/mL). Renal biopsy demonstrated numerous glomerular crescents, widespread IgG4-positive lymphoplasmacytic infiltrate and mesangial positivity for IgA. PTU was stopped and he was treated with steroids, plasma exchange and cyclophosphamide with sustained improvement in his renal function.

Conclusions
This case of drug-induced AAV presented a unique and intriguing collection of serological and histological features. We propose that the PTU-induced AAV resulted in epiphenomena of anti-GBM antibody production and an IgG4-cell-rich tubulointerstitial infiltrate. It is uncertain whether the mesangial IgA deposition preceded or resulted from the AAV.
A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway
Authors: Al-Khayal Khayal , Vaali-Mohammed Mansoor-Ali , Elwatidy Mohammed , Bin Traiki Thamer , Al-Obeed Omar , Azam Mohammad , Khan Zahid , Abdulla Maha , Ahmad Rehan 
Published: July 2020

Abstract
Background
Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer.

Methods
Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/− 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA.

Results
In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells.

Conclusion
Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.
Protocol of the QUATTRO-II study: a multicenter randomized phase II study comparing CAPOXIRI plus bevacizumab with FOLFOXIRI plus bevacizumab as a first-line treatment in patients with metastatic colorectal cancer
Authors: Miyo Masaaki , Kato Takeshi , Yoshino Takayuki , Yamanaka Takeharu , Bando Hideaki , Satake Hironaga , Yamazaki Kentaro , Taniguchi Hiroya , Oki Eiji , Kotaka Masahito , Oba Koji , Miyata Yoshinori , Muro Kei , Komatsu Yoshito , Baba Hideo , Tsuji Akihito 
Published: July 2020

Abstract
Background
First-line treatment with FOLFOXIRI plus bevacizumab (BEV) is highly effective and regarded as one of the standards-of-care for patients with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea as side effects. AXEPT, an Asian phase III study, showed that modified CAPIRI+BEV [capecitabine (CAP: 1600 mg/m2), irinotecan (IRI: 200 mg/m2), and BEV (7.5 mg/m2)] was non-inferior to FOLFIRI+BEV as a second-line therapy for mCRC patients and was associated with a lower incidence of hematologic toxicities. Thus, a reduced dose of the CAP and IRI regimen in combination with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) may be more feasible than FOLFOXIRI+BEV, without compromising efficacy.

Methods
QUATTRO-II is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses of OX and IRI will be investigated as a safety lead-in. In Step 2, patients will be randomized to the recommended dose of either CAPOXIRI+BEV or FOLFOXIRI+BEV. Induction triplet chemotherapy plus BEV treatments will be administered for up to 4 months followed by fluoropyrimidine plus BEV maintenance. The primary endpoint is progression-free survival (PFS). The similarity in PFS between the two arms will be evaluated by observing whether the point estimate of hazard ratio (HR) for PFS falls between 0.80 and 1.25. Ensuring a 70% probability that the observed HR will be “0.8 < HR < 1.25” under the assumption of the true HR of 1.0, and 100 patients will be evaluated during the 3-year study period. Secondary endpoints include overall survival, overall response rate, safety, and patient reported outcome (PRO) (FACT/GOG-Ntx4).

Discussion
Considering the lower incidence of hematologic toxicities with modified CAPIRI+BEV than with FOLFIRI+BEV, CAPOXIRI+BEV may be a promising treatment option if sufficient efficacy and lower hematologic toxicities are indicated in this study. Additionally, a lower incidence of peripheral sensory neuropathy (PSN) reported following CAPEOX treatment compared to that after FOLFOX in ACHIEVE, an adjuvant phase III trial, suggest that CAPOXIRI+BEV can mitigate OX-induced PSN.

Trial registration
Clinicaltrials.gov NCT04097444. Registered September 20, 2019, https://clinicaltrials.gov/ct2/show/study/NCT04097444/ Japan Registry of Clinical Trials jRCTs041190072. Registered October 9, 2019.
Determinants of caregiver burden of persons with disabilities in a rural district in Egypt
Authors: Ghazawy Eman Ramadan , Mohammed Eman Sameh , Mahfouz Eman Mohamed , Abdelrehim Marwa Gamal 
Published: July 2020

AbstractBackgroundFamily caregivers are critical partners in the plan of care of people with disabilities. The study aims to demonstrate the factor structure and internal consistency of the Caregiver Burden Inventory (CBI) among the studied caregivers of disabled persons and to determine the effects of patients’ and caregivers’ characteristics on the burden and its dimensions.MethodsA cross-sectional study among 260 family caregivers of disabled patients was carried out in a randomly chosen rural area, Minia, Egypt, 2019. Exploratory factor analysis (EFA) was conducted to determine the factorial validity of the CBI. Multiple linear regression was used to identify the significant factors affecting the burden.ResultsFactor analysis resulted in a five-factor solution using 20 items (four for each dimension) accounting for 72.7% of the total variance. The CBI and its dimensions showed high internal consistency (Cronbach’s alpha value > 0.70). Education of caregiver, family income, mental impairments, and mixed disabilities were significant predictors of total CBI burden.ConclusionsCBI is an effective multidimensional measure of the caregiver burden of disabled subjects. Caregivers experienced a distinct level of burden that is determined by caregiver and care recipient characteristics. Therefore, support and individualized counseling services should be optimized.