bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclophosphamide rescue therapy for relapsed low-grade alimentary lymphoma after chlorambucil treatment in cats
Authors: Kim Changseok , Wouda Raelene M , Borrego Juan , Chon Esther 
Published: March 2021

Objectives The aims of this study were to evaluate the response, outcome and prognostic factors in cats with clinically presumed relapsed low-grade alimentary lymphoma (LGAL) receiving cyclophosphamide as a first-line rescue therapy after failing chlorambucil treatment. Methods The medical records of 20 cats (from three institutions, between 2002 and 2017) treated with cyclophosphamide for relapsed LGAL after initial treatment with chlorambucil were retrospectively reviewed. Progression-free survival (PFS), overall survival time (OST) and the association of select variables with measures of outcome were assessed. Adverse events (AEs) were also described. Results Eighteen cats (90%) achieved a complete clinical response (CR) for a median duration of 239 days. The median PFS was 215 days. The median OST was 1065 days. The only clinical factor associated with a longer PFS was achievement of a CR with cyclophosphamide treatment. Cyclophosphamide was associated with few and reversible constitutional, gastrointestinal and hematologic AEs. Conclusions and relevance Cyclophosphamide appears to be a safe and effective first-rescue therapeutic option for cats with relapsed LGAL.
Magical Mathematical Formulas for Nanoboxes
Authors: Kaatz Forrest H. , Bultheel Adhemar 
Published: March 2021

AbstractHollow nanostructures are at the forefront of many scientific endeavors. These consist of nanoboxes, nanocages, nanoframes, and nanotubes. We examine the mathematics of atomic coordination in nanoboxes. Such structures consist of a hollow box with n shells and t outer layers. The magical formulas we derive depend on both n and t. We find that nanoboxes with t = 2 or 3, or walls with only a few layers generally have bulk coordinated atoms. The benefits of low-coordination in nanostructures is shown to only occur when the wall thickness is much thinner than normally synthesized. The case where t = 1 is unique, and has distinct magic formulas. Such low-coordinated nanoboxes are of interest for a myriad variety of applications, including batteries, fuel cells, plasmonic, catalytic and biomedical uses. Given these formulas, it is possible to determine the surface dispersion of the nanoboxes. We expect these formulas to be useful in understanding how the atomic coordination varies with n and t within a nanobox.
Pattern recognition in lymphoid malignancies using CytoGPS and Mercator
Authors: Abrams Zachary B. , Tally Dwayne G. , Zhang Lin , Coombes Caitlin E. , Payne Philip R. O. , Abruzzo Lynne V. , Coombes Kevin R. 
Published: March 2021

Abstract
Background
There have been many recent breakthroughs in processing and analyzing large-scale data sets in biomedical informatics. For example, the CytoGPS algorithm has enabled the use of text-based karyotypes by transforming them into a binary model. However, such advances are accompanied by new problems of data sparsity, heterogeneity, and noisiness that are magnified by the large-scale multidimensional nature of the data. To address these problems, we developed the Mercator R package, which processes and visualizes binary biomedical data. We use Mercator to address biomedical questions of cytogenetic patterns relating to lymphoid hematologic malignancies, which include a broad set of leukemias and lymphomas. Karyotype data are one of the most common form of genetic data collected on lymphoid malignancies, because karyotyping is part of the standard of care in these cancers.

Results
In this paper we combine the analytic power of CytoGPS and Mercator to perform a large-scale multidimensional pattern recognition study on 22,741 karyotype samples in 47 different hematologic malignancies obtained from the public Mitelman database.

Conclusion
Our findings indicate that Mercator was able to identify both known and novel cytogenetic patterns across different lymphoid malignancies, furthering our understanding of the genetics of these diseases.
Transcriptome profiling of Lymnaea stagnalis (Gastropoda) for ecoimmunological research
Authors: Seppälä Otto , Walser Jean-Claude , Cereghetti Teo , Seppälä Katri , Salo Tiina , Adema Coen M. 
Published: March 2021

