bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research Trends on the Rotator Cuff Tendon: A Bibliometric Analysis of the Past 2 Decades
Authors: Lei Lei , Zhang Chi , Sun Fu-Hua , Xie Yujie , Liang Bin , Wang Li , Pang Guoyin , Chen Ruyan , Jiang Wei , Ou Xia , Miyamoto Akira , Wang Jianxiong 
Published: January 2021

Background: Clinical research on the rotator cuff tendon is increasing, and new approaches are being applied to rotator cuff disease. Considering the integration of research resources and research trends, it is necessary to conduct an analysis of recent research on the topic. Purpose: To identity the research trends, influential journals, key researchers, and core countries of rotator cuff tendon research between 2000 and 2019. Study Design: Cross-sectional study. Methods: All the literature related to rotator cuff tendon research was retrieved from the Web of Science Core Collection on January 7, 2020. Qualitative and quantitative analyses were processed based on Web of Science and CiteSpace. Results: A total of 4131 studies, which included 3830 articles and 301 reviews, were obtained. There was an upward trend of studies on the topic, with small fluctuations in the past 2 decades. The United States had the most studies, and the number of studies from other countries increased over the study period. Most of the funding sources came from the United States. Articles in the Journal of Shoulder and Elbow Surgery had the most citations for rotator cuff research. Frontier topics, such as arthroscopic repair, mesenchymal stem cell, and “platelet-rich plasma, were identified. The number of citations in 2018 ( r = 0.280; P = .005) and 2019 ( r = 0.307; P = .002) had a weak positive correlation with publication date, indicating that the more recently published articles had a higher number of citations. Conclusion: Valuable information on rotator cuff research based on bibliometric analysis was identified. Arthroscopic repair, mesenchymal stem cell, and platelet-rich plasma might be the research frontiers in this field, and researchers should focus on these topics in future studies.
An in situ, micro-scale investigation of inorganically and organically driven rare-earth remobilisation during weathering
Authors: Kalintsev Alexander , Brugger Joël , Etschmann Barbara , Ram Rahul 
Published: January 2021

AbstractAt present, a significant portion of rare-earth elements (REEs) are sourced from weathering profiles. The mineralogy of the protolith plays an important role in controlling the fate of REEs during weathering, as accessory minerals contain the bulk the REE budget in most rocks, and different minerals vary in their susceptibilities to weathering processes. REE supergene deposits (‘adsorption clay deposits’) are associated with deep weathering in tropical environments, which often precludes characterisation of the incipient steps in REE liberation from their host minerals in the protolith. Here we have targeted a weathered REE-enriched lithology from a sub-arid environment undergoing relatively rapid uplift, namely the Yerila Gneiss from the Northern Flinders Ranges, Australia, where regolith was shallow or absent and parent rock material had yet to completely break down. Results from X-ray fluorescence mapping, scanning electron microscopy (SEM), SEM-focussed ion beam milling (FIB-SEM), inductively-coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS highlight the migration pathways of REEs and associated U and Th from allanite-(Ce) grains that are the main REE host within Yerila Gneiss material. Migration of light REEs and Th away from the allanite-(Ce) grains via radial cracks resulting from allanite-(Ce) metamictisation was interpreted to result from weathering, as Ce is partially present in its tetravalent oxidation state and Th mobility is most easily explained by the involvement of organic ligands. FIB-SEM provides further evidence for the importance of biogenic processes in REE+U/Th mobility and fractionation in uranothorite-associated spheroidal structures associated with the weathering of allanite-(Ce). Organic carbon was also found in association with a xenotime-(Y) grain; in this case, REE liberation is most likely a by-product of biogenic phosphate utilisation. These results highlight that local controls (at mineral interfaces) mediated by biota and/or biogenic organic matter can control the initiation of REE (+Th,U) mobilisation during weathering.
How I treat warm autoimmune hemolytic anemia
Authors: Barcellini Wilma , Fattizzo Bruno 
Published: January 2021

