bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric magnetic resonance imaging for bladder cancer: a comprehensive systematic review of the Vesical Imaging-Reporting and Data System (VI-RADS) performance and potential clinical applications
Authors: Séguier Denis , Puech Philippe , Kool Ronald , Dernis Léa , Gabert Héléna , Kassouf Wassim , Villers Arnauld , Marcq Gautier 
Published: August 2021

Background: The Vesical Imaging-Reporting and Data System (VI-RADS) score is a novel standardized approach to image and report bladder cancer (BC) with multiparametric MRI (mpMRI). Objectives: To describe and evaluate the performance of the VI-RADS score using mpMRI and assess its potential clinical applications and limitations. Methods: A systematic review was conducted using the MEDLINE and EMBASE electronic bibliographic databases between June 2020 and December 2020. All reports deemed relevant to describe the VI-RADS score and assess its performance and applications were retrieved. Results presentation stands as narrative, purely descriptive synthesis based on aggregate studies data. Results: A total of 20 relevant studies were retrieved: three meta-analyses, five prospective studies, and twelve retrospective studies. The retrospective studies covered 1676 patients, while the prospective studies included a total number of 468 patients. Pooled sensitivity, specificity to differentiate muscle-invasive from non-muscle-invasive bladder cancer, ranged from 74.1% to 97.3%, and 77% to 100%, respectively. The chosen VI-RADS score thresholds for this discrimination varied across studies. The interreader agreement ranged from 0.73 to 0.95. Currently, the potential clinical applications of VI-RADS consist of initial BC risk stratification, assessment of neoadjuvant therapies response, and bladder sparing approaches, although further validation is required. Conclusions: The VI-RADS score helps to discriminate muscle invasive from non-muscle invasive BC with good performance and reproducibility. A simple algorithm based on four basic questions may enhance its popularization. Further studies are required to validate the clinical applications.
Primary histiocytic sarcoma in the brain with renal metastasis causing internal ophthalmoparesis and external ophthalmoplegia in a Maine Coon cat
Authors: Monteiro Susana , Hughes Katherine , Genain Marie-Aude , Alves Lisa 
Published: August 2021

Case summary An 11-year-old neutered male Maine Coon cat was presented for investigation of anisocoria and depression. Neurological examination was consistent with a lesion at the level of the middle cranial fossa, and biochemistry was indicative of moderate renal functional impairment. MRI of the brain identified an extra-axial mass lesion at the level of the middle cranial fossa, T2-weighted hyperintense and strongly homogeneously contrast enhancing with dural tail. The cat was euthanased after 6 weeks of palliative treatment with corticosteroids. Histopathology and immunohistochemistry of the brain, the intra-cranial mass and the renal masses found on necropsy were consistent with histiocytic sarcoma. Relevance and novel information Central nervous system histiocytic sarcoma is a rare finding in cats. This original case report describes the neurological presentation, novel MRI characteristics and pathological findings of suspected primary histiocytic sarcoma affecting the brain with renal metastasis in a cat.
Biomechanical Comparison of a Novel Tibial Fixation Technique Versus Interference Screw Fixation for ACL Reconstruction Using Soft Tissue Grafts
Authors: Sun Tinghan , Zhang Hangzhou 
Published: August 2021