AbstractBackgroundHost immune function can contribute to numerous ecological/evolutionary processes. Ecoimmunological studies, however, typically use one/few phenotypic immune assays and thus do not consider the complexity of the immune system. Therefore, “omics” resources that allow quantifying immune activity across multiple pathways are needed for ecoimmunological models. We applied short-read based RNAseq (Illumina NextSeq 500, PE-81) to characterise transcriptome profiles ofLymnaea stagnalis(Gastropoda), a multipurpose model snail species. We used a genetically diverse snail stock and exposed individuals to immune elicitors (injury, bacterial/trematode pathogens) and changes in environmental conditions that can alter immune activity (temperature, food availability).ResultsImmune defence factors identified in the de novo assembly covered elements broadly described in other gastropods. For instance, pathogen-recognition receptors (PRR) and lectins activate Toll-like receptor (TLR) pathway and cytokines that regulate cellular and humoral defences. Surprisingly, only modest diversity of antimicrobial peptides and fibrinogen related proteins were detected when compared with other taxa. Additionally, multiple defence factors that may contribute to the phenotypic immune assays used to quantify antibacterial activity and phenoloxidase (PO)/melanisation-type reaction in this species were found. Experimental treatments revealed factors from non-self recognition (lectins) and signalling (TLR pathway, cytokines) to effectors (e.g., antibacterial proteins, PO enzymes) whose transcription depended on immune stimuli and environmental conditions, as well as components of snail physiology/metabolism that may drive these effects. Interestingly, the transcription of many factors (e.g., PRR, lectins, cytokines, PO enzymes, antibacterial proteins) showed high among-individual variation.ConclusionsOur results indicate several uniform aspects of gastropod immunity, but also apparent differences betweenL. stagnalisand some previously examined taxa. Interestingly, in addition to immune defence factors that responded to immune elicitors and changes in environmental conditions, many factors showed high among-individual variation across experimental snails. We propose that such factors are highly important to be included in future ecoimmunological studies because they may be the key determinants of differences in parasite resistance among individuals both within and between natural snail populations.
Blinatumomab-induced T cell activation at single cell transcriptome resolution
Authors: Huo Yi , Sheng Zhen , Lu Daniel R. , Ellwanger Daniel C. , Li Chi-Ming , Homann Oliver , Wang Songli , Yin Hong , Ren Ruibao 
Published: March 2021

AbstractBackgroundBi-specific T-cell engager (BiTE) antibody is a class of bispecific antibodies designed for cancer immunotherapy. Blinatumomab is the first approved BiTE to treat acute B cell lymphoblastic leukemia (B-ALL). It brings killer T and target B cells into close proximity, activating patient’s autologous T cells to kill malignant B cells via mechanisms such as cytolytic immune synapse formation and inflammatory cytokine production. However, the activated T-cell subtypes and the target cell-dependent T cell responses induced by blinatumomab, as well as the mechanisms of resistance to blinatumomab therapy are largely unknown.ResultsIn this study, we performed single-cell sequencing analysis to identify transcriptional changes in T cells following blinatumomab-induced T cell activation using single cells from both, a human cell line model and a patient-derived model of blinatumomab-mediated cytotoxicity. In total, the transcriptome of 17,920 single T cells from the cell line model and 2271 single T cells from patient samples were analyzed. We found that CD8+ effector memory T cells, CD4+ central memory T cells, naïve T cells, and regulatory T cells were activated after blinatumomab treatment. Here, blinatumomab-induced transcriptional changes reflected the functional immune activity of the blinatumomab-activated T cells, including the upregulation of pathways such as the immune system, glycolysis, IFNA signaling, gap junctions, and IFNG signaling. Co-stimulatory (TNFRSF4 and TNFRSF18) and co-inhibitory (LAG3) receptors were similarly upregulated in blinatumomab-activated T cells, indicating ligand-dependent T cell functions. Particularly, B-ALL cell expression of TNFSF4, which encodes the ligand of T cell co-stimulatory receptor TNFRSF4, was found positively correlated with the response to blinatumomab treatment. Furthermore, recombinant human TNFSF4 protein enhanced the cytotoxic activity of blinatumomab against B-ALL cells.ConclusionThese results reveal a target cell-dependent mechanism of T-cell activation by blinatumomab and suggest that TNFSF4 may be responsible for the resistant mechanism and a potential target for combination therapy with blinatumomab, to treat B-ALL or other B-cell malignancies.
CIPK11: a calcineurin B-like protein-interacting protein kinase from Nitraria tangutorum, confers tolerance to salt and drought in Arabidopsis
Authors: Lu Lu , Chen Xinying , Wang Pengkai , Lu Ye , Zhang Jingbo , Yang Xiuyan , Cheng Tielong , Shi Jisen , Chen Jinhui 
Published: March 2021