Abstract
Warm autoimmune hemolytic anemia (wAIHA) is caused by increased erythrocyte destruction by immunoglobulin G (IgG) autoantibodies, with or without complement activation. Antibody-dependent cell-mediated cytotoxicity by macrophages/activated lymphocytes occurs in the lymphoid organs and spleen (extravascular hemolysis). The ability of the bone marrow (BM) to compensate determines clinical severity. The different pathogenic mechanisms, their complex interplay, and changes over time may explain wAIHA’s great clinical heterogeneity and unpredictable course. The disease may be primary, drug induced, or associated with lymphoproliferative neoplasms, autoimmune and infectious diseases, immunodeficiencies, solid tumors, or transplants. Therapeutic interventions include steroids, splenectomy, immunosuppressants, and rituximab; the latter is increasingly used in steroid-refractory cases based on evidence from the literature and a few prospective trials. We present 5 patient case studies highlighting important issues: (1) the diagnosis and proper use of steroid therapy, (2) the concerns about the choice between rituximab and splenectomy in second-line treatment, (3) the need of periodical re-evaluation of the disease to assess the possible evolution of relapsed/refractory cases in myelodysplastic and BM failure syndromes, and (4) the difficulties in managing cases of severe/acute disease that are at high risk of relapse. Incorporating novel targeted therapies into clinical practice will be an exciting challenge in the future.
How I treat cold agglutinin disease
Authors: Berentsen Sigbjørn 
Published: January 2021

AbstractThe last decades have seen great progress in the treatment of cold agglutinin disease (CAD). Comparative trials are lacking, and recommendations must be based mainly on nonrandomized trials and will be influenced by personal experience. Herein, current treatment options are reviewed and linked to 3 cases, each addressing specific aspects of therapy. Two major steps in CAD pathogenesis are identified, clonal B-cell lymphoproliferation and complement-mediated hemolysis, each of which constitutes a target of therapy. Although drug treatment is not always indicated, patients with symptomatic anemia or other bothersome symptoms should be treated. The importance of avoiding ineffective therapies is underscored. Corticosteroids should not be used to treat CAD. Studies on safety and efficacy of relevant drugs and combinations are briefly described. The author recommends that B cell–directed approaches remain the first choice in most patients requiring treatment. The 4-cycle bendamustine plus rituximab combination is highly efficacious and sufficiently safe and induces durable responses in most patients, but the time to response can be many months. Rituximab monotherapy should be preferred in frail patients. The complement C1s inhibitor sutimlimab is an emerging option in the second line and may also find its place in the first line in specific situations.
How I treat microangiopathic hemolytic anemia in patients with cancer
Authors: Thomas M. R. , Scully M. 
Published: January 2021

AbstractMicroangiopathic hemolytic anemia (MAHA) with thrombocytopenia, suggests a thrombotic microangiopathy (TMA), linked with thrombus formation affecting small or larger vessels. In cancer patients, it may be directly related to the underlying malignancy (initial presentation or progressive disease), to its treatment, or a separate incidental diagnosis. It is vital to differentiate incidental thrombotic thrombocytopenia purpura or atypical hemolytic uremic syndrome in cancer patients presenting with a TMA, as they have different treatment strategies, and prompt initiation of treatment impacts outcome. In the oncology patient, widespread microvascular metastases or extensive bone marrow involvement can cause MAHA and thrombocytopenia. A disseminated intravascular coagulation (DIC) picture may be precipitated by sepsis or driven by the cancer itself. Cancer therapies may cause a TMA, either dose-dependent toxicity, or an idiosyncratic immune-mediated reaction due to drug-dependent antibodies. Many causes of TMA seen in the oncology patient do not respond to plasma exchange and, where feasible, treatment of the underlying malignancy is important in controlling both cancer-TMA or DIC driven disease. Drug-induced TMA should be considered and any putative causal agent stopped. We will discuss the differential diagnosis and treatment of MAHA in patients with cancer using clinical cases to highlight management principles.
Hematologic disorder–associated Cxcr4 gain-of-function mutation leads to uncontrolled extrafollicular immune response
Authors: Alouche Nagham , Bonaud Amélie , Rondeau Vincent , Hussein-Agha Rim , Nguyen Julie , Bisio Valeria , Khamyath Mélanie , Crickx Etienne , Setterblad Niclas , Dulphy Nicolas , Mahevas Matthieu , McDermott David H. , Murphy Philip M. , Balabanian Karl , Espéli Marion 
Published: January 2021