Background: Controversy remains regarding the optimal technique for tibial fixation of soft tissue grafts in anterior cruciate ligament (ACL) reconstruction. Purpose/Hypothesis: To compare the biomechanical outcomes of a novel transtibial tubercle fixation technique with those of a commonly utilized interference screw fixation at the tibial site. Our hypothesis was that transtibial tubercle fixation achieves higher ultimate failure loads than interference screw fixation. Study Design: Controlled laboratory study. Methods: We used 24 matched porcine tibias and digital extensor tendons, from which 12 grafts and tibial tunnels were prepared using the novel transtibial tubercle fixation technique and 12 were prepared using the interference screw fixation technique. The specimens underwent a cyclic loading test (50-250 N applied for 1000 cycles at a frequency of 1 Hz), followed by a load-to-failure test. The slippage, stiffness, and ultimate failure loads were compared between the techniques. Results: No differences in slippage were found during the cyclic loading test, and no graft fixation or tibial complex failures occurred during cyclic testing in either group. The transtibial tubercle fixation technique had higher ultimate failure loads (mean ± SD, 756.28 ± 123.43 N) as compared with interference screw fixation (602.15 ± 81.62 N; P < .05). The grafts in the transtibial tubercle fixation group were less stiff than those in the interference screw fixation group (84.43 vs 101.23 N/mm; P < .05). Conclusion: Transtibial tubercle fixation achieved higher ultimate failure loads than interference screw fixation in the load-to-failure test. Clinical Relevance: The novel transtibial tubercle fixation technique compared favorably with interference screw fixation during ACL reconstruction. This technique does not require hardware, has a low cost, theoretically eliminates the risk of complications associated with hardware implantation (eg, graft damage and pain attributed to retained hardware requiring removal), and is relatively easy to perform.
TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling
Authors: Peña Oscar A. , Lubin Alexandra , Hockings Catherine , Rowell Jasmine , Jung Youngrock , Hoade Yvette , Dace Phoebe , Valdivia Leonardo E. , Tuschl Karin , Böiers Charlotta , Virgilio Maria C. , Richardson Simon , Payne Elspeth M. 
Published: August 2021

Abstract
Myelodysplastic syndrome (MDS) is a hematological malignancy characterized by blood cytopenias and predisposition to acute myeloid leukemia (AML). Therapies for MDS are lacking, particularly those that have an impact in the early stages of disease. We developed a model of MDS in zebrafish with knockout of Rps14, the primary mediator of the anemia associated with del(5q) MDS. These mutant animals display dose- and age-dependent abnormalities in hematopoiesis, culminating in bone marrow failure with dysplastic features. We used Rps14 knockdown to undertake an in vivo small-molecule screening, to identify compounds that ameliorate the MDS phenotype, and we identified imiquimod, an agonist of Toll-like receptor-7 (TLR7) and TLR8. Imiquimod alleviates anemia by promoting hematopoietic stem and progenitor cell expansion and erythroid differentiation, the mechanism of which is dependent on TLR7 ligation and Myd88. TLR7 activation in this setting paradoxically promoted an anti-inflammatory gene signature, indicating cross talk via TLR7 between proinflammatory pathways endogenous to Rps14 loss and the NF-κB pathway. Finally, in highly purified human bone marrow samples from anemic patients, imiquimod led to an increase in erythroid output from myeloerythroid progenitors and common myeloid progenitors. Our findings have both specific implications for the development of targeted therapeutics for del(5q) MDS and wider significance identifying a potential role for TLR7 ligation in modifying anemia.
Coevolving JAK2V617F+relapsed AML and donor T cells with PD-1 blockade after stem cell transplantation: an index case
Authors: Penter Livius , Gohil Satyen H. , Huang Teddy , Thrash Emily M. , Schmidt Dominik , Li Shuqiang , Severgnini Mariano , Neuberg Donna , Hodi F. Stephen , Livak Kenneth J. , Zeiser Robert , Bachireddy Pavan , Wu Catherine J. 
Published: August 2021