AbstractBackgroundTheCIPKsare a group of plant-specific Ser/Thr protein kinases acting in response to calcium signaling, which plays an important role in the physiological and developmental adaptation of plants to adverse environments. However, the functions of halophyte-derivedCIPKs are still poorly understood, that limits a potential application ofCIPKsfrom halophytes for improving the tolerance of glycophytes to abiotic stresses.ResultsIn this study, we characterized theNtCIPK11gene from the halophyteNitraria tangutorumand subsequently analyzed its role in salt and drought stress tolerance, usingArabidopsisas a transgenic model system.NtCIPK11expression was upregulated inN. tangutorumroot, stem and blade tissues after salt or drought treatment. OverexpressingNtCIPK11inArabidopsisimproved seed germination on medium containing different levels of NaCl. Moreover, the transgenic plants grew more vigorously under salt stress and developed longer roots under salt or drought conditions than the WT plants. Furthermore,NtCIPK11overexpression altered the transcription of genes encoding key enzymes involved in proline metabolism inArabidopsisexposed to salinity, however, which genes showed a relatively weak expression in the transgenicArabidopsisundergoing mannitol treatment, a situation that mimics drought stress. Besides, the proline significantly accumulated inNtCIPK11-overexpressing plants compared with WT under NaCl treatment, but that was not observed in the transgenic plants under drought stress caused by mannitol application.ConclusionsWe conclude thatNtCIPK11promotes plant growth and mitigates damage associated with salt stress by regulating the expression of genes controlling proline accumulation. These results extend our understanding on the function of halophyte-derivedCIPKgenes and suggest thatNtCIPK11can serve as a candidate gene for improving the salt and drought tolerance of glycophytes through genetic engineering.
Genome-wide analysis and expression profile of the bZIP gene family in poplar
Authors: Zhao Kai , Chen Song , Yao Wenjing , Cheng Zihan , Zhou Boru , Jiang Tingbo 
Published: March 2021

AbstractBackgroundThe bZIP gene family, which is widely present in plants, participates in varied biological processes including growth and development and stress responses. How do the genes regulate such biological processes? Systems biology is powerful for mechanistic understanding of gene functions. However, such studies have not yet been reported in poplar.ResultsIn this study, we identified 86 poplar bZIP transcription factors and described their conserved domains. According to the results of phylogenetic tree, we divided these members into 12 groups with specific gene structures and motif compositions. The corresponding genes that harbor a large number of segmental duplication events are unevenly distributed on the 17 poplar chromosomes. In addition, we further examined collinearity between these genes and the related genes from six other species. Evidence from transcriptomic data indicated that the bZIP genes in poplar displayed different expression patterns in roots, stems, and leaves. Furthermore, we identified 45 bZIP genes that respond to salt stress in the three tissues. We performed co-expression analysis on the representative genes, followed by gene set enrichment analysis. The results demonstrated that tissue differentially expressed genes, especially the co-expressing genes, are mainly involved in secondary metabolic and secondary metabolite biosynthetic processes. However, salt stress responsive genes and their co-expressing genes mainly participate in the regulation of metal ion transport, and methionine biosynthetic.ConclusionsUsing comparative genomics and systems biology approaches, we, for the first time, systematically explore the structures and functions of the bZIP gene family in poplar. It appears that the bZIP gene family plays significant roles in regulation of poplar development and growth and salt stress responses through differential gene networks or biological processes. These findings provide the foundation for genetic breeding by engineering target regulators and corresponding gene networks into poplar lines.
Effects of dexmedetomidine on intraoperative hemodynamics, recovery profile and postoperative pain in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial
Authors: Ye Qin , Wang Fangjun , Xu Hongchun , Wu Le , Gao Xiaopei 
Published: March 2021

Abstract
Background
To investigate the optimal dose of dexmedetomidine to maintain hemodynamic stability, prevent of cough and minimize postoperative pain for patients undergoing laparoscopic cholecystectomy.

Methods
One hundred twenty patients were randomly divided into D1, D2, D3 and NS groups, and dexmedetomidine 0.4, 0.6, 0.8μg/kg and normal saline were administrated respectively. Patients’ heart rate, systolic blood pressure and diastolic blood pressure were measured at T1-T7. The incidence of cough was recorded. Other parameters were noted, the time of spontaneous respiratory recovery and extubation, visual analogue scale scores and dosage of tramadol.

Results
The heart rate, systolic blood pressure and diastolic blood pressure of D2 and D3 groups has smaller fluctuations at T2–3 and T7 compared with NS and D1 groups (P < 0.05). The incidence of cough was lower in D2 and D3 groups than NS group (P < 0.05). The visual analogue scale scores and tramadol dosage of D2 and D3 groups were lower than NS group (P < 0.05). The time of spontaneous respiratory recovery and extubation in D3 group was longer than that in D1 and D2 groups (P < 0.05).

Conclusions
Intravenous infusion of 0.6μg/kg dexmedetomidine before induction can maintain hemodynamic stability, decrease cough during emergence, relieve postoperative pain of patients undergoing laparoscopic cholecystectomy.