Abstract
The extrafollicular immune response is essential to generate a rapid but transient wave of protective antibodies during infection. Despite its importance, the molecular mechanisms controlling this first response are poorly understood. Here, we demonstrate that enhanced Cxcr4 signaling caused by defective receptor desensitization leads to exacerbated extrafollicular B-cell response. Using a mouse model bearing a gain-of-function mutation of Cxcr4 described in 2 human hematologic disorders, warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and Waldenström macroglobulinemia, we demonstrated that mutant B cells exhibited enhanced mechanistic target of rapamycin signaling, cycled more, and differentiated more potently into plasma cells than wild-type B cells after Toll-like receptor (TLR) stimulation. Moreover, Cxcr4 gain of function promoted enhanced homing and persistence of immature plasma cells in the bone marrow, a phenomenon recapitulated in WHIM syndrome patient samples. This translated in increased and more sustained production of antibodies after T-independent immunization in Cxcr4 mutant mice. Thus, our results establish that fine-tuning of Cxcr4 signaling is essential to limit the strength and length of the extrafollicular immune response.
Self-inflicted gunshot injury to the external genitalia: a case report and review of literature
Authors: Obi Anselm Okwudili , Ulebe Augustine Obasi , Nnadozie Ugochukwu Uzodinmma , Maduba Charles Chidiebele , Okorie Chukwudi Ogonnaya , Anikwe Obinna Nnabuife 
Published: January 2021

Abstract
Background
Gunshot wounds of the external genitalia are rare. Rarer still are civilian self-inflicted gunshot wounds of the external genitalia. The protocol for the management of gunshot wounds of the penis especially with respect to urethral injuries is not fully established.

Case presentation
We present a 27-year-old male undergraduate student, who accidentally shot himself in the penis. He sustained American Association for the Surgery of Trauma (AAST) grades IV to V injuries to the penis, scrotum and left testes. He was managed in a multistage, multi-disciplinary fashion including staged buccal mucosal graft repair of 4 cm proximal penile urethral defect with satisfactory cosmetic and functional outcome.

Conclusions
Excellent functional and cosmetic results may be obtained after severe penetrating trauma to the external genitalia even in low resource centres in the hands of non-reconstructive urologists. Buccal mucosal graft is a viable option for two stage reconstruction of the urethra.
MHC class I evolution; from Northern pike to salmonids
Authors: Grimholt U. , Lukacs M. 
Published: January 2021

Abstract
Background
Salmonids are of major importance both as farmed and wild animals. With the changing environment comes changes in pathogenic pressures so understanding the immune system of all salmonid species is of essence. Major histocompatibility complex (MHC) genes are key players in the adaptive immune system signalling infection to responding T-cells populations. Classical MHC class I (MHCI) genes, defined by high polymorphism, broad expression patterns and peptide binding ability, have a key role in inducing immunity. In salmonids, the fourth whole genome duplication that occurred 94 million years ago has provided salmonids with duplicate MHCI regions, while Northern Pike, a basal sister clade to salmonids, represent a species which has not experienced this whole genome duplication.

Results
Comparing the gene organization and evolution of MHC class I gene sequences in Northern pike versus salmonids displays a complex picture of how many of these genes evolved. Regional salmonid Ia and Ib Z lineage gene duplicates are not orthologs to the Northern pike Z lineage sequences. Instead, salmonids have experienced unique gene duplications in both duplicate regions as well as in the Salmo and Oncorhynchus branch. Species-specific gene duplications are even more pronounced for some L lineage genes.