Abstract
Relapse of myeloproliferative neoplasms (MPNs) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes, as therapeutic approaches to reinstate effective graft-versus-leukemia (GVL) responses remain suboptimal. Immune escape through overexpression of PD-L1 in JAK2V617F-mutated MPN provides a rationale for therapeutic PD-1 blockade, and indeed, clinical activity of nivolumab in relapsed MPN post-HSCT has been observed. Elucidation of the features of response following PD-1 blockade in such patients could inform novel therapeutic concepts that enhance GVL. Here, we report an integrated high-dimensional analysis using single-cell RNA sequencing, T-cell receptor sequencing, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), and assay for transposase-accessible chromatin using sequencing (scATAC-seq), together with mass cytometry, in peripheral blood mononuclear cells collected at 6 timepoints before, during, and after transient response to PD-1 blockade from an index case of relapsed MPN following HSCT. Before nivolumab infusion, acute myeloid leukemia (AML) blasts demonstrated high expression of chemokines, and T cells were characterized by expression of interferon-response genes. This baseline inflammatory signature disappeared after nivolumab infusion. Clinical response was characterized by transient expansion of a polyclonal CD4+ T-cell population and contraction of an AML subpopulation that exhibited megakaryocytic features and elevated PD-L1 expression. At relapse, the proportion of the AML subpopulation with progenitor-like features progressively increased, suggesting coevolution of AML blasts and donor-derived T cells. We thus demonstrate how single-cell technologies can provide complementary insight into cellular mechanisms underlying response to PD-1 blockade, motivating future longitudinal high-dimensional single-cell studies of GVL responses in relapsed myeloid disease.
Fast and SNP-aware short read alignment with SALT
Authors: Quan Wei , Liu Bo , Wang Yadong 
Published: August 2021

Abstract
Background
DNA sequence alignment is a common first step in most applications of high-throughput sequencing technologies. The accuracy of sequence alignments directly affects the accuracy of downstream analyses, such as variant calling and quantitative analysis of transcriptome; therefore, rapidly and accurately mapping reads to a reference genome is a significant topic in bioinformatics. Conventional DNA read aligners map reads to a linear reference genome (such as the GRCh38 primary assembly). However, such a linear reference genome represents the genome of only one or a few individuals and thus lacks information on variations in the population. This limitation can introduce bias and impact the sensitivity and accuracy of mapping. Recently, a number of aligners have begun to map reads to populations of genomes, which can be represented by a reference genome and a large number of genetic variants. However, compared to linear reference aligners, an aligner that can store and index all genetic variants has a high cost in memory (RAM) space and leads to extremely long run time. Aligning reads to a graph-model-based index that includes all types of variants is ultimately an NP-hard problem in theory. By contrast, considering only single nucleotide polymorphism (SNP) information will reduce the complexity of the index and improve the speed of sequence alignment.

Results
The SNP-aware alignment tool (SALT) is a fast, memory-efficient, and SNP-aware short read alignment tool. SALT uses 5.8 GB of RAM to index a human reference genome (GRCh38) and incorporates 12.8M UCSC common SNPs. Compared with a state-of-the-art aligner, SALT has a similar speed but higher accuracy.

Conclusions
Herein, we present an SNP-aware alignment tool (SALT) that aligns reads to a reference genome that incorporates an SNP database. We benchmarked SALT using simulated and real datasets. The results demonstrate that SALT can efficiently map reads to the reference genome with significantly improved accuracy. Incorporating SNP information can improve the accuracy of read alignment and can reveal novel variants. The source code is freely available at https://github.com/weiquan/SALT.
TLGP: a flexible transfer learning algorithm for gene prioritization based on heterogeneous source domain
Authors: Wang Yan , Xia Zuheng , Deng Jingjing , Xie Xianghua , Gong Maoguo , Ma Xiaoke 
Published: August 2021

AbstractBackgroundGene prioritization (gene ranking) aims to obtain the centrality of genes, which is critical for cancer diagnosis and therapy since keys genes correspond to the biomarkers or targets of drugs. Great efforts have been devoted to the gene ranking problem by exploring the similarity between candidate and known disease-causing genes. However, when the number of disease-causing genes is limited, they are not applicable largely due to the low accuracy. Actually, the number of disease-causing genes for cancers, particularly for these rare cancers, are really limited. Therefore, there is a critical needed to design effective and efficient algorithms for gene ranking with limited prior disease-causing genes.ResultsIn this study, we propose a transfer learning based algorithm for gene prioritization (called TLGP) in the cancer (target domain) without disease-causing genes by transferring knowledge from other cancers (source domain). The underlying assumption is that knowledge shared by similar cancers improves the accuracy of gene prioritization. Specifically, TLGP first quantifies the similarity between the target and source domain by calculating the affinity matrix for genes. Then, TLGP automatically learns a fusion network for the target cancer by fusing affinity matrix, pathogenic genes and genomic data of source cancers. Finally, genes in the target cancer are prioritized. The experimental results indicate that the learnt fusion network is more reliable than gene co-expression network, implying that transferring knowledge from other cancers improves the accuracy of network construction. Moreover, TLGP outperforms state-of-the-art approaches in terms of accuracy, improving at least 5%.ConclusionThe proposed model and method provide an effective and efficient strategy for gene ranking by integrating genomic data from various cancers.
Web-based LinRegPCR: application for the visualization and analysis of (RT)-qPCR amplification and melting data
Authors: Untergasser Andreas , Ruijter Jan M. , Benes Vladimir , van den Hoff Maurice J. B. 
Published: August 2021