Trial registration
ChiCTR1900024801, registered at the Chinese Clinical Trial Registry, principal investigator: Qin Ye, date of registration: July 28, 2019.
Consistency and applicability of different brief screen instrument of cognitive function in elderly population
Authors: Lu Lixia , Chen Lin , Wu Weiwen , Wang Yang , Liu Zhenbao , Xu Jun , Yang Qianhong , Zhao Jun , Liu Liangxian , Yu Hui 
Published: March 2021

Abstract
Background
Screening for cognitive impairment (CI) is often hampered by lack of consensus as to which screening instrument to use. The aim is to assess the consistence and applicability of different CI screening tools.

Method
In a cross-sectional study from October 2017 to September 2018 in 7 communities in Shanghai, China, elder (≧60) residential volunteers with no history of major cardiovascular diseases, cancers and other comorbidities known to affect cognitive functions were recruited. The participants underwent tests with 7 cognitive function screening instruments. Multivariate linear regressions were performed to test correlations between demographic characteristics, including gender, age, education, and marital status, with cognitive test scores. Mini-Mental State Examination (MMSE) score adjusted according to the correlation coefficients was used to detect CI with a cutoff of 24. Other cognitive function scores were compared between participants with and without CI. In addition, Pearson’s correlation test was used to detect association between different test scores.

Results
172 participants with relatively low education levels were included. Age and education showed significant association with cognitive test scores. Using adjusted MMSE, 39.6% of participants were identified with CI, while the percentage was 87.2% when adjusted Montreal Cognitive Assessment (MoCA) with cutoff of 26 was used. Analysis of “abnormal” test scores showed that MMSE had the highest percentage of valid data (98.8%). MoCA and Isaacs test of Verbal Fluency (VF) score had correlation with most the other scores, while MMSE only significantly associated with VF and MoCA.

Conclusions
MMSE may still present the most applicable tools for quick screen of cognitive functions, especially when environmental conditions may interfere with participants’ attention.
ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer
Authors: Fonseca Aline Simoneti , Ramão Anelisa , Bürger Matheus Carvalho , de Souza Jorge Estefano Santana , Zanette Dalila Lucíola , de Molfetta Greice Andreotti , de Araújo Luiza Ferreira , de Barros e Lima Bueno Rafaela , Aguiar Graziela Moura , Plaça Jessica Rodrigues , Alves Cleidson de Pádua , dos Santos Anemari Ramos Dinarte , Vidal Daniel Onofre , Silva Gyl Eanes Barros , Panepucci Rodrigo Alexandre , Peria Fernanda Maris , Feres Omar , da Rocha José Joaquim Ribeiro , Zago Marco Antonio , Silva Wilson Araújo 
Published: March 2021

AbstractBackgroundColorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in theAPC, DCC, KRASandTP53genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition.MethodsTen paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations inAPC, KRASandTP53genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients.ResultsGene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2,p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, theETV4stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays againstETV4resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealedKRASandTP53gene pathogenic mutations, exclusively in the adenocarcinomas samples.ConclusionOur study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on theETV4gene, which demonstrated involvement in proliferation and migration.
Toward developing a metastatic breast cancer treatment strategy that incorporates history of response to previous treatments
Authors: Olow Aleksandra K. , Veer Laura van ’t , Wolf Denise M. 
Published: March 2021

Abstract
Background
Information regarding response to past treatments may provide clues concerning the classes of drugs most or least likely to work for a particular metastatic or neoadjuvant early stage breast cancer patient. However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account.

Methods
To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log (OR)) of responding to each drug given knowledge of (intrinsic/prior) response to all other agents. This OR matrix assumes (1) response is based on intrinsic rather than acquired characteristics, and (2) intrinsic sensitivity remains unchanged at the time of the next decision point. Fisher’s exact test is used to identify predictive pairs and groups of agents (BH p < 0.05). Recommendation systems are used to make further drug recommendations based on past ‘history’ of response.

Results
Of the 90 compounds, 57 have sensitivity profiles significantly associated with those of at least one other agent, mostly targeted drugs. Nearly all associations are positive, with (intrinsic/prior) sensitivity to one agent predicting sensitivity to others in the same or a related class (OR > 1). In vitro conditional response patterns clustered compounds into five predictive classes: (1) DNA damaging agents, (2) Aurora A kinase and cell cycle checkpoint inhibitors; (3) microtubule poisons; (4) HER2/EGFR inhibitors; and (5) PIK3C catalytic subunit inhibitors. The apriori algorithm implementation made further predictions including a directional association between resistance to HER2 inhibition and sensitivity to proteasome inhibitors.

Conclusions
Investigating drug sensitivity conditioned on observed sensitivity or resistance to prior drugs may be pivotal in informing clinicians deciding on the next line of breast cancer treatments for patients who have progressed on their current treatment. This study supports a strategy of treating patients with different agents in the same class where an associated sensitivity was observed, likely after one or more intervening treatments.