Conclusions
Although both Northern pike as well as salmonids have expanded their U and Z lineage genes, these gene duplications occurred separately in pike and in salmonids. However, the similarity between these duplications suggest the transposable machinery was present in a common ancestor. The salmonid MHCIa and MHCIb regions were formed during the 94 MYA since the split from pike and before the Oncorhynchus and Salmo branch separated. As seen in tetrapods, the non-classical U lineage genes are diversified duplicates of their classical counterpart. One MHCI lineage, the L lineage, experienced massive species-specific gene duplications after Oncorhynchus and Salmo split approximately 25 MYA. Based on what we currently know about L lineage genes, this large variation in number of L lineage genes also signals a large functional diversity in salmonids.
Multiple freeze-thaw cycles lead to a loss of consistency in poly(A)-enriched RNA sequencing
Authors: Kellman Benjamin P. , Baghdassarian Hratch M. , Pramparo Tiziano , Shamie Isaac , Gazestani Vahid , Begzati Arjana , Li Shangzhong , Nalabolu Srinivasa , Murray Sarah , Lopez Linda , Pierce Karen , Courchesne Eric , Lewis Nathan E. 
Published: January 2021

Abstract
Background
Both RNA-Seq and sample freeze-thaw are ubiquitous. However, knowledge about the impact of freeze-thaw on downstream analyses is limited. The lack of common quality metrics that are sufficiently sensitive to freeze-thaw and RNA degradation, e.g. the RNA Integrity Score, makes such assessments challenging.

Results
Here we quantify the impact of repeated freeze-thaw cycles on the reliability of RNA-Seq by examining poly(A)-enriched and ribosomal RNA depleted RNA-seq from frozen leukocytes drawn from a toddler Autism cohort. To do so, we estimate the relative noise, or percentage of random counts, separating technical replicates. Using this approach we measured noise associated with RIN and freeze-thaw cycles. As expected, RIN does not fully capture sample degradation due to freeze-thaw. We further examined differential expression results and found that three freeze-thaws should extinguish the differential expression reproducibility of similar experiments. Freeze-thaw also resulted in a 3′ shift in the read coverage distribution along the gene body of poly(A)-enriched samples compared to ribosomal RNA depleted samples, suggesting that library preparation may exacerbate freeze-thaw-induced sample degradation.

Conclusion
The use of poly(A)-enrichment for RNA sequencing is pervasive in library preparation of frozen tissue, and thus, it is important during experimental design and data analysis to consider the impact of repeated freeze-thaw cycles on reproducibility.

Graphical abstract
Neutrophil extracellular traps are present in the airways of ENaC-overexpressing mice with cystic fibrosis-like lung disease
Authors: Tucker Samantha L. , Sarr Demba , Rada Balázs 
Published: January 2021

Abstract
Background
Neutrophils are key components of the exacerbated inflammation and tissue damage in cystic fibrosis (CF) airways. Neutrophil extracellular traps (NETs) trap and kill extracellular pathogens. While NETs are abundant in the airways of CF patients and have been hypothesized to contribute to lung damage in CF, the in vivo role of NETs remains controversial, partially due to lack of appropriate animal models. The goal of this study was to detect NETs and to further characterize neutrophil-mediated inflammation in the airways of mice overexpressing the epithelial sodium channel (βENaC-Tg mice on C57BL/6 background) in their lung with CF-like airway disease, in the absence of any apparent bacterial infections.

Methods
Histology scoring of lung tissues, flow cytometry, multiplex ELISA, immunohistochemistry and immunofluorescence were used to characterize NETs and the airway environment in uninfected, βENaC-Tg mice at 6 and 8 weeks of age, the most chronic time points so far studied in this model.