Abstract
Background
The analyses of amplification and melting curves have been shown to provide valuable information on the quality of the individual reactions in quantitative PCR (qPCR) experiments and to result in more reliable and reproducible quantitative results.

Implementation
The main steps in the amplification curve analysis are (1) a unique baseline subtraction, not using the ground phase cycles, (2) PCR efficiency determination from the exponential phase of the individual reactions, (3) setting a common quantification threshold and (4) calculation of the efficiency-corrected target quantity with the common threshold, efficiency per assay and Cq per reaction. The melting curve analysis encompasses smoothing of the observed fluorescence data, normalization to remove product-independent fluorescence loss, peak calling and assessment of the correct peak by comparing its melting temperature with the known melting temperature of the intended amplification product.

Results
The LinRegPCR web application provides visualization and analysis of a single qPCR run. The user interface displays the analysis results on the amplification curve analysis and melting curve analysis in tables and graphs in which deviant reactions are highlighted. The annotated results in the tables can be exported for calculation of gene-expression ratios, fold-change between experimental conditions and further statistical analysis. Web-based LinRegPCR addresses two types of users, wet-lab scientists analyzing the amplification and melting curves of their own qPCR experiments and bioinformaticians creating pipelines for analysis of series of qPCR experiments by splitting its functionality into a stand-alone back-end RDML (Real-time PCR Data Markup Language) Python library and several companion applications for data visualization, analysis and interactive access. The use of the RDML data standard enables machine independent storage and exchange of qPCR data and the RDML-Tools assist with the import of qPCR data from the files exported by the qPCR instrument.

Conclusions
The combined implementation of these analyses in the newly developed web-based LinRegPCR (https://www.gear-genomics.com/rdml-tools/) is platform independent and much faster than the original Windows-based versions of the LinRegPCR program. Moreover, web-based LinRegPCR includes a novel statistical outlier detection and the combination of amplification and melting curve analyses allows direct validation of the amplification product and reporting of reactions that amplify artefacts.
Integrative analysis of metabolome and transcriptome profiles provides insight into the fruit pericarp pigmentation disorder caused by ‘Candidatus Liberibacter asiaticus’ infection
Authors: Wang Feiyan , Wu Yunli , Wu Wen , Huang Yongjing , Zhu Congyi , Zhang Ruimin , Chen Jiezhong , Zeng Jiwu 
Published: August 2021

Abstract
Background
Mandarin ‘Shatangju’ is susceptible to Huanglongbing (HLB) and the HLB-infected fruits are small, off-flavor, and stay-green at the maturity period. To understand the relationship between pericarp color and HLB pathogen and the effect mechanism of HLB on fruit pericarp coloration, quantitative analyses of HLB bacterial pathogens and carotenoids and also the integrative analysis of metabolome and transcriptome profiles were performed in the mandarin ‘Shatangju’ variety with four different color fruits, whole green fruits (WGF), top-yellow and base-green fruits (TYBGF), whole light-yellow fruits (WLYF), and whole dark-yellow fruits (WDYF) that were infected with HLB.

Results
the HLB bacterial population followed the order WGF > TYBGF > WLYF > WDYF. And there were significant differences between each group of samples. Regarding the accumulation of chlorophyll and carotenoid, the chlorophyll-a content in WGF was the highest and in WDYF was the lowest. The content of chlorophyll-b in WGF was significantly higher than that in other three pericarps. There were significant differences in the total content of carotenoid between each group. WGF and TYBGF pericarps were low in phytoene, γ-carotene, β-cryptoxanthin and apocarotenal, while other kinds of carotenoids were significantly higher than those in WDYF. And WLYF was only short of apocarotenal. We comprehensively compared the transcriptome and metabolite profiles of abnormal (WGF, TYBGF and WLYF) and normal (WDYF, control) pericarps. In total, 2,880, 2,782 and 1,053 differentially expressed genes (DEGs), including 121, 117 and 43 transcription factors were identified in the three comparisons, respectively. The qRT-PCR confirmed the expression levels of genes selected from transcriptome. Additionally, a total of 77 flavonoids and other phenylpropanoid-derived metabolites were identified in the three comparisons. Most (76.65 %) showed markedly lower abundances in the three comparisons. The phenylpropanoid biosynthesis pathway was the major enrichment pathway in the integrative analysis of metabolome and transcriptome profiles.

Conclusions
Synthesizing the above analytical results, this study indicated that different color pericarps were associated with the reduced levels of some carotenoids and phenylpropanoids derivatives products and the down-regulation of proteins in flavonoids, phenylpropanoids derivatives biosynthesis pathway and the photosynthesis-antenna proteins.
Positive DAT-SCAN in SPG7: a case report mimicking possible MSA-C
Authors: Bellini Gabriele , Del Prete Eleonora , Unti Elisa , Frosini Daniela , Siciliano Gabriele , Ceravolo Roberto 
Published: August 2021

Abstract
Background
Spastic Paraplegia type 7 (SPG7) is one of the most common autosomal recessive Hereditary Spastic Paraplegias (HSP); Spastic Paraplegias (SPGs) can present as hereditary ataxias. However, ataxia is frequently the symptom of presentation of many other hereditary/sporadic disorders, such as Multiple system atrophy type C (MSA-C), an α-synuclein sporadic neurodegenerative disorder, in which cerebellar ataxia is one of the main clinical features. Dopamine Transporter imaging (DAT-SCAN), associated with clinical features, can be a helpful tool in order to distinguish MSA-C from other causes of ataxia.

Case-presentation
We present the case of a 70-year-old man with gait difficulties over a period of 3 years and frequent backward/lateral falls. He also reported urinary urge incontinence, but no symptoms that are compatible with orthostatic hypotension. On neurological examination he showed ataxic gait, spasticity in the left lower limb and trunk and limb ataxia, especially on the left side. Mild hypokinesia was found in all 4 limbs, especially in the left foot. MRI revealed atrophy of the cerebellar hemispheres and vermis. DAT-SCAN imaging revealed bilateral nigro-striatal degeneration, which was compatible with a diagnosis of possible MSA-C. Considering the atypical disease course (the patient walked without any support after 3 years), we carried out a genetic investigation for Ataxia, and a mutation in SPG7 was found.

Conclusions
DAT-SCAN imaging, evaluated together with the clinical findings, can be useful for differentiating MSA from other possible causes of adult-onset Ataxia. Indeed, patients with MSA-C generally show a decreased uptake of dopamine transporters in DAT-SCAN imaging. Ours is the first case reported in the literature of a patient with SPG7 mutation with nigrostriatal degeneration and a clinical presentation of a possible MSA-C. Performing genetic investigations in patients with an atypical disease course is important to avoid MSA-mimicries.
Identifying the correct diagnosis is important not only for prognostic reasons, but also for possible future genetic therapies.
Comprehensive analysis of coagulation indices for predicting survival in patients with biliary tract cancer
Authors: Ke Xindi , Jin Bao , You Wen , Chen Yang , Xu Haifeng , Zhao Haitao , Lu Xin , Sang Xinting , Zhong Shouxian , Yang Huayu , Mao Yilei , Du Shunda 
Published: August 2021

Abstract
Background
Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC.

Methods
The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram.

Results
Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging.

Conclusions
The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.