Results
Excessive neutrophilic infiltration characterized the lungs of uninfected, βENaC-Tg mice at 6 and 8 weeks of age. The bronchoalveolar lavage fluid (BALF) of βENaC-Tg mice contains increased levels of CF-associated cytokines and chemokines: KC, MIP-1α/β, MCP-1, G-CSF, IL-5, and IL-6. The BALF of βENaC-Tg mice contain MPO-DNA complexes, indicative of the presence of NETs. Immunofluorescence and flow cytometry of BALF neutrophils and lung tissues demonstrated increased histone citrullination, a NET-specific marker, in βENaC-Tg mice.

Conclusions
NETs are detected in the airways of βENaC-Tg mice, in the absence of bacterial infections. These data demonstrate the usefulness of the βENaC-Tg mouse to serve as a model for studying the role of NETs in chronic CF airway inflammation.
Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance
Authors: Wang Xingyi , Liu Hui , Siddique Kadambot H. M. , Yan Guijun 
Published: January 2021

AbstractBackgroundPre-harvest sprouting (PHS) in wheat can cause severe damage to both grain yield and quality. Resistance to PHS is a quantitative trait controlled by many genes located across all 21 wheat chromosomes. The study targeted a large-effect quantitative trait locus (QTL)QPhs.ccsu-3A.1for PHS resistance using several sets previously developed near-isogenic lines (NILs). Two pairs of NILs with highly significant phenotypic differences between the isolines were examined by RNA sequencing for their transcriptomic profiles on developing seeds at 15, 25 and 35 days after pollination (DAP) to identify candidate genes underlying the QTL and elucidate gene effects on PHS resistance. At each DAP, differentially expressed genes (DEGs) between the isolines were investigated.ResultsGene ontology and KEGG pathway enrichment analyses of key DEGs suggested that six candidate genes underlieQPhs.ccsu-3A.1responsible for PHS resistance in wheat. Candidate gene expression was further validated by quantitative RT-PCR. Within the targeted QTL interval, 16 genetic variants including five single nucleotide polymorphisms (SNPs) and 11 indels showed consistent polymorphism between resistant and susceptible isolines.ConclusionsThe targeted QTL is confirmed to harbor core genes related to hormone signaling pathways that can be exploited as a key genomic region for marker-assisted selection. The candidate genes and SNP/indel markers detected in this study are valuable resources for understanding the mechanism of PHS resistance and for marker-assisted breeding of the trait in wheat.
Non-targeted and targeted metabolomics profiling of tea plants (Camellia sinensis) in response to its intercropping with Chinese chestnut
Authors: Wu Tian , Zou Rui , Pu Dian , Lan Zengquan , Zhao Bingyu 
Published: January 2021

Abstract
Background
Intercropping is often used in the tea producing areas where land resources are not so abundant, and the produced green tea is tasted more delicious through a tea-Chinese chestnut intercropping system according to the experience of indigenous farmers. The length and weight of tea leaf increase under this intercropping system and their root systems are stratified vertically and coordinate symbiosis. However, the delicacy mechanism under the intercropping is not fully understood.

Results
Green tea from the Chinese chestnut–tea intercropping system established in the 1980s ranked highest compared with a pure tea plantation from the same region. Based on the non-targeted metabolomics, 100 differential metabolites were upregulated in the tea leaves from intercropping system relative to monoculture system. Twenty-one amino acids were upregulated and three downregulated in response to the intercropping based on the targeted metabolomics; half of the upregulated amino acids had positive effects on the tea taste. Levels of allantoic acid, sugars, sugar alcohols, and oleic acid were higher and less bitter flavonoids in the intercropping system than those in monoculture system. The upregulated metabolites could promote the quality of tea and its health-beneficial health effects. Flavone and flavonol biosynthesis and phenylalanine metabolism showed the greatest difference. Numerous pathways associated with amino acid metabolism altered, suggesting that the intercropping of Chinese chestnut–tea could greatly influence amino acid metabolism in tea plants.

Conclusions
These results enhance our understanding of the metabolic mechanisms by which tea quality is improved in the Chinese chestnut–tea intercropping system and demonstrate that there is great potential to improve tea quality at the metabolomic level by adopting such an intercropping